Efficacy and safety of lowering immunosuppression to treat CMV infection in renal transplant recipients on valaciclovir prophylaxis: a pilot study.

BACKGROUND: Routine cytomegalovirus (CMV)-pp65 antigenaemia monitoring shows that some patients will develop pp65 antigenaemia during valaciclovir prophylaxis or after cessation of treatment. The aim of this pilot study was to evaluate the safety and efficacy of lowering immunosuppression in kidney transplant recipients who exhibit mildly symptomatic CMV infections while on valaciclovir prophylaxis. METHODS: We selected 12 patients who experienced mildly symptomatic CMV infections defined as a positive CMV-pp65 antigenaemia test associated with either neutropenia, asthenia or arthralgia, but no fever. All of them received prophylaxis with valaciclovir for at least 3 months. Testing for CMV-pp65 antigenaemia was performed weekly for 6 months. RESULTS: The mildly symptomatic infections occurred at a median interval of 69 days after transplantation-during prophylaxis in eight cases and after valaciclovir discontinuation in the other four cases. All of them were effectively managed by lowering immunosuppressive therapy, leading to the disappearance of symptoms and CMV antigenaemia reduction. No immunological complication or recurrence of CMV infection or disease was noted. I.v. ganciclovir never became necessary. CONCLUSION: The mildly symptomatic CMV infections occurring in valaciclovir-treated patients may be managed efficiently and without immunologic complication by lowering immunosuppressive therapy.     

Clinical impact of drug-eluting stents in changing referral practices for coronary surgical revascularization in a tertiary care center

BACKGROUND: The long-term benefits of angioplasty are limited by the occurrence of restenosis. Drug-eluting stents with a projected restenosis rate of close to 0% are soon to become available. The short- and long-term consequences of this advance to the cardiac surgical volume remain unclear. METHODS: A total of 196 consecutive coronary angiograms and medical records of patients referred for coronary bypass surgery were reviewed. Considering the hypothetical premise of having drug-eluting stents with a near zero restenosis rate, we reviewed each case to determine if surgical revascularization was still the preferred option for revascularization. RESULTS: The mean age was 60 (+/-10.6) years. Seventy-two percent of patients were male. Considering the availability of drug-eluting stents 154 (79%) would still have been sent to surgery, representing a 21% decrease in the number of surgical revascularizations. Angiographic characteristics predicting coronary bypass revascularization were the presence of chronic total occlusion (odds ratio [OR]: 9.1; confidence interval [CI]: 2.1 to 39), left main coronary artery stenosis (OR: 9.6; CI: 1.27 to 73), and need for valvular surgery (OR: 7.38; CI: 1.3 to 157). The most common predictors of a change in clinical management from surgical to percutaneous revascularization if drug-eluting stents were available were diffuse coronary narrowing (OR: 15.78), restenotic lesions (OR: 27.86), and small coronary arteries (OR: 26). CONCLUSIONS: Drug-eluting stents may have a significant impact on cardiac surgery volume (approximately a 21% decrease in our center). It may also direct patients with small vessels, diffuse narrowing, or restenotic lesions and diabetic patients to percutaneous therapy.     

Sonoelastography of the prostate: comparison with systematic biopsy findings in 492 patients

OBJECTIVE: The aim of this study was to assess the value of sonoelastography (SE) for prostate cancer detection in comparison with systematic biopsy findings. MATERIAL AND METHODS: Four hundred and ninety two PSA screening volunteers (mean age: 61.9+/-8.6) with an total PSA >1.25 ng/mL and a free to total PSA ration of <18% underwent SE of the prostate before 10 core systematic prostate biopsy. Tissue elasticity of the peripheral zone was investigated only. Tissue elasticity was displayed from red (soft) to green (intermediate) and to blue (hard). Only hard lesions (blue) were considered to be suspicious for prostate cancer. The peripheral zone of the prostate was divided in 3 regions on each side: base, mid-gland, apex. A different investigator performed systematic biopsy, and the biopsy findings were compared with the SE findings. RESULTS: In 125 of 492 patients (25.4%) systematic biopsy demonstrated prostate cancer. Cancer was detected in 321 of 2952 (11%) outer gland areas (74 in the base, 106 in the mid-gland, 141 in the apex). The Gleason score ranged from 3 to 10 (mean: 6.5). In SE 533 of 2952 (18.1%) suspicious areas were detected and 258 of these areas (48.4%) showed cancer. Most of the false-positive findings (275/533 areas; 51.6%) were associated with chronic inflammation and atrophy especially at the basal prostate areas. The sensitivity by entire organ was calculated with 86% and the specificity 72%. The analysis by outer gland areas showed the highest sensitivity in the apex (79%). The specificity by outer gland areas ranged between 85% and 93%. The correlation between SE findings and biopsy results was high (p<0.001). CONCLUSION: Sonoelastography findings showed a good correlation with the systematic biopsy results. The best sensitivity and specificity was found in the apex region. Sonoelastography seems to offer a new approach for differentiation of tissue stiffness of the prostate and may therefore improve prostate cancer detection.     

Ventricular remodeling and mitral valve modifications in dilated cardiomyopathy: new insights from anatomic study

OBJECTIVE: The purpose of this study was to analyze the behavior of the mitral valve ring and the left ventricle in dilated cardiomyopathy. METHODS: We analyzed 68 fixed adult human hearts, divided into 48 hearts with dilated cardiomyopathy of ischemic or idiopathic origin and 20 hearts free of pathologic heart conditions. Digital images of the mitral ring perimeter, attachment of the anterior and posterior leaflets, and fibrous and muscular portions were collected. We also measured the internal perimeter of the left ventricle, the distance from the septum to the anterior and posterior papillary muscles, the distance between the papillary muscles, and the extension of interventricular septum. RESULTS: The analysis of the results showed proportional distribution of the ring's fibrous portion (r2 = 0.98) and muscular portion (r2 = 0.99) according to the degree of mitral valve dilation. Linear regression revealed that the perimeters of anterior and posterior leaflet attachments (r2 = 0.96 and r2 = 0.98, respectively) also had a proportional relation. We did not observe proportionality between the degree of dilation of the mitral ring and the left ventricle. It was observed that dilation of the left ventricle takes place globally in its segments. CONCLUSION: Differently from what was thought, in ischemic or idiopathic dilated cardiomyopathy, dilation of mitral ring is proportional and does not exclusively affect the posterior portion. The degree of left ventricular dilation does not determine the degree of dilation of the mitral ring because they are independent processes. These observations shed new light on the techniques used to correct mitral valve insufficiency in dilated cardiomyopathy.     

The impact of a cardioprotective protocol on the incidence of cardiac complications after aortic abdominal surgery

We analyzed a local database including 468 consecutive patients who underwent elective aortic abdominal surgery over an 8-yr period in a single institution. A new cardioprotective perioperative protocol was introduced in January 1997, and we questioned whether perioperative cardiac outcome could be favorably influenced by the application of a stepwise cardiovascular evaluation based on the American College of Cardiology/American Heart Association guidelines and by the use of antiadrenergic drugs. Clonidine was administered during surgery, and beta-blockers were titrated after surgery to achieve heart rates less than 80 bpm. We compared data of two consecutive 4-yr periods (1993-1996 [control period] versus 1997-2000 [intervention period]). Implementation of American College of Cardiology/American Heart Association guidelines was associated with increased preoperative myocardial scanning (44.3% vs 20.6%; P < 0.05) and coronary revascularization (7.7% vs 0.8%; P < 0.05). During the intervention period, there was a significant decrease in the incidence of cardiac complications (from 11.3% to 4.5%) and an increase in event-free survival at 1 yr after surgery (from 91.3% to 98.2%). Multivariate regression analysis showed that the combined administration of clonidine and beta-blockers was associated with a decreased risk of cardiovascular events (odds ratio, 0.3; 95% confidence interval, 0.1-0.8), whereas major bleeding, renal insufficiency, and chronic obstructive pulmonary disease were predictive of cardiac complications. In conclusion, cardiac testing was helpful to identify a small subset of high-risk patients who might benefit from coronary revascularization. Sequential and selective antiadrenergic treatments were associated with improved postoperative cardiac outcome. IMPLICATIONS: Implementation of American College of Cardiology/American Heart Association guidelines and use of antiadrenergic drugs were associated with better cardiac outcomes after major vascular surgery.     

Trends of lymphadenectomy in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy

Introduction

To evaluate temporal trends in the delivery and extent of lymphadenectomy (LND) in radical nephroureterectomy (RNU) performed in upper tract urothelial carcinoma (UTUC) patients.

Methods

We evaluated a multi institutional collaborative database composed by 1512 consecutive patients diagnosed with UTUC treated with RNU between 1990 and 2016. Year of surgery were grouped in five periods: 1990–1996, 1997–2002, 2003–2007, 2008–2012 and 2013–2016. Data about LND were available for all patients and numbers of nodes removed and positive were reported by dedicate uropathologists. The Mann–Whitney and Chi square tests were used to compare the statistical significance of differences in medians and proportions, respectively.

Results

Five hundred forty-five patients (36.0%) received a concomitant LND while 967 (64.0%) did not; 41.9% of open RNU patients received a concomitant LND compared to 24.4% of laparoscopic RNU patients. The rate of concomitant LND increased with time in the overall, laparoscopic and open RNU patients (all p?<?0.03). Patients treated with open RNU also had an increasing likelihood to receive an adequate concomitant LND (p?<?0.001) while those undergoing a laparoscopic approach did not (p?=?0.1). Patients treated with concomitant LND had a median longer operative time of 20 min (p?=?0.01). There were no differences in perioperative outcomes and complications between patients who received a concomitant LND and those who did not (p?>?0.1).

Conclusion

Although an increased trend was observed, most patients treated with RNU did not receive LND. Surgeons using a laparoscopic RNU were less likely to perform a concomitant LND, and when done, they remove less nodes.

     

Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy

Background

The Prostate CAncer gene 3 (PCA3) assay has shown promise as an aid in prostate cancer (pCA) diagnosis in identifying men with a high probability of a positive (repeat) biopsy.

Objective

This study evaluated the clinical utility of the PROGENSA PCA3 assay.

Design, setting, and participants

This European prospective, multicentre study enrolled men with one or two negative biopsies scheduled for repeat biopsy.

Measurements

After digital rectal examination (DRE), first-catch urine was collected to measure PCA3 mRNA concentration and to calculate the PCA3 score. The PCA3 score was compared to biopsy outcome. The diagnostic accuracy of the PCA3 assay was compared to percent of free prostate-specific antigen (%fPSA).

Results and limitations

In 463 men, the positive repeat biopsy rate was 28%. The higher the PCA3 score, the greater the probability of a positive repeat biopsy. The PCA3 score (cut-off of 35) had a greater diagnostic accuracy than %fPSA (cut-off of 25%). The PCA3 score was independent of the number of previous biopsies, age, prostate volume, and total prostate-specific antigen (PSA) level. Moreover, the PCA3 score was significantly higher in men with high-grade prostate intraepithelial neoplasia (HGPIN) versus those without HGPIN, clinical stage T2 versus T1, Gleason score ≥7 versus <7, and “significant” versus “indolent” (clinical stage T1c, PSA density [PSAD] <0.15 ng/ml, Gleason score in biopsy ≤6, and percent positive cores ≤33%) pCA.

Conclusions

The probability of a positive repeat biopsy increases with rising PCA3 scores. The PCA3 score was superior to %fPSA for predicting repeat prostate biopsy outcome and may be indicative of clinical stage and significance of pCa.     

Peripheral neural lesion-induced stress urinary incontinence in anaesthetized female cats

OBJECTIVES

To characterize the effect of acute unilateral and bilateral lesion of the pelvic and pudendal nerves, and nerves innervating the iliococcygeous and pubococcygeous muscles during sneezing in anaesthetized female cats, on intravesical pressure (IVP), urethral pressure (UPs) and external urethral sphincter (EUS) activity.

MATERIALS AND METHODS

In seven anaesthetized female cats UPs along the urethra (UPs1–4) and IVPs were recorded in the emptied bladder during sneezing before and after unilateral and then bilateral peripheral neural lesions. UPs were measured using microtip transducer catheters with UP4 positioned in the distal urethra where the EUS is located. Urine leakage was also noted, after urethral catheter removal and bladder filling.

RESULTS

During sneezing, in intact cats, the magnitude of UP4 was larger than those of IVP and UPs1–3. The area under the curve of both anal sphincter and EUS electromyography was increased. There was no urine leakage. After unilateral neural lesions, the mean magnitude of response was similar all along the urethra and in the bladder. The distal UP response was significantly lower than that recorded in intact cats. In addition, there was urine leakage in six of the seven cats. Bilateral neural lesions caused permanent urine leakage and significant decreases in all the UP responses.

CONCLUSION

In female cats, during sneezing, neurally driven reflex contractions of EUS leading to an increase in distal UP contribute to active urethral closure mechanisms and ensure urinary continence.     

Chondroid cystic malformation of the lung with trisomy 8 mosaicism: a new cystic lung malformation

Neonatal cystic disorders of the lungs are a heterogeneous malformative group including giant lobar hyperinflation, congenital pulmonary airway malformations, intralobar pulmonary sequestration, and bronchogenic cyst. Here, we describe a giant cystic pulmonary malformation in a 5-year-old girl, morphologically characterized by a highly disorganized proliferation of numerous cartilage islands, abundant mesenchymal tissue with abundant adipose differentiation, and epithelium-lined cysts. Cytogenetic analysis revealed an isolated trisomy 8, as the sole karyotype anomaly, a finding further confirmed by a whole-genome single nucleotide polymorphism array genotyping. The trisomy 8 was observed by fluorescent in situ hybridization within the malformation, and also in adjacent pulmonary parenchyma. A search of the literature revealed only 2 cases having similarities with the present case, but bearing different names. We believe that this lesion differs from congenital pulmonary airway malformations and from adult-type pulmonary hamartomas. We propose for this malformative mass the name "chondroid cystic malformation of the lung."     

Pathological features of Gleason score 6 prostate cancers in the low and intermediate range of prostate‐specific antigen level: is there a difference?

OBJECTIVE

To assess the pathological features of Gleason score 6 prostate cancers after radical prostatectomy in the low (<4 ng/mL) and intermediate range of prostate‐specific antigen level (4–10 ng/mL), as such prostate cancers are considered to be well differentiated tumours with a low risk for recurrence after therapy.

PATIENTS AND METHODS

In all, 1354 patients with T1c prostate cancer and PSA levels of <10.0 ng/mL had a radical retropubic prostatectomy. Patients with Gleason score 6 tumours were divided into two groups, those with PSA levels of <4 and 4.0–10.0 ng/mL. Extracapsular extension, positive surgical margins, biochemical recurrence (BCR) and mean time to BCR were evaluated.

RESULTS

Of the 1354 patients, there were 437 (32.3%) with Gleason score 6 prostate cancers. Patients in the low PSA group had less extraprostatic disease than those with a higher level (5.9% vs 14.5%) and both groups had an almost equal proportion of positive surgical margins (9.4% vs 11.0%). In the low PSA group there was statistically significantly shorter BCR than in the high PSA group, with a mean time to BCR of 1.7 vs 3.1 years.

CONCLUSIONS

These results show a statistically significantly higher rate of extraprostatic disease and earlier BCR in men with a high than a low PSA level even in Gleason score 6 prostate cancer. As the rate of BCR and extracapsular extension are significantly related to prostate cancer mortality, these findings further support the concept of screening using low PSA levels.