Go, Ronald S.

AbstractBackgroundData on the effect of systemic immunoglobulin light chain amyloidosis (AL amyloidosis) on thyroid function are limited.ObjectiveTo assess the prevalence of hypothyroidism in AL amyloidosis patients and determine its predictors.Methods1142 newly diagnosed AL amyloidosis patients were grouped based on the thyroid‐stimulating hormone (TSH) measurement at diagnosis: hypothyroid group (TSH above upper normal reference; >5 mIU L−1; n = 217, 19% of study participants) and euthyroid group (n = 925, 81%). Predictors for hypothyroidism were assessed in a binary multivariate model. Survival between groups was compared using the log‐rank test and a multivariate analysis.ResultsPatients with hypothyroidism were older, more likely to present with renal and hepatic involvement and had a higher light chain burden compared to patients in the euthyroid group. Higher proteinuria in patients with renal involvement and lower albumin in patients with hepatic involvement were associated with hypothyroidism. In a binary logistic regression model, age ≥65 years, female sex, renal involvement, hepatic involvement, kappa light chain restriction and amiodarone use were independently associated with hypothyroidism. Ninety‐three per cent of patients in the hypothyroid group with free thyroxine measurement had normal values, consistent with subclinical hypothyroidism. Patients in the hypothyroid group had a shorter survival compared to patients in the euthyroid group (4‐year survival 36% vs 43%; P = 0.008), a difference that was maintained in a multivariate analysis.ConclusionA significant proportion of patients with AL amyloidosis present with hypothyroidism, predominantly subclinical, which carries a survival disadvantage. Routine assessment of TSH in these patients is warranted.

AbstractAutoimmune hemolytic anemia (AIHA) is an uncommon entity that presents diagnostic, prognostic, and therapeutic dilemmas despite being a well-recognized entity for over 150 years. This is because of significant differences in the rates of hemolysis and associated diseases and because there is considerable clinical heterogeneity. In addition, there is a lack of clinical trials required to refine and update standardized and evidence-based therapeutic approaches. To aid the clinician in AIHA management, we present four vignettes that represent and highlight distinct clinical presentations with separate diagnostic and therapeutic pathways that we use in our clinical practice setting. We also review the parameters present in diagnostic testing that allow for prognostic insight and present algorithms for both diagnosis and treatment of the AIHA patient in diverse situations. This is done in the hope that this review may offer guidance in regard to personalized therapy recommendations. A section is included for the diagnosis of suspected AIHA with negative test results, a relatively infrequent but challenging situation, in order to assist in the overall evaluation spectrum for these patients.

Abstract We describe a series of 102 patients diagnosed from January 1, 1990 to December 31, 2015 with Type 1 monoclonal cryoglobulinemia (MoC). Symptoms were seen in 89 (87%) patients, including: cutaneous symptoms in 64 (63%) patients, with purpura (n = 43, 42%) and ulcers/gangrene (n = 35, 34%) being most common; neurological findings in 33 (32%) patients, most frequently sensory neuropathy (n = 24, 24%); vasomotor symptoms, mainly Raynaud's phenomenon in 25 (25%); arthralgias in 24 (24%); and renal manifestations, primarily glomerulonephritis in 14 (14%) patients. An underlying lymphoproliferative disorder was identified in 94 (92%) subjects; MGUS—39, myeloma—20, lymphoplasmacytic lymphoma—21 and others—14. Treatment was initiated in 73 (72%) patients, primarily for cryoglobulinemia‐related symptoms in 57. Treatment regimens consisted of: steroids ± alkylating agents in 29 (40%), novel myeloma therapies in 16 (22%), rituximab with alkylating agents in 12 (16%) and rituximab ± steroids in 11 (15%) patients; 22 patients received plasmapheresis. Six patients underwent autologous stem cell transplant. Cryocrit at treatment initiation, change in cryocrit and time to nadir cryocrit were predictive of symptom improvement. Treatment directed toward the underlying clonal disorder resulted in improvement (n = 47) or stabilization (n = 16) of symptoms in the majority of patients and disappearance of cryoglobulin in over one‐half.

Venous thromboembolism (VTE) contributes to significant morbidity, mortality, and socioeconomic burden. There is a paucity of literature regarding sex-based sociodemographic differences in VTE presentation and short-term outcomes. We aimed to compare clinical outcomes between men and women hospitalized for VTE management. We performed a retrospective analysis using data from the National Inpatient Sample (NIS) database from 2012 to 2013. Inclusion criteria were age 18 years and older and a primary discharge diagnosis of VTE. Sociodemographic features and medical comorbidities were analyzed, as were hospital length of stay and in-hospital mortality rates. A total of 107,896 patients met the inclusion criteria; 53% were female. Median age was 65 years (interquartile range 51–77) and women were older than men (65 vs 62 years, p<0.001). There were significant differences between men and women with respect to race, primary insurance payer and medical comorbidities, and small differences with respect to VTE location. Female sex was associated with a small but significantly longer hospital length of stay (mean ratio 1.04, 95% CI 1.03–1.05, p<0.001) but no significant difference in in-hospital mortality (2.2% vs 2.1%, p=0.15). In a multivariate model, there was no significant difference between women and men with respect to hospital length of stay or in-hospital mortality. In conclusion, we used data from the NIS to study over 100,000 patients hospitalized for VTE, and identified several sex-based disparities in sociodemographic factors and location of VTE. However, in a multivariable analysis correcting for these factors, sex was not associated with significant differences in clinical outcomes.

AbstractWe analyzed the outcomes following initial relapse or refractory disease in systemic light chain amyloidosis (AL) and the impact of type of therapy employed.A total of 1327 patients with AL seen at Mayo Clinic within 90 days of diagnosis, between 2006 and 2015, were reviewed. The study included 366 patients experiencing a documented hematological or organ relapse or refractory disease requiring start of second line therapy. Overall survival (OS) and time to next treatment (TTNT) were calculated from start of second line treatment.The median time to require second line treatment was 16.2 months (1‐93) from the start of first line therapy. At relapse, patients received proteasome inhibitors (PI; 45.1%), immunomodulators (IMiD; 22.7%), alkylators (9%), PI and IMiD combination (4.1%), autologous transplant (3.8%), steroids and other therapies (4.9%). Among these, 124 (33.9%) required change or reinstitution of therapy. The median time to require third line treatment was 31 months (95% CI; 24, 40.5) and the median overall survival (OS) was 38.8 months (95% CI; 29.6, 52.6) from the start of second line treatment. Retreatment with same therapy at relapse significantly reduced TTNT (22 m vs 32.3 m; P = .01) as compared to different therapy; but did not have any impact OS (30.8 m vs 51.1 m; P = .5). In conclusion, this study provides important information about outcomes of patients with AL who require second line treatment for relapsed/refractory disease . Treatment with a different therapy at relapse improves time to next therapy but does not impact OS.