Long-term Results Of Therapy Research Articles

Long-term outcome of cutaneous melanoma patients treated with boron neutron capture therapy (BNCT).

ABSTRACTOur aim was to assess the long-term clinical outcome of boron neutron capture therapy (BNCT) using 10B-para-boronophenylalanine (BPA) as the boron delivery agent for cutaneous melanoma. Eight patients (eight lesions) were treated between October 2003 and April 2014. Their ages ranged from 48 to 86 years at the time of treatment. All of the targets were primary lesions and they were located on the sole or face. No patient had evidence of regional lymph node involvement, distant metastases or an active secondary cancer. The clinical stage was cT1-2N0M0 and performance scores were <2. BNCT was carried out at the Kyoto University Research Reactor (KUR). The patients were irradiated with an epithermal neutron beam between the curative tumor dose and the tolerable skin dose. Eight patients were evaluated and six showed a complete response (CR), while two patients had a partial response (PR). Of the two patients with a PR, one has remained a PR with brown spots persisting for 7.5 years following BNCT. The tumor in the other patient recurred after 6 years at the site of persisting brown macula. The overall control rate (CR + PR without recurrence) for the cohort was 88% (7/8). There have never been any adverse events >Grade 2 for the long follow-up period. Our results suggest that BNCT may be a promising treatment modality in the management of early stage cutaneous melanoma when wide local excision is not feasible.

Long-term outcomes of therapist-guided Internet-delivered cognitive behavior therapy for pediatric obsessive-compulsive disorder

Cognitive behavior therapy (CBT) is the recommended first-line intervention for children and adolescents with obsessive-compulsive disorder (OCD), but is not broadly accessible. Internet-delivered CBT (ICBT) with minimal therapist support is efficacious and cost-effective, at least in the short term. Whether the therapeutic gains of ICBT for OCD are sustained in the long run is unknown. In this study, 61 adolescents with OCD who participated in a randomized trial of ICBT were followed-up 3 and 12 months after treatment. The proportion of treatment responders and remitters remained stable from post-treatment to 3-month follow-up and increased significantly from 3-month to 12-month follow-up. This study suggests that the gains of ICBT for youth with OCD are not only maintained long-term, but that further improvements continue to occur during follow-up.

Long-term outcomes of internet-delivered cognitive behaviour therapy for paediatric anxiety disorders: towards a stepped care model of health care delivery

Internet-delivered cognitive behaviour therapy (ICBT) is emerging as a powerful tool to fill the gap between demand and availability of evidence-based treatment for paediatric anxiety disorders. However, it is still unclear how to best implement it in routine clinical care. 123 children (8–12 years) with anxiety disorders underwent a 12-week ICBT programme with limited therapist support. Participants were assessed 3- and 12-month post-ICBT (3MFU and 12MFU, respectively). Non-remitters who still fulfilled diagnostic criteria for their principal anxiety disorder at 3MFU were offered additional manualised “face-to-face” (F2F) CBT. The aim of the study was to emulate a stepped-care model of health care delivery, where the long-term treatment gains of ICBT as well as the potential benefit of proving addition treatment to non-remitters of ICBT were evaluated. Remitters of ICBT (n = 73) continued to improve throughout the study period (pre-ICBT to 12MFU; Cohen’s d = 2.42). At 12MFU, 89% (n = 65) were free from their principal anxiety disorder. Of all the participants classed as non-remitters at 3MFU (n = 37), 48.6% (n = 18) accepted the offer to receive additional F2F CBT. These participants also improved with a large effect from pre-ICBT to 12MFU (Cohen’s d = 2.27), with the largest effect occurring during F2F CBT. At 12MFU, 83% (n = 15) were free from their principal anxiety disorders. The majority of non-remitters declining additional F2F CBT (63.2%; n = 12) did so due to already receiving treatment at their local CAMHS, prior to 3MFU. The effects of ICBT for anxiety disorders are durable at least up to 1 year after the end of treatment. Patients who fail to fully benefit from ICBT improved further with additional F2F sessions at our clinic, suggesting that it may be feasible to implement ICBT within a stepped-care model of health care delivery.

Long-term outcome of endovascular therapy for acute basilar artery occlusion

The long-term functional outcome of acute basilar artery occlusion (BAO) patients who received modern endovascular therapy (EVT) is unclear. We sought to assess the long-term functional outcome of BAO patients treated with EVT and determine the prognostic factors associated with favorable outcome. We enrolled consecutive BAO patients who received EVT between December 2012 and December 2018 in this observational study. Baseline characteristics and outcomes were presented. Multivariable logistic regression analysis was performed to identify the prognostic factors associated with long-term outcome. Among the 177 BAO patients included in this study, 80 patients (45.2%) obtained favorable outcome and 97 patients (54.8%) had unfavorable outcome at long-term follow-up with a median observation time of 12 months (interquartile range, 3–19). A total of 67 patients (37.9%) died. National Institutes of Health Stroke Scale (NIHSS), posterior circulation Alberta Stroke Program Early Computed Tomography Score (pc-ASPECTS), time from stroke onset to recanalization, and recanalization condition were identified as independent predictors for long-term outcome. Over 40% of BAO patients who were treated with modern EVT achieved favorable outcome at long-term follow-up. NIHSS, pc-ASPECTS, time from stroke onset to recanalization, and recanalization condition were identified as independent prognostic factors of long-term outcome.

Effectiveness of continuous unsupervised exercise therapy after above-knee femoropopliteal bypass.

Exercise therapy has acceptable outcomes for patients with intermittent claudication, although few reports exist regarding the results of continuous exercise therapy after surgical reconstruction for intermittent claudication. This study aimed to analyze the long-term outcomes of unsupervised exercise therapy for patients after above-knee femoropopliteal bypass. We retrospectively analyzed 69 patients (69 limbs, 69 grafts) who underwent above-knee femoropopliteal bypass from April 2009 to March 2018 in our hospital. At six months after above-knee femoropopliteal bypass, we evaluated the maintenance of unsupervised exercise therapy. Patients who continued unsupervised exercise therapy or discontinued unsupervised exercise therapy were assessed via 1:1 propensity matching. Long-term outcomes such as patency, survival, and major adverse cardiovascular events were compared between the groups after matching. We also analyzed the maintaining rate of unsupervised exercise therapy in a study cohort. Twenty-nine (42%) patients continued unsupervised exercise therapy until six months after above-knee femoropopliteal bypass. The discontinued unsupervised exercise therapy had higher proportions of female sex (p = 0.015) and cerebrovascular disease (p = 0.025) than did the continued unsupervised exercise therapy. The mean follow-up period was 65 ± 36 months. After propensity matching, the rates of the following factors were significantly higher in the continued unsupervised exercise therapy than in the discontinued unsupervised exercise therapy: primary patency (97% vs. 61%, p = 0.0041), secondary patency (100% vs. 69%, p = 0.0021), and freedom from major adverse cardiovascular events (61% vs. 24%, p = 0.0071) at five years. Both groups had a similar survival rate. The maintaining rate of unsupervised exercise therapy in the study cohort was 44% at six months, 41% at one year, 36% at three years, 25% at five years, and 25% at seven years. The findings of this study suggested superior long-term outcomes, including graft patency and freedom from major adverse cardiovascular events, with unsupervised exercise therapy after open bypass than with the usual therapy. Unsupervised exercise therapy may be recommended for the patients after open bypass.

Re: Association of Presalvage Radiotherapy PSA Levels after Prostatectomy with Outcomes of Long-Term Antiandrogen Therapy in Men with Prostate Cancer.

Re: Association of Presalvage Radiotherapy PSA Levels after Prostatectomy with Outcomes of Long-Term Antiandrogen Therapy in Men with Prostate Cancer.

Long-Term Outcome of Endovascular Therapy for Large or Giant Thrombosed Intracranial Aneurysms

Large or giant thrombosed intracranial aneurysms (LGTIAs) are highly associated with poor prognosis and remain a challenging disease to treat by either surgery or endovascular treatment (EVT). EVT is considered more difficult for complicated aneurysm like LGTIAs. To understand long-term clinical and angiographic outcomes of EVT for LGTIAs, we retrospectively analyzed our single-center data on multimodality EVT for patients with LGTIAs. From the data of 35 EVT procedures performed in 31 consecutive patients with LGTIAs at our institution between December 2004 and December 2018, the rate of periprocedural complications, clinical outcomes at 12 months after EVT, and the rate of aneurysm recurrence were analyzed, and their related factors were evaluated. Initial EVTs were performed by deconstructive (n= 10) or reconstructive (n= 21) techniques. Although 5 patients (16%) died during the periprocedural period, 23 (74%) had good outcome at 12 months after the procedures. Among 26 patients with long-term follow-up, aneurysm recurrence was observed in 6 patients (23.1%; median time from treatment, 33.2 months). Aneurysm recurrence was significantly higher in patients with basilar artery aneurysm (P= 0.0421) and stroke (P= 0.0307); however, there was no significant difference between the procedures and devices used. Multimodality EVT for LGTIAs was performed with similar clinical outcomes and better radiologic outcomes compared with previous reports. New innovative techniques and devices are expected to be helpful for long-term aneurysm occlusion.

Detection of activating mutations in RAS/RAF/MEK/ERK and JAK/STAT signaling pathways

The study of activating mutations (NRAS,KRAS,FLT3,JAK2,CRLF2genes) of RAS/RAF/MEK/ERK and JAK/STAT signaling pathways in B-cell acute lymphoblastic leukemia (B-ALL) in adult patients which are included in Russian multicenter clinical trials. Within the multicenter study there were 119 adult patients included withde novoB-ALL. The study was considered as prospective and retrospective. The group withBCR-ABL1-negative B-ALL consisted of up to 93 patients (45 male and 48 female, at the age of 17 to 59, the median age 31), they were treated according to the protocols ALL-2009, ALL-2016. The median follow-up lasted for 19 months (1119). The group withBCR-ABL1-positive B-ALL with up to 26 patients (10 male and 16 female, at the age of 23 to 78, the median age 34 years) was included in the study as well. The treatment was carried out according to the protocols ALL-2009 and ALL-2012 in combination with tyrosine kinase inhibitors. The median follow-up lasted for 23 months (4120). The molecular analysis of activating mutations inNRAS,KRASgenes (RAS/RAF/MEK/ERK signaling pathway) andJAK2,CRLF2genes (JAK/STAT signaling cascade) was performed via Sanger sequencing. The internal tandem duplications (ITDs) inFLT3gene were studied by fragment analysis. The evaluation of CRLF2 expression was fulfilled via flow cytometry. Activating mutations inNRAS,KRAS,FLT3genes were found in 22 (23.6%) patients withBCR-ABL1-negative B-ALL. In total, 23 mutations were revealed in theNRAS(n=9),KRAS(n=12), andFLT3(n=2) genes, according to statistics that was significantly more frequent than withBCR-ABL1-positive B-ALL, these genes mutations were not identified in patients (p=0.007). The frequency of mutations detection inKRASandNRASgenes in patients withBCR-ABL1-negative B-ALL was comparable as 12.9% (12 of 93) to 9.7% (9 of 93), respectively (p=0.488). One patient was simultaneously revealed 2 mutations in theKRASgene (in codons 13 and 61).FLT3-ITD mutations were detected in 3.5% (2 of 57) cases ofBCR-ABL1-negative B-ALL. In patients withBCR-ABL1-positive B-ALLFLT3-ITD mutations were not assessed. Violations in the JAK/STAT signaling cascade were detected in 4 (4.3%) patients withBCR-ABL1-negative B-ALL. They were represented by the missense mutations ofJAK2gene (n=3) and the overexpression of CRLF2 (n=2); in one patient were detected the overexpression of CRLF2 and a mutation inJAK2gene simultaneously. No mutations were found inCRLF2gene. In patients withBCR-ABL1-positive B-ALL noJAK2mutations were detected. As long as analyzing demographic and clinical laboratory parameters between groups of patients with and without mutations, there were no statistically significant differences obtained. In the analyzed groups of patients, long-term therapy results did not differentiate according to the mutations presence inNRAS,KRAS,FLT3,JAK2genes. Also, substantive differences were not shown in the rate of the negative status achievement of the minimum residual disease between patients with and without activating mutations in the control points of the protocol (on the 70th, 133rd and 190th days). NRAS,KRAS,FLT3,JAK2activating mutations do not affect the long-term results of the therapy and the rate of the negative status achievement of the minimum residual disease in patients withBCR-ABL1-negative B-ALL treated by the Russian multicenter clinical trials.

Urodynamics tests for the diagnosis and management of bladder outlet obstruction in men: the UPSTREAM non-inferiority RCT.

Lower urinary tract symptoms (LUTS) in men may indicate bladder outlet obstruction (BOO) or weakness, known as detrusor underactivity (DU). Severe bothersome LUTS are a common indication for surgery. The diagnostic tests may include urodynamics (UDS) to confirm whether BOO or DU is the cause, potentially reducing the number of people receiving (inappropriate) surgery. The primary objective was to determine whether a care pathway including UDS is no worse for symptom outcome than one in which it is omitted, at 18 months after randomisation. Rates of surgery was the key secondary outcome. This was a pragmatic, multicentre, two-arm (unblinded) randomised controlled trial, incorporating a health economic analysis and qualitative research. Urology departments of 26 NHS hospitals in England. Men (aged ≥ 18 years) seeking further treatment, potentially including surgery, for bothersome LUTS. Exclusion criteria were as follows: unable to pass urine without a catheter, having a relevant neurological disease, currently undergoing treatment for prostate or bladder cancer, previously had prostate surgery, not medically fit for surgery and/or unwilling to be randomised. Men were randomised to a care pathway based on non-invasive routine tests (control) or routine care plus invasive UDS (intervention arm). The primary outcome was International Prostate Symptom Score (IPSS) at 18 months after randomisation and the key secondary outcome was rates of surgery. Additional secondary outcomes included adverse events (AEs), quality of life, urinary and sexual symptoms, UDS satisfaction, maximum urinary flow rate and cost-effectiveness. A total of 820 men were randomised (UDS, 427; routine care, 393). Sixty-seven men withdrew before 18 months and 11 died (unrelated to trial procedures). UDS was non-inferior to routine care for IPSS 18 months after randomisation, with a confidence interval (CI) within the margin of 1 point (-0.33, 95% CI -1.47 to 0.80). A lower surgery rate in the UDS arm was not found (38% and 36% for UDS and routine care, respectively), with overall rates lower than expected. AEs were similar between the arms at 43-44%. There were more cases of acute urinary retention in the routine care arm. Patient-reported outcomes for LUTS improved in both arms and satisfaction with UDS was high in men who received it. UDS was more expensive than routine care. From a secondary care perspective, UDS cost an additional £216 over an 18-month time horizon. Quality-adjusted life-years (QALYs) were similar, with a QALY difference of 0.006 in favour of UDS over 18 months. It was established that UDS was acceptable to patients, and valued by both patients and clinicians for its perceived additional insight into the cause and probable best treatment of LUTS. The trial met its predefined recruitment target, but surgery rates were lower than anticipated. Inclusion of UDS in the diagnostic tests results in a symptom outcome that is non-inferior to a routine care pathway, but does not affect surgical rates for treating BOO. Results do not support the routine use of UDS in men undergoing investigation of LUTS. Focus should be placed on indications for selective utilisation of UDS in individual cases and long-term outcomes of diagnosis and therapy. Current Controlled Trials ISRCTN56164274. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 42. See the NIHR Journals Library website for further project information.

Does ADHD Symptomatology Influence Treatment Outcome and Dropout Risk in Eating Disorders? A longitudinal Study.

Attention-deficit/hyperactivity disorder (ADHD) and its symptoms have been shown to be present in patients with eating disorders (EDs) and are associated with increased psychopathology and more dysfunctional personality traits. This study aimed to assess if the presence of ADHD symptoms in patients with EDs affects their short and long-term therapy outcome. A total of 136 consecutively treated ED patients were considered in this study. Baseline pre-treatment evaluation included the Adult ADHD Self-Report Scale (ASRS v1.1) for ADHD symptoms and the assessment of eating symptomatology using the Eating Disorders Inventory (EDI-2). Treatment outcome was evaluated in terms of ED symptoms after cognitive behavioral therapy (CBT) and dropout rate during treatment. Furthermore, we evaluated ED symptoms in treatment completers after a follow-up of 8 years on average. Path analyses assessed the potential mediational role of the EDI-2 total score in the relationship between ADHD and treatment outcome. Results showed that baseline symptoms of ADHD indirectly affected treatment outcome after CBT; the ASRS positive screening was related to higher eating symptomatology (standardized coefficient B = 0.41, p = 0.001, 95% CI: 0.26 to 0.55), and the presence of high ED levels contributed to the increase of dropout (B = 0.15, p = 0.041, 95% CI: 0.03 to 0.33) and a worse treatment outcome (B = 0.18, p = 0.041, 95% CI: 0.01 to 0.35). No direct effect was found between the ASRS positive screening with the risk of dropout (B = −0.08, p = 0.375) and worse treatment outcome (B = −0.07, p = 0.414). These results suggest the relevance of identifying specific treatment approaches for patients with ADHD symptoms and severe eating symptomatology.

Adherence and long-term outcomes of therapy in paediatric patients in Greece using the easypod™ electromechanical device for growth hormone treatment: The phase IV multicentre easypod™ connect observational study (ECOS)

BackgroundThe easypod™ injection device allows automatic recording and transmission of adherence data from patients receiving recombinant human growth hormone (rhGH [Saizen®]) to treat growth disorders. This analysis aimed to evaluate the adherence of Saizen® administered via easypod™ in a cohort of Greek patients from the easypod™ connect observational study (ECOS). MethodsThe phase IV, open-label, multicentre, observational, and longitudinal ECOS study (EMR200104–520, NCT01363674) enrolled patients treated for a minimum of 6 months and up to 3 years. The primary endpoint was to assess the mean rate of adherence to treatment at different time points, where good adherence was defined as ≥85%. Change in height, height standard deviation score (SDS), height velocity and height velocity SDS were evaluated after 1 year of treatment as secondary endpoints, together with the impact of adherence on growth outcomes using the Spearman's product moment. ResultsOf the 180 patients enrolled, 86 were included in the analysis. The mean adherence to Saizen®, as recorded via easypod™, was high at each individual time point, and was maintained at 95.5% after 1 year of treatment. Clinically meaningful positive changes were also noted for all of the secondary endpoints (median increase in height = 7.25 cm, height SDS = 0.32, median height velocity = 7.62 cm/year and height velocity SDS = 1.65). However, no significant correlation was noted between adherence and growth outcomes. ConclusionsrhGH replacement therapy using Saizen® with easypod™ led to full compliance to the treatment in a representative Greek population from ECOS, and provided additional insights on how the easypod™ device can assist physicians in monitoring adherence and help to optimise linear growth in paediatric patients with growth disorders.

Long-term outcomes of medical therapy versus successful recanalisation for coronary chronic total occlusions in patients with and without type 2 diabetes mellitus

BackgroundIn this study, we compared the outcomes of medical therapy (MT) with successful percutaneous coronary intervention (PCI) in chronic total occlusions (CTO) patients with and without type 2 diabetes mellitus.MethodsA total of 2015 patients with CTOs were stratified. Diabetic patients (n = 755, 37.5%) and non-diabetic patients (n = 1260, 62.5%) were subjected to medical therapy or successful CTO-PCI. We performed a propensity score matching (PSM) to balance the baseline characteristics. A comparison of the major adverse cardiac events (MACE) was done to evaluate long-term outcomes.ResultsThe median follow-up duration was 2.6 years. Through multivariate analysis, the incidence of MACE was significantly higher among diabetic patients compared to the non-diabetic patients (adjusted hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.09–1.61, p = 0.005). Among the diabetic group, the rate of MACE (adjusted HR 0.61, 95% CI 0.42–0.87, p = 0.006) was significantly lower in the successful CTO-PCI group than in the MT group. Besides, in the non-diabetic group, the prevalence of MACE (adjusted HR 0.85, 95% CI 0.64–1.15, p = 0.294) and cardiac death (adjusted HR 0.94, 95% CI 0.51–1.70, p = 0.825) were comparable between the two groups. Similar results as with the early detection were obtained in propensity-matched diabetic and non-diabetic patients. Notably, there was a significant interaction between diabetic or non-diabetic with the therapeutic strategy on MACE (p for interaction = 0.036).ConclusionsFor treatment of CTO, successful CTO-PCI highly reduces the risk of MACE in diabetic patients when compared with medical therapy. However, this does not apply to non-diabetic patients.

Long-Term Outcomes of Radioiodine Therapy for Juvenile Graves Disease with Emphasis on Subsequently Detected Thyroid Nodules: A Single Institution Experience from Japan

To investigate the long-term outcomes of radioiodine therapy (RIT) for juvenile Graves disease (GD) and the ultrasonographic changes of the thyroid gland. All of 117 juvenile patients (25 males and 92 females, aged 10 to 18 &lsqb;median 16] years) who had undergone RIT for GD at our clinic between 1999 and 2018 were retrospectively reviewed. Each RIT session was delivered on an outpatient basis. The maximum 131I dose per treatment was 13.0 mCi, and the total 131I dose per patient was 3.6 to 29.8 mCi (median, 13.0 mCi). 131I administration was performed once in 89 patients, twice in 26, and three times in 2 patients. Ultrasonography of the thyroid gland was regularly performed after RIT. The duration of follow-up after the initial RIT ranged from 4 to 226 (median 95) months. At the latest follow-up more than 12 months after RIT (n = 111), the patients' thyroid functions were overt hypothyroidism (91%), subclinical hypothyroidism (2%), normal (5%), or subclinical hyperthyroidism (2%). New thyroid nodules were detected in 9 patients, 4 to 17 years after initial RIT. Patients with newly detected thyroid nodules underwent RIT with lower doses of 131I and had larger residual thyroid volumes than those without nodules. None of the patients were diagnosed with thyroid cancer or other malignancies during the follow-up period. Over a median follow-up period of 95 months (range, 4 to 226 months), RIT was found to be effective and safe in juvenile GD. However, cumulative evidence from further studies is required to confirm the long-term safety of RIT for juvenile GD. ATD = antithyroid drug; GD = Graves disease; KI = potassium iodide; LT4 = levothyroxine; MMI = methimazole; PTU = propylthiouracil; RAIU = radio-active iodine uptake; RIT = radioiodine therapy; 99mTc = technetium-99m; TSH = thyrotropin.

Long-term clinical outcomes of salvage pelvic radiation therapy for oligo-recurrent pelvic lymph nodes after definitive external-beam radiation therapy for non-metastatic prostate cancer.

Although salvage external-beam radiation therapy (EBRT) is an attractive treatment option for pelvic lymph nodal recurrence (PeNR) in patients with prostate cancer (PCa), limited data are available regarding its long-term efficacy. This study examined the long-term clinical outcomes of patients who underwent salvage pelvic radiation therapy (sPRT) for oligo-recurrent pelvic lymph nodes after definitive EBRT for non-metastatic PCa. Patients who developed PeNR after definitive EBRT and were subsequently treated with sPRT at our institution between November 2007 and December 2015 were retrospectively analyzed. The prescribed dose was 45–50.4 Gy (1.8–2 Gy per fraction) to the upper pelvis, with up to 54–66 Gy (1.8–2 Gy per fraction) for recurrent nodes. Long-term hormonal therapy was used as neoadjuvant and/or adjuvant therapy. The study population consisted of 12 consecutive patients with PeNR after definitive EBRT (median age: 73 years). The median follow-up period was 58.9 months. The 5-year overall survival, PCa-specific survival, biochemical failure-free, clinical failure-free, and castration-resistant PCa-free rates were 82.5, 100.0, 62.3, 81.8, and 81.8%, respectively. No grade 2 or higher sPRT-related late toxicities occurred. In conclusion, more than half of the study patients treated with sPRT had a long-term disease-free status with acceptable morbidities. Moreover, most of the patients maintained hormonal sensitivity. Therefore, this approach may be a promising treatment method for oligo-recurrent pelvic lymph nodes.

Long-term β-blocker therapy and clinical outcomes after acute myocardial infarction in patients without heart failure: nationwide cohort study.

To investigate the association between long-term β-blocker therapy and clinical outcomes in patients without heart failure (HF) after acute myocardial infarction (AMI). Between 2010 and 2015, a total of 28970 patients who underwent coronary revascularization for AMI with β-blocker prescription at hospital discharge and were event-free from death, recurrent myocardial infarction (MI), or HF for 1 year were enrolled from Korean nationwide medical insurance data. The primary outcome was all-cause death. The secondary outcomes were recurrent MI, hospitalization for new HF, and a composite of all-cause death, recurrent MI, or hospitalization for new HF. Outcomes were compared between β-blocker therapy for ≥1 year (N = 22707) and β-blocker therapy for <1 year (N = 6263) using landmark analysis at 1 year after index MI. Compared with patients receiving β-blocker therapy for <1 year, those receiving β-blocker therapy for ≥1 year had significantly lower risks of all-cause death [adjusted hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.72-0.91] and composite of all-cause death, recurrent MI, or hospitalization for new HF (adjusted HR 0.82; 95% CI 0.75-0.89), but not the risks of recurrent MI or hospitalization for new HF. The lower risk of all-cause death associated with persistent β-blocker therapy was observed beyond 2 years (adjusted HR 0.86; 95% CI 0.75-0.99) but not beyond 3 years (adjusted HR 0.87; 95% CI 0.73-1.03) after MI. In this nationwide cohort, β-blocker therapy for ≥1 year after MI was associated with reduced all-cause death among patients with AMI without HF.

Heart Transplant Using Hepatitis C-Seropositive and Viremic Organs in Seronegative Recipients.

BackgroundHepatitis C virus (HCV)-seropositive donor hearts are underutilized for orthotopic heart transplantation (OHT). The advancement of direct-acting antiviral agent (DAA) treatment for HCV makes utilizing HCV-seropositive and viremic donor organs in HCV-seronegative recipients a possibility.Material/MethodsFrom 1997 to 2019, adult patients who underwent OHT at our institution were retrospectively reviewed. Ten HCV-seronegative patients received HCV-seropositive donor hearts, 3 of which tested nucleic acid-positive. Kaplan-Meier curves were performed for survival analyses. This study was approved by the Institutional Review Board.ResultsRecipient median age was 57.5 years old, and 2 (20%) were female. Donor median age was 42 years old, and 3 (30%) were female. One donor was cured from HCV with DAA prior to OHT. Four recipients developed hepatitis C viremia immediately after OHT. DAA treatment was completed in 3 recipients who demonstrated cure. Thirty-day and 1-year survival rates were both 80%.ConclusionsWe describe 10 HCV-seronegative patients who received HCV-seropositive donor hearts at our institution, with excellent short-term outcomes, even in those who received nucleic acid testing positive organs. DAA can be effective in treating hepatitis C viremia before and after OHT, with excellent recipient survival. Large clinical studies are needed to further evaluate the long-term outcomes of DAA therapy in patients after heart transplantation.

Long-term outcomes of intensity-modulated radiation therapy (IMRT) and high dose rate brachytherapy as adjuvant therapy after radical hysterectomy for cervical cancer

ObjectiveCompared with 3D-planned pelvic radiation, intensity-modulated radiation therapy (IMRT) has been shown to reduce acute toxicity in cervical cancer patients after radical hysterectomy. This study evaluated late toxicity and patterns...

Retrospective chart review of urinary glycosaminoglycan excretion and long-term clinical outcomes of enzyme replacement therapy in patients with mucopolysaccharidoses

BackgroundMucopolysaccharidoses (MPS) are a group of rare, inherited metabolic diseases that result from a deficiency in one of several lysosomal enzymes essential for stepwise glycosaminoglycan (GAG) degradation, leading to GAG accumulation and widespread cellular pathology and clinical disease. Although disease presentation is heterogeneous, the clinical hallmarks are largely comparable across several MPS subtypes. Extensive data have shown that the level of urinary GAG (uGAG) excretion above normal is strongly correlated with disease severity and clinical outcomes in MPS diseases. Thus, change in uGAG excretion may have significant value as a potential primary endpoint in clinical trials of MPS diseases that are too rare to study using traditional clinical endpoints. MethodsA retrospective medical chart review was undertaken of patients with MPS I, II, and VI who had been treated long term with enzyme replacement therapy (ERT). The relationship between uGAG reduction and clinical outcomes relevant to the major clinical manifestations of these MPS diseases was evaluated. A multi-domain responder index (MDRI) score was calculated, measuring the following 4 domains: 6-min walk test, pulmonary function, growth rate, and Clinician Global Impression of Change. For each domain, a minimal important difference (MID) was defined based on published information of these outcome measures in MPS and other diseases. ResultsOf the 50 patients evaluated, 18 (36%) had MPS I, 23 (46%) had MPS II, and 9 (18%) had MPS VI. Forty-two were clinical practice patients and 8 had participated in clinical trials. Across all MPS subtypes, the mean (± SD) uGAG level at baseline was 66.0 ± 51.5 mg/mmol creatinine (n = 48) and there was a mean reduction of 54.6% following ERT. Analysis of the MDRI score based on the MID defined for each domain showed a greater magnitude of improvement in patients with increased uGAG reduction when compared with those patients with lower uGAG reduction for all assessed uGAG thresholds, and a trend toward a higher likelihood of positive mean MDRI score in patients with a uGAG reduction ≥40%. ConclusionsIn this retrospective study, uGAG reduction was associated with long-term clinical outcomes as assessed by a number of approaches, supporting the use of uGAG reduction as a biomarker primary endpoint.

Safety and Long-term Outcomes of Defibrillator Therapy in Patients With Right-Sided Implantable Cardiac Devices in Adults With Congenital Heart Disease

BackgroundImplantable cardioverter-defibrillators (ICDs) have been proven to prevent sudden cardiac death in adult congenital heart disease (ACHD) patients. Although the left side is chosen by default, implantation from the right side is often required. However, little is known about the efficacy and safety of right-sided ICDs in ACHD patients. MethodsIn this study we reviewed a total of 191 ACHD patients undergoing ICD/cardioverter resynchronisation therapy-defibrillator (CRT-D) implantation at our hospital between 2001 and 2019 (134 men and 57 women; age [mean ± standard deviation], 41.5 ± 14.8 years). ResultsTwenty-seven patients (14.1%) had right-sided devices. The most common causes of right-sided implantation were persistent left superior vena cava and vein occlusion (37.0%). Although procedure time (202.8 ± 60.5 minutes vs 143.8 ± 69.1 minutes, P = 0.008) was longer and the procedural success was lower (92.6% vs 99.4%, P = 0.008) for right-sided devices, no difference in R-wave and pacing threshold were noted. Among the 47 patients (24.6%) who underwent defibrillation threshold testing (DFT), no difference in DFT was observed (25.2 ± 5.3 J vs 23.8 ± 4.1 J, P = 0.460). During the median follow-up of 42.4 months, appropriate ICD therapy was observed in 5 (18.5%) and 30 (18.3%) patients for right- and left-sided ICDs/CRTDs, respectively (P = 0.978). No significant difference was seen in complications between them. ConclusionsImplantation of an ICD on the right side is technically challenging, but it is feasible as an alternative approach for ACHD patients with contraindications to left-sided device implantation.

Long-term outcome of perioperative pain therapy assessed based on routine data (LOPSTER)

Long-term outcome of perioperative pain therapy assessed based on routine data (LOPSTER)