Proximity to HIV is associated with a high rate of HIV testing among men who have sex with men living in Douala, Cameroon

In low- and middle-income countries, men who have sex with men (MSM) are 19 times more likely to be HIV positive compared with background populations. Criminalisation and social rejection of homosexuality in most sub-Saharan African countries reinforce stigma and exclude MSM from prevention activities, including HIV testing. This paper's purpose is to identify factors associated with never having been HIV tested (NHT), among a sample of Cameroonian MSM. In 2008, a community-based study was conducted in Douala, the economic capital city of Cameroon, by a local NGO Alternatives-Cameroun, recruiting participants through the snowball technique and administering a questionnaire during face-to-face interviews. Proximity to HIV was investigated according to the following criteria: knowing at least one person living with HIV and having been exposed to HIV prevention interventions. NHT was defined as reporting to have never been HIV tested. A logistic regression was used to identify factors associated with NHT. Among the 165 MSM of our study group who reported that they were not HIV positive, 19% reported NHT. Factors independently associated with NHT were as follows: being younger, being Muslim, not having a steady male partner, not knowing any person living with HIV and never having been exposed to HIV prevention interventions. In this MSM population, a small proportion reported that they had never been HIV tested and among these, the percentage was higher among individuals not in proximity to HIV. Despite the hostile context of sub-Saharan African countries towards MSM, local and national HIV testing campaigns to date may have played a substantial role in raising HIV awareness in the MSM population living in Douala, and peer-based counselling may have educated those in contact with Alternatives-Cameroun regarding the positive value of HIV testing. This result is a further argument for continuing community-based prevention and extending it to difficult-to-reach MSM.     

Failure of temozolomide and conventional doses of pegvisomant to attain biochemical control in a severe case of acromegaly

It has been suggested that treatment with adequate dose titration of pegvisomant, a GH antagonist, up to a maximum of 40 mg daily, can achieve IGF-1 normalisation in virtually all patients with acromegaly. On the other hand, temozolomide (TMZ), an alkylating cytostatic agent, has been reported to reduce pituitary tumour size and hormone hypersecretion in a small number of aggressive pituitary macroadenomas. In this paper we report the case of a patient resistant to very high doses of pegvisomant used in combination with somatostatin analogs (SSA) and to TMZ therapy. The patient, initially a 22 year-old man with an invasive GH-secreting pituitary macroadenoma (IGF-1, 371% upper limit of normal), had active acromegaly despite a repeat transsphenoidal surgery followed by radiotherapy and SSA (octreotide 800 μg sc daily) (IGF-1, 262% ULN). In combination with SSA, pegvisomant was started at 20 mg daily and doses were titrated up to 60 mg daily. IGF-1 was moderately reduced and stabilized at 200% ULN after 1 year of treatment. Serum pegvisomant level was 30,500 ng/l, the denaturalized GHBP concentration 1,120 pM and the endogenous GH level was 220 μg/l. Pegvisomant was stopped and TMZ therapy was given for 5 cycles. However, the patient reported an increase of acromegaly symptoms and the serum IGF-1 was raised to the same level prior to pegvisomant therapy. Consequently, pegvisomant was tried again with doses up to 100 mg daily finally resulting in normalisation of serum IGF-1 level and improvement of acromegaly symptoms and patient well-being. We conclude that in some patients with severe acromegaly refractory to multimodal therapy, biochemical control may be difficult to attain with conventional doses of pegvisomant or TMZ therapy.     

A review of the invasive mosquitoes in Europe: ecology, public health risks, and control options

There has been growing interest in Europe in recent years in the establishment and spread of invasive mosquitoes, notably the incursion of Aedes albopictus through the international trade in used tires and lucky bamboo, with onward spread within Europe through ground transport. More recently, five other non-European aedine mosquito species have been found in Europe, and in some cases populations have established locally and are spreading. Concerns have been raised about the involvement of these mosquito species in transmission cycles of pathogens of public health importance, and these concerns were borne out following the outbreak of chikungunya fever in Italy in 2007, and subsequent autochthonous cases of dengue fever in France and Croatia in 2010. This article reviews current understanding of all exotic (five introduced invasive and one intercepted) aedine species in Europe, highlighting the known import pathways, biotic and abiotic constraints for establishment, control strategies, and public health significance, and encourages Europe-wide surveillance for invasive mosquitoes.     

The impact of lymph node status and features on oncological outcomes in urothelial carcinoma of the upper urinary tract (UTUC) treated by nephroureterectomy

Purpose

Prognostic impact of lymphadenectomy during radical nephroureterectomy (RNU) for urothelial carcinoma of the upper urinary tract (UTUC) is controversial. Our aim was to assess the impact of lymph node status (LNS) on survival in patients treated by RNU.

Methods

In our multi-institutional, retrospective database, 714 patients with non-metastatic UTUC had undergone RNU between 1995 and 2010. LNS was tested as prognostic factor for survivals through univariate and multivariable Cox regression analysis.

Results

Median age was 70 years [interquartile range (IQR), 60–75] with median follow-up of 27 months (IQR, 10–50). Overall, lymphadenectomy was performed in 254 patients (35.5 %). Among these patients, 204 (80 %) had negative lymph nodes (pN0) and 50 (20 %) had positive lymph nodes (pN1/2). The 5-year cancer-specific survival (CSS) was 81 % [95 % confidence interval (CI), 73–88 %] for pN0 patients, 85 % (95 % CI, 80–90 %) for pNx patients and 47 % (95 % CI, 24–69 %) for pN1/2 patients (p < 0.001). Metastasis-free survival (MFS) and overall survival (OS) rates were significantly lower in pN1/2 patients than in pN0 and pNx patients (p < 0.05). On multivariable analysis, LNS did not appear as an independent prognostic factor for CSS, OS or MFS (p > 0.05). In case of lymph node involvement, extra-nodal extension was marginally associated with worse CSS (log rank p = 0.07). The retrospective design was the main limitation.

Conclusion

LNS is helpful for survival stratification in patients treated with RNU for UTUC. However, LNS did not appear as an independent predictor of survival in this retrospective series and needs to be investigated in a large multicentre, prospective evaluation.     

Palliative Resection for Advanced Gastric and Junctional Adenocarcinoma: Which Patients will Benefit from Surgery?

Background

Whereas palliative chemotherapy offers a median survival of approximately 10 months in advanced gastric and junctional adenocarcinoma (AGJA), the survival impact of primary tumor resection is controversial. Our purpose was to identify which AGJA patients benefit from palliative resection.

Methods

In 3,202 AGJA patients scheduled for surgery in 21 French centers between 1997 and 2010, prognostic factors were identified in palliative group and the impact of each combination of these factors on survival was studied.

Results

Surgery was defined as palliative due to solid organ metastasis (5.6 %), localized (4.6 %) or diffuse (2.3 %) peritoneal carcinomatosis (PC), or incomplete tumoral resection (12.8 %). Median survival of AGJA patients resected with a palliative intent (n = 677) was longer than in nonresected patients (n = 532; 11.9 vs. 8.5 months, P < 0.001). Multivariable analyses identified ASA score III-IV (P < 0.001) as a predictor of postoperative mortality and solid organ metastasis (P = 0.009), localized PC (P = 0.004), diffuse PC (P = 0.046), and signet ring cell histology (SRC; P = 0.02) as predictors of survival. Only ASA I–II patients with incomplete resection without metastasis or PC, one site solid organ metastasis without PC, or localized PC without SRC had a survival benefit after palliative surgery with median survivals from 12.0 to 18.3 months. Nonresected ASA I–II patients with same risk factors had median survivals from 3.5 to 8.8 months (P < 0.05 for each).

Conclusions

In AGJA, patient and tumor-related factors should be used to select candidates for palliative surgery in association with chemotherapy.     

Lipopolysaccharides,but not Angiotensin ll,lnduces Direct Pro‐lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells

Angiotensin II (Ang II) might induce pro‐inflammatory effects directly in the vascular wall independently of its haemodynamic effects. The aim of our study was to investigate the putative direct pro‐inflammatory and vasomotor effects of Ang II and compare to those of lipopolysaccharides (LPS) in mouse isolated mesenteric resistance‐sized arteries (MRA) supported by experiments in cultured human primary endothelial and vascular smooth muscle cells. Results showed that 24‐hr organ culture of mouse MRA with 10 nM Ang II had, unlike 100 ng/mL LPS, no effects on IL‐6 or MCP‐1 secretion, VCAM1 mRNA expression or endothelial function, while Ang II significantly decreased maximal vasomotor responses to phenylephrine. In support, 24‐hr organ culture of mouse MRA significantly suppressed Agtr1a mRNA and augmented Tlr4 mRNA along with attenuated vasomotor responses to Ang II. Moreover, contrary to LPS and TNF‐α, Ang II and [Sar1]‐Ang II had no concentration‐ or time‐dependent effects on IL‐6 and MCP‐1 secretion in human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (HASMC). AGTR1 or AGTR2 mRNA expression was undetectable in HUVEC, whereas HASMC expressed only AGTR1 mRNA. In summary, contrary to previous studies and the observed effects of LPS, we could not demonstrate direct vascular pro‐inflammatory effects of Ang II ex vivo or in vitro. As indicated by our results, down‐regulation or desensitization of AT₁R during culture may explain our findings.