Long-term Remission Rates Research Articles

Effect of oligofructose on resistance to postoperative high-fat diet-induced damage of metabolism in diabetic rats after sleeve gastrectomy.

BACKGROUNDSleeve gastrectomy (SG) can induce prominent remission of type 2 diabetes mellitus. However, the long-term remission rate of diabetes usually decreases over time. Oligofructose has been verified to modulate host metabolism. The aim of this study was to explore the protective effect of oligofructose on high-fat diet (HFD)-induced metabolic dysfunction after SG.AIMTo study the effect and mechanism of oligofructose on diabetic remission in diabetic rats after SG.METHODSSG and SHAM operation were performed on diabetes rats induced with an HFD, nicotinamide, and low-dose streptozotocin. Then the rats in the SHAM and SG groups were continuously provided with the HFD, and the rats in sleeve gastrectomy-oligofructose group were provided with a specific HFD containing 10% oligofructose. Body weight, calorie intake, oral glucose tolerance test, homeostasis model assessment of insulin resistance, lipid profile, serum insulin, glucagon-like peptide 1 (GLP-1), total bile acids, lipopolysaccharide (LPS), and colonic microbiota levels were determined and compared at the designated time points. All statistical analyses were performed using Statistic Package for Social Science version 19.0 (IBM, United States), and the statistically significant difference was considered at P < 0.05.RESULTSAt 2 wk after surgery, rats that underwent SG exhibited improved indexes of glucose and lipid metabolism. Compared with the SG group, the rats from SG-oligofructose group exhibited better parameters of glucose and lipid metabolism, lower body weight (526.86 ± 21.51 vs 469.25 ± 21.84, P < 0.001), calorie intake (152.14 ± 9.48 vs 129.63 ± 8.99, P < 0.001), homeostasis model assessment of insulin resistance (4.32 ± 0.57 vs 3.46 ± 0.52, P < 0.05), and LPS levels (0.19 ± 0.01 vs 0.16 ± 0.01, P < 0.05), and higher levels of insulin (1.17 ± 0.17 vs 1.58 ± 0.16, P < 0.001) and GLP-1 (12.39 ± 1.67 vs 14.94 ± 1.86, P < 0.001), and relative abundances of Bifidobacterium (0.0034 ± 0.0014 vs 0.0343 ± 0.0064, P < 0.001), Lactobacillus (0.0161 ± 0.0037 vs 0.0357 ± 0.0047, P < 0.001), and Akkermansia muciniphila (0.0050 ± 0.0024 vs 0.0507 ± 0.0100, P < 0.001) at the end of the study. However, no difference in total bile acids levels was observed between the two groups.CONCLUSIONOligofructose partially prevents HFD-induced glucose and lipid metabolism damage after SG, which may be due to the changes of calorie intake, insulin, GLP-1, LPS, and the gut microbiota in rats.

Issue Highlights

Issue Highlights

Lateral one-third gland resection in Cushing patients with failed adenoma identification leads to low remission rates: long-term observations from a small, single-center cohort

BackgroundCurrently, there are no guidelines for neurosurgeons treating patients with Cushing’s disease (CD) when intraoperative adenoma identification is negative. Under these circumstances, a total hypophysectomy or hemi-hypophysectomy on the side indicated by inferior petrosal sinus sampling (IPSS) is the approach being used, although there is a subsequent risk of hypopituitarism. Data on whether one-third lateral pituitary gland resection results in cure of hypercortisolism and low rates of hypopituitarism remain inconclusive.MethodsRetrospective single-center study of CD patients with failed intraoperative adenoma identification and subsequent resection of the lateral one-third of the pituitary gland as predicted by IPSS. We assessed (i) histopathological findings, (ii) early and long-term remission rates, and (iii) rates of additional pituitary hormone insufficiency.ResultsTen women and three men met the inclusion criteria. At 3 months, remission was noted in six (46%) patients: three (23%) had histologically confirmed adenomas, two (15%) had ACTH hyperplasia, and one patient (8%) was positive for Crooke’s hyaline degeneration. New pituitary hormone deficits were noted in two patients (15%). After a median (±SD) follow-up of 14±4 years, recurrence was noted in two (15%) patients. Long-term control of hypercortisolism was attained by 10 patients (77%), with additional therapies required in nine (69%) of them.ConclusionsIn CD patients with failed intraoperative adenoma visualization, lateral one-third gland resection resulted in low morbidity and long-term remission in 31% of patients without the need for additional therapies. Bearing in mind the sample size of this audit, the indication for lateral one-third-gland resection has to be critically appraised and discussed with the patients before surgery.

Predictors of Remission in Lupus Nephritis Pati

Background: Lupus nephritis (LN) is a common and serious manifestation of SLE, occurring in more than half of patients with SLE during their course of illness, in 10–25% of such patients, kidney disorder progresses to end-stage renal disease (ESRD). Objective: To determine the predictors of remission in patients with biopsy-proven lupus nephritis, and to assess the long-term renal remission rate in our lupus nephritis patients. Patients and Methods: This is a retrospective observational study carried out at the Rheumatology and Nephrology Units, Internal Medicine Department, Menoufia and Mansoura Universities Hospitals, Egypt for a 1-year duration between 1 June 2019 and 1 June 2020. A total of 60 patients with biopsy-proven LN were studied. Results: In the current study, after six months of follow-up, about two-thirds of patients achieved remission. The urinary protein creatinine ratio (UPCR) of 4.9 g/g, systemic lupus erythematosus disease activity index (SLEDAI) of 20 and Hb of 8.8 g/dl at the third month are valuable for predicting remission at the sixth month in active lupus nephritis. On multivariate analysis, serum creatinine (SCr) at the time of diagnosis is the only independent predictor of remission (complete or partial) at 6 months. According to the receiver operating characteristic curve, the cut-off value of SCr ≤ 2.9 mg/dL with 100% specificity and 98 % sensitivity was a predictor for renal remission. Conclusion:The UPCR of 4.9 g/g, SLEDAI of 20 and Hb of 8.8 g/dl at the third month are valuable for predicting remission at the sixth month in active lupus nephritis. Serum creatinine level ≤2.9 mg/dL at the time of diagnosis was the only independent predictor of complete remission at 6 months.

Moral injury: the effect on mental health and implications for treatment

Moral injury: the effect on mental health and implications for treatment

Short- and long-term outcomes of immediate and delayed treatment in epilepsy diagnosed after one or multiple seizures

ObjectivesTo compare the outcomes between immediate and deferred treatments in patients diagnosed after one or multiple (two or more) seizures. MethodsOur observational study investigated seizure recurrence and 12-month seizure remission in patients with newly diagnosed epilepsy, comparing immediate to deferred treatment in patients diagnosed after one seizure or after two or more seizures. ResultsOf 598 patients (62% male, median age 39 years), 347 (58%) were treated at diagnosis and 251 (42%) received deferred or no treatment. Seizure recurrence was higher with deferred treatment both in patients diagnosed after two or more seizures (n = 363; adjusted hazard ratio [aHR] = 2.38, 95% confidence interval [CI]: 1.79–3.14, p < 0.001) and after one seizure (n = 235; aHR = 1.41, 95% CI: 0.995–1.99, p = 0.05). Cumulative seizure recurrence rates at two years in patients diagnosed after two or more seizures were 73% with deferred treatment and 49% with immediate treatment (risk-factor-corrected number-needed-to-treat [NNT] = 4), and in those diagnosed after one seizure the rates were 60% and 51% (NNT = 8). Of 380 patients with eligible follow-up (median 4.3 years), 287 (76%) had been in seizure remission for at least one year and 211 (56%) remained in remission at last follow-up. Long-term remission rates were similar between immediate and deferred treatments, and between patients diagnosed after one seizure and those with two or more seizures. SignificanceImmediate rather than deferred treatment was less likely to influence seizure recurrence in patients diagnosed with epilepsy after a single seizure than in those diagnosed after two or more seizures, and showed no differences in long-term seizure freedom.

Treatment Strategy for Perianal Fistulas in Crohn Disease Patients: The Surgeon's Point of View.

Perianal fistula is a frequent complication and one of the subclassifications of Crohn disease (CD). It is the most commonly observed symptomatic condition by colorectal surgeons. Accurately classifying a perianal fistula is the initial step in its management in CD patients. Surgical management is selected based on the type of perianal fistula and the presence of rectal inflammation; it includes fistulotomy, fistulectomy, seton procedure, fistula plug insertion, video-assisted ablation of the fistulous tract, stem cell therapy, and proctectomy with stoma creation. Perianal fistulas are also managed medically, such as antibiotics, immunomodulators, and biologics including anti-tumor necrosis factor-alpha agents. The current standard treatment of choice for perianal fistula in CD patients is the multidisciplinary approach combining surgical and medical management; however, the rate of long-term remission is low and is reported to be 50% at most. Therefore, the optimum management strategy for perianal fistulas associated with CD remains controversial. Currently, the goal of management for CD-related perianal fistulas are controlling symptoms and maintaining long-term anal function without proctectomy, while monitoring progression to anorectal carcinoma. This review evaluates perianal fistula in CD patients and determines the optimal surgical management strategy based on recent evidence.

How I treat immune thrombocytopenia – a global view

How I treat immune thrombocytopenia – a global view

Long-term remission and biologic persistence rates: 12-year real-world data

BackgroundBiologic therapies have greatly improved outcomes in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Yet, our ability to predict long-term remission and persistence or continuation of therapy remains limited. This study explores predictors of remission and persistence of the initial biologic therapy in patients after 12 years. Furthermore, outcomes with adalimumab and etanercept are compared.Patients and methodsRA and PsA patients were prospectively recruited from a biologic clinic. Outcomes on commencing therapy, at 1 year and 12 years were reviewed. Demographics, medications, morning stiffness, patient global health score, tender and swollen joint counts, antibody status, CRP and HAQ were collected. Outcomes at 1 year and 12 years are reported and predictors of biologic persistence and EULAR-defined remission (DAS28-CRP < 2.6) are examined with univariate and multivariate analysis.ResultsA total of 403 patients (274 RA and 129 PsA) were analysed. PsA patients were more likely to be male, in full-time employment and have completed higher education. PsA had higher remission rates than RA at both 1 year (60.3% versus 34.5%, p < 0.001) and 12 years (91.3% versus 60.6%, p < 0.001). This difference persisted when patients were matched for baseline disease activity (p < 0.001). Biologic continuation rates were high for RA and PsA at 1 year (49.6% versus 58.9%) and 12 years (38.2% versus 52.3%). In PsA, patients starting on etanercept had lower CRP at 12 years (p = 0.041). Multivariate analysis showed 1-year continuation [OR 4.28 (1.28–14.38)] and 1-year low-disease activity [OR 3.90 (95% CI 1.05–14.53)] was predictive of a 12-year persistence. Persistence with initial biologic at 12 years [OR 4.98 (95% CI 1.83–13.56)] and male gender [OR 4.48 (95% CI 1.25–16.01)] predicted 12 year remission.ConclusionsThis is the first study to show better response to biologic therapy in PsA compared to RA at 12 years. Long-term persistence with initial biologic agent was high and was predicted by biologic persistence and low-disease activity at 1 year. Interestingly, PsA patients had higher levels of employment, educational attainment, and long-term remission rates compared to RA patients.

SS-4 High dose chemotherapy with autologous hematopoietic stem cell transplantation for CNS lymphoma

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDT-ASCT) is listed as a consolidation therapy option for primary central nervous system (CNS) lymphoma in the guidelines of western countries. The advantages of HDT-ASCT for primary CNS lymphoma as consolidation are believed to be high rates of long-term remission and lower neurotoxicity, even though its eligibility is limited to younger fit patients. In the Japanese guideline, HDT-ASCT for primary CNS lymphoma is however not recommended in daily practice, mainly because thiotepa was unavailable since 2011. The Japanese registry data for hematopoietic transplantation have shown that primary CNS lymphoma patients were treated with various HDT regimens and thiotepa-containing HDT was associated with better progression free survival (P=.019), lower relapse (P=.042) and a trend toward a survival benefit (Kondo E et al, Biol Blood Marrow Transplant 2019). A pharmacokinetic study of thiotepa(DSP-1958) in HDT-ASCT for lymphoma was conducted in 2017, and thiotepa was approved for HDT-ASCT in lymphoma this March, meaning that optimal HDT regimen for CNS lymphoma is now available in Japan. The treatment strategy of CNS lymphoma needs further development to improve survival and reduce toxicity.

Serum T3 Level and Duration of Minimum Maintenance Dose Therapy Predict Relapse n Methimazole-Treated Graves Disease.

BackgroundMethimazole (MMI) has been advocated as a preferred option for most Graves disease (GD) patients. However, long-term remission after a course of MMI treatment is achieved in only 20% to 40% of patients, depending on the duration of follow-up.ObjectiveTo evaluate clinical factors for predicting relapse of GD in Thai patients after MMI treatment.MethodsA retrospective analysis was performed of newly diagnosed patients with GD who achieved remission of hyperthyroid GD after at least 12 months of MMI treatment. Long-term outcomes were assessed and predictive factors of early and late relapse were evaluated.ResultsA total of 443 patients with newly diagnosed GD who were treated with MMI for at least 12 months from 1985 to 2019, and were able to discontinue medication, were studied. The mean age at diagnosis was 37.0 ± 11.4 years and 81.7% were female. Of the 320 patients (72.2%) who achieved initial remission after MMI treatment for 23 months, 106 patients (33.1%) experienced late relapse during the mean follow-up duration of 9.7 years after MMI withdrawal. The remission rates decreased from 36.4% at the first year after stopping MMI to only 20.7% at 10 years. High initial serum triiodothyronine (T3) level and duration of minimum maintenance dose therapy (MMDT) of <6 months were associated with late disease relapse after remission.ConclusionThe long-term remission rate of Graves hyperthyroidism was achieved in one-fifth of MMI-treated Thai patients. Predictive markers for late relapse included high initial serum T3 level and a duration of MMDT of <6 months.

Ixazomib with or without Rituximab Following Immunochemotherapy and Autologous Stem Cell Transplant in Mantle Cell Lymphoma

Background: Maintenance rituximab administered post autologous stem cell transplant (ASCT) in mantle cell lymphoma (MCL) is associated with improved overall survival (OS). Maintenance approaches with the proteasome inhibitor, bortezomib, are associated with improved progression-free survival (PFS), although its use is limited by peripheral neuropathy (Kaplan et al, 2020). We conducted a phase 1 study to evaluate the safety of maintenance therapy with ixazomib, an oral proteasome inhibitor, alone and in combination with rituximab for patients with MCL completing ASCT in first remission. Methods: Adult patients with MCL completing an ASCT in first partial or complete remission and who remained progression-free were enrolled between days 70-180 post-ASCT. Initially, patients received ixazomib monotherapy in cohorts of three using a standard 3+3 design. Patients self-administered ixazomib on days 1, 8, and 15 of each 28-day cycle at one of 3 dose levels: 2.3mg, 3mg, or 4mg. Patients continued therapy until disease progression, intolerance, or completion of 10 cycles. While we were enrolling to the 4mg dose level, the LYMA trial reported an OS benefit associated with maintenance rituximab (Le Gouill et al, 2017), so the protocol was amended to explore the combination of ixazomib and rituximab. Combination therapy consisted of ixazomib 4mg (given at the same schedule) and rituximab 375 mg/m2 given on day 1 of cycles 1, 3, 5, 7, and 9. The primary objective of the study was to evaluate the safety of this treatment and determine the maximum tolerated dose (MTD) while secondary objectives included efficacy. Results Twelve patients enrolled in the trial and received at least one dose of study therapy. Seven patients received ixazomib monotherapy (3mg = 3 patients, 4mg= 4 patients), and 5 patients received combination with rituximab and 4mg ixazomib. In all patients, the median age was 58 years (range 42-73 years) and 75% of the patients were male. Five patients had a high risk MIPI score. All patients entered the study in complete remission. Pre-transplant induction was R-HyperCVAD (n=6), VR-CAP/R-DHAP (n=2), NORDIC regimen (n=2), R-CHOP/R-DHAP (n=1), and R-DHAX (n=1). Transplant conditioning regimens were BEAM (n=7) or Bu/Cy/VP-16 (n=5). In the monotherapy group, 6 patients completed all 10 cycles of therapy. One patient experienced a dose limiting toxicity (DLT) which consisted of grade 3 neutropenia following cycle 1. In addition to the patient who experienced a DLT, one patient discontinued therapy early due to persistent abdominal pain that was ultimately determined to be unrelated to study therapy after an extensive evaluation. Two patients required dose reductions due to grade 3 hematologic toxicities. Two patients in the combination therapy group completed 10 cycles of therapy. Two patients experienced DLTs which consisted of grade 4 neutropenia, and 1 patient opted to discontinue therapy early due to persistent grade 2 peripheral neuropathy. In all patients, common adverse events (AEs) regardless of attribution were abdominal pain (n=6), leukopenia (n=5), nausea (n=4), thrombocytopenia (n=4), and peripheral neuropathy (n=3). Grade 3/4 AEs were thrombocytopenia (n=1) and neutropenia (n=4). No grade 3/4 peripheral neuropathy was observed. With a median follow up of 29.6 months, no patients experienced disease progression and all are alive. Due to the myelosuppression-related DLT's encountered in the combination arm, the study was closed to further accrual. Conclusions Our findings suggest adding rituximab to ixazomib at the evaluated dose and schedule as post-ASCT maintenance is associated with myelosuppression, and we would suggest future studies evaluate an alternative dose/schedule to mitigate this risk. The lack of early progressions is encouraging, confirming the findings from CALGB50403 that proteasome inhibition may provide therapeutic benefit in this setting. Further evaluation of rituximab-containing post-induction combination therapies may identify a safer dosing strategy while improving long-term remission rates. Disclosures Allen: Bayer: Consultancy, Other; Curio Sciences: Honoraria; Clinical Care Options: Speakers Bureau; Research to Practice: Speakers Bureau; Imbrium: Consultancy, Other. Waller:Verastem Oncology, Inc: Consultancy, Research Funding. Flowers:Bayer: Consultancy; Denovo Biopharma: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; BeiGene: Consultancy; Celgene: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Karyopharm: Consultancy; OptumRx: Consultancy; Pharmacyclics/Janssen: Consultancy; Spectrum: Consultancy; Acerta: Research Funding; Millennium/Takeda: Consultancy, Research Funding; TG Therapeutics: Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; Kite: Research Funding; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees. Cohen:Genentech, BMS, Novartis, LAM, BioInvent, LRF, ASH, Astra Zeneca, Seattle Genetics: Research Funding; Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo: Consultancy.

Trials in Progress: A Phase I Study to Evaluate the Safety and Pharmacokinetic Profiles of CB-5339 in Participants with Relapsed/Refractory Acute Myeloid Leukemia or Relapsed/Refractory Intermediate or High-Risk Myelodysplastic Syndrome

Trials in Progress: A Phase I Study to Evaluate the Safety and Pharmacokinetic Profiles of CB-5339 in Participants with Relapsed/Refractory Acute Myeloid Leukemia or Relapsed/Refractory Intermediate or High-Risk Myelodysplastic Syndrome

PARTIAL SPLENIC EMBOLIZATION AS A TREATMENT FOR INTRACRANIAL HEMORRHAGE CAUSED BY IMMUNE THROMBOCYTOPENIC PURPURA

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Immune Thrombocytopenic Purpura (ITP) is a disease of immune mediated platelet destruction and decreased production. Autoimmune platelet destruction occurs in tissue macrophages, mainly in the spleen. Initial treatment for ITP includes steroids and, for patients who require quicker elevation of platelet count, intravenous immunoglobulin (IVIG). Second line treatments include rituximab and newer agents that work by thrombopoiesis stimulation. Splenectomy, also a second line treatment, is generally used only after all medical options have failed due to potential complications. We report a case of partial splenic embolization (PSE) in a patient with refractory ITP presenting with acute intracranial hemorrhage (ICH). CASE PRESENTATION: A 38-year-old male with refractory ITP, initially treated with steroids, IVIG, and maintenance eltrombopag, presented to an academic medical center with two days of headache followed by acute onset weakness and slurred speech the day of presentation. Platelet count was 6k/uL; computed tomography (CT) found a pontine hemorrhage measuring 1.8x1.9x1.7cm causing effacement of the right ambient and pre-pontine cistern. He was initially treated with 4mcg/kg romiplostim, 60g IVIG, 40mg dexamethasone, 4U platelets and intubated for airway protection. Repeat laboratory results showed platelet count of 3k/uL; repeat CT showed expanding hemorrhage with worsening mass effect. Due to his worsening condition, we administered recombinant factor VIIa and performed an emergent PSE using approximately 3 ml of 300-500 µm embospheres via a right common femoral artery approach. Within nine hours of PSE, his platelet count increased to 218k/uL. Repeat CT showed stable hemorrhage; MRI did not show an underlying cause for his bleed. His platelets continued to increase, neurologic status improved and he was extubated. When the patient’s platelet count dropped to 79k/uL 11 days post-embolization, he underwent laparoscopic splenectomy. DISCUSSION: Splenectomy used to treat ITP has a high long-term remission rate.2 While there have been small, retrospective studies in the use of PSE with promising results, we found no reports in which PSE was used in an adult with ICH. Due to this presentation’s emergent nature, an active ICH and risk of bleeding, we opted for PSE rather than splenectomy for both speed and a presumed lower immediate complication rate. The PSE stabilized the patient by stopping the ICH and raising platelet count, enabling the patient to undergo laparoscopic splenectomy at a later date. CONCLUSIONS: PSE can be a safe alternative or bridge to splenectomy in patients with acute bleed due to ITP. Reference #1: Kuwana M, et al. Splenic macrophages maintain the anti-platelet autoimmune response via uptake of opsonized platelets in patients with immune thrombocytopenic purpura. J Thromb Haemost. 2009;7(2):322-329 Reference #2: Mikhael J, Northridge K, Lindquist K, Kessler C, Deuson R, Danese M. Short-term and long-term failure of laparoscopic splenectomy in adult immune thrombocytopenic purpura patients: a systematic review. Am J Hematol. 2009;84(11):743-748. DISCLOSURES: No relevant relationships by Lewis Eisen, source=Web Response No relevant relationships by Nader Emami, source=Web Response No relevant relationships by David Hirschl, source=Web Response No relevant relationships by David Schecter, source=Web Response

PDB25 Long-Term Drug Survival and Low Remission Rates in Dyslipidemia Patients Having Drug Safety Concerned and Safety Literacy

PDB25 Long-Term Drug Survival and Low Remission Rates in Dyslipidemia Patients Having Drug Safety Concerned and Safety Literacy

Overexpression of TIGIT in NK and T Cells Contributes to Tumor Immune Escape in Myelodysplastic Syndromes.

ObjectiveTargeting immune checkpoints, such as PD-1, represents a promising approach for cancer immunotherapy, achieving long-term disease remission rates in numerous types of cancer. T cell immunoglobulin and ITIM domain (TIGIT) is a checkpoint receptor associated with the antitumor roles of NK and T cells. Notably, the blockade of TIGIT has been revealed as a potential promising approach in cancer immunotherapy. However, the therapeutic potential of blocking TIGIT in myelodysplastic syndrome (MDS) remains unclear and further research is required to reveal their role.MethodsFresh peripheral blood (PB) and bone marrow (BM) were obtained from patients with MDS and healthy donors (HDs) at the Tianjin Medical University General Hospital between January 21 2018 and March 22 2019. The present study investigated the expression levels of TIGIT on NK and T cells using flow cytometry (FCM) and PCR. In addition, other checkpoint receptors, such as CD226 and PD-1, were also investigated. To determine the mechanisms of antitumor immunity, the functions of NK and T cells expressing TIGIT were determined.ResultsTIGIT was found to be highly expressed on NK and T cells of the PB, where it was involved in disease progression and the immune escape of MDS. The high expression levels of TIGIT were associated with decreased NK and T cell function, and significantly lower secretions of activation factors, such as CD107a, IFN-γ and TNF-α. Notably, blocking TIGIT enhanced the antitumor effects of NK and T cells.ConclusionThe results of the present study suggested that targeting TIGIT alone or in combination with PD-1 may be a promising anticancer therapeutic strategy in MDS.

Consolidation Therapy in Primary Central Nervous System Lymphoma.

Primary central nervous system lymphoma is a complex disease with no agreed-upon standard-of-care therapy. Induction therapy involves multiagent chemotherapy based on high-dose methotrexate, with several regimens available. We have a preference for a regimen using rituximab, methotrexate (3.5g/m2), procarbazine, and vincristine (R-MPV) for initial induction therapy, given the favorable balance between toxicities and very high response rates (80-90%), which allow for decreasing disease burden and increasing the effectiveness of consolidation treatments. However, in the absence of consolidation therapies, R-MPV is not an effective regimen to achieve long-term remission.Based on high rates of long-term remission, our first choice for consolidation therapy is high-dose chemotherapy with autologous stem-cell transplant using thiotepa, busulfan, and cyclophosphamide as a myeloablative regimen, with a curative intent. This typically applies to patients with a favorable performance status at the end of induction, typically with ECOG performance status of 2 or better, adequate organ function, and age younger than 70. Patients with a high transplant-related mortality risk may still be considered for milder myeloablative regimens such as carmustine/thiotepa.For patients who are not transplant candidates, we typically offer consolidation with reduced dose whole-brain radiation therapy (WBRT) (23.4Gy), which seems to be associated with lower risks of neurotoxicity as compared with higher doses of radiation. For patients who are not transplant candidates and that do not accept the risk of cognitive decline from the radiotherapy, we typically offer consolidation high-dose cytarabine, provided the patient understands the high risk of relapse. For these patients, a clinical trial is strongly recommended.

Significance of inflammation restricted to adventitial/periadventitial tissue on temporal artery biopsy

ObjectiveTo evaluate the characteristics and significance of inflammation restricted (RI) to the adventitial and/or periadventitial tissue on temporal artery biopsy (TAB). MethodsWe studied a retrospective cohort of 80 patients with RI, extending our earlier series of 39 patients. For comparison purposes, we collected the same data from 254 patients with transmural inflammation (TMI) and 81 TAB-negative patients. A review of the literature was also performed. ResultsA final diagnosis of giant cells arteritis (GCA) and/or polymyalgia rheumatica (PMR) was observed in 86% of patients with RI. Compared to TMI, GCA diagnosis was significantly less frequently observed in patients with RI and in those TAB-negative (p < 0.0001), while cranial manifestations were significantly less frequent (p = 0.001) and ESR and CRP values at diagnosis significantly reduced (p < 0.0001). PMR, permanent visual loss, and large vessel involvement at diagnosis were equally present in the 3 subgroups. The median duration of prednisone therapy, the cumulative prednisone dosages, and the relapse and long-term remission rates were similar between patients with GCA-RI and those with TMI. The positive likelihood ratios (LRs) of pathological evidence of RI at TAB for GCA or GCA/PMR diagnoses were 0.88 (CI, 0.61–1.27) and 1.15 (CI, 0.67–1.99), while that of inflammation limited to adventitia was 1.37 (CI, 0.59–3.19) and 3.77 (CI, 0.53–26.72). In the literature review, the positive LR of RI for GCA diagnosis was 0.92 (CI, 0.68–1.25). ConclusionA large part of the patients with RI have GCA/PMR, however, the diagnostic value of RI for GCA diagnosis is not relevant.

Laparoscopic Sleeve Gastrectomy for Type 2 Diabetes Mellitus: Long-Term Result and Recurrence of Diabetes.

Laparoscopic sleeve gastrectomy (LSG) is becoming a primary bariatric/metabolic surgical procedure for treating obesity and related type 2 diabetes mellitus (T2D). This study presents the long-term outcome of LSG about the remission and recurrence of T2D. A total of 59 obese patients (38 women and 21 male) with T2D (mean body mass index [BMI] 37.6 ± 5.1kg/m2) who underwent LSG from 2006 to 2014 with complete 5years followed up were selected for present study. The remission of T2D was evaluated in stratified groups using the ABCD scoring system which is composed of the age, BMI, C-peptide, and duration of T2D. The weight loss at 5years after surgery was 23.5% and the mean BMI decreased to 27.7 ± 4.5kg/m2. The mean HbA1c decreased from 8.1 to 6.1% at 5years. The 1-year and 5-year complete remission rate (HbA1c < 6.0%) was 62.7% and 42.4%. Thirteen patients (35.1%) out of 37 patients who had their T2D remission at 1year had their T2D recurrent at 5years. Patients with ABCD score higher than 5 had a higher long-term T2D remission rate and less recurrence of their T2D than those with ABCD score less than 5. The remission and recurrence of T2D after were associated with a weight loss more than 20%. LSG is an effective procedure for T2D treatment but a significant portion of patients had their T2D recurrence at long-term. LSG is better recommended to patients with their ABCD score ≥ 5 and dedication to maintain a good weight loss is important.

Long-Term Diabetes Remission Rates after Bariatric Surgery: Surprisingly Low in Spite of Sustained Weight Loss.

Long-Term Diabetes Remission Rates after Bariatric Surgery: Surprisingly Low in Spite of Sustained Weight Loss.