Long-term Results Of Therapy Research Articles

Long-term outcomes of endoscopic therapy versus surgical resection for 2–5 cm gastric gastrointestinal stromal tumors: A population-based comparative study

BackgroundEndoscopic therapy (ET) of gastrointestinal stromal tumors (GIST) has become a viable treatment. We intended to compare long-term outcomes of ET versus surgical resection for 2–5 cm GIST using the Surveillance, Epidemiology, and End Results (SEER) database. MethodsA multicenter retrospective study was conducted to compare the long-term outcomes of patients treated with ET and surgical resection for GIST. The multivariate Cox proportional hazards models were used to identify predictors for patients survival. To balance the clinicopathologic characteristics, a 1:1 propensity score matching (PSM) was utilized. ResultsA total of 749 patients with 2–5 cm GIST were enrolled, of whom 113 accepted ET and 636 underwent surgical resection. Before PSM, there was no significant difference in long-term outcomes between ET and surgical resection (5-year overall survival (OS): 93.5% vs. 91.6%, P=0.374; 5-year cancer-specific survival (CSS): 99.1% vs. 96.5%, P=0.546; 10-year OS: 71.1% vs. 78.2%, P=0.374; 10-year CSS: 93.6% vs. 92.7%, P=0.546). After adjusting for the relevant variables using the multivariable Cox proportional hazards models, we observed that the ET and surgical resection groups were similar in OS (HR 0.726, 95%CI 0.457-1.153, P=0.175) and CSS (HR 1.286, 95%CI 0.474-3.488, P=0.621). After PSM, the long-term OS and CSS of patients with 2–5 cm GIST after ET and surgical resection were comparable. ConclusionsWe found that the long-term survival of patients with 2–5 cm gastric GIST after ET and surgical resection were comparable. Further high-quality studies are needed to confirm the role of ET in 2–5 cm GIST.

Long-term outcomes of anti-vascular endothelial growth factor therapy with and without posterior scleral reinforcement on myopic maculopathy in myopic choroidal neovascularization eyes

BackgroundAnti-vascular endothelial growth factor (anti-VEGF) therapy is used for myopic choroidal neovascularization (mCNV). Patchy chorioretinal atrophy (pCRA) enlargement has been reported in mCNV cases associated with vision loss. Our aim was to compare the long-term effectiveness of anti-VEGF therapy alone versus anti-VEGF followed by posterior scleral reinforcement (PSR) in controlling myopic maculopathy in mCNV eyes.MethodsWe performed a retrospective review of the medical records of 95 high myopia patients (refractive error ≥ 6.00 diopters, axial length ≥ 26.0 mm) with mCNV. Patients were treated with anti-VEGF alone (group A) or anti-VEGF followed by PSR (group B). The following data were collected: refractive error, best corrected visual acuity (BCVA), ophthalmic fundus examination, ocular coherence tomography and ocular biometry at 12 and 24 months pre- and postoperatively. The primary outcomes were changes in pCRA and BCVA.ResultsIn 26 eyes of 24 patients, the mean pCRA size significantly increased from baseline (0.88 ± 1.69 mm2) to 12 months (1.57 ± 2.32 mm2, t = 3.249, P = 0.003) and 24 months (2.17 ± 2.79 mm2, t = 3.965, P = 0.001) postoperatively. The increase in perilesional pCRA in group B (n = 12) was 98.2% and 94.2% smaller than that in group A (n = 14) at 12 and 24 months (Beta 0.57 [95% CI 0.01, 191 1.13], P = 0.048). In group B, 7 eyes (58.3%) gained more than 2 lines of BCVA compared with only 4 eyes (28.6%) in group A at 24 months.ConclusionAnti-VEGF therapy followed by PSR achieved better outcomes than anti-VEGF therapy alone in controlling the development of myopic maculopathy in mCNV and may constitute a better treatment option by securing a better long-term VA outcome.

Ocular Mucous Membrane Pemphigoid: The Effect of Risk Factors at Presentation on Treatment Outcomes

PurposeAnalyze the influence of risk factors at presentation in the long-term immunosuppressive therapy (IMT) outcomes of ocular mucous membrane pemphigoid (OMMP). DesignRetrospective multicenter study. ParticipantsOMMP patients seen at Duke Eye Center, Tecnologico de Monterrey, and Hospital Clinic of Barcelona from 1990–2022. MethodsData at presentation on demographics, direct immunofluorescence and ocular findings, extraocular sites of involvement (EOM) and prior treatments, in patients with a clinical and/or laboratory diagnosis of OMMP, were analyzed with multivariable analysis and Kaplan-Meier plots to identify factors associated with adverse outcomes. Main outcome measures(1) inflammatory control (no conjunctival inflammation in both eyes at three months on IMT); (2) relapse (new-onset inflammation after absolute control in either eye); (3) progression (≥1 cicatrizing stage progression in either eye); and (4) vision loss (>2 Snellen lines). Results117 patients (234 eyes), 61% (71/117) women, with a mean age of 66.6 (standard deviation (SD) 12.4, range: 37–97) years and a median follow-up of 34 (interquartile range Q1 16, Q3 66; range: 3–265) months. Inflammatory control was achieved in 57% (67/117) patients, with high-risk EOM (HR-EOM), including esophageal, nasopharyngeal, and/or genital [adjusted odds ratio (aOR) 12.51; 95% confidence interval (CI), 2.61–59.99; P=0.002] and corneal scarring (aOR 3.06; 95% CI, 1.15–8.14; P=0.025) as significant risk factors for persistent inflammation. Disease relapse, progression, and vision loss occurred in 20% (23/117), 12% (14/117), and 27% (32/117) of patients, respectively. Baseline corneal scarring was a risk factor for relapse [adjusted hazard ratio 4.14; 95% CI, 1.61–10.62; P=0.003], progression (aOR 11.46; 95% CI, 1.78–73.75; P=0.010), and vision loss (aOR 3.51; 95% CI, 1.35–9.10, P=0.010). HR-EOM was associated with stage progression (aOR 34.57; 95% CI, 6.57–181.89; P<0.001) and vision loss (aOR 8.42; 95% CI, 2.50–28.42, P=0.001). There were no significant differences between IMT regimes and relapse (P=0.169). ConclusionsOMMP presenting with HR-EOMs and corneal scarring has an increased risk of stage progression and vision loss. Corneal scarring and severe inflammation at baseline were associated with an increased risk of relapse. A disease progression staging system incorporating both the HR-EOMs and corneal involvement is required to predict the visual outcome of OMMP better.

Efficacy of optimised thiopurine therapy in patients with moderate-to-severe ulcerative colitis: retrospective long-term follow-up from two randomised trials

Objective The long-term outcome of thiopurine therapy in patients with ulcerative colitis (UC) enrolled in prospective trials have not been evaluated. We aimed to assess the effects of optimised thiopurine maintenance therapy for UC. Methods Long-term data were obtained from patients from our center enrolled in two randomised, prospective, open-label, controlled studies comprising 66 thiopurine-naïve moderate-to-severe patients with UC consisting of a low dose azathioprine (AZA)/allopurinol combination or AZA monotherapy. Following the randomised trials, treatment was adjusted according to adverse effects and metabolites. Patients requiring optimisation initially on AZA monotherapy treatment were switched to low dose AZA in combination with allopurinol, low dose 6-mercaptopurin in combination with allopurinol, or 6-mercaptopurin treatment alone, and those treated with low dose AZA in combination with allopurinol were switched to low dose 6-mercaptopurin in combination with allopurinol or 6-mercaptopurin alone. Results A total of 62 patients were included in the analysis; 31 were initially treated with AZA monotherapy and 31 with low dose AZA in combination with allopurinol. Initial treatment was tolerated by 67% patients (7 AZA monotherapy and 28 low dose AZA in combination with allopurinol), increasing to 94% (58 patients) post-adjustment. After a median 52-month follow-up period, 38 (93%) out of the 41 primary responding patients-maintained clinical remission without steroids, biologics or surgery. The four intolerant patients and the 17 not responding to optimisation were more likely to require colectomy (odds ratio 16.36; 95% confidence interval 3.08–87.03, p < 0.0001). Conclusion Optimised thiopurine therapy demonstrated effective long-term treatment for patients with ulcerative colitis.

Anti-intercellular adhesion molecule 1 monomaintenance therapy induced long-term liver allograft survival without chronic rejection

Calcineurin inhibitors (CNIs) are essential in liver transplantation (LT); however, their long-term use leads to various adverse effects. The anti–intercellular adhesion molecule (ICAM)-1 monoclonal antibody MD3 is a potential alternative to CNI. Despite its promising results with short-term therapy, overcoming the challenge of chronic rejection remains important. Thus, we aimed to investigate the outcomes of long-term MD3 therapy with monthly MD3 monomaintenance in nonhuman primate LT models. Rhesus macaques underwent major histocompatibility complex–mismatched allogeneic LT. The conventional immunosuppression group (Con-IS, n = 4) received steroid, tacrolimus, and sirolimus by 4 months posttransplantation. The induction MD3 group (IN-MD3, n = 5) received short-term MD3 therapy for 3 months with Con-IS. The maintenance MD3 group (MA-MD3, n = 4) received MD3 for 3 months, monthly doses by 2 years, and then quarterly. The MA-MD3 group exhibited stable liver function without overt infection and had significantly better liver allograft survival than the IN-MD3 group. Development of donor-specific antibody and chronic rejection were suppressed in the MA-MD3 group but not in the IN-MD3 group. Donor-specific T cell responses were attenuated in the MA-MD3 group. In conclusion, MD3 monomaintenance therapy without maintenance CNI provides long-term liver allograft survival by suppressing chronic rejection, offering a potential breakthrough for future human trials.

Efficacy of leuprorelin in spinal and bulbar muscular atrophy: a 3-year observational study.

This study aimed to investigate the long-term effects and functional outcomes of androgen suppression therapy using leuprorelin among Korean patients with spinal and bulbar muscular atrophy (SBMA). This observational study enrolled patients with genetically confirmed SBMA who provided informed consent. Leuprorelin was administered via subcutaneous injection every 12weeks. The primary outcome measure was the change in total Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS) scores. A total of 48 SBMA patients were evaluated in this study. Among them, 39 patients underwent androgen suppression therapy over a 3-year period. The total SBMAFRS score decreased from 41.72 ± 5.55 to 36.74 ± 7.74 (p < 0.001) in patients who completed their treatment. The subgroup with a baseline SBMAFRS score of ≥ 42 had a significantly lower decline in SBMAFRS score than did those with a baseline SBMAFRS score of ≤ 41. We determined that at a baseline, SBMAFRS cutoff value of 41.5 could predict good prognosis, with a corresponding area under the curve of 0.689. Despite androgen suppression therapy, all enrolled participants exhibited a decrease in the overall SBMAFRS score. However, those with a baseline SBMAFRS of ≥ 42 showed a mild decrease in scores, indicating a more favorable prognosis. These findings suggest that a higher baseline motor function was a key prognostic indicator in SBMA treatment and that initiating early leuprorelin treatment in patients with high baseline function may lead to good clinical outcomes.

Thirty-year outcomes of low-intensity anticoagulation for mechanical aortic valve.

The long-term safety, efficacy, and outcomes of low-intensity anticoagulation for mechanical heart valves remain unclear. This study aimed to evaluate the long-term outcomes of low-intensity anticoagulation therapy after aortic valve replacement (AVR) with a mechanical prosthesis. This retrospective cohort study consulted medical records and conducted a questionnaire to investigate 519 patients who underwent single AVR with the St. Jude Medical bileaflet valve and were in sinus rhythm. All patients were followed up with an international normalized ratio (INR) target of 1.6-2.5, and their INR values were checked throughout the follow-up period. The survival rate, incidence of major adverse cardiac and cerebrovascular events (MACCE), and risk factors for cardiac death and MACCE were investigated. The total follow-up was 9793 patient-years, and the follow-up periods were 19.9 (standard deviation [SD]: 7.9) years. The mean INR was 2.03 (SD: 0.54). Survival rates from cardiac death were 93.6% in 20years and 85.2% in 30years. Advanced age ≥ 70years was the only significant risk factor for cardiac death and MACCE, and the INR < 2.0 was not significant risk factor for MACCE including thromboembolism or bleeding events. Low-intensity anticoagulation with an INR of 1.6-2.5 for patients with sinus rhythm after AVR with a bileaflet mechanical valve is safe and effective, even over 30years.

(085) Long-Term Outcomes of Testosterone Replacement Therapy Delaying Biochemical Recurrence Post-RARP: Frequency-Matched Case-Control Study

Abstract Introduction Testosterone Replacement Therapy (TRT) is known to improve functional and sexual outcomes in hypogonadal men. TRT historically has been contraindicated for the management of hypogonadism in men with prostate cancer (PC). Objective In 2020, we demonstrated in a cohort of 850 men that TRT reduced biochemical recurrence (BCR) by 50% (median follow-up 3.5 yrs.). The present study extends the follow up to 5.25 years Methods A retrospective review of prospectively collected data between December 2009 and June 2018 undergoing robotic radical prostatectomy by a single surgeon was conducted. 152 patients were administered TRT post-RP with a calculated free testosterone (cFT; below the 25%) and were frequency matched to 420 patients not receiving TRT with respect to pathological stage (p-stage) and Gleason Grade Group (GGG). Biochemical recurrence (BCR) was defined as two consecutive prostate specific antigen (PSA) blood tests &amp;gt;0.2 ng/mL. An adjusted Kaplan-Meier (KM) graph was used to analyze rate and time to BCR. Results Baseline differences in demographics were observed in BMI (p = 0.006) and follow up time (p = 0.0023), and cFT (p = 0.0156). While overall BCR was not significantly different between the two groups, a difference was observed in time to recurrence. In adjusted KM analysis, patients with a higher calculated free testosterone were less likely to have a BCR (p = 0.05). In the same analysis, patients with a higher GGG, p-stage, and preoperative PSA (p &amp;lt;0.01) were more likely to have a BCR. Patients receiving TRT had similar rates of BCR (p = 0.676). However, if they recurred, there was an average delay of 1.4 years. Conclusions TRT was observed to have a continuing protective effect in preventing and delaying BCR in patients post-RARP when compared to patients who did not receive TRT. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Advisory board and speaker for Coloplast; consultant for Cynosure; advisory board and speaker for Halozyme; intellectual property with Masimo; advisory board for Promescent; consultant for Sprout; advisory board for Xialla.

Primary response in GHD children treatment as apredictor for long-term therapy effectiveness therapy effectiveness.

Short stature in growth hormone deficiency (GHD) can be treated with recombinant human growth hormone (rhGH), which is proven to be both safe and effective. However, aconsiderable number of patients does not achieve satisfying therapy outcomes. To evaluate the predictive effect of height increase in the first year of rhGH treatment on long-term therapy outcomes. 165 short-stature children (mean age 10.72 ±3.33 years; 63% males), diagnosed with GHD, treated with rhGH for at least one year (mean follow-up 4.32 ±1.80 years), divided into 2 groups according to the change in height standard deviation score (SDS) after the first year of rhGH treatment: good responders (GR) and poor responders (PR). Then, in one-year intervals, patient's chronological age, bone age, height, weight, insulin-like growth factor level, and rhGH dose were all assessed. In the GR group, mean height velocity SDS up to five years of observation was 1.19 ±0.41/year and in the PR group 0.59 ±0.38/year. The differences were statistically significant (p<0.05). The primary response to the rhGH treatment in GHD children seems to be agood predictor for long-term therapy outcomes.

Long-term survival outcomes of endoscopic therapy vs. surgical resection in patients with cardia gastrointestinal stromal tumor.

The ideal surgical approach for treating cardia gastrointestinal stromal tumor (GIST) is not clearly established. This study aimed to assess the long-term survival results among patients who received endoscopic therapy (ET) or surgical resection (SR) for cardia GIST. Cardia GIST patients from 2000 to 2019 were selected from the surveillance, epidemiology, and end result (SEER) database. Multiple imputation (MI) was applied to handle missing data, and propensity score matching (PSM) was carried out to mitigate selection bias during comparisons. Demographic and clinical characteristics' effects on overall survival (OS) and cancer-specific survival (CSS) were assessed using Kaplan-Meier analyses and multivariate Cox proportional hazard models. A total of 330 patients with cardia GIST were enrolled, including 47 (14.2%) patients with ET and 283 (85.8%) patients with SR. The 5-year OS and CSS rates in the ET and SR groups were comparable [before PSM, (OS) (76.1% vs. 81.2%, P = 0.722), (CSS) (95.0% vs. 89.3%, P = 0.186); after PSM, (OS) (75.4% vs. 85.4%, P = 0.540), (CSS) (94.9% vs. 92.0%, P = 0.099)]. Moreover, there was no significant difference between ET and SR in terms of long-term OS (hazard ratio [HR] 0.735, 95% confidence interval [CI] 0.422-1.282) and CSS (HR 1.560, 95% CI 0.543-4.481). Our study found no significant disparity in long-term survival outcomes between ET and SR in cardia GIST patients, implying that ET could be a valid surgical strategy for treating cardia GIST.

Long-term clinical outcomes of combined modality therapy for advanced-stage Hodgkin lymphoma in the PET era: A retrospective study.

The role of consolidation radiation therapy (CRT) after complete metabolic response to chemotherapy in advanced-stage (stage III and IV) Hodgkin lymphoma (HL) is controversial. This study was undertaken to assess the clinical outcomes in terms of event free survival, local failure free survival and overall survival in individuals with advanced HL treated with chemotherapy and CRT. A retrospective review was conducted to study the long-term clinical outcomes in individuals diagnosed with HL and treated with chemotherapy and CRT from 2012 to 2016 at a tertiary cancer care hospital in India. Data from 203 study participants with advanced-stage HL were analyzed. Positron emission tomography-computed tomography (PET-CT) was done at baseline and after 2 cycles for response assessment. The median age at presentation was 32 yr [interquartile range (IQR): 26-46]. Early metabolic response (after 2 cycles) and delayed metabolic response (after 4 or 6 cycles) were observed in 74.4 and 25.6 per cent of individuals, respectively. With a median follow up of 52 months (IQR: 40-67), the five-year event-free survival (EFS), local failure-free survival (LFFS) and overall survival (OS) were 83.2, 95.1 and 94.6 per cent, respectively. On univariate analysis, extranodal disease was associated with inferior EFS (P=0.043). Haemoglobin <10.5 g/dl (P=0.002) and Hasenclever index >3 (P=0.00047) were associated with poorer OS. Relapses were observed in 28/203 (13.8%) study participants with predominance at central nodal stations. The median time to relapse was 19.4 months (IQR: 13-33). Local relapse alone (at the irradiated site) was observed in 5/28 study participants, systemic (distant) relapse in 14/28 individuals, while both systemic and local relapse was observed in 9/28 participants. Extranodal disease (P=0.05), bulky disease (P=0.005) and haemoglobin concentration ≤10.5 g/dl (P=0.036) were significant predictors for disease relapse. Individuals with advanced-stage HL treated with anthracycline-based chemotherapy (anthracycline-based chemotherapy with doxorubicin, bleomycin, vinblastine and dacarbazine regimen) and CRT had excellent long-term outcomes. As isolated infield failures are uncommon, selective consolidation with conformal RT to high-risk sites improves final disease outcomes.

Long-term outcomes of cyclosporin induction and ustekinumab maintenance combination therapy in patients with steroid-refractory acute severe ulcerative colitis.

Effective management of patients with acute severe ulcerative colitis (ASUC) is a major challenge and there remains a paucity of available maintenance treatment options after efficacious cyclosporin induction therapy. We investigated the long-term effectiveness and safety of cyclosporin and ustekinumab combination therapy in patients with steroid refractory ASUC. Monocentric, prospective study. We included patients with steroid refractory ASUC with multiple failed prior advanced therapies, who were treated with cyclosporin and ustekinumab combination therapy. Among the 11 included patients, 10 had prior failure to infliximab and 8 failed at least three previous biological therapies. The mean baseline Mayo and Lichtiger scores were 10.9 (9-12) and 13.3 (11-14), respectively. Ustekinumab was initiated 3.2 weeks (1-8) after initiation of cyclosporin treatment and combination therapy was continued for a mean of 11.5 (4-20) weeks. Clinical response was achieved in six patients at week 16 and clinical steroid-free clinical remission in five patients at week 48. Endoscopic remission was achieved in five patients at week 16 and together with histological remission in five patients at week 52. Intestinal ultrasound demonstrated mean bowel wall thickening in the sigmoid colon of 5.5 mm at baseline and 3.5 mm at week 52, respectively. Two patients had to undergo colectomy (mean 4.5 months, range 3-6) and three stopped ustekinumab therapy due to ineffectiveness. Overall, combination therapy was well tolerated. Combination of cyclosporin and ustekinumab therapy allowed nearly half of ASUC patients to reach clinical and endoscopic remission after 52 weeks, warranting further studies. Not applicable.

Long-term results of therapy for chronic myeloid leukemia: a 20-year analysis of the use of tyrosine kinase inhibitors in Russia

Introduction. In Russia, within the framework of the GIPAP program, in the period from 2001 to 2007 at the National Medical Research Center for Hematology, imatinib therapy was initiated in 235 patients in the chronic phase of chronic myelogenous leukemia (CML).Aim: to analyze the long-term results of therapy in patients with CML who started imatinib therapy as part of the GIPAP program.Methods. A retrospective analysis of the results of therapy was performed in 235 patients with СР CML, who received imatinib under the GIPAP program from 2001 to 2007 at the National Medical Research Center for Hematology. The protocols for therapy and monitoring of the residual disease of patients at various time intervals were determined by the clinical recommendations relevant at that time in the conditions of real clinical practice and the possibilities of the patient’s region of residence. Overall survival and survival without discontinuation of imatinib therapy, univariate and multivariate analysis of overall survival were performed. The cumulative incidence of responses was calculated. An analysis of response factors, the probability of death from concomitant diseases and death from CML was carried out.Results. The median follow-up of living patients at the time of analysis was 17.3 years (IQR 15.5–18.5). 70 (30 %) patients died, with the median time to death from the start of therapy being 7.8 years (IQR 3.7–13.6). The overall 10-year, 15-year and 20-year survival rates were 82 %, 74 % and 62 %. The cause of death in 43 cases (61%) was the progression of CML to the phase of acceleration or blast crisis and death out of remission for an unspecifi ed cause. 27 (39%) patients died from causes not related to CML. Patient age at initiation of imatinib therapy, length of time from diagnosis to initiation of imatinib therapy, and Sokal and ELTS risk groups at disease onset were identifi ed as signifi cant for survival by univariate analysis. Multivariate analysis showed independent predictive value for overall survival for age at initiation of imatinib therapy, length of illness before imatinib treatment, and ELTS risk group at disease onset. Among patients who died from CML progression, the proportion of patients who did not achieve CCyR for the entire period of therapy before death was 83% (35/42), while among patients who died from concomitant diseases, the proportion of patients without CCyR for the entire period of therapy was 11 % (p &lt; 0.0001). The median duration of imatinib therapy was 11.4 years (0.8–21 years). 40 people died during imatinib therapy, 103 patients are alive and continue therapy with imatinib, 92 patients received at least one second-generation of Tyrosine kinase inhibitors (TKI) (TKI2), of which 62 people are alive and continue treatment with TKI. No more than two lines of TKI therapy were received by 49 (21 %) patients, and three or more lines were prescribed to 43 (18 %) patients. The median duration of therapy after switching to TKI2 was 7.8 years (0.1–15.6 years). Overall 15-year survival after switching to TKI2 was 59 %. On therapy with imatinib, during the entire observation period, complete cytogenetic response (CCyR) was achieved in 171 patients (73 %), another 18 patients (8 %) achieved CCyR for the fi rst time after switching to TKI2. Major (MMR) and deep molecular response (DMR) were achieved with imatinib in 129 (56 %) and 124 (53 %) patients, with TKI2 TKI2 therapy in 38 (16 %) and 33 (14 %) patients, respectively. Multivariate analysis showed an independent predictive value of only the time period from diagnosis to the start of imatinib treatment for achieving molecular responses to TKI therapy.Conclusion. After 20 years of monitoring patients on TKI therapy, we still cannot say that survival in CML is comparable to the survival of normal population. Long-term follow-up confi rms the fact that tumor reduction to at least the level of CCyR is the most signifi cant surrogate marker associated with a reduced risk of death from CML. Timely diagnosis of the disease, rapid initiation of targeted therapy and the fastest possible induction of cytogenetic and molecular responses is a very important mechanism for reducing the risk of resistant course and progression of CML.

Factors associated with long-term outcomes of CD19 chimeric antigen receptor T-cell therapy for relapsedrefractory chronic lymphocytic leukemia 6-year follow-up

Factors associated with long-term outcomes of CD19 chimeric antigen receptor T-cell therapy for relapsedrefractory chronic lymphocytic leukemia 6-year follow-up

Effectiveness of a blended booster programme for the long-term outcome of cognitive behavioural therapy for MS-related fatigue: A randomized controlled trial

Background: Cognitive behavioural therapy (CBT) reduces MS-related fatigue. However, studies on the long-term effects show inconsistent findings. Objective: To evaluate whether a blended booster programme improves the outcome of CBT for MS-related fatigue on fatigue severity at 1-year follow-up. Method: A multicentre randomized clinical trial in which 126 patients with MS were allocated to either a booster programme or no booster programme (control), after following 20-week tailored CBT for MS-related fatigue. Primary outcome was fatigue severity assessed with the Checklist Individual Strength fatigue subscale 1 year after start of treatment (T52). Mixed model analysis was performed by a statistician blinded for treatment-allocation to determine between-group differences in fatigue severity. Results: Fatigue severity at 1-year follow-up did not differ significantly between the booster (N = 62) and control condition (N = 64) (B = −2.01, 95% confidence interval (CI) = −4.76 to 0.75). No significant increase in fatigue severity was found at T52 compared with directly post-treatment (T20) in both conditions (B = 0.44, 95% CI = −0.97 to 1.85). Conclusion: Effects of CBT were sustained up to 1 year in both conditions. The booster programme did not significantly improve the long-term outcome of CBT for MS-related fatigue. Trial registration: Dutch Trial Register (NTR6966), registered 18 January 2018 https://www.trialregister.nl/trial/6782

Long-term Hepatitis B and Liver Outcomes Among Adults Taking Tenofovir-Containing Antiretroviral Therapy for HBV/HIV Coinfection in Zambia.

Long-term outcomes of tenofovir-containing antiretroviral therapy (ART) for hepatitis B virus (HBV)/human immunodeficiency virus (HIV) coinfection were evaluated in Zambia. A prospective cohort of adults with HIV and hepatitis B surface antigen (HBsAg)-positivity was enrolled at ART initiation. On tenofovir-containing ART, we ascertained HBV viral load (VL) non-suppression, alanine aminotransferase (ALT) elevation, serologic end-points, progression of liver fibrosis based on elastography, and hepatocellular carcinoma (HCC) incidence. We also described a subgroup (low HBV VL and no/minimal fibrosis at baseline) that, under current international guidelines, would not have been treated in the absence of their HIV infection. Among 289 participants at ART start, median age was 34 years, 40.1% were women, median CD4 count was 191 cells/mm3, 44.2% were hepatitis B e antigen-positive, and 28.4% had liver fibrosis/cirrhosis. Over median 5.91 years of ART, 13.6% developed HBV viral non-suppression, which was associated with advanced HIV disease. ALT elevation on ART was linked with HBV VL non-suppression. Regression of fibrosis and cirrhosis were common, progression to cirrhosis was absent, and no cases of HCC were ascertained. HBsAg seroclearance was 9.4% at 2 and 15.4% at 5 years, with higher rates among patients with low baseline HBV replication markers. Reassuring long-term liver outcomes were ascertained during tenofovir-based ART for HBV/HIV coinfection in Zambia. Higher than expected HBsAg seroclearance during ART underscores the need to include people with HIV in HBV cure research.

Abstract 13670: Prevalence and Long-Term Outcomes of Intravenous Iron Sucrose Therapy in Heart Failure With Reduced Ejection Fraction: A Single Institution Retrospective Cohort Study

Background: Iron deficiency (ID) is prevalent in heart failure with reduced ejection fraction (HFrEF) defined as left ventricular ejection fraction (LVEF) ≤ 40%. Most trials used in the 2022 AHA/ACC guidelines studied iron carboxymaltose; most had a short follow-up and evaluated heart failure readmissions. We explored the prevalence of iron use, long-term therapeutic benefits, and impact on all-cause readmission for patients with HFrEF. Methods: In this retrospective cohort study, we analyzed electronic medical record data from a university hospital from 2016 to 2021 with an ICD-10 code of systolic heart failure (LVEF &lt; 50%) and ID, or iron deficiency anemia (IDA) (n=619). Intravenous (IV) iron sucrose group was matched to a control group (n = 43) by propensity score matching for age and sex. Conditional logistic regression was utilized to estimate unadjusted odds ratios (uOR) with 95% confidence interval (CI), while Mann-Whitney test was utilized to compare median values of nonparametric estimates. Statistical analysis was done in SAS version 9.4. Results: 66.7% of the studied population were male and 61.1% were ≥ 65 years. The common comorbid conditions were ischemic cardiomyopathy (39.6%), chronic kidney disease (CKD) (26.2%), and gastrointestinal (GI) bleeding (12.3%). ID was present in 115 (18.6%); IDA in 95 (15.4%) and 43 (6.9%) received IV iron sucrose. IV iron administration was significantly associated with LVEF 41-49% (uOR = 2.65, 95% CI: 1.10 - 6.43), GI bleeding (uOR = 16.00, 95% CI: 2.12 - 120.65), chronic kidney disease (uOR = 3.67, 95% CI: 1.49 - 9.04), iron deficiency (uOR = 26.00, 95% CI: 3.53 - 191.60]) and iron deficiency anemia (uOR = 24.00, 95% CI: 3.23 - 177.41). LVEF ≤40% was non-significantly associated with all-cause mortality (uOR = 1.50, 95% CI: 0.61 - 3.67). The IV iron group had a higher median rate of 6-year readmissions (8 [IQR:8] vs.1 [2]; p&lt;0.001), and blood transfusions (11 [24] vs. 3.5 [2]; p=0.05). Conclusions: Patients with HFrEF were less likely to receive IV iron sucrose and more likely to die. Those with frequent blood transfusions, GI hemorrhage, and CKD were more likely to receive IV iron. The study indicates the impact of disease severity and comorbidities on management. Larger studies are needed to investigate this postulation.

Long-Term Survival and Failure Outcomes of Single-Fraction Stereotactic Body Radiation Therapy in Early Stage NSCLC

IntroductionThis study aims to report our 13-year institutional experience with single-fraction stereotactic body radiation therapy (SF-SBRT) for early stage NSCLC. MethodsA single-institutional retrospective review of patients with biopsy-proven peripheral cT1-2N0M0 NSCLC undergoing definitive SF-SBRT between September 2008 and May 2022 was performed. All patients were treated to 27 Gy with heterogeneity corrections or 30 Gy without. Primary outcomes were overall survival and progression-free survival. Secondary outcomes included local failure, nodal failure, distant failure, and second primary lung cancer. ResultsAmong 263 eligible patients, the median age was 76 years (interquartile range [IQR]: 70–81 y) and median follow-up time was 27.2 months (IQR: 14.25–44.9 mo). Median tumor size was 1.9 cm (IQR: 1.4–2.6 cm), and 224 (85%) tumors were T1. There were 92 patients (35%) alive at the time of analysis with a median follow-up of 34.0 months (IQR: 16.6–50.0 mo). Two- and five-year overall survival was 65% and 26%, respectively. A total of 74 patients (28%) developed disease progression. Rates of five-year local failure, nodal failure, distant failure, and second primary lung cancer were 12.7%, 14.7%, 23.5%, and 12.0%, respectively. ConclusionsConsistent with multiple prospective randomized trials, in a large real-world retrospective cohort, SF-SBRT for peripheral early stage NSCLC was an effective treatment approach.

High serum levels of inflammatory markers are associated with early recurrence in patients with high-grade serous ovarian cancer after platinum therapy

ObjectiveTo determine if inflammatory biomarkers can predict the long-term outcome of platinum therapy in patients with high-grade serous ovarian cancer. MethodsWomen diagnosed with high-grade serous epithelial ovarian cancer (n = 70) at a single institution were enrolled in a prospective serum collection study between 2005 and 2020. Seventeen markers of inflammation and oxidative stress were measured in serum samples on a chemistry analyzer. Association was tested for serum levels with progression-free survival (PFS), time to recurrence (TTR), overall survival (OS), and time to death (TTD) using Cox proportional hazards and Kaplan-Meier curves. Patient survival was censored at 10 years. ResultsHigher serum levels of LDH were associated with worse PFS (HR 2.57, p = 0.028). High serum levels of BAP (HR 0.38, p = 0.025), GSP (HR 0.40, p = 0.040), HDL-c (HR 0.27, p = 0.002), and MG (HR 0.36, p = 0.017) were associated with improved PFS. Higher expression of LDH was associated with worse OS (HR 2.16, p = 0.023). Higher levels of CK.nac (HR 0.39, p = 0.033) and HDL-c (HR 0.35, p = 0.029) were associated with improved OS. Similar outcomes were found with TTR and TTD analyses. ConclusionGeneral inflammatory biomarkers may serve as a guide for prognosis and treatment benefit. Future studies needed to further define their role in predicting prognosis or how these markers may affect response to therapy.

Allogenic Acellular Dermal Matrix and Xenogeneic Dermal Matrix as Connective Tissue Graft Substitutes for Long-Term Stability Gingival Recession Therapy: A Systematic Review and Meta-Analysis.

Connective tissue graft (CTG) serves as a gold standard for gingival recession therapy. Yet the availability of CTG is limited, and it increases patient morbidity. Allogenic acellular dermal matrix (AADM) and xenogeneic dermal matrix (XDM) have been proven to be effective substitutes of CTG although the long-term stability is unclear. The aim of this study was to analyze the long-term stability outcome of gingival recession therapy using AADM and XDM compared to CTG. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted independently from several online databases (PubMed, Scopus, and Embase). Five of 233 publications were included for final qualitative analysis and meta-analysis focusing on the mean difference of clinical parameters such as recession depth (RD), recession width (RW), probing depth (PD), clinical attachment loss (CAL), tissue thickness (TT), keratinized tissue width (KTW), and mean root coverage (MRC). Meta-analyses of RD, RW, CAL, TT, KTW, and MRC display an overall mean of 0.2 mm (95% confidence interval [CI]: -0.45 to -0.05), 0.29 mm (95% CI: -0.65 to 0.08), 0.2 mm (95% CI: -0.69 to 0.29), 0.25 mm (95% CI: -0.53 to 0.03), 0.26 mm (95% CI: -0.5 to 0.02), and 9.19% (95% CI: -13.95 to -4.43]), respectively, favoring the CTG. PD was the only parameter that favored the AADM or XDM with an overall mean of 0.03 mm (95% CI: -0.05 to 0.11). In all, if the long-term stability is the goal, the CTG is considered superior for gingival recession therapy. However, if it is contraindicated, the AADM and XDM might be considered as alternatives.