Thrasivoulos-George Tzellos

The International Criteria for Behcet's Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria

Behçets disease (BD) is a chronic, relapsing, inflammatory vascular disease with no pathognomonic test. Low sensitivity of the currently applied International Study Group (ISG) clinical diagnostic criteria led to their reassessment.

Re‐evaluation of the risk for major adverse cardiovascular events in patients treated with anti‐IL‐12/23 biological agents for chronic plaque psoriasis: a meta‐analysis of randomized controlled trials

Objective  To detect a detrimental or beneficial effect of anti‐IL‐12/23 biological agents (ustekinumab and briakinumab) for the treatment of chronic plaque psoriasis on major adverse cardiovascular events (MACEs).

Extrinsic ageing in the human skin is associated with alterations in the expression of hyaluronic acid and its metabolizing enzymes

Abstract:  Extrinsic skin ageing or ‘photoageing’, as opposed to intrinsic skin ageing, is the result of exposure to external factors, mainly ultraviolet irradiation. Glycosaminoglycans (GAG) and particularly hyaluronic acid (HA) are major components of the cutaneous extracellular matrix involved in tissue repair. However, their involvement in extrinsic skin ageing remains elusive. In this study, we investigated the expression of HA and its metabolizing enzymes in photoexposed and photoprotected human skin tissue specimens, obtained from the same patient. Total GAG were isolated, characterized using specific GAG‐degrading enzymes and separated by electrophoresis on cellulose acetate membranes and polyacrylamide gels. Quantitation of HA in total GAG was performed using ELISA. Gene expression of hyaluronan synthases (HAS), hyaluronidases (HYAL) and HA receptors CD44 and receptor for HA‐mediated motility (RHAMM) was assessed by RT‐PCR. We detected a significant increase in the expression of HA, of lower molecular mass, in photoexposed skin as compared with photoprotected skin. This increase was associated with a significant decrease in the expression of HAS1 and an increase in the expression of HYAL1‐3. Furthermore, the expression of HA receptors CD44 and RHAMM was significantly downregulated in photoexposed as compared with photoprotected skin. These findings indicate that extrinsic skin ageing is characterized by distinct homoeostasis of HA. The elucidation of the role of HA homoeostasis in extrinsic skin ageing may offer an additional approach in handling cutaneous ageing.

Efficacy, safety and tolerability of green tea catechins in the treatment of external anogenital warts: a systematic review and meta-analysis.

Background  External anogenital warts (EGWs) are non‐malignant skin tumours caused by human papillomavirus. They are one of the fastest growing sexually transmitted diseases. Current treatments are unsatisfactory. Green tea sinecatechin Polyphenon E ointment is a botanical extract from green tea leaves exhibiting anti‐oxidant, anti‐viral and anti‐tumour properties.

The facial skeleton in patients with osteoporosis: a field for disease signs and treatment complications.

Osteoporosis affects all bones, including those of the facial skeleton. To date the facial bones have not drawn much attention due to the minimal probability of morbid fractures. Hearing and dentition loss due to osteoporosis has been reported. New research findings suggest that radiologic examination of the facial skeleton can be a cost-effective adjunct to complement the early diagnosis and the follow up of osteoporosis patients. Bone-mass preservation treatments have been associated with osteomyelitis of the jawbones, a condition commonly described as osteonecrosis of the jaws (ONJ). The facial skeleton, where alimentary tract mucosa attaches directly to periosteum and teeth which lie in their sockets of alveolar bone, is an area unique for the early detection of osteoporosis but also for the prevention of treatment-associated complications. We review facial bone involvement in patients with osteoporosis and we present data that make the multidisciplinary approach of these patients more appealing for both practitioners and dentists. With regard to ONJ, a tabular summary with currently available evidence is provided to facilitate multidisciplinary practice coordination for the treatment of patients receiving bisphosphonates.

An Evidence-Based Review of Risk-Reductive Strategies for Osteonecrosis of the Jaws Among Cancer Patients

PURPOSE Bone antiresorptive treatment is associated with osteonecrosis of the jaws. Interventions used to treat this complication are diverse, controversial, and largely empirical but certain risk factors could help in its avoidance. The aim of this evidence-based review is to elucidate any interventions that are effective in reducing the risk for development of ONJ in cancer patients receiving bone antiresorptive therapy and to quantify the effectiveness of such interventions. MATERIALS & METHODS We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and other trial registries through January 2012. We selected randomized controlled trials (RCTs). Cohort studies were included only as long as there are no RCTs on the same modality. RESULTS Twelve studies were included in the systematic review while nine studies contributed to the various comparisons. Prescribing denosumab (DSB) instead of zoledronic acid (ZA) may not be expected to reduce risk ONJ (RR:0.71 [99% CI: 0.41-1.24], I2=0%). Prescribing clodronate (RR:10.15 [99% CI: 2.43-42.35], I2=0%) or pamidronate (RR:4.41 [99% CI: 1.90-10.24], I2=16%) instead of ZA may reduce risk for ONJ. Dental extractions remain the most potent risk factor for ONJ (RR:14.04, [99% CI: 10.36-19.03], I2=0%) and their avoidance can be considered an effective risk-reductive intervention. ONJ risk can be reduced by dental prophylactic measures (RR:0.45, [99% CI: 0.23-0.85], I2=7%). CONCLUSIONS DSB and ZA might cause ONJ more frequently compared with chlodornate or pamidronate. Prescription pamidronate and clodronate helps avoid the complication. Reducing the administered dose for denosumab and zoledronic acid might reduce risk for ONJ as well. More randomized clinical trials comparing reduced doses of these regimens against those currently approved are needed.

Nodular basal cell carcinoma is associated with increased hyaluronan homeostasis

Background  Basal cell carcinoma (BCC) is one of the most frequent forms of malignancy in humans. Although BCC is a tumour of low degree of malignancy, if left untreated, it can be locally aggressive, eat away at tissues and cause ulceration. Nodular is the most common subtype of BCC (>50%). Although apparently non‐invasive, micronodular, a certain subgroup of nodular, is likely to recur. Glycosaminoglycans (GAGs), such as hyaluronic acid (HA), are extracellular matrix molecules of high importance in malignant transformation, metastasis and other complex remodelling processes.

Denosumab in castration-resistant prostate cancer

www.thelancet.com Vol 379 May 12, 2012 e50 Submissions should be made via our electronic submission system at http://ees.elsevier.com/ thelancet/ because the benefi ts or harms are determined irrespective of treatment duration. By use of this approach, NNT for bone-metastasis-free survival (where the event is bone metastasis or death) was 21·4 (1/[(370 placebo events/1134·2 placebo patient-years)– (335 denosu mab events/1198·2 denosumab patient-years)]) and NNH for osteo necrosis of the jaw was 38·0 (1/[(33/1254·7)– (0/1206·4)]). On the basis of these calculations, the NNH for osteonecrosis of the jaw is almost twice the NNT for bone-metastasisfree survival, consistent with a favourable benefi t:risk profi le. Additionally, NNT/NNH methods do not take into account any qualitative diff erences between the benefi t and the harm. Bone metastases are irreversible, life-changing events that are systemic in nature, associated with progressive and signifi cant morbidity, and trigger initiation of systemic antineoplastic treatments such as chemotherapy, immune therapy, or second-line hormonal therapy. Osteonecrosis of the jaw is a localised event, and in our study was generally mild to moderate in severity. In patients who developed osteo necrosis of the jaw, no discernible worsening in patient-reported outcomes, including pain, were noted throughout the development of the event, and, by contrast with the statements made by Kyrgidis and Tzellos, dental interventions to treat osteo necrosis of the jaw did not usually require hospital admission. At the time our trial was started, whether denosumab was associated with osteonecrosis of the jaw was not known. Comprehensive measures to detect and adjudicate osteonecrosis of the jaw were put in place, but with no specifi c requirement for preventive dentistry. In accordance with current guidelines for treatment with antiresorptive therapies, patients should have appropriate preventative dentistry before treatment initiation, and maintain good oral hygiene and Denosumab in castration-resistant prostate cancer

p16 post-hoc analyses and Simpson's paradox.

www.thelancet.com/oncology Vol 14 October 2013 e436 2 Abr amsen N, Kelsey S, Safar P, Sutten-Tyrrell K. Simpson’s paradox and clinical trials: What you fi nd is not necessarily what you prove. Ann Emerg Med 1992; 21: 1480–82. 3 Wag ner CH. Simpson’s paradox in real life. Am Stat 1982; 36: 46–48. 4 Ver morken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008; 359: 1116–27. 5 Yus uf S, Wittes J, Probstfi eld J, Tyroler HA. Analysis and interpretation of treatment eff ects in subgroups of patients in randomized clinical trials. JAMA 1991; 266: 93–98. stratifi cation by the Karnosfk sy score, with a greater proportion of patients with good performance status in EXTREME. We suggest that the reason for the improved outcome in the SPECTRUM study, but also for the higher proportion of patients receiving pre vious chemotherapy, might be the selection of a subgroup of patients with slower disease progression. Such a group would have higher chances of receiving previous chemotherapy (and thus increased rates of such chemotherapy) and could also fare better in overall survival (as these patients did in the p16 negative post-hoc subgroup analyses). Therefore, the result of the post-hoc analyses based on the p16 tumour status might be a result of Simpson’s paradox, with slower disease progression as a plausible confounder. For this reason, medically interesting, data-derived group eff ects should be reported only as post-hoc analyses and without citation of signifi cance levels, so that the resultant hypotheses can be tested in subsequent studies. To exclude this paradox, baseline stratifi cation for p16 tumour status would be required. Vermorken and colleagues discuss that the retrospective analysis of p16 tumour status was prospectively designed (although this design is not reported on ClinicalTrials. gov) and because paraffin-embedded tumour samples were available at baseline, having used this variable in the baseline stratifi cation process would have elucidated this issue.