Efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients: 24-week results of POWER 1

BACKGROUND: The ongoing phase IIb POWER 1 (TMC114-C213) trial is designed to assess efficacy and safety of the protease inhibitor (PI) TMC114 (darunavir) in treatment-experienced HIV-1-infected patients. DESIGN: This randomized, partially blinded, 24-week dose-finding study compared efficacy and safety of four doses of TMC114 plus low-dose ritonavir (TMC114/r) with investigator-selected control PI(s) (CPI[s]). METHODS: Patients with one or more primary PI mutation and HIV RNA > 1000 copies/ml received optimized background therapy, plus TMC114/r 400/100 mg once daily, 800/100 mg once daily, 400/100 mg twice daily or 600/100 mg twice daily, or CPI(s). The primary endpoint (intent-to-treat) compared proportions of patients achieving viral load reduction >or= 1.0 log10 copies/ml from baseline. RESULTS: In total, 318 patients were treated. Baseline mean viral load was 4.48 log10 copies/ml; median CD4 cell count was 179 cells/microl. In the CPI arm 62% of patients discontinued (virological failure: 54%); 10% of TMC114/r patients discontinued. More TMC114/r (69-77%) than CPI patients (25%) reached the primary endpoint (P < 0.001); 43-53% of TMC114/r patients and 18% of the CPI arm achieved viral load < 50 copies/ml (P < 0.001). TMC114/r demonstrated greater mean CD4 cell count increases versus CPI(s) (68-124 versus 20 cells/microl; P < 0.05). TMC114/r 600/100 mg twice daily demonstrated the highest virological and immunological responses. Adverse event incidence was similar between treatments; headache and diarrhoea were more common with CPI(s). CONCLUSIONS: TMC114/r demonstrated statistically higher 24-week virological response rates and CD4 cell count increases than CPI(s). TMC114/r 600/100 mg twice daily has received regulatory approval in treatment-experienced patients.     

Scinticisternography in presenile and senile degenerative disease

86 patients suffering from various senile and presenile degenerative diseases were studied using scinticisternography with In¹¹¹-DTPA. Flow reversal and delayed clearance were observed in 62 of these patients. These alterations, possibly related to the cerebrospinal fluid dynamics, show the aspecificity of the SC picture. The SC picture does not seem to be correlated to the clinical signs.

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Sommario Sono stati sottoposti a scinticisternografia (SC) con In¹¹¹-DTPA 86 pazienti affetti da malattie degenerative del SNC dell'età presenile e senile. Si sono osservati 62 casi con inversione del flusso liquoralee/o ritardata clearance dell'isotopo. Queste alterazioni, probabilmente legate alla dinamica liquorale, evidenziano l'aspecificità dei risultati della SC, i quali non sembrano correlati alla sintomatologia clinica.

     

Accidental pleural puncture by a thoracic epidural catheter

We report the occurrence of an accidental pleural puncture by an epidural catheter that happened during the attempted induction of thoracic epidural anaesthesia using a paramedian approach in an awake patient. The incorrect placement of the catheter was recognised while the patient was undergoing thoracoscopic surgery. The possibility of accidental pleural puncture during attempted thoracic epidural catheter placement by either the paramedian or the midline approach should be borne in mind. A misplaced catheter may injure lung tissue and result in a potentially dangerous intra-operative tension pneumothorax.     

Wisdom teeth in the fracture line]

The evaluation of 139 mandibular fractures with wisdom teeth in the fracture line permits to draw the following conclusions: 1. Partially retained teeth in the fracture line frequently lead to infections. For this reason, they should be removed on principle prior to immobilization. 2. Retained teeth or tooth germs caused in no case an infection; consequently, they must not be removed. 3. Fully erupted teeth produced but occasionally an infection of the fracture line. In such cases, the therapy will depend on the functional value of the respective tooth.     

Primary and secondary heart tumours in dogs and cats

Primary and secondary neoplasms of the canine and feline heart are uncommon. During a 2-year period, 83 dogs suffering from primary cardiac (n=11), extracardiac benign (n=6) or malignant (n=66) tumours and 30 cats with primary cardiac (n=1) or extracardiac (n=29) malignant tumours were examined. Echocardiography revealed four cases of primary cardiac neoplasms in dogs, but secondary heart tumours were not detected. After necropsy, tissue samples from the heart and tumours were examined histologically and immunohistochemically. In dogs, primary neoplasms included seven haemangiosarcomas, two chemodectomas, one rhabdomyosarcoma, and one neurofibrosarcoma. In 24 of 66 dogs examined, metastases of extracardiac neoplasms were found in the heart (15 carcinomas, six malignant lymphomas, three haemangiosarcomas). In cats, one case of primary haemangiosarcoma of the pericardium and five cases of secondary cardiac tumours (two malignant lymphomas, three carcinomas) occurred. Cardiac neoplasms in cats were not identified clinically but were detected by detailed gross sectioning of the heart (n=2) or histopathological examinations (n=3). This study showed an unexpectedly high number (36%) of dogs with cardiac metastases.     

Histomorphological and immunohistochemical characterization of equine granulosa cell tumours

Benign (n=33) and malignant metastasizing (n=1) granulosa cell tumours (GCTs) from 34 mares aged 3-21 years, and normal (control) ovaries from nine mares aged 3-10 years, were examined histologically and immunohistochemically (for inhibin alpha, glutathione S-transferase alpha [GSTalpha], c-erbB-2 oncoprotein [cerb], cytokeratin, vimentin, desmin and alpha-actin), the results being related where appropriate to clinical signs and endocrinological data. Availability permitting, serum samples from GCT-affected mares before and several weeks after ovariectomy were examined for the following hormones: oestradiol, progesterone and testosterone (by radioimmunoassay); and inhibin B (by a cross-reactive ELISA). Histological examination revealed that the GCTs were predominantly well differentiated neoplasms. The metastasizing GCT differed immunohistochemically from the benign GCTs in respect of the expression patterns of vimentin, cerb and GSTalpha in the granulosa cells. A notable feature was the presence of Leydig-like cells in mares with stallion-like behaviour or elevated serum testosterone, or both. GSTalpha immunolabelling indicated that the Leydig-like cells were potential producers of steroid hormone. From the immunohistochemical and endocrinological findings it was concluded that GCTs produce abnormally high concentrations of inhibin, which reduce the release of follicle-stimulating hormone, leading to atrophy of the contralateral ovary-a finding in 27 of the mares.     

Metric substage according to micro and extensive lamina propria invasion improves prognostics in T1 bladder cancer

Background

Reliable prognosticators for T1 bladder cancer (T1BC) are urgently needed. Objective: To compare the prognostic value of 2 substage systems for T1BC in patients treated by transurethral resection (TUR) and adjuvant bacillus Calmette-Guérin therapy.

Organ-sparing surgery is the treatment of choice in benign testicular tumors

Purpose

Ablation of the testis has been the reference standard for malignant and benign testicular tumors in the past. Nowadays, an organ-sparing surgery (OSS) can be attempted in special cases. Removal of a testis for a benign lesion should be avoided. In this retrospective survey, we analyze the results and long-term follow-up of OSS in benign testicular tumors.

Methods

Charts of all patients that underwent OSS because of a benign testicular tumor between 1999 and 2011 at our department were searched and the data from patients were collected. Before surgery, all patients underwent ultrasound (US) and complete staging. Surgery was performed under US or palpation guidance. Frozen-section examination of the tumor and tumor bed biopsies was obtained. All patients underwent postoperative follow-up. We retrospectively reviewed surgical technique, histology, epidemiology, and outcome in all patients.

Results

In the study period, 40 benign testicular tumors were surgically removed in 37 consecutive patients. Definitive histology did not report of any malignant histopathologic features in all patients. All patients are free of disease after a mean follow-up of 63 months (range 10–120). During this period, two patients developed a second leydig cell tumor (LCT) on the contralateral side; another patient had a second LCT within the same testicle, but on the opposite pole. All patients underwent a subsequent organ-sparing tumor resection.

Conclusions

An overtreatment for benign testicular tumors should be avoided. Our initial results indicate that OSS in benign tumors is a safe, feasible treatment for patients.