A systematic review of the literature on localized gastrointestinal tract amyloidosis: Presentation, management and outcomes.

PURPOSE: Localized gastrointestinal tract amyloidosis is uncommon and little is known regarding this entity. There is no current standard of care for the management of localized amyloidosis. The objective of this study was to evaluate the characteristics, available treatments, outcomes and surveillance of these patients. METHODS: We conducted a systematic review of cases reported in the literature from 1962 to 2021. Patients with gastrointestinal amyloidosis reported in English literature were included in the analysis. We described and summarized the patient's characteristics, treatments, clinical presentations, outcomes and surveillance. RESULTS: The systematic review of reported clinical cases included 62 patients. In these patients, the most common site of amyloid deposition was the stomach (42%). The median age of diagnosis is 64.4 years old; there is a 2:1 prevalence among males (63%) to females (37%); abdominal pain is the most common type of presentation (41%), although patients could also be asymptomatic. There is a high curative rate (100%) with resection alone. Among patients treated with a type of systemic therapy, 80% achieved a complete response. The minority of cases reported a type of surveillance post treatment, and among those 62% pursued serial clinical evaluations alone. CONCLUSION: To our knowledge, this is the first and largest systematic review of the literature in gastrointestinal tract amyloidosis. This is more common among males and seems to have an excellent curative rate (100%) with surgery alone. Systemic therapy is an option for those with non-resectable amyloidomas. Serial clinical evaluations should be part of the standard surveillance care in these patients.

Risk of hepatitis B reactivation and cytomegalovirus related infections with Mogamulizumab: A retrospective study of international pharmacovigilance database.

BACKGROUND: Mogamulizumab (Moga) is a C-C chemokine receptor-4 antibody approved in the United States for relapsed /refractory mycosis fungoides and Sézary syndrome. Few cases reported an increased risk of hepatitis B reactivation and cytomegalovirus (CMV) related infection post-Moga. However, literature is limited to mainly case reports and series, while no study has used the Food and Drug Administration adverse events reporting system (FARES) database to investigate the relationship. METHODS: Using United States Food and Drug Administration adverse events reporting system database, we collected all cases of hepatitis B reactivation and CMV related infection between January 1, 2011, and December 31, 2019, for Moga and other drugs. The reporting odds ratio (ROR) was calculated, which was considered significant when the lower limit of 95% confidence interval (CI) >1. FINDINGS: Three hundred and thirty-eight total adverse cases were reported for Moga during the study period, with 261 cases reported indication for use, including cutaneous T cell lymphoma (47.04%), and adult T cell leukemia/lymphoma (30.18%). Eight cases were reported for hepatitis B reactivation with Moga use, compared to 2290 cases with other medications. The ROR is 143.67 (p<0.001, 95% CI, 71.17-290.04). CMV related infection was noted in 17 cases using Moga, while 12,849 cases with others. The ROR is 55.89 (p<0.001, 95% CI, 34.31-91.06). In the Moga group, five deaths occurred in hepatitis B reactivation patients and nine deaths with CMV cases. INTERPRETATION: A signal has been identified between Moga exposure and hepatitis B reactivation as well as CMV related infection. A consideration in future studies should be placed on determining the relationship and investigating the need for pre-treatment screening, close monitoring, and utilization of prophylaxis in this population-based on pre-treatment risks. FUNDING: None.

Saddle pulmonary embolism and clot in transit in COVID-19 infection: a case report of catastrophic venous thromboembolism.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a coagulopathy favouring thrombosis over bleeding that imparts a poor prognosis. Clot in transit (CIT) is considered a rare entity and the most severe form of venous thromboembolism (VTE), carrying a higher mortality than isolated pulmonary embolism (PE). The incidence of this phenomenon in patients with COVID-19 infection is unknown and likely under-recognized. CASE SUMMARY: During the peak of the COVID-19 pandemic in New York City, a 70-year-old Hispanic female presented with syncope due to a saddle PE further complicated by a highly mobile CIT. Polymerase chain reaction was positive for COVID-19 infection, however, there was no evidence of lung parenchymal involvement or hyper-inflammation. Based on consensus from a multidisciplinary team, aspiration thrombectomy was attempted to treat this extreme case of VTE, however, the patient died during the procedure. DISCUSSION: This case raises awareness to the most catastrophic form of VTE, presenting in an early phase of COVID-19 infection without the typical hyper-inflammation and severe lung injury associated with development of COVID-related coagulopathy. It also serves to inform on the critical role echocardiography has in the comprehensive evaluation and re-evaluation of hospitalized patients with COVID-19, and the importance of a multidisciplinary organized approach in clinical decision-making for this complex and poorly understood disease and its sequelae.

Targeting the anterior superior iliac spine yields significantly longer bone marrow cores.

Pathologists and haematologists generally agree that the length of the biopsy core is a good surrogate for the diagnostic quality of the bone marrow. Previous studies suggested that the angulation of the biopsy needle from the posterior superior iliac spine (PSIS) could influence the length of the biopsy cores, targeting the anterior superior iliac spine (ASIS) from the PSIS would yield longer specimens than the traditional angulation technique (TAT), where the biopsy needle is directed straight in, perpendicular to the plane of the back. Twenty five adult haematology patients were prospectively recruited by haematologists-in-training (HITs), who were trained to target the ASIS using a lateral angulationtechnique (LAT). The mean length of biopsy cores was 16 mm and that was significantly longer (p=0.003) than a comparable group of bone marrow biopsies previously obtained by HITs using the TAT approach. These results support the LAT as a new standard of haematology practice. TRIAL REGISTRATION NUMBER: NCT 02524613.

A Multidisciplinary Patient Navigation Program Improves Compliance With Adjuvant Breast Cancer Therapy in a Public Hospital.

Cancer health disparities affecting low-income and minority patients have been well documented to lead to poor outcomes. This report examines the impact of patient navigation on adherence to prescribed adjuvant breast cancer treatment. A multidisciplinary patient navigation program was initiated at a public safety net hospital to improve compliance with 3 National Quality Forum measures: (1) administration of combination chemotherapy for women with Stage (defined by the American Joint Committee on Cancer [AJCC]) T1c, II, or III hormone receptor-negative breast cancer within 120 days; (2) administration of endocrine therapy for women with AJCC Stage T1c, II, or III hormone receptor-positive breast cancer within 365 days; and (3) radiation therapy for women receiving breast-conserving surgery within one year. Implementation of a multidisciplinary patient navigation program reduced time to treatment and improved compliance with adjuvant therapy for breast cancer in an underserved minority community.

Primary Hepatic Small Cell Carcinoma: Two Case Reports, Molecular Characterization and Pooled Analysis of Known Clinical Data.

Primary hepatic small cell carcinoma (HSCC) is a rare malignancy that has previously been described in only few case reports. The clinicopathological course, natural history, molecular markers and ideal treatment strategy for this tumor have not been fully elucidated. Herein, we report on two cases of spontaneously arising, metastatic primary HSCC that were treated at our Institution. Both patients succumbed to their disease within two months of initial presentation. Both cases underwent postmortem examination and no evidence of a pulmonary or other non-hepatic small cell primary was found. Unlike pulmonary small cell tumors, these two hepatic primaries showed only locoregional spread and very few distant metastases. Formalin-fixed samples were obtained at autopsy and sequenced using single-nucleotide polymorphism arrays and whole-genome sequencing. Four mutations in the epidermal growth factor receptor (EGFR) gene known to be associated with response to tyrosine kinase inhibitors (TKIs) were detected in one of the two HSCC samples. A systematic review and pooled analysis of all previously reported cases of primary HSCCs was conducted. The median overall survival was estimated at 4 months. Surgical resection was significantly associated with longer overall survival (hazard ratio =0.13, 95% confidence interval=0.03-0.69). Although several case reports of primary HSCC have been reported prior to this publication, to our knowledge this is the first time that molecular and systematic analysis has been conducted in order to more fully characterize this rare disease. Our results indicate that surgical resection, when feasible, may be a valid option in primary HSCC, and that some tumors may respond to TKIs against EGFR.

More than a headache: a case of cetuximab-induced aseptic meningitis.

While the wide belief is that monoclonal antibodies, due to their large size, would not be able to penetrate the blood-brain barrier, we present a rare case of aseptic meningitis induced by intravenous cetuximab administration. A 58-year-old man with tonsillar squamous cell cancer presented with headache and fever, which started approximately 1 h after his first dose of cetuximab (loading dose of 400 mg/m(2) equalling 800 mg). CT scan of the head was non-revealing and laboratory tests including complete blood count, serum comprehensive metabolic panel and coagulation profile were within normal limits. Aseptic meningitis in the setting of cetuximab therapy has been reported on 6 previous occasions. Consistent with these prior reports, it is interesting to note that this case also occurred after administration of the initial higher loading dose of Cetuximab. This is of interest as Cetuximab is more frequently being dosed at 500 mg/m(2) (higher dose) every 2 weeks in colorectal cancer.

36-year-old female with catastrophic antiphospholipid syndrome treated with eculizumab: a case report and review of literature.

Catastrophic antiphospholipid syndrome (CAPS) is a rare but potentially life-threatening condition characterized by diffuse vascular thrombosis, leading to multiple organ failure developing over a short period of time in the presence of positive antiphospholipid antibodies (aPL). CAPS is a severe form of antiphospholipid syndrome, developing in about 1% of cases of classic antiphospholipid syndrome, manifesting as microangiopathy, affecting small vessels of multiple organs. It is acute in onset, with majority of cases developing thrombocytopenia and less frequently hemolytic anemia and disseminated intravascular coagulation. Lupus anticoagulant and anticardiolipin antibodies have been reported as predominant antibodies associated with CAPS. Treatment options often utilized in CAPS include anticoagulation, steroids, plasma exchange, cyclophosphamide therapy, and intravenous immunoglobulin therapy. Even though the reported incidence of this condition is considered to be low, the mortality rate is approaching 50%. The high rate of mortality should warrant greater awareness among clinicians for timely diagnosis and treatment of this life-threatening condition. Studies have shown that complement activation plays a key role in the pathogenesis of aPL mediated thrombosis in CAPS. We report a case of a 36-year-old female admitted with clinical and laboratory findings consistent with CAPS successfully treated with eculizumab, a terminal complement inhibitor.

Acquired Von Willebrand's Syndrome in Systemic Lupus Erythematosus.

Acquired von Willebrand syndrome (AVWS) is an uncommon, underdiagnosed, and heterogeneous disease which is increasingly recognized as a cause of bleeding diatheses. Systemic lupus erythematosus (SLE) is an infrequent cause of AVWS. Herein, we report a case of AVWS diagnosed during the initial presentation of SLE in a previously healthy young man with no family history of bleeding diathesis who presented with worsening epistaxis, gastrointestinal bleeding, and anasarca. He was found to have severe anemia and prolonged activated partial thromboplastin time (aPTT) with severely decreased levels of von Willebrand factor (VWF) measurements in addition to markedly decreased factor VIII levels. Further evaluation revealed nephrotic syndrome and interstitial lung disease due to SLE. He initially received combination therapy with intravenous immunoglobulin (IVIG) and von Willebrand factor/factor VIII concentrates without significant improvement. Treatment with steroids, cyclophosphamide, and rituximab was followed by clinical improvement evidenced by cessation of bleeding. The short follow-up did not allow us to definitely prove the therapeutic effect of immunosuppressive treatment on AVWS in SLE patients. This case adds to the literature supporting the relationship between AVWS and SLE and highlights the importance of combination therapy in the treatment of severe AVWS as well as the role of IVIG, cyclophosphamide, and rituximab in AVWS associated with SLE.

Phase II study of the proteasome inhibitor bortezomib (PS-341, Velcade) in chemotherapy-naïve patients with advanced stage non-small cell lung cancer (NSCLC).

The primary objective of this study was to determine the objective response rate of bortezomib as a first-line therapy in patients advanced stage NSCLC. Advanced/metastatic NSCLC patients with measurable disease, adequate organ function, ECOG performance status of 0-2, and no prior chemotherapy for metastatic disease were eligible. Patients received intravenously bolus bortezomib 1.3mg/m(2)/day on days 1, 4, 8 and 11 every 21 days for a maximum of 8 cycles, or until disease progression, or unacceptable toxicity. Tumor response was evaluated after every 2 cycles of therapy. This single-arm phase II study employed the Simon's two-stage design. The study was terminated in the first stage after 14 patients enrolled at 4 institutions. No objective response was observed. Three patients (21%) had stable disease and received 8, 6 and 4 cycles of treatment; the duration of stable disease was 11.5, 4.2 and 3.4 months, respectively. Median time to progression was 1.3 months (95% CI, 0.6-3.0 months); median overall survival (OS) was 9.9 months (95% CI, 2.2-27.0 months). Twelve patients received at least one dose of bortezomib. There were no grade 4 toxicities or treatment related deaths. Grade 3 toxicities included fatigue (N=1, 8%), deep vein thrombosis (N=1, 8%) and thrombocytopenia (N=1, 8%). Although well tolerated, bortezomib monotherapy is not active in this cohort of chemotherapy-naïve, metastatic NSCLC.