The prognostic value of serum methotrexate area under curve in elderly primary CNS lymphoma patients

Studies on pharmacokinetics and pharmacodynamics of high-dose methotrexate chemotherapy (HD-MTX) in elderly primary central nervous system lymphoma (PCNSL) patients are rare. MTX exposure time has recently been proposed as an outcome determining factor in PCNSL. We investigated 49 immunocompetent PCNSL patients (female N=30, male N=19, median age 73 years) who were treated according to HD-MTX-based protocols. A two-compartment pharmacokinetic model was used to describe the MTX clearance. Response to treatment was assessed by MRI. We used multivariable models to investigate the association between MTX exposure and tumor response as well as survival. Dose normalized MTX peak serum levels [C (max), μmol/L g] and dose normalized area under the curve [AUC(dn), μmol h/L g] were higher in females than in males, respectively [59.4 (f) vs. 48.1 (m), P<0.001; 373.2 (f) vs. 271.9 (m), P=0.008]. Increasing AUC was inversely correlated with tumor response. AUC values above 2,126 h?μmol/L were independently associated with shorter overall and progression-free survival [hazard ratio (HR), 4.56, 95 % CI 1.74-11.94; HR 2.87, 95 % CI 1.18-7.00]. Exceedingly high MTX AUC levels can have a negative impact on progression-free and overall survivals in elderly PCNSL patients.     

SpyGlass® single-operator peroral cholangioscopy in the evaluation of indeterminate biliary lesions: a single-center, prospective, cohort study

Background

SpyGlass^® single-operator peroral cholangioscopy appears to be a promising technique to overcome some limitations of conventional peroral cholangioscopy. We aimed to prospectively evaluate the SpyGlass system in a cohort of patients with indeterminate biliary lesions.

Methods

Patients with indeterminate strictures or filling defects at endoscopic retrograde cholangiopancreatography (ERCP) were consecutively enrolled. After SpyGlass visual evaluation, targeted biopsies were taken with the SpyBite^® and histopathological assessment was made by two experienced gastrointestinal pathologists. SpyBite-targeted biopsy results were evaluated by assessing agreement with surgical specimens and by evaluation of final, clinical follow-up-based diagnosis.

Results

Fifty-two patients participated in the study. In 7 cases, definite diagnosis (stones, varices) was made by SpyGlass endoscopic evaluation. In 42 of the remaining 45 cases, material suitable for histopathology assessment was provided by the SpyBite. Overall, a definite diagnosis was made in 49 (7 + 42; 94 %) cases. Agreement of SpyBite biopsy results with surgical specimen diagnosis was found in 38/42 (90 %) cases; sensitivity, specificity, and positive and negative predictive values were 88, 94, 96, and 85 %, respectively. Procedure-related complications consisted of one case of mild cholangitis and one case of mild pancreatitis.

Conclusions

In our series, the SpyGlass system allowed adequate biopsy sampling and definite diagnosis with high accuracy in the vast majority of patients with indeterminate biliary lesions. Its use was associated with a low complication rate. Further refinements of the technique are warranted, but the SpyGlass system has the potential to become a diagnostic standard for the assessment of indeterminate biliary lesions.     

Measuring quality of life in aphasia: Results from two scales

Background: Although aphasia affects quality of life (QoL), the impact within specific domains (e.g., psychosocial, communication) is poorly understood. Moreover, the complex and multidimensional nature of QoL renders it difficult to measure accurately using a single global scale.

Aims: Using two recently developed QoL scales, the Stroke and Aphasia Quality of Life Scale‐39, (SAQOL; Hilari, Byng, Lamping, & Smith, 2003a Hilari, K., Byng, S., Lamping, D. L. and Smith, S. C. 2003a. Stroke and Quality of Life Scale‐39 (SAQOL‐39): Evaluation of acceptability, reliability and validity.. Stroke, 34: 1944–1950. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) and the American Speech Language Hearing Association's Quality of Communication Life Scale (QCL; Paul et al., 2004 Paul, D. R., Frattali, C. M., Holland, A. L., Thompson, C. K., Caperton, C. J. and Slater, S. C. 2004. Quality of Communication Life Scale, Rockville, MD: The American Speech‐Language‐Hearing Association.  [Google Scholar]), this study aimed to document the domains of QoL that were most affected for participants with aphasia compared to control participants, as well as to determine the relationship between the two scales, their sub‐domains, and linguistic variables in aphasia.

Methods & Procedures: The two scales were administered to a group of 19 participants with aphasia (14 male, 5 female), ages ranging from 27 to 79 years, and 19 age‐ and gender‐matched control participants. Various types and severity of aphasia were represented in the aphasia group. The performances of aphasia and control groups were compared, and correlation analyses examined the relationship between the two scales and their sub‐domains in the aphasia group only.

Outcomes & Results: Compared to control participants, QoL was lower in participants with aphasia, with the communication sub‐domain of SAQOL and socialisation/activities sub‐domain of QCL being the most affected areas of functioning. Between the two scales, the communication sub‐domain of SAQOL correlated with the socialisation/activities sub‐domain and the QCL mean. Moreover, linguistic variables correlated strongly with psychosocial, communication and socialisation/activities sub‐domains of QoL.

Conclusions: Measuring QoL using the SAQOL and the QCL captures different but equally important aspects of experiences of living with aphasia. When interpreted together, they provide a holistic picture of functioning in aphasia that includes broad overviews of QoL from the SAQOL and a finer‐grained analysis of communication impairments on QoL from the QCL.     

How attentional boost interacts with reward: the effect of dopaminergic medications in Parkinson's disease

There is widespread evidence that dopamine is implicated in the regulation of reward and salience. However, it is less known how these processes interact with attention and recognition memory. To explore this question, we used the attentional boost test in patients with Parkinson's disease (PD) before and after the administration of dopaminergic medications. Participants performed a visual letter detection task (remembering rewarded target letters and ignoring distractor letters) while also viewing a series of photos of natural and urban scenes in the background of the letters. The aim of the game was to retrieve the target letter after each trial and to win as much virtual money as possible. The recognition of background scenes was not rewarded. We enrolled 26 drug‐naïve, newly diagnosed patients with PD and 25 healthy controls who were evaluated at baseline and follow‐up. Patients with PD received dopamine agonists (pramipexole, ropinirole, rotigotine) during the 12‐week follow‐up period. At baseline, we found intact attentional boost in patients with PD: they were able to recognize target‐associated scenes similarly to controls. At follow‐up, patients with PD outperformed controls for both target‐ and distractor‐associated scenes, but not when scenes were presented without letters. The alerting, orienting and executive components of attention were intact in PD. Enhanced attentional boost was replicated in a smaller group of patients with PD (n = 15) receiving l ‐3,4‐dihydroxyphenylalanine (L‐DOPA). These results suggest that dopaminergic medications facilitate attentional boost for background information regardless of whether the central task (letter detection) is rewarded or not.     

Use of human liver and EpiSkin™ S9 subcellular fractions as a screening assays to compare the in vitro hepatic and dermal metabolism of 47 cosmetics-relevant chemicals

The abundance of xenobiotic metabolizing enzymes (XMEs) is different in the skin and liver; therefore, it is important to differentiate between liver and skin metabolism when applying the information to safety assessment of topically applied ingredients in cosmetics. Here, we have employed EpiSkin™ S9 and human liver S9 to investigate the organ-specific metabolic stability of 47 cosmetic-relevant chemicals. The rank order of the metabolic rate of six chemicals in primary human hepatocytes and liver S9 matched relatively well. XME pathways in liver S9 were also present in EpiSkin S9; however, the rate of metabolism tended to be lower in the latter. It was possible to rank chemicals into low-, medium- and high-clearance chemicals and compare rates of metabolism across chemicals with similar structures. The determination of the half-life for 21 chemicals was affected by one or more factors such as spontaneous reaction with cofactors or non-specific binding, but these technical issues could be accounted for in most cases. There were seven chemicals that were metabolized by liver S9 but not by EpiSkin S9: 4-amino-3-nitrophenol, resorcinol, cinnamyl alcohol and 2-acetylaminofluorene (slowly metabolized); and cyclophosphamide, benzophenone, and 6-methylcoumarin. These data support the use of human liver and EpiSkin S9 as screening assays to indicate the liver and skin metabolic stability of a chemical and to allow for comparisons across structurally similar chemicals. Moreover, these data can be used to estimate the systemic bioavailability and clearance of chemicals applied topically, which will ultimately help with the safety assessment of cosmetics ingredients.     

Comparison of Spinal Cord Stimulation Outcomes Between Preoperative Opioid Users and Nonusers: A Cohort Study of 467 Patients

ObjectivesSpinal cord stimulation (SCS) is a surgical treatment modality reserved for a subset of patients with neuropathic pain in which conventional pharmacologic treatment has proven insufficient. Previous studies have suggested a possible negative relationship between opioid use at referral and subsequent success of SCS therapy. The aim of this cohort study was to investigate whether preoperative opioid use was associated with inferior SCS outcomes.Materials and MethodsData were obtained from the Danish Neurizon Neuromodulation Database and comprised preoperative registrations of analgesic use, postoperative Patients’ Global Impression of Change (PGIC) ratings, pre- and postoperative pain intensity scores (Numeric Rating Scale), and detailed surgical data. Patients were dichotomized according to preoperative opioid use (users vs nonusers) with subsequent assessment of the latest PGIC rating, reduction in pain intensity, and current treatment status (implanted/explanted). In addition, daily preoperative opioid dosages were quantified in oral morphine equivalents (OME) and correlated to the treatment outcomes.ResultsA total of 467 patients were included; 296 consumed opioids before SCS implantation (median 80 OME/d). Preoperative opioid use was not associated with the latest PGIC rating, reduction in pain intensity (30% or 50%), or risk of undergoing explantation (median follow-up = 3.0 years). Likewise, preoperative median OME per day of opioid users was not correlated with any of the defined outcomes.ConclusionsPreoperative opioid usage did not predict the outcome of SCS therapy in a large cohort of patients permanently implanted with an SCS system. The results do not support withholding otherwise well-indicated SCS therapy in patients with chronic neuropathic pain conditions based merely on preoperative opioid usage.     

Age at hysterectomy as a predictor for subsequent pelvic organ prolapse repair

Introduction and hypothesis

The aim of this study was to investigate the association between patient age at the time of hysterectomy and subsequent pelvic organ prolapse (POP) surgery.

Methods

We gathered data on all benign hysterectomies and POP surgeries performed in Denmark on Danish women from 1977 to 2009 from the Danish National Patient Registry. The cohort consisted of 154,882 hysterectomized women, who were followed up for up to 32 years. Survival analysis for each age group at hysterectomy was performed using Kaplan–Meier product limit methods.

Results

For all hysterectomized women, we found that low age at hysterectomy yielded a lower risk of subsequent POP surgery than did hysterectomy at an older age. This difference diminished after stratification by indication; all non-POP hysterectomies had a low cumulative incidence at 8–11 % at the end of the follow-up period. For all women hysterectomized, the predominant compartment for POP surgery was the posterior. Women hysterectomized when aged over 66 years had a higher proportion of POP surgery in the apical compartment than in the other age groups (p?=?0.000).

Conclusion

Our findings indicate that age at hysterectomy only marginally influences the risk of subsequent POP surgery for women hysterectomized for indications other than POP. If POP is the indication for hysterectomy, the risk of undergoing subsequent POP surgery increases substantially.

     

Routine Postoperative Monitoring after Bariatric Surgery in Morbidly Obese Patients with Severe Obstructive Sleep Apnea: ICU Admission is not Necessary

Background and Study Aim

Obstructive sleep apnea (OSA) occurs in 70–80 % of bariatric surgery patients. Patients with severe OSA (apnea/hypopnea index (AHI) >30/h) are postoperatively admitted to an intensive care unit (ICU) for continuous monitoring, to prevent complications. The aim of this study was to assess the necessity of routine postoperative monitoring at an ICU of severe OSA patients after bariatric surgery, attempting to prevent and detect cardiorespiratory complications.

Methods

Patients undergoing bariatric surgery from November 2010 to July 2013 were entered into a database. Minimal follow-up was 1 month. Poly(somno)graphy (P(S)G) was routinely performed. Patients with severe OSA were admitted to the ICU for the first postoperative night. Oxygen saturation was continuously measured. The database was reviewed regarding patient characteristics, CPAP use, re-intubations, desaturations (saturation <90 % and severe <85 %), and complications.

Results

Severe OSA was present in 151 of the 794 patients, and all 151 were admitted to the ICU. Thirty who underwent revisional surgery were excluded. Forty-seven percent was male, median age was 51 years (27.0–68.0), and median body mass index (BMI) was 46.6 (kg/m²) (34.0–77.6). No deaths, re-intubations, or cardiopulmonary complications occurred. Eighty-two (67.8 %) patients used continuous positive airway pressure (CPAP). Twenty-one (17.4 %) patients experienced desaturations with a median of 2.0 (1–8). Six patients (5.0 %) had one episode of severe desaturation.

Conclusion

Patients with severe OSA and adequate CPAP use are at low risk of cardiopulmonary complications after (laparoscopic) bariatric surgery. Routine admission to an ICU might be superfluous. However, continuous digital oximetry remains essential.