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Three-year follow-up after intracoronary beta-radiation therapy for in-stent restenosis.

BACKGROUND: Most studies that proved intracoronary radiation therapy (IRT) to be highly effective to reduce recurrent restenosis after treatment of in-stent restenosis (ISR) have looked at time periods up to 12 months. Whether the beneficial effect from radiation is sustained during long-term follow-up remains a concern. This study sought to evaluate the effectiveness of IRT using a beta-emitter during a 3-year follow-up period. METHODS: One hundred twenty-eight consecutive symptomatic patients (mean age, 63 +/- 11 years) with 134 in-stent restenotic lesions were treated for ISR with IRT (noncentred beta-emitter, Novoste; radiation dosis 21.1 +/- 3.1 Gy). Six-month angiographic follow-up was obtained in 104 patients (81%) with 105 lesions (78%). All patients underwent 36-month clinical follow-up. RESULTS: Six-month angiographic restenosis rate was 22% in stent (29% in lesion) with an in-stent late loss of 0.49 +/- 0.62 mm. Target lesion resvascularization (TLR) at 6-month follow-up was performed in 23 cases (18%). MACE (death, myocardial infarction, and target vessel revascularisation) was observed in 24 patients (19%). At 36-month follow-up, TLR increased to 36 cases (28%) and MACE was observed in 47 patients (37%). In a multivariate analysis, minimal lumen diameter before treatment of ISR using IRT was the only predictor of recurrent TLR at 36 months (OR = 0.131; 95% CI, 0.068-0.254; p = 0.002). In a subgroup of patients (N = 15) without restenosis at 6-month angiography but with clinically driven recurrent late angiography (mean, 18 +/- 7 months); in-lesion late loss increased from 0.47 +/- 0.54 mm at 6 months to 1.27 +/- 0.76 mm at repeated angiography (p = 0.005). CONCLUSION: There is a considerable number of delayed recurrent restenosis post IRT for ISR. This is due to ongoing late loss more than 6-month post IRT. The minimal lumen diameter before IRT predicts the need for recurrent TLR at 36 months.

Aged↗

Neurotransmitter phenotypes of intermediate zone reticular formation projections to the motor trigeminal and hypoglossal nuclei in the rat.

Numerous studies suggest an essential role for the intermediate (IRt) and parvocellular (PCRt) reticular formation (RF) in consummatory ingestive responses. Although the IRt and PCRt contain a large proportion of neurons with projections to the oromotor nuclei, these areas of the RF are heterogeneous with respect to neurotransmitter phenotypes. Glutamatergic, GABAergic, cholinergic, and nitrergic neurons are all found in the PCRt and IRt, but the projections of neurons with these phenotypes to the motor trigeminal (mV) and hypoglossal nucleus (mXII) has not been fully evaluated. In the present study, after small injections of Fluorogold (FG) into mV and mXII, sections were processed immunohistochemically to detect retrogradely labeled FG neurons in combination with the synthetic enzymes for nitric oxide (nitric oxide synthase) or acetylcholine (choline acetyltransferase) or in situ hybridization for the synthetic enzyme for GABA (GAD65/67) or the brainstem vesicular transporter for glutamate (VGLUT2). In three additional cases, FG injections were made into one motor nucleus and cholera toxin (subunit b) injected in the other to determine the presence of dual projection neurons. Premotor neurons to mXII (pre-mXII) were highly concentrated in the IRt. In contrast, there were nearly equal proportions of premotor-trigeminal neurons (pre-mV) in the IRt and PCRt. A high proportion of pre-oromotor neurons were positive for VGLUT2 (pre-mXII: 68%; pre-mV: 53%) but GABAergic projections were differentially distributed with a greater projection to mV (25%) compared to mXII (8%). Significant populations of cholinergic and nitrergic neurons overlapped pre-oromotor neurons, but there was sparse double-labeling (<10%). The IRt also contained a high proportion of neurons that projected to both mV and MXII. These different classes of premotor neurons in the IRt and PCRt provide a substrate for the rhythmic activation of lingual and masticatory muscles.

Acetylcholine↗

Does the effect of central 5-hydroxytryptamine depletion on timing depend on motivational change?

In a previous experiment we found that destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways by microinjection of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei resulted in impaired acquisition of temporal differentiation under an interresponse-time-greater-than-15-s (IRT > 15 s) schedule of sucrose reinforcement. This paper reports three experiments, the results of which bear on the interpretation of that finding. In Experiment 1, 32 rats were trained for 120 sessions under the IRT > 15 s schedule; then 16 received lesions of the 5HTergic pathways and 16 received sham lesions. Comparisons of the IRT frequency distributions of the two groups showed that the lesion produced a significant reduction of the mean IRT and an increase in the dispersion of IRTs, as expressed by the coefficient of variation. Obtained reinforcement rates were significantly reduced in the lesioned group, but response rates were not significantly altered. Levels of 5HT and 5-hydroxyindoleacetic acid were markedly reduced in all forebrain areas examined, without significant change in noradrenaline and dopamine levels. The results indicate that destruction of the 5HTergic pathways disrupts performance as well as acquisition of temporal differentiation. Experiments 2 and 3 examined whether changes in deprivation level and reinforcer magnitude, which are known to affect reinforcer value, would influence temporal differentiation in a similar fashion to destruction of the 5HTergic pathways. In experiment 2, 20 rats were trained under the IRT > 15 s schedule while maintained at 80% or 90% of free-feeding body weight; the more severe deprivation condition was associated with a longer mean IRT and a lower coefficient of variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Capacitative Ca2+ entry associated with alpha1-adrenoceptors in rat aorta.

In rat aorta, depletion of internal Ca2+ stores by addition of noradrenaline (1 microM) induces a biphasic response (an initial phasic response and a tonic one) mediated by two different intracellular Ca2+ pools. This response cannot be repeated, suggesting a depletion of internal Ca2+ stores sensitive to noradrenaline. In absence of the agonist, this depletion is the signal for the entry of extracellular Ca2+, not only to refill the stores but also, under our experimental conditions, to activate the contractile proteins thus inducing an increase in the resting tone (IRT) that constitutes functional evidence of this Ca2+ entry. The ionic channels involved in the mechanism of the IRT have been studied in the present work. The fact that the addition of nimodipine (10(-15)-10(-11) M) selectively inhibits the IRT suggests that this mechanical response is mediated by Ca2+ influx through dihydropyridine-sensitive Ca2+ channels. Moreover, the inhibitory action of nimodipine is attenuated by glibenclamide (10 microM). Cromakalim (10(-10)-10(-6) M) also inhibits the IRT concentration dependently, and this inhibition is antagonized by glibenclamide (10 microM). These results relate the ATP-dependent K+ channels to the mechanism of the IRT. The refilling of the two internal Ca2+ compartments sensitive to noradrenaline was, like the IRT, altered in presence of the compounds tested, since the subsequent contractile response to noradrenaline was decreased. The present results suggest that nimodipine treatment inhibits the refilling of the Ca2+ compartment responsible for the tonic contraction induced by noradrenaline in Ca2+-free medium, whereas the refilling of the Ca2+ pool responsible for the phasic response to noradrenaline remained unaltered. Both the phasic and tonic responses to noradrenaline in Ca2+-free medium decreased after treatment with cromakalim. We can therefore assume that the refilling of both Ca2+ compartments sensitive to noradrenaline was inhibited. In conclusion, these results are consistent with the contraction of the rat aorta in response to noradrenaline in Ca2+-free medium consisting of an initial phasic response and a tonic one. The former is due to the release of internal Ca2+ from a compartment refilled through a special channel that is cromakalim but not dihydropyridine sensitive. The tonic response is due to Ca2+ release from another compartment refilled through a cromakalim- and dihydropyridine-sensitive Ca2+ channel. The Ca2+ entry through this latter channel intervenes in the IRT observed during the refilling of these stores previously depleted by noradrenaline, and the opening state of this channel is also modulated by ATP-dependent K2+ channels.

Animals↗

Neonatal screening for cystic fibrosis, using immunoreactive trypsin assay in dried blood spots.

Our previous studies suggested that assay of immunoreactive trypsin (IRT) in dried blood spots might be a valuable neonatal screening test for cystic fibrosis (CF). We have developed a convenient, sensitive, human trypsin radioimmunoassay, which uses a 3-mm diameter disc of dried blood. The molecular species assayed in blood is trypsinogen. A retrospective study of 24 known cases of CF and appropriate controls confirmed that an elevated blood level of IRT is characteristic of all newborn CF infants, whether or not they have residual exocrine pancreatic function. IRT levels did, however, decline with time of sample storage. Guthrie cards from 5040 newborns were prospectively assayed: 2% of tests were reassayed because of elevated IRT. Thirty-three second samples (0.67% of the total) were requested, 32 were received, and 31 had normal IRT values. The baby with an elevated result had no clinical symptoms of CF at one month of age, normal stool trypsin activity, but 2 sweat tests gave grossly abnormal results. In contrast, a second infant in whom CF was diagnosed around the same time, had a similar 5-day blood spot IRT value, but severe clinical symptoms of CF and no stool trypsin activity. No false negatives are yet known. We conclude that blood spot IRT assay is a reliable and convenient neonatal screening test for CF.

Clinical Enzyme Tests↗

Behavioral effects of cocaine and its interaction with d-amphetamine and morphine in rats.

Drugs of abuse are commonly co-abused, and frequently these combinations produce effects which cannot be predicted by studying the effects of the individual drugs. To investigate the behavioral interactions which occur following combinations of cocaine plus amphetamine or cocaine plus morphine, rats were trained to respond under a differential reinforcement of low rates (DRL) schedule (10-14 sec). Cocaine (0.1-10 mg/kg) and d-amphetamine (0.1-3 mg/kg) decreased the percentage of reinforced responses (efficiency) at doses which had no effect on overall rate of responding. Following moderate doses of either drug, the interresponse time (IRT) distribution showed an increase in the percentage of shorter (less than 10 sec) IRT's. Morphine (0.1-10 mg/kg) also decreased efficiency, but the decrease which occurred was only observed at doses which also decreased overall response rates. As might be expected, the IRT distribution for morphine showed a dose-related increase in the percentage of long IRT's (greater than 14 sec). When doses of morphine which had no significant effect when administered alone (1 or 3 mg/kg) were combined with cocaine, the cocaine dose-response curve for efficiency was shifted down and to the left and response rates were increased. Analysis of the IRT distribution showed that the combination of an ineffective dose of cocaine, 1 mg/kg, plus 3 mg/kg morphine produced a shift in the IRT distribution to the left (an increase in the percentage of short IRT's). When cocaine was combined with 0.3 mg/kg d-amphetamine, a dose which had no effect when given alone, no significant interactions were observed on efficiency or overall rate of responding.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamines↗

Fractionated high-dose-rate and pulsed-dose-rate brachytherapy: first clinical experience in squamous cell carcinoma of the tonsillar fossa and soft palate.

PURPOSE: Fractionated high-dose-rate (fr.HDR) and pulsed-dose-rate (PDR) brachytherapy (BT) regimens, which simulate classical continuous low-dose-rate (LDR) interstitial radiation therapy (IRT) schedules, have been developed for clinical use. This article reports the initial results using these novel schedules in squamous cell carcinoma (SCC) of the tonsillar fossa (TF) and/or soft palate (SP). METHODS AND MATERIALS: Between 1990 and 1994, 38 patients with TF and SP tumors (5 T1, 22 T2, 10 T3, and 1 T4) were treated by fr.HDR or PDR brachytherapy, either alone or in combination with external irradiation (ERT). Half of the patients were treated with fr.HDR, which entailed twice-daily fractions of > or = 3 Gy. The other 19 patients were administered PDR, which consisted of pulses of < or = 2 Gy delivered 4-8 times/day. The median cumulative dose of IRT +/- ERT series was 66 Gy (range 55-73). The results in these patients treated by brachytherapy were compared to 72 patients with similar tumors treated in our institute with curative intent, using ERT alone. The median cumulative dose of ERT-only series was 70 Gy (range 40-77). RESULTS: Excellent locoregional control was achieved with the use of IRT +/- ERT, with only 13% (5 of 38) developing local failure, and salvage surgery being possible in three of the latter (60%). Neither BT scheme (fr.HDR vs. PDR) nor tumor site (TF vs. SP) significantly influenced local control rates. The type and severity of the side effects observed are comparable to those reported in the literature for LDR-IRT. These results contrast sharply with our ERT-only series, in which 39% of patients (28 of 72) developed local failure, with surgical salvage being possible only in three patients (11%). Taking the data set of 110 patients, in a univariate analysis IRT, T stage, N stage, overall treatment time (OTT), and BEDcor10 (biological effective dose with a correction for the OTT) were significant prognostic factors for local relapse-free survival (LRFS) and overall survival (OS) at 3 years. Using Cox proportional hazard analysis, only T stage and BEDcor10 remained significant for LRFS (p < 0.001 and 0.008, respectively), as well as for OS (p < 0.001 and 0.003, respectively). With regard to the current (IRT) and historical (ERT) series, for the LRFS at 3 years, dose-response relationships were established, significant, however, only for the BEDcor10 (p = 0.03). CONCLUSION: The 3-year LRFS of approximately 90% for TF and SP tumors reported here is comparable with the best results in the literature, particularly given the fact that 30% of the patients (11 of 38) presented with T3/4 tumors. When compared with our historical (ERT-only) controls, the patients treated with IRT had superior local control. A dose-response relationship was established for the BEDcor10.

Brachytherapy↗

Muscle invasive bladder cancer treated by transurethral resection, followed by external beam radiation and interstitial iridium-192.

PURPOSE: To evaluate the results of transurethral resection (TUR), external beam radiotherapy (EBRT), and interstitial radiation (IRT) with iridium-192, using the afterloading technique in patients with muscle invasive bladder cancer. METHODS AND MATERIALS: From May 1989 until September 1995, 66 patients with primary, solitary muscle invasive bladder cancer were treated with TUR, EBRT, and IRT, aiming at bladder preservation. According to the protocol, in three patients low-dose EBRT was applied, whereas 63 patients received high-dose EBRT. Immediately prior to IRT, 42 patients underwent a lymphnode dissection, and in 16 cases a partial cystectomy was performed. For IRT, two to five catheters were used and IRT was started within 24 h after surgery. The majority of patients received 30 Gy of IRT, with a mean dose rate of .58 Gy/h. In three patients, additional EBRT was applied following IRT. Follow-up consisted of regular cystoscopies, mostly done during joint clinics of urologist and radiation oncologist, with urine cytology routinely performed. The median follow-up period was 26 months. The Kaplan-Meier method was used for the determination of survival rates. RESULTS: In seven patients, a bladder relapse developed. The probability of remaining bladder relapse free at 5 years was 88%. The bladder was preserved in 98% of the surviving patients. Metastases developed in 16 patients, and the probability of remaining metastasis free at 5 years was 66%. The cumulative 5-year overall and bladder and distant relapse free survival were 48% and 69%, respectively. Acute toxicity was not serious in the majority of cases; surgical correction of a persisting vesicocutaneous fistula was necessary in two patients, whereas a wound toilet had to be performed in another patient. Serious late toxicity (bladder, RTOG Grade 3) was experienced by only one patient. CONCLUSIONS: Interstitial radiation preceded by TUR and EBRT, in a selected group of patients with muscle invasive bladder cancer, yields an excellent bladder tumor control rate with a high probability of bladder preservation. Survival was mainly dependent on the development of distant metastases. Serious acute and late toxicity was rare.

Adenocarcinoma↗

The outcome of percutaneous coronary intervention in patients with in-stent restenosis who failed intracoronary radiation therapy.

OBJECTIVES: This study reports the outcome of patients who failed intracoronary radiation therapy (IRT) for the treatment of in-stent restenosis (ISR). BACKGROUND: Intracoronary radiation therapy has demonstrated a reduction in the recurrence rate of restenosis for patients with ISR. However, 10% to 30% of these patients require repeat intervention to the irradiated site. METHODS: Of 961 patients who were assigned to gamma or beta radiation for the treatment of diffuse ISR, we evaluated the outcome of 282 (29%) consecutive patients who failed IRT and compared them with the 679 (71%) patients who had successful IRT. For patients who failed radiation, the mean time to the first target vessel revascularization (TVR) was 173 +/- 127 days after the index procedure and the total duration of follow-up was 494 +/- 304 days. RESULTS: Patients who failed IRT were younger (60 +/- 10 vs. 63 +/- 11 years, p = 0.002) and had a higher incidence of restenting (51% vs. 41%, p = 0.003). The majority (55%) of the restenotic lesions after IRT failure were focal (< or =10 mm), with a mean lesion length of 11.9 +/- 1.9 mm. Of the 257 patients who had subsequent TVR after failed IRT, 68 (26%) underwent coronary artery bypass grafting and 189 (74%) underwent percutaneous coronary intervention using balloon in 61%, restenting in 26%, atheroablation in 11%, and the cutting balloon in 2% of cases. At six months, 6% of patients died, 1% had Q-wave MI, 17% had repeat TVR, and the overall rate of major adverse cardiac events was 21%. CONCLUSIONS: The predominant angiographic pattern of lesions in patients who failed IRT is focal restenosis, with these lesions responding well to conventional revascularization methods.

Aged↗

Predictors of late cardiac events following treatment with Sr-90 beta-irradiation for instent restenosis.

BACKGROUND: Intracoronary radiation therapy (IRT) with Sr-90 using the Novoste Beta-Cath system has been shown to be an effective therapy for instent restenosis (ISR), but the temporal occurrence of cardiac events and the predictors of late complications require further investigation. METHODS: We analyzed the demographics, lesion characteristics and clinical outcomes of 138 consecutive patients with ISR treated with IRT from September 1998 to March 2002. Major adverse cardiac events (MACE) were defined as death, myocardial infarction (MI) or target vessel revascularization (TVR). Characteristics of early (< or =8 months) and late (>8 months) failures were analyzed. RESULTS: Thirty-two (23.1%) of 138 patients had MACE on follow-up; 25% (8/32) of failures occurred late after treatment with IRT. A comparison of the clinical and angiographic profile of early and late failures using univariate analysis indicates no correlations to late failure following IRT. Duration to failure after IRT was 14.25+/-3.69 months in the late group compared to 4.63+/-2.86 months in the early group (P<.001). CONCLUSIONS: Late MACE after IRT with Sr-90 for ISR occur beyond the traditional period for clinical restenosis in 25% of cases and are difficult to predict. Further study is warranted to identify patients at risk for the development of late complications after IRT.

Aged↗

The responsiveness of headache impact scales scored using 'classical' and 'modern' psychometric methods: a re-analysis of three clinical trials.

BACKGROUND: While item response theory (IRT) offers many theoretical advantages over classical test theory in the construction and scoring of patient based measures of health few studies compare scales constructed from both methodologies head to head. OBJECTIVE: Compare the responsiveness to treatment of migraine specific scales scored using summated rating scale methods vs. IRT methods. METHODS: The data came from three clinical studies of migraine treatment that used the Migraine Specific Quality of Life Questionnaire (MSQ). Five methods of quantifying responsiveness were used to evaluate and compare changes from pre- to post-treatment in MSQ scales scored using Likert and IRT scaling methods. RESULTS: Changes in all MSQ scale scores from pre- to post-treatment were highly significant in all three studies. A single index scored from the MSQ using IRT methods was determined to be more responsive than any one of the MSQ subscales across the five methods used to quantify responsiveness. Across 13 of the 15 tests (5 responsiveness methods * 3 studies) conducted, the single index scored from the MSQ using IRT methods was the most responsive measure. CONCLUSIONS: IRT methods increased the responsiveness of the MSQ to the treatment of migraine. The results agree with the psychometric evidence that suggest that it is feasible to score a single index from the MSQ using IRT methods. This approach warrants further testing with other measures of migraine impact.

Adult↗

Item response theory and the measurement of motor behavior.

Item response theory (IRT) has been the focus of intense research and development activity in educational and psychological measurement during the past decade. Because this theory can provide more precise information about test items than other theories usually used in measuring motor behavior, the application of IRT in physical education and exercise science merits investigation. In IRT, the difficulty level of each item (e.g., trial or task) can be estimated and placed on the same scale as the ability of the examinee. Using this information, the test developer can determine the ability levels at which the test functions best. Equating the scores of individuals on two or more items or tests can be handled efficiently by applying IRT. The precision of the identification of performance standards in a mastery test context can be enhanced, as can adaptive testing procedures. In this tutorial, several potential benefits of applying IRT to the measurement of motor behavior were described. An example is provided using bowling data and applying the graded-response form of the Rasch IRT model. The data were calibrated and the goodness of fit was examined. This analysis is described in a step-by-step approach. Limitations to using an IRT model with a test consisting of repeated measures were noted.

Educational Measurement↗

Development of a screening system for cystic fibrosis: meconium or blood spot trypsin assay or both?

High blood trypsin levels during early days of life are found in newborns subsequently diagnosed to be affected by cystic fibrosis. The authors compared the validity of the traditional meconium test with the blood immunoreactive trypsin (IRT) assay, carried out in parallel on 113,302 neonates from three regions of North-eastern Italy. The meconium test showed a sensitivity of 57.7%. The sensitivity of the IRT test was higher (96.1%). It was possible to identify by IRT 10 out of 11 false negative CFs at the meconium test. A shortcoming of neonatal IRT, however, is its low specificity; 1.6% of the newborns had to be retested. A new screening policy was therefore proposed and carried out on 69,640 newborns: the Lactase test (LACT) on meconium was introduced as a complementary assay in IRT positive newborns. If LACT exceeded 2 U/g dry meconium, a confirmatory sweat test was immediately requested; if LACT test was negative and IRT exceeded 85 micrograms/l, IRT was repeated. Postneonatal retesting values above 25 micrograms/l required a sweat test. As a result, the estimated prevalence of CF was 1:4,352, the sensitivity was 93.3%; the specificity turned out to be 99.6%, considering all false positive newborns investigated with retesting and/or direct sweat test.

Albumins↗

Simultaneous evaluation of the Doppler-derived transmitral flow velocity waveform and left ventricular isovolumic relaxation time in patients with coronary artery disease.

We studied the usefulness of simultaneous evaluation of the Doppler-derived transmitral flow velocity waveform and left ventricular isovolumic relaxation time (IRT) in patients with coronary artery disease (CAD). Subjects consisted of 26 healthy volunteers, 54 patients with prior myocardial infarction (MI), and 27 patients with CAD but without prior MI. IRT was measured as the time from the beginning of the aortic valve closure sound to the onset of transmitral flow. Peak filling velocity during early diastole (E-wave velocity), peak filling velocity during atrial contraction (A-wave velocity), and IRT were compared among the three groups. No significant difference in A-wave velocity was found among these groups. Whereas E-wave velocity was significantly lower and IRT was significantly longer in patients with CAD but without prior MI than in healthy subjects, no significant differences in E-wave velocity or IRT were observed between patients with prior MI and healthy subjects. We then divided the patients with prior MI into two subgroups, one consisting of 45 patients with mean pulmonary capillary wedge pressure (mPCWP) < 16 mm Hg and the other consisting of 9 patients with mPCWP > or = 16 mm Hg. There was no significant difference in A-wave velocity between the two subgroups and healthy subjects. E-wave velocity was significantly lower in patients with MI and lower mPCWP than in healthy subjects, however, no significant difference in E-wave velocity was found between the patients with MI and higher mPCWP and the healthy subjects. On the other hand, IRT was significantly longer in those with lower mPCWP and significantly shorter in those with higher mPCWP than in healthy subjects. In conclusion, normal transmitral flow velocity waveform with short IRT suggests a 'pseudonormal' pattern due to elevated mPCWP in patients with CAD.

Adult↗

Outcomes of Suture Tape-Augmented ACL Reconstruction in Patients With High Internal Rotational Tibial Subluxation: A Minimum 3-Year Cohort Study.

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) using hamstring tendon (HT) autografts faces persistent challenges of graft failure, especially in patients with high internal rotational tibial subluxation (IRTS). HYPOTHESIS: Patients with high IRTS who undergo HT autograft ACLR with suture tape augmentation (STA) will have lower graft failure rates and superior clinical outcomes as compared with those without STA. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This retrospective cohort study included patients with high IRTS-defined as lateral minus medial anterior tibial subluxation >5.8 mm based on prior studies-who underwent primary ACLR using HT autografts with STA and had a minimum follow-up of 3 years. Propensity score matching (1:1) was performed to identify a control group of patients with similarly high IRTS who underwent HT ACLR without STA. Postoperative outcomes were assessed by the International Knee Documentation Committee score, Lysholm score, and Tegner activity scale, as well as by return-to-sport status and graft failure. Clinically meaningful improvements were evaluated by the minimal clinically important difference, Patient Acceptable Symptom State, and substantial clinical benefit. RESULTS: This study included 62 patients with high IRTS: 31 with STA and 31 matched controls. The mean IRTS was 6.6 mm (range, 5.9-8.9) in the STA group and 6.8 mm (range, 5.8-8.7) in the control group. The mean patient age was 32.9 years (range, 20-50), and the mean follow-up was 3.8 years (range, 3.1-5.0). At final follow-up, the STA group showed significantly higher proportions of patients achieving the minimal clinically important difference (93.5% vs 74.2%; P = .038), Patient Acceptable Symptom State (96.8% vs 74.2%; P = .012), and substantial clinical benefit (54.8% vs 25.8%; P = .020). The return-to-sport rate was also higher in the STA group (74.2% vs 48.4%; P = .037). Additionally, the STA group demonstrated a lower graft failure rate (0% vs 12.9%; P = .039). CONCLUSION: For patients with high IRTS, STA in ACLR with HT autografts is associated with improved clinical outcomes, a higher return-to-sport rate, and a lower risk of graft failure at midterm follow-up.

Humans↗

Drug-eluting stents versus repeat vascular brachytherapy for patients with recurrent in-stent restenosis after failed intracoronary radiation.

Recurrent in-stent restenosis (ISR) following intracoronary radiation therapy (IRT) continues to be a therapeutic challenge. The present study aims to evaluate the clinical outcomes of patients who were treated with drug-eluting stent (DES) implantation versus repeat IRT for recurrent ISR after brachytherapy failure. A cohort of 88 patients who were previously treated with brachytherapy for ISR and presented with angina and recurrence of angiographic restenosis were evaluated for treatment with either DES [sirolimus-eluting stents (SES) or paclitaxel-eluting stents (PES); n = 34] or percutaneous coronary intervention (PCI) and repeat radiation (gamma or beta radiation; n = 54). The two groups had similar baseline clinical and angiographic characteristics. The in-hospital outcomes were similar between both groups. At long-term follow-up of 9.7 +/- 4.1 months for the DES group and 10.3 +/- 3.5 months for the repeat IRT group, there were no deaths or myocardial infarctions (MI). There was a trend toward more target vessel revascularization-major adverse cardiac events (TVR-MACE) in the DES group (p = 0.09). In addition, the patients in the DES group had a significantly lower survival rate compared to those in the repeat IRT group (p = 0.018). For patients who had recurrent ISR following IRT, either DES implantation or repeat radiation is safe and is associated with excellent immediate outcomes. Yet, at long-term follow-up, repeat IRT was associated with less recurrences and need for repeat revascularization when compared to DES implantation. Therefore, repeat IRT should be considered as an option for this difficult patient subset.

Aged↗

Immunoreactive trypsin in acute pancreatitis: elevated levels do not correlate with hyperamylasaemia.

Immunoreactive trypsin (IRT) was measured in the serum of patients presenting with acute pancreatitis (AP) and compared to serum amylase levels. Both were elevated beyond the normal range at presentation (mean IRT 557 +/- 252 micrograms/l, range 181-1000 micrograms/l, mean control IRT 42 +/- 14 micrograms/l, range 15-82 micrograms/l; mean amylase 4500 +/- 3200 IU/l, range 600-10,500 IU/l, control amylase mean 175 +/- 43 IU/l, range 48-320 IU/l). There was minimal correlation between IRT and amylase elevation but both returned to normal at the same rate in patients who recovered. In 2 patients with persistently elevated IRT levels, one was found to have a pancreatic pseudocyst and the other subsequently died from alcoholic haemorrhagic pancreatitis. IRT is no better than amylase as a single diagnostic assay in AP but may be greatly elevated when amylase elevation is minimal. The combination of the two may improve diagnostic accuracy and persistent elevation of IRT may be of prognostic importance.

Acute Disease↗

The pancreatitis-associated protein (PAP). A new candidate for neonatal screening of cystic fibrosis.

Neonatal screening of cystic fibrosis (CF) is presently based on immunoreactive trypsin (IRT) assay in blood spots, whose low specificity is a matter of concern. Because the pancreatitis-associated protein (PAP) proved to be a better serum marker of pancreatic alteration than exocrine enzymes, it might be an interesting alternative for CF screening. We report here a preliminary evaluation of the PAP test, conducted in retrospect on blood spots from groups of neonates already screened for CF with the IRT. Neonates with elevated IRT were submitted to subsequent analysis of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Neonates with normal IRT (n = 990) or high IRT but normal genotype (n = 28) had normal PAP. Elevated PAP was observed in all CF neonates (n = 11). False-positives for the PAP test were found only among neonates with high IRT and heterozygotes for a mutation in the CFTR gene (6 out of 17 cases). That group represents less than 0.2% of newborns. These results therefore suggest that PAP discriminates CF neonates with a significantly better specificity than IRT.

Antigens, Neoplasm↗