Novel Bone-Targeting Agent for Enhanced Delivery of Vancomycin to Bone

We examined the pharmacokinetic properties of vancomycin conjugated to a bone-targeting agent (BT) with high affinity for hydroxyapatite after systemic intravenous administration. The results confirm enhanced persistence of BT-vancomycin in plasma and enhanced accumulation in bone relative to vancomycin. This suggests that BT-vancomycin may be a potential carrier for the systemic targeted delivery of vancomycin in the treatment of bone infections, potentially reducing the reliance on surgical debridement to achieve the desired therapeutic outcome.     

A Patient-Centered Vision of Care for ESRD: Dialysis as a Bridging Treatment or as a Final Destination?

The ESRD population is heterogeneous, including patients without severe comorbidity for whom dialysis is a bridge to transplantation or a long-term maintenance treatment, as well as patients with a limited life expectancy as a result of advanced age or severe comorbidity for whom dialysis will be the final treatment destination. The complex medical and social context of this latter group fits poorly in the homogeneous, disease-centered, and process-driven approach of many clinical practice guidelines for dialysis. In this commentary, we argue that the standards of treatment allocated to each individual patient should be defined not merely by his or her disease state, but also by his or her preferences and prognosis. In this more patient-centered approach, three attainable treatment goals with a corresponding therapeutic approach could be defined: (1) dialysis as bridging or long-term maintenance treatment, (2) dialysis as final treatment destination, and (3) active medical management without dialysis. For patients with a better overall prognosis, this approach will emphasize complication prevention and long-term survival. For patients with a limited overall prognosis, strictly disease-centered interventions often impose a treatment burden that does not translate into a proportional improvement in quantity or quality of life. For these patients, a patient-centered approach will place more emphasis on palliative management strategies that are less disease specific.     

Effect of Costus igneus stem extract on calcium oxalate urolithiasis in albino rats

The effects of aqueous and ethanolic extracts of Costus igneus (stem) and isolated compounds lupeol and stigmasterol on calcium oxalate urolithiasis have been studied in male albino Wistar rats. Ethylene glycol feeding resulted in hyperoxaluria as well as increased renal excretion of calcium and oxalate. The increased deposition of stone-forming constituents in the urine, serum, and kidney homogenate of urolithic rats was significantly (p?<?0.05) lowered by treatment using aqueous and ethanolic extracts of C. igneus (stem), and isolated compounds lupeol and stigmasterol. The calcium oxalate crystal deposition in the kidney was significantly greater in ethylene glycol-induced urolithic rats. After administration of aqueous and ethanolic extract of C. igneus, the deposition of calcium and oxalate was significantly lowered. Treatment with lupeol and stigmasterol significantly reduced the deposition of calcium and oxalate in the kidney, and also in the blood serum; the lipid profile serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels at 50 and 100?mg/kg were significantly (p?<?0.05) lowered in urolithiatic rats. From this study, we conclude that both the treatments with aqueous and ethanolic extract of C. igneus (stem) and isolated compounds lupeol and stigmasterol had an inhibitory effect on calcium oxalate urinary stone. Lupeol and stigmasterol were identified from the stem of C. igneus by high-performance thin layer chromatography technique. The isolated compounds were confirmed by Fourier transform infrared (FTIR) and ¹³C NMR spectra.     

Clinical investigational studies for validation of a next-generation sequencing in vitro diagnostic device for cystic fibrosis testing

Purpose: Clinical investigational studies were conducted to demonstrate the accuracy and reproducibility of the Illumina MiSeqDx CF System, a next-generation sequencing (NGS) in vitro diagnostic device for cystic fibrosis testing. Methods: Two NGS assays – a Clinical Sequencing Assay (Sequencing Assay) and a 139-Variant Assay (Variant Assay) – were evaluated in both an Accuracy Study and a Reproducibility Study, with comparison to bi-directional Sanger sequencing and PCR as reference methods. For each study, positive agreement (PA), negative agreement (NA), and overall agreement (OA) were evaluated. Results: In the Accuracy Study, the Sequencing Assay achieved PA of 99.7% including the polyTG/polyT region and PA of 100% excluding the region. The Variant Assay achieved PA of 100%. NA and OA were >99.99% for both Assays. In the Reproducibility Study, the Sequencing Assay achieved PA of 99.2%; NA and OA were both 99.7%. The Variant Assay achieved PA of 99.8%; NA and OA were both 99.9%. Sample pass rates were 99.7% in both studies for both assays. Conclusion: This is the first systematic evaluation of a NGS platform for broad clinical use as an in vitro diagnostic, including accuracy validation with multiple reference methods and reproducibility validation at multiple clinical sites. These NGS-based Assays had accurate and reproducible results which were comparable to or better than other methods currently in clinical use for clinical genetic testing of cystic fibrosis.     

Equal 3-Year Outcomes for Kidney Transplantation Alone in HCV-Positive Patients With Cirrhosis

Kidney transplantation alone in clinically compensated patients with cirrhosis is not well documented. Current guidelines list cirrhosis as a contraindication for kidney transplantation alone. This is an Institutional Review Board–approved retrospective study. We report our experience with a retrospective comparison between transplants in hepatitis C virus–positive (HCV⁺) patients without cirrhosis and HCV⁺ patients with cirrhosis. All of the patients were followed for at least a full 3-year period. All of the deaths and graft losses were recorded and analyzed using Kaplan-Meier methodology. One- and three-year cumulative patient survival rates for noncirrhotic patients were 91% and 82%, respectively. For cirrhotic patients, one- and three-year cumulative patient survival rates were 100% and 83%, respectively (P = NS). One- and three-year cumulative graft survival rates censored for death were 94% and 81%, and 95% and 82% for the noncirrhosis and cirrhosis groups, respectively (P = NS). Comparable patient and allograft survival rates were observed when standard kidney allograft recipients were analyzed separately. This study is the longest follow-up document in the literature showing that HCV⁺ clinically ompensated patients with cirrhosis may undergo kidney transplantation alone as a safe and viable practice.Key words: Kidney, Transplantation, Cirrhotic patients, SafetyHepatitis C virus (HCV) affects 200 million people.¹ Approximately 85% of people with HCV will develop chronic infection; of those, 10% to 30% will develop cirrhosis. The prevalence of HCV within the dialysis population is as high as 13%.² HCV is a negative prognostic indicator for survival on dialysis and after kidney transplantation. There is an increased risk of death among long-term hemodialysis patients infected with HCV.³ Importantly, overall survival in these patients is improved after kidney transplantation compared with dialysis.⁴ Liver biopsies are indicated in all HCV-positive candidates considered for kidney transplantation. Up to 12% of asymptomatic patients will have cirrhosis. Those with cirrhosis (while on dialysis) have a 35% higher death rate than their counterparts without cirrhosis.⁵Established cirrhosis is an important predictor of death after renal transplantation and is considered a relative contraindication to isolated renal transplantation. American Association for Study of Liver Disease (AASLD) guidelines recommend end-stage renal disease patients with cirrhosis be evaluated for dual-organ transplantation. The core curriculum in nephrology and the Kidney Disease: Improving Global Outcomes (KDIGO) initiative consider HCV-related cirrhosis a contraindication to kidney transplantation alone (KTA).^6,7 Some authors consider cirrhosis a relative contraindication for KTA because the prospect of survival for graft and patient is dismal.⁸The use of KTA in asymptomatic patients with cirrhosis has not been extensively studied. Reports often exclude patients with cirrhosis,⁹ are limited by small numbers, or combine clinically compensated patients with cirrhosis with those who have only mild fibrosis.¹⁰ The United Network for Organ Sharing (UNOS) database does not track biopsy results, so registry data cannot be mined.We performed 18 KTAs on clinically compensated patients with cirrhosis (CCCs) and compared the results to those from a control group of HCV-positive KTA recipients without cirrhosis. We surmised that the results would be equivalent between groups.     

Detection of thyrotropin-receptor messenger ribonucleic acid (mRNA) and thyroglobulin mRNA transcripts in peripheral blood of patients with thyroid disease: sensitive and specific markers for thyroid cancer

Because thyroid cancer cells express functional TSH receptors (TSHR), TSHR-mRNA in peripheral blood might serve as a tissue-/cancer-specific marker. We measured circulating TSHR-mRNA by RT-PCR in 51 normal controls, 27 patients with benign thyroid disease, 67 patients with treated differentiated thyroid cancer (DTC), and eight patients with newly diagnosed DTC, preoperatively. Results were compared with thyroglobulin (Tg) mRNA and serum Tg levels. TSHR-mRNA signals were not detected in normal controls and in 24 of 27 (89%) patients with benign thyroid disease. All 19 patients with treated DTC with evidence of distant or local disease tested positive for TSHR-mRNA (sensitivity 100%). Among patients with no evidence of disease, TSHR-mRNA was detected in 1 in 48 (specificity 98%). Six of the eight newly diagnosed DTC patients tested preoperatively were positive for TSHR-mRNA. The concordance between TSHR-mRNA and Tg-mRNA and between TSHR-mRNA and serum Tg was 95%. Fourteen patients with DTC (21%) had Tg antibodies, three with local disease (all positive for TSHR-mRNA), and 11 with no evidence of disease (all negative for TSHR-mRNA).Our results indicate that TSHR-mRNA and/or Tg-mRNA in peripheral blood are both equally sensitive and specific markers for monitoring thyroid cancer patients. Their principal value resides in the Tg antibody-positive patients in whom a positive or a negative mRNA value might have indicated or obviated the need for a whole-body scan. Furthermore, the high specificity combined with their ability to predict thyroid cancer preoperatively suggests a potential role in detecting thyroid cancer in patients with thyroid nodules.     

Cardioversion: What to choose? Etomidate or propofol

Context:

Electrical cardioversion is a short painful procedure to regain normal sinus rhythm requiring anaesthesia for haemodynamic stability, sedation, analgesia and early recovery.

Aims:

To compare propofol and etomidate as sedatives during cardioversion.

Settings and Design:

Single centred, prospective and randomized single blind study comprising 60 patients.

Subjects and Methods:

Patients more than 18 years, American Society of Anesthesiologists I/II/III grades undergoing elective cardioversion, randomly divided to receive propofol 1 mg/kg intravenous (IV) bolus followed by 0.5 mg/kg (Group P, n = 30) or etomidate (Group E, n = 30) 0.1 mg/kg followed by 0.05 mg/kg. All patients received IV fentanyl (1 μg/kg) before procedure. Heart rate, blood pressure (BP) (systolic BP [SBP], diastolic BP [DBP], mean arterial pressure), respiratory rate, Aldrete recovery score (ARS) and Ramsay sedation score (RSS) were assessed at 1, 2, 5, 10, 15, 20 and 30 min post cardioversion. Incidence of hypotension, respiratory depression and side effects were compared.

Statistical analysis used:

Student''s unpaired t-test, Chi-square test and Mann–Whitney test. P < 0.05 was taken as significant.

Results:

Group P showed significant fall in SBP, DBP, and mean BP at 2 min after cardioversion. Hypotension (33.3% Group P vs. 16.65% Group E) occurred more with propofol (P < 0.05). Group E showed better ARS at 1, 2, 5, 10, 15 and 20 min. Time required to attain RSS = 2 (659.1 s Group P and 435.7 s Group E) indicated longer recovery with propofol. Left atrial size (35.5-42.5 mm) did not affect success rate of cardioversion (80% Group P vs. 83.3% Group E). Incidence of myoclonus (Group E 26.67% vs. Group P 0%) showed significant difference.

Conclusions:

Etomidate/fentanyl is superior over propofol/fentanyl during cardioversion for quick recovery and haemodynamic stability.