Familial Screening for the Prevention of Rare Diseases: A Focus on Lipodystrophy in Southern Saudi Arabia.

BACKGROUND: Lipodystrophy is a relatively rare, complex disease characterised by a deficiency of adipose tissue and can present as either generalised lipodystrophy (GLD) or partial lipodystrophy (PLD). The prevalence of this disease varies by region. This study aimed to identify the genetic variations associated with lipodystrophy in the southern part of Saudi Arabia. METHODOLOGY:  We conducted a retrospective study by recruiting nine patients from six families, recruiting the proband whole exome sequencing results or any other genetic test results, screening other family members using Sanger sequencing and analysing the carrier status of the latter. These patients were recruited from the Endocrinology and Diabetes Clinic at Jazan General Hospital and East Jeddah Hospital, both in the Kingdom of Saudi Arabia. RESULT: Eight patients were diagnosed with GLD, and one was diagnosed with PLD. Of the six families, four were consanguineously married from the same tribe, while the remaining belonged to the same clan. The majority of GLD patients had an AGPAT2 c.158del mutation, but some had a BSCL2 c.942dup mutation. The single PLD case had a PPARG c.1024C > T mutation but no family history of the disease. In all families evaluated in this study, some family members were confirmed to be carriers of the mutation observed in the corresponding patient. CONCLUSION:  Familial screening of relatives of patients with rare, autosomal recessive diseases, such as lipodystrophy, especially when there is a family history, allows the implementation of measures to prevent the onset or reduced severity of disease and reduces the chances of the pathogenic allele being passed onto future generations. Creating a national registry of patients with genetic diseases and carriers of familial pathogenic alleles will allow the assessment of preventive measures and accelerate disease intervention via gene therapy.

Lipoatrofia semicircular en trabajadores de oficinas: una situación que no desaparece tan rápidamente / Semicircular lipoatrophy in public office workers. A situation that does not disappear so quickly

Introducción: La lipoatrofia semicircular (LS) es un trastorno caracterizado por depresiones en forma de banda en la cara anterolateral de los muslos. Objetivos: determinar la prevalencia de los casos de LS en varias instituciones públicas y privadas de la Provincia de Barcelona, España. Material y Métodos: se realizó estudio retrospectivo, en 969 trabajadores de oficinas públicas y privadas, entre 2018 y 2022. A todos los casos se les realizó examen físico completo con mediciones, fotografía y seguimiento de las lesiones. Los resultados fueron analizados mediante el programa Instat Graphpad 3.10 y se aplicó la prueba de Fischer para determinar la significancia estadística. Resultados: se diagnosticaron 96 casos de los cuales 92 eran mujeres. Prevalencia: 9,9%. El promedio de edad fue 49 años (27-64). La mayoría de las lesiones se localizaron en los muslos en forma bilateral. Las lesiones de LS al final del estudio no desaparecieron en el 60% de los casos, mientras que en un 40% si lo hicieron. Conclusiones: Las lesiones de LS toman un tiempo muy variable para revertir, suele ser un proceso lento cuya duración se mide habitualmente en años. Ni el teletrabajo, ni el índice de masa corporal, tuvieron relación estadísticamente significativa en la desaparición de las lesiones. (AU)

Introduction: Semicircular lipoatrophy (LS) is a disorder characterized by band-shaped depressions on the anterolateral aspect of the thighs. Objectives: to determine the prevalence of LS cases in various public and private institutions in the Province of Barcelona, Spain. Material and Methods: a retrospective study was carried out on 969 workers from public and private offices, between 2018 and 2022. All cases underwent a complete physical examination with measurements, photography, and follow-up of injuries. The results were analyzed using the Instat Graphpad 3.10 program and the Fischer test was applied to determine statistical significance. Results: 96 cases were diagnosed, of which 92 were women. Prevalence: 9.9%. The average age was 49 years (27-64). Most of the lesions were located on the thighs bilaterally. LS lesions at the end of the study did not disappear in 60% of cases, while in 40% they did. Conclusions: LS lesions take a highly variable time to reverse, it is usually a slow process whose duration is usually measured in years. Neither teleworking nor the body mass index had a statistically significant relationship in the disappearance of the lesions (AU)

Lipoatrophy in children, adolescents and adults with insulin pump treatment: Is there a beneficial effect of insulin glulisine?

AIM: To investigate whether zinc-free insulin is an effective treatment option for lipoatrophy. METHODS: Controlled, randomized, open-label parallel study in young people with type 1 diabetes, pump treatment and lipoatrophy at injection sites. Participants underwent dermatological examination and evaluation of affected areas using ultrasound and magnetic resonance imaging (MRI). After randomization, half of themswitched to insulin glulisine (intervention group) for 6 months. The control group continued their treatment with zinc-containing insulin and switched to insulin glulisine 6 months later. Both groups were followed-up until month 12. Primary endpoint was the increase of the relative thickness of the subcutaneous fat layer of the most atrophic site at 6 months as documented by MRI. RESULTS: Fourteen participants were included into the study. While relative thickness of subcutaneous fat tissue was comparable between intervention (-60% [-98.8 - -17.6], n = 7) and control group (-50% [-72.7 - -1.0], P = .511; median (range), n = 7)at baseline, it improved in the intervention (-14.3% [-85.7-83.3] vs -31.3% (-66.7-0), P = .031), but not in the control group (P = .125) after 6 months. At 12 months, relative fat thickness (P = .003), number (P = .015) and size of most atrophic sites (P = .001) were improved in the intervention group. Number (P = .018) and size of most atrophic sites (P = .008) were also reduced in the control group between 6 and 12 months. CONCLUSIONS: Although the present pilot study is based on a small sample, the data give first hint that the use of the zinc-free insulin glulisine may be beneficial in people with diabetes, pump and lipoatrophy.

Análise de percepção da insulinoterapia em diabéticos tipo 1 no Serviço de Apoio e Assistência aos Diabéticos e seus Familiares / Analysis of type 1 diabetes patients' perception of insulin therapy at the service of care and support to diabetics and their family

Objetivo: Analisar a percepção dos diabéticos tipo 1 sobre a insulinoterapia. Métodos: Trata-se de estudo epidemiológico analítico de percepção, tendo sido realizado com pacientes de um Serviço de Apoio e Assistência aos Diabéticos e seus Familiares, no período de abril a agosto de 2018. Resultados: Os 33 diabéticos tipo 1 avaliados eram predominantemente do sexo feminino (60,6%) e a média de idade foi de 21±9 anos. A maioria afirmou portar o Cartão de Identificação do Diabético (78,8%). Mais de dois terços dos pacientes afirmaram saber quando aplicar a insulina de correção. A aferição da glicemia capilar foi relatada por 78,8%. Das insulinas utilizadas no esquema basal, a glargina e a NPH foram citadas como as mais utilizadas. Do total de pacientes, 97% referiram fazer autoaplicação, e 90,9% disseram posicionar a agulha corretamente sobre a pele. Quanto aos locais de aplicação, 84,8% realizavam rodízio. A maioria dos pacientes (78,8%) que aplicavam a insulina não referiu desconforto durante ou após a aplicação, e 69,7% mostraram conhecimento sobre o significado de distrofia. Conclusão: O serviço de educação continuada desenvolvido pelo Serviço de Apoio e Assistência aos Diabéticos e seus Familiares é efetivo na aquisição de bons hábitos e dos devidos cuidados para esses pacientes. A educação do indivíduo com diabetes tipo 1 e de sua família, bem como o acompanhamento por uma equipe multidisciplinar, é essencial para o bom controle da doença,

Objective: To analyze the perception of type 1 diabetes (DM 1) patients of insulin therapy. Methods: This is an epidemiological study of analysis of perception and was performed at the service for care and support of diabetes patients and their families from April to August 2018. Results: The 33 type 1 diabetes mellitus patients evaluated were predominantly female (60.6%) and the mean age was 21 years ± 9 years. Most reported having the diabetes medical ID card (78.8%). More than two thirds of the patients reported knowing when to apply the correction insulin. The capillary glycemia measurement was reported by 78.8%. Of the insulins used in the baseline regimen, Glargine and NPH were cited as the most used. Of the total patients, 97% reported self-application and 90.9% reported positioning the needle correctly on the skin. As for the application sites, 84.8% reported rotating sites. Most patients (78.8%) who applied insulin did not report discomfort during or after application, and 69.7% showed knowledge about the meaning of dystrophy. Conclusion: The continuing education service developed by the Service for Care and Support of Diabetics and their Families is effective in promoting good habits and the proper care of these patients for their disease.The education of the individual with type 1 diabetes and of his/her family, as well as follow-up by a multidisciplinary team, is essential for good disease control.

An Effective Intervention for Diabetic Lipohypertrophy: Results of a Randomized, Controlled, Prospective Multicenter Study in France.

BACKGROUND: Lipohypertrophy (LH) is highly prevalent and is potentially harmful to insulin-injecting patients. METHODS: In this study, we assessed the impact of injection technique (IT) education, including use of a 4-mm pen needle on insulin-treated patients with clinically observed LH in a randomized, controlled, prospective multicenter study in France with follow-up of 6 months. Intensive education and between-visit reinforcement were given to the intervention group. Control patients received similar messages at study outset. RESULTS: A total of 123 patients were recruited (age 52.1 ± 15.7 years; men 70.7%; body mass index >30 kg/m2: 34.2%; type 1: 53.7%; years with diabetes mellitus: 18.1 ± 10.5), of which 109 patients were included in the final analysis. The intervention group (n = 53) showed a significant decrease of total daily dose of insulin (average at baseline: 54.1 IU) at 3 months (T-3) and 6 months (T-6), reaching just over 5 IU versus baseline (P = 0.035). Corresponding, although not significant, decreases occurred in controls (n = 56); between-group differences were not significant. There were significant decreases in HbA1c (up to 0.5%) at T-3 and T-6 in both groups, with no significant differences between groups. A significant number of intervention patients improved their IT habits; about half achieved ideal IT habits by T-3 versus a quarter of control patients. By T-6, 2/3 of intervention patients achieved either ideal or acceptable IT habits, while only 1/3 of control patients did. CONCLUSIONS: Our intervention was effective in both study arms, however, to a greater degree and more rapidly in the intervention group. Widespread application of this intervention could be highly cost-effective.

Cardiovascular risk and dyslipidemia among persons living with HIV: a review.

BACKGROUND: Aim of this review is to focus the attention on people living with HIV infection at risk of developing a cardiovascular event. What is or what would be the most suitable antiretroviral therapy? Which statin or fibrate to reduce the risk? How to influence behavior and lifestyles? DISCUSSION: Prevention of cardiovascular disease (CVD) risk remains the first and essential step in a medical intervention on these patients. The lifestyle modification, including smoking cessation, increased physical activity, weight reduction, and the education on healthy dietary practices are the main instruments. Statins are the cornerstone for the treatment of hypercholesterolemia. They have been shown to slow the progression or promote regression of coronary plaque, and could also exert an anti-inflammatory and immunomodulatory effect. However the current guidelines for the use of these drugs in general population are dissimilar, with important differences between American and European ones. The debate between American and European guidelines is still open and, also considering the independent risk factor represented by HIV, specific guidelines are warranted. Ezetimibe reduces the intestinal absorption of cholesterol. It is effective alone or in combination with rosuvastatin. It does not modify plasmatic concentrations of antiretrovirals. A number of experimental new classes of drugs for the treatment of hypercholesterolemia are being studied. Fibrates represent the first choice for treatment of hypertriglyceridemia, however, the renal toxicity of fibrates and statins should be considered. Omega 3 fatty acids have a good safety profile, but their efficacy is limited. Another concern is the high dose needed. Other drugs are acipimox and tesamorelin. Current antiretroviral therapies are less toxic and more effective than regimens used in the early years. Lipodistrophy and dyslipidemia are the main causes of long-term toxicities. Not all antiretrovirals have similar toxicities. Protease Inhibitors may cause dyslipidemia and lipodystrophy, while integrase inhibitors have a minimal impact on lipids profile, and no evidence of lipodystrophy. There is still much to be written with the introduction of new drugs in clinical practice. CONCLUSIONS: Cardiovascular risk among HIV infected patients, interventions on behavior and lifestyles, use of drugs to reduce the risk, and switch in antiretroviral therapy, remain nowadays major issues in the management of HIV-infected patients.

Myristic acid potentiates palmitic acid-induced lipotoxicity and steatohepatitis associated with lipodystrophy by sustaning de novo ceramide synthesis.

Palmitic acid (PA) induces hepatocyte apoptosis and fuels de novo ceramide synthesis in the endoplasmic reticulum (ER). Myristic acid (MA), a free fatty acid highly abundant in copra/palmist oils, is a predictor of nonalcoholic steatohepatitis (NASH) and stimulates ceramide synthesis. Here we investigated the synergism between MA and PA in ceramide synthesis, ER stress, lipotoxicity and NASH. Unlike PA, MA is not lipotoxic but potentiated PA-mediated lipoapoptosis, ER stress, caspase-3 activation and cytochrome c release in primary mouse hepatocytes (PMH). Moreover, MA kinetically sustained PA-induced total ceramide content by stimulating dehydroceramide desaturase and switched the ceramide profile from decreased to increased ceramide 14:0/ceramide16:0, without changing medium and long-chain ceramide species. PMH were more sensitive to equimolar ceramide14:0/ceramide16:0 exposure, which mimics the outcome of PA plus MA treatment on ceramide homeostasis, than to either ceramide alone. Treatment with myriocin to inhibit ceramide synthesis and tauroursodeoxycholic acid to prevent ER stress ameliorated PA plus MA induced apoptosis, similar to the protection afforded by the antioxidant BHA, the pan-caspase inhibitor z-VAD-Fmk and JNK inhibition. Moreover, ruthenium red protected PMH against PA and MA-induced cell death. Recapitulating in vitro findings, mice fed a diet enriched in PA plus MA exhibited lipodystrophy, hepatosplenomegaly, increased liver ceramide content and cholesterol levels, ER stress, liver damage, inflammation and fibrosis compared to mice fed diets enriched in PA or MA alone. The deleterious effects of PA plus MA-enriched diet were largely prevented by in vivo myriocin treatment. These findings indicate a causal link between ceramide synthesis and ER stress in lipotoxicity, and imply that the consumption of diets enriched in MA and PA can cause NASH associated with lipodystrophy.

Expression of seipin in adipose tissue rescues lipodystrophy, hepatic steatosis and insulin resistance in seipin null mice.

OBJECTIVES: Gene mutations in an ER protein seipin result in congenital generalized lipodystrophy (CGL) in humans, accompanied with hepatic steatosis and insulin resistance. Seipin gene is highly expressed in the brain, testis and adipose tissue. Seipin globally deficient mice (SKO) displayed similar phenotypes as human counterparts. It has been demonstrated that adipose-specific seipin knockout mice at elder age were indistinguishable from SKO mice. Due to the large mass of adipose tissue in the body, we hypothesized that seipin in adipose tissue might be responsible for the multiple metabolism-related abnormalities in SKO mice. METHODS AND RESULTS: Transgenic mice with adipose-specific expression of human seipin gene driven by aP2 promoter were generated and crossed with SKO mice to obtain adipose-specific seipin reconstitute (Seipin-RE) mice. In comparison with wild-type (WT) and SKO mice, the Seipin-RE mice exhibited normal plasma triglyceride and non-esterified fatty acids upon fasting, recovered adipose tissue mass, restored epididymal and subcutaneous fat pads morphology and partially recovered plasma leptin and adiponectin levels. Moreover, hepatic steatosis and insulin resistance was also absent in these mice. CONCLUSION: Our study demonstrates that expression of seipin in adipose tissue alone could rescue dyslipidemia, lipodystrophy, hepatic steatosis and insulin resistance in SKO mice.

The lipo-facelift: merging the face-lift and liposculpture: eight years experience and a preliminary observational study.

BACKGROUND: Since the introduction of the classic submucosal aponeurotic system (SMAS) face-lift, the surgical approach to improve the changes of an aging face has evolved, and significant technical improvements have been made. However, several problems still have not been solved satisfactorily. These problems include facial lipodystrophy and changes in skin and skin texture. METHODS: The Lipo-Facelift procedure consists of facial liposculpturing performed simultaneously with a biplanar, bivectorial SMAS face-lift procedure. The authors analyzed pre- and postsurgical photographs of 12 patients with a Lipo-Facelift after 3 and 12 months and analyzed their charts for complications. Furthermore, O2C measurement was performed to assess improved microcirculation. The longest follow-up period was 8 years. RESULTS: The Lipo-Facelift demonstrated very satisfying results. Initial swelling and bruising were seen as well as two cases of wound-healing disorders, but no surgical intervention or revision was needed. The findings show lasting improvement of skin quality and a youthful appearance. CONCLUSION: The Lipo-Facelift corrects age-related skin and SMAS changes as well as age-related lipodystrophy, improves skin circulation and skin revitalization, and provides a lasting and natural result. The skin quality resulting from simultaneous lipofilling can be explained by improved angiogenesis due to transferred growth factors in the lipoaspirate. Also, differentiation of progenitor cells to fibroblasts and increased production of collagen contribute to firmer skin. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Lipoatrofia semicircular, una visión general a una patología laboral emergente en Chile / Semicircular lipatrophy, an overview of emerging labor pathology in Chile

La Lipoatrofia Semicircular (LS) es una enfermedad idiopática, que se caracteriza por una atrofia reversible y localizada, ya sea total o parcial, del tejido adiposo subcutáneo y que se ubica en zonas de contacto de la piel de las extremidades con el inmobiliario. Se caracteriza por presentarse en brotes endémicos, cuyo único factor en común es el lugar de trabajo. Sus causas son desconocidas, pero en la actualidad se proponen factores asociados como: el contacto de la zona afectada con inmobiliario, presencia de radiación electromagnética, presencia de descargas electroestáticas y humedad ambiental relativa baja. Un modelo actual para explicar la patogenia de esta enfermedad involucra la participación de descargas electrostáticas, que probablemente activarían la liberación de factor de necrosis tumoral a (TNF-a) y desencadenaría la fagocitosis de adipocitos. Actualmente no tiene un tratamiento médico, siendo las medidas preventivas de mitigación de los factores previamente mencionados las que producen una reversión de la lesión. Por otro lado, la presencia de estos brotes generan un gran impacto mediático por lo que también debe ser abordada comunicacionalmente. La presente revisión pretende sintetizar la literatura sobre el tema para exponer el conocimiento actual y lograr una noción de esta nueva enfermedad, tras su primera presentación en brote en nuestro país.

Lipoatrophia semicircularis (LS) (also known as "Semicircular lipoa-trophy") is an idiopathic disease, which is characterized by a reversible and localized atrophy, either total or partial, of subcutaneous adipose tissue and located in areas of skin contact with the real estate tips. It is characterized by appearing in endemic outbreaks whose only common factor is the workplace. Its causes are unknown, but currently associated factors have been proposed, such as: the contact area with the office furniture, the presence of electromagnetic radiation, electrostatic discharge and presence of low relative humidity. A current model to explain the pathogenesis of this disease involves the participation of electrostatic discharges, which probably activate the release of tumor necrosis factor a (TNF-a) and it would trigger phagocytosis of adipocytes. Currently there is no medical treatment, being proactive mitigation measures of the before mentioned factors, those that produce a reversion of the injury. On the other hand, the presence of these buds generates great media impact so it must be also addressed from a communication standpoint. The present review aims to summarize the literature on the subject to present current knowledge and achieve a notion of this new disease, after its first appearance in outbreak in our country.

[Systemic glucocorticoid therapy: associated measures]. / Corticothérapie systémique : les mesures d'accompagnement.

Long-term treatment with glucocorticoids results in many adverse effects. Prevention of osteoporosis is well codified, but prevention of other adverse effects is not. If there is some consensus on the prevention of glucocorticoid-induced adverse events, there are also many habits since interventional studies are lacking. A low caloric and low carbohydrate diet as well as a regular physical training are certainly necessary to avoid lipodystrophy, weight gain and diabetes mellitus. Some patients benefit from the repeated intervention of a dietetic or nutrition specialist. Physical training is often neglected though it is efficacious to limit severity of glucocorticoid-induced myopathy and probably to reduce vascular risk. Low sodium intake has no effect on lipodystrophy and its efficacy to prevent hypertension is doubtful. Benzodiazepines may be useful against anxiety, insomnia and nervousness when these symptoms are cumbersome. Anti-ulcer drugs are generally not indicated because glucocorticoids are not ulcerogenic. Hypokaliemia rarely occurs, so we prefer controlling serum potassium level 1 and 3 months after glucocorticoid initiation rather than systematically prescribe potassium supplementation. Patients on glucocorticoids are at increased risk for cardiovascular events. Due to the lack of studies specific to patients on long-term glucocorticoid therapy, the rules for the prescription of statins are the same as in the general population. There is no known prevention for cutaneous atrophy. However, use of adhesive tape should be strictly avoided when skin atrophy is severe. Prevention of infections is developed elsewhere.

Insulina aspart en población pediátrica / Insulin aspart in the pediatric population

La introducción de los análogos rápidos de insulina en los últimos 15 años, entre ellos la insulina aspart, ha supuesto un cambio importante en las pautas de administración de insulina con generalización de la pauta de inyección múltiple. Las características farmacocinéticas de la insulina aspart (con acción mucho más corta y pico de acción más elevado que la regular) la hace especialmente adecuada para mejorar las glucemias postprandiales, con un número menor de hipoglucemias nocturnas. La tolerancia y seguridad es buena, y la presencia de lipodistrofia rara, necesitando una vigilancia clínica. En niños pequeños, con régimen de vida irregular, su administración postprandial se ha mostrado efectiva y una buena alternativa en estos casos

The introduction of insulin analogues 15 years ago, including insulin aspart, has represented a major change in insulin administration and has allowed intensive insulin therapy to become the treatment of choice. The pharmacokinetic properties of insulin aspart (rapid onset and shorter duration than regular insulin) improve postprandial glycemic control and reduce nocturnal hypoglycemic episodes. The tolerability and safety of insulin aspart are good and lipoatrophy is uncommon, requiring clinical monitoring. In infants and toddlers, who have unpredictable habits, postprandial administration of insulin aspart has shown effective results

Ritonavir-induced lipoatrophy and dyslipidaemia is reversed by the anti-inflammatory drug leflunomide in a PPAR-γ-dependent manner.

BACKGROUND: The complex interplay between viral infection and virus-activated inflammatory pathways with protease inhibitors (PIs) contributes to the increased risk of developing atherosclerosis and coronary artery disease in HIV-infected patients. Leflunomide is an antirheumatic drug whose administration to HIV-1-infected persons effectively decreases T-cell turnover and activation. In this study we have investigated the effects of leflunomide on dyslipidaemia and lipodistrophy induced by ritonavir in rodents. METHODS: Mice were administered ritonavir (5 mg/kg/day) alone or in combination with leflunomide (40 mg/kg/day) for 12 days. Expression of nuclear receptor and lipidogenetic genes was measured in liver and adipose tissues. RESULTS: Administration of the HIV PI ritonavir to mice increased plasma triacylglycerols, free fatty acids and cholesterol levels, and this effect was reverted by cotreatment with leflunomide. Ritonavir administration was associated with reduced epididymal fat/body weight ratio and increased liver content of triacylglycerols content. These effects were reverted by leuflunomide. Histopathology analysis shows that exposure to ritonavir causes inflammation of epididymal fat as demonstrated by dense leukocytes infiltration as well as by increased levels of proinflammatory mediators and reduced expression and activity of peroxisome proliferator-activated receptor-γ (PPAR-γ). Leflunomide reduced epididymal fat inflammatory-metabolic alteration induced by ritonavir and restored PPAR-γ expression in the epididymal fat. CONCLUSIONS: We have shown that the anti-inflammatory drug leflunomide protects against ritonavir-induced inflammation and dysmetabolism in adipose tissue and might be a promising strategy in the setting of HIV-infected patients at risk for HIV-induced dyslipidaemia.

An outbreak of 400 cases of lipoatrophia semicircularis in Barcelona: effectiveness of control measures.

OBJECTIVE: From February 2007 to October 2008, 1137 cases of lipoatrophia semicircularis were registered in distinct workplaces (WPs) in Barcelona. A protocol to establish control measures was designed. This study pretends to evaluate the effectiveness of these measures. METHODS: In this case study, the outbreak course in relation to the implemented measures (relative humidity >50%, ground-mass electrical discharge, and avoidance of sharp-ended table edges) was analyzed. The study population consisted of 417 workers from four different WPs diagnosed between February 2007 and October 2008. RESULTS: Cumulative incidences were 61.6% (WP1), 24.1% (WP2), 8.8% (WP4), and 5.5% (WP3). Based on discharges confirmed by medical services, healing rate was highest in WP1 (93%), followed by WP2 (82%), WP4 (62%), and WP3 (22%). CONCLUSIONS: When the three basic measures were promptly and jointly applied, 90% of the cases were resolved within 6 months.

Metabolic-inflammatory changes, and accelerated atherosclerosis in HIV patients: rationale for preventative measures.

Human immunodeficiency virus (HIV)-infected patients are at a significantly higher risk from coronary heart diseases (CHD) and myocardial infarction (MI) compared to gender- and age-matched non-infected individuals. Combination antiretroviral therapy (cART) has transformed a fatal illness into a chronic stable condition. However, cART induces metabolic abnormalities in HIV-infected patients, while its role in vascular atherosclerosis is still under investigation. The use of cART is linked to inflammation - a key mechanism in atherosclerotic progression and destabilisation that precedes clinical events like MI. There is evidence of visceral fat abnormal distribution in HIV infected patients, and inflammatory changes in HIV infected patients drive the initiation, progression and, ultimately, thrombotic clinical complications induced by atherosclerosis. Visceral adipose tissue, a virtual factory for manufacturing pro-inflammatory mediators, affects the liver function. The inflamed liver promotes the development of pro-atherogenic dyslipidaemia. Pro-inflammatory cytokines released by adipocytes travel to the skeletal muscles and other peripheral tissues, worsening insulin sensitivity and leading to hyperglycaemia. Increased high sensitivity C-reactive protein (hs-CRP) inflammatory marker is associated with endothelial dysfunction in HIV-infected patients. Increased levels of monocytic nuclear factor kappa-B (NFkappa-B), a master switch in the inflammatory cascade, are documented in patients with elevated hs-CRP levels. It can be assumed that, as a result of NFkappa-B activation, hs-CRP up-regulates cytokines that contribute to MI by recruiting leukocytes and promoting thrombosis. This review focuses on the association of HIV-infection, metabolic abnormalities and known mechanisms involved in inducing accelerated atherosclerosis and inflammation in HIV-infected patients, as well as the role of lipid lowering agents in potentially preventing CHD.

[Lipoatrophy after use of long acting insulin glargine analogue in a 32-year-old patient with type 1 diabetes]. / Lipoatrofia po zastosowaniu dlugo dzialajacego analogu insuliny glarginy u 32-letniej pacjentki z cukrzyca typu 1.

A case of a 32-year-old woman with type 1 diabetes diagnosed 1.5 year before presention. The patient was referred to the diabetology department due to decompensation of diabetes and excessive hypodermic atrophy of both thighs. Early symptoms of lipoatrophy appeared after 1.5-2 months of insulin glargine use, in spite of frequently changed hypodermic needles and injection sites on both thighs. Simultaneously, deterioration of diabetes compensation was observed (hyperglycaemia between meals and in the morning), which was corrected by the patient with extra injections of a short acting analogue. Additional examinations confirmed type 1 diabetes (C-peptide <0.01 ng/ml) with concomitant hypothyroidism in the course oh Hashimoto disease. After change of insulin (Insulatard twice daily, Novo Rapid with meals) and injection site (administration to hypodermic tissues of arms and abdomen was started), diabetes compensation was achieved. At follow-up visit after 12 months, diabetes was still under control - HbA1c 6.8%. Moreover, progress of lipoatrophy is not observed.

Tenofovir como estrategia para evitar o detener efectos adversos / Tenofovir as a strategy to avoid or limit adverse effects

La utilización de los análogos de los nucleósidos, especialmente de los análogos de la timidina, producen una depleción del ADN mitocondrial que es la causa de muchos de los efectos adversos de esta familia de fármacos antirretrovirales, entre ellos de la lipodistrofia. La ausencia de un tratamiento específico de la lipoatrofia y su relación directa con la exposición a estavudina y zidovudina, ha conducido a diferentes autores a explorar la evolución de la lipoatrofia y de otros efectos secundarios del tratamiento antirretroviral tras sustituir el análogo de la timidina por tenofivir DF. Estudios prospectivos observacionales y ensayos clínicos aleatorizados que incluyen a más de 2.000 pacientes han demostrado que la sustitución de los análogos de la timidina por tenofovir aumenta la grasa corporal total, sobre todo en la cara y las extremidades, mejora el perfil lipídico y metabólico de los pacientes y eleva los valores de hemoglobina cuando se suspende la zidovudina. Todo ello manteniendo o incluso aumentando la eficacia antiviral e inmunológica del tratamiento antirretroviral. La abundancia de datos científicos que avalan que el cambio de zidovudina o estavudina a tenofovir mejora la lipoatrofia convierte a esta estrategia terapéutica en una recomendación firme del tratamiento antirretroviral

The use of nucleoside analogues, especially that of thymidine analogues, depletes mitochondrial DNA, which is the cause of many of the adverse effects of this family of antiretroviral drugs, among them lipodystrophy. The absence of a specific treatment for lipoatrophy and its direct association with stavudine and zidovudine exposure has led several authors to examine the development of lipoatrophy and of other secondary effects of antiretroviral therapy after substituting a thymidine analogue with tenofovir DF. Prospective observational studies and randomized clinical trials including more than 2000 patients have demonstrated that substituting thymidine with tenofovir increases total body fat, especially in the face and extremities, improves lipid and metabolic profiles in patients, and increases hemoglobin levels when zidovudine is discontinued. These changes are accompanied by maintenance or even an increase of the antiviral and immunological efficacy of antiretroviral therapy. Because of the wealth of scientific data supporting the improvement in lipoatrophy when zidovudine or stavudine are substituted by tenofovir, this strategy can be strongly recommended in antiretroviral therapy (AU)