SWIFT: prospective 48-week study to evaluate efficacy and safety of switching to emtricitabine/tenofovir from lamivudine/abacavir in virologically suppressed HIV-1 infected patients on a boosted protease inhibitor containing antiretroviral regimen.

BACKGROUND: In the United States, emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) is a preferred nucleoside reverse transcriptase inhibitor (NRTI) backbone with lamivudine/abacavir (3TC/ABC) as a commonly used alternative. For patients infected with human immunodeficiency virus (HIV-1) virologically suppressed on a boosted protease inhibitor (PI) + 3TC/ABC regimen, the merits of switching to FTC/TDF as the NRTI backbone are unknown. METHODS: SWIFT was a prospective, randomized, open-label 48-week study to evaluate efficacy and safety of switching to FTC/TDF. Subjects receiving 3TC/ABC + PI + ritonavir (RTV) with HIV-1 RNA < 200 c/mL ≥3 months were randomized to continue 3TC/ABC or switch to FTC/TDF. The primary endpoint was time to loss of virologic response (TLOVR) with noninferiority measured by delta of 12%. Virologic failure (VF) was defined as confirmed rebound or the last HIV-1 RNA measurement on study drug ≥200 c/mL. RESULTS: In total, 311 subjects were treated in this study (155 to PI + RTV + FTC/TDF, 156 to PI + RTV + 3TC/ABC). Baseline characteristics were similar between the arms: 85% male, 28% black, median age, 46 years; and median CD4 532 cells/mm(3). By TLOVR through week 48, switching to FTC/TDF was noninferior compared to continued 3TC/ABC (86.4% vs 83.3%, treatment difference 3.0% (95% confidence interval, -5.1% to 11.2%). Fewer subjects on FTC/TDF experienced VF (3 vs 11; P = .034). FTC/TDF showed greater declines in fasting low-density lipoproteins (LDL), total cholesterol (TC), and triglycerides (TG) with significant declines in LDL and TC beginning at week 12 with no TC/HDL ratio change. Switching to FTC/TDF showed improved NCEP thresholds for TC and TG and improved 10-year Framingham TC calculated scores. Decreased estimated glomerular filtration rate [corrected] (eGFR) was observed in both arms with a larger decrease in the FTC/TDF arm. CONCLUSIONS: Switching to FTC/TDF from 3TC/ABC maintained virologic suppression, had fewer VFs, improved lipid parameters and Framingham scores but decreased eGFR. CLINICALTRIALS.GOV IDENTIFIER: NCT00724711.

Final 192-week efficacy and safety of once-daily darunavir/ritonavir compared with lopinavir/ritonavir in HIV-1-infected treatment-naïve patients in the ARTEMIS trial.

OBJECTIVE: This paper presents the final analysis of once-daily darunavir/ritonavir (DRV/r) vs. lopinavir/ritonavir (LPV/r) in treatment-naïve HIV-1-infected adults. METHODS: ARTEMIS (AntiRetroviral Therapy with TMC114 ExaMined In naïve Subjects; NCT00258557) was a randomized, open-label, phase-III, 192-week trial. Patients were stratified by baseline HIV-1 RNA and CD4 count, and randomized to once-daily DRV/r 800/100 mg or LPV/r 800/200 mg total daily dose (either once or twice daily) plus tenofovir/emtricitabine. RESULTS: Of 689 randomized patients receiving treatment (DRV/r: 343; LPV/r: 346), 85 and 114 patients in the DRV/r and LPV/r arms, respectively, had discontinued by week 192. Noninferiority was shown in the primary endpoint of virological response (HIV-1 RNA < 50 copies/mL) [DRV/r: 68.8%; LPV/r: 57.2%; P < 0.001; intent to treat (ITT)/time to loss of virological response; estimated difference in response 11.6% (95% confidence interval 4.4-18.8%)]. Statistical superiority in virological response of DRV/r over LPV/r was demonstrated for the primary endpoint (P = 0.002) and for the ITT non-virological-failure-censored analysis (87.4% vs. 80.8%, respectively; P = 0.040). No protease inhibitor (PI) primary mutations developed and only low levels of nucleoside reverse transcriptase inhibitor (NRTI) resistance developed in virological failures in both groups. Significantly fewer discontinuations because of adverse events were observed with DRV/r (4.7%) than with LPV/r (12.7%; P = 0.005). Grade 2-4 treatment-related diarrhoea was significantly less frequent with DRV/r than with LPV/r (5.0% vs. 11.3%, respectively; P = 0.003). DRV/r was associated with smaller median increases in total cholesterol and triglyceride levels than LPV/r. Changes in low- and high-density lipoprotein cholesterol were similar between groups. Similar increases in aspartate aminotransferase and alanine aminotransferase for DRV/r and LPV/r were observed. CONCLUSION: Over 192 weeks, once-daily DRV/r was noninferior and statistically superior in virological response to LPV/r, with a more favourable gastrointestinal profile, demonstrating its suitability for long-term use in treatment-naïve patients.

Safety and efficacy of heliox as a treatment for upper airway obstruction due to radiation-induced laryngeal dysfunction.

The mixture of helium and oxygen, called heliox, has been successfully used in the management of different respiratory diseases since 1935. Despite several reports on its usefulness, it is not widely available in acute care facilities and it remains somewhat controversial. In this article we present the case of a 69-year-old woman in whom bilateral vocal cord paralysis developed after radiation therapy and in whom heliox was successfully used to manage her upper airway obstruction. Although heliox offers an additional tool in the treatment of various airway and pulmonary problems, it can be used only as a temporizing agent to allow time for appropriate therapy of the underlying process. Given its beneficial physiologic and clinical effects, it seems that further studies are warranted to define a clear and concise protocol for its use in the emergency setting.

Echocardiographic parameters in reversible idiopathic dilated cardiomyopathy.

BACKGROUND: Reversible idiopathic dilated cardiomyopathy (IDCM) is a rare entity. It has been hypothesized that the degree of left ventricular end diastolic dilation is an important independent predictor of prognosis. We undertook a study to identify cases of reversible IDCM and to evaluate the echocardiographic findings in these patients. METHODS: We identified 5 patients with IDCM who showed normalization of left ventricular function over a follow up period of 5 months. The findings were compared with those of 10 patients with IDCM who did not show improvement of left ventricular function. The mean (+/-SE) left atrial and left ventricular (LV) dimensions and ejection fraction at baseline and follow-up were compared in both groups. RESULTS: There were no statistical differences between the mean (+/-SE) left atrium sizes in the cases and control group at baseline [4.52 (+/-0.24) cm v4.6 (+/-0.13) cm; P = 0.758]. Also, no differences were observed between mean (+/-SE) LV dimensions in diastole and systole in both groups at baseline [LV diastole, 6.72 (+/-0.35) cm versus 6.56 (+/-0.22) cm; P = 0.711; LV systole, 5.6 (+/-0.27) cm versus 5.59 (+/-0.29) cm; P = 0.712] as well as in mean (+/-SE) ejection fraction [24% (+/-3.96) versus 21.7% (+/-3.30); P = 0.623]. CONCLUSION: Based on initial echocardiographic parameters, chamber dimensions and baseline LV ejection fraction are not predictors of reversibility.

Idiopathic adulthood ductopenia: case report and review of the literature.

The clinical and pathological findings of idiopathic ductopenia were studied in a 30-year-old woman who initially manifested jaundice and pruritus. Serum biochemical tests of liver function indicated severe and progressive cholestasis. Viral hepatitis markers and circulating autoantibodies were absent. The patient had a normal cholangiogram and lacked evidence of inflammatory bowel disease. Histological examination of a liver specimen showed severe cholestasis and absence of interlobular bile ducts. Severe jaundice and intractable pruritus developed in the patient and served as the indications for liver transplantation 4 months after initial examination. Transplantation resulted in prompt and complete resolution of the jaundice and pruritus. Two types of idiopathic adulthood ductopenia associated with different prognoses are recognized. Patients with type 1 idiopathic adulthood ductopenia are asymptomatic or manifest symptoms of cholestatic liver disease. They tend to have less destruction of the intrahepatic bile ducts on liver biopsy specimens. Their clinical course ranges from spontaneous improvement to progression to biliary cirrhosis. In contrast, patients with type 2 idiopathic adulthood ductopenia generally manifest initial symptoms of decompensated biliary cirrhosis, have extensive destruction of the intrahepatic bile ducts on liver biopsy, and frequently require orthotopic liver transplantation.

Long-term remission of refractory stiff-man syndrome after treatment with intravenous immunoglobulin.

The stiff-man syndrome is a rare neuromuscular disorder characterized by progressive rigidity, stiffness, and intermittent spasm of axial and extremity muscles. Its etiology is unknown. Different therapeutic regimens have been used with variable success. We present a case of refractory stiff-man syndrome, in which the symptoms were successfully controlled by the administration of intravenous immunoglobulin (IVIg). This case gives evidence that IVIg can be a safe and an efficient treatment of refractory stiff-man syndrome. The exact indication for and the cost-effectiveness of IVIg in the treatment of this rare entity remain to be determined.

Jejunal telangiectasias as a cause of massive bleeding in a patient with scleroderma.

Telengiectasias (arteriovenous malformations) can be seen in scleroderma throughout the gastrointestinal tract, including the stomach, small bowel and colon. Massive gastrointestinal bleeding rarely results from these malformations in scleroderma. The case of a patient presenting with severe jejunal bleeding secondary to telangiectasias with special regard to the management is discussed. This case emphasizes the importance of endoscopic examination combined with mesenteric angiography in patients with scleroderma who present with a high index of suspicion of telangiectasias as a source of bleeding.

Resolution of adult respiratory distress syndrome after recovery from fulminant hepatic failure.

Adult respiratory distress syndrome (ARDS) complicating the course of fulminant hepatic failure is nearly always fatal without orthotopic liver transplantation. We report the case of a 50-year-old woman with fulminant hepatic failure and ARDS that resolved after her recovery from the acute liver failure without liver transplantation. The pathogenesis is discussed, particularly with regard to liver-lung interactions.

Massive subfascial hematoma after alteplase therapy for acute myocardial infarction.

The authors report a case of a patient who received alteplase for acute myocardial infarction and developed spontaneous subfascial hematoma without any evidence of direct trauma. Subfascial hematoma remains a rare and self-limited complication of thrombolytic therapy. The development of cutaneous ecchymosis associated with a sudden fall in hemoglobin after the administration of alteplase should strongly suggest the possibility of diffuse subfascial hematoma. Physicians should be aware of the possible association between the use of alteplase and the development of subfascial hemorrhage.

Schwannoma of posterior mediastinum: a case report and concise review.

In the vast majority of cases, schwannoma (neurilemmoma) of the posterior mediastinum arises from 1 of the intercostal nerves and most often is manifested by an asymptomatic solitary mass on a radiograph. This case report emphasizes the importance of new imaging studies in the diagnosis of this classic tumor of the mediastinum, with special regard to the differential diagnosis of such a tumor.

Fatal alveolar hemorrhage and Abciximab (ReoPro) therapy for acute myocardial infarction.

We describe two cases of diffuse alveolar hemorrhage and development of ARDS in patients who underwent percutaneous transluminal coronary angioplasty (PTCA) with stenting in whom Abciximab (ReoPro) was used in combination with other agents interfering with the hemostatic mechanism. The development of pulmonary infiltrates, associated with a fall in hemoglobin after the administration of Abciximab, should strongly suggest the possibility of diffuse alveolar hemorrhage. Physicians should be aware of the possible association between the use of Abciximab and the development of alveolar hemorrhage.

[Characteristics of rapid progressors in HIV infection]. / Caractéristiques des progresseurs rapides au cours de l'infection par le VIH.

Approximately 10% of HIV-infected patients, the rapid progressors, progress to AIDS within the first 2 to 3 years of HIV infection. Their biological characteristics are not clearly known. They have a particular phenotype (DR) of major histocompatibility complex class-II. Anti-HIV antibodies are not neutralizing and may even be facilitators in vitro. Progressors CTL responses are also defective and the production of the cytokines, specially the chemokines RANTES, MIP-1 alpha et MIP-1 beta which may have a role in inhibition of cellular infection by HIV, is impaired. In addition, the rapid progressors have high levels of inflammatory markers which suppose a chronic activation of the immune system. The virological findings are more inconsistent. A uniform finding is a high viral load that does not fall dramatically after primary HIV infection. Some rapid progressors may be infected with more rapidly replicating, virulent HIV strains. However, the question regarding the homogeneity or the other characteristics of viral load remains to be resolved.