What is the impact of cardiovascular and renal complications on the benefit/risk ratio of the NSAIDs?

Long-term studies of NSAIDs have demonstrated cardiovascular toxicity which poses a general problem of the benefit risk between the relief of the patient's symptoms and the risk of digestive and cardiovascular toxicity. The digestive complications and the risk factors associated with the ingestion of NSAIDs have been defined by numerous studies but the prevention of this digestive toxicity can be attempted. The benefit-risk ratio caused by the digestive and cardiovascular toxicities of the NSAIDs and COX-2 inhibitors must be evaluated for each individual before starting a treatment. For a treatment of short duration in patients with a low risk of digestive and cardiovascular complications, the risk of digestive toxicity must be taken into consideration first and the COX-2 inhibitors are favoured. For a treatment of long duration the risk must be evaluated with the greatest care. In the case of cardiovascular risk factors, the cardiovascular risk must be evaluated and the treatment must be prescribed at the lowest dose for the shortest duration. In patients with very high risk of digestive and cardiovascular complications, since the digestive and cardiovascular extra-mortality associated with the ingestion of NSAIDs or COX-2 inhibitors is high, it is advised to abandon this type of long-term treatment.     

Involvement of WNT/β-catenin Signaling in the Treatment of Osteoporosis

Osteoblast differentiation is predominantly regulated by the WNT/β-catenin signaling (canonical WNT pathway), which, together with bone morphogenetic proteins, acts as the master regulator of osteogenesis. The recent characterization of the canonical WNT pathway in the regulation of bone modeling and remodeling provided important insights for our understanding of the pathophysiology of a number of conditions and of the mechanism of action of hormones or drugs with important effect on bone metabolism. This review is mainly focused on the growing therapeutic implications of these new findings. WNT/β-catenin signaling plays a key role in bone tissue by determining the differentiation of stem cells into mature osteoblasts rather than into chondrocytes and adipocytes. Its regulation is predominantly driven by the production of two WNT signaling antagonists: sclerostin (SOST) and Dickkopf-related protein 1 (DKK1). The most proximate regulator of SOST expression by osteocytes and its serum levels is bone mechanical load. SOST expression is increased with advancing age, by glucocorticoid treatment and during treatment with antiresorptive agents such as bisphosphonates and denosumab, while it is decreased by parathyroid hormone excess or administration of estrogens. Correlation between DKK1 serum levels and bone formation in various pathological conditions or during osteoporosis treatment has been reported. Inhibitors of the negative regulators of WNT/β-catenin signaling (“inhibiting the endogenous inhibitors”) are potential candidates for the prevention and treatment of bone loss. Inactivating monoclonal antibodies against SOST appears to be the most attractive strategy because SOST is the only component of the WNT pathway expressed almost exclusively by osteocytes.     

Does the novel PET/CT imaging modality impact on the treatment of patients with metastatic colorectal cancer of the liver?

OBJECTIVE: To compare the diagnostic value of contrast-enhanced CT (ceCT) and 2-[18-F]-fluoro-2-deoxyglucose-PET/CT in patients with metastatic colorectal cancer to the liver. BACKGROUND: Despite preoperative evaluation with ceCT, the tumor load in patients with metastatic colorectal cancer to the liver is often underestimated. Positron emission tomography (PET) has been used in combination with the ceCT to improve identification of intra- and extrahepatic tumors in these patients. We compared ceCT and a novel fused PET/CT technique in patients evaluated for liver resection for metastatic colorectal cancer. METHODS: Patients evaluated for resection of liver metastases from colorectal cancer were entered into a prospective database. Each patient received a ceCT and a PET/CT, and both examinations were evaluated independently by a radiologist/nuclear medicine physician without the knowledge of the results of other diagnostic techniques. The sensitivity and the specificity of both tests regarding the detection of intrahepatic tumor load, extra/hepatic metastases, and local recurrence at the colorectal site were determined. The main end point of the study was to assess the impact of the PET/CT findings on the therapeutic strategy. RESULTS: Seventy-six patients with a median age of 63 years were included in the study. ceCT and PET/CT provided comparable findings for the detection of intrahepatic metastases with a sensitivity of 95% and 91%, respectively. However, PET/CT was superior in establishing the diagnosis of intrahepatic recurrences in patients with prior hepatectomy (specificity 50% vs. 100%, P = 0.04). Local recurrences at the primary colo-rectal resection site were detected by ceCT and PET/CT with a sensitivity of 53% and 93%, respectively (P = 0.03). Extrahepatic disease was missed in the ceCT in one third of the cases (sensitivity 64%), whereas PET/CT failed to detect extrahepatic lesions in only 11% of the cases (sensitivity 89%) (P = 0.02). New findings in the PET/CT resulted in a change in the therapeutic strategy in 21% of the patients. CONCLUSION: PET/CT and ceCT provide similar information regarding hepatic metastases of colorectal cancer, whereas PET/CT is superior to ceCT for the detection of recurrent intrahepatic tumors after hepatectomy, extrahepatic metastases, and local recurrence at the site of the initial colorectal surgery. We now routinely perform PET/CT on all patients being evaluated for liver resection for metastatic colorectal cancer.     

Compression of the outlets of the leptomeningeal veins —the cause of intracranial plateau waves

Summary A case of otitic hydrocephalus, or intracranial hypertension secondary to inflammatory thrombosis of the left lateral sinus is described. Persistently elevated intracranial pressure, which did not respond to medical treatment, led to visual deterioration. A venous bypass graft was inserted between the left lateral sinus and jugular vein and was followed by rapid resolution of the raised intracranial pressure. The indications for this procedure are discussed.     

Does the position of the patient affect the presence and/or degree of reflux in an ileal conduit urinary diversion?

OBJECTIVE: To assess the effect of patient position (supine, sitting or standing) on ileo-ureteric reflux in patients with an ileal conduit urinary diversion, in whom such reflux is normally detected when they are supine during a retrograde loopogram. PATIENTS AND METHODS: The study included 10 patients with an ileal conduit as a primary urinary diversion; a loopogram was obtained with the patient upright or supine and a further film taken with the patient supine but at 45 degrees to the ground. RESULTS: When supine, free ileo-ureteric reflux occurred into both ureterorenal units in eight patients. The remaining two patients, who had previously undergone unilateral nephrectomy, also had reflux into their existing renal units. Of the 18 units, 15 had grade III and three had grade IV reflux. In the upright and 45 degrees position, reflux still occurred in al ureterorenal units. The patient's position did not affect the degree of reflux in 16 units, but in one unit with grade IV reflux and another with grade III reflux, the reflux was one grade less severe. CONCLUSIONS: Ileo-ureteric reflux is common after ileal conduit diversion and may contribute to the likelihood of renal deterioration. The presence and/or degree of reflux is generally not affected by the position of the patient.     

Role of TGFβ in the anti-estrogen response/resistance of human breast cancer

Transforming growth factor (TGF) has potent inhibitory effects upon epithelial proliferation and malignant progression may be associated with breakdown of the autocrine and paracrine inhibitory loops in which TGF participates. The therapeutic effects of anti-estrogens may be partially attributable to boosting of local endogenous levels of TGF. This article reviews the evidence in support of TGF being a proximate effector in mediation of the anti-neoplastic effects of anti-estrogens. Both the conventional estrogen receptor (ER)³ dependent and ER independent mechanisms of action are likely to be involved. Evidence for preferential stromal induction of TGF by anti-estrogens is emphasized, together with the therapeutic potential of this strategy for improving outcome in early breast cancer irrespective of ER status.     

A urogynecologist’s view of the pelvic floor effects of vaginal delivery/cesarean section for the urologist

Pregnancy and parturition have been implicated in the development of pelvic floor dysfunction. These disorders include urinary incontinence, fecal incontinence, pelvic organ prolapse, and other pelvic and sexual dysfunctions. The urologist caring for women with urinary dysfunction needs to be familiar with the causes of pelvic floor dysfunction and their implications. Defects of the pelvic floor have clearly resulted from the traumatic effect of vaginal delivery. The likely mechanisms of injuries during vaginal delivery involve stretching and compression of the pudendal nerve and peripheral branches, as well as an additional tearing of muscles and connective tissue. Optimal management of labor and optimal techniques of repair of unavoidable sphincteric lacerations, ante- and postpartum pelvic floor muscle conditioning, and timely and proper indications for cesarean delivery will minimize the effect of incidental traumatic delivery.     

Emerging studies of the urinary proteome: the end of the beginning?

PURPOSE OF REVIEW: Urinary proteomics is a rapidly growing field, holding the promise of discovery of biomarkers of various disease processes and elucidation of pathophysiologic mechanisms of disease states. This may be true not only for renal disease but for diseases of other organs and systemic disorders. RECENT FINDINGS: Recent advances in separation technologies and rapid, high-throughput, and accurate protein detection and identification now permit rigorous examination of complex biological fluids. This review sketches the progress achieved in recent years and the existing hurdles in describing a normal urinary proteome, its aberrations in pathological conditions, and the search for biomarkers of several renal and non-renal diseases. SUMMARY: The first wave of urinary proteomic studies has now arrived and their results are summarized. Future lines of investigation are delineated.     

The aponeurosis of the “slacksole” of the foot

Summary A case is presented with folded sole of the foot caused by absence of the aponeurosis and hypertrophy of the muscles of the little toe. Operative treatment gave a good result.     

Dimensions of Growth? Examining the Distinctiveness of the Five Factors of the Posttraumatic Growth Inventory

Posttraumatic growth, defined as positive transformation following trauma, is commonly measured using the Posttraumatic Growth Inventory (PTGI; Tedeschi & Calhoun, 1996) and is postulated to comprise five distinct domains: Changes in Relationships, Life Possibilities, Personal Strength, Spirituality, and Appreciation of Life. However, research has indicated that the model fit is not good and the factors are highly intercorrelated. Further, no studies have formally examined the heterogeneity of correlations of the five factors with external constructs. In an effort to examine the construct validity of the five‐factor model of the PTGI, the present study aimed to examine the degree to which the theorized five factors demonstrate meaningful differential associations with relevant external correlates. Participants were 400 undergraduate students who reported having experienced a stressful event and completed the Life Events Checklist for DSM‐5, PTGI, Posttraumatic Stress Disorder Checklist for DSM‐5, Grit Scale‐12, Connor‐Davidson Resilience Scale‐10, and Work and Social Adjustment Scale. We found few instances of significant differentiation, and effect sizes for pairwise comparisons were generally small, Cohen's qs = 0.01–0.35. Although factor analytic evidence suggests there are five distinct underlying constructs, our results indicated that these factors do not significantly differ in their associations with external correlates. Implications for use of the PTGI and future research directions are discussed.     

Does the fabella contribute to the reinforcement of the posterolateral corner of the knee by inducing the development of associated ligaments?

The fabellofibular (FF) and arcuate ligaments are closely colocated at the posterolateral corner of the knee. However, a bony fabella is often absent in Japanese subjects. We investigated these structures morphometrically using 212 knees. A thick FF ligament was found in 38.1% (40/105) of knees with a hard fabella. When identified histologically, a bony fabella accompanied a thick FF in 82.8% (24/29). Conversely, a thin or indefinite FF ligament and an elastic-textured fabella co-existed in 77.9% (60/70) of knees. There were no strong correlations between the morphology of the fabella and the arcuate ligament. Thus, a hard or bony fabella seemed to relate to thickening of the FF ligament. In contrast, the thicknesses of the FF and arcuate ligaments were negatively correlated. When the FF ligament was more than 5mm thick, indicating that it was as strong as the lateral collateral ligament, no arcuate ligament could be identified. Conversely, a thin or indefinite FF ligament often accompanied a well-developed arcuate ligament (61.9%, 96/155). Our observations suggest that these ligaments act in a complementary manner to stabilize the posterolateral corner. A possible common function is fixation of the popliteal tendon on the joint capsule and lateral meniscus, rather than direct stabilization against rotation stress.     

Comparison of gene expression of the oncogenic Wnt/β-catenin signaling pathway components in the mouse and human epididymis

β-catenin is an integral part of the Wnt signaling pathway and has been linked to tumorigenesis and multiple developmental processes. The high β-catenin expression with low tumor incidence in the human epididymis is thus intriguing. In the present study, the β-catenin gene and protein was found to be highly expressed in the murine caput epididymidis, and the protein mainly localized along the lateral plasma membranes of adjacent epithelial cells throughout both human and mouse epididymides. Furthermore, the adult mouse epididymis was found to express almost all the Wnt/β-catenin signaling pathway genes that were determined previously by our group in the human organ. Despite the differences in epididymal structure, the similar location of β-catenin and the high concordance of this pathway''s components’ gene expression in both the adult human and mouse epididymides make the mouse a suitable animal model for studying the anti-tumor mechanism of the epididymis. In addition, both the mRNA and protein expression of β-catenin shared a similar spatial expression as the mRNA of Ros1, a proto-oncogene and a key developmental regulator of the initial segment of the mouse epididymis. The observations on the parallel temporal expression of β-catenin and Ros1 during postnatal development raise the possibility that the canonical Wnt signaling pathway has an additional role in the postnatal development of mouse epididymis.