[Paradoxical tuberculosis reaction]. / Réaction paradoxale tuberculeuse.

Paradoxical tuberculosis reaction is defined as the aggravation of lesions present at diagnosis or the development of new lesions under anti-tuberculosis treatment, after exclusion of other alternate causes. It affects 5 to 30% of tuberculosis patients, with a variable prevalence depending on the site of infection and the clinical background. The diagnosis of paradoxical reaction is one of elimination, and requires having ruled out therapeutic failure, notably linked to poor compliance and/or to the presence of mycobacterial antibiotic resistance. The severity of paradoxical tuberculosis reaction lies in its neurological impairment. Despite its clinical importance, the mechanisms involved remain poorly understood and its management is not consensual. Corticosteroids are the cornerstone in the medical management. The role of anti-TNF agents, currently proposed in cases of corticodependence or corticoresistance, remains to be properly defined.

[Sinus node dysfunction associated with cardiac sarcoidosis: A case report]. / Dysfonction sinusale au cours de la sarcoïdose cardiaque: à propos d'un cas.

INTRODUCTION: Sarcoidosis is a multisystemic granulomatous disease of unknown cause occurring in young adults. Cardiac sarcoidosis patients are at increased risk for atrioventricular blocks and ventricular arrhythmias. Sinus node dysfunction is scarcely reported. OBSERVATION: We report a case of cardiac sarcoidosis revealed by a sinus node dysfunction and focus on cardiac and thoracic imaging to guide diagnosis. CONCLUSION: Sinus node dysfunction may be the first manifestation of cardiac sarcoidosis. In unexplained sinus node dysfunction in young patients, advanced cardiac imaging is a key to cardiac sarcoidosis diagnostic. Early recognition of cardiac sarcoidosis enables to start immunosuppressive treatment and discuss implantable cardioverter defibrillator implantation.

Incretin-based drugs and risk of lung cancer among individuals with type 2 diabetes.

AIM: To assess whether dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists are associated with an increased lung cancer risk among individuals with type 2 diabetes. METHODS: We conducted a population-based cohort study using the UK Clinical Practice Research Datalink. We identified 130 340 individuals newly treated with antidiabetes drugs between January 2007 and March 2017, with follow-up until March 2018. We used a time-varying approach to model use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists compared with use of other second- or third-line antidiabetes drugs. We used Cox proportional hazards models to estimate the adjusted hazard ratios, with 95% CIs, of incident lung cancer associated with use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists, separately, by cumulative duration of use, and by time since initiation. RESULTS: A total of 790 individuals were newly diagnosed with lung cancer (median follow-up 4.6 years, incidence rate 1.5/1000 person-years, 95% CI 1.4-1.6). Compared with use of second-/third-line drugs, use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists was not associated with an increased lung cancer risk (hazard ratio 1.07, 95% CI 0.87-1.32, and hazard ratio 1.02, 95% CI 0.68-1.54, respectively). There was no evidence of duration-response relationships. CONCLUSIONS: In individuals with type 2 diabetes, use of incretin-based drugs was not associated with increased lung cancer risk.

A systematic review of observational studies of the association between pioglitazone use and bladder cancer.

AIM: To conduct a systematic review of all observational studies on the effect of pioglitazone on the risk of bladder cancer. METHODS: The MEDLINE and EMBASE databases were queried for papers published between 1 January 2000 and 30 October 2017. We took into consideration observational studies (both retrospective and prospective) that included participants with Type 2 diabetes prescribed anti-hyperglycaemic drugs. RESULTS: While some studies reported an association, others did not, and meta-analyses of these studies showed a significantly increased risk; however, while meta-analysis is a powerful and practical statistical tool, its results should be considered with caution when applied to widely heterogeneous studies. We describe how many of these studies are affected by different types of bias, most notably time-related biases, which should preclude a pooled analysis that would result in biased estimation of the risk. CONCLUSIONS: Given existing data, it is not appropriate to pool the outcomes of highly heterogeneous studies and further rigorously conducted observational research is needed to clarify the role of pioglitazone use on the incidence of bladder cancer.

[Use of the autologous dorsal dermis in reconstruction of the posterior palpebral lamella in blepharopoiesis]. / Utilisation du derme dorsal autologue en reconstruction lamellaire palpébrale postérieure en blépharopoïèse.

OBJECTIVES: Blepharopoiesis represents a double aesthetic and functional challenge. If anterior lamellar reconstruction is less discussed, the variety of posterior lamellar substitutes testifies that none is ideal. We report here our experience of the use of autologous dermal dermis as posterior lamellar substitutes in bilamellar blepharopoiesis. PATIENTS AND METHOD: We performed a single-center retrospective observational study of seven patients undergoing blepharopoiesis using dorsal dermal autograft as posterior lamellar substitute. RESULTS: Between September 2011 and January 2017, seven patients aged of 80.9 years on average were cared for. The defect, affecting in 6 cases on 7 the lower eyelid, concerned almost three-quarter of the length of the eyelid. These defects followed the excision of basal cell carcinomas. Procedures performed under local anesthesia have simple follow-up without complications of the donor site. The superficial surface of the graft in contact with eyeball was covered in 2.4 months with a non-keratinized squamous epithelium like the conjunctiva. Two patients presented ocular functional signs during 2 months without keratitis. Two patients required a second correction procedure. CONCLUSION: The use of the dorsal dermis seems reliable, simple, fast, possible under local anesthesia and sedation, achievable in one operative time, outpatient, without temporary tarsorraphy. The graft is available in large quantities and its removal is not morbid. The good functional and esthetic results suggest that the autologous dermal dermis could represent the main alternative to palatal fibromucosa as a posterior lamellar substitute in old population.

Aromatase inhibitors and the risk of colorectal cancer in postmenopausal women with breast cancer.

Background: A large trial of postmenopausal women with breast cancer reported an imbalance in colorectal cancer events with aromatase inhibitors (AIs), compared with tamoxifen in the adjuvant setting. This unexpected signal was observed within 3 years of randomization. To date, no observational studies have examined this important safety question in the natural setting of clinical practice. Thus, the objective of this study was to determine whether AIs, when compared with tamoxifen, are associated with increased risk of colorectal cancer in postmenopausal women with breast cancer. Patients and methods: Using the UK Clinical Practice Research Datalink, we identified women, at least 55 years of age, with breast cancer newly treated with either AIs or tamoxifen between 1 January 1996 and 30 September 2015, with follow-up until 30 September 2016. High-dimensional propensity score-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of incident colorectal cancer associated with AIs when compared with tamoxifen overall, by cumulative duration of use, and time since initiation. All exposures were lagged by 1 year for latency considerations. Results: A total of 9701 and 8893 patients initiated AIs and tamoxifen as first-line hormonal therapy (median follow-up of 2.4 and 2.9 years, respectively). Compared with tamoxifen, AIs were not associated with an increased risk of colorectal cancer (incidence rates of 150 per 100 000 person-years in both groups; adjusted HR: 0.90, 95% CI: 0.53-1.52). Similarly, there was no evidence of an association with cumulative duration of use (P-heterogeneity = 0.54), and time since initiation (P-heterogeneity = 0.66). Conclusions: In this first population-based study, the use of AIs was not associated with an increased risk of colorectal cancer. These findings should provide reassurance to the concerned stakeholders.

Cardiotoxicity of aromatase inhibitors and tamoxifen in postmenopausal women with breast cancer: a systematic review and meta-analysis of randomized controlled trials.

Background: Aromatase inhibitors (AIs) have been associated with cardiovascular disease in adjuvant randomized controlled trials (RCTs) comparing these drugs to tamoxifen. However, it is unclear whether this risk is real or due to cardioprotective effects of tamoxifen. To address this question, we conducted a systematic review and meta-analysis of all RCTs of AIs and tamoxifen in adjuvant and extended adjuvant setting. Patients and methods: We searched PubMed, Embase (OVID), Cochrane CENTRAL, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov from inception to June 2016 for all RCTs comparing cardiovascular and cerebrovascular safety of AIs to tamoxifen, AIs to placebo or no-treatment, or tamoxifen to placebo or no-treatment in the adjuvant or extended adjuvant setting. Relative risks (RRs) were pooled using DerSimonian and Laird random-effects models with analyses stratified by RCT design. Results: A total of 19 RCTs were included in the meta-analysis (n = 62 345). In the adjuvant setting, AIs were associated with a 19% (RR: 1.19, 95% confidence interval [CI]: 1.07-1.34) increased risk of cardiovascular events compared with tamoxifen. AIs were not associated with an increased risk compared with placebo in the extended-adjuvant setting (RR: 1.01, 95% CI: 0.85-1.20). In the adjuvant setting, tamoxifen was associated with a 33% (RR: 0.67, 95% CI: 0.45-0.98) decreased risk compared with placebo or no-treatment. The results from extended adjuvant RCTs comparing tamoxifen to placebo were inconclusive but suggestive of a small protective effect (RR: 0.91, 95% CI: 0.77-1.07). Conclusions: The increased risk of cardiovascular events with AIs relative to tamoxifen is likely the result of cardioprotective effects of the latter. This new evidence should be considered when assessing the benefits and risks of AIs in the treatment of breast cancer.

Effect of preoperative treatment strategies on the outcome of patients with clinical T3, non-metastasized rectal cancer: A comparison between Dutch and Canadian expert centers.

AIM: High-dose-rate brachytherapy (HDRBT) appears to be associated with less treatment-related toxicity compared with external beam radiotherapy in patients with rectal cancer. The present study compared the effect of preoperative treatment strategies on overall survival, cancer-specific deaths, and local recurrences between a Dutch and Canadian expert center with different preoperative treatment strategies. PATIENTS AND METHODS: We included 145 Dutch and 141 Canadian patients with cT3, non-metastasized rectal cancer. All patients from Canada were preoperatively treated with HDRBT. The preoperative treatment strategy for Dutch patients consisted of either no preoperative treatment, short-course radiotherapy, or chemoradiotherapy. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs) comparing overall survival. We adjusted for age, cN stage, (y)pT stage, comorbidity, and type of surgery. Primary endpoint was overall survival. Secondary endpoints were cancer-specific deaths and local recurrences. RESULTS: Five-year overall survival was 70.9% (95% CI 62.6%-77.7%) in Dutch patients compared with 86.9% (80.1%-91.6%) in Canadian patients, resulting in an adjusted HR of 0.70 (95% CI 0.39-1.26; p = 0.233). Of 145 Dutch patients, 6.9% (95% CI 2.8%-11.0%) had a local recurrence and 17.9% (95% CI 11.7%-24.2%) patients died of rectal cancer, compared with 4.3% (95% CI 0.9%-7.5%) local recurrences and 10.6% (95% CI 5.5%-15.7%) rectal cancer deaths out of 141 Canadian patients. CONCLUSION: We did not detect statistically significant differences in overall survival between a Dutch and Canadian expert center with different treatment strategies. This finding needs to be further investigated in a randomized controlled trial.

Dipeptidyl peptidase-4 inhibitors and the risk of community-acquired pneumonia in patients with type 2 diabetes.

AIMS: To determine whether the use of dipeptidyl peptidase-4 (DPP-4) inhibitors is associated with an increased risk of community-acquired pneumonia. METHODS: The UK Clinical Practice Research Datalink and the Hospital Episodes Statistics database were used to conduct a nested case-control analysis within a cohort of new users of antidiabetic drugs between 2007 and 2012. Incident cases of hospitalization for community-acquired pneumonia were matched with up to 20 controls on age, duration of treated diabetes, calendar year and duration of follow-up. Conditional logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for hospitalization for community-acquired pneumonia associated with current use of DPP-4 inhibitors compared with current use of two or more oral antidiabetic drugs. RESULTS: The cohort included 49,653 patients, of whom 562 were hospitalized for community-acquired pneumonia during follow-up (incidence rate 5.2/1000 person-years). Compared with current use of two or more oral antidiabetic drugs, current use of DPP-4 inhibitors was not associated with an increased risk of hospitalized community-acquired pneumonia overall (adjusted OR 0.80, 95% CI 0.50-1.29) or according to duration of use (p for trend = 0.57). CONCLUSIONS: The use of DPP-4 inhibitors was not associated with an increased risk of hospitalization for community-acquired pneumonia. Additional research is needed to assess the association between these drugs and other serious infections.

Long-term effects of insulin glargine on the risk of breast cancer.

AIMS/HYPOTHESIS: There have been growing concerns regarding the long-term effects of insulin glargine (A21Gly,B31Arg,B32Arg human insulin) on the risk of breast cancer. METHODS: We used the UK's General Practice Research Database (GPRD) to identify a cohort of women aged 40 years or over with type 2 diabetes, treated with insulin during 2002-2006 and followed until the first breast cancer diagnosis or 31 December 2009. After the users of insulin glargine had been matched with users of other insulins on age, calendar time and duration of prior insulin use, the HR of breast cancer associated with insulin glargine use was estimated using a Cox proportional hazards model, adjusted for known risk factors for breast cancer. RESULTS: The cohort comprised 15,227 women, including 4,579 glargine users and 10,648 users of other insulins, of which 246 developed breast cancer during up to 8 years follow-up (incidence rate 4.1 per 1,000 per year). Insulin glargine use was not associated with an increased risk of breast cancer during the first 5 years of use (HR 0.9; 95% CI 0.7-1.3). The risk tended to increase after 5 years (HR 1.8; 95% CI 0.8-4.0), and significantly so for the women who had been on insulin before starting glargine (HR 2.7; 95% CI 1.1-6.5). CONCLUSIONS/INTERPRETATION: The risk of breast cancer in women with type 2 diabetes is not increased during the first 5 years of insulin glargine use. However, longer-term use may increase this risk, particularly in women with longstanding use of insulin before starting insulin glargine.

Isotretinoin therapy and the incidence of acne relapse: a nested case-control study.

BACKGROUND: Previous studies on predictors of acne relapse in patients treated with isotretinoin had either small sample sizes, short follow-up periods, or lacked population-based data. OBJECTIVES: To identify and quantify predictors of acne relapse, and predictors of receiving a second isotretinoin treatment. METHODS: Using the Régie de l'Assurance Maladie du Québec (RAMQ) and Quebec's hospital discharge (Med-Echo) administrative databases, a population-based cohort of 17 351 first-time isotretinoin users was assembled between 1984 and 2003. A nested case-control analysis was performed to determine predictors of acne relapse (as defined by receiving an antiacne medication). A second nested case-control analysis was performed to determine predictors of receiving a second isotretinoin treatment. The index date of cases was the calendar date of dispensing an antiacne medication (isotretinoin or other). Five controls were matched to each case on follow-up time. Rate ratios were estimated using conditional logistic regression. RESULTS: A total of 7100 (41%) subjects experienced an acne relapse. These were matched to 35 500 controls. Being male, under 16 years of age and living in an urban area, and receiving isotretinoin cumulative doses greater than 2450 mg and an isotretinoin treatment longer than 121 days were statistically associated (P < 0.05) with acne relapse. The publishing of the different Canadian acne guidelines had no impact on the incidence of acne relapse (P > 0.05). A total of 4443 (26%) subjects required a second isotretinoin treatment. These were matched to 22 215 controls. There was a greater probability of receiving a second isotretinoin treatment after the publishing of the Canadian acne guidelines (P < 0.05). CONCLUSION: A relatively high rate of subjects experienced an acne relapse after an isotretinoin treatment.

Formation of an adherent polyacrylonitrile/carbon nanotubes composite film onto a polyacrylonitrile brush electrografted on copper.

An adherent polymer film based on a composite of polyacrylonitrile/multiwall carbon nanotubes (PAN/MWNTs) have been elaborated on a copper substrate. The first layer is an electrografted PAN brush on which of a subsequent layer of PAN/carbon nanotubes composite has been deposited by simple dipping from solution in dimethylformamide (DMF). MWNTs have been previously chemically functionalized with 3-cyanopropyltrichlorosilane to promote de-bundling and homogeneous dispersion of the carbon nanotubes in the composite.

Reliability of a device measuring triceps surae muscle fatigability.

OBJECTIVE: To examine the test-retest reliability of a protocol using an apparatus designed to standardise the standing heel rise test for the triceps surae muscle. SUBJECTS: 40 healthy subjects volunteered to test short and medium term test-retest reliability (group SM, median age 24 years), and a convenience sample of 38 subjects with a history of unilateral deep vein thrombosis (DVT) volunteered to test long term test-retest reliability (group L, median age 52 years). DESIGN: Subjects carried out 23 heel rises per minute until either the pace or the height could no longer be maintained. Group SM subjects repeated the test 30 minutes later (short term), and again 48 hours later (medium term). Subjects in group L did the test on the unaffected leg, and repeated the test one week later (long term). RESULTS: The median number of heel rises achieved per trial in group SM was 34 (range 16 to 120). The intraclass coefficient (ICC) was 0.93 (SEM 2.1) for both 30 minute and 48 hour test-retest reliability. In group L, the median number of heel rises was 27 (range 9 to 97), with ICC 0.88 and SEM 3.4. CONCLUSIONS: The apparatus is a simple and inexpensive standardised tool that reliably measures triceps surae fatigability in subjects with no current injury. Future research should assess its use in injured patients.

Effect of graduated elastic compression stockings on leg symptoms and signs during exercise in patients with deep venous thrombosis: a randomized cross-over trial.

Graduated elastic compression stockings (ECS) are often prescribed after deep venous thrombosis (DVT) to alleviate acute symptoms and to prevent and treat post-thrombotic syndrome (PTS). In patients with DVT, leg symptoms tend to worsen with exercise. The effects of ECS use during exercise have not been studied. Objectives were to determine whether ECS improve symptoms and signs and increase exercise capacity when worn during treadmill exercise by patients with prior DVT, with or without PTS. The methods employed a randomized cross-over trial. We recruited subjects who had a first episode of unilateral DVT at least 1 year earlier and categorized them as having, or not having, the PTS using a validated scale. Subjects underwent two identical treadmill exercise sessions at least 1 week apart, and were randomly assigned to wear knee-length 30 mmHg ECS on the affected leg during one of the two sessions. Venous symptoms, leg volume, leg circumference and calf muscle flexibility were measured in the affected leg before and after both exercise sessions. Subjects achieved similar percentage maximum predicted heart rates during both sessions. Comparing the ECS to no ECS session, there were no significant differences in treadmill time (21.2 vs. 21.2 min, P = 0.94), gain in leg volume (71 vs. 73 mL, P = 0.83), or change in soleus or gastrocnemius flexibility, whether or not PTS was present. Symptoms in general worsened slightly with exercise regardless of whether or not ECS were worn and did not differ according to PTS status. Per-subject analysis showed that use of ECS resulted in global improvement of symptoms in 25% of subjects, global worsening in 33% of subjects, and had no or inconsistent effects in 42% of subjects. Whether or not PTS was present, the use of ECS during exercise by patients with prior DVT did not improve symptoms and signs during exercise or increase exercise capacity.