Pulmonary Haemosiderosis Secondary to Hereditary Haemochromatosis; a Case Report

Introduction: Hereditary haemochromatosis (HH) is an autosomal recessive disease of increased intestinal absorption of iron, leading to accumulation in tissues which may progress to organ damage, most commonly in the liver. Iron deposition in the liver can lead to cirrhosis and hepatocellular carcinoma. Other common manifestations of haemochromatosis include diabetes, bronzing of the skin, arthropathy and cardiomyopathy. Here, we describe a case of pulmonary haemosiderosis secondary to HH. Case Description: A 49-year-old male with no medical history or family history of iron overload presented with fatigue, shortness of breath and chest pain after a recent finding of elevated ferritin. The patient was found to have biallelic C282Y mutations of the human homeostatic iron regulator protein (HFE) protein and after further workup with laboratory tests and imaging was diagnosed with HH with secondary pulmonary haemosiderosis. The patient is receiving twice weekly phlebotomies and has had an overall improvement in his symptoms. Practical Implications: The presentation of haemochromatosis can vary widely depending on the severity of iron overload and the presence of conditions that predispose organ dysfunction. Pulmonary haemosiderosis is a very rare manifestation of HH. This report illustrates the various manifestations of this disease and provides insight into this rare presentation to improve the diagnosis of this disease.&nbsp

Impact of Detectable Monoclonal Protein at Diagnosis on Outcomes in Marginal Zone Lymphoma: A Multicenter Cohort Study

Given the paucity of data surrounding the prognostic relevance of monoclonal paraprotein (M-protein) in marginal zone lymphoma (MZL), we sought to evaluate the impact of detecting M-protein at diagnosis on outcomes in patients with MZL in a large retrospective cohort. The study included 547 patients receiving first-line therapy for MZL. M-protein was detectable at diagnosis in 173 (32%) patients. There was no significant difference in the time from diagnosis to initiation of any therapy (systemic and local) between the M-protein and no M-protein groups. Patients with M-protein at diagnosis had significantly inferior progression-free survival (PFS) compared with those without M-protein at diagnosis. After adjusting for factors associated with inferior PFS in univariate models, presence of M-protein remained significantly associated with inferior PFS (hazard ratio, 1.74; 95% confidence interval, 1.20-2.54; P = .004). We observed no significant difference in the PFS based on the type or quantity of M-protein at diagnosis. There were differential outcomes in PFS based on the first-line therapy in patients with M-protein at diagnosis, in that, those receiving immunochemotherapy had better outcomes compared with those receiving rituximab monotherapy. The cumulative incidence of relapse in stage 1 disease among the recipients of local therapy was higher in the presence of M-protein; however, this did not reach statistical significance. We found that M-protein at diagnosis was associated with a higher risk of histologic transformation. Because the PFS difference related to presence of M-protein was not observed in patients receiving bendamustine and rituximab, immunochemotherapy may be a preferred approach over rituximab monotherapy in this group and needs to be explored further

Myelodysplastic Syndrome with Transfusion Dependence Treated with Venetoclax

Myelodysplastic syndromes are characterized by ineffective hematopoiesis in one or more lineages of the bone marrow. They are a group of heterogeneous clonal stem cell malignancies with a high risk to progress to acute myeloid leukemia. Currently, there are no curative FDA-approved medications for myelodysplastic syndromes. Hematopoietic cell transplantation is potentially the only curative option; however, treatment is often unavailable due to age and comorbidities. Hypomethylating agents, azacitidine and decitabine, and the immunomodulatory agent, lenalidomide, are the only FDA approved medications for the treatment of MDS, all of which are noncurative. Venetoclax, an inhibitor of the antiapoptotic protein BCL-2 used to treat chronic lymphocytic leukemia, is currently being evaluated in clinical trials as a monotherapy in high-risk myelodysplastic syndromes/acute myeloid leukemia. We present a patient with transfusion-dependent myelodysplastic syndromes refractory to the current standard of care treatment not a candidate for hematopoietic cell transplantation who responded well to monotherapy treatment with venetoclax and has since remained transfusion-independent

Factors affecting mortality in patients with COPD exacerbations requiring ICU admission

Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) often require hospital admission and have a significant mortality rate. Patients with AECOPD who need intensive care (ICU) have higher mortality rates. Identifying factors associated with increased mortality might change approaches to treatment and improve communication with patients’ families about prognosis. Methods: Patients with AECOPD (ICD 9 code 491.21) directly admitted to the ICU between 1/1/2006 and 12/31/2010 were retrospectively reviewed. The inclusion criteria were age 45 years or older, diagnosis of AECOPD, and admission to an ICU. The exclusion criteria included any history of another respiratory disease or decompensated cardiac disease. The primary goal was to determine factors which affect survival. Result: Two hundred and seventeen patients were included this study. The mean ages were 70.4±10.4 years in the in-hospital death group and 66.4±10.9 years in the survivors. The overall mortality rate was 12%.  Multivariate analysis showed that the mortality rate was significantly associated with a low mean arterial blood pressure (MAP) (odds ratio [OR] 0.91, 95% confidence interval [CI] 0.86-0.96), an intubation event (OR 6.12, 95% CI 1.24-30.87), and an elevated blood urea nitrogen (BUN) (OR 1.06, 95% CI 1.01-1.12) (p<0.05 for each factor). Conclusion: This study identified clinical parameters associated with increased mortality in patients with AECOPD admitted to an ICU. These factors include a low MAP, intubation, and a high BUN and are easily obtained during the initial evaluation of the patient. They reflect the severity of the acute exacerbation and complications in other organ systems

Early versus Late Discontinuation of Maintenance Therapy in Multiple Myeloma

Maintenance therapy after autologous stem cell transplant (ASCT) in multiple myeloma (MM) is the standard treatment and recommended to be continued until disease progression. However, in the real world, patients discontinue treatment due to various reasons. We sought to determine the effect of early versus late discontinuation on survival outcomes in MM patients who underwent ASCT at The Ohio State University. We retrospectively reviewed 340 patients who underwent ASCT from 2005 to 2016 and received maintenance therapy for at least six months without progression. We compared the outcomes of patients who received maintenance for three years or less (early group) to the patients who continued maintenance beyond three years (late group). Lenalidomide (89%) and bortezomib (10%) were the most common agents used for maintenance chemotherapy. In Kaplan–Meier analysis, patients in the late group had prolonged progression-free (PFS) (p p < 0.001). The 5-year estimated OS in late group was 96% vs. 79% in the early group and 5-year PFS was 80% in late group vs. 50% in the early group. The most common reasons for discontinuation of maintenance in early group were adverse events (55.9%) and patient preference (22.5%). For the late group, it was disease progression (23.9%) and adverse events (14.3%). Fifty-five percent of patients in the late group were still on maintenance treatment at the last follow-up. Continuation of maintenance therapy was thus associated with improved outcomes, while adverse events prevented most patients from continuing treatment