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Cancers Oct 2023To provide the first report on proton radiotherapy (PRT) in the management of advanced nasopharyngeal angiofibroma (JNA) and evaluate potential benefits compared to...
PURPOSE
To provide the first report on proton radiotherapy (PRT) in the management of advanced nasopharyngeal angiofibroma (JNA) and evaluate potential benefits compared to conformal photon therapy (XRT).
METHODS
We retrospectively reviewed 10 consecutive patients undergoing PRT for advanced JNA in a definitive or postoperative setting with a relative biological effectiveness weighted dose of 45 Gy in 25 fractions between 2012 and 2022 at the Heidelberg Ion Beam Therapy Center. Furthermore, dosimetric comparisons and risk estimations for short- and long-term radiation-induced complications between PRT plans and helical XRT plans were conducted.
RESULTS
PRT was well tolerated, with only low-grade acute toxicities (CTCAE I-II) being reported. The local control rate was 100% after a median follow-up of 27.0 (interquartile range 13.3-58.0) months. PRT resulted in considerable tumor shrinkage, leading to complete remission in five patients and bearing the potential to provide partial or complete symptom relief. Favorable dosimetric outcomes in critical brain substructures by the use of PRT translated into reduced estimated risks for neurocognitive impairment and radiation-induced CNS malignancies compared to XRT.
CONCLUSIONS
PRT is an effective treatment option for advanced JNA with minimal acute morbidity and the potential for reduced radiation-induced long-term complications.
PubMed: 37894389
DOI: 10.3390/cancers15205022 -
Therapeutic Advances in Gastroenterology 2023Ustekinumab (UST) is indicated for the treatment of Crohn's disease (CD) and Ulcerative Colitis (UC). Despite having shown clinical effectiveness in the real world, some...
BACKGROUND
Ustekinumab (UST) is indicated for the treatment of Crohn's disease (CD) and Ulcerative Colitis (UC). Despite having shown clinical effectiveness in the real world, some patients may lose response over time or need a higher dose to achieve it. In this context, UST intravenous (IV) maintenance has been proposed.
OBJECTIVES
The primary endpoint of our study was to evaluate the efficacy and safety of maintenance IV UST treatment in Inflammatory Bowel Disease (IBD) patients who present with partial response or loss of response to subcutaneous (SC) UST.
DESIGN
We performed a monocentric observational retrospective study including patients with active IBD on maintenance treatment with IV UST.
METHODS
The clinical response and remission was analyzed at week 12, defined as either Harvey-Bradshaw Index ⩽ 4 for CD or partial Mayo Score ⩽ 2 for UC. The reduction of objective markers of disease activity, fecal calprotectin, and C-reactive protein was evaluated. Moreover, UST trough levels were measured pre- and post-UST IV maintenance and any adverse events were assessed.
RESULTS
We included 23 patients. Clinical remission at week 12 was achieved by 43.5% of the patients. The proportion of patients in clinical response after 12 weeks on UST IV maintenance was 82.6%. After a median follow-up of 9.3 months all patients remained on IV UST maintenance. No adverse events were recorded in any patient for the duration of the study.
CONCLUSIONS
IV UST maintenance treatment was able to recapture response in most of the patients who had lost response to SC maintenance.
PubMed: 37655058
DOI: 10.1177/17562848231191670 -
Journal of Crohn's & Colitis Jan 2024Maintenance treatment for ulcerative colitis may be discontinued for multiple reasons. This post hoc analysis assessed the efficacy and safety of re-treatment with... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
Maintenance treatment for ulcerative colitis may be discontinued for multiple reasons. This post hoc analysis assessed the efficacy and safety of re-treatment with filgotinib, an oral, once-daily, Janus kinase 1 preferential inhibitor, in the phase 2b/3 SELECTION trial and its long-term extension [LTE] study in ulcerative colitis.
METHODS
Partial Mayo Clinic Score [pMCS] response and remission were evaluated in patients who received induction with filgotinib 200 mg [FIL200] or 100 mg [FIL100], were randomized to treatment withdrawal [placebo] during maintenance, and following disease worsening, were re-treated with open-label FIL200 in the LTE study. Factors were evaluated for association with pMCS remission at LTE week 12, and safety outcomes were reported.
RESULTS
Analyses included 86 patients [FIL200: n = 51; FIL100: n = 35]. Median time to disease worsening following treatment withdrawal was 15.1 weeks (95% confidence interval [CI]: 9.1-18.7) for FIL200-induced patients and 9.6 weeks [95% CI: 6.3-12.0] for FIL100-induced patients. Three-quarters [75%] of patients achieved a pMCS response within 4-5 weeks of re-treatment in both groups. At LTE week 48, pMCS remission was achieved by 45.1% and 51.4% of FIL200- and FIL100-induced patients, respectively. Factors independently associated with restoring efficacy included no concomitant use of corticosteroids at induction baseline, and high albumin levels, pMCS remission, and endoscopic score at maintenance baseline. No new safety signals were reported among re-treated patients.
CONCLUSIONS
In induction responders, re-treatment with FIL200 following temporary withdrawal from therapy restores response and/or remission in the majority of patients within 12 weeks. Re-treatment is well-tolerated. ClinicalTrials.gov identifiers: NCT02914522, NCT02914535.
Topics: Humans; Colitis, Ulcerative; Pyridines; Triazoles; Induction Chemotherapy; Janus Kinase Inhibitors; Remission Induction; Treatment Outcome
PubMed: 37540206
DOI: 10.1093/ecco-jcc/jjad123 -
PloS One 2023Colonoscopy is necessary for diagnosing and surveilling patients with ulcerative colitis, though it may cause disease flares. Colonoscopy with carbon dioxide (CO2)... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIM
Colonoscopy is necessary for diagnosing and surveilling patients with ulcerative colitis, though it may cause disease flares. Colonoscopy with carbon dioxide (CO2) insufflation decreases abdominal discomfort; however, its effect on exacerbation incidence in ulcerative colitis remains unclear. Therefore, this study aimed to evaluate the colonoscopy effects using CO2 insufflation in patients with ulcerative colitis.
METHODS
Overall, 96 remissive patients with ulcerative colitis (partial Mayo score ≤ 2) who underwent total colonoscopy between March 2015 and December 2019 at Osaka University Hospital were enrolled and blindly randomized to the CO2 (n = 45) and air (n = 51) insufflation group (UMIN-CTR, number: UMIN000018801). The post-procedural abdominal discomfort and the clinical relapse (partial Mayo score ≥ 3) rate within 8 weeks were evaluated.
RESULTS
Baseline backgrounds did not differ between the groups. The mean abdominal fullness and pain scores were significantly lower in the CO2 group than in the Air group immediately (p = 0.0003, p = 0.0003) and 30 min (p < 0.0001, p < 0.0001) after colonoscopy. While the overall clinical relapse rate remained unchanged between the groups, the clinical relapse rate at 8 weeks after colonoscopy was significantly lower in the CO2 group than in the Air group in patients not in complete remission (Mayo endoscopic subscore ≥ 1, p = 0.049; or partial Mayo score ≥ 1, p = 0.022).
CONCLUSIONS
CO2 insufflation can reduce abdominal discomfort in remissive patients with ulcerative colitis and decrease clinical relapse at 8 weeks after colonoscopy for those not in complete remission.
Topics: Humans; Colitis, Ulcerative; Carbon Dioxide; Insufflation; Colonoscopy; Chronic Disease; Fabaceae
PubMed: 37590283
DOI: 10.1371/journal.pone.0290329 -
Mediterranean Journal of Rheumatology Dec 2023We report a longitudinal observational cohort of idiopathic inflammatory myositis (IIM) focusing on the long-term clinical outcome and associated parameters.
BACKGROUND
We report a longitudinal observational cohort of idiopathic inflammatory myositis (IIM) focusing on the long-term clinical outcome and associated parameters.
METHODS
IIM patients were classified as per Bohan and Peter criteria. In those with ≥ 24 months of follow-up; the treatment response, functional outcomes, and damage at last follow-up were recorded. Complete clinical response and clinical remission as defined by Oddis et al., was used to define outcomes at last follow-up.
RESULTS
The cohort consists of 175 patients, mean age 40.9 (+12.6) years, M:F 1:3.3; and the major subsets were dermatomyositis (44.6%), overlap myositis (25.7%), antisynthetase syndrome (6.3%), polymyositis (14.3%), and juvenile DM/OM (8.6%). Ninety-four patients have followed up for 24 months or more, with the median (IQR) of 65(35,100.7) months. Of them, 74.1% and 11.8% had complete and partial clinical responses respectively at the last follow-up. In our cohort 40.2% were off-steroids and 13.8% were in clinical remission at the last follow-up. Complete clinical response was associated with better functional outcomes and lesser damage as determined by HAQ-DI of 0[OR10.9; 95%CI (3.3,160)], MRS [OR 3.2; 95%CI (1.4,7.3)] and lesser MDI [OR 1.7; 95% CI (1.1,2.7)] respectively as compared to partial response (unadjusted analysis). Baseline parameters and IIM subsets did not significantly influence the functional outcome and damage. The mortality rate in our cohort is 24/175 (13.7%), the disease-specific mortality rate being 9.1%. Large majority of deaths were early, associated with active disease.
CONCLUSION
We report good long-term outcomes in all major myositis subsets. Partial clinical response to treatment is associated with worse functional outcomes and damage accrual. Death occurs early in association with active disease.
PubMed: 38282927
DOI: 10.31138/mjr.280823.lto -
Frontiers in Immunology 2023Anti-CD19 chimeric antigen receptor (CAR)-T cells not only target CD19-positive malignant lymphoma cells but also normal B cells. The utility of CAR-T cell therapy has...
Anti-CD19 chimeric antigen receptor (CAR)-T cells not only target CD19-positive malignant lymphoma cells but also normal B cells. The utility of CAR-T cell therapy has been reported in rheumatoid arthritis and systemic lupus erythematosus; however, its use in Sjögren's disease (SjD) remains unknown. In this study, we describe the case of a 76-year-old woman with active SjD for 10 years who was diagnosed with diffuse large B-cell lymphoma. After receiving anti-CD19 CAR-T cell therapy, she achieved complete remission (CR) on day 28. Since the onset of her 10-year history with SjD, she was negative for antinuclear antibodies and anti-Ro-52 for the first time on day 90 after CAR-T cell therapy. Six months after CAR-T cell therapy, the CR status was maintained, serum cytokine levels returned to their normal levels, and dry mouth symptoms improved. The EULAR Sjögren's Syndrome Disease Activity Index score decreased from 5 to 2, indicating a partial remission of SjD activity compared with that before CAR-T cell treatment. In the early stage of treatment, she presented with grade 2 cytokine release syndrome and grade 1 neurotoxicity, which were completely controlled after an active intervention. This case highlights the potential application of CAR-T cells in treating autoimmune diseases, such as SjD.
Topics: Humans; Female; Aged; Receptors, Chimeric Antigen; Sjogren's Syndrome; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Antigens, CD19; Cell- and Tissue-Based Therapy
PubMed: 38173731
DOI: 10.3389/fimmu.2023.1298815 -
Gastroenterology Jan 2024Endoscopic assessment of ulcerative colitis (UC) typically reports only the maximum severity observed. Computer vision methods may better quantify mucosal injury detail,... (Clinical Trial)
Clinical Trial
BACKGROUND & AIMS
Endoscopic assessment of ulcerative colitis (UC) typically reports only the maximum severity observed. Computer vision methods may better quantify mucosal injury detail, which varies among patients.
METHODS
Endoscopic video from the UNIFI clinical trial (A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis) comparing ustekinumab and placebo for UC were processed in a computer vision analysis that spatially mapped Mayo Endoscopic Score (MES) to generate the Cumulative Disease Score (CDS). CDS was compared with the MES for differentiating ustekinumab vs placebo treatment response and agreement with symptomatic remission at week 44. Statistical power, effect, and estimated sample sizes for detecting endoscopic differences between treatments were calculated using both CDS and MES measures. Endoscopic video from a separate phase 2 clinical trial replication cohort was performed for validation of CDS performance.
RESULTS
Among 748 induction and 348 maintenance patients, CDS was lower in ustekinumab vs placebo users at week 8 (141.9 vs 184.3; P < .0001) and week 44 (78.2 vs 151.5; P < .0001). CDS was correlated with the MES (P < .0001) and all clinical components of the partial Mayo score (P < .0001). Stratification by pretreatment CDS revealed ustekinumab was more effective than placebo (P < .0001) with increasing effect in severe vs mild disease (-85.0 vs -55.4; P < .0001). Compared with the MES, CDS was more sensitive to change, requiring 50% fewer participants to demonstrate endoscopic differences between ustekinumab and placebo (Hedges' g = 0.743 vs 0.460). CDS performance in the JAK-UC replication cohort was similar to UNIFI.
CONCLUSIONS
As an automated and quantitative measure of global endoscopic disease severity, the CDS offers artificial intelligence enhancement of traditional MES capability to better evaluate UC in clinical trials and potentially practice.
Topics: Humans; Artificial Intelligence; Colitis, Ulcerative; Colonoscopy; Computers; Remission Induction; Severity of Illness Index; Ustekinumab
PubMed: 37832924
DOI: 10.1053/j.gastro.2023.09.049 -
Animals : An Open Access Journal From... Jul 2023Chemotherapy and cyclooxygenase inhibitors (COXi) are primary treatments for canine urethral transitional cell carcinoma (uTCC), a tumor known for its aggressiveness and...
Chemotherapy and cyclooxygenase inhibitors (COXi) are primary treatments for canine urethral transitional cell carcinoma (uTCC), a tumor known for its aggressiveness and poor prognosis. This retrospective study aimed to evaluate the clinico-pathological characteristics, treatment modalities, and prognostic factors of 35 dogs with confirmed uTCC that received chemotherapy and COXi. Upon admission, urethral obstruction (UO) and urinary tract infection (UTI) were observed in seven (20%) dogs each. Gemcitabine ( = 20; 57.1%) and vinblastine ( = 10; 28.6%) were commonly used as first-line therapies, with four dogs also receiving radiation therapy. Based on RECIST, one (2.9%) dog achieved complete remission, nine (25.7%) partial remission, 20 (57.14%) showed stable disease, and five (14.3%) progressed. Among dogs with UO, six (85.7%) showed resolution or improvement after the first chemotherapy dose. The median time to local progression was 171 days (range: 107-235), and the median survival time was 333 days (range: 158-508). Dogs with UO upon admission had a higher risk of local progression, while both UO and UTI were associated with an increased risk of overall disease progression and tumor-related death. Additionally, gemcitabine significantly improved metastatic control. This study identified UO and UTI as negative prognostic factors, highlighting the importance of a multimodal approach in managing uTCC.
PubMed: 37508172
DOI: 10.3390/ani13142395 -
Frontiers in Pharmacology 2023Treatment of relapsed or refractory acute myeloid leukemia (R/R AML) and myeloid sarcoma (MS) has presented challenges for decades. Studies on selinexor in combination...
Real-world experience with selinexor-containing chemotherapy-free or low-dose chemotherapy regimens for patients with relapsed/refractory acute myeloid leukemia and myeloid sarcoma.
Treatment of relapsed or refractory acute myeloid leukemia (R/R AML) and myeloid sarcoma (MS) has presented challenges for decades. Studies on selinexor in combination with various standard or intensive chemotherapy regimens for the treatment of R/R AML have demonstrated promising results. This study aimed to evaluate the efficacy and safety of chemotherapy-free or low-dose chemotherapy regimens with selinexor for R/R AML and MS patients. Ten patients with R/R AML or MS who received chemotherapy-free or low-dose chemotherapy regimens in combination with selinexor at Tongji Hospital from October 2021 to August 2022 were included in this study. The primary endpoint was overall response rate (ORR) and secondary endpoints included complete remission (CR), CR with incomplete hematological recovery (CRi), partial remission (PR), transplantation rate, and safety. All patients were evaluable for response, achieving CR in four (40.0%) patients and CRi in two (20.0%) patients for a total CR/CRi of 60.0%. The ORR was 80.0% when patients with PR were included. Five (50.0%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after treatment with selinexor-containing regimens. At the end of the follow-up, seven (70.0%) patients were alive, and three patients died of transplant-related complications or disease progression. The most frequently reported nonhematologic adverse events (AEs) in patients were grade 1 or 2 asymptomatic hyponatremia. The chemotherapy-free or low-dose chemotherapy regimens in combination with selinexor for R/R AML are feasible and tolerable and provide an opportunity for patients to receive transplantation.
PubMed: 37601075
DOI: 10.3389/fphar.2023.1217701 -
Kidney International Reports Aug 2023The prognostic value of PLA2R antibody (Ab) test in clinical practice remains unclear. We aimed to evaluate its ability in predicting hard outcomes in primary membranous...
INTRODUCTION
The prognostic value of PLA2R antibody (Ab) test in clinical practice remains unclear. We aimed to evaluate its ability in predicting hard outcomes in primary membranous nephropathy (PMN) after adjustments to conventional markers of disease activity.
METHODS
A total of 222 patients diagnosed with PMN from January 2003 to July 2019 having had a serum PLA2R Ab test, were included from 3 centers in the north of England. Baseline conventional markers, PLA2R-Ab-status (positive vs. negative), Ab-titer (high vs. low), and time of testing (pre-PLA2R era vs. PLA2R era) were evaluated for association with outcomes. Primary outcome was time to progression (composite of doubling of creatinine, stage 5 chronic kidney disease, or death). Secondary outcomes were time to partial remission (PR) and time to immunosuppression. Cox proportional hazard testing was used.
RESULTS
During a median follow-up of 5.26 years, progression was seen in 65 (29.3%) and PR in 179 of 222 patients (80.6%). There was a clear association of estimated glomerular filtration rate (eGFR) (standardized hazard ratio [HR] = 0.767, < 0.05) and urine protein-to-creatinine ratio (uPCR) (HR = 1.44, < 0.005) with time to progression among all patients, and eGFR (HR = 0.606, < 0.005) in Ab-positive patients. Baseline Ab-positivity was not associated with time to progression (adjusted hazard ratio [aHR] = 0.93, = 0.71) or time to PR (aHR = 0.84, = 0.13). Similarly, baseline high Ab-titer was not associated with time to progression (aHR = 1.07, = 0.77) or time to PR (aHR = 0.794, = 0.08).
CONCLUSION
Once adjusted to conventional markers of disease activity, baseline PLA2R Ab-positivity or Ab-titer do not predict disease progression or time to PR. Further studies are needed to harness the utility of PLA2R Ab test in prognostication in PMN.
PubMed: 37547510
DOI: 10.1016/j.ekir.2023.05.019