Impact of stereotactic body radiation therapy on geriatric assessment and management for older patients with head and neck cancer using G8

PurposeManagement of head and neck cancers (HNC) in older adults is a common but challenging clinical scenario. We assess the impact of Stereotactic Body Radiation Therapy (SBRT) on survival utilizing the Geriatric-8 (G8) questionnaire.Materials and methods171 HNC patients, deemed medically unfit for definitive treatment, were treated with SBRT ± systemic therapy. G8 questionnaires were collected at baseline, at 4–6 weeks, and at 2–3 months post-treatment. Patients were stratified according to their baseline G8 score: <11 as ‘vulnerable’, 11–14 as ‘intermediate’, and >14 as ‘fit’. Overall survival (OS) was assessed through univariate Kaplan Meier analysis. Repeated measures ANOVA was used to determine if baseline characteristics affected G8 score changes.ResultsMedian follow-up was seventeen months. 60% of patients presented with recurrent HNC, 30% with untreated HNC primaries, and 10% with metastatic non-HNC primaries. Median age was 75 years. Median Charlson Comorbidity Index score was 2. 51% of patients were ‘vulnerable’, 37% were ‘intermediate’, and 12% were ‘fit' at baseline, with median survival of 13.2, 24.3, and 41.0 months, respectively (p = .004). Patients who saw a decrease in their follow-up G8 score (n = 69) had significantly lower survival than patients who had stable or increased follow-up G8 scores (n = 102), with median survival of 8.6 vs 36.0 months (p < .001).ConclusionThe G8 questionnaire may be a useful tool in upfront treatment decision-making to predict prognosis and prevent older patients from receiving inappropriate anti-cancer treatment. Decline in follow-up G8 scores may also predict worse survival and aid in goals of care following treatment.     

Monstrous gout devastating hands and feet

Clinical Rheumatology -     

Silicone rubber mould cast polyethylmethacrylate-hydroxyapatite plate used for repairing a large skull defect.

INTRODUCTION: Reconstruction of the cranial vault is performed for various reasons and precise repair of the defect is important. A modified method of cranioplasty is presented using three-dimensional (3D) models and polyethylmethacrylate mixed with hydroxyapatite, cast in a silicone rubber mould. PATIENT AND METHOD: A large custom made cranial implant was produced using data acquired from 3D computer tomography, rapid prototyping and cast in a silicone rubber mould. This plate was then applied to a 53 year-old man who had undergone a decompressive fronto-parieto-temporo-occipital craniotomy. The bone flap had been lost due to infection. The cranioplasty was performed at 1 year after the initial operation. RESULTS: The cranial plate fitted precisely into the defect and needed no correction at the time of surgery. The stability of the reconstruction plate was increased by the presence of thin margins allowed by silicone rubber elasticity. No complications occurred and the final functional and aesthetic results were good. CONCLUSION: The use of 3D imaging and rapid prototyping allow precise repair of large skull defects, with good aesthetic and functional results. At the same time, silicone rubber moulds permit the production of very thin details needed not only for cosmetic reasons but for reconstruction plate stability as well.     

Preliminary data of a prospective clinical study on the Osseotite NT implant: 18-month follow-up

PURPOSE: This article provides preliminary clinical results on the Osseotite NT implant, which was developed to simplify surgical procedure and cover an extended range of indications. Placement characteristics of NT and standard Osseotite implants were also compared in an in vitro study. MATERIALS AND METHODS: The in vitro placement characteristics of NT and standard Osseotite implants of 4.0 mm diameter and 8.5 to 15 mm in length were compared. In addition, a total of 182 NT implants (96 maxillary and 86 mandibular) were placed in 92 patients; of these, 87.9% were placed using a 1-stage technique. The implants were placed in healed sites (43.9%), fresh extraction sockets (37.4%), or recent extraction sites (2 months postextraction) (18.7%). Before restoration, healing times of 3 to 4 months in the mandible and 5 to 6 months in the maxilla were allowed. The entered implant length in the osteotomy site before contacting the bony walls (EILOS) was compared, as well as the number of turns and the time required to seat the implants. Cumulative survival rates (CSRs) were calculated for up to 18 months of follow-up after surgery. RESULTS: The EILOS was between 47.3% and 57.6% of implant length for the NT implants; for the standard implants, it was between 12.0% and 21.2%. With the NT implants, the number of turns and the placement time were reduced by 61% to 64% and 61% to 65%, respectively. In the clinical study, 4 implants failed during the healing period; none failed after prosthesis placement. The CSR was 97.79% for implants placed into fresh or recent extraction sites; in healed sites, the CSR was 98.75%. The cumulative prosthetic success rate was 100%. DISCUSSION: This new implant design is seated with special drills; the drilling sequence requires less time and less torque than that used for standard implants. The low failure rate after prosthetic loading was consistent with that observed for standard Osseotite implants. CONCLUSION: These preliminary data suggest that the NT implant can be predictable in healed sites and fresh or relatively recent extraction sockets.     

Distribution of Anopheles daciae and other Anopheles maculipennis complex species in Serbia

Parasitology Research - Malaria is one of the most severe health problems facing the world today. Until the mid-twentieth century, Europe was an endemic area of malaria, with the Balkan countries...     

In vitro selection of resistance in Haemophilus influenzae by amoxicillin-clavulanate,cefpodoxime, cefprozil,azithromycin, and clarithromycin

Abilities of amoxicillin-clavulanate, cefpodoxime, cefprozil, azithromycin, and clarithromycin to select resistant mutants of Haemophilus influenzae were tested by multistep and single-step methodologies. For multistep studies, 10 random strains were tested: 5 of these were beta-lactamase positive. After 50 daily subcultures in amoxicillin-clavulanate, MICs did not increase more than fourfold. However, cefprozil MICs increased eightfold for one strain. Clarithromycin and azithromycin gave a >4-fold increase in 8 and 10 strains after 14 to 46 and 20 to 50 days, respectively. Mutants selected by clarithromycin and azithromycin were associated with mutations in 23S rRNA and ribosomal proteins L4 and L22. Three mutants selected by clarithromycin or azithromycin had alterations in ribosomal protein L4, while five had alterations in ribosomal protein L22. Two mutants selected by azithromycin had mutations in the gene encoding 23S rRNA: one at position 2058 and the other at position 2059 (Escherichia coli numbering), with replacement of A by G. One clone selected by clarithromycin became hypersusceptible to macrolides. In single-step studies azithromycin and clarithromycin had the highest mutation rates, while amoxicillin-clavulanate had the lowest. All resistant clones were identical to parents as observed by pulsed-field gel electrophoresis. The MICs of azithromycin for azithromycin-resistant clones were 16 to >128 micro g/ml, and those of clarithromycin for clarithromycin-resistant clones were 32 to >128 micro g/ml in multistep studies. For strains selected by azithromycin, the MICs of clarithromycin were high and vice versa. After 50 daily subcultures in the presence of drugs, MICs of amoxicillin-clavulanate and cefpodoxime against H. influenzae did not rise more than fourfold, in contrast to cefprozil, azithromycin, and clarithromycin, whose MICs rose to variable degrees.     

Unraveling the mode of action of the antimalarial choline analog G25 in Plasmodium falciparum and Saccharomyces cerevisiae

Pharmacological studies have indicated that the choline analog G25 is a potent inhibitor of Plasmodium falciparum growth in vitro and in vivo. Although choline transport has been suggested to be the target of G25, the exact mode of action of this compound is not known. Here we show that, similar to its effects on P. falciparum, G25 prevents choline entry into Saccharomyces cerevisiae cells and inhibits S. cerevisiae growth. However, we show that the uptake of this compound is not mediated by the choline carrier Hnm1. An hnm1Delta yeast mutant, which lacks the only choline transporter gene HNM1, was not altered in the transport of a labeled analog of this compound. Eleven yeast mutants lacking genes involved in different steps of phospholipid biosynthesis were analyzed for their sensitivity to G25. Four mutants affected in the de novo cytidyldiphosphate-choline-dependent phosphatidylcholine biosynthetic pathway and, surprisingly, a mutant strain lacking the phosphatidylserine decarboxylase-encoding gene PSD1 (but not PSD2) were found to be highly resistant to this compound. Based on these data for S. cerevisiae, labeling studies in P. falciparum were performed to examine the effect of G25 on the biosynthetic pathways of the major phospholipids phosphatidylcholine and phosphatidylethanolamine. Labeling studies in P. falciparum and in vitro studies with recombinant P. falciparum phosphatidylserine decarboxylase further supported the inhibition of both the de novo phosphatidylcholine metabolic pathway and the synthesis of phosphatidylethanolamine from phosphatidylserine. Together, our data indicate that G25 specifically targets the pathways for synthesis of the two major phospholipids, phosphatidylcholine and phosphatidylethanolamine, to exert its antimalarial activity.