Biosimilarity. Do not confuse biosimilar and biocopy. Example of tenecteplase.

Non-innovator biological products (NIBPs) or 'biocopies' are available in several countries at lower prices than biosimilars. These drugs, sometimes so-called 'biosimilars', may not meet all of the quality criteria expected of clinically equivalent products. NIBPs can exhibit major differences in physicochemical and pharmacological properties compared with their reference biological but may be presented to prescribers based on clinical trial data and claimed clinical equivalence. Tenecteplase (TNK-tpA) is a recombinant derivative of tissue plasminogen activator, used as a third-generation thrombolytic agent for treatment of acute myocardial infarction. A TNK-tPA presented as biosimilar to the originator (Metalyse®, Boehringer Ingelheim; TNKase®, Roche/Genentech) is now available for use in India (Elaxim®, Gennova Pharmaceuticals). Elaxim® is not approved in Europe or the USA but has been proposed in several countries as a replacement for the originator. Based on available literature, we discuss why this biocopy cannot be considered biosimilar to the originator tenecteplase. We describe clear differences in physicochemical and pharmacological properties. For example, the biocopy demonstrates clot lysis activity that is substantially lower than the originator and contains high concentrations of foreign proteins that confer potential for immunological reactions. Clinical data on the biocopy are limited; randomized trials to demonstrate the absence of difference in efficacy and safety between the biocopy and originator have not been conducted. This example demonstrates that confirmation of similarity, by close examination of pharmaceutical quality attributes, and preclinical and clinical data, is mandatory before presenting to prescribers a biological product as clinically equivalent.

[Associated factors and sub-clinical myocardial dysfunction in obese patients with masked hypertension]. / L'hypertension artérielle masquée chez les obèses : facteurs associés et atteinte myocardique infraclinique.

INTRODUCTION: Obesity is a worldwide health problem. Masked hypertension is a relatively recent reported entity with a diagnostic problem. The aim of this study was to determine the clinical and paraclinical characteristics and to identify the predictive factors of masked hypertension in obese patients. METHODS: It is a prospective study including obese patients with normal arterial pressure at office. All of these patients were given ambulatory blood pressure measurement (ABPM) to screen for masked hypertension, laboratory tests and a complete echocardiography study. RESULTS: A total of 50 patients were included. The mean age was 46.52±10.4 years. The mean systolic blood pressure (BP) at office was 120.8±8.8mmHg and the mean diastolic BP was 75±7.3mmHg. The prevalence of masked hypertension in obese adults was 36% with a predominantly non-dipper profile (38%). The study of echocardiographic parameters found dilated left atrium (LA) in 16 patients (32%). The left ventricle (LV) was hypertrophied in 32 patients (64%). The overall LV global longitudinal strain (GLS) was on average -18.85±0.9% and the LA GLS was on average 37.35±4.5%. In our study, metabolic syndrome, low HDL cholesterol, elevated fasting blood glucose, hyperuricemia, LA dilatation, LV hypertrophy, diastolic LV dysfunction and altered myocardial deformities were factors associated with masked hypertension in obese adults. CONCLUSION: It is important to screen for hypertension by ambulatory measurement in at-risk obese patients who present associated cardiovascular risk factors to reduce morbidity and mortality. Echocardiography and speckle tracking analysis could be helpful in detection sub-clinical myocardial deterioration in obese patients with masked hypertension.

Q fever presenting as myocarditis.

We report the case of a 19-year-old healthy adolescent, living in an urban area, admitted because of acute chest pain and extensive anterior ST elevation. Coronary arteries were normal on coronary angiography; troponins were very high, echocardiography revealed a preserved global systolic function but an alteration of the longitudinal strain in the inferolateral wall. Cardiac MRI confirmed the diagnosis of acute myocarditis. As part of the etiological workup, Coxiella burnetii serology showed an acute infection. The diagnosis of Coxiella burnetii myocarditis was retained and the patient was treated with doxycycline and corticosteroid therapy. The myocardial localization of this germ is unusual but can be serious, hence the interest of a Coxiella serology in endemic countries face to any acute myocarditis.

[Impact of socioeconomic factors on blood pressure control: Observational study about 2887 hypertensive patients]. / Impact des facteurs socioéconomiques sur l'équilibre de la pression artérielle : étude observationnelle à propos de 2887 hypertendus.

INTRODUCTION: Despite therapeutic progress, less than half of hypertensive patients are controlled. The objective of this study was to examine the links between blood pressure control and socioeconomic factors. METHODS: We used data collected in the cardiology department of Sfax University Hospital as part of the Tunisian national hypertension registry. We studied the associations between the socio-economic variables (educational level, profession, medical insurance) and optimal blood pressure control (SBP<140mmHg and DBP<90mmHg) using logistic regression models. RESULTS: The average age of our population was 65 and the sex ratio was 0.95. We found, as expected, the clinical and behavioral factors associated with a good blood pressure control, namely: female sex, low-sodium diet, therapeutic compliance, and regular physical activity. However, obesity and an increased number of antihypertensive drugs have been associated with poor blood pressure control. The study of the effect of socio-economic variables on BP control finds a significant gradient against the most disadvantaged social categories for our three social variables in the univariate analysis. The inclusion of clinical and behavioral factors in the multivariate analysis attenuated these associations but did not fully explain them. CONCLUSION: Our study shows that there are social inequalities in the control of blood pressure. Social justice and improving living conditions are probably the real solutions to the problem of these social inequalities in health.

Subclinical left ventricle impairment following breast cancer radiotherapy: Is there an association between segmental doses and segmental strain dysfunction?

BACKGROUND: Cardiotoxicity following breast cancer radiotherapy (RT) represents one of the most redoubtable toxicities. The Global longitudinal strain measurement (GLS) based on 2D speckle tracking imaging (STI) allows detection of left ventricular (LV) dysfunction at a subclinical stage. The aim of this prospective study was to detect patients at risk of cardiotoxicity using echocardiographic parameters and to determine the association between segmental RT doses and early cardiac toxicity. MATERIAL AND METHODS: The STI was performed prior to RT and at 3, 6 and 12 months after. The association between subclinical LV dysfunction, defined as a reduction of GLS more than 10% from the initial value, radiation doses to different LV segments and non-radiation factors were performed based on multivariate analyses. RESULTS: From June 2017 to August 2018, a total of 103 female patients were included. Sixty patients had left sided RT. Seven patients (7.8%) developed a GSL impairment. The segmental alterations predominated in the anteroseptal and apical LV segments. The mean Dmean in altered segments was significantly higher than in non-altered segments (6.7 ± 8.8Gy-7.8 ± 8.9Gy vs 4.9 ± 7.9-5.4 ± 8.2Gy; p < 0.05). Age > 55 years and obesity were important confounding factors that should be considered during radiotherapy planning. CONCLUSION: The results of our study show that radiation dose is correlated with the subclinical LV segments' alteration. Global heart delineation seems to be insufficient during the breast radiotherapy planning. Segmental delineation of the LV may be an interesting alternative to limit segmental doses and to reduce the risk of subclinical alterations. A mean dose of 5Gy could be proposed in exposed heart segment.

Endovascular treatment of an immediate postoperative transplant renal artery stenosis with a polymer free drug eluting stent.

The transplant renal artery stenosis occurred up to 23% after kidney transplantation. Endovascular treatment has become the treatment of choice of this complication, but could be challenging in immediate postoperative anastomotic narrowing. We report the case of a adolescent with early renal graft artery stenosis located in the anastomosis and diagnosed 3 days after renal transplantation, with necessity of haemodialysis. This complication was treated by angioplasty on the 25th day, using a polymer free drug eluting stent with a good result. We discussed the precautions and technical features of this procedure.

Culture-independent genome sequencing of Coxiella burnetii from a native heart valve of a Tunisian patient with severe infective endocarditis.

We report draft genome of a Coxiella burnetii strain sequenced from the native valve of a patient presenting with severe endocarditis in Tunisia. The genome could be sequenced without a cellular or axenic culture step. The MST5 strain was demonstrated to be closely related to the published reference genome of C. burnetii CbuK_Q154.

Interest of speckle tracking in the detection of cardiac involvement in pregnant women with hypertensive disorder.

INTRODUCTION: Pre-eclampsia is associated with many cardiovascular disorders present even in asymptomatic women. Several echocardiographic parameters are used to identify them. However, these parameters may be normal until late in the course of the disease process. Which justifies using new and more sensitive techniques. PURPOSE: We sought to test the hypothesis of subclinical cardiac involvement in such patients, based on speckle tracking, and to check its sensitivity compared to the usual methods. METHODS: We conducted a comparative case-control study, which included thirty pregnant women with hypertensive disorder and thirty healthy ones. The filling pressure of the left ventricle (LV) and strain peaks are measured for all women. RESULTS: Usual parameters were in favour of diastolic dysfunction in patients. Eighteen patients with high LV filling pressure were recorded, eight of them had at least one complication, which corresponded to a specificity of 77% and a sensitivity of 47%. However, global longitudinal strain (GLS) was severely altered in patients (p < .001). Moreover, there was a strong correlation of GLS with the usual parameters. Thus, for a threshold value of -18%, GLS had the best sensitivity of 87% and a specificity of 42% to predict complications. There was no significant difference for the radial and circumferential strain. CONCLUSION: GLS is more sensitive than other usual echocardiographic parameters in the detection of subclinical cardiac dysfunction in pregnant women with hypertensive disorder. It is strongly correlated with complications. Future larger studies could validate the integration of 2D-strain in the management of such patients.

[Deep benign fibrous histiocytoma: a case report]. / L'histiocytofibrome bénin profond: à propos d'un cas.

Bening fibrous histiocytoma is one of the most frequent benign tumors. Most tumors are found in the skin, particularly on the limbs. Tumor size is usually small. According to the WHO, a deep location is found for less than 1% of all benign fibrous histiocytomas. Most deep tumors occur in the subcutaneous tissue. Deep locations in other organs have also been reported. We report a case and discuss the pathological and clinical aspects of this rare tumor.

[Clear cell tumor of the lung. A case report with review of the literature]. / La tumeur à cellules claires du poumon. A propos d'un cas avec revue de la littérature.

Clear-cell tumor of the lung is a rare entity of unknown etiology and histogenesis. This neoplasm typically presents as an asymptomatic, peripheral, sharply rounded mass in the lung, and histologically composed of large cells with a clear cytoplasm rich in glycogen, blended with an abundant network of sinusoid-type vessels. Immunohistochemical and ultrastructural procedures lead to diagnosis. We describe a primary pulmonary clear cell "sugar" tumor observed in a 28-year-old woman, and give a review of the literature. Clinical aspects, differential diagnosis, therapy and histogenetic aspects are discussed.

Surface osteosarcoma: Clinical features and therapeutic implications.

INTRODUCTION: Surface osteosarcoma are rare variant of osteosarcoma that include parosteal osteosarcoma, periosteal osteosarcoma and high grade surface osteosarcoma. These lesions have different clinical presentation and biological behavior compared to conventional osteosarcoma, and hence need to be managed differently. GOAL: The aim of this study is to analyze the clinico-pathological features and outcome of a series of surface osteosarcoma in an attempt to define the adequate treatment of this rare entity. PATIENT AND METHOD: It is a retrospective and bicentric study of 18 surface osteosarcoma that were seen at the KASSAB's Institute and SAHLOUL Hospital from 2006 to 2013. The authors reviewed the clinical and radiologic features, histologic sections, treatments, and outcomes in this group of patients. RESULTS: Seven patients were male (38.9%) and 11 were female (61.1%) with mean age of 25 years (range from 16 to 55 years). Eleven lesions were in the femur and 7 in the tibia. We identified 11 parosteal osteosarcoma (six of them were dedifferentiated), 3 periosteal osteosarcoma and 4 high grade surface osteosarcoma. Six patients had neoadjuvant chemotherapy and all lesions had surgical resection. Margins were wide in 15 cases and intra lesional in 3 cases. Histological response to chemotherapy was poor in all cases. The mean follow up was 34.5 months. Six patients (33.3%) presented local recurrence and 8 patients (44.4%) presented lung metastases. Six patients (33.3%) died from the disease after a mean follow up of 12 months (6-30 months); all of them had high grade lesions. CONCLUSION: Histological grade of malignancy is the main point to assess in surface osteosarcoma since it determines treatment and prognosis. Low grade lesions should be treated by wide resection, while high grade lesions need more aggressive surgical approach associated to post operative chemotherapy.

[Cardiogenic pulmonary edema following ß2 agonist infusion for acute, severe asthma]. / Œdème aigu du poumon secondaire à l'administration intraveineuse de ß2 mimétiques pour asthme aigu grave.

We report the case of a severe acute pulmonary edema secondary to the administration of salbutamol to a patient admitted for severe asthma. The diagnosis of acute pulmonary edema was suspected on the clinical examination, chest radiography, biological (plasmatic Pro-BNP rate) and echocardiographic findings. Rapid improvement under dobutamine and mechanical ventilation argue in favour of cardiogenic pulmonary edema. The young age of our patient, the absence of history of cardiovascular disease and the chronology of this complication onset regarded to salbutamol infusion could suggest ß2 agonist involvement in this event. The improvement of cardiac function on echocardiography and the normal results obtained with myocardial perfusion scintigraphy performed 35 days later show the left ventricular reversible dysfunction.

Early biliary pseudolithiasis during ceftriaxone therapy for acute pyelonephritis in children: a prospective study in 34 children.

The prolonged biological half-life of Ceftriaxone, allowing once-daily dosing, has contributed to the large diffusion of this third-generation cephalosporin in children. Ceftriaxone is known to induce reversible precipitates in the gallbladder of adults and children. A prospective study was conducted during 1997 in 34 children admitted for the treatment of acute pyelonephritis. Ceftriaxone (intravenous daily single-dose of 50 mg/kg under 2g/day) was initially used. A first gallbladder sonogram, performed before the first or second injection, was normal in all cases. A second evaluation was performed before the fifth and last injection. On this second evaluation the presence of one (n = 3) or two gallstones was recorded in 5 children (15%) on a sonogram made after 3 (n = 4) or 5 (n = 1) injections. Their median age was 7 years (range 4 months to 11 years). All five children remained symptom-free and the normalization of the sonographic patterns was constant on the last sonogram performed 2 (n = 1), 3 (n = 2) and 5 months (n = 2) after discontinuation of Ceftriaxone. This study confirms the possibility of precocious biliary lithiasis under Ceftriaxone therapy in childhood and their spontaneous dissolution after discontinuation of the drug. They seem unpredictable and independent of the age, sex in a cohort homogeneous for the nature of the infection, modality of a short- and low-dose therapy. Clinicians and radiologists should be aware of this complication as an etiology of a so-called primary cholelithiasis and to prevent anxiety or unnecessary cholecystectomy. The antibacterial and pharmacokinetic benefits of Ceftriaxone outweigh the problem of reversible biliary pseudolithiasis with this drug.

[Common bile duct calculi and agenesis of the gallbladder. Physiopathological considerations. Apropos of 2 cases]. / Lithiase cholédocienne et agénésie vésiculaire. Réflexions sur la physiopathologie. A propos de 2 cas.

Could the association of common duct stones and agenesis of the gallbladder be a coincidence or are they related to a cause and effect phenomenon? After having dealt with different physiopathological hypothesis, the authors think that common duct stones result from that congenital absence of the gallbladder. A method to ascertain their hypothesis is put forward.

[Multiple hydatid cyst of the liver: indication for a conservative treatment in uncomplicated univesicular localizations. Apropos of 19 cases]. / Le kyste hydatique multiple du foie: indication du traitement "conservateur" dans les localisations univésiculaires non compliquées. A propos de 19 cas.

Results are reported of treatment of multiple hydatid cysts of liver in 19 patients (63 cysts) between 1981 and 1985. The relative frequency and severity of forms of multiple localization are emphasized as well as particular features related to extra-hepatic abdominal localizations. Diagnosis is assisted by ultrasound and particularly CT scan imaging in multiple forms. Since surgical excision remains the only potentially curative treatment for hydatid cyst, conservative therapy by puncture-sterilization and aspiration, with or without combined medical treatment, can be proposed when certain localizations make conventional surgery difficult and dangerous for vital prognosis.

[Complications and sequelae of benign thyroid surgery]. / Complications et séquelles de la chirurgie thyroïdienne bénigne.

A series of 640-operations performed on benign thyroid gland during 8 years is presented. The pre and post operative mortality is 0.62 per cent. Late recurrent nerve paralysis occurred in 2.6 per cent. 27 patients had transit hypocalcemia and 8 had permanent hypoparathyroidism or 1.2 per cent. These complications has been studied in relation with patient benign thyroid affection and operation. In case of thyroidectomy without search for recurrent laryngeal nerve, nervous paralysis are frequent when if parathyroid gland are rare, for these lata are protected. Systematic dissection of recurrent nerve reduce nervous sequelae, but increase hypoparathyroidism, mainly by devascularisation of parathyroids glands. Complications and sequelae of thyroid surgery can yet be reduced by a rigorous surgical technic, a most sure experience and a systematic dissection of recurrent nerve and gland parathyroid in case of bilateral operation.

[Risk to the parathyroid glands in surgery of the thyroid]. / Le risque parathyroïdien en chirurgie thyroïdienne.

From 1981 to 1987, 305 patients underwent surgery in this department for thyroid disorders, including 7 reinterventions for total thyroidectomy, with a mortality of 0.75% and a specific morbidity of 13.4%. The overall incidence of post-operative parathyroid insufficiency was 4.6%. This was higher after bilateral thyroidectomy (7.6%) than after unilateral thyroidectomy (0.7%). The early parathyroid risk was also higher after surgery for hyperthyroidism (9.7%) than after surgery for euthyroid goitres (2.4%). The true incidence of post-operative parathyroid insufficiency can only be evaluated by systematic clinical and biological investigation. Parathyroid insufficiency is due to devascularisation of one or several parathyroids during the course of thyroidectomy, or occasionally due to accidental resection with the thyroid lobe. The prevention of post-operative parathyroid insufficiency requires a surgical technique which limits any devascularisation of the parathyroid glands and if the vascular supply to a parathyroid is put at risk then autotransplantation should be performed.

Effects of a low-intensity dynamic-resistance training protocol using an isokinetic dynamometer on muscular strength and aerobic capacity after coronary artery bypass grafting.

OBJECTIVE: Study the effect of muscle strength training on muscle strength, maximal oxygen uptake (VO2max), hemodynamic and anthropometric parameters as well as quality of life after coronary artery bypass grafting (CABG). METHODS: After CABG surgery, 32 patients were randomized into two groups. The first group was to perform aerobic-type training with a cycle ergometer (AT=16). The second group was to perform low-intensity muscle strength training of the quadriceps and hamstrings using an isokinetic dynamometer (i.e. 20 to 30% of peak torque) (ST=16). Before and after the strength training program we conducted a stress test, evaluation of isokinetic force production, 6-minute walking test, body impedance analysis (BIA) and SF-36 quality of life test. RESULTS: Compared to the AT group, the ST group showed better results with improved quadriceps strength (48.2% vs. 8.2%), VO2max (P<.001) and diastolic blood pressure at rest (P=0.01). Quality of life improved in both groups. CONCLUSION: The dynamic-resistance muscle strength training protocol using isokinetic dynamometer can safely (i.e. without clinical symptoms or changes to the ECG and arterial blood pressure) improve muscle strength and VO2max without any major risks in patients post-CABG. These findings should encourage additional studies to validate the relevance of these strength training modalities in rehabilitation centers.