Patterns and predictors of persistent opioid use following hip or knee arthroplasty.

OBJECTIVE: The relationship between arthroplasty and long-term opioid use in patients with knee or hip osteoarthritis is not well studied. We examined the prevalence, patterns and predictors of persistent opioid use after hip or knee arthroplasty. METHOD: Using claims data (2004-2013) from a US commercial health plan, we identified adults who underwent hip or knee arthroplasty and filled ≥1 opioid prescription within 30 days after the surgery. We defined persistent opioid users as patients who filled ≥1 opioid prescription every month during the 1-year postoperative period based on group-based trajectory models. Multivariable logistic regression was used to determine preoperative predictors of persistent opioid use after surgery. RESULTS: We identified 57,545 patients who underwent hip or knee arthroplasty. The mean ± SD age was 61.5 ± 7.8 years and 87.1% had any opioid use preoperatively. Overall, 7.6% persistently used opioids after the surgery. Among patients who used opioids in 80% of the time for ≥4 months preoperatively (n = 3023), 72.1% became persistent users. In multivariable analysis, knee arthroplasty vs hip, a longer hospitalization stay, discharge to a rehabilitation facility, preoperative opioid use (e.g., a longer duration and greater dosage and frequency), a higher comorbidity score, back pain, rheumatoid arthritis, fibromyalgia, migraine and smoking, and benzodiazepine use at baseline were strong predictors for persistent opioid use (C-statistic = 0.917). CONCLUSION: Over 7% of patients persistently used opioids in the year after hip or knee arthroplasty. Given the adverse health effects of persistent opioid use, strategies need to be developed to prevent persistent opioid use after this common surgery.

Defective replication stress response inhibits lymphomagenesis and impairs lymphocyte reconstitution.

DNA replication stress promotes genome instability in cancer. However, the contribution of the replication stress response to the development of malignancies remains unresolved. The DNA replication stress response protein SMARCAL1 stabilizes DNA replication forks and prevents replication fork collapse, a cause of DNA breaks and apoptosis. While the fork regression/remodeling functions of SMARCAL1 have been investigated, its in vivo functions in replication stress and cancer are unclear. Using a gamma radiation (IR)-induced replication stress T-cell lymphoma mouse model, we observed a significant inhibition of lymphomagenesis in mice lacking one or both alleles of Smarcal1. Notably, a quarter of the Smarcal1-deficient mice did not develop tumors. Moreover, hematopoietic stem/progenitor cells (HSPCs) and developing thymocytes in Smarcal1-deficient mice showed increased DNA damage and apoptosis during the proliferation burst following IR and an impaired ability to repopulate the thymus after IR. Additionally, mice lacking Smarcal1 showed significant HSPC defects when challenged to respond to other replication stress stimuli. Thus, our data reveal the critical function of the DNA replication stress response and, specifically, Smarcal1 in hematopoietic cell survival and tumor development. Our results also provide important insight into the immunodeficiency observed in individuals with mutations in SMARCAL1 by suggesting that it is an HSPC defect.

[Chronic sports injuries of the knee joint]. / Chronische Sportverletzungen des Kniegelenks.

Chronic sports injuries of the knee joint are common and mainly caused by repetitive (micro) trauma and exertion. Chronic insertion tendinopathies and avulsion fractures and symptoms related to entrapment, friction and impingement can be pathophysiologically distinguished in athletes. In this review, we depict the characteristic magnetic resonance imaging (MRI) findings of the most commonly occurring pathologies.

Multidetector CT of pancreatic ductal adenocarcinoma: Effect of tube voltage and iodine load on tumour conspicuity and image quality.

OBJECTIVES: To compare a low-tube-voltage with or without high-iodine-load multidetector CT (MDCT) protocol with a normal-tube-voltage, normal-iodine-load (standard) protocol in patients with pancreatic ductal adenocarcinoma (PDAC) with respect to tumour conspicuity and image quality. METHODS: Thirty consecutive patients (mean age: 66 years, men/women: 14/16) preoperatively underwent triple-phase 64-channel MDCT examinations twice according to: (i) 120-kV standard protocol (PS; 0.75 g iodine (I)/kg body weight, n = 30) and (ii) 80-kV protocol A (PA; 0.75 g I/kg, n = 14) or protocol B (PB; 1 g I/kg, n = 16). Two independent readers evaluated tumour delineation and image quality blindly for all protocols. A third reader estimated the pancreas-to-tumour contrast-to-noise ratio (CNR). Statistical analysis was performed with the Chi-square test. RESULTS: Tumour delineation was significantly better in PB and PA compared with PS (P = 0.02). The evaluation of image quality was similar for the three protocols (all, P > 0.05). The highest CNR was observed with PB and was significantly better compared to PA (P = 0.02) and PS (P = 0.0002). CONCLUSION: In patients with PDAC, a low-tube-voltage, high-iodine-load protocol improves tumour delineation and CNR leading to higher tumour conspicuity compared to standard protocol MDCT. KEY POINTS: • Low-tube-voltage high-iodine-load MDCT improves pancreatic cancer conspicuity compared to a standard protocol. • The pancreas-to-tumour attenuation difference increases significantly by reducing the tube voltage. • The radiation exposure dose decreases by reducing the tube voltage.

Age- and Level-Dependence of Fatty Infiltration in Lumbar Paravertebral Muscles of Healthy Volunteers.

BACKGROUND AND PURPOSE: Normative age-related decline in paravertebral muscle quality is important for reference to disease and risk identification in patients. We aimed to establish age- and vertebral level-dependence of paravertebral (multifidus and erector spinae) muscle volume and fat content in healthy adult volunteers. MATERIALS AND METHODS: In this prospective study multifidus and erector spinae fat signal fraction and volume at lumbar levels L1-L5 were measured in 80 healthy volunteers (10 women and men per decade, 20-62 years of age) by 2-point Dixon 3T MR imaging. ANOVA with post hoc Bonferroni correction compared fat signal fraction and volume among subgroups. Pearson and Spearman analysis were used for correlations (P < .05). RESULTS: Fat signal fraction was higher in women (17.8% ± 10.7%) than men (14.7% ± 7.8%; P < .001) and increased with age. Multifidus and erector spinae volume was lower in women (565.4 ± 83.8 cm(3)) than in men (811.6 ± 98.9 cm(3); P < .001) and was age-independent. No differences in fat signal fraction were shown between the right and left paravertebral muscles or among the L1, L2, and L3 lumbar levels. The fat signal fraction was highest at L5 (women, 31.9% ± 9.3%; men, 25.7% ± 8.0%; P < .001). The fat signal fraction at L4 correlated best with total lumbar fat signal fraction (women, r = 0.95; men, r = 0.92, P < .001). Total fat signal fraction was higher in the multifidus compared with erector spinae muscles at L1-L4 for both sexes (P < .001). CONCLUSIONS: Lumbar paravertebral muscle fat content increases with aging, independent of volume, in healthy volunteers 20-62 years of age. Women, low lumbar levels, and the multifidus muscle are most affected. Further study examining younger and older subjects and the functional impact of fatty infiltrated paravertebral muscles are warranted.

MR imaging features for improved diagnosis of hepatocellular carcinoma in the non-cirrhotic liver: Multi-center evaluation.

PURPOSE: To determine MR-imaging features for the differentiation between hepatocellular carcinoma (HCC) and benign hepatocellular tumors in the non-cirrhotic liver. MATERIAL AND METHODS: 107 consecutive patients without liver cirrhosis (46 male; 45 ± 14 years) who underwent liver resection due to suspicion of HCC were included in this multi-center study. The following imaging features were assessed: lesion diameter and demarcation, satellite-lesions, central-scar, capsule, fat-content, hemorrhage, vein-infiltration and signal-intensity (SI) on native T1-, T2- and dynamic-enhanced T1-weighted images (center versus periphery). In addition, contrast-media (CM) uptake in the liver specific phase was analyzed in a sub-group of 42 patients. RESULTS: Significant differences between HCC (n=55) and benign lesions (n=52) were shown for native T1-, T2- and dynamic-enhanced T1-SI, fat-content, and satellite-lesions (all, P<.05). Independent predictors for HCC were T1-hypointensity (odds-ratio, 4.81), T2-hypo-/hyperintensity (5.07), lack of central tumor-enhancement (3.36), and satellite-lesions (5.78; all P<0.05). Sensitivity and specificity of HCC was 91% and 75% respectively for two out-of four independent predictors, whereas specificity reached 98% for all four predictors. Sub-analysis, showed significant differences in liver specific CM uptake between HCC (n=18) and benign lesions (n=24; P<0.001) and revealed lack of liver specific CM uptake (odds-ratio, 2.7) as additional independent feature for diagnosis of HCC. CONCLUSION: Independent MRI features indicating HCC are T1-hypointensity, T2-hypo- or hyperintensity, lack of central tumor-enhancement, presence of satellite-lesions and lack of liver specific CM-uptake. These features may have the potential to improve the diagnosis of HCC in the non-cirrhotic liver.

A matter of trust: patient barriers to primary medication adherence.

Primary medication adherence occurs when a patient properly fills the first prescription for a new medication. Primary adherence only occurs about three-quarters of the time for antihypertensive medications. We assessed patients' barriers to primary adherence and attributes of patient-provider discussions that might improve primary adherence for antihypertensives. In total, 26 patients with incomplete primary adherence for an antihypertensive, identified using their retail pharmacy claims, participated in four focus groups. Following a moderators' guide developed a priori, moderators led patients in a discussion of patients' attitudes and experiences with hypertension and receiving an antihypertensive medication, barriers to primary adherence, and their preferences for shared decision making and communication with providers. Three authors analysed and organized data into salient themes, including patients' anger about and suspicion of their hypertension diagnosis, the need for medication and providers' credibility. A trusting patient-provider relationship, shared decision-making support, full disclosure of side effects and cost sensitivity were attributes that might enhance primary adherence. Developing decision support interventions that strengthen the patient-provider relationship by enhancing provider credibility and patient trust prior to prescribing may provide more effective approaches for improving primary adherence.

Outpatient calcium-channel blockers and the risk of postpartum haemorrhage: a cohort study.

OBJECTIVE: To determine whether outpatient exposure to calcium-channel blockers (CCBs) at the time of delivery is associated with an increased risk for postpartum haemorrhage (PPH). DESIGN: Cohort study. SETTING: United States of America. POPULATION OR SAMPLE: Medicaid beneficiaries. METHODS: We identified a cohort of 9750 patients with outpatient prescriptions for CCBs, methyldopa, or labetalol for pre-existing or gestational hypertension whose days of supply overlapped with delivery; 1226 were exposed to CCBs. The risk of PPH was compared in those exposed to CCBs to those exposed to methyldopa or labetalol. Propensity score matching and stratification were used to address potential confounding. MAIN OUTCOME MEASURES: The occurrence of PPH during the delivery hospitalisation. RESULTS: There were 27 patients exposed to CCBs (2.2%) and 232 patients exposed to methyldopa or labetalol (2.7%) who experienced PPH. After accounting for confounders, there was no meaningful association between CCB exposure and PPH in the propensity score matched (odds ratio 0.77, 95% CI 0.50-1.18) or stratified (odds ratio 0.79, 95% CI 0.53-1.19) analyses. Similar results were obtained across multiple sensitivity analyses. CONCLUSIONS: The outpatient use of CCBs in late pregnancy for the treatment of hypertension does not increase the risk of PPH.

[Acute gastrointestinal bleeding - diagnosis with computed tomography]. / Akute Gastrointestinale Blutung - Diagnose mit der Computertomographie.

Computed tomography represents a fast, non-invasive and accurate imaging modality for the diagnosis of acute gastrointestinal bleeding by providing information about localization and source of bleeding. Owing to its robustness and wide availability, it has the potential to be the first line imaging test in patients with acute life-threatening bleeding, for helping in the planning of interventional or surgical procedures.

Retrieval and cryopreservation of sperm from spermatocele fluid.

OBJECTIVES: To evaluate the amount, motility, and viability of sperm in fluid aspirated from naturally occurring spermatoceles and to investigate the effect of cryopreservation of sperm retrieved from spermatoceles. Assisted reproductive technologies have led to successful pregnancies and deliveries using sperm harvested from the epididymis and/or testis of infertile men. METHODS: Aspiration of spermatocele fluid and analysis of the fluid obtained was performed on 20 patients before elective spermatocelectomy. Randomly selected samples (n = 5) were washed using a 70% Percoll gradient, and repeated semen analysis was performed. The washed specimens were cryopreserved in liquid nitrogen, and repeated semen analysis was performed on the thawed specimens. RESULTS: All spermatoceles (n = 20) had viable sperm present (count range 54 x 10(4) to 326 x 10(6)) and 16 (80%) of 20 contained motile sperm. The average percentage of motile sperm was 5%. The average sperm motility and average percent viability of sperm recovered after Percoll gradient improved compared with sperm in the initial spermatocele aspirates (motility 5%, range 0% to 25% and viability 36%, range 2% to 91% before Percoll vs. motility 13%, range 2% to 38% and viability 39%, range 10% to 92% after Percoll). Sperm retrieved after cryopreservation demonstrated reduced motility and viability; however, motile and viable sperm were recovered from all washed and cryopreserved samples. CONCLUSIONS: Our results suggest that spermatocele fluid may contain sufficient numbers of sperm for use with assisted reproductive technologies. Motile and viable sperm can be recovered after cryopreservation and storage of sperm obtained from a spermatocele. Spermatocele fluid may be an additional source of sperm for assisted reproductive technologies.

Catalase-like and superoxide dismutase-like activities in human seminal plasma.

Human spermatozoa are highly susceptible to oxidative injury but are naturally protected from such injury by the antioxidant properties of seminal plasma. We measured catalase-like and superoxide dismutase (SOD)-like activities in the seminal plasma of fertile and vasectomized men in order to gain insight into the potential source(s) and function(s) of these antioxidants in semen. Semen samples were obtained from fertile men ( n=11) and men post-vasectomy ( n=16). Catalase-like activity was measured by the decrease in hydrogen peroxide concentration after incubation with seminal plasma. SOD-like activity was measured as the inhibition of nitroblue tetrazolium reduction due to superoxide anion generation by xanthine plus xanthine oxidase. Mean seminal catalase-like activity (+/-1SD) in the fertile group was not significantly different from that of the post-vasectomy group (389+/-163 and 325+/-119 U/ml, respectively). Similarly, mean seminal SOD-like activity in the fertile group was not significantly different from that of the post-vasectomy group (37+/-10 and 36+/-10 U/ml, respectively). Our data suggest that the testis and epididymis are not an important source of catalase-like and SOD-like activities in semen. These findings indicate that antioxidants in semen are primarily of post-testicular origin and probably serve to protect ejaculated spermatozoa from oxidative stress such as that which occurs in the female reproductive tract.

Perinephric abscess presenting as chronic diarrhea.

Perinephric abscess is an uncommon diagnosis with a variable presentation and high mortality. We report an unusual case of a patient with a perinephric abscess who presented with chronic diarrhea and weight loss.

Comparison of modified one- and two-layer microsurgical vasovasostomy.

OBJECTIVE: To compare the outcome of a modified one-layer and two-layer vasovasotomy (VV) in two groups of similar men undergoing vasectomy reversal. PATIENTS AND METHODS: The charts and surgical records of all surgical procedures performed on men undergoing a modified one- or two-layer VV between June 1992 and July 1994 were retrospectively reviewed. A successful outcome (patency) was defined as sperm present at follow-up (mean follow-up 8 weeks). A modified one-layer VV was used in 17 men (group 1) and a two-layer VV in 23 (group 2). RESULTS: Sperm were present in both groups if surgery was undertaken after vasal obstruction lasting < 36 months. The modified one- and two-layer VV had equal patency (88% and 90%, respectively) when undertaken after an obstructed interval of 36-96 months; outcomes were poorer if surgery was performed after > 96 months. The mean operative duration was 96 min for a modified one-layer VV and 167 min for the two-layer VV. CONCLUSIONS: The simpler and faster modified one-layer VV provides sufficient accuracy for successful vasectomy reversal in most cases. For most patients, both procedures have equivalent patency.

Effect of angiotensin II on rat renal cortical 11beta-hydroxysteroid dehydrogenase.

Renal 11beta-hydroxysteroid dehydrogenases (11beta-HSDs) are subject to modulation by various endogenous factors. 11beta-HSDs convert glucocorticoids into inactive 11-ketones and thereby determine tissue levels of active glucocorticoids and thus the extent of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation. As such, modulation of the activity of renal 11beta-HSDs may contribute to the cascade of regulatory events involved in renal electrolyte water handling. We investigated whether renal 11beta-HSDs are modulated by elevated circulating angiotensin II. In rats infused for 2 wk with angiotensin II (250 ng/[kg x min] subcutaneously), plasma angiotensin II, aldosterone, and corticosterone were raised 5.1-, 10.7-, and 2.3-fold, respectively, compared with control rats. Angiotensin II infusion raised corticosterone 11beta-oxidation 1.46- and 1.35-fold in renal cortical proximal and distal tubules (enriched by Percoll centrifugation), respectively, but had no effect on 11beta-HSD1 and 11beta-HSD2 mRNA levels (semiquantitative reverse transcriptase polymerase chain reaction), except for distal tubular 11beta-HSD1 mRNA, which was decreased to 50%. In vitro treatment of freshly isolated tubules with angiotensin II for 45 min prior to assessment of 11beta-HSD activity showed no direct acute effects of angiotensin II on tubular corticosterone 11beta-oxidation. The enhanced renal tubular corticosterone 11beta-oxidation in vivo may partly protect renal GR and MR from elevated plasma corticosterone on angiotensin II infusion.

High dietary potassium chloride intake augments rat renal mineralocorticoid receptor selectivity via 11beta-hydroxysteroid dehydrogenase.

Glucocorticoid access to renal corticosteroid receptors is regulated by 11beta-hydroxysteroid dehydrogenases (11beta-HSDs), converting 11beta-hydroxyglucocorticoids into inactive 11-ketones. This mechanism plays a key role in maintaining normal salt-water homeostasis and blood pressure. To study whether renal cortical proximal and distal tubular 11beta-HSDs are modulated, upon shifting the electrolyte status (and may thereby contribute to adjusting the salt-water homeostasis), rats were treated for 14 days with diets with low (0.058 w/w%), normal (0.58%, which is the KCl content of standard European laboratory rat food) or high (5.8%) potassium chloride content. In proximal tubules, dietary KCl had no effect regarding corticosterone 11beta-oxidation in intact cells as well as 11beta-HSD1 and 11beta-HSD2 protein (Western blotting) and mRNA levels (semi-quantitative RT-PCR). In distal tubules, the low KCl diet also had no effect. However, distal tubules of rats fed the high KCl diet showed increased corticosterone 11beta-oxidation rates (1.6-fold, P<0.01) and 11beta-HSD2 protein (4-fold, P<0.01), whereas 11beta-HSD1 protein was decreased (no longer detected, P<0.05). Distal tubular 11beta-HSD mRNA levels were not changed upon dietary treatment. Our results suggest that upon dietary KCl loading distal tubular mineralocorticoid receptor selectivity for aldosterone is increased because of enhanced corticosterone 11beta-oxidation. This may contribute to the fine-tuning of salt-water homeostasis by the kidney.

Secondary penile carcinoma from squamous cell carcinoma of the lung.

Secondary penile carcinoma is an unusual clinical entity that has a poor prognosis. We report a case of primary squamous cell carcinoma of the lung with a metastasis to the glans penis, which developed 8 months after treatment for the primary malignancy.

Renal cell carcinoma metastatic to the contralateral ureter.

The ureter is an uncommon location for cancer metastases, the majority of which are due to nonurologic cancers such as stomach and breast.(1) Renal cell carcinoma (RCC) metastatic to the ureter has been reported infrequently. We report a case of metachronous metastatic RCC to the contralateral ureter.

[Fatal asthma. Description and study of risk factors, in the heart of an asthmatic population followed by the College of Pneumonology of the Southwest]. / Asthme mortel. Description et étude des facteurs de risque, au sein d'une population d'asthmatiques suivis par le Collège de Pneumologie du Sud-Ouest.

OBJECTIVES: To describe asthma deaths and to identify the principal short term risk factors in a population followed by twelve thoracic physicians in the South West of France between 1989 and 1995. METHODS: A multicentre clinical study in 312 pure asthmatics recruited freely and reviewed on average 37.4 months later by the same specialist. The attribution of deaths due to asthma was discussed case by case. Predicted risk factors for survival have been researched from variables on the identify card (T0) and analyses using Cox's model. RESULTS: Twenty one subjects died, 16 were due to asthma. This was an annual mortality due to asthma of 1.6%. Seven deaths occurred at home (an acute crisis was the most common) and nine in hospital (respiratory prolonged distress). The principal variables linked to poor survival were: advanced years, asthma with continuous dyspnoea, previous stay in intensive care unit, taking inhaled beta 2 mimetics continuously after inclusion, decreasing FEV1 (P < 0.001). Other variables had a weaker link: duration of asthma, exacerbation of asthma at T0 (P = 0.01), social and psychological problems (P = 0.05), severity of disease at T0 (1992 consensus) were linked to asthma mortality: 75% of the deaths concerned severe asthmatics but 25% occurred in an unforeseen fashion in moderate asthmatics. The presence of personal allergy and of rhinitis was linked to better survival independent of age and severity of asthma. CONCLUSION: This study has shown that it was possible to determine predicted risk factors for asthma deaths in the short term at the time of consultation with an asthmatic and so, to identify the most threatened subjects. The institution of assistance programs could be beneficial as a result of the knowledge of these risk factors.