Immunocryosurgery for basal cell carcinoma: results of a pilot, prospective, open-label study of cryosurgery during continued imiquimod application

Background/aim  Theoretical considerations support the combination of cryosurgery and topical imiquimod to treat basal cell carcinomas (BCC). The aim of the present study was to test the feasibility and efficacy of 'cryosurgery during continued imiquimod application' ('immunocryosurgery') to treat 'high-risk-for-recurrence' BCCs.
Methods  Thirteen patients with 21 biopsy-proven tumours (4 of 21 relapses after prior surgery) were included. After 2–5 weeks (median, 3) of daily 5% imiquimod cream application, the tumours were treated by liquid N₂ cryosurgery (spray, two cycles, 10–20 s) and imiquimod was continued for additional 2–12 weeks (median, 4). The outcome after at least 18 months of follow-up (18–24 months) is currently reported.
Results  Nineteen of 21 tumours responded promptly to immunocryosurgery; two tumours required additional treatment cycles to clear. Thus, the clinical clearance rate was 100%. Only 1 of 21(5%) tumour relapsed after at least 18 months of follow-up (cumulative efficacy: 95%).
Conclusions  'Immunocryosurgery' is a promising non-surgical combination modality to treat 'high-risk-for-recurrence BCCs'. Initial evidence is suggestive of an at least additive effect of the two combined modalities. Further studies comparing immunocryosurgery directly with cryosurgery and imiquimod monotherapies will confirm the reported results.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

Neurocysticercosis in radiographically imaged seizure patients in U.S. emergency departments

Neurocysticercosis appears to be on the rise in the United States, based on immigration patterns and published cases series, including reports of domestic acquisition. We used a collaborative network of U.S. emergency departments to characterize the epidemiology of neurocysticercosis in seizure patients. Data were collected prospectively at 11 university-affiliated, geographically diverse, urban U.S. emergency departments from July 1996 to September 1998. Patients with a seizure who underwent neuroimaging were included. Of the 1,801 patients enrolled in the study, 38 (2.1%) had seizures attributable to neurocysticercosis. The disease was detected in 9 of the 11 sites and was associated with Hispanic ethnicity, immigrant status, and exposure to areas where neurocysticercosis is endemic. This disease appears to be widely distributed and highly prevalent in certain populations (e.g., Hispanic patients) and areas (e.g., Southwest).     

Impact of body mass index on fasting blood glucose concentration among Helicobater pylori carriers

BACKGROUND/AIMS: Despite the fact that Helicobacter pylori (Hp) is regarded as a major gastroduodenal pathogen, it has recently been suggested to be an important factor for non-gastroenterologic conditions such as diabetes mellitus. Accordingly, it seems that Hp infection may have implications in glycemic control and in fasting plasma glucose concentrations. As overnutrition and obesity are directly related to impaired glucose tolerance, the aim of the present study was to determine whether Hp infection leads to alterations in fasting plasma glucose concentrations of Hp carriers and especially in relation to their body mass index. METHODS: Serum was obtained from 224 young, male navy recruits. An enzyme-linked immunosorbent assay to detect Hp-specific IgG serum antibodies as well as gastroscopy along with biopsy was used to identify the infected individuals. Serum levels of glucose, urea, creatinine and uric acid were also determined. Non-fasting subjects and persons with abnormal oral glucose tolerance curve test were excluded. RESULTS: Among Hp-positive individuals, obese persons presented with a significantly lower mean blood glucose level than non-obese persons. Obese Hp-contaminated participants had significantly lower mean fasting blood glucose concentrations as well as a significantly smaller percentage of participants with abnormal elevated blood glucose levels than obese participants negative to Hp infection. CONCLUSIONS: Our data suggest that obesity in combination with Hp infection may induce an enhanced response to insulin leading to reduced fasting blood glucose levels, among Hp-positive obese persons in comparison to Hp-positive lean persons.     

A cohort study on Helicobacter pylori serology before and after induction in the Hellenic Navy

BACKGROUND AND AIMS: To determine whether military personnel are at increased risk of Helicobacter pylori (HP) infection in proportion to their occupation during their national service in the armed forces. MATERIALS AND METHODS: Serum samples were obtained from 142 young male Hellenic Navy recruits (mean age, 23.6 years; range, 20-30 years). The first specimen was obtained during their induction into the Hellenic Navy, and the second was obtained after having served for 8 months in different services within Greece. An enzyme-linked immunosorbent assay was used to detect HP-specific immunoglobulin G antibodies. Statistical analysis was performed using the sign test, logistic regression, and the chi 2 test. RESULTS: The crude seropositivity rate increased from 19.01% to 28.16% (p = 0.007). Of the 115 initially seronegative subjects, 17 (14.8%) seroconverted. The most important predictive variable for seroconversion was deployment in a crowded commission (> 20 subjects) combined with the absence of air conditioning in personnel sleeping quarters (p = 0.03, odds ratio = 3.14). CONCLUSION: Our data suggest that the risk of HP infection increases among 20- to 30-year-old individuals during their national service. Degrading environmental conditions may play a major role in HP transmission between young adults who serve in the armed forces.     

检查前用药可降低乳腺钼钯X线检查中的不适

目的验证乳腺钼钯X线检查前给予对乙酰氨基酚、布洛酚和(或)4%利多卡因凝胶能否减轻检查不适或提高普查中有恐惧感妇女的满意度。方法本前瞻性研究为     

A Systematic Review and Network Meta-Analysis to Evaluate the Comparative Efficacy of Interventions for Unfit Patients with Chronic Lymphocytic Leukemia

Introduction

Rituximab plus fludarabine and cyclophosphamide (RFC) is the standard of care for fit patients with untreated chronic lymphocytic leukemia (CLL); however, its use is limited in ‘unfit’ (co-morbid and/or full-dose F-ineligible) patients due to its toxicity profile. We conducted a systematic review and Bayesian network meta-analysis (NMA) to determine the relative efficacy of commercially available interventions for the first-line treatment of unfit CLL patients.

Methods

For inclusion in the NMA, studies had to be linked via common treatment comparators, report progression-free survival (PFS), and/or overall survival (OS), and meet at least one of the five inclusion criteria: median cumulative illness score >6, median creatinine clearance ≤70 mL/min, existing co-morbidities, median age ≥70 years, and no full-dose F in the comparator arm. A manual review, validated by external experts, of all studies that met at least one of these criteria was also performed to confirm that they evaluated first-line therapeutic options for unfit patients with CLL.

Results

In unfit patients, the main NMA (five studies for PFS and four for OS) demonstrated clear preference in terms of PFS for obinutuzumab + chlorambucil (G-Clb) versus rituximab + chlorambucil (R-Clb), ofatumumab + chlorambucil (O-Clb), fludarabine and chlorambucil (median hazard ratios [HRs] 0.43, 0.33, 0.20, and 0.19, respectively), and a trend for better efficacy versus rituximab + bendamustine (R-Benda) and RFC-Lite (median HR 0.81 and 0.88, respectively). OS results were generally consistent with PFS data, (median HR 0.48, 0.53, and 0.81, respectively) for G-Clb versus Clb, O-Clb, and R-Clb 0.35 and 0.81 versus F and R-Benda, respectively); however, the OS findings were associated with higher uncertainty. Treatment ranking reflected improved PFS and OS with G-Clb over other treatment strategies (median rank of one for both endpoints).

Conclusion

G-Clb is likely to show superior efficacy to other treatment options selected in our NMA for unfit treatment-naïve patients with CLL.

Funding

F. Hoffmann-La Roche Ltd.