Challenges in evaluating surgical innovation

Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures-for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential.

One-year outcomes of repeated adjunctive photodynamic therapy during periodontal maintenance: a proof-of-principle randomized-controlled clinical trial

BACKGROUND: Single photodynamic therapy (PDT) has been effective in initial periodontal therapy, but only improved bleeding on probing (BoP) in maintenance patients after a single use. Repeated PDT has not been addressed. OBJECTIVES: To study the possible added benefits of repeated adjunctive PDT to conventional treatment of residual pockets in patients enrolled in periodontal maintenance. MATERIAL AND METHODS: Ten maintenance patients with 70 residual pockets [probing pocket depth (PPD)>or=5 mm] were randomly assigned for treatment five times in 2 weeks (Days 0, 1, 2, 7, 14) with PDT (test) or non-activated laser (control) following debridement. The primary outcome variable was PPD, and the secondary variables were clinical attachment level (CAL) and BoP. These were assessed at 3, 6 and 12 months following the interventions. RESULTS: Greater PPD reductions were observed in the test (-0.67 +/- 0.34; p=0.01) compared with the control patients (-0.04 +/- 0.33; NS) after 6 months. Significant CAL gain (+0.52 +/- 0.31; p=0.01) was noted for the test, but not in the control (-0.27 +/- 0.52; NS) patients after 6 months. BoP percentages decreased significantly in test (97-64%, 67%, 77%), but not control patients after 3, 6 and 12 months. CONCLUSIONS: Repeated (five times) PDT adjunctive to debridement yielded improved clinical outcomes in residual pockets in maintenance patients. The effects were best documented after 6 months.

Risk of complications after abdominal paracentesis in cirrhotic patients: a prospective study

BACKGROUND ; AIMS: Complications and technical problems of paracentesis in cirrhotic patients are infrequent. However, the severity and the incidence of these events and their risk factors have not been assessed prospectively. METHODS: Cirrhotic patients (n = 171) undergoing paracentesis were included. Of the 515 paracenteses, 8.8% were diagnostic, and 91.2% were therapeutic. Technical features, demographic data, and adverse events during a period of 72 hours after the procedure were examined. RESULTS: Major complications occurred in 1.6% of procedures and included 5 bleedings and 3 infections, resulting in death in 2 cases. Major complications were associated with therapeutic but not diagnostic procedures and tended to be more prevalent in patients with low platelet count (<50 10(9)/L), Child-Pugh stage C, and in alcoholic cirrhosis patients. Technical problems occurred in 5.6%. The most frequent complication was a leak of ascites at the puncture site (5.0%), and in 89.5% there were no complications. CONCLUSIONS: The safety of paracentesis in cirrhotic patients might be decreased if risk factors, which depend on the characteristics of the patient and of the procedure itself, are present.

Haematologic data, iron parameters and molecular findings in two new cases of iron-refractory iron deficiency anaemia

Matriptase-2 (Tmprss6), a type II transmembrane serine protease, has an essential role in iron homoeostasis as a hepcidin regulator. Recently, patients with TMPRSS6 mutations and suffering from iron-refractory iron deficiency anaemia (IRIDA) have been reported. We describe two new cases of IRIDA, one patient of Swiss origin and the second of Italian origin. The first case results from a large deletion of 1054 nucleotides corresponding to an in frame deletion of 30 amino acid residues in the low-density lipoprotein receptor-1/-2 (LDLR-1/-2) domains and from a missense mutation in CUB1 (S304L). In the second case, a homozygous G-->C mutation in the last nucleotide of exon 15 and which modified the consensus sequence of the 5' splice donor site of intron 15 (AGgt-->ACgt) was identified. Both patients had a high hepcidin level and low serum iron and transferrin saturation compared to age-matched controls. Continuous perfusion of i.v. iron 4 h/d x 5 d in the first case resulted in a significant rise in haemoglobin. These new cases of IRIDA illustrate the importance of LDLR-1/-2 and CUB1 domains in matriptase-2 function as well as the role of matriptase-2 in hepcidin regulation. Furthermore a deletional form of TMPRSS6 (in LDLR-1/-2 domains) resulting in IRIDA is described for the first time. These cases reinforce the belief that patients suffering from IRIDA have no specific geographical or ethnic distribution and are sporadic secondary to different mutations of the matriptase-2 gene.

Role of CYP27A1 in progesterone metabolism in vitro and in vivo

In the kidney, progesterone is inactivated to 20alpha-dihydro-progesterone (20alpha-DH-progesterone) to protect the mineralocorticoid receptor from progesterone excess. In an attempt to clone the enzyme with 20alpha-hydroxysteroid activity using expression cloning in CHOP cells and a human kidney expression library, serendipitously cDNA encoding CYP27A1 was isolated. Overexpression of CYP27A1 in CHOP cells decreased progesterone conversion to 20alpha-DH-progesterone in a dose-dependent manner, an effect enhanced by cotransfection with adrenodoxin and adrenodoxin reductase. Incubation of CHOP cells with 27-hydroxycholesterol, a product of CYP27A1, increased the ratio of progesterone/20alpha-DH-progesterone in a concentration-dependent manner, indicating that the effect of CYP27A1 overexpression was mediated by 27-hydroxycholesterol. In order to analyze whether these observations are relevant in vivo, progesterone and 20alpha-DH-progesterone were measured by GC-MS in 24-h urine of CYP27A1 gene knock out (ko) mice and their control wild type (wt) and heterozygote (hz) littermates. In CYP27A1 ko mice, urinary progesterone concentrations were decreased, 20alpha-DH-progesterone increased and the progesterone/20alpha-DH-progesterone ratio decreased threefold (p<0.001). Thus, CYP27A1 modulates progesterone concentrations. The underlying mechanism is inhibition of 20alpha-hydroxysteroid dehydrogenase by 27-hydroxycholesterol. Key words: Progesterone, sterol 27-hydroxylase, 27-hydroxycholesterol, 20a-steroid dehydrogenase, 20a-DH-progesterone.