Response to highly active antiretroviral therapy strongly predicts outcome in patients with AIDS-related lymphoma

BACKGROUND: AIDS-related lymphoma (ARL) remains a frequent complication of HIV infection. We analyzed the outcome of patients with ARL with respect to the use and efficacy of highly active antiretroviral therapy (HAART) and to potential prognostic factors. METHODS: This multicenter cohort study included patients with systemic ARL diagnosed between 1990-2001. We evaluated overall survival and the effects of several variables on overall survival using the Kaplan-Meier method and the extended Cox proportional hazards model. Response to HAART was used as a time-dependent variable and was defined as a CD4 cell count increase of >/= 100 x 106 cells/l and/or at least one viral load < 500 copies/ml during the first 2 years following diagnosis of ARL. RESULTS: Among 203 patients with ARL, median overall survival was 9.0 months [95% confidence interval (CI), 7.6-12.4 months]. In the univariate analyses, age < 60 years, no previous AIDS, CD4 cell counts >/= 200 x 106 cells/l, hemoglobin > 11 g/dl, Ann Arbor stages I-II and A, no extranodal lesion, response to HAART, and complete remission showed statistically significant association with prolonged overall survival. In the multivariate Cox model, the only factors independently associated with overall survival were response to HAART [relative hazard (RH), 0.32; 95% CI, 0.16-0.62], complete remission (RH, 0.24; 95% CI, 0.15-0.36), previous AIDS (RH, 1.92; 95%CI, 1.23-3.01) and extranodal involvement (RH, 2.85; 95% CI, 1.47-5.51). CONCLUSIONS: Efficacy of HAART was independently associated with prolonged survival in this large cohort of patients with ARL. Information on patient's response to HAART is crucial for the evaluation of future treatment strategies.     

Mononeuropathy multiplex and chylothorax as earlier manifestations of pulmonary tuberculosis

Mononeuropathy multiplex (MNM) and chylothorax are rare clinical disorders. The concurrence of these two disorders with Mycobacterium tuberculosis infection has not been reported. We herein report a patient who was initially diagnosed with fever of unknown origin and MNM, and then developed chylothorax. Pulmonary tuberculosis was proved 1 month after chylothorax appeared. With low-dose prednisolone 15 mg day(-1) and anti-tuberculosis drugs, all these disorders completely resolved 1 year later.     

Therapy and prophylaxis of opportunistic infections in HIV-infected patients: a guideline by the German and Austrian AIDS societies (DAIG/ÖAG) (AWMF 055/066)

Introduction

There was a growing need for practical guidelines for the most common OIs in Germany and Austria under consideration of the local epidemiological conditions.

Materials and methods

The German and Austrian AIDS societies developed these guidelines between March 2010 and November 2011. A structured Medline research was performed for 12 diseases, namely Immune reconstitution inflammatory syndrome, Pneumocystis jiroveci pneumonia, cerebral toxoplasmosis, cytomegalovirus manifestations, candidiasis, herpes simplex virus infections, varizella zoster virus infections, progressive multifocal leucencephalopathy, cryptosporidiosis, cryptococcosis, nontuberculosis mycobacteria infections and tuberculosis. Due to the lack of evidence by randomized controlled trials, part of the guidelines reflects expert opinions. The German version was accepted by the German and Austrian AIDS Societies and was previously published by the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF; German Association of the Scientific Medical Societies).

Conclusion

The review presented here is a translation of a short version of the German–Austrian Guidelines of opportunistic infections in HIV patients. These guidelines are well-accepted in a clinical setting in both Germany and Austria. They lead to a similar treatment of a heterogeneous group of patients in these countries.

     

Increased incidence of Leydig cell tumours of the testis in the era of improved imaging techniques

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Leydig cell tumours (LCTs) of the testis are rare tumours, accounting for 1–3% of all testicular neoplasms. Our data indicate that using scrotal ultrasound with high resolution imaging in routine checkups leads to an earlier detection of LCTs. Most patients underwent an organ‐sparing surgery and no androgen deprivation was observed.

OBJECTIVE

? To report an observed high frequency of Leydig cell tumours (LCTs) diagnosed at our centre.

PATIENTS AND METHODS

? Charts of all patients who underwent surgery for a testicular tumour between 1999 and 2008 at our department were searched and data from patients with LCT were collected. ? Before surgery all patients underwent ultrasound and complete staging. In all but two patients with LCT an organ‐sparing surgery was performed. Surgery was performed under ultrasound or palpation guidance. ? All patients underwent postoperative follow‐up. We retrospectively reviewed surgical technique, histology, epidemiology and outcome in all LCT patients.

RESULTS

? In the study period, 197 testicular tumours were surgically removed of which 29 were diagnosed as LCT (14.7% of 197; further study group) in 25 patients. Mean age of patients with LCT was 45 years (range 21–68 years). ? Tumour size ranged from 1.2 to 80 mm (mean 10.23 mm). In two patients (8%) the lesion was palpable whereas incidental diagnosis was made in seven patients (28%). ? In the remaining patients diagnosis was made by ultrasound performed for testicular pain (six patients, 24%) or during infertility or erectile dysfunction evaluation (10 patients, 40%). ? Definitive histology reported no malignant histopathological features in all but one patient; this particular patient experienced tumour progression after 2 months and died from advanced disease 1 year later. All other patients are free of disease after a mean follow up of 56 months (range 7–93 months). ? During this period one patient developed a second LCT on the contralateral side; another patient had a recurrence within the same testicle, but on the opposite pole. Both underwent a subsequent organ‐sparing tumour resection.

CONCLUSION

? The percentage of LCT (14.7% of all testicular tumours removed) was significantly higher than expected from the literature. One possible explanation for this phenomenon is the increasing use of better ultrasound technology and the subsequent increased detection of small nodules that have not been found in historical series. Use of ‘observation‐only’ for very small lesions detected at infertility clinics is under debate.     

FGFR3 mutations in seborrheic keratoses are already present in flat lesions and associated with age and localization.

Somatic activating fibroblast growth factor 3 (FGFR3) mutations in human skin can cause seborrheic keratoses, one of the most frequent skin tumors in man. However, details of the involved mechanisms remain elusive. We analyzed 65 acanthotic seborrheic keratoses with varying vertical diameters for FGFR3 mutations using a SNaPshot multiplex assay. Immunohistochemistry was performed for Ki-67, bcl-2 and FGFR3 protein in all seborrheic keratoses and 19 normal skin samples. FGFR3 mutations were detected in 37 of 65 seborrheic keratoses (57%). These mutations were found both in flat (initial) and thick seborrheic keratoses. FGFR3 mutations were significantly associated with increased age and localization on the head and neck (P<0.01). Ki-67 expression was significantly higher in seborrheic keratoses than in normal epidermis independent of the FGFR3 status (P<0.001). Furthermore, FGFR3 mutations were associated with an increased expression of bcl-2 and FGFR3 protein (P<0.05). Our results indicate that FGFR3 mutations can occur early in the pathogenesis of at least a subset of seborrheic keratoses. Increased age appears to be a risk factor for these mutations. The preferential occurrence of FGFR3 mutations in seborrheic keratoses of the head and neck suggests a causative role for cumulative lifetime ultraviolet light exposure.     

Oxytocin and vasopressin hexapeptide fragments have opposing influences on conditioned freezing behavior.

We investigated the influence of C-terminal fragments of oxytocin (OT) and arginine vasopressin (AVP) on conditioned freezing behavior. Subcutaneous injections of 0.3 microgram AVP(4-9) or OT(4-9) given to rats after shock training or before behavioral observation significantly altered fear-induced freezing behavior. Animals treated with OT hexapeptide froze less than controls, while animals treated with AVP hexapeptide froze more. These results support the concept that the hexapeptide metabolites of oxytocin and vasopressin can selectively modulate certain behavioral processes, and that these peptides have opposite effects on performance in behavioral tests designed to evaluate memory consolidation and retrieval.     

Three-dimensional power Doppler imaging of ovarian stromal blood flow in women with endometriosis undergoing in vitro fertilization.

OBJECTIVE: The aims of this retrospective study were to investigate whether the quantification of ovarian stromal blood flow and/or leptin concentration are predictive of in vitro fertilization (IVF) outcomes in women after laparoscopic ovarian cystectomy for large endometriomas. METHODS: Twenty-two women undergoing IVF after laparoscopic surgery for ovarian endometriomas (> 6 cm) comprised the study group. Twenty-six women with tubal factor infertility constituted the control group. Ovarian stromal blood flow was evaluated by three-dimensional (3D) power Doppler ultrasound imaging using virtual organ computer-aided analysis (VOCAL( trade mark )). Serum and follicular fluid (FF) leptin concentrations were quantified using an enzyme-linked immunosorbent assay kit. RESULTS: There were significantly decreased ovarian stromal blood flow parameters (including vascularization index, flow index (FI), and vascularization flow index) in the endometriosis group without an evident difference in total ovarian volume on the day of human chorionic gonadotropin. The value of FF leptin demonstrated a negative correlation with ovarian stromal FI in the control group, but there was a loss of this effect in the endometriosis group. CONCLUSIONS: Quantification of ovarian stromal blood flow by 3D power Doppler ultrasound in women with endometriosis may provide an important prognostic indicator in those undergoing IVF.     

Clindamycin pharmacokinetics and tissue penetration after head and neck surgery

Penetration of clindamycin into surgical wounds was studied in 10 patients undergoing radical head and neck surgery. Patients received one preoperative and three postoperative intravenous doses of clindamycin 600 mg. During surgery, samples of plasma and sternocleidomastoid muscle were obtained. Additional plasma samples were collected just before the fourth dose of clindamycin, just after that dose was infused, and 1, 2, 4, 6, 8, and 12 hours after dosing. Samples of wound exudate were collected at 2, 4, 6, 8, and 12 hours after the fourth dose. The muscle, plasma, and wound exudate samples were assayed for clindamycin base by a gas-liquid chromatographic method. Plasma and wound exudate samples obtained during surgery and one and eight hours after the fourth dose were assayed by a radial immunodiffusion technique for content of alpha 1-acid glycoprotein (AAG), the major binding protein for clindamycin. Pharmacokinetic values for plasma and wound drainage were calculated and compared. Concentrations of clindamycin in muscle (three to six hours after the first dose) ranged from 0.6 to 5.1 micrograms/g; the ratio of tissue to plasma concentrations ranged from 0.24 to 0.82. The highest mean clindamycin concentration in wound drainage was 4.9 micrograms/mL after the fourth dose, approximately 90% of simultaneous plasma concentrations. Concentrations in wound exudate exceeded those measured in plasma four hours after the dose, and elimination from the wound was slower than from plasma. AAG concentrations in plasma increased from a mean of 89 mg/dL intraoperatively to 134 mg/dL postoperatively. AAG was present in wound exudate in concentrations that were approximately 53% of those observed in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)