Ontogeny of the Vertebral Column of Eleutherodactylus johnstonei (Anura: Eleutherodactylidae) Reveals Heterochronies Relative to Metamorphic Frogs

Over the last century, the morphogenesis of the vertebral column has been considered as a highly conserved process among anurans. This statement is based on the study of few metamorphic taxa, ignoring the role of developmental mechanisms underlying the evolution of specialized life‐histories. Direct development in anurans has been regarded as evolutionarily derived and involves developmental recapitulation and repatterning at different levels in all amphibian taxa studied so far. Herein, we analyze the vertebral column morphogenesis of the direct‐developing frog Eleutherodactylus johnstonei, describing the sequence of chondrification and ossification, based on cleared and double‐stained specimens from early stage embryos to adults. In general, our results show that the morphogenesis of the vertebral column in E. johnstonei recapitulates the ancestral tadpole‐like pattern of development. However, the analysis of the sequence of events using heterochrony plots shows important heterocronies relative to metamorphic species, such as a delay in the chondrification of the vertebral centra and in osteogenesis. These ontogenetic peculiarities may represent derived traits in direct‐developing frogs and are possibly correlated with its unusual life history. In addition, several features of the vertebral column of E. johnstonei are highly variable from its typical morphology. We report some malformations and small deviations, which do not seem to affect the survival of individuals. These anomalies have also been found in other frogs, and include many vertebral defects, such as vertebral fusion, and vertebral preclusion and/or induction. Anat Rec, 296:00000–#2013, 2013. © 2013 Wiley Periodicals, Inc.     

When to perform bone scan in patients with newly diagnosed prostate cancer: external validation of a novel risk stratification tool

Purpose

To externally validate the performance characteristics of the Briganti’s risk stratification tool for baseline staging bone scan in patients with newly diagnosed prostate cancer (PCa).

Methods

From 2009 onwards, a consecutive series of patients with PCa were enrolled. All patients were staged to evaluate the presence of bone metastasis (BM) with a conventional total-body Tc 99 m MDP scintigraphy performed regardless of baseline PCa characteristics. The area under the curve (AUC) estimates were used to test the accuracy of the Briganti’s risk stratification tool that recommended staging baseline bone scan for patients with a biopsy Gleason score >7 or with a prostate-specific antigen (PSA) >10 ng/ml and palpable disease (cT2/T3). The new tool was compared to the European Association of Urology (EAU) guideline.

Results

A total of 313 patients were consecutively enrolled. Median age was 68 (range 49–95 years), and median PSA was 7 ng/ml (range 0.81–2,670). Twenty (6.4 %) patients presented BMs. Patients with BMs were significantly older, with higher PSA and a higher Gleason score (p = 0.001). The novel Briganti’s model was significantly (p = 0.001) more accurate (AUC: 0.75; CI: 0.632–0.859) than the EAU guideline (AUC: 0.64; CI: 0.52–0.761) for the prediction of BMs.

Conclusions

Our study validated in a group of patients with PCa the novel risk stratification tool proposed by Briganti, which presented a higher accuracy for baseline staging bone scan when compared with the EAU guideline. In our experience, this approach would further reduce (about 60 %) the use of staging baseline bone scan without compromising the ability to detect BMs in patients with PCa.     

The safety and efficacy of high-dose daptomycin combined with rifampicin for the treatment of Gram-positive osteoarticular infections

Purpose

Treatment of Gram-positive osteoarticular infections requires an adequate surgical approach combined with intensive antimicrobial therapy. The aim of this study was to evaluate the safety and efficacy of a combined regimen of high-dose daptomycin and rifampicin, in patients with various types of Gram-positive osteoarticular infections.

Methods

This single centre, non-comparative, prospective study evaluated the safety and efficacy of a combined regimen of intravenous daptomycin (8 mg/kg/day) and oral rifampicin (600 mg/day) in patients with Gram-positive osteoarticular infections, with a minimal follow-up of one year. Creatine phosphokinase, transaminases, bilirubinaemia, and serum creatinine, were measured at baseline and regular intervals.

Results

The median daily doses of daptomycin and rifampicin, administered for a median duration of 21 (range, 10–122) days to 16 patients (median age, 63.5 years; 11 males, five females) presenting with staphylococcal (n = 15) or streptococcal (n = 1) osteoarticular infections, were 8.15 (range, 6.6–8.9) mg/kg/day and 600 (range, 600–900) mg/day, respectively. The combined regimen of daptomycin and rifampicin was well tolerated by all except one patient, without requiring treatment adjustment or discontinuation. One patient developed allergic responses probably due to rifampicin after 42 days. Fifteen (94 %) patients showed favourable clinical and microbiological outcomes.

Conclusions

The combined regimen of high-dose daptomycin and rifampicin was well tolerated and may provide a useful alternative to standard glycopeptide therapy for Gram-positive osteoarticular infections.     

Refractory gastroesophageal reflux disease as diagnosed by impedance-pH monitoring can be cured by laparoscopic fundoplication

Background

Some patients with typical (heartburn/regurgitation) symptoms of gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI) therapy. Impedance-pH monitoring can identify PPI-refractory patients who could benefit from laparoscopic fundoplication, but outcome data are scarce. We aimed to assess whether PPI-refractory GERD as diagnosed by impedance-pH monitoring can be cured by laparoscopic fundoplication.

Methods

Forty-four consecutive GERD patients with heartburn/regurgitation refractory to high-dose PPI therapy entered a 3-year outcome assessment following robot-assisted laparoscopic fundoplication. Preoperative on-PPI impedance-pH diagnostic criteria consisted of positive symptom association probability (SAP)/symptom index (SI), and/or abnormal percentage esophageal acid exposure time (%EAET), and/or abnormal number of total refluxes. GERD cure was defined by 3-year postoperative off-PPI normal impedance-pH findings with persistent symptom remission.

Results

Preoperatively, 24 of 38 (63 %) patients who completed the outcome assessment had a positive SAP/SI, 20 of 38 (53 %) for weakly acidic refluxes; 3 of 38 (8 %) patients had an abnormal %EAET, 11 of 38 (29 %) an abnormal number of total refluxes only. Postoperatively, heartburn/regurgitation recurred in 3 patients; abnormal impedance-pH findings were found in two of them, and they responded to PPI therapy. GERD cure was achieved in 34 of 38 (89 %) patients, 11 of 11 with an abnormal number of total refluxes as the only preoperative abnormal impedance-pH finding. Postoperatively, there was a significant decrease of the %EAET (1 vs. 0.1 %, P = 0.002) and of the number of total refluxes (68 vs. 8, P = 0.001), with the latter finding mainly due to a decrease in the number of weakly acidic refluxes.

Conclusions

Normal reflux parameters and persistent symptom remission at 3-year follow-up can be achieved with laparoscopic fundoplication in the majority of patients with PPI-refractory GERD as diagnosed by impedance-pH monitoring. On-PPI impedance-pH diagnostic criteria should include SAP/SI positivity, an abnormal %EAET, and an abnormal number of total refluxes. Weakly acidic refluxes have a major role in the pathogenesis of PPI-refractory GERD.