Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014.

BACKGROUND: In low-immunological risk kidney transplant recipients (KTRs), reduced exposure to calcineurin inhibitor (CNI) appears particularly attractive for avoiding adverse events, but may increase the risk of developing de novo Donor Specific Antibodies (dnDSA). METHODS: CNI exposure was retrospectively analyzed in 247 non-HLA immunized first KTRs by taking into account trough levels (C0) collected during follow-up. Reduced exposure to CNI was defined as follows: C0 less than the lower limit of the international targets for ≥50% of follow-up. RESULTS: During a mean follow-up of 5.0 ± 2.0 years, 39 patients (15.8%) developed dnDSA (MFI ≥1000). Patients with DSA were significantly younger (46.6 ± 13.8 vs. 51.7 ± 14.0 years, p = 0.039), received more frequently poorly-matched grafts (59% with 6-8 A-B-DR-DQ HLA mismatches vs. 34.6%, p = 0.016) and had more frequently a reduced exposure to CNI (92.3% vs. 62.0%, p = 0.0002). Reduced exposure to CNI was associated with an increased risk of dnDSA (multivariable HR = 9.77, p = 0.002). Reduced exposure to CNI had no effect on patient survival, graft loss from any cause including death, or post-transplant cancer. CONCLUSIONS: Even in a low-immunological risk population, reduced exposure to CNI is associated with increased risk of dnDSA. Benefits and risks of under-immunosuppression must be carefully evaluated before deciding on CNI minimization.

Early liver metastases in resectable periampullary cancer: Incidence and risk factors.

PURPOSE: The aim of the present study was to estimate the incidence of very early hepatic metastases (HMs) (<6 months) and their imaging patterns after cephalic duodenopancreatectomy (CDP) for periampullary carcinoma (excluding duodenal carcinoma) and to identify their associated risk factors. METHODS: From January 2003 to June 2016, all patients who underwent surgical treatment for periampullary carcinoma by CDP at our institution and with adequate pre- and postoperative CT scans were included. Univariate and multivariate logistic regressions were performed to determine factors associated with very early HM and recurrence. RESULTS: Of the 132 patients included retrospectively, 27 (20.5%) patients developed HMs. The mean time to diagnosis of HM was 103.9±55.2days. HMs were multiple in 81.4% of cases and bilobar in 59.3% of cases; their mean maximum size was 16.7±12.7mm. In univariate logistic analysis, lymphovascular emboli were significantly associated with HM (p=0.02). No independent risk factors for HM were found in multivariate analysis. In multivariate logistic analysis, two independent risk factors were identified for the occurrence of early recurrence: tumor size >23mm on preoperative CT scan (OR: 3.3; 95% CI: [1.2-9.3]; p=0.02) and tumor differentiation (poor vs. good: OR 15.5; 95 CI [1.5-158.3]; moderate vs. good: OR: 17.1; 95% CI: [1.9-154.4]; p=0.04). CONCLUSIONS: Nearly one in five patients developed HM after CDP within 6 months with a highly consistent pattern. A thorough preoperative assessment, combining CT scan and MRI with a delay of less than three weeks before surgery, appears essential. A routine systematic postoperative CT scan at 8 weeks is also required prior to initiating adjuvant chemotherapy. The type of surgical intervention does not seem to be a risk factor, although the risk of HM occurrence appears to be related to the lymphovascular invasion of the tumor and maybe its degree of differentiation, elements not assessable by imaging.

Prevalence of Tritrichomonas foetus in several subpopulations of Alabama beef bulls.

The objective of this study was to estimate the prevalence of Tritrichomonas foetus infections in Alabama (USA) beef bulls through prospective and retrospective surveys. The prospective survey included 240 Alabama beef bulls that were sampled between January 2005 and March 2006. Preputial smegma was collected from the 240 bulls with a dry pipette and cultured in an InPouch TF T. foetus culture pouch (BioMed Diagnostics; White City, OR, USA). The samples were evaluated microscopically once a day for 6 days for growth resembling T. foetus. To avoid false-positives due to fecal trichomonads, all suspect cultures were sent to both the Alabama Department of Agriculture Veterinary Diagnostic Laboratory in Auburn, AL, USA and the Auburn University College of Veterinary Medicine Parasitology Laboratory (Auburn, AL, USA) for polymerase chain reaction (PCR) confirmatory assays. Of the 240 bulls cultured in the prospective survey, 3 (1.25%) cultures were considered suspect on microscopic evaluation. However, PCR-based assays were negative for T. foetus, suggesting that the samples most likely contained fecal trichomonads. The retrospective analysis included 374 T. foetus cultures performed at the Alabama Department of Agriculture Veterinary Diagnostic Laboratory between October 2002 and March 2005. Of the 374 bulls included in the retrospective analysis, only 1 (0.27%) was confirmed positive by a PCR-based assay.

Precision and accuracy of self-measured peak expiratory flow rates in chronic obstructive pulmonary disease.

BACKGROUND: The precision and accuracy of self-measured peak expiratory flow rates (PEFR) have not been determined for patients with chronic obstructive pulmonary disease (COPD). METHODS: Twenty-eight male veterans recorded their PEFR twice daily, before and after bronchodilators, for 6 months. Spirometry was also done in the pulmonary function laboratory up to 11 times per patient during the observation period. A 4-week "baseline" was identified for each patient. Baseline coefficients of variation (CV) were calculated for the morning (AM) and evening (PM) PEFR, before (PRE) and after (POST) bronchodilators. RESULTS: The baseline CVs for AMPRE, AMPOST, PMPRE and PMPOST were 14.9+/-6.9%, 12.6+/-5.6%, 14.9+/-4.8%, and 11.2+/-6.0%, respectively. There were strong correlations between self-measured PEFR and values obtained in the pulmonary function laboratory on the same day. CONCLUSIONS: Self-measured PFFRs are reasonably precise and accurate in patients with COPD.

A multivariate model for predicting respiratory status in patients with chronic obstructive pulmonary disease.

OBJECTIVE: To develop and validate a multivariate model for predicting respiratory status in patients with advanced chronic obstructive pulmonary disease (COPD). DESIGN: Prospective, double-blind study of peak flow monitoring. SETTING: Albuquerque Veterans Affairs Medical Center. PATIENTS: Male veterans with an irreversible component of airflow obstruction on baseline pulmonary function tests. MEASUREMENTS: This study was conducted between January 1995 and May 1996. At entry, subjects were instructed in the use of the modified Medical Research Council Dyspnea Scale and a mini-Wright peak flow meter equipped with electronic storage. For the next 6 months, they recorded their dyspnea scores once daily and peak expiratory flow rates twice daily, before and after the use of bronchodilators. Patients were blinded to their peak expiratory flow rates, and medical care was provided in the customary manner. Readings were aggregated into 7-day sampling intervals, and interval means were calculated for dyspnea score and peak expiratory flow rate parameters. Intervals from all subjects were then pooled and randomized to separate groups for model development (training set) and validation (test set). In the training set, logistic regression was used to identify variables that predicted future respiratory status. The dependent variable was the log odds that the subject would attain his highest level of dyspnea in the next 7 days. The final model was used to stratify the test set into "high-risk" and "low-risk" categories. The analysis was repeated for 3-day intervals. MAIN RESULTS: Of the 40 patients considered eligible for study, 8 declined to participate, 4 could not master the technique of peak flow monitoring, and 6 had no fluctuations in their dyspnea level. The remaining 22 subjects form the basis of this report. Fourteen (64%) of the latter completed the 6-month protocol. Data from the 8 who were dropped or died were included up to the point of withdrawal. For 7-day forecasts, mean dyspnea score and mean daily prebronchodilator peak expiratory flow rate were identified as predictor variables. The adjusted odds ratio (OR) for mean dyspnea score was 2.71 (95% confidence interval [CI] 1.79, 4.12) per unit. For mean prebronchodilator peak expiratory flow rate, it was 1.05 (95% CI 1.01, 1.09) per percentage predicted. For 3-day forecasts, the model was composed of mean dyspnea score and mean daily bronchodilator response. The ORs for these terms were 2.66 (95% CI 2.06, 3.44) per unit and 0.980 (95% CI 0.962, 0.998) per percentage of improvement over baseline, respectively. For a given level of dyspnea, higher pre-bronchodilator peak expiratory flow rate and lower bronchodilator response were poor prognostic findings. When the models were applied to the test sets, "high-risk" intervals were 4 times more likely to be followed by maximal symptoms than "low-risk" intervals. CONCLUSIONS: Dyspnea scores and certain peak expiratory flow rate parameters are independent predictors of respiratory status in patients with COPD. However, our results suggest that monitoring is of little benefit except in patients with the most advanced form of this disease, and its contribution to their management is modest at best.

Patient compliance with peak flow monitoring in chronic obstructive pulmonary disease.

BACKGROUND: The factors affecting patient compliance with peak flow monitoring in advanced chronic obstructive pulmonary disease (COPD) were examined using a prospective, blinded study. METHODS: Twenty-eight male veterans were instructed in the use of an electronic, hand-held peak flow meter and the modified Medical Research Council dyspnea scale. They then entered a 6-month monitoring phase in which they recorded a dyspnea score once daily and peak expiratory flow rates twice daily, before and after bronchodilator use. The meter displays were disabled so that the patients were blinded to their values. Medical care was provided in the customary manner. Compliance was defined as the ratio of recorded values to all values specified by the protocol, exclusive of those missing due to circumstances beyond the patient's control. RESULTS: Of 40 patients who met the entry criteria for this study, 8 refused to participate and 4 could not master the technique. The remaining 28 patients were enrolled. Overall, 25 (63% of those eligible) adhered to the protocol until its conclusion or until they became unable to comply because of medical or social problems. Compliance was 89.8+/-15.0%. Of those followed for longer than 150 days, linear regression showed that only one patient had a decline in compliance over time (r=0.84, P=0.04). Compliance was lower in the afternoons (P < 0.001) and on days with higher dyspnea scores (P < 0.001). No other clinical factors had an effect on patient measurements. CONCLUSIONS: A substantial proportion of patients with advanced COPD can be trained in the technique of peak flow monitoring. Compliance is high if patients are enrolled in a long-term, structured program of supervision and periodic retraining.

Estimating the burden of musculoskeletal disorders in the community: the comparative prevalence of symptoms at different anatomical sites, and the relation to social deprivation.

BACKGROUND: Epidemiologically-based rheumatology healthcare needs assessment requires an understanding of the incidence and prevalence of musculoskeletal disorders in the community, of the reasons why people consult in primary care, and of the proportion of people who would benefit from referral to secondary care and paramedical services. This paper reports the first phase of such a needs assessment exercise. SPECIFIC OBJECTIVE: To estimate the relative frequency of musculoskeletal pain in different, and multiple, anatomical sites in the adult population. SETTING: Three general practices in the former Tameside and Glossop Health Authority, Greater Manchester, UK, a predominantly urban area. DESIGN: Population survey. METHODS: An age and sex stratified sample of 6000 adults from the three practices was mailed a questionnaire that sought data on demographic factors, musculoskeletal symptoms (pain in the past month lasting for more than a week), and physical disability (using the modified Health Assessment Questionnaire--mHAQ). The areas of pain covered were neck, back, shoulder, elbow, hand, hip, knee, and multiple joints. The Carstairs index was used as a measure of social deprivation of the postcode sector in which the person lived. RESULTS: The response rate after two reminders was 78.5%. Non-responders were more likely to live in areas of high social deprivation. People who lived in more deprived areas were also more likely to report musculoskeletal pain, especially backpain. After adjusting for social deprivation the rates of musculoskeletal pain did not differ between the practices and so their results were combined. After adjustment for social deprivation, the most common site of pain was back (23%; 95% CI 21, 25) followed by knee (19%; 95% CI 18, 21), and shoulder (16%; 95% CI 14, 17). The majority of subjects who reported pain had pain in more than one site. The prevalence of physical disability in the community rose with age. It was highest in those with multiple joint problems but was also high in those with isolated back or knee pain. CONCLUSION: Musculoskeletal pain is common in the community. People who live in socially deprived areas have more musculoskeletal symptoms. Estimates of the overall burden of musculoskeletal pain that combine the results of site specific surveys will be too high, those that do not adjust for socioeconomic factors will be too low.

Time course of respiratory decompensation in chronic obstructive pulmonary disease: a prospective, double-blind study of peak flow changes prior to emergency department visits.

The aim of this study was to look at changes in peak expiratory flow rates (PEFR) prior to emergency department visits for decompensated chronic obstructive pulmonary disease (COPD). It was designed as a prospective, double-blind study at the Albuquerque Veterans Affairs Medical Center. Twelve patients with an irreversible component of airflow obstruction on pulmonary function tests were assessed. At entry, all subjects were instructed in the use of a mini-Wright peak flow meter with electronic data storage. They then entered a 6-month monitoring phase in which they recorded PEFR twice daily, before and after bronchodilators. The meter displays were disabled so that the patients and their physicians were blinded to all values. Medical care was provided in the customary manner. Patients were considered to have respiratory decompensation if they required treatment for airflow obstruction in the Emergency Department (ED) and no other causes of dyspnea could be identified. Simple linear regression was used to model changes in PEFR over time. The 12 subjects had 22 episodes of respiratory decompensation during 1741 patient-days of observation. Two episodes could not be analysed because of missing values. Ten episodes in seven subjects were characterized by a significant linear decline in at least one peak flow parameter prior to presentation. The mean rates of change for the four daily parameters varied from 0.22% to 0.27% predicted per day (or 1.19 to 1.44 1 min-1 day-1). The average decrement in these parameters ranged from 30.0 to 33.8 1 min-1 (or 18.6%-25.9% of their baseline values). No temporal trends were found for the 10 episodes occurring in the other five subjects. We concluded that respiratory decompensation is characterized by a gradual decline in PEFR in about half of cases. Future studies should be done to elucidate the mechanisms of respiratory distress in the other cases.

Expression of transforming growth factor-alpha and epidermal growth factor receptor is increased following bleomycin-induced lung injury in rats.

To investigate the potential role of transforming growth factor-alpha (TGF-alpha) and the epidermal growth factor receptor (EGF-R) in the fibroproliferative response to acute lung injury, we determined lung steady-state TGF-alpha and EGF-R mRNA levels, TGF-alpha protein levels, and the distribution of TGF-alpha and EGF-R immunoreactive protein of bleomycin-injured and control rat lungs. At 2 and 4 days after a single intratracheal injection of bleomycin, TGF-alpha mRNA levels increased to 159% and 184% of control values, respectively. EGF-R mRNA levels increased to 163%, 314%, and 170% of control values at 1, 7, and 14 days after bleomycin instillation. TGF-alpha protein levels in whole lung extracts increased to 230% of control values at 4 days after bleomycin administration. TGF-alpha and EGF-R immunoreactivity was detected in macrophages, alveolar septal cells, and airway epithelium of control and bleomycin-injured animals with an apparent increase in the intensity and number of specifically immunostained cells following lung injury. TGF-alpha and EGF-R immunoreactive proteins were detected in foci of cellular proliferation and in areas of intraalveolar fibrosis. We conclude that TGF-alpha and the EGF-R are present in normal and bleomycin-injured rat lung and that the expression of this growth factor and its receptor are up-regulated following lung injury. These results suggest that increased expression of TGF-alpha and the EGF-R may be an important mechanism that modulates the fibroproliferative response to acute lung injury.

A mathematical method for the measurement of bone motion with skin-mounted accelerometers.

The methods of dynamic programming and generalized cross-validation are used to estimate the acceleration of bone motion using skin-mounted accelerometers. Numerical experiments are performed to demonstrate the usefulness and limitations of the methods.

Smoothing noisy data using dynamic programming and generalized cross-validation.

Smoothing and differentiation of noisy data using spline functions requires the selection of an unknown smoothing parameter. The method of generalized cross-validation provides an excellent estimate of the smoothing parameter from the data itself even when the amount of noise associated with the data is unknown. In the present model only a single smoothing parameter must be obtained, but in a more general context the number may be larger. In an earlier work, smoothing of the data was accomplished by solving a minimization problem using the technique of dynamic programming. This paper shows how the computations required by generalized cross-validation can be performed as a simple extension of the dynamic programming formulas. The results of numerical experiments are also included.

Numerical experiments with a new differentiation filter.

A dynamic programming filter which provides estimates of the first and second derivative of empirical displacement data is investigated numerically. This filter uses a weighted least squares criteria in estimating the derivatives. The filter equations are presented together with several numerical examples. These examples are taken from references that proposed other techniques.