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1.
Eur Heart J Case Rep ; 8(5): ytae188, 2024 May.
Article in English | MEDLINE | ID: mdl-38711683

ABSTRACT

Background: Nail-Patella syndrome (NPS) is an autosomal-dominant pleiotropic condition characterized by pelvic and skeletal abnormalities and most commonly affecting a tetrad of nails, knees, elbows, and iliac horns, the iliac horns being pathognomonic for the condition. The most well-documented extra-skeletal manifestation is renal involvement with alteration in Type III collagen. No documented cases of NPS with anomalous coronary arteries or aneurysms, acute coronary occlusion, or successfully coronary interventions exist in the medical literature. Case summary: A 62-year-old female with a medical history significant for NPS diagnosed 50 years ago presented to the emergency department with a chief complaint of chest pain. She recently developed end-stage renal disease managed with peritoneal dialysis within the last year. Angiography revealed 100% right coronary artery occlusion with an anomalous take-off from the left circumflex artery. She demonstrated diffuse coronary aneurysms in the right coronary artery, mid-left anterior descending artery, and other epicardial vessels. Two drug-eluting stents were placed in overlapping fashion. Following careful apposition, the aneurysmal segment was successfully stented without complication. The patient was discharged without complication 2 days later. Discussion: Our case shows the first reported case of coronary vascular anomalies and successful coronary revascularization in a patient with NPS in the medical literature. Given the recently reported vascular anomalies and known collagen alterations seen in patients with the genetic disorder, clinicians should suspect further systemic vascular anomalies with their own unique therapeutic challenges when encountering patients with this rare genetic syndrome.

2.
Blood Adv ; 7(24): 7393-7401, 2023 12 26.
Article in English | MEDLINE | ID: mdl-37874912

ABSTRACT

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma; data indicate that blastoid and pleomorphic variants have a poor prognosis. We report characteristics and outcomes of patients with blastoid/pleomorphic variants of MCL. We retrospectively studied adults with newly diagnosed MCL treated from 2000 to 2015. Primary objectives were to describe progression-free survival (PFS) and overall survival (OS). Secondary objectives included characterization of patient characteristics and treatments. Of the 1029 patients with MCL studied, a total of 207 neoplasms were blastoid or pleomorphic variants. Median follow-up period was 82 months (range, 0.1-174 months); median PFS was 38 months (95% confidence interval [CI], 28-66) and OS was 68 months (95% CI, 45-96). Factors associated with PFS were receipt of consolidative autologous hematopoietic transplantation (auto-HCT; hazard ratio [HR], 0.52; 95% CI, 0.31-0.80; P < .05), MCL International Prognostic Index (MIPI) intermediate (HR, 2.3; 95% CI, 1.2-4.3; P < .02) and high (HR, 3.8; 95% CI, 2.0-7.4; P < .01) scores, and complete response to induction (HR, 0.29 (95% CI, 0.17-0.51). Receipt of auto-HCT was not associated with OS (HR, 0.69; 95% CI, 0.41-1.16; P = .16) but was associated with MIPI intermediate (HR, 5.7; 95% CI, 2.5-13.2; P < .01) and high (HR, 10.8; 95% CI, 4.7-24.9; P < .01) scores. We report outcomes in a large cohort of patients with blastoid/pleomorphic variant MCL. For eligible patients, receipt of auto-HCT after induction was associated with improved PFS but not OS. Higher MIPI score and auto-HCT ineligibility were associated with worse survival.


Subject(s)
Lymphoma, Mantle-Cell , Adult , Humans , Lymphoma, Mantle-Cell/therapy , Lymphoma, Mantle-Cell/drug therapy , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Risk Assessment , Progression-Free Survival
3.
Blood Adv ; 7(23): 7361-7368, 2023 12 12.
Article in English | MEDLINE | ID: mdl-37756532

ABSTRACT

Maintenance rituximab in mantle cell lymphoma (MCL) has improved survival and supports exploration of maintenance with novel agents. We evaluated the safety and efficacy of ibrutinib maintenance (I-M) after induction in patients with treatment-naive MCL. Patients with MCL with complete response (CR) or partial response to frontline chemoimmunotherapy ± autologous stem cell transplantation (auto-SCT) received I-M 560 mg daily for up to 4 years. Primary objective was 3-year progression-free survival (PFS) rate from initiation of I-M. Minimal residual disease (MRD) assessments by next-generation sequencing (NGS) on peripheral blood were measured before I-M initiation and at 1, 6, and 18 to 24 months after initiation. Among 36 patients, the median age was 60 years (range, 46-90). For frontline treatment, 18 patients (50%) had consolidation with auto-SCT in CR1 before I-M. At median follow-up of 55.7 months, 17 patients (47%) completed full course I-M (median, 37.5 cycles; range, 2-52). The 3-year PFS and overall survival (OS) rates were 94% and 97%, respectively. With prior auto-SCT, 3-year PFS and OS rates were both 100%. The most common treatment-related adverse event with I-M was infection (n = 31; 86%), typically low grade; the most common grade 3/4 toxicities were hematologic. In 22 patients with MRD assessments, all were MRD negative after induction. Six became MRD positive on I-M, with 2 reverting to MRD-negative status with continued I-M, and all maintain radiographic CR with the exception of 1 with disease progression. I-M is feasible in MCL after frontline chemoimmunotherapy with manageable toxicities although significant. Changes in NGS-MRD were noted in limited patients during maintenance with few progression and survival events. This trial was registered at www.clinicaltrials.gov as #NCT02242097.


Subject(s)
Hematopoietic Stem Cell Transplantation , Lymphoma, Mantle-Cell , Humans , Adult , Middle Aged , Lymphoma, Mantle-Cell/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Transplantation, Autologous
4.
EJHaem ; 4(1): 108-114, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36819145

ABSTRACT

Background: TAK-659, a novel oral SYK inhibitor, has demonstrated efficacy in heavily pretreated diffuse large B-cell lymphoma (DLBCL). We report results of a phase I single-institution escalation study of front-line treatment with R-CHOP and TAK-659 in treatment-naïve high-risk DLBCL. Methods: Patients with high-risk DLBCL were treated with R-CHOP for 1 cycle, followed by combined R-CHOP and TAK-659 for an additional five cycles, with TAK-659 dosing escalated from 60 mg, to 80 mg, to 100 mg daily, based on a 3 + 3 design. The primary objective was to determine the safety and establish the maximum tolerated dose (MTD) of TAK-659 in this setting. Results: Twelve patients were enrolled. Dose level 3 (100 mg) was established as the MTD. Dose level 1 (60 mg) maintained a similar area under the curve (AUC) to the MTD. With a median follow-up of 21 months, 92% of patients achieved complete response (CR). The most common treatment-emergent adverse events were lymphopenia (100%), infection (50%, n = 3 opportunistic), aspartate aminotransferase elevation (100%), and alanine aminotransferase elevation (83%). Conclusion: A TAK-659 dose of 60 mg was well tolerated, did not require dose modifications, and maintained a similar AUC to the MTD. The combination of R-CHOP and TAK-659 in patients with newly diagnosed high-risk DLBCL produces promising CR rates.

5.
Oncotarget ; 14: 57-70, 2023 01 26.
Article in English | MEDLINE | ID: mdl-36702329

ABSTRACT

We report an updated analysis from a phase I study of the spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase 3 inhibitor mivavotinib, presenting data for the overall cohort of lymphoma patients, and the subgroup of patients with diffuse large B-cell lymphoma (DLBCL; including an expanded cohort not included in the initial report). Patients with relapsed/refractory lymphoma for which no standard treatment was available received mivavotinib 60-120 mg once daily in 28-day cycles until disease progression/unacceptable toxicity. A total of 124 patients with lymphoma, including 89 with DLBCL, were enrolled. Overall response rates (ORR) in response-evaluable patients were 45% (43/95) and 38% (26/69), respectively. Median duration of response was 28.1 months overall and not reached in DLBCL responders. In subgroups with DLBCL of germinal center B-cell (GCB) and non-GCB origin, ORR was 28% (11/40) and 58% (7/12), respectively. Median progression free survival was 2.0 and 1.6 months in the lymphoma and DLBCL cohorts, respectively. Grade ≥3 treatment-emergent adverse events occurred in 96% of all lymphoma patients, many of which were limited to asymptomatic laboratory abnormalities; the most common were increased amylase (29%), neutropenia (27%), and hypophosphatemia (26%). These findings support SYK as a potential therapeutic target for the treatment of patients with B-cell lymphomas, including DLBCL. Trial registration: ClinicalTrials.gov number: NCT02000934.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Vascular Endothelial Growth Factor Receptor-1 , Humans , Treatment Outcome , Syk Kinase , Lymphoma, Large B-Cell, Diffuse/pathology , Protein Kinase Inhibitors/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
6.
Haematologica ; 108(3): 705-716, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36226495

ABSTRACT

Mivavotinib (TAK-659) is an investigational type 1 tyrosine kinase inhibitor with dual activity against spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase 3 (FLT3). We conducted a phase Ib study to investigate the safety, tolerability, and efficacy of mivavotinib in patients with refractory and/or relapsed (R/R) acute myeloid leukemia (AML). Both daily (QD) and twice daily (BID) dosing regimens were evaluated. A total of 43 patients were enrolled, and there were 5 complete responses (4 with incomplete count recovery). In the QD dosing regimen, the maximum tolerated dose (MTD) was not reached up to 160 mg QD per protocol; 140 mg QD was identified as the recommended phase II dose. In the BID dosing regimen, the MTD was 60 mg BID. Thirty patients (70%) experienced a bleeding event on study; the majority were grades 1 or 2, were resolved without mivavotinib modification, and were not considered related to study treatment. Eleven patients (26%) experienced grade ≥3 bleeding events, which were observed most frequently with the 80 mg BID dose. We conducted platelet aggregation studies to investigate the potential role of mivavotinib-mediated SYK inhibition on platelet function. The bleeding events observed may have been the result of several confounding factors, including AML disease status, associated thrombocytopenia, and high doses of mivavotinib. Overall, these findings indicate that the activity of mivavotinib in R/R AML is modest. Furthermore, any future clinical investigation of this agent should be undertaken with caution, particularly in thrombocytopenic patients, due to the potential bleeding risk of SYK inhibition. ClinicalTrials.gov: NCT02323113.


Subject(s)
Leukemia, Myeloid, Acute , fms-Like Tyrosine Kinase 3 , Humans , Protein Kinase Inhibitors/adverse effects , Pyrimidines/adverse effects , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Syk Kinase
7.
EJHaem ; 3(1): 139-153, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35846221

ABSTRACT

There is a need for additional treatment options for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who do not benefit from available therapies. We examined combinations of the cereblon E3 ligase modulator (CELMoD) agent avadomide (CC-122), the selective, ATP-competitive mammalian target of rapamycin kinase inhibitor CC-223, and the potent, selective, covalent Bruton tyrosine kinase inhibitor CC-292 in patients with relapsed/refractory (R/R) DLBCL. In the multicenter, phase Ib CC-122-DLBCL-001 study (NCT02031419), the dose-escalation portion explored combinations of CC-122, CC-223, and CC-292 administered as doublets or triplets with rituximab in patients with chemorefractory DLBCL. Primary endpoints were safety, tolerability, and dose-limiting toxicities; additional endpoints included pharmacokinetics, pharmacodynamics, biomarkers, and preliminary efficacy. As of December 1, 2017, 106 patients were enrolled across four cohorts. The median age was 65 years (range 24-84 years), and patients had a median of 3 (range 1-10) prior to regimens. A total of 101 patients (95.3%) discontinued, most commonly due to disease progression (49.1%). The most common any-grade adverse events (AEs) across treatment arms were gastrointestinal and hematologic; the most common grade 3/4 AEs were hematologic. CC-122 was well tolerated, with no unexpected safety concerns. Preliminary efficacy was observed in three of four treatment arms. CC-122 plus rituximab was considered suitable for dose expansion, whereas CC-223 and CC-292 combinations were associated with enhanced toxicity and/or insufficient improvement in responses. CC-122 plus rituximab was well tolerated, with preliminary antitumor activity in patients with R/R DLBCL. This innovative study demonstrates the feasibility of assessing the tolerability and preliminary efficacy of novel combinations utilizing a multi-arm dose-finding design.

8.
Curr Oncol ; 28(5): 3659-3667, 2021 09 21.
Article in English | MEDLINE | ID: mdl-34590610

ABSTRACT

Desmoid tumors (aggressive fibromatosis) are soft tissue mesenchymal tumors that can be locally invasive and life-threatening. Depending on the location, these tumors are often unresectable or tend to recur after surgery. To date, there are no approved systemic therapies for desmoid tumors. These tumors typically harbor mutations in the ß-catenin oncogene CTNNB1 or the tumor suppressor gene adenomatous polyposis coli, resulting in constitutive activation of the WNT pathway. The Notch pathway is part of the underlying cause for desmoid tumor development, possibly due to crosstalk with the WNT pathway, providing a rationale for Notch inhibition as a therapeutic strategy. The gamma secretase activation of the Notch receptor can be targeted with investigational gamma secretase inhibitors. In this case report, we follow the course of 2 patients with desmoid tumors treated with the highly potent, parenterally administered investigational gamma secretase inhibitor AL101, resulting in long-lasting responses. Case 1 reports on a patient with a mesenteric desmoid tumor who participated in a phase 1 trial and then transitioned into a compassionate use program; Case 2 reports on a patient with recurrent pelvic tumors receiving AL101 through a compassionate use program. After tumor progression on other systemic therapies, Cases 1 and 2 had confirmed partial responses (41% and 60% maximal tumor size decrease from baseline) recorded after 1.0 and 1.6 years of treatment with AL101, with a duration of response of 8.6+ and 2.6+ years, respectively. Also, in a phase 1 study of AL102, a potent orally administered gamma secretase inhibitor that shares structural features with AL101, a patient with a desmoid tumor was noted to have tumor shrinkage. Formal clinical testing of AL102 for the treatment of patients with desmoid tumors that are not amenable to surgery or are refractory to/recurrent from other prior therapies is currently underway.


Subject(s)
Fibromatosis, Aggressive , Soft Tissue Neoplasms , Adult , Amyloid Precursor Protein Secretases , Fibromatosis, Aggressive/drug therapy , Fibromatosis, Aggressive/genetics , Humans , Mutation , Neoplasm Recurrence, Local
9.
Leuk Lymphoma ; 62(14): 3493-3500, 2021 12.
Article in English | MEDLINE | ID: mdl-34338127

ABSTRACT

Treatment strategies for post-transplant lymphoproliferative disorders (PTLD) consist of response-adapted risk-stratified methods using immunosuppression reduction, immunotherapy, and chemotherapy. We investigated the efficacy of Brentuximab vedotin given concurrently with Rituximab (BV + R) once weekly for four weeks, followed by optional consolidation, and up to one year of maintenance. Among 20 assessable patients, BV + R therapy resulted in an overall response rate of 75% (95% CI 51 to 91, p = 0.044) with 60% achieving a complete response. Median time to best response was 28 days. Two-year progression-free survival and overall survival rates were 75 and 90%, respectively. Most common severe grade 3/4 treatment-related toxicities included neutropenia (40%), hypertension (30%), infection (25%), and peripheral neuropathy (15%). BV + R is a novel and effective therapeutic strategy that achieved rapid and durable remissions in previously untreated PTLD patients; however, this treatment platform requires further modification due to the high rates of treatment-related toxicity.Key pointsBrentuximab vedotin + Rituximab showed ORR and CR rates of 75 and 60% in patients with immunosuppression-associated lymphoid malignanciesHigh rates of treatment delay were attributed to treatment-related toxicity; further dosing optimization of this regimen is required.


Subject(s)
Immunoconjugates , Lymphoma , Lymphoproliferative Disorders , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Brentuximab Vedotin , Herpesvirus 4, Human , Humans , Immunoconjugates/adverse effects , Immunosuppression Therapy , Ki-1 Antigen , Lymphoma/diagnosis , Lymphoma/drug therapy , Lymphoma/etiology , Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/drug therapy , Lymphoproliferative Disorders/etiology , Rituximab/adverse effects
10.
J Patient Saf ; 17(3): 157-165, 2021 04 01.
Article in English | MEDLINE | ID: mdl-29994818

ABSTRACT

OBJECTIVES: Preoperative anticoagulation management (PAM) is a complex, multidisciplinary process important to patient safety. The Functional Resonance Analysis Method (FRAM) is a novel method to study how complex processes usually go right at the frontline (labeled Safety-II) and how this relates to predefined procedures. This study aimed to assess PAM in everyday practice and explore the usability and utility of FRAM. METHODS: The study was conducted at an Australian and European Cardiothoracic Surgery Department. A FRAM model of work-as-imagined was developed using (inter)national guidelines. Semistructured interviews with 18 involved professionals were used to develop models reflecting work-as-done at both sites, which were presented to staff for validation. Workload in hours was estimated per process step. RESULTS: In both centers, work-as-done differed from work-as-imagined, such as in the division of tasks among disciplines (e.g., nurses/registrars rather than medical specialists), but control mechanisms had been developed locally to ensure safe care (e.g., crosschecking with other clinicians). Centers had organized the process differently, revealing opportunities for improvement regarding patient information and clustering of clinic visits. Presenting FRAM models to staff initiated discussion on improvement of functions in the model that are vital for success. Overall workload was estimated at 47 hours per site. CONCLUSIONS: This FRAM analysis provided insight into PAM from the perspective of frontline clinicians, revealing essential functions, interdependencies and variability, and the relation with guidelines. Future studies are warranted to study the potential of FRAM, such as for guiding improvements in complex systems.


Subject(s)
Anticoagulants , Anticoagulants/adverse effects , Australia , Humans
11.
Brain Behav ; 11(1): e01933, 2021 01.
Article in English | MEDLINE | ID: mdl-33300691

ABSTRACT

INTRODUCTION: Agenesis of the corpus callosum (AgCC) is characterized by the congenital partial or complete absence of the corpus callosum. Several strains of mice have been reported to carry AgCC, with the BTBR T+ Itpr3tf /J (BTBR) inbred mouse strain consistently showing a complete absence of the corpus callosum, as well as a variable reduction in the size of the hippocampal commissure. While much research has focused on the social deficits of the BTBR strain, little research on its cognitive behavior has been conducted. The goal of our study was to compare two facets of executive functioning, spatial working memory, and sustained attention between the BTBR and C57BL/6J (B6) strains. METHODS: Spatial working memory was measured utilizing a delayed matching-to-position (DMTP) task and sustained attention was measured utilizing an operant task in which mice were trained to distinguish signal and nonsignal events. RESULTS: Both the BTBR and B6 mice demonstrated a predictable decline in performance on the DMTP task as the delay interval increased and predictable increase in performance on the sustained attention task as the duration of the signal event increased. Although no significant differences were found between strains on the performance of these tasks, there was a significant difference in learning the association between lever pressing and food reward. Histological investigation confirmed the complete absence of commissural fibers from the corpus callosum, but also the hippocampal commissure, counter to a previous study. CONCLUSION: The results suggest spatial working memory and sustained attention are unaffected by the absence of these commissural fibers alone.


Subject(s)
Corpus Callosum , Memory, Short-Term , Animals , Attention , Disease Models, Animal , Executive Function , Mice , Mice, Inbred C57BL , Mice, Inbred Strains , Social Behavior
12.
J Community Hosp Intern Med Perspect ; 10(6): 597-599, 2020 Oct 29.
Article in English | MEDLINE | ID: mdl-33194138

ABSTRACT

Papillary fibroelastomas are a rare cardiac neoplasm typically found on the left side of the heart, and most commonly on the aortic valve, which can present with cardiac or neurologic symptoms. A 51-year-old woman with no cardiac history presented to a resident clinic with complaints of left-sided facial paresthesias and palpitations for 1 month. Echocardiographic imaging showed a mass on the aortic annulus, concerning for a cardiac tumor. Due to the risk of possible embolization, if the tumor was a myxoma, the patient required intrathoracic surgery. During the intrathoracic procedure the mass was confirmed to be a papillary fibroelastoma and the patient had the mass removed without any complications. Papillary fibroelastomas are found in less than 1% of the population but can present clinically with a wide variety of symptoms. Patients with this neoplasm are at risk for severe complications, due to embolization, potentially causing cerebrovascular accidents or myocardial infarctions. We present a case of a papillary fibroelastoma producing both cardiac and neurologic symptoms.

13.
Eur Heart J Case Rep ; 4(5): 1-5, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33204989

ABSTRACT

BACKGROUND: SARS-CoV-2 is a novel viral illness originating out of Wuhan China in late 2019. This global pandemic has infected nearly 3 million people and accounted for 200 000 deaths worldwide, with those numbers still climbing. CASE SUMMARY: We present a 54-year-old patient who developed respiratory failure requiring endotracheal intubation from her infection with SARS-CoV-2. This patient was subsequently found to have a right ventricular thrombus and bilateral pulmonary emboli, likely contributing to her respiratory status. On the 14th day of hospitalization, the patient was successfully extubated, and 5 days later was discharged to the rehabilitation unit. DISCUSSION: SARS-CoV-2 presents primarily with pulmonary symptoms; however, many patients, particularly those who are severely ill, exhibit adverse events related to hypercoagulability. The exact mechanism explaining this hypercoagulable state has yet to be elucidated, but these thrombotic events have been linked to the increased inflammation caused by SARS-CoV-2. This novel viral illness is still largely misunderstood, but the hypercoagulable state, seen in severely ill patients, appears to play a major role in disease progression and prognosis.

15.
Clin Cancer Res ; 26(14): 3546-3556, 2020 07 15.
Article in English | MEDLINE | ID: mdl-32327472

ABSTRACT

PURPOSE: TAK-659 is an investigational, dual SYK/FLT3 inhibitor with preclinical activity in B-cell malignancy models. This first-in-human, dose-escalation/expansion study aimed to determine the safety, tolerability, MTD/recommended phase II dose (RP2D), and preliminary efficacy of TAK-659 in relapsed/refractory solid tumors and B-cell lymphomas. PATIENTS AND METHODS: Patients received continuous, once-daily oral TAK-659, 60-120 mg in 28-day cycles, until disease progression or unacceptable toxicity. The study applied an accelerated dose-escalation design to determine the MTD and RP2D. In the expansion phase, patients with lymphoma were enrolled in five disease cohorts at the MTD. RESULTS: Overall, 105 patients were enrolled [dose escalation, n = 36 (solid tumors, n = 19; lymphoma, n = 17); expansion, n = 69]. The MTD was 100 mg once daily. TAK-659 absorption was fast (T max ∼2 hours) with a long terminal half-life (∼37 hours). Exposure generally increased with dose (60-120 mg), with moderate variability. The most common treatment-related adverse events were generally asymptomatic and reversible elevations in clinical laboratory values. Among 43 response-evaluable patients with diffuse large B-cell lymphoma, 8 (19%) achieved a complete response (CR) with an overall response rate (ORR) of 28% [23% intent-to-treat (ITT)]. Responses were seen in both de novo and transformed disease and appeared independent of cell-of-origin classification. Among 9 response-evaluable patients with follicular lymphoma, 2 (22%) achieved CR with an ORR of 89% (57% ITT). CONCLUSIONS: TAK-659 has single-agent activity in patients with B-cell lymphoma. Further studies of the drug in combination, including an evaluation of the biologically optimal and safest long-term dose and schedule, are warranted.


Subject(s)
Drugs, Investigational/administration & dosage , Lymphoma, Follicular/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Protein Kinase Inhibitors/administration & dosage , Pyrimidines/administration & dosage , Pyrrolidinones/administration & dosage , Administration, Oral , Adult , Aged , Aged, 80 and over , Dose-Response Relationship, Drug , Drug Administration Schedule , Drugs, Investigational/adverse effects , Female , Humans , Male , Middle Aged , Protein Kinase Inhibitors/adverse effects , Pyrimidines/adverse effects , Pyrrolidinones/adverse effects , Syk Kinase/antagonists & inhibitors , Treatment Outcome , Young Adult , fms-Like Tyrosine Kinase 3/antagonists & inhibitors
16.
Am J Case Rep ; 21: e921633, 2020 Feb 28.
Article in English | MEDLINE | ID: mdl-32107365

ABSTRACT

BACKGROUND Acute bacterial pericarditis is rare, and the incidence numbers have been declining in the modern antibiotic era. Purulent bacterial pericarditis is a fatal disease in which mortality rates can reach 100% if left untreated. CASE REPORT We present a case of primary purulent bacterial pericarditis with polymicrobial growth including Micromonas micro, Prevotella intermedia and Fusobacterium species, all of which are anaerobic flora of the oral cavity. Constant re-accumulation of the purulent pericardial effusion led the patient to have recurrent echocardiographic and clinical cardiac tamponade requiring recurrent pericardiocentesis' and eventually a pericardial window. CONCLUSIONS Although rare, bacterial pericarditis has been noted to lead to clinical and echocardiographic tamponade. Early diagnosis and treatment are necessary for improving clinical outcomes. It is important to have a suspicion for purulent pericarditis, due to its high level of mortality, in patients who present with non-specific symptoms and pleuritic chest pain.


Subject(s)
Bacteria, Anaerobic/drug effects , Cardiac Tamponade/microbiology , Cardiac Tamponade/therapy , Pericarditis/microbiology , Pericarditis/therapy , Adult , Anti-Bacterial Agents/therapeutic use , Fusobacterium/drug effects , Humans , Male , Pericardiocentesis , Prevotella intermedia/drug effects , Rare Diseases
17.
Leuk Lymphoma ; 60(13): 3266-3271, 2019 12.
Article in English | MEDLINE | ID: mdl-31225766

ABSTRACT

Diffuse large B-cell lymphoma (DLBCL) transformed from follicular lymphoma (FL) (tDLBCL) has been traditionally associated with an aggressive course, but more recent studies have shown longer survivals. The clinical significance of concurrent FL at the time of diagnosis of DLBCL (cDLBCL/FL) is less clear. We compared outcomes of tDLBCL, cDLBCL/FL, and de novo DLBCL (dDLBCL) and then evaluated the impact of double hit (DH) rearrangements (MYC with BCL2 and/or BCL6) in these subgroups' outcomes. The progression free survival (PFS) and overall survival (OS) were not significantly different among the three groups (dDLBCL, tDLBCL, and cDLBCL/FL). The effect of DH on survival was then analyzed in two subgroups: (1) dDLBCL and (2) tDLBCL + cDLBCL/FL. PFS and OS were significantly shorter in lymphomas with DH in each of these two subgroups. We conclude that DH status drives outcomes in all DLBCLs, regardless of their transformation status.


Subject(s)
Cell Transformation, Neoplastic/genetics , Lymphoma, Follicular/mortality , Lymphoma, Large B-Cell, Diffuse/mortality , Neoplasms, Multiple Primary/mortality , Neoplasms, Second Primary/mortality , Aged , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Combined Chemotherapy Protocols , Female , Gene Rearrangement , Humans , Lymphoma, Follicular/complications , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/genetics , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/etiology , Lymphoma, Large B-Cell, Diffuse/genetics , Male , Middle Aged , Neoplasms, Multiple Primary/drug therapy , Neoplasms, Multiple Primary/genetics , Neoplasms, Multiple Primary/pathology , Neoplasms, Second Primary/drug therapy , Neoplasms, Second Primary/genetics , Neoplasms, Second Primary/pathology , Progression-Free Survival , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-6/genetics , Proto-Oncogene Proteins c-myc/genetics , Retrospective Studies , Rituximab/therapeutic use , Time Factors
18.
Br J Haematol ; 186(2): 255-262, 2019 07.
Article in English | MEDLINE | ID: mdl-31044423

ABSTRACT

Intravascular large B-cell lymphoma (IVLBCL) is a rare entity, with a generally aggressive course that may vary based on geographic presentation. While a United States (US) registry study showed relatively good outcomes with IVLBCL, clinicopathological and treatment data were unavailable. We performed a detailed retrospective review of cases identified at 8 US medical centres, to improve understanding of IVLBCL and inform management. We compiled data retrieved via an Institutional Review Board-approved review of IVLBCL cases identified from 1999 to 2015 at nine academic institutions across the US. We characterized the cohort's clinical status at time of diagnosis, presenting diagnostic and clinical features of the disease, treatment modalities used and overall prognostic data. Our cohort consisted of 54 patients with varying degrees of clinical features. Adjusting for age, better performance status at presentation was associated with increased survival time for the patients diagnosed in vivo (hazard ratio: 2·12, 95% confidence interval 1·28, 3·53). Based on the data we have collected, it would appear that the time interval to diagnosis is a significant contributor to outcomes of patients with IVLBCL.


Subject(s)
Academic Medical Centers , Lymphoma, Large B-Cell, Diffuse , Age Factors , Aged , Disease-Free Survival , Female , Humans , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large B-Cell, Diffuse/therapy , Male , Middle Aged , Retrospective Studies , Survival Rate , United States/epidemiology
19.
J Clin Oncol ; 37(6): 471-480, 2019 02 20.
Article in English | MEDLINE | ID: mdl-30615550

ABSTRACT

PURPOSE: Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger. PATIENTS AND METHODS: We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score-weighted (PSW) analysis were performed. RESULTS: Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2). CONCLUSION: In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation , Lymphoma, Mantle-Cell/therapy , Rituximab/therapeutic use , Adult , Age Factors , Aged , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/mortality , Humans , Lymphoma, Mantle-Cell/mortality , Lymphoma, Mantle-Cell/pathology , Male , Middle Aged , North America , Progression-Free Survival , Retrospective Studies , Risk Assessment , Risk Factors , Rituximab/adverse effects , Time Factors , Transplantation, Autologous , Young Adult
20.
Article in English | MEDLINE | ID: mdl-32002157

ABSTRACT

Infective endocarditis (IE) is a focus of infection which effects the endocardium, specifically the heart valves or intra-cardiac devices. A 64-year-old male with gastric carcinoma and no prior cardiac history presented to the emergency room with altered mental status. Initial investigations showed the patient had a leukocytosis with a left shift. Blood cultures taken upon arrival eventually grew Esherichia coli, thought to be from the urinary tract, although initial urinalysis was delayed until after initiation of antibiotics. Electrocardiogram showed sinus bradycardia with frequent premature atrial contractions. Chest X-Ray showed bilateral pleural effusions, which were eventually drained and found to be growing E. coli. Transthoracic echocardiogram was done which showed moderate-sized tricuspid valve vegetation with severe tricuspid regurgitation. IE has been increasing in incidence throughout the years. In prior decades IE was a disease primarily affecting patients with known rheumatic heart disease, prosthetic heart valves, and intravenous drug abusers however more commonly it is becoming healthcare acquired. E. coli is not often seen to be a culprit of IE. We present a rare case of E. coli endocarditis of a native tricuspid valve.

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