Association of cytokine gene polymorphisms with peripheral neuropathy susceptibility in people living with HIV in Greece.

Relatively little research has been done in recent years to understand what leads to the unceasingly high rates of HIV sensory neuropathy despite successful antiretroviral treatment. In vivo and in vitro studies demonstrate neuronal damage induced by HIV and increasingly identified ART neurotoxicity involving mitochondrial dysfunction and innate immune system activation in peripheral nerves, ultimately all pathways resulting in enhanced pro-inflammatory cytokine secretion. Furthermore, many infectious/autoimmune/malignant diseases are influenced by the production-profile of pro-inflammatory and anti-inflammatory cytokines, due to inter-individual allelic polymorphism within cytokine gene regulatory regions. Associations of cytokine gene polymorphisms are investigated with the aim of identifying potential genetic markers for susceptibility to HIV peripheral neuropathy including ART-dependent toxic neuropathy. One hundred seventy-one people living with HIV in Northern Greece, divided into two sub-groups according to the presence/absence of peripheral neuropathy, were studied over a 5-year period. Diagnosis was based on the Brief Peripheral Neuropathy Screening. Cytokine genotyping was performed by sequence-specific primer-polymerase chain reaction. Present study findings identify age as an important risk factor (p < 0.01) and support the idea that cytokine gene polymorphisms are at least involved in HIV peripheral-neuropathy pathogenesis. Specifically, carriers of IL1a-889/rs1800587 TT genotype and IL4-1098/rs2243250 GG genotype disclosed greater relative risk for developing HIV peripheral neuropathy (OR: 2.9 and 7.7 respectively), while conversely, carriers of IL2+166/rs2069763 TT genotype yielded lower probability (OR: 3.1), all however, with marginal statistical significance. The latter, if confirmed in a larger Greek population cohort, may offer in the future novel genetic markers to identify susceptibility, while it remains significant that further ethnicity-oriented studies continue to be conducted in a similar pursuit.

Epidemiology of HIV-associated peripheral neuropathy in people living with human immunodeficiency virus infection in Greece.

BACKGROUND: Peripheral neuropathy is among the most common complications among people with HIV with prevalence rates varying widely among studies (10-58%). OBJECTIVE: This study aims to assess the prevalence of HIV-associated peripheral neuropathy among HIV-positive people in Northern Greece monitored during the last 5-year period and investigate possible correlations with antiretroviral therapy, disease staging, and potential risk factors, as there is no prior epidemiological record in Greek patients. METHODS: Four hundred twenty patients were divided into a group with peripheral neuropathy (n = 269), and those without (n = 151). Peripheral neuropathy was assessed with a validated Peripheral Neuropathy Screening tool. Statistical analyses were performed with SPSS, were two-tailed, and p-value was set at 0.05. RESULTS: The incidence of peripheral neuropathy was estimated at 35.9%. Age was found to correlate with higher odds of developing HIV-peripheral neuropathy, rising by 4%/year. Females encountered 77% higher probability to develop peripheral neuropathy. Stage 3 of the disease associated with higher occurrence of peripheral neuropathy (96% as compared to stage-1 patients). Among patients with peripheral neuropathy, the duration of antiretroviral therapy was found to be longer than in those without. CONCLUSIONS: Peripheral neuropathy remains one of the most common complications regardless of the antiretroviral-therapy type, indicating the involvement of other risk factors in its occurrence, such as the stage of the disease, age and gender. Therefore, the treating physician should screen patients as early and frequently as possible upon HIV-diagnosis to prevent the progression of this debilitating condition so that prolonged life-expectancy is accompanied by a good quality of life.

Limb Salvage in Patients With Severe Critical Limb Ischemia (CLI) After Referral for a Second Opinion to a Dedicated CLI Center.

The complexity of critical limb ischemia (CLI) requires dedicated multidisciplinary teams of different care providers, who will supervise the full cycle of CLI care. Until CLI treatment is fully centralized, such dedicated teams may work as second-opinion tools before major amputation is undertaken in CLI patients. The aim of the study is to assess the effectiveness of a well-timed referral to a dedicated CLI-center of patients scheduled to major amputation elsewhere. A retrospective analysis of all CLI-patients treated in our department between January 2019 and March 2020 was conducted. Only patients scheduled for a major amputation elsewhere and referred to our clinic were included. Primary endpoint was amputation-free survival, whereas technical success, limb salvage, minor amputation rate, re-admission at 30 days, and frequency of medication change from other disciplines were the secondary endpoints. Sixteen patients with 19 treated limbs were identified and included in this analysis. The WIfI (wound, infection and foot ischemia) clinical stage on admission was 2 in 4 limbs (21%), 3 in 5 limbs (26%), and 4 in 10 limbs (53%). All patients underwent advanced endovascular revascularization. Minor amputation was performed in 8 patients (42%). Amputation-free survival at 6 months was 93% with limb salvage rate of 100%. Technical success and re-admission rates at 30 days was 95% and 6%, respectively. There was a medication adjustment from other specialties in 13 (81%) patients. Patients in severe stages of CLI scheduled to major amputation reached high limb salvage and survival rate, since they are referred for a second opinion to a dedicated multidisciplinary CLI team.