Utility of PCA3 in patients undergoing repeat biopsy for prostate cancer.

BACKGROUND: Men with persistently elevated and/or rising PSA levels after negative prostate biopsy often undergo multiple repeat biopsies. Prostate cancer antigen 3 (PCA3) has emerged as a predictor of prostate cancer. METHODS: We sought to define the utility of PCA3 in combination with other clinical data in predicting the risk of prostate cancer on repeat biopsy. We retrospectively obtained PCA3, PSA, PSA density (PSAD), digital rectal examination (DRE) and transrectal ultrasound (TRUS) findings from 103 patients at a single institution who had at least one prior negative prostate biopsy. The sensitivity and specificity of PCA3 in detecting prostate cancer was determined. Receiver operating characteristics curves were produced for each variable individually and in multivariable analysis, controlling for PCA3, PSAD, TRUS, PSA and DRE. A nomogram was created, internally validated and compared to another recently published nomogram. RESULTS: Of the 103 patients, 37 (31%) had prostate cancer on repeat biopsy. The sensitivity and specificity of PCA3 (using a cut point of 25) was 0.67 and 0.64, respectively. In multivariable analyses, PCA3 was independently associated with prostate cancer (odds ratio: 1.02, 95% confidence interval: 1.01-1.04), with area under the curve (AUC) of 0.64. A multivariable model containing PCA3, PSAD, PSA, DRE and TRUS findings showed the most diagnostic accuracy (AUC: 0.82). CONCLUSIONS: In the setting of prior negative biopsies, PCA3 was independently associated with prostate cancer in a multivariable model. In combination with other clinical data, PCA3 is a valuable tool in assessing the risk of prostate cancer on repeat biopsy.

Restrictive right ventricular physiology and right ventricular fibrosis as assessed by cardiac magnetic resonance and exercise capacity after biventricular repair of pulmonary atresia and intact ventricular septum.

BACKGROUND: The hypertrophic myocardium, myocardial fiber disarray, and endocardial fibroelastosis in pulmonary atresia and intact ventricular septum (PAIVS) may provide anatomic substrates for restrictive filling of the right ventricle. HYPOTHESIS: Restrictive right ventricle (RV) physiology is related to RV fibrosis and exercise capacity in patients after biventricular repair of PAIVS. METHODS: A total of 27 patients, age 16.5 +/- 5.6 years, were recruited after biventricular repair of PAIVS. Restrictive RV physiology was defined by the presence of antegrade diastolic pulmonary flow and RV fibrosis assessed by late gadolinium enhancement (LGE) cardiac magnetic resonance. Their RV function was compared with that of 27 healthy controls and related to RV LGE score and exercise capacity. RESULTS: Compared with controls, PAIVS patients had lower tricuspid annular systolic and early diastolic velocities, RV global longitudinal systolic strain, systolic strain rate, and early and late diastolic strain rates (all P < 0.05). A total of 22 (81%, 95% confidence interval: 62%-94%) PAIVS patients demonstrated restrictive RV physiology. Compared to those without restrictive RV physiology (n = 5), these 22 patients had lower RV global systolic strain, lower RV systolic and early diastolic strain rates, higher RV LGE score, and a greater percent of predicted maximum oxygen consumption (all P < 0.05). CONCLUSION: Restrictive RV physiology reflects RV diastolic dysfunction and is associated with more severe RV fibrosis but better exercise capacity in patients after biventricular repair of PAIVS.

Diffuse large B-cell lymphoma of the central nervous system in mycophenolate mofetil-treated patients with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) are susceptible to the development of lymphoproliferative disorders and postulated causes include intrinsic defects in immune surveillance and iatrogenic administration of immunosuppressants. Since the introduction of mycophenolate mofetil (MMF) to the immunosuppressive regimen for the management of post-organ transplantation, there have been reports of primary lymphoma of the central nervous system (PCNSL). MMF has been widely used to treat active SLE patients with Class IV lupus nephritis. In addition to two previously reported cases of PCNSL among SLE patients on long-term MMF, we report a third patient who has been on treatment with MMF for 8 years. The histology showed features compatible with diffuse large B-cell lymphoma with strong immunohistochemical staining for CD20 and positive signal for Epstein-Barr virus (EBV)-encoded RNA by in-situ hybridization that is similar to other case reports, suggesting EBV driven B-cell lymphoproliferative disease. The patient responded to withdrawal of MMF, intravenous methotrexate, rituximab and whole brain radiotherapy. With the increasing use of MMF in active renal as well as non-renal exacerbations of SLE, PCNSL should be included in the differential diagnosis in patients who present with gradual onset of focal neurological deficit.

Effect of antibiotics on the bacterial load of meticillin-resistant Staphylococcus aureus colonisation in anterior nares.

Prevalence of hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA) infection or colonisation has been associated with antimicrobial consumption. The impact of antibiotic treatment on nasal colonisation is unknown. We conducted a three-month prospective study of 116 patients with extranasal MRSA infection or colonisation, whose nasal MRSA bacterial loads were determined during and after various antibiotic courses over a period of three weeks. Environmental swabs were also taken from the near patient environment. Concomitant nasal MRSA carriage was observed in 76.7% of extranasal MRSA-colonised or -infected patients. The median nasal MRSA bacterial load increased significantly from 2.78 (range 0-6.15) to 5.30 (range 2.90-8.41) log(10) cfu per swab (cfu/swab) (P<0.001) over 21 days during beta-lactam therapy. It also increased from 0 (range 0-4.00) to 4.30 (range 0-7.46) log(10)cfu/swab (P=0.039) over 14 days during fluoroquinolone therapy. Median bacterial loads were significantly higher for beta-lactam- and fluoroquinolone-treated patients on day 7 [4.78, range 0-7.30], day 14 [4.30, range 0-7.60] and day 21 [5.30, range 2.90-8.41] than controls not receiving antibiotics (P<0.05). These loads then decreased by 2-5log(10)cfu/swab 2 weeks after discontinuation of antibiotics. The environment of patients receiving beta-lactam agents (relative risk: 3.55; 95% confidence interval: 1.30-9.62; P=0.018) or fluoroquinolones (4.32; 1.52-12.31; P=0.008) demonstrated more MRSA contamination than the environment around control patients (0.79; 0.67-0.93; P=0.002). Patients on beta-lactam or fluoroquinolone therapy have increased incidence of MRSA colonisation and higher nasal bacterial loads, and appear to spread their MRSA into the near patient environment.

Outbreak of human metapneumovirus infection in psychiatric inpatients: implications for directly observed use of alcohol hand rub in prevention of nosocomial outbreaks.

Nosocomial outbreaks of infectious diseases in psychiatric facilities are not uncommon but the implementation of infection control measures is often difficult. Here, we report an outbreak of an acute respiratory illness in a psychiatric ward between 29 July and 20 August 2005 involving 31 patients. Human metapneumovirus was detected in seven (23%) patients by reverse transcription-polymerase chain reaction and nucleotide sequencing. A review of outbreak surveillance records showed that six nosocomial outbreaks occurred in the year 2005, of which four (67%) were confirmed or presumably related to a respiratory viral infection. Directly observed deliveries of alcohol hand rub 4-hourly during daytime to all psychiatric patients was instituted in December 2005. Only one nosocomial respiratory viral outbreak occurred in the following year. The total number of patients and staff involved in nosocomial outbreaks due to presumed or proven respiratory virus infections decreased significantly from 60 to six (P<0.001), whereas those due to all types of nosocomial outbreaks also decreased from 70 to 24 (P=0.004). Alcohol hand rub has been shown to have potent bactericidal and virucidal activity against a wide range of nosocomial pathogens. Regular use of directly observed alcohol hand rub may decrease the incidence and scale of nosocomial outbreaks due to enveloped respiratory viruses especially in mentally incapacitated patients.

Lymphopenia at presentation is associated with increased risk of infections in patients with systemic lupus erythematosus.

BACKGROUND: Patients with systemic lupus erythematosus (SLE) frequently suffer from infections, but the predisposing risk factors, as well as the exact frequency and nature of such infections, are not fully understood. AIM: To describe the frequency, types and risk factors for infections in a group of Chinese patients in the early stage of SLE in Hong Kong. DESIGN: Retrospective record study. METHODS: We reviewed the case records of 91 Chinese SLE patients, presenting <12 months after SLE diagnosis. Details of major infections (requiring intravenous antimicrobial therapy, or any confirmed mycobacterial infection) and minor infections were reviewed. Clinical and laboratory features, the systemic lupus erythematosus disease activity index (SLEDAI) at presentation and drug treatment were recorded and analysed. RESULTS: There were 48 major infections and 62 minor infections during 260 patient-years of follow-up. A lymphocyte count < or =1.0 x 10(9)/l at presentation was independently associated with an increased risk for major infection: hazard ratio 4.7 (95%CI 1.6-13.7), p = 0.005. SLEDAI, use of corticosteroids and immunosuppressive therapy were all not associated with increased risk of infection. DISCUSSION: Lymphopenia was an important risk factor for major infections in this group of Chinese patients in the early stages of SLE. SLE patients with lymphopenia at presentation should be closely monitored for the development of infective complications.

Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study.

BACKGROUND: Clarithromycin is frequently used to treat community-acquired pneumonia in elderly persons. Like erythromycin, it may interact with other drugs by interfering with metabolism by cytochrome P450 enzymes and with the P-glycoprotein transporter system. Colchicine, used for treatment of acute gout and for prophylaxis, may cause bone marrow toxicity. It is metabolized by CYP3A4 and is transported by P-glycoprotein. Initial case reports suggested potentially fatal interactions between clarithromycin and colchicine. METHODS: A retrospective study was conducted with 116 patients who were prescribed clarithromycin and colchicine during the same clinical admission. Case-control comparisons were made between patients who received concomitant therapy with the 2 drugs and patients who received sequential therapy. We assessed the clinical presentations and outcomes of the 2 patient groups and analyzed the risk factors associated with fatal outcomes. RESULTS: Nine (10.2%) of the 88 patients who received the 2 drugs concomitantly died. Only 1 (3.6%) of the 28 patients who received the drugs sequentially died. Multivariate analysis of the 88 patients who received concomitant therapy showed that longer overlapped therapy (relative risk [RR], 2.16; 95% confidence interval [CI], 1.41-3.31; P< or =.01), the presence of baseline renal impairment (RR, 9.1; 95% CI, 1.75-47.06; P<.001), and the development of pancytopenia (RR, 23.4; 95% CI, 4.48-122.7; P<.001) were independently associated with death. CONCLUSIONS: Clarithromycin increases the risk of fatal colchicine toxicity, especially for patients with renal insufficiency. Since there are other drugs for treatment of pneumonia and gout, these 2 drugs should not be coprescribed, because of the risk of fatality.

Reduced bone mineral density in male Severe Acute Respiratory Syndrome (SARS) patients in Hong Kong.

During the Severe Acute Respiratory Syndrome (SARS) outbreak in Hong Kong in 2003, patients were treated with very high doses of corticosteroid and ribavirin. The detrimental effects of such treatment on the bone mineral density (BMD) of SARS patients are unknown. To compare the BMD of SARS patients with normal range data, a cross-sectional survey was conducted. The bone mineral density of 224 patients with SARS, who were treated with an average of 2753 mg (SD = 2152 mg) prednisolone and 29,344 mg (SD = 15,849 mg) of ribavirin was compared to normal data. Six percent of men had a hip BMD Z score of < or =-2 (P = 0.057 for testing the hypothesis that >2.5% of subjects should have a Z score of < or =-2). Moreover, there was a negative association (r = -0.25, P = 0.023) between the duration of steroid therapy and BMD in men. We conclude that male SARS patients had lower BMD at the hip than normal controls, and this could be attributed to prolonged steroid therapy.

Pulmonary artery thrombosis in a patient with severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is an emerging infectious disease with both pulmonary and extra-pulmonary manifestations. Although coagulation abnormalities are common in these patients, clinically overt thromboembolic events are rarely reported. This report describes the first case of pulmonary artery thrombosis in a patient with laboratory confirmed SARS.

Viral loads in clinical specimens and SARS manifestations.

A retrospective viral load study was performed on clinical specimens from 154 patients with laboratory-confirmed severe acute respiratory syndrome (SARS); the specimens were prospectively collected during patients' illness. Viral load in nasopharyngeal aspirates (n = 142) from day 10 to day 15 after onset of symptoms was associated with oxygen desaturation, mechanical ventilation, diarrhea, hepatic dysfunction, and death. Serum viral load (n = 53) was associated with oxygen desaturation, mechanical ventilation, and death. Stool viral load (n = 94) was associated with diarrhea, and urine viral load (n = 111) was associated with abnormal urinalysis results. Viral replications at different sites are important in the pathogenesis of clinical and laboratory abnormalities of SARS.

Medical treatment of viral pneumonia including SARS in immunocompetent adult.

Since no randomized controlled trials have been conducted on the treatment of viral pneumonia by antivirals or immunomodulators in immunocompetent adults, a review of such anecdotal experience are needed for the more rational use of such agents. Case reports (single or case series) with details on their treatment and outcome in the English literature can be reviewed for pneumonia caused by human or avian influenza A virus (50 patients), varicella zoster virus (120), adenovirus (29), hantavirus (100) and SARS coronavirus (SARS-CoV) (841). Even with steroid therapy alone, the mortality rate appeared to be lower when compared with conservative treatment for pneumonia caused by human influenza virus (12.5% vs. 42.1%) and hantavirus (13.3% vs. 63.4%). Combination of an effective antiviral, acyclovir, with steroid in the treatment of varicella zoster virus may be associated with a lower mortality than acyclovir alone (0% vs. 10.3%). Combination of interferon alfacon-1 plus steroid, or lopinavir/ritonavir, ribavirin plus steroid were associated with a better outcome than ribavirin plus steroid (0% vs. 2.3% vs. 7.7%, respectively). Combination of lopinavir/ritonavir plus ribavirin significantly reduced the virus load of SARS-CoV in nasopharyngeal, serum, stool and urine specimens taken between day 10 and 15 after symptom onset when compared with the historical control group treated with ribavirin. It appears that the combination of an effective antiviral and steroid was associated with a better outcome. Randomized therapeutic trial should be conducted to ascertain the relative usefulness of antiviral alone or in combination with steroid.

Severe acute respiratory syndrome (SARS): epidemiology and clinical features.

Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease with a significant morbidity and mortality. The major clinical features include persistent fever, chills/rigor, myalgia, malaise, dry cough, headache, and dyspnoea. Older subjects may present without the typical febrile response. Common laboratory features include lymphopenia, thrombocytopenia, raised alanine transaminases, lactate dehydrogenase, and creatine kinase. The constellation of compatible clinical and laboratory findings, together with certain characteristic radiological features and lack of clinical response to broad spectrum antibiotics, should arouse suspicion of SARS. Measurement of serum RNA by real time reverse transcriptase-polymerase chain reaction technique has a detection rate of 75%-80% in the first week of the illness.

Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel coronavirus, but its immunopathological mechanisms have not yet been fully elucidated. We investigated changes in plasma T helper (Th) cell cytokines, inflammatory cytokines and chemokines in 20 patients diagnosed with SARS. Cytokine profile of SARS patients showed marked elevation of Th1 cytokine interferon (IFN)-gamma, inflammatory cytokines interleukin (IL)-1, IL-6 and IL-12 for at least 2 weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumour necrosis factor (TNF)-alpha, anti-inflammatory cytokine IL-10, Th1 cytokine IL-2 and Th2 cytokine IL-4. The chemokine profile demonstrated significant elevation of neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-gamma-inducible protein-10 (IP-10). Corticosteroid reduced significantly IL-8, MCP-1 and IP-10 concentrations from 5 to 8 days after treatment (all P < 0.001). Together, the elevation of Th1 cytokine IFN-gamma, inflammatory cytokines IL-1, IL-6 and IL-12 and chemokines IL-8, MCP-1 and IP-10 confirmed the activation of Th1 cell-mediated immunity and hyperinnate inflammatory response in SARS through the accumulation of monocytes/macrophages and neutrophils.

Viral replication in the nasopharynx is associated with diarrhea in patients with severe acute respiratory syndrome.

The role of severe acute respiratory syndrome (SARS) coronavirus as an enteric pathogen was investigated in a cohort of 142 patients with SARS who were treated with a standard treatment protocol. Data from daily hematological, biochemical, radiological, and microbiological investigations were prospectively collected, and the correlation of these findings with diarrhea was retrospectively analyzed. Sixty-nine patients (48.6%) developed diarrhea at a mean (+/- standard deviation [SD]) of 7.6+/-2.6 days after the onset of symptoms. The diarrhea was most severe at a mean (+/-SD) of 8.8+/-2.4 days after onset, with a maximum frequency of 24 episodes per day (median, 5 episodes; range, 3-24 episodes). A higher mean virus load in nasopharyngeal specimens obtained on day 10 after the onset of symptoms was significantly associated with the occurrence of diarrhea (3.1 log10 vs. 1.8 log10 copies/mL; P=.01) and mortality (6.2 vs. 1.7 log10 copies/mL; P<.01). However, diarrhea was not associated with mortality. The lung and the gastrointestinal tract may react differently to SARS coronavirus infection. Additional investigation of the role of SARS coronavirus in the pathogenesis of diarrhea in patients with SARS should be conducted.

Treatment of severe acute respiratory syndrome with convalescent plasma.

In March 2003, an outbreak of severe acute respiratory syndrome started in Hong Kong. A 57-year-old woman had a typical presentation, including fever, non-productive cough, malaise, lymphopenia, and raised liver aminotransferases. The clinical course and successful treatment with convalescent plasma, ribavirin, and corticosteroids are discussed.

Clinical course of peritonitis due to Pseudomonas species complicating peritoneal dialysis: a review of 104 cases.

BACKGROUND: Peritonitis due to Pseudomonas species is a serious complication in continuous ambulatory peritoneal dialysis (CAPD) patients. The clinical course of peritonitis due to Pseudomonas complicating CAPD remains unclear. METHODS: All of the Pseudomonas species episodes of peritonitis in our dialysis unit were studied from 1995 to 1999. During this period, there were 859 episodes of peritonitis recorded, 113 of which were caused by the Pseudomonas species. Nine episodes were excluded because they were mixed growth. The remaining 104 episodes in 68 patients were reviewed. RESULTS: The underlying renal diagnosis and prevalence of comorbid conditions of the 68 patients were similar to those found in our entire dialysis population. There was a history of antibiotic therapy within 30 days of the onset of peritonitis due to the Pseudomonas species in 69 episodes (66.3%). In 47 episodes (45.2%) there was a concomitant exit site infection. The overall primary response rate was 60.6% and the complete cure rate was 22.1%. The presence of exit site infection was associated with a lower primary response rate (22 in 47 vs. 41 in 57 episodes, P < 0.01) and a lower complete cure rate (5 in 47 vs. 18 in 57 episodes, P < 0.02). The episodes that had received recent antibiotic therapy had a significantly lower complete cure rate than the de novo cases (8 in 69 vs. 15 in 35 episodes, P < 0.001). Episodes receiving third-generation cephalosporin as part of the initial antibiotic regimen had a significantly higher primary response rate than the ones that initially received aminoglycoside (54 in 81 episodes vs. 8 in 22 episodes, P < 0.05), but their complete cure rates were similar. Twenty-four cases failed to respond to antibiotics and the Tenckhoff catheter was removed. The chance of returning to CAPD was higher when the Tenckhoff catheter was removed on day 10 than on day 15 (9 in 14 cases vs. 5 in 10 cases), although the result was not statistically significant. The Tenckhoff catheter was removed and replaced at another site simultaneously in another 14 cases after the effluent cleared up. None of these patients had a relapse of peritonitis within three months. CONCLUSIONS: Recent antibiotic therapy is the major risk factor for peritonitis due to the Pseudomonas species. Exit site infection and recent antibiotic therapy are associated with poor therapeutic response to antibiotics. When the therapeutic response is suboptimal, early Tenckhoff catheter removal may help preserve the peritoneum for further peritoneal dialysis. Elective Tenckhoff catheter exchange after clearing up the peritoneal dialysis effluent may also reduce the likelihood of relapse. It is desirable to use third-generation cephalosporin in the initial antibiotic regimen for peritonitis treatment in localities with a high incidence of peritonitis due to the Pseudomonas species.

The role of lean body mass as a nutritional index in Chinese peritoneal dialysis patients--comparison of creatinine kinetics method and anthropometric method.

OBJECTIVE: To compare, in Chinese continuous ambulatory peritoneal dialysis (CAPD) patients, the creatinine kinetics method (LBM-CK) and the anthropometric method (LBM-AM) for determining lean body mass (LBM). DESIGN: Single-center cross-sectional study. PATIENTS AND METHODS: We studied 151 unselected CAPD patients (78 males, 73 females). We calculated LBM-CK and LBM-AM using standard formulas. The results of the two methods were then compared by the Bland and Altman method. Dialysis adequacy and other nutritional indices, including total Kt/V, weekly creatinine clearance (CCr), residual glomerular filtration rate (GFR), protein nitrogen appearance (PNA), subjective global assessment (SGA), and serum albumin, were measured simultaneously. RESULTS: The mean age of the patients was 55.6 +/- 12.2 years, and the mean duration of dialysis was 33.6 +/- 28.5 months. The mean body mass index (BMI) was 22.7 +/- 3.7. The average LBM-AM was 43.6 +/- 8.0 kg; the average LBM-CK was 33.0 +/- 9.3 kg. The difference between the calculated LBM-AM and LBM-CK was 10.7 kg, with LBM-AM always giving a higher value; the limits of agreement were -5.8 kg and 27.1 kg. The difference between the two measures correlated with residual GFR (Pearson r = 0.629, p < 0.001). After normalizing for desired body weight, LBM-AM was only modestly correlated with serum albumin level. No correlations were found between overall SGA score or normalized protein nitrogen appearance (nPNA) and LBM-AM or LBM-CK. CONCLUSIONS: In Chinese patients at least, a substantial discrepancy exists between LBM-AM and LBM-CK. The difference is especially marked in patients with significant residual renal function. The optimal method for determining LBM remains obscure in Chinese CAPD patients. Moreover, LBM correlated poorly with other nutritional indices. Multiple parameters should be taken into consideration in an assessment of nutritional status of CAPD patients.