Surgery for aortic coarctation: a 30 years experience.

OBJECTIVE: A retrospective study to review the experience of a single center with surgery for aortic coarctation over a period of 30 years (1970-1999). METHODS: Criteria for inclusion: (a) aortic coarctation, isolated or associated with congenital heart defect; (b) surgery between 1970 and 1999. Data recorded: (1) date of surgery; (2) age at surgery; (3) associated lesions; (4) surgical technique; (5) simultaneous surgical procedures; (6) early and late surgical results in term of: (a) deaths; (b) need for reoperation because of re-coarctation or other cardiac lesion; (c) residual/recurrent pressure gradient, evaluated at cuff/Doppler at rest; (d) systemic hypertension, requiring medical treatment. RESULTS: One hundred and forty-one patients underwent surgery for aortic coarctation: 30 neonates, 29 infants, 45 children and 37 adults. Associated lesions were found in 8/37 (=21.6%) adults and in 73/104 (=70.1%) pediatric patients. There were no hospital deaths. During the follow-up there were one late death in the adults group (1/37=2.7%) and three late deaths in the pediatric group (3/104=2.9%), all unrelated with aortic coarctation. Re-operation because of re-coarctation occurred only in ten late survivors of the pediatric group (10/101=9.9%), 9/10 operated on before 1980 (P<0.00001). End-to-end anastomosis, enlarged to the aortic arch in neonates, was associated with the lowest incidence of re-coarctation (P<0.005). A significant (>20 mmHg at rest) pressure gradient was found in none of the adults, and in seven of the 91 pediatric patients (7/91=7.7%) late survivors. Three adults (3/36=8.3%) late survivors are on medical treatment to control systemic hypertension. CONCLUSIONS: The long-term results of our retrospective study confirm that surgery has to be considered the gold standard for the treatment of aortic coarctation. The interventional angioplasty techniques have to provide long-term outcome at least similar to the results obtained with surgery.

Can the trabecular bone score be considered as a major clinical risk factor of osteoporotic fractures? A meta-like analysis.

To have an added value over BMD, a CRF of osteoporotic fracture must be predictable of the fracture, independent of BMD, reversible and quantifiable. Many major recognized CRF exist. Out of these factors many of them are indirect factor of bone quality. TBS predicts fracture independently of BMD as demonstrated from previous studies. The aim of the study is to verify if TBS can be considered as a major CRF of osteoporotic fracture. Existing validated datasets of Caucasian women were analyzed. These datasets stem from different studies performed by the authors of this report or provided to our group. However, the level of evidence of these studies will vary. Thus, the different datasets were weighted differently according to their design. This meta-like analysis involves more than 32000 women (≥50years) with 2000 osteoporotic fractures from two prospective studies (OFELY&MANITOBA) and 7 cross-sectional studies. Weighted relative risk (RR) for TBS was expressed for each decrease of one standard deviation as well as per tertile difference (TBS=1.300 and 1.200) and compared with those obtained for the major CRF included in FRAX®. Overall TBS RR obtained (adjusted for age) was 1.79 [95%CI-1.37-2.37]. For all women combined, RR for fracture for the lowest compared with the middle TBS tertile was 1.55[1.46-1.68] and for the lowest compared with the highest TBS tertile was 2.8[2.70-3.00]. TBS is comparable to most of the major CRF and thus could be used as one of them. Further studies have to be conducted to confirm these first findings.

Adjuvant or radical fractionated stereotactic radiotherapy for patients with pituitary functional and nonfunctional macroadenoma.

Purpose: To evaluate the efficacy and toxicity of stereotactic fractionated radiotherapy (SFRT) for patients with pituitary macroadenoma (PMA).Methods and Materials: Between March 2000 and March 2009, 27 patients (male to female ratio, 1.25) with PMA underwent SFRT (median dose, 50.4 Gy). Mean age of the patients was 56.5 years (range, 20.3 - 77.4). In all but one patient, SFRT was administered for salvage treatment after surgical resection (transphenoidal resection in 23, transphenoidal resection followed by craniotomy in 2 and multiple transphenoidal resections in another patient). In 10 (37%) patients, the PMAs were functional (3 ACTH-secreting, 3 prolactinomas, 2 growth hormone-secreting and 2 multiple hormone-secretion). Three (11.1%) and 9 (33.3%) patients had PMA abutting and compressing the optic chiasm, respectively. Mean tumor volume was 2.9 +/- 4.6 cm(3). Eighteen (66.7%) patients had hypopituitarism prior to SFRT. The mean follow-up period after SFRT was 72.4 +/- 37.2 months.Results: Tumor size decreased for 6 (22.2%) patients and remained unchanged for 19 (70.4%) other patients. Two (7.4%) patients had tumor growth inside the prescribed treatment volume. The estimated 5-year tumor growth control was 95.5% after SFRT. Biochemical remission occurred in 3 (30%) patients with functional PMA. Two patients with normal anterior pituitary function before SFRT developed new deficits 25 and 65 months after treatment. The 5-year survival without new anterior pituitary deficit was thus 95.8%. Five patients with visual field defect had improved visual function and 1 patient with no visual defect prior to SFRT, but an optic chiasm abutting tumor, had a decline in visual function. The estimated 5-year vision and pituitary function preservation rates were 93.2% and 95.8%, respectively.Conclusions: SFRT is a safe and effective treatment for patients with PMA, although longer follow-up is needed to evaluate long-term outcomes. In this study, approximately 1 patient with visual field defect out of two had an improved visual.

Metabolic syndrome and the risk of breast cancer in postmenopausal women.

BACKGROUND: Only a few small studies investigated the association between postmenopausal breast cancer and metabolic syndrome (MetS) as a single entity. Materials and methods: We analyzed the data of two Italian and Swiss case-control studies conducted between 1983 and 2007, including 3869 postmenopausal women with incident breast cancer and 4082 postmenopausal controls admitted to the same hospitals as cases for acute conditions. MetS was defined as the presence of at least three components among diabetes, drug-treated hypertension, drug-treated hyperlipidemia, and obesity. RESULTS: The odds ratios (ORs) of postmenopausal breast cancer were 1.33 [95% confidence interval (CI) 1.09-1.62] for diabetes, 1.19 (95% CI 1.07-1.33) for hypertension, 1.08 (95% CI 0.95-1.22) for hyperlipidemia, 1.26 (95% CI 1.11-1.44) for body mass index ≥30 kg/m(2), and 1.22 (95% CI 1.09-1.36) for waist circumference ≥88 cm. The risk of postmenopausal breast cancer was significantly increased for women with MetS (OR = 1.75, 95% CI 1.37-2.22, for three or more MetS components, P for trend for increasing number of components < 0.0001) and the risk was higher at older age (OR = 3.04, 95% CI 1.75-5.29, at age ≥70 years for three or more MetS components). CONCLUSIONS: This study supports a direct association between MetS and postmenopausal breast cancer risk.

Patterns of pain freedom response in 497 cases with classical trigeminal neuralgia and at least one year of follow-up treated by gamma knife radiosurgery

Purpose: To identify patterns of initially pain freedom response in patients with classical trigeminal neuralgia (CTN) with Gamma Knife surgery (GKS) and to compare their associated hypoesthesia and recurrence rates. Methods: In this study we analysed only 497 patients treated between July 1992 and November 2010, with a follow-up longer than 1 year, after excluding megadolichobasilar artery and multiple sclerosis related trigeminal neuralgia, as well as the second GKS treatments so as to have only cases with CTN and single radiosurgical treatment. GKS using a Gamma Knife (model B or C or Perfexion) was performed, based on both MRI and computer tomography (CT) targeting. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.8 mm (range 4.5-14) anteriorly to the emergence of the nerve. A median maximum dose of 85 Gy (range 70-90) was delivered. After empiric methods but also by using a chart with clear cut-off periods of pain free distribution, we were able to divide the initially pain free patients into 3 separate groups: within the first 48 hours, after 48 hours till 30 days and after 30 days, respectively. Results: The median follow- up period was 43.75 months (range 12-174.41). Four hundred and fifty-four patients (91.75%) were initially pain free in a median time of 10 days (range 1-459): 169 (37.2%) became pain free within the first 48 hours (pf<=48 h), compared to 194 (42.8%) between the 3-rd day and the day 30 (pf (>48 h, <=30 d)), inclusively and 91 (20%) patients after 30 days (pf>30d). Differences in terms of postoperative hypoesthesia were found with a p value of 0.014 as follows: the group pf<=48 h had 18 (13.7%) compared to pf (>48 h, <=30 d) with 30 (19%) and pf>30d with 22 (30.5%) patients developing a postoperative GKS hypoesthesia. One hundred and fifty seven (34.4%) patients initially pain free experienced a recurrence with a median delay of 24 months (range 0.62-150.06). There were no statistically significant differences between the three groups concerning recurrence (p value of 0.515). Conclusions: An important number of patients (169 cases, 37.2%) became pain free in the first 48 hours. Hypoesthesia rate was higher within the group becoming pain free after 30 days with a statistically significant difference between the three populations (p= 0.014). Further analysis will eventually help to elucidate the differences observed among groups.

Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C.

BACKGROUND/AIMS: While several risk factors for the histological progression of chronic hepatitis C have been identified, the contribution of HCV genotypes to liver fibrosis evolution remains controversial. The aim of this study was to assess independent predictors for fibrosis progression. METHODS: We identified 1189 patients from the Swiss Hepatitis C Cohort database with at least one biopsy prior to antiviral treatment and assessable date of infection. Stage-constant fibrosis progression rate was assessed using the ratio of fibrosis Metavir score to duration of infection. Stage-specific fibrosis progression rates were obtained using a Markov model. Risk factors were assessed by univariate and multivariate regression models. RESULTS: Independent risk factors for accelerated stage-constant fibrosis progression (>0.083 fibrosis units/year) included male sex (OR=1.60, [95% CI 1.21-2.12], P<0.001), age at infection (OR=1.08, [1.06-1.09], P<0.001), histological activity (OR=2.03, [1.54-2.68], P<0.001) and genotype 3 (OR=1.89, [1.37-2.61], P<0.001). Slower progression rates were observed in patients infected by blood transfusion (P=0.02) and invasive procedures or needle stick (P=0.03), compared to those infected by intravenous drug use. Maximum likelihood estimates (95% CI) of stage-specific progression rates (fibrosis units/year) for genotype 3 versus the other genotypes were: F0-->F1: 0.126 (0.106-0.145) versus 0.091 (0.083-0.100), F1-->F2: 0.099 (0.080-0.117) versus 0.065 (0.058-0.073), F2-->F3: 0.077 (0.058-0.096) versus 0.068 (0.057-0.080) and F3-->F4: 0.171 (0.106-0.236) versus 0.112 (0.083-0.142, overall P<0.001). CONCLUSIONS: This study shows a significant association of genotype 3 with accelerated fibrosis using both stage-constant and stage-specific estimates of fibrosis progression rates. This observation may have important consequences for the management of patients infected with this genotype.

Fissures du labrum glénoïdal postérieur et lésions associées de l'épaule: une étude en arthroscanner [Fissures of the posterior labrum and associated lesions: CT arthrogram evaluation]

PURPOSE: To describe osseous, chondral and tendinous lesions associated with fissures of the posterior labrum. To better understand the pathological processes leading to fissure of the posterior labrum. Materials and methods. Retrospective study of 43 CT arthrograms performed in 43 patients that showed a fissure of the posterior labrum. The following associated lesions were noted: osseous and chondral remodeling of the humeral head and/or glenoid and articular surface fissures of the rotator cuff. Based on type of associated lesions, patients were separated into one of four pathological subgroups: posterior instability, posterosuperior or internal impingement, anterior instability and isolated fissure of the posterior labrum. RESULTS: Sixteen patients (37.2%) of patients showed posterior instability, 12 (27.9%) showed lesions of internal impingement, and 11 (25.6%) showed lesions of anterior instability. Only 4 patients (9.3%) had an isolated fissure of the posterior labrum. CONCLUSION: Posterior instability, internal impingement and anterior instability are the main pathologies leading to fissure of the posterior labrum, which seldom occurs in isolation. Evaluation of these associated lesions allows understanding of the underlying pathological processes leading to fissure of the posterior labrum.

Prevalence of normal weight obesity in the general population

Background and Aims: normal weight obesity (NWO) has been defined as an excessive body fat (BF) associated with a normal body mass index (BMI). Little is known regarding its prevalence in the general population or which cut-offs for BF should be used. Methods: convenience sample of 1,523 Portuguese adults. BF was measured by validated hand-held bioimpedance. NWO was defined as a BMI<25 kg/m2 and a %BF mass>30%, along other published criteria. Results: prevalence of NWO was 10.1% in women and 3.2% in men. In women, prevalence of NWO increased considerably with age, and virtually all women aged over 55 with a BMI<25 kg/m2 were actually considered as NWO. Using gender specific cut-offs for BF (29.1% in men and 37.2% in women) led to moderately lower of NWO in women. Using gender- and age-specific cut-points for %BF considerably decreased the prevalence of NWO in women (0.5 to 2.5% depending on the criterion) but not in men (1.9 to 3.4%). Conclusions: gender- and age- specific or at least gender-specific, instead of single cut-offs for %BF, should be used to characterize and study NWO.

La réhabilitation psychosociale a l'aube du XXIème siècle. I: Principes, population cible et pathologie en cause

The relatively recent development of the psychosocial rehabilitation has its origins mainly in the progress of modern psychopharmacology, the assertion of the rights of the patients and the result of the studies showing that the evolution of persons suffering from severe and persistent mental illnesses can prove to be positive in many cases. In spite of the heterogeneity of the experiences and of the theoretical references, the core principles of the psychosocial rehabilitation imposed themselves. These principles can be classified according to three levels, that of relational ethics, that of the method of intervention and that of the institutional device. A recent study showed that 2.4@1000 of the general adult population of the Canton of Vaud live in sociotherapeutic and rehabilitation accommodations. In this sample, there is a important percentage of relatively young persons (55.3% are under 40). In institutional accommodation there is a majority of patients suffering from major personality disorders and addiction (40.6%), followed by psychotic disorders (37.2%), persistent mood disorders (12.3%), neurotic disorders (6.6%) and psycho-organic disorders (3.3%). In home based rehabilitation, the ratio of patients with psychotic disorders is more important (53.1%). This difference would indicate that people with schizophrenia would have a better social outcome than personality disorders with addiction

Major bleeding risk in anticoagulated patients receiving concomitant antiplatelet therapy: A prospective study.

INTRODUCTION: Current literature suggesting a higher bleeding risk during combination therapy compared to oral anticoagulation alone is primarily based on retrospective studies or specific populations. We aimed to prospectively evaluate whether unselected medical patients on oral anticoagulation have an increased risk of bleeding when on concomitant antiplatelet therapy. MATERIAL AND METHODS: We prospectively studied consecutive adult medical patients who were discharged on oral anticoagulants between 01/2008 and 03/2009 from a Swiss university hospital. The primary outcome was the time to a first major bleed on oral anticoagulation within 12months, adjusted for age, international normalized ratio target, number of medications, and history of myocardial infarction and major bleeding. RESULTS: Among the 515 included anticoagulated patients, the incidence rate of a first major bleed was 8.2 per 100 patient-years. Overall, 161 patients (31.3%) were on both anticoagulant and antiplatelet therapy, and these patients had a similar incidence rate of major bleeding compared to patients on oral anticoagulation alone (7.6 vs. 8.4 per 100 patient-years, P=0.81). In a multivariate analysis, the association of concomitant antiplatelet therapy with the risk of major bleeding was not statistically significant (hazard ratio 0.89, 95% confidence interval, 0.37-2.10). CONCLUSIONS: The risk of bleeding in patients receiving oral anticoagulants combined with antiplatelet therapy was similar to patients receiving oral anticoagulants alone, suggesting that the incremental bleeding risk of combination therapy might not be clinically significant.

Can the trabecular bone score (TBS) be considered as a major clinical risk factor (CRF) of osteoporotic fractures? A meta-like analysis

Abstract: To have an added value over BMD, a CRF of osteoporotic fracture must be predictable of the fracture, independent of BMD, reversible and quantifiable. Many major recognized CRF exist.Out of these factorsmany of themare indirect factor of bone quality. TBS predicts fracture independently of BMD as demonstrated from previous studies. The aim of the study is to verify if TBS can be considered as a major CRF of osteoporotic fracture. Existing validated datasets of Caucasian women were analyzed. These datasets stem from different studies performed by the authors of this report or provided to our group. However, the level of evidence of these studies will vary. Thus, the different datasets were weighted differently according to their design. This meta-like analysis involves more than 32000 women (≥50 years) with 2000 osteoporotic fractures from two prospective studies (OFELY&MANITOBA) and 7 crosssectional studies. Weighted relative risk (RR) for TBS was expressed for each decrease of one standard deviation as well as per tertile difference (TBS=1.300 and 1.200) and compared with those obtained for the major CRF included in FRAX®. Overall TBS RR obtained (adjusted for age) was 1.79 [95%CI-1.37-2.37]. For all women combined, RR for fracture for the lowest comparedwith themiddle TBS tertilewas 1.55[1.46- 1.68] and for the lowest compared with the highest TBS tertile was 2.8[2.70-3.00]. TBS is comparable to most of the major CRF (Fig 1) and thus could be used as one of them. Further studies have to be conducted to confirm these first findings.

A phase I pharmacokinetic study of hypoxic abdominal stop-flow perfusion with gemcitabine in patients with advanced pancreatic cancer and refractory malignant ascites

PURPOSE: As no curative treatment for advanced pancreatic and biliary cancer with malignant ascites exists, new modalities possibly improving the response to available chemotherapies must be explored. This phase I study assesses the feasibility, tolerability and pharmacokinetics of a regional treatment of gemcitabine administered in escalating doses by the stop-flow approach to patients with advanced abdominal malignancies (adenocarcinoma of the pancreas, n = 8, and cholangiocarcinoma of the liver, n = 1). EXPERIMENTAL DESIGN: Gemcitabine at 500, 750 and 1,125 mg/m(2) was administered to three patients at each dose level by loco-regional chemotherapy, using hypoxic abdominal stop-flow perfusion. This was achieved by an aorto-caval occlusion by balloon catheters connected to an extracorporeal circuit. Gemcitabine and its main metabolite 2',2'-difluorodeoxyuridine (dFdU) concentrations were measured by high performance liquid chromatography with UV detection in the extracorporeal circuit during the 20 min of stop-flow perfusion, and in peripheral plasma for 420 min. Blood gases were monitored during the stop-flow perfusion and hypoxia was considered stringent if two of the following endpoints were met: pH </= 7.2, pO(2) nadir ratio </=0.70 or pCO(2) peak ratio >/=1.35. The tolerability of this procedure was also assessed. RESULTS: Stringent hypoxia was achieved in four patients. Very high levels of gemcitabine were rapidly reached in the extracorporeal circuit during the 20 min of stop-flow perfusion, with C (max) levels in the abdominal circuit of 246 (+/-37%), 2,039 (+/-77%) and 4,780 (+/-7.3%) mug/ml for the three dose levels 500, 750 and 1,125 mg/m(2), respectively. These C (max) were between 13 (+/-51%) and 290 (+/-12%) times higher than those measured in the peripheral plasma. Similarly, the abdominal exposure to gemcitabine, calculated as AUC(t0-20), was between 5.5 (+/-43%) and 200 (+/-66%)-fold higher than the systemic exposure. Loco-regional exposure to gemcitabine was statistically higher in presence of stringent hypoxia (P < 0.01 for C (max) and AUC(t0-20), both normalised to the gemcitabine dose). Toxicities were acceptable considering the complexity of the procedure and were mostly hepatic; it was not possible to differentiate the respective contributions of systemic and regional exposures. A significant correlation (P < 0.05) was found between systemic C (max) of gemcitabine and the nadir of both leucocytes and neutrophils. CONCLUSIONS: Regional exposure to gemcitabine-the current standard drug for advanced adenocarcinoma of the pancreas-can be markedly enhanced using an optimised hypoxic stop-flow perfusion technique, with acceptable toxicities up to a dose of 1,125 mg/m(2). However, the activity of gemcitabine under hypoxic conditions is not as firmly established as that of other drugs such as mitomycin C, melphalan or tirapazamine. Further studies of this investigational modality, but with bioreductive drugs, are therefore warranted first to evaluate the tolerance in a phase I study and later on to assess whether it does improve the response to chemotherapy.

Patterns of pain-free response in 497 cases of classic trigeminal neuralgia treated with Gamma Knife surgery and followed up for least 1 year.

Object The goal of this study was to establish whether clear patterns of initial pain freedom could be identified when treating patients with classic trigeminal neuralgia (TN) by using Gamma Knife surgery (GKS). The authors compared hypesthesia and pain recurrence rates to see if statistically significant differences could be found. Methods Between July 1992 and November 2010, 737 patients presenting with TN underwent GKS and prospective evaluation at Timone University Hospital in Marseille, France. In this study the authors analyzed the cases of 497 of these patients, who participated in follow-up longer than 1 year, did not have megadolichobasilar artery- or multiple sclerosis-related TN, and underwent GKS only once; in other words, the focus was on cases of classic TN with a single radiosurgical treatment. Radiosurgery was performed with a Leksell Gamma Knife (model B, C, or Perfexion) using both MR and CT imaging targeting. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.8 mm (range 4.5-14 mm) anterior to the emergence of the nerve. A median maximum dose of 85 Gy (range 70-90 Gy) was delivered. Using empirical methods and assisted by a chart with clear cut-off periods of pain free distribution, the authors were able to divide patients who experienced freedom from pain into 3 separate groups: patients who became pain free within the first 48 hours post-GKS; those who became pain free between 48 hours and 30 days post-GKS; and those who became pain free more than 30 days after GKS. Results The median age in the 497 patients was 68.3 years (range 28.1-93.2 years). The median follow-up period was 43.75 months (range 12-174.41 months). Four hundred fifty-four patients (91.34%) were initially pain free within a median time of 10 days (range 1-459 days) after GKS. One hundred sixty-nine patients (37.2%) became pain free within the first 48 hours (Group PF(≤ 48 hours)), 194 patients (42.8%) between posttreatment Day 3 and Day 30 (Group PF((>48 hours, ≤ 30 days))), and 91 patients (20%) after 30 days post-GKS (Group PF(>30 days)). Differences in postoperative hypesthesia were found: in Group PF(≤ 48 hours) 18 patients (13.7%) developed postoperative hypesthesia, compared with 30 patients (19%) in Group PF((>48 hours, ≤ 30 days)) and 22 patients (30.6%) in Group PF(>30 days) (p = 0.014). One hundred fifty-seven patients (34.4%) who initially became free from pain experienced a recurrence of pain with a median delay of 24 months (range 0.62-150.06 months). There were no statistically significant differences between the patient groups with respect to pain recurrence: 66 patients (39%) in Group PF(≤ 48 hours) experienced pain recurrence, compared with 71 patients (36.6%) in Group PF((>48 hours, ≤ 30 days)) and 27 patients (29.7%) in Group PF(>30 days) (p = 0.515). Conclusions A substantial number of patients (169 cases, 37.2%) became pain free within the first 48 hours. The rate of hypesthesia was higher in patients who became pain free more than 30 days after GKS, with a statistically significant difference between patient groups (p = 0.014).

Cognitive impairment in elderly medical inpatients: detection and associated six-month outcomes.

OBJECTIVE: The authors examined the relationship of cognitive impairment at hospital admission to 6-month outcome (hospital readmission, nursing home admission, and death) in a cohort of elderly medical inpatients. METHODS: A group of 401 medical inpatients age 75 and older underwent a comprehensive geriatric assessment at hospital admission and were followed up for 6 months. Cognitive impairment was defined as a score <24 on the Mini-Mental State Exam. Detection was assessed through blinded review of discharge summary. Follow-up data were gathered from the centralized billing system (hospital and nursing home admissions) and from proxies (death). RESULTS: Cognitive impairment was present in 129 patients (32.3%). Only 48 (37.2%) were detected; these had more severe impairment than undetected cases. During follow-up, cognitive impairment, whether detected or not, was associated with death and nursing home admission. After adjustment for health, functional, and socioeconomic status, an independent association remained only for nursing home admission in subjects with detected impairment. Those with undetected impairment appeared to be at intermediate risk, but this relationship was not statistically significant. CONCLUSION: In these elderly medical inpatients, cognitive impairment was frequent, rarely detected, and associated with nursing home admission during follow-up. Although this association was stronger in those with detected impairment, these results support the view that acute hospitalization presents an opportunity to better detect cognitive impairment in elderly patients and target further interventions to prevent adverse outcomes such as nursing home admission.

Interruptions of cART limits CD4 T-cell recovery and increases the risk for opportunistic complications and death.

BACKGROUND: A major goal of antiretroviral therapy (ART) for HIV-1-infected persons is the recovery of CD4 T lymphocytes, resulting in thorough protection against opportunistic complications. Interruptions of ART are still frequent. The long-term effect on CD4 T-cell recovery and clinical events remains unknown. METHODS: Immunological and clinical endpoints were evaluated in 2491 participants of the Swiss HIV Cohort Study initiating ART during a mean follow-up of 7.1 years. Data were analysed in persons with treatment interruptions (n = 1271; group A), continuous ART, but intermittent HIV-1 RNA at least 1000 copies/ml (n = 469; group B) and continuous ART and HIV-1 RNA constantly less than 1000 copies/ml (n = 751; group C). Risk factors for low CD4 T-cell counts and clinical events were analysed using Cox proportional hazards models. RESULTS: In groups A-C, CD4 T lymphocytes increased to a median of 427, 525 and 645 cells/μl at 8 years. In group A, 63.0 and 37.2% reached above 350 and 500 CD4 T cells/μl, whereas in group B 76.3 and 55.8% and in group C 87.3 and 68.0% reached these thresholds (P < 0.001). CD4 T-cell recovery directly depended on the cumulative duration of treatment interruptions. In addition, participants of group A had more Centers for Disease Control and Prevention B/C events, resulting in an increased risk of death. Major risk factors for not reaching CD4 T cells above 500 cells/μl included lower baseline CD4 T-cell count, higher age and hepatitis C virus co-infection. CONCLUSION: In persons receiving continuous ART larger CD4 T-cell recovery and a reduced risk for opportunistic complications and death was observed. CD4 T-cell recovery was smaller in persons with treatment interruptions more than 6 months.