Heberprot-P en el tratamiento de las úlceras del pie diabético / Heberprot-P in the treatment of diabetic foot ulcers

RESUMEN Introducción: El pie diabético es una de las complicaciones más temible de la diabetes mellitus; es el causante del 80 % de las amputaciones no traumáticas a nivel mundial. Durante décadas se han utilizados diferentes tratamientos para la cicatrización del pie diabético; los factores de crecimiento han revolucionado esta terapéutica. La participación de un equipo multidisciplinario con el cumplimiento de los protocolos de actuación y el empleo del Heberprot-P disminuyen el índice de amputaciones en pacientes con esta afección. Objetivo: Presentar la evolución de pacientes con úlceras del pie diabético, en diferentes estadios clínicos, tratados con Heberprot-P. Desarrollo: Se presentan 3 casos clínicos; el primero es un paciente masculino, de 56 años, diabético, con amputación transmetatarsiana abierta en la cual se realizaron 16 aplicaciones del Heberprot-P y se colocó un injerto de piel, la lesión cerró en 45 días. El segundo es un paciente de 58 años, diabético e hipertenso, con lesión en el pie derecho, con una cirugía vascular previa; se realizaron 19 aplicaciones del Heberprot-P y la lesión cicatrizó en 49 días. El tercer caso es un paciente de 55 años, que ingresa por la una lesión extensa en el pie derecho, se le realizaron 22 aplicaciones de Heberprot-P, se logró el cierre de la lesión en 85 días y se evitó la amputación. Conclusiones: Los casos presentados evolucionaron de forma favorable con el tratamiento de Heberprot-P.

ABSTRACT Introduction: The diabetic foot is one of the most feared complications of diabetes mellitus; It is the cause of 80 % of non-traumatic amputations worldwide. For decades, different treatments have been used to heal diabetic foot; growth factors have revolutionized this therapy. The participation of a multidisciplinary team with compliance with the action protocols and the use of Heberprot-P decrease the rate of amputations in patients with this condition. Objective: To present the evolution of patients with diabetic foot ulcers, in different clinical stages, treated with Heberprot-P. Development: Three clinical cases are presented; The first is a male patient, 56 years old, diabetic, with open transmetatarsal amputation in which 16 applications of Heberprot-P were performed and a skin graft was placed, the lesion closed in 45 days. The second is a 58-year-old patient, diabetic and hypertensive, with a right foot injury, with previous vascular surgery; 19 applications of Heberprot-P were performed and the lesion healed in 49 days. The third case is a 55-year-old patient, who was admitted due to an extensive injury to his right foot, 22 applications of Heberprot-P were performed, closure of the injury was achieved in 85 days and amputation was avoided. Conclusions: The presented cases evolved favorably with Heberprot-P treatment.

Computational models as predictors of HIV treatment outcomes for the Phidisa cohort in South Africa.

BACKGROUND: Selecting the optimal combination of HIV drugs for an individual in resource-limited settings is challenging because of the limited availability of drugs and genotyping. OBJECTIVE: The evaluation as a potential treatment support tool of computational models that predict response to therapy without a genotype, using cases from the Phidisa cohort in South Africa. METHODS: Cases from Phidisa of treatment change following failure were identified that had the following data available: baseline CD4 count and viral load, details of failing and previous antiretroviral drugs, drugs in new regimen and time to follow-up. The HIV Resistance Response Database Initiative's (RDI's) models used these data to predict the probability of a viral load < 50 copies/mL at follow-up. The models were also used to identify effective alternative combinations of three locally available drugs. RESULTS: The models achieved accuracy (area under the receiver-operator characteristic curve) of 0.72 when predicting response to therapy, which is less accurate than for an independent global test set (0.80) but at least comparable to that of genotyping with rules-based interpretation. The models were able to identify alternative locally available three-drug regimens that were predicted to be effective in 69% of all cases and 62% of those whose new treatment failed in the clinic. CONCLUSION: The predictive accuracy of the models for these South African patients together with the results of previous studies suggest that the RDI's models have the potential to optimise treatment selection and reduce virological failure in different patient populations, without the use of a genotype.

Morbidity and mortality according to latest CD4+ cell count among HIV positive individuals in South Africa who enrolled in project Phidisa.

BACKGROUND: Short-term morbidity and mortality rates for HIV positive soldiers in the South African National Defence Force (SANDF) would inform decisions about deployment and HIV disease management. Risks were determined according to the latest CD4+ cell count and use of antiretroviral therapy (ART) for HIV positive individuals in the SANDF and their dependents. METHODS AND FINDINGS: A total of 7,114 participants were enrolled and followed for mortality over a median of 4.7 years (IQR: 1.9, 7.1 years). For a planned subset (5,976), progression of disease (POD) and grade 4, potentially life-threatening events were also ascertained. CD4+ count and viral load were measured every 3 to 6 months. Poisson regression was used to compare event rates by latest CD4+ count (<50, 50-99, 100-199, 200-349, 350-499, 500+) with a focus on upper three strata, and to estimate relative risks (RRs) (ART/no ART). Median entry CD4+ was 207 cells/mm3. During follow-up over 70% were prescribed ART. Over follow-up 1,226 participants died; rates ranged from 57.6 (< 50 cells) to 0.8 (500+ cells) per 100 person years (py). Compared to those with latest CD4+ 200-349 (2.2/100 py), death rates were significantly lower (p<0.001), as expected, for those with 350-499 (0.9/100 py) and with 500+ cells (0.8/100 py). The composite outcome of death, POD or grade 4 events occurred in 2,302 participants (4,045 events); rates were similar in higher CD4+ count strata (9.4 for 350-499 and 7.9 for 500+ cells) and lower than those with counts 200-349 cells (13.5) (p<0.001). For those with latest CD4+ 350+ cells, 63% of the composite outcomes (680 of 1,074) were grade 4 events. CONCLUSION: Rates of morbidity and mortality are lowest among those with CD4+ count of 350 or higher and rates do not differ for those with counts of 350-499 versus 500+ cells. Grade 4 events are the predominant morbidity for participants with CD4+ counts of 350+ cells.

Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a South African cohort with advanced HIV disease.

BACKGROUND: Levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer predict mortality in HIV patients on antiretroviral therapy (ART) with relatively preserved CD4+ T cell counts. We hypothesized that elevated pre-ART levels of these markers among patients with advanced HIV would be associated with an increased risk of death following the initiation of ART. METHODS: Pre-ART plasma from patients with advanced HIV in South Africa was used to measure hsCRP, IL-6 and D-dimer. Using a nested case-control study design, the biomarkers were measured for 187 deaths and two controls matched on age, sex, clinical site, follow-up time and CD4+ cell counts. Odds ratios were estimated using conditional logistic regression. In addition, for a random sample of 100 patients, biomarkers were measured at baseline and 6 months following randomization to determine whether ART altered their levels. RESULTS: Median baseline biomarkers levels for cases and controls, respectively, were 11.25 vs. 3.6 mg/L for hsCRP, 1.41 vs. 0.98 mg/L for D-dimer, and 9.02 vs. 4.20 pg/mL for IL-6 (all p<0.0001). Adjusted odds ratios for the highest versus lowest quartile of baseline biomarker levels were 3.5 (95% CI: 1.9-6.7) for hsCRP, 2.6 (95%CI 1.4-4.9) for D-dimer, and 3.8 (95% CI: 1.8-7.8) for IL-6. These associations were stronger for deaths that occurred more proximal to the biomarker measurements. Levels of D-dimer and IL-6, but not hsCRP, were significantly lower at month 6 after commencing ART compared to baseline (p<0.0001). CONCLUSIONS: Among patients with advanced HIV disease, elevated pre-ART levels of hsCRP, IL-6 and D-dimer are strongly associated with early mortality after commencing ART. Elevated levels of inflammatory and coagulation biomarkers may identify patients who may benefit from aggressive clinical monitoring after commencing ART. Further investigation of strategies to reduce biomarkers of inflammation and coagulation in patients with advanced HIV disease is warranted. TRIAL REGISTRATION: Parent study: ClinicalTrials.gov NCT00342355.

Lactic acidosis and symptomatic hyperlactataemia in a randomized trial of first-line therapy in HIV-infected adults in South Africa.

BACKGROUND: Lactic acidosis (LA) is a potentially life-threatening complication of antiretroviral (ARV) therapy. Few randomized prospective studies have compared LA between different ARV regimens. METHODS: Characterization of cases of LA (serum lactate >5 mmol/l and arterial pH<7.35 or bicarbonate <20 mmol/l) and symptomatic hyperlactataemia (SH; serum lactate >2.2 mmol/l and symptoms) was made in a randomized open-label 2×2 factorial study of stavudine/lamivudine (d4T/3TC)-based versus didanosine/zidovudine-based therapy and lopinavir/ritonavir-based versus efavirenz (EFV)-based therapy in 1,771 HIV-infected adults initiating therapy between 2004 and 2008. RESULTS: The LA incident rate was 3.5/1,000 person-years (95% CI 1.8-5.9), and for combined LA/SH was 11.0/1,000 person-years (95% CI 7.9-14.9). There were two deaths (15% mortality) among 13 LA cases; all 11 survivors experienced symptom resolution and started new ARV regimens. LA cases were more likely to be female (OR 7.19, 95% CI 1.84-40.75; P=0.001) and had a higher body mass index (BMI; P<0.0001) compared with non-cases. There was no increase in LA according to ARV regimen, age or CD4(+) T-cell count at randomization. When combined, LA/SH cases (n=41) were more often female (OR 4.76, 95% CI 2.36-10.08; P<0.0001), had increased BMI (P<0.0001), were more likely to be assigned d4T/3TC (OR 3.17, 95% CI 1.50-7.28; P=0.001) and were more likely to be assigned EFV (OR 2.18, 95% CI 1.08-4.61; P=0.026). CONCLUSIONS: Female sex and increased BMI were associated with severe LA in this large randomized trial of first-line ARV in South Africa. While female sex, increased BMI and d4T are previously described risk factors for the development of clinically significant lactate elevations, the independent risk associated with EFV is a novel observation warranting further investigation.