Human Immunodeficiency Virus (HIV) 2 Superinfection in a Patient Receiving Antiretroviral Therapy With Longstanding HIV-1 Viral Load Suppression.

Dual human immunodeficiency virus (HIV) 1 and HIV-2 superinfections are rare but challenging. A HIV-1-infected patient receiving effective antiretroviral therapy was investigated for a severe CD4+ cell count decline. HIV-2 superinfection was diagnosed and genotypic test revealed mutations conferring resistance to most drug class, limiting options for treatment.

Life-Threatening Everolimus-Associated Pneumonitis: A Case Report and a Review of the Literature.

INTRODUCTION: Noninfective pneumonitis is a class-related effect within mammalian target of rapamycin (mTOR) inhibitors, including everolimus, and can occasionally be severe. CASE REPORT: A 62-year-old man, medicated with everolimus due to a heart transplantation 17 years previously and with chronic kidney disease, was admitted to the intensive care unit (ICU) with acute respiratory failure, cardiovascular shock, and impaired renal function requiring dialysis. Computed tomography (CT) scan revealed right upper lobe consolidation. Extensive microbiological workup, autoimmune testing, and cytology were negative and echocardiography showed preserved heart function. Everolimus levels were normal (5.7-6.1 ng/mL) and the drug was suspended at day 9. The patient was difficult to ventilate and responded poorly to broad-spectrum antibiotic and antifungal therapy. On day 25, CT scan and bronchoscopy revealed left-sided alveolar hemorrhage, and corticosteroid pulses were performed. The patient gradually improved. After discharge and 6 months of follow-up, clinical recovery was complete and chest imaging substantially improved. DISCUSSION: Pneumonitis occurs in up to 4.3% of transplant recipients using everolimus for immunosuppression. Despite usually presenting as a mild and self-limited disease, severe cases have been described. Alveolar hemorrhage can occur and is associated with poor outcome. Everolimus levels do not seem to accurately predict toxicity. Corticosteroid therapy has been used with success in severe disease. We review the pathophysiological, clinical, and management-related aspects of this entity with emphasis on its potential severity. CONCLUSION: Our case was a rare occurrence of severe life-threatening pulmonary disease related to everolimus. Awareness of the potential severity of this entity is important for the management of patients using mTOR inhibitors.

Ischaemic stroke in HIV-infected patients: a case-control study.

OBJECTIVES: The aim of the study was to provide insights into the contributions of HIV infection stage, antiretroviral therapy (ART) and vascular risk factors to the occurrence of ischaemic stroke in HIV-infected patients. METHODS: We performed a case-control study of HIV-infected patients followed in our clinic. We compared patients hospitalized between January 2006 and June 2014 with an ischaemic stroke or transient ischaemic attack to age- and gender-matched controls without stroke. RESULTS: Of 2146 patients followed in our clinic, we included 23 cases (20 men and three women; mean age 51.3 years) and 23 controls. Eighty-three per cent of cases had had a stroke and 17% a transient ischaemic attack. According to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, small-vessel occlusion was the most frequent aetiology, followed by large-artery atherosclerosis and cardioembolism. Compared with controls, stroke was statistically significantly associated with diabetes, smoking and low concentrations of high-density lipoprotein (HDL) cholesterol. Illegal drug use, a low CD4 count and a high viral load were also associated with ischaemic cerebral events. There were no statistically significant differences between cases and controls in Centers for Disease Control and Prevention (CDC) HIV stage, CD4 count nadir and HIV infection time-to-event. No statistically significant differences were found concerning ART or treatment compliance. CONCLUSIONS: In our single centre study, we found associations of illegal drug use, HIV replication and some traditional vascular risk factors with the occurrence of ischaemic cerebral events. The paradigm of the care of HIV-infected patients is changing. Concomitant diseases in the ageing patient with HIV infection, including cerebrovascular disease, must also be addressed in view of their impacts on morbidity and mortality. Apart from controlling the HIV infection and immunosuppression with ART, vascular risk factors must also be addressed.

Assessment of gas compression and lung volume during air stacking maneuver.

PURPOSE: We reasoned that the application of positive pressure through air stacking (AS) technique could cause gas compression and the absolute lung volumes could be estimated. The aim of this study was to estimate the amount of gas compression (ΔV comp) during AS in healthy subjects positioned at 45° trunk inclination and verify if the simultaneous measurements of chest wall volume changes (ΔV CW), by optoelectronic plethysmography, and changes in lung volume (ΔV ao), by pneumotachograph, combined with pressure variation at the airways opening (ΔP ao) during AS are able to provide reliable data on absolute lung volumes. METHODS: Twenty healthy subjects (mean age 23.5 ± 3.8 years) were studied during a protocol that included slow vital capacity and AS maneuvers. V comp was calculated by subtracting ΔV ao and ΔV CW occurring during AS and total lung capacity (TLC) was estimated by applying Boyle-Mariote's law using V comp and ΔP ao. RESULTS: During AS, 0.140 ± 0.050 L of gas was compressed with an average ΔP ao of 21.78 ± 6.18 cmH2O. No significant differences between the estimated TLC (-0.03 ± 3.0% difference, p = 0.6020), estimated FRC (-2.0 ± 12.4% difference, p = 0.5172), measured IC (1.2 ± 11.2% difference, p = 0.7627) and predicted values were found. CONCLUSION: During AS, a significant gas compression occurs and absolute lung volumes can be estimated by simultaneous measurements of ΔV CW, ΔV ao and ΔP ao.

Pain reduction and improvement of function following ultrasound-guided intra-articular injections of triamcinolone hexacetonide and hyaluronic acid in hip osteoarthritis.

The scientific literature has shown positive results regarding intra-articular injections of hyaluronic acid in osteoarthritic joints. When injecting in the hip joint, the guidance of ultrasound can provide higher injection accuracy and repeatability. However, due to the methodological limitations in the current available literature, its recommendation in the current practice is still controversial. This study shows that ultrasound-guided intra-articular injections of triamcinolone hexacetonide and hyaluronic acid can improve pain, function and quality of life in patients with symptomatic and radiographic hip osteoarthritis. In addition, the administration of triamcinolone hexacetonide and hyaluronic acid to the hip joint in these patients can delay the need for interventional surgery.

Artroscopía del tobillo en el tratamiento de la fractura de Bosworth / Ankle arthroscopy in treatment of Bosworth fracture

Resumen: La fractura de Bosworth corresponde a un patrón de fractura-luxación del tobillo con luxación fija del segmento proximal de la fíbula posterior al maléolo posterior de la tibia. Es una lesión poco frecuente que requiere un alto índice de sospecha para su diagnóstico. La luxación fija de la fíbula impide la reducción cerrada, por lo que se impone una reducción abierta y la osteosíntesis de los fragmentos de fíbula y/o tibia. Presentamos un caso clínico de una paciente que sufrió esta lesión asociada a fractura del maléolo interno; fue sometida a tratamiento quirúrgico, asimismo se procedió a la artroscopía anterior del tobillo para evaluar la estabilidad de la sindesmosis, exéresis de fragmentos osteocondrales libres, desbridamiento y microfracturas de lesiones condrales inestables del astrágalo. Un año después la paciente permanece con dolor residual ocasional y un rango de movimiento normal comparado con el tobillo contralateral. La fractura de Bosworth es una lesión grave y poco frecuente que requiere un diagnóstico precoz y tratamiento quirúrgico urgente. La utilización de la artroscopía en su tratamiento agudo permite el diagnóstico y tratamiento de la patología intraarticular asociada y asiste en la evaluación de la reducción adecuada de la fractura y de la estabilidad de la sindesmosis tibiofibular.

Abstract: The Bosworth fracture is a pattern of fracture-dislocation of the ankle joint with fixed dislocation of the proximal part of the fibula behind the posterior malleolus. It is a rare injury, which requires high index of suspicion for diagnosis. Fixed dislocation of the fibula does not allow for closed reduction, so open reduction and fixation of fibula or tibia is required. We present a case report of a patient who suffered a Bosworth fracture, with associated medial malleolus fracture. She underwent surgical treatment with open reduction and internal fixation of the fibula and tibia. We also performed anterior arthroscopy of the ankle, to evaluate the tibiofibular syndesmosis, remove loose osteochondral fragments, and perform debridement and microfracture of unstable chondral lesions of the talus. One year after injury, she remains with occasional pain and a normal range of motion comparing to the contralateral ankle joint. Bosworth fracture is a serious and rare injury, which requires early diagnosis and urgent surgical treatment. Performing ankle arthroscopy in the acute treatment of the Bosworth fracture allows for diagnosis and treatment of associated intra-articular injuries, as well as assisting with adequate fracture reduction and evaluation of the tibiofibular syndesmosis stability.

[Ankle arthroscopy in treatment of Bosworth fracture]. / Artroscopía del tobillo en el tratamiento de la fractura de Bosworth.

The Bosworth fracture is a pattern of fracture-dislocation of the ankle joint with fixed dislocation of the proximal part of the fibula behind the posterior malleolus. It is a rare injury, which requires high index of suspicion for diagnosis. Fixed dislocation of the fibula does not allow for closed reduction, so open reduction and fixation of fibula or tibia is required. We present a case report of a patient who suffered a Bosworth fracture, with associated medial malleolus fracture. She underwent surgical treatment with open reduction and internal fixation of the fibula and tibia. We also performed anterior arthroscopy of the ankle, to evaluate the tibiofibular syndesmosis, remove loose osteochondral fragments, and perform debridement and microfracture of unstable chondral lesions of the talus. One year after injury, she remains with occasional pain and a normal range of motion comparing to the contralateral ankle joint. Bosworth fracture is a serious and rare injury, which requires early diagnosis and urgent surgical treatment. Performing ankle arthroscopy in the acute treatment of the Bosworth fracture allows for diagnosis and treatment of associated intra-articular injuries, as well as assisting with adequate fracture reduction and evaluation of the tibiofibular syndesmosis stability.

La fractura de Bosworth corresponde a un patrón de fractura-luxación del tobillo con luxación fija del segmento proximal de la fíbula posterior al maléolo posterior de la tibia. Es una lesión poco frecuente que requiere un alto índice de sospecha para su diagnóstico. La luxación fija de la fíbula impide la reducción cerrada, por lo que se impone una reducción abierta y la osteosíntesis de los fragmentos de fíbula y/o tibia. Presentamos un caso clínico de una paciente que sufrió esta lesión asociada a fractura del maléolo interno; fue sometida a tratamiento quirúrgico, asimismo se procedió a la artroscopía anterior del tobillo para evaluar la estabilidad de la sindesmosis, exéresis de fragmentos osteocondrales libres, desbridamiento y microfracturas de lesiones condrales inestables del astrágalo. Un año después la paciente permanece con dolor residual ocasional y un rango de movimiento normal comparado con el tobillo contralateral. La fractura de Bosworth es una lesión grave y poco frecuente que requiere un diagnóstico precoz y tratamiento quirúrgico urgente. La utilización de la artroscopía en su tratamiento agudo permite el diagnóstico y tratamiento de la patología intraarticular asociada y asiste en la evaluación de la reducción adecuada de la fractura y de la estabilidad de la sindesmosis tibiofibular.

An unusual case of delayed-type hypersensitivity to ceftriaxone and meropenem.

Recent studies have demonstrated a low cross-reactivity between ß-lactam antibiotics and carbapenems in IgE-mediated reactions. There are no studies on cross-reactivity of meropenem in patients with non-immediate hypersensitivity to cephalosporins. We describe a case of a 13-year-old male, admitted in Neurosurgery with a severe extradural empyema complicating frontal sinusitis, submitted to an emergent bifrontal craniotomy. A generalized maculopapular exanthema, fever and malaise, appeared by the 7th day of meningeal doses of ceftriaxone, clindamycin and vancomycin. Those were replaced by meropenem, with posterior worsening of the reaction and mucosal involvement. A new scheme with amikacin, metronidazole and linezolid was done with improvement. Skin prick, intradermal and patch tests to penicillins, ceftriaxone and meropenem were negative. Lymphocyte transformation test was positive to ceftriaxone and negative to meropenem.Non-immediate T cell mechanism seems to be involved. Diagnosis work-up couldn't exclude cross-reactivity between ceftriaxone and meropenem.

Lung cancer: the immune system and radiation.

Lung cancer has a known relationship with smoking and is one of the leading causes of cancer-related death worldwide. Although the number of studies discussing lung cancer is vast, treatment efficacy is still suboptimal due to the wide range of factors that affect patient outcome. This review aims to collect information on lung cancer treatment, specially focused on radiation therapy. It also compiles information regarding the influence of radiotherapy on the immune system and its response to tumour cells. It evaluates how immune cells react after radiation exposure and the influence of their cytokines in the tumour microenvironment. The literature analysis points out that the immune system is a very promising field of investigation regarding prognosis, mostly because the stromal microenvironment in the tumour can provide some information about what can succeed in the future concerning treatment choices and perspectives. T cells (CD4+ and CD8+), interleukin-8, vascular endothelial growth factor and transforming growth factor-ß seem to have a key role in the immune response after radiation exposure. The lack of large scale studies means there is no common consensus in the scientific community about the role of the immune system in lung cancer patients treated with radiotherapy. Clarification of the mechanism behind the immune response after radiation can lead to better treatments and better quality life for patients.

IL-4 and IL-6 levels and adipose tissue distribution in HIV-1 patients under antiretroviral therapy.

PURPOSE: Combined antiretroviral therapy (cART) for the treatment of HIV-1 infection has been associated with complications, including lipodystrophy. Several interleukins have been implicated in the pathology and physiology of lipodystrophy. The present study aimed to compare the levels of IL-4 and IL-6 in HIV-1 patients under cART with and without, clinically and fat mass ratio defined, lipodystrophy and in four different groups of fat distribution: (1) no lipodystrophy; (2) isolated central fat accumulation; (3) isolated lipoatrophy and (4) mixed forms of lipodystrophy. METHODS: In the present cross-sectional study we evaluated IL-4 and IL-6 levels, insulin resistance and insulin sensitivity indexes in 86 HIV-infected adults under cART. RESULTS: No significant differences in IL-4 and IL-6 levels between the four groups of body composition were observed. Patients with HOMA-IR >4 presented higher levels of IL-6 and lower levels of IL-4, although without statistical significance. No correlation between IL-6, or IL-4, HOMA-IR and quantitative body fat mass distribution was found. CONCLUSION: Although there was a tendency for patients with isolated lipoatrophy and isolated fat accumulation to present higher IL-6 levels, these differences were not statistically significant. No differences were found relating IL-4 levels.

Infliximab therapy increases the frequency of circulating CD16(+) monocytes and modifies macrophage cytokine response to bacterial infection.

Crohn's disease (CD) has been correlated with altered macrophage response to microorganisms. Considering the efficacy of infliximab treatment on CD remission, we investigated infliximab effects on circulating monocyte subsets and on macrophage cytokine response to bacteria. Human peripheral blood monocyte-derived macrophages were obtained from CD patients, treated or not with infliximab. Macrophages were infected with Escherichia coli, Enterococcus faecalis, Mycobacterium avium subsp. paratuberculosis (MAP) or M. avium subsp avium, and cytokine levels [tumour necrosis factor (TNF) and interleukin (IL)-10] were evaluated at different time-points. To evaluate infliximab-dependent effects on monocyte subsets, we studied CD14 and CD16 expression by peripheral blood monocytes before and after different infliximab administrations. We also investigated TNF secretion by macrophages obtained from CD16(+) and CD16(-) monocytes and the frequency of TNF(+) cells among CD16(+) and CD16(-) monocyte-derived macrophages from CD patients. Infliximab treatment resulted in elevated TNF and IL-10 macrophage response to bacteria. An infliximab-dependent increase in the frequency of circulating CD16(+) monocytes (particularly the CD14(++) CD16(+) subset) was also observed (before infliximab: 4·65 ± 0·58%; after three administrations: 10·68 ± 2·23%). In response to MAP infection, macrophages obtained from CD16(+) monocytes were higher TNF producers and CD16(+) macrophages from infliximab-treated CD patients showed increased frequency of TNF(+) cells. In conclusion, infliximab treatment increased the TNF production of CD macrophages in response to bacteria, which seemed to depend upon enrichment of CD16(+) circulating monocytes, particularly of the CD14(++) CD16(+) subset. Infliximab treatment of CD patients also resulted in increased macrophage IL-10 production in response to bacteria, suggesting an infliximab-induced shift to M2 macrophages.

Acute hepatitis E complicated by Guillain-Barre syndrome in Portugal, December 2012--a case report.

Autochthonous hepatitis E virus (HEV) infection has been increasingly reported in Europe and the United States, mostly arising from genotype 3 and less frequently genotype 4. We report here on a patient with HEV genotype 3a infection complicated by Guillain-Barré syndrome in Portugal in December 2012. We draw attention to the diagnosis of autochthonous HEV infection and to its rare, but important, neurological complications.

Acute acalculous cholecystitis in malaria: a review of seven cases from an adult cohort.

PURPOSE AND METHODS: Acute acalculous cholecystitis (AAC) is an uncommon condition related to serious clinical conditions, such as surgery, trauma, burn injuries and sepsis. The diagnosis of AAC remains challenging to make, since it generally occurs as a secondary event in acutely ill patients with another disease. Imaging evaluation is crucial, and well-known criteria are accepted for the diagnosis. To our knowledge, only case reports of AAC related to 12 malaria adult patients have been published. In this series, seven cases of AAC from a cohort of 42 adult patients with severe imported falciparum malaria [according to the World Health Organization (WHO) criteria] are presented. The aim is to report the cases and look for malaria conditions that may affect the incidence of this unusual malaria complication. RESULTS: Ultrasonography revealed gallbladder with wall thickening in all patients, plus other(s) major criteria. Each patient presented five to nine WHO severe malaria criteria: all had hyperparasitaemia and hyperbilirubinaemia. All patients developed renal failure, six pulmonary oedema/acute respiratory distress syndrome (ARDS) (five were mechanically ventilated) and five shock. Treatment was non-operative in five patients, cutaneous cholecystostomy was done in two and the outcome was favourable in all. CONCLUSIONS: Patients with AAC have significantly more commonly five or more criteria of severe malaria: renal insufficiency, pulmonary oedema/ARDS, parasitaemia higher than 30 %, nosocomial infection and a prolonged intensive care unit (ICU) stay. Increased awareness for this unusual and potentially severe complication of malaria is needed.

Population mobility and the changing epidemics of HIV-2 in Portugal.

INTRODUCTION: Portugal is the European country with the highest frequency of HIV-2 infection, which is mainly concentrated in West Africa. The cumulative number of notified HIV-2 infections in Portugal was 1813 by the end of December 2008. To better characterize the dynamics of HIV-2 infection in the country and to obtain data that may be of use in the prevention of the spread of HIV-2, we evaluated a large pooled sample of patients. PATIENTS AND METHODS: Five Portuguese hospitals provided data on HIV-2-infected patients from 1984 to the end of 2007. Data concerning demographic characteristics and clinical variables were extracted. Patients were stratified according to date of diagnosis in approximately 5-year categories. RESULTS: The sample included 442 patients, accounting for 37% of all HIV-2 infections notified in Portugal during that period. HIV-2-infected patients showed clearly different characteristics according to the period of diagnosis. Until 2000, the majority of HIV-2-infected patients were Portuguese-born males living in the north of the country. From 2000 to 2007, most of the patients diagnosed with HIV-2 infection had a West African origin, were predominantly female and were living in the capital, Lisbon. The average age at diagnosis and loss to follow-up significantly increased over time. CONCLUSION: HIV-2 infection has been documented in Portugal since the early 1980s and its epidemiology appears to reflect changes in population movement. These include the movements of soldiers and repatriates from African territories during the independence wars and, later, migration and mobility from high-endemicity areas. The findings of this study stress the importance of promoting migrant-sensitive health care.

Prevalence of obesity and its relationship to clinical lipodystrophy in HIV-infected adults on anti-retroviral therapy.

BACKGROUND: Combination antiretroviral therapy (cART) is associated with lipodystrophy (lipoatrophy and lipoaccumulation) and several metabolic abnormalities that together can contribute to an increased cardiovascular risk. The aim of this study was to evaluate the prevalence of obesity in patients on cART according to the presence of clinical lipodystrophy (CL) and to analyze factors associated with obesity. METHODS: We evaluated 368 HIV-infected adults on cART. RESULTS: CL was present in 59.0%. Independently of gender, patients with CL were more frequently underweight [5.7% (21/368)] and of normal weight [47.3% (174/368)], and less frequently overweight [33.2% (122/368)] or obese [13.9% (51/368)]. Mean body mass index was higher in patients with abdominal prominence regardless of the presence of clinical lipoatrophy. Patients with CL had lower waist circumference, higher waist/hip and fat mass ratio and lower total and subcutaneous fat, without significant difference in visceral fat but with a higher visceral/subcutaneous fat ratio, as evaluated by CT at abdominal level. CL was significantly less frequent in overweight [odds ratio (OR)=0.21, 95% confidence interval (CI): 0.05-0.92] and obese (OR=0.05, 95%CI: 0.01-0.26) patients, when compared to underweight ones, independent of age, gender, duration of infection, cART regimen, virological suppression, and HIV-infection risk factor. CONCLUSIONS: Being overweight or obese is highly prevalent in HIV-infected patients on cART. Patients with CL were more frequently under- or normal weight, and less frequently overweight or obese. Obesity is a condition that should be considered in HIV patients on cART.

Assessment of body fat composition disturbances by bioimpedance analysis in HIV-infected adults.

HIV-lipodystrophy syndrome is characterized by different patterns of body fat distribution (BFD) which are identified by clinical and body composition (BC) assessment, including bioimpedance analysis (BIA). Our aim was to compare BC in HIV-infected patients on combination antiretroviral therapy (cART) according to 4 distinct phenotypes of BFD (G1-no lipodystrophy, G2-isolated central fat accumulation, G3-lipoatrophy, G4-mixed forms of lipodystrophy) and assessed factors associated with them. Anthropometry and BIA were performed in 344 HIV-1 patients. G2 and G4 phenotype patients had significantly higher fat mass (FM) but no differences were observed in fat-free mass (FFM) and total body water among the 4 phenotypes. Significant negative associations were found between the presence of lipoatrophy and female gender, body mass index (BMI), waist (WC), hip (HC) and thigh circumferences, and total body FM estimated by BIA. After adjustment for gender, cART duration and BMI, G3 had significant lower WC [odds ratio (OR)=0.84; 0.78- 0.90] and HC (OR=0.88; 0.81-0.96) mean. Independently of gender, cART duration and BMI, G2 remained significantly associated with higher WC (OR=1.11; 1.05-1.18) and HC (OR=1.15; 1.07-1.23) mean, and with FM estimated by BIA [FM as %, OR=1.17 (1.09-1.26); and FM as kg, OR=1.15 (1.06- 1.25)]. There was a significant positive association between G4 and female gender (OR=1.66; 1.01-2.75), BMI (OR=1.10; 1.04-1.17) and WC (OR=1.15; 1.09-1.21). The similar FFM along the BFD spectrum describes the actual BC of these patients without sarcopenia. In a clinical setting, BIA is an easy and useful tool to evaluate fat mass and FFM and gives us a picture of BC that was not possible with anthropometry.