Multiple Relapses
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2021 ◽  
Vol 42 (Supplement_1) ◽  
V Scheggi ◽  
N Ceschia ◽  
F Vanni ◽  
I Merilli ◽  
E Sottili ◽  

Abstract Introduction Injection drug use (IDU) is a known risk factor for infective endocarditis (IE) and is associated with frequent recurrences, but its prognostic impact is still debated. Moreover, the potential futility of surgery in this population is an unsolved matter. Purpose We aimed to determine the clinical characteristics, the therapeutic strategy, and the prognostic impact of injection drug use IE (IDUIE). Method We retrospectively included in the analysis 454 consecutive episodes of definite active IE admitted in a single surgical centre from January 2012 to December 2020; 14 out of them where a subsequent infective episode of the same patient. Results IDUIE cases were 63 (13.8%), without significant proportional differences over time. IDUIE patients were significantly younger (43.95±10.12 vs 67.84±13.33, p 0.00) and presented fewer comorbidities (p<0.001). They were admitted with a first episode of IE only in 60.3% of cases vs 92.8% of non-IDU (p<0.001). Embolism was present at admission in a higher percentage (60.3 vs 38.4%, p<0.001). IDUIE was more frequently associated with spondylodiscitis (15.9 vs 7.4%, p=0.026). The infection was less frequently left-sided than in non-IDU patients (57.1 vs 97.2%, p<0.001) and was more often polimicrobic (12.7 vs 4.9%, p=0.015). Most patients were positive for Staphylococcus aureus (54.0 vs 12.8%, p<0.001), while Streptococci were significantly less frequent in patients with IDUIE (11 vs 25%, p=0.015). The proportion of patients undergoing surgery was similar among the two groups (85.5 vs 78.8%, NS). IDUIE patients treated medically for absence of surgical indication had a better survival than patients undergoing surgery for complicated IE (p<0.001). IDUIE was associated with a higher proportion of relapse during follow-up (28.3 vs 3.3%, p<0.001). It was not associated with higher mortality (Figure 1) but was an independent predictor of mortality in multivariable analysis including age (HR per unit 1.048, 95% CI 1.038–1.063, p=0.00) and drug abuse (HR 3.2, 95% CI 1.8–5.6, p=0.00; Figure 2). Among IDUIE patients, we did not find predictors of futility of surgery, not even multiple relapses. Conclusions IDUIE represents a considerable proportion of overall cases of IE, mainly affecting young people. Staphylococcus aureus is the most common microbiologic agent. IDUIE is not associated with higher mortality but drug abuse is an independent predictor of mortality. Considering that patient with uncomplicated IE treated medically have a better prognosis, we should reserve surgery to patients with a strict indication for it. On the other hand, since there are no predictors of futility of surgery, all patients with a complicated IE should undergo surgery without delay. The main determinant of prognosis in these patients is not IE but drug abuse itself. For this reason, increased focus on addiction treatment following hospital discharge is mandatory to improve long term prognosis. FUNDunding Acknowledgement Type of funding sources: None.

2021 ◽  
Vol 21 (1) ◽  
Valentina Scheggi ◽  
Stefano Del Pace ◽  
Nicole Ceschia ◽  
Francesco Vanni ◽  
Irene Merilli ◽  

Abstract Background Intravenous drug abuse (IDA) is a known risk factor for infective endocarditis (IE) and is associated with frequent relapses, but its prognostic impact is still debated. The potential futility of surgery in this population is a further issue under discussion. We aimed to describe the clinical characteristics, the therapeutic strategy, and the prognosis associated with IDA in IE. Methods We retrospectively analysed 440 patients admitted to a single surgical centre for definite active IE from January 2012 to December 2020. Results Patients reporting IDA (N = 54; 12.2%) were significantly younger (p < 0.001) and presented fewer comorbidities (p < 0.001). IDA was associated with a higher proportion of relapses (27.8 vs. 3.3%, p < 0.001) and, at multivariable analysis, was an independent predictor of long-term mortality (HR 2.3, 95%CI 1.1–4.7, p = 0.015). We did not register multiple relapses in non-IDA patients. Among IDA patients, we observed 1 relapse after discharge in 9 patients, 2 relapses in 5 patients and 3 relapses in 1 patient. In IDA patients, neither clinical and laboratory variables nor the occurrence of even multiple relapses emerged as indicators of an adverse risk–benefit ratio of surgery in patients with surgical indication. Conclusions IE secondary to IDA affects younger patients than those with IE not associated with IDA. Probably due to this difference, IE secondary to IDA is not associated with significantly higher mortality, whereas the negative, long-term prognostic impact of IDA emerges in multivariate analysis. Considering the good prognosis of patients with uncomplicated IE treated medically, surgery should be reserved to patients with a strict- guidelines-based indication. However, since there are no clear predictors of an unfavourable risk–benefit ratio of surgery in patients with surgical indication, all patients with a complicated IE should be operated, irrespective of a history of IDA.

Steven Toh ◽  
Chean Chung Shen

Chronic relapsing inflammatory optic neuropathy (CRION) is a recently described form of recurrent isolated subacute optic neuropathy, with accumulating evidence that it is a nosological distinct entity. The condition is highly responsive to systemic steroid treatment and prone to relapse on steroid withdrawal. Diagnosis and management of this condition is often challenging. This 33-year-old lady with family history of multiple sclerosis (MS), with uniocular visual loss of her right eye since 2 years old without apparent cause, presented with reduction of vision and loss of colour vision in the left eye, associated with painful eye movement. There was internuclear ophthalmoplegia but slit lamp examination were unremarkable. She had no other related sensory or motor symptoms. Magnetic resonance imaging (MRI) did not reveal any features of MS. Aquaporin-4 antibody, anti-MOG and gene testing for Leber’s hereditary optic neuropathy were all negative. Metabolic, infective, and other autoimmune causes were also excluded. Visual evoked potential studies of left eye showed a mild reduction in amplitude with no prolongation of latency. Her multiple optic neuritis recurrences were treated with intravenous steroids followed by tapering regime of oral prednisolone with good effect. Knowledge of this rare condition as part of the differential diagnoses of possible aetiologies of optic neuropathy is important among Ophthalmologists, as prompt diagnosis and steroid treatment helped reduce the associated risk of blindness. Multiple relapses after initial successful treatment of inflammatory optic neuropathy should raise the suspicion of CRION.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S19

2021 ◽  
Vol 20 (1) ◽  
Anielle de Pina-Costa ◽  
Ana Carolina Rios Silvino ◽  
Edwiges Motta dos Santos ◽  
Renata Saraiva Pedro ◽  
José Moreira ◽  

Abstract Background The relapsing nature of Plasmodium vivax infection is a major barrier to its control and elimination. Factors such as adequate dosing, adherence, drug quality, and pharmacogenetics can impact the effectiveness of radical cure of P. vivax and need to be adequately evaluated. CYP2D6 pathway mediates the activation of primaquine (primaquine) into an active metabolite(s) in hepatocytes, and impaired activity has been linked to a higher risk of relapse. Cases presentation Three patients diagnosed with P. vivax malaria presented repeated relapses after being initially treated with chloroquine (25 mg/kg) and primaquine (3.5 mg/kg in 14 days) at a non-endemic travel clinic. Recurring episodes were subsequently treated with a higher dose of primaquine (7 mg/kg in 14 days), which prevented further relapses in two patients. However, one patient still presented two episodes after a higher primaquine dose and was prescribed 300 mg of chloroquine weekly to prevent further episodes. Impaired CYP2D6 function was observed in all of them. Conclusion Lack of response to primaquine was associated with impaired CYP2D6 activity in three patients presenting multiple relapses followed in a non-endemic setting. Higher primaquine dosage was safe and effectively prevented relapses in two patients and should be further investigated as an option in Latin America. It is crucial to investigate the factors associated with unsuccessful radical cures and alternative therapeutic options.

2021 ◽  
pp. 1-5
Tomás Palanques-Pastor ◽  
Juan Eduardo Megías-Vericat ◽  
Virginia Bosó Ribelles ◽  
Inés Gómez Seguí ◽  
José Luis Poveda Andrés

Acquired thrombocytopenic thrombotic purpura (aTTP) is an autoantibody-mediated disease against the enzyme A Disintegrin and Metalloprotease domain with ThromboSpondin-1 type motif 13, which until now has been treated with plasma exchange (PEX) and corticosteroids. A 29-year-old female patient, who presented with aTTP in the context of pregnancy, has developed multiple relapses after treatment with PEX, corticosteroids, and rituximab. Recently, caplacizumab, a nanobody against von Willebrand factor, has been approved for the treatment of aTTP. In our patient, caplacizumab achieved better disease control, with a lower platelet count restoration time, days of PEX and hospitalization duration, as compared to standard therapy, reproducing the results of clinical trials. Caplacizumab represents a significant advance in the treatment of aTTP, especially in cases of recurrent relapses.

2021 ◽  
pp. 983-988
Daniel Cirotski ◽  
Jyoti Panicker

Osteosarcoma is the most common primary bone cancer in all age groups. Metastasis mostly occurs with high-grade tumors disseminating to the lungs and other bones. Spread to the pancreas is rare and undocumented in the low-grade subtypes. Additionally, it is uncommon for the disease course of low-grade subtypes to involve multiple relapses. We present a 35-year-old woman with parosteal osteosarcoma who has experienced an atypical metastasis to the pancreas as well as multiple local and pulmonary relapses. The lesion was identified incidentally on routine imaging, and the patient underwent resection. We compare our case to the other reports of pancreatic metastasis in the literature. Despite being especially rare, clinicians ought to be aware of pancreatic metastasis of osteosarcoma. Furthermore, despite parosteal osteosarcoma’s less aggressive disease course, it can uncommonly lead to multiple relapses. We present a rare case exemplifying these phenomena in the prognostically favorable histologic subtype of parosteal osteosarcoma.

2021 ◽  
Vol 19 (1) ◽  
Ding Nie ◽  
Qiuyue Fang ◽  
Bin Li ◽  
Jianhua Cheng ◽  
Chuzhong Li ◽  

Abstract Background Pituitary adenomas are one type of intracranial tumor, which can be divided into microadenoma (≤ 1 cm), macroadenoma (> 1 cm), and giant adenoma (≥ 4 cm) according to their diametral sizes. They are benign, typically slow-progressing, whereas the biological behavior of some of them is invasive, which presents a major clinical challenge. Treatment of some pituitary adenomas is still difficult due to drug resistance or multiple relapses, usually after surgery, medication, and radiation. At present, no clear prediction and treatment biomarkers have been found in pituitary adenomas and some of them do not cause clinical symptoms, so patients are often found to be ill through physical examination, and some are even found through autopsy. With the development of research on pituitary adenomas, the immune response has become a hot spot and may serve as a novel disease marker and therapeutic target. The distribution and function of immune cells and their secreted molecules in pituitary adenomas are extremely complex. Researchers found that infiltration of immune cells may have a positive effect on the treatment and prognosis of pituitary adenomas. In this review, we summarized the advance of tumor immunity in pituitary adenomas, revealing the immunity molecules as potential biomarkers as well as therapeutic agents for pituitary adenomas. Conclusion The immune studies related to pituitary adenomas may help us find relevant immune markers. At the same time, the exploration of immunotherapy also provides new options for the treatment of pituitary adenomas.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7508-7508
Stephen J. Schuster ◽  
Michael J. Dickinson ◽  
Martin H. Dreyling ◽  
Joaquín Martínez ◽  
Arne Kolstad ◽  

7508 Background: Most pts with r/r FL experience multiple relapses and progressively worse clinical outcomes with each line of therapy, underlining a need for novel therapies. Tisa-cel has demonstrated durable responses and manageable safety in adult pts with r/r diffuse large B-cell lymphoma. Here we report the primary analysis of ELARA, an international, single-arm phase 2 trial of tisa-cel in adult pts with r/r FL. Methods: Eligible pts (≥18 y) had r/r FL (grades [Gr] 1-3A) after ≥2 lines of therapy or had failed autologous stem cell transplant. Bridging therapy was permitted followed by disease assessment prior to tisa-cel infusion. Pts received tisa-cel (0.6-6×108 CAR+ viable T cells) after lymphodepleting chemotherapy. The primary endpoint was complete response rate (CRR) by central review per Lugano 2014 criteria. Secondary endpoints included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and cellular kinetics. Predefined primary analysis occurred when ≥90 treated pts had ≥6 mo of follow-up. Results: As of September 28, 2020, 98 pts were enrolled and 97 received tisa-cel (median follow-up, 10.6 mo). At study entry, median age among treated pts was 57 y (range, 29-73), 85% had stage III-IV disease, 60% had a FLIPI score ≥3, 65% had bulky disease, and 42% had LDH > upper limit of normal. The median number of prior therapies was 4 (range, 2-13); 78% of pts were refractory to their last treatment (76% to any ≥2 prior regimens) and 60% progressed within 2 y of initial anti-CD20–containing treatment. Of 94 pts evaluable for efficacy, the CRR was 66% (95% CI, 56-75) and the ORR was 86% (95% CI, 78-92). CRRs/ORRs were comparable among key high-risk subgroups. Estimated DOR (CR) and PFS rates at 6 mo were 94% (95% CI, 82-98) and 76% (95% CI, 65-84), respectively. Of 97 pts evaluable for safety, 65% experienced Gr ≥3 adverse events within 8 weeks post-infusion, most commonly neutropenia (28%) and anemia (13%). Any-grade cytokine release syndrome (per Lee scale) occurred in 49% of pts (Gr ≥3, 0%). Any-grade neurological events (per CTCAE v4.03) occurred in 9% of pts (Gr 3, 0%; Gr 4, 1 pt and recovered). Three pts died from progressive disease. Cellular kinetic parameters for tisa-cel were estimated using transgene levels (by qPCR) in peripheral blood. Cmax and AUC0-28d were similar between responders (CR or partial response) and non-responders (stable or progressive disease). Maximum transgene levels were reached by a median of 10 days in responders and 12.9 days in non-responders; transgene persistence was detected up to 370 days and 187 days, respectively. Conclusions: These data demonstrate the efficacy and acceptable safety of tisa-cel in pts with r/r FL, including high-risk pts after multiple lines of prior therapy, and suggest that tisa-cel may be a promising therapy for pts with r/r FL. Clinical trial information: NCT03568461.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e22000-e22000
O. Bulent Zulfikar ◽  
Basak Koc

e22000 Background: The prognosis of children and adolescents with acute lymphoblastic leukemia (ALL) has dramatically improved. This success is associated with both by multiagent chemotherapy regimens and by definition of clinical, biological and treatment response that allow the administration of risk-adapted therapy, including allogeneic hematopoietic stem cell transplantation (HSCT). In treatment of relapsed and resistance ALL, allogeneic HSCT continues to play a major curative role. In the present study, we desciribed the patients who underwent HSCT in our clinic in the last 21 years. Methods: From 1999 to 2020, 147 patients who diagnosed with ALL and treated with the COG protocols at the Istanbul University Oncology Institute were retrospectively reviewed and 17 of them relapsed. HSCT was applied 7 of the relapsed cases and also 3 resistant cases who had suitable matched donors. The demographic features, laboratory findings and treatment responses of 10 patients were recorded from the patients’ medical records. Results: All 10 patients were B-ALL with median diagnosis age of 79.5 months (range: 32-195) and 5 were male. Characteristics of patients given in Table 1. HSCT was performed due to late relaps in 7 patients. Three of the 7 relaps were only bone marrow and other 4 had combined. Patient #2 had both breast, conjunctiva and bone marrow for the 1st relaps and only conjunctiva for the 2nd one and this patient had also t(9;22) in the 1st relaps. Patient #3 had bone marrow+central nervous system relaps and patient #7 had bone marrow for the 1st relaps and testis and bone marrow for the 2nd one. Other 3 had poor response to treatment and Minimal Residual Disease (MRD) was high in End of Introduction (EoI) and End of Consolidation (EoC)). All patients had allogeneic HSCT and 8 are alive. Conclusions: HSCT remains the standard-of-care treatment for ALL patients who carry high-risk features predicting leukemia recurrence and for those experiencing high-risk first relapse or multiple relapses. Additionally, defining the indications of HSCT are dynamic and it could change according to treatment options as well as new molecular and biological findings. It is important to identify the patients who have high relapse risk and HSCT should have priority in patients whom MRD is high in EoI and EoC.[Table: see text]

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5029-5029
Stephen B Benzinger ◽  
Ryan Ashkar ◽  
Rafat Abonour ◽  
Mohammad Issam Abu Zaid ◽  
Nabil Adra ◽  

5029 Background: Pts with stage I testicular germ cell tumors (GCT) have a 15-year DFS of 99%. However, 1% are not cured, despite orchiectomy and systemic therapy at relapse. Predictive variables for relapse in this small population have not been identified. Methods: Pts undergoing HDCT with PBSCT as salvage therapy for relapsed GCT after an initial diagnosis of stage I disease managed with orchiectomy and surveillance were evaluated from a database at Indiana University. Patient demographics, disease characteristics, adherence to standard surveillance guidelines for stage I disease, prognostic variables, treatment received in the first-line setting, pattern of relapse, and outcomes were analyzed. Results: From 1/92 to 10/19, 71 pts (34 seminoma, 37 NSGCT) initially diagnosed with stage I GCT managed with orchiectomy and surveillance but subsequently relapsed and eventually required HDCT with PBSCT were identified. Median f/u time was 5.1 years (range, 1.1-18.8). Median age was 34.1. First-line chemo consisted of BEP or EP in most pts. Risk category at relapse: good/intermediate/poor (52/8/11). Pattern of initial relapse included 22 (seminoma n=13, NSGCT n=9) with RPLN only. Relapse and death after HDCT occurred in 2 of these 22 pts. Strict adherence to standard surveillance guidelines was observed in 62/71 pts. Relapse and/or death after HDCT occurred in 3 of 9 with inadequate surveillance follow-up. At a minimum of 1 yr follow-up, 54 of 71 (76%) remain alive, including 47 (66%) who have no evidence of disease (NED). Conclusions: Most patients in this series progressed despite appropriate surveillance and first-line chemotherapy. Pattern of relapse was also not indicative of further progression in most patients. Further investigation should evaluate disease biology that puts patients with potentially easily curable disease at risk of multiple relapses.[Table: see text]

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