What do we know about the cardiovascular toxicity of the NSAIDs?

Following the arterial thrombotic risk of rofecoxib (myocardial infarct and cerebral ischemic accidents) that led to its withdrawal from the market, the other coxibs then the NSAIDs have also been blacklisted. The factors responsible for the cardiovascular risk associated with the ingestion of the NSAIDs, selective or not, are not clearly identified. The objective of this review was to collect the available data from the literature, which would allow a better evaluation of the risk and its causes, principally on the basis of the results of randomised studies, but also of case reports and meta-analyses. There is an increase in the risk of arterial thrombotic events under coxibs and traditional NSAIDs, however the risk is variable in the both classes. The cardiovascular risk linked to celecoxib seems variable and modest, and at a standard dose and for usual treatment durations, the risk is probably inexistant. While the real risk of classical NSAIDs is difficult to appreciate from the available results, it can be concluded that the cardiovascular risk of naproxen is low. While part of the cardiovascular consequences of rofecoxib could be associated with increased arterial pressure, these effects are not exclusive to the coxibs since they have been observed with the conventional NSAIDs. However the increase in arterial pressure cannot probably explain everything. Similarly the cardiac insufficiency associated more particularly with rofecoxib, especially in some groups of patients (very old subjects) is not a new type of complication and does not seem to be more frequent with coxibs than with classical NSAIDs. No short-term arterial thrombotic risk of the coxibs and NSAIDs has been clearly demonstrated.     

What do we know about the clinical impact of complete withdrawal of immunosuppression in liver transplantation?

The liver is a privileged organ with a lower incidence of rejection than other organs. However, immunosuppressive regimens are still required to control the alloreactive T-lymphocyte response after transplantation. These treatments may lead to severe complications, such as infectious diseases, cancers, cardiovascular diseases, and chronic renal insufficiency. In clinical transplantation, there is increasing evidence that some liver transplant recipients who cease taking immunosuppressive drugs maintain allograft function, suggesting that tolerance is already present. This strategy is feasible in 25% to 33% of liver transplant recipients. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression (IS) withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with it. In preliminary studies, IS withdrawal was safely achieved in selected liver transplant patients, and improved not only kidney function, but also other IS-associated side-effects such as hypercholesterolemia, hyperuricemia, hypertension, and diabetes control. However, longer follow-up periods are needed to confirm the benefits of IS withdrawal in liver transplant patients.     

Isolated extraabdominal colonic tissue: What do we know about it?

A newborn presenting with an isolated ectopic colonic tissue arising from the vulva without any associated anomaly is reported. The clinicopathologic features of this rare entity are discussed with special emphasis on embryologic basis.     

What do we know about atypical femoral fractures? Insights and enigmas

Although the existence of atypical femoral fractures is well established and bisphosphonate therapy is thought to be a major risk factor, the underlying mechanisms are poorly understood. Epidemiological data show that atypical femoral fractures account for only a small proportion of diaphyseal subtrochanteric femoral fractures, being about 100 times less common than proximal femoral fractures. Consequently, the existence of atypical femoral fractures does not call into question the extremely favorable risk/benefit ratio of bisphosphonate therapy in patients with osteoporosis. Clearly, the number of fractures prevented by bisphosphonate therapy far exceeds the number of atypical femoral fractures potentially related to bisphosphonates.     

How much do we know about the prevention of diseases of the joints and spine?

The questioner "How much do we know about prevention of joint and spine diseases" are presented. Questioner contained 10 questions and two possible answers. This investigation involved 120 medical stuff members, 187 patients on physical therapy and 204 patients with same medical problems without physical therapy. Results are showing no statistically important difference between that two group of patients. More interesting is that there is no difference between medical doctors, physiotherapists and medical technicians comparing to patients. To improve those bad results of medical stuff we suggest that it should be organized in physiatrist ordinations consultations and continuous education with practical examples and advices separately for medical stuff members and patients.     

What do we know about the reliability and validity of physical examination tests used to examine the upper extremity?

The literature regarding the reliability and validity of commonly used clinical tests for disorders of the upper extremity was reviewed. Formal literature search, standard texts, and experts in the field of upper extremity were consulted to locate relevant articles. Range of motion and strength testing of the upper limb have been shown to be reliable, while various tests used for the diagnosis of conditions in the upper limb, such as carpal tunnel syndrome and rotator cuff tendinopathy, have been shown to have varying degrees of validity. Overall, however, we determined that there is little evidence regarding the reliability and validity of physical examination for the upper extremity and specifically less information available regarding the reliability of diagnostic physical examination tests and the validity of impairment measures used for the upper limb. Further studies in this area are warranted in view of the impact of these findings on the treatment of patients.     

What would we like to know, and what do we not know about fibroblast growth factor 23?

Recently, a new view of the molecular mechanisms of phosphate homeostasis and secondary hyperparathyroidism pathogenesis has been proposed, with fibroblast growth factor 23 (FGF23) as a novel player in the field. FGF23 is a 32-kDa peptide secreted by the osteocytes involved in the control of phosphate homeostasis and calcitriol metabolism. FG23 is constantly elevated in advanced chronic kidney disease (CKD) patients, and recent studies have indicated that high levels are associated with the progression of CKD and with higher mortality rates in hemodialysis patients. In the CKD population, high serum FGF23 concentration seems to predict the occurrence of refractory secondary hyperparathyroidism, by inducing a resistance of the parathyroid glands to FGF23, and to be associated with higher mortality risk in incident hemodialysis patients. FGF23 appears to be involved in bone metabolism, but a direct effect of FGF23 on bone disease in humans has not yet been elucidated, even if the inhibitory effect of FGF23 on osteoblast activity that has been described in animal models and hereditary rickets is clearly connected with FGF23 deficiency. The association between altered levels of FGF23 and bone disease could be mainly due to the dysregulation of phosphate-handling and vitamin D metabolism, more than to a direct antiosteoblastic activity of FGF23. FGF23 appears to be a new biomarker, which is independently associated with several cardiovascular risk factors such as endothelial dysfunction, arterial stiffness and left ventricular hypertrophy, in the general population as well as in early CKD. All of the above have been related to cardiovascular and general mortality. Until now, we know that elevated FGF23 levels in dialysis patient are associated with several cardiovascular adverse outcomes mentioned above; the clinical relevance of high FGF23 values in dialysis patients remains unclear, because therapy with active vitamin D sterols further increases FGF23 levels but, on the other hand, is associated with a survival benefit in dialysis patients. This paradox highlights the need for future prospective randomized trials to evaluate the correlation between vitamin D therapy and FGF23 levels in dialysis patients. In the clinical setting, there are still different FGF23 actions that need investigation. In this sense, increased knowledge of mineral metabolism disorder alterations in CKD may be used to improve diagnostics and select future treatments.     

Hoffa’s fat pad tumours: What do we know about them?

Purpose

We report on a group of patients with tumours in the Hoffa’s fat pad (HFP), their clinical presentation, histological type and treatment, including two synovial sarcomas with their clinical follow-up, which have not been described previously in the literature.

Methods

We performed a retrospective review of our prospectively collected database of 25 cases of HFP tumours with at least six months follow-up.

Results

The gender, age at presentation (over and under 16 years of age), clinical features, history of trauma, treatment chosen, and complications were recorded. The mean age of the patients was 32 years (three to 47). Six patients were under 16 years old. Pain was the most common symptom, present in 92 % (n = 23/25). The final diagnoses included 23 (92 %) benign tumours and two (8 %) malignant tumours. The most common benign tumour was pigmented villonodular synovitis (PVNS) (48 % n = 12). The two malignant tumours were synovial sarcomas and both presented in patients under 16 years old.

Conclusions

Hoffa’s fat pad tumours are an uncommon and rarely diagnosed group of lesions that can be misinterpreted as any knee pathology. Although the majority of HFP tumours are benign, malignant tumours should be considered in the differential diagnosis for the paediatric population.     

Breast tomosynthesis: What do we know and where do we stand?

Digital breast tomosynthesis (DBT) is a new imaging technology that addresses the limitation caused by overlapping structures in conventional two-dimensional digital mammography owing to the acquisition of a series of low-dose projection images. This unique technique provides a dual benefit to patients screened for breast cancer. First, DBT increases the cancer detection rate mostly by highlighting architectural distortions and allowing better assessment of masses shape and margins. Second, DBT helps reduce recall rate by discarding asymmetries related to overlapping tissue. However, DBT is not included in the majority of cancer screening programs worldwide. Several issues still need to be addressed such as over-diagnosis and over-treatment, lack of reduction of interval breast cancer, quality control and storage, and radiation dose. In the diagnostic setting, DBT increases the diagnostic accuracy and reduces the number of indeterminate lesions in symptomatic women. Its aforementioned performances regarding asymmetries, masses and architectural distortions allow reducing the number of additional views while working-up a screening-detected lesion. Tumor size is also better assessed at DBT as well as multicentricity, two significant benefits in the staging of breast cancer. Finally, DBT allows a better analysis of scars and helps reduce the rate of indeterminate findings after surgery. Although somewhat limited by high breast density, DBT globally outperforms digital mammography in both screening and diagnostic breast imaging. Additional research is however needed, particularly on relevant screening outcomes. This review describes the main performances of breast DBT in breast cancer screening and diagnosis and the resulting consequences in both settings.     

Carcinogenic potential of polypropylene mid-urethral slings: what do we know so far?

Introduction and hypothesis

Polypropylene (PP) mesh has come under increased scrutiny owing to previous FDA safety communications regarding the risks of mesh in trans-vaginal surgery and ensuing class action litigation for post-operative complications. Additional concerns have been raised regarding a possible link between implanted PP mesh and the long-term development of malignancy. Until recently, no research was specifically committed to the exploration of such a link. Our objective was to provide an overview of the recent literature focusing on any association between the use of PP mesh for midurethral sling procedures and the development of malignancy.

Methods

Multiple online research databases were searched for information related to any possible carcinogenic potential of PP mesh.

Results

There was no increased incidence in the development of malignancy after midurethral sling procedures using PP mesh in any of the studies.

Conclusion

Given the scarcity of evidence suggesting otherwise, the likelihood of PP mesh causing malignancy is exceptionally low. However, with few studies and an unknown latency period between exposure and diagnosis, more observational data would prove useful to exclude causality.

     

What do we know and not know about mirabegron,a novel β3 agonist,in the treatment of overactive bladder?

Introduction and hypothesis

Mirabegron is a novel β3-adrenoceptor agonist recently approved by Japanese, American, and European authorities for overactive bladder (OAB) therapy. Here we review existing knowledge on this new class of medication, analyze existing literature on the topic, and make recommendations regarding its administration and necessary future studies.

Methods

We reviewed the current literature and analyzed mirabegron efficacy, safety, and suitability for treating OAB symptoms. We performed a systematic search of Medline/PubMed, and Embase. Studies exploring mechanisms involved in the effects of mirabegron were included. Searches were limited to the English language.

Results

Two phase II and two large-scale phase III multinational randomized controlled trials have supported mirabegron efficacy and tolerability with up to 12 weeks of therapy in OAB patients. The reported frequency and severity of treatment-emergent and serious adverse events were similar to antimuscarinics but with more than threefold lower incidence of dry mouth than with tolterodine. However, effects on the cardiovascular system, cognitive functions, pharmacokinetic interactions with other drugs, and long-term adverse events have not yet been fully investigated.

Conclusion

Anticholinergic drugs should remain the first-line pharmacologic treatment for OAB until head-to-head comparative study eventually shows that mirabegron has equivalent or superior efficacy. However, it seems logical to use mirabegron as second-line treatment of OAB in patients who are poor responders or intolerant to anticholinergics.     

What to do in failed hemispherotomy? Our clinical series and review of the literature

Hemispherotomy is an established surgical technique to cure or palliate selected, mostly young patients suffering from refractory epilepsy. However, a few patients continue to have seizures despite the surgical hemispherical disconnection. We present a case series of patients who underwent redo hemispherotomy after a first unsuccessful hemispherical disconnection and provide a roadmap for subsequent workup and treatment. The institutional database of epilepsy surgery was reviewed. Twenty-four patients who underwent hemispherotomies for refractory epilepsy were identified between 2007 and 2016. Patients’ notes were checked for demographics, history, clinical presentation, preoperative workup, medical treatment, age at first hemispherotomy, and surgical technique. Complications, histopathology, postoperative antiepileptic drug, and postoperative neurological follow-up were documented. Engel class was used to determine the outcome after surgery. Three patients (one hemimegalencephaly, one perinatal stroke, and one Rasmussen’s disease) underwent redo hemispherotomy after electroencephalography and MRI studies with particular importance given to diffusion tensor imaging (DTI) to demonstrate residual connection between hemispheres. In one case, redo disconnection followed by a frontal lobectomy rendered the patient seizure-free (Engel class I). In one case, the seizure frequency remained the same but generalized seizures disappeared (Engel class III), and in one case, seizure frequency was considerably reduced after the redo disconnection (Engel class II), with a minimum follow-up of 2 years. Surgical aspects, possible reasons of failure of first hemispherotomy, and rationale that led to second-look surgery are presented. Reasons for failure can be related to patient’s selection and/or surgical aspects. Hemispherotomy is a technically demanding procedure and requires accurate preoperative workup. Redo hemispherotomy is a valid option on the basis of further epileptological and radiological workup to demonstrate residual interhemispheric connections and/or rule out bi-hemispheric epileptic activity.     

Non-invasive urinary diagnosis of bladder cancer. What do we know?

Although the current system of classifying bladder cancer by stage and histological grade is very useful, it is still difficult to predict the natural progression of the disease either with or without therapy. Cystoscopy and urine cytology are currently the gold standards in the monitoring and diagnosis of bladder cancer. Classical urine cytology is, however, at least in the diagnosis of G1-tumors, characterized by a relatively low sensitivity. In the last few years, the molecular biological investigation of the basic mechanisms involved in carcinogenesis has provided a host of markers which are of potential diagnostic value for bladder cancer. We provide a current, comprehensive review of the literature on bladder tumor markers and summarize their diagnostic and prognostic potential. At present, no diagnostic marker with a comparable sensitivity and specificity to cystoscopy exists, given that cystoscopy has never been evaluated. The combined analysis of several tumor markers seems to be the most promising approach as an adjunct to cystoscopy. Moreover, the increasing simplification of test systems will increase their acceptance by clinicians.     

Remission of proteinuria in primary glomerulonephritis: we know the goal but do we know the price?

Membranous nephropathy, focal segmental glomerulosclerosis and IgA nephropathy are the most commonly recognized types of primary glomerulonephritis that progress to end-stage renal disease. Persistent proteinuria is a major determinant of such progression. Reduction of proteinuria slows progression of renal disease and improves renal survival, but many of the agents used to reduce proteinuria carry a considerable risk of toxicity. The assessment of benefit versus risk of these medications can be further complicated by the temporal disconnect between the onset of benefit and of serious adverse events. In addition, relapses are common in these disorders and there is often a need for retreatment. Such retreatment might lead to repeated and/or prolonged drug exposure and to the oversight or underestimation of the cumulative dose of these agents because of the potentially extended interval between relapses. Consequently, it is very important to constantly review each patient's status and take into account their age, comorbid conditions and cumulative drug exposure when assessing treatment options. The potentially delayed development of adverse events also emphasizes the need for long-term surveillance of patients who receive immunosuppressive treatment for glomerular disease, often well beyond their drug exposure period and even when the treatment has been successful.