Pre-treatment neutrophil to lymphocyte ratio as a biomarker of frailty and predictor of survival among older adults with multiple myeloma.

INTRODUCTION: Neutrophil to Lymphocyte Ratio (NLR) combines a marker of inflammation and reduced cell turnover to reflect age related alterations in the immune system. Whether NLR can serve as a biomarker of frailty and predict survival among older adults with Multiple Myeloma (MM) is unknown. MATERIALS AND METHODS: We used an electronic health record-derived database to identify older adults (age ≥ 60y) with incident MM diagnosed between 1/2011 and 2/2020, with known pre-treatment absolute neutrophil and lymphocyte count up to 90 days before the start of therapy. The calculated NLR values were stratified into quartiles (Q1-Q4). We constructed a previously validated, simplified frailty index combining age, comorbidity and ECOG performance status. We measured the association between NLR quartiles and this frailty index using a logistic regression, adjusted for age, sex and race/ethnicity. We used Kaplan Meier methods and multivariable Cox regression to assess the impact of NLR on overall survival adjusting for potential confounders. RESULTS: We identified 1729 older adults with newly diagnosed MM, at a median age of 73y (IQR: 67-78y). The median NLR was 2.13 (IQR: 1.44 to 3.31). Of the 1135 evaluable patients, 55% met criteria for frailty. Multivariable analysis revealed a 2.1-fold higher odds of frailty (95%CI = 1.42-3.10, p < 0.001) for patients in the NLR Q4 group vs. NLR Q1 group. In a multivariable analysis, adjusting for age, sex, race/ethnicity, M-protein type, stage, high risk cytogenetics, baseline creatinine, LDH and type of first line therapy, patients in NLR Q4 group had a 1.51 times increased hazards of death (95%CI = 1.15-1.98, p 0.002) when compared to those in NLR Q1 group. CONCLUSION: NLR, a readily available laboratory biomarker, is associated with frailty measured using a simplified frailty index as well as inferior overall survival among older adults with MM. Future studies should explore its value as a screening tool to identify frail older adults with MM.

Risk, Outcomes, and Predictors of Clostridium difficile Infection in Lymphoma: A Nationwide Study.

OBJECTIVE: The risk of Clostridium difficile infection (CDI) has not been well studied in patients with lymphoma. We thus sought to determine the risk of CDI in hospitalizations with lymphoma along with its trend, outcomes, and predictors using a large database. METHODS: Hospital discharge data from the Nationwide Inpatient Sample (NIS) from 2007 to 2011 were used for the study. Using the International Classification of Diseases, Ninth Revision, Clinical Modification codes, all adult patients aged 18 years or older having a primary diagnosis of lymphoma were queried for the presence of CDI as any of the secondary diagnoses. The risk of CDI in lymphoma and its yearly trend were assessed. We performed multivariate logistic regression to determine the independent risk factors of CDI in lymphoma. Furthermore, we studied mortality and other adverse outcomes of CDI in patients with lymphoma. RESULTS: There were 236,312 discharges (weighted) with the primary diagnosis of lymphoma. CDI was present in 2.13% of patients with lymphoma versus 0.8% in the nonlymphoma group (P < 0.001). On multivariate analysis, the significant predictors of CDI in lymphoma were presence of infection (odds ratio [OR] 3.1, 95% confidence interval [CI] 2.7-3.6), stem cell transplant (OR 2.7, 95% CI 2.3-3.4), graft-versus-host disease (OR 1.9, 95% CI 1.4-2.8), race (Asian vs white, OR 1.6, 95% CI 1.1-2.4), chemotherapy (OR 1.6, 95% CI 1.4-1.8), gastrointestinal surgery (OR 1.4, 95% CI 1.2-1.7), and Charlson Comorbidity Index (CCI) (CCI of 2 vs 0-1: OR 1.2, 95% CI 1.1-1.4; CCI of 3 vs 0-1: OR 1.3, 95% CI 1.03-1.6). CDI in lymphoma was associated with worse hospital outcomes such as increased mortality (17% vs 8%), increased length of stay (23.6 vs 9.9 days), mean total hospital charges ($197,015 vs $79,392), rate of intubation (13% vs 4% vs 13%), and rate of total parenteral nutrition (11% vs 3%). CONCLUSIONS: Hospitalization with lymphoma was associated with an increased risk of CDI. The significant predictors for CDI in lymphoma were infection, stem cell transplant, graft-versus-host disease, race, chemotherapy, gastrointestinal surgery, and Charlson Comorbidity Index. CDI in lymphoma was associated with increased mortality and other adverse outcomes warranting a need of more vigilance for CDI in patients with lymphoma.

Hot and malignant - a case of invasive papillary carcinoma in hyperthyroid patient with hot nodules.

Introduction: Malignant thyroid nodules are clinically euthyroid and appear as cold nodules on scintigraphy. Malignancy in hyper-functioning thyroid nodule is rare. Case report: A 48-year-old male with painless swelling on the right side of his neck for the last 4 months complained of feeling hot all the time, sweating and unintentionally losing about 20 pounds. On physical examination, there was a 3-cm mobile, non-tender mass on the right supra-clavicular area biopsy of which was consistent with metastatic papillary carcinoma of thyroid. Neck imaging showed a cystic mass in the right supra-clavicular fossa region, bilateral neck adenopathy and multiple thyroid nodules. Subsequent thyroid radionuclide scans showed three hyper-functioning nodules, which were later demonstrated to be a follicular variant of papillary microcarcinoma. He was treated with total thyroidectomy followed by radioactive iodine thyroid ablation therapy. Conclusion: Physicians need to be aware and vigilant for the possibilities of malignancy in a hyper-functioning thyroid nodule when evaluating any thyroid nodule.

The Characteristics and Trends in Adrenocortical Carcinoma: A United States Population Based Study.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. Data on the incidence of ACC, however, are scarce and not recent. The purpose of this study was to characterize the tumor and the patients developing ACC over the last four decades using a large population based database. METHODS: We identified all cases of ACC diagnosed between 1973 - 2014 from the Surveillance, Epidemiology, and End Results-18 registry. Descriptive analyses were used for all extracted demographic, clinical, pathological, therapeutic and survival data, and were compared between the four time periods of 1973 to 1984, 1985 to 1994, 1995 to 2004 and 2005 to 2014 using Chi-square tests for categorical variables and one-way analysis of variance for continuous variables. RESULTS: There were a total of 2,014 cases of ACC between 1973 and 2014 with an age-adjusted incidence of 1.02 per million populations. The median age at diagnosis was 55 years with the majority of them being females and whites. The proportion of cases by different genders, races and age at diagnosis had not changed significantly over time. These malignancies were mostly the only primary malignancy, unilateral and of high grades at diagnosis. Surgical resection of the tumor remained the mainstay of treatment. However, there was a significant increase in the use of adjuvant radiotherapy, adjuvant chemotherapy and chemotherapy alone in recent times. The median survival time was 17 months, but continues to decrease in recent time periods. CONCLUSIONS: ACC continues to be a rare malignancy in the United States. However, most cases continue to be diagnosed only in advanced stages and are associated with poor survival. These findings underline the need for specific diagnostics tools with new and more effective treatment options.

Real-World Clinical Efficacy and Tolerability of Direct-Acting Antivirals in Hepatitis C Monoinfection Compared to Hepatitis C/Human Immunodeficiency Virus Coinfection in a Community Care Setting.

Background/Aims: Limited data exist comparing the safety and efficacy of direct-acting antivirals (DAAs) in hepatitis C virus (HCV) monoinfected and HCV/human immunodeficiency virus (HIV) coinfected patients in the real-world clinic practice setting. Methods: All HCV monoinfected and HCV/HIV coinfected patients treated with DAAs between January 2014 and October 2017 in community clinic settings were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy, factors affecting sustained virologic response at 12 weeks (SVR12) after treatment, and adverse reactions were compared between the groups. Results: A total of 327 patients were included in the study, of which 253 were HCV monoinfected, and 74 were HCV/HIV coinfected. There was a statistically significant difference observed in SVR12 when comparing HCV monoinfection and HCV/HIV coinfection (94% and 84%, respectively, p=0.005). However, there were no significant factors identified as a predictor of a reduced response. The most common adverse effect was fatigue (27%). No significant drug interaction was observed between DAA and antiretroviral therapy. None of the patients discontinued the treatment due to adverse events. Conclusions: In a real-world setting, DAA regimens have lower SVR12 in HCV/HIV coinfection than in HCV monoinfection. Further studies involving a higher number of HCV/HIV coinfected patients are needed to identify real predictors of a reduced response.

Secondary Salivary Gland Malignancy in Thyroid Cancer: A United States Population Based Study.

BACKGROUND: There is an increased risk of second primary malignancies with thyroid cancer. However, the risk and characters of secondary salivary gland malignancy (sSGM) in patients with thyroid cancer have not been evaluated before. METHODS: We used the Surveillance Epidemiology and End Results (SEER) 18 registry to identify thyroid cancer patients from 1973 to 2014. We then calculated the risk of sSGM using standardized incidence ratio and excess risk. Separately, all cases of primary salivary gland malignancy (pSGM) diagnosed between 1973 - 2014 were extracted from the SEER 18 registry, and their characteristics compared with sSGM using independent samples t-test for continuous variables and Chi-square tests for categorical variables. RESULTS: There were a total of 68,339 cases of primary thyroid cancer. Of these, 18 patients developed sSGM with the observed to expected ratio being 3.58 (95% CI: 2.12 to 5.65; P < 0.05) and excess risk being 0.48 per 10,000 population. The incidence of sSGM remained higher between 6 months to 10 years from the time of diagnosis of thyroid carcinoma. The risk of developing sSGM was significantly higher if they were below 60 years of age (O/E: 4.51; 95% CI: 2.33 - 7.88; P < 0.05), were females (O/E: 4.91; 95% CI: 2.80 - 7.97; P < 0.05), were whites (O/E: 3.04; 95% CI: 1.62 - 5.1 9; P < 0.05), had well-differentiated thyroid carcinoma (O/E: 9.70; 95% CI: 3.90 - 19.98; P < 0.05) or were treated with radioactive iodine (O/E: 5.26; 95% CI: 2.72 - 9.19; P < 0.05). While the proportion of females developing sSGM was significantly greater than those developing pSGM (88.9% vs. 44%; P < 0.05), there was no statistical difference between pSGM and sSGM in terms of the age at diagnosis, the proportion of patients diagnosed before 60 years of age, anatomic site of origin or the histological grade of tumor. CONCLUSIONS: Patients with thyroid cancers are at an increased risk of developing sSGM than the general population. This risk is greater if the person is below 60 years of age, female, white, with well-differentiated thyroid carcinoma or is treated with radioactive iodine.

Acquired Amegakaryocytic Thrombocytopenia and Pure Red Cell Aplasia in Thymoma.

Association of thymoma with myasthenia gravis, pure red cell aplasia, and aplastic anemia is well documented. However, thymoma complicated by acquired amegakaryocytic thrombocytopenia (AAMT) is rarely reported. Here, we present a case of a 60-year-old male with past medical history of recurrent invasive thymoma who presented with cough and blood in sputum. He was found to have severe normocytic normochromic anemia and thrombocytopenia that did not improve with intravenous steroids or multiple transfusions of red cells and platelets. Subsequent bone marrow biopsy showed severely depleted megakaryocytes and erythroid precursor cells with relative myeloid hyperplasia suggestive of amegakaryocytic thrombocytopenia and red cell aplasia. He was started on oral cyclosporine but subsequently developed leukopenia and refused any further treatment or diagnostic procedures and left the hospital against medical advice. AAMT, thus, may be a very early presentation of impending aplastic anemia, and treating physicians need to be aware of this entity.

Lung consolidation as a rare presentation of lymphoplasmacytic lymphoma with extramedullary Waldenström's macroglobulinemia.

Objectives: Lymphoplasmacytic lymphoma (LPL) is a mature B cell lymphoma that usually involves the bone marrow, spleen and lymph nodes. Extramedullary involvement, including the lung, is rarely reported. Case description: A 73-year-old female initially presented to our hospital complaining of productive cough of white-colour sputum for three weeks duration. She reported unintentional weight loss of ten pounds over the last five months. There was no history of haemoptysis, fever, night sweats, chills, recent infections or hospitalization. Chest imaging showed right lower lobe consolidation, small right pleural effusion. She was treated with oral antibiotic for pneumonia. After two months, a follow up chest imaging revealed persistent right lower lobe consolidation. Therefore, she was worked up for the possibility of malignancy. Bronchoscopy showed polypoid nodularities surrounded by black discoloured mucosa in the sub-segmental bronchi of the right lower lobe, and biopsy specimen revealed atypical B cell lymphocytic infiltrate. Polymerase chain reaction confirmed a clonal B-cell gene rearrangement supportive for a low-grade B-cell Lymphoma. Subsequently; serum immunofixation showed IgM of 1491 mg/dL (normal range 26-217 mg/dl) with normal levels of IgG and IgA. Urine contained free kappa light chains. Cytology with immunophenotyping of pleural fluid revealed lymphoplasmacytic lymphocytes. This combination of lab and bronchoscopy findings established the diagnosis of extramedullary Waldenström's macroglobulinemia. Conclusion: Waldenström's macroglobulinemia, a manifestation of LPL, is associated with an IgM monoclonal gammopathy in the blood. Extramedullary involvement including the lung is rarely seen in LPL. Physicians need to be aware of this rare presentation.

Secondary acute myeloid leukemia in survivors of Hodgkin lymphoma.

BACKGROUND: This large population-based study determined the epidemiology and outcomes of secondary acute myeloid leukemia (sAML) developing in Hodgkin lymphoma survivors. METHODS: We utilized the Surveillance Epidemiology and End Results (SEER) 9 database to identify 104 cases of sAML. RESULTS: Patients with sAML (median age: 47 years; 82% <60 years) were significantly younger than de novo AML cases (66 years; p < 0.01). sAML had worse overall survival (OS) than de novo AML (p < 0.01). OS was better in younger patients and in more recent years. CONCLUSION: Older patients with sAML have a dismal OS and should be enrolled in trials of novel therapies. Younger patients have improved OS and hence may benefit from curative intent intensive therapy and allogeneic transplant.

Demographic and other characteristics of nodal non-Hodgkin's lymphoma managed in academic versus non-academic centers.

BACKGROUND: Cancer therapy and outcomes are known to be affected by various demographic features and hospital types. We aimed to identify the characteristics of non-Hodgkin's lymphoma (NHL) patients associated with receipt of care at academic centers. METHOD: This is a retrospective study of all patients diagnosed with nodal NHL between 2000 and 2011 in the National Cancer Database (NCDB), who received the diagnosis, and all or part of their initial therapy in the reporting hospital (n = 243,436). Characteristics of patients receiving care in academic versus nonacademic centers were compared using the Chi-square test. RESULTS: Approximately 27% received care in academic centers. Patients receiving care in nonacademic centers, compared with academic centers, were more likely to be ⩾60 years (69% versus 58%, p < .0001), White (89% versus 80%, p < .0001) and have lower educational attainment (>12% without high school diploma: 72% versus 69%, p < .0001) and economic status (household income <$49,000: 66% versus 61%, p < 0.0001). Patients receiving care in nonacademic centers were less likely to travel ⩾25 miles (21% versus 26%, p < 0.0001). White patients, compared with non-Whites, were more likely to be ⩾60 years (70% versus <50%, p < 0.0001), which probably explains less care in academic centers. CONCLUSIONS: Patients ⩾60 years and those with poorer educational attainment and economic status were less likely to receive care in academic centers. Care in academic centers required a longer commute. Elderly patients frequently have inferior outcomes and may benefit from clinical trials with novel agents and expertise at academic centers.

Chemotherapy use in stage III colon cancer: a National Cancer Database analysis.

BACKGROUND: Although adjuvant chemotherapy in stage III colon cancer improves overall survival, prior studies have shown that it is underused. We analyzed different factors that may influence its use. METHODS: This is a retrospective study of stage III colon cancer patients (n = 207,718) diagnosed between 2000 and 2011 in the National Cancer Data Base (NCDB). The NCDB contains ~70% of new cancer diagnosis from >1500 American College of Surgeons accredited cancer programs in the United States and Puerto Rico. The chi-squared test was used to determine any difference in characteristics of patients who did or did not receive chemotherapy. RESULTS: A total of 35% of all stage III colon cancer patients, and 38% of stage III cases undergoing surgery, did not receive adjuvant chemotherapy. The use of chemotherapy had increased in recent years (64% in 2007-2011 versus 59% in 2000-2002; p < 0.0001). Its use was lower in whites (61%), females (60%), patients ⩾60 years (55%), patients with one or more comorbidities (55%), nonacademic centers (62%), those with medicare insurance (52%), lower education (61%) and income levels (59%, all p < 0.0001). The nonwhite and uninsured were more likely to be <60 years old. CONCLUSION: More than one-third did not receive adjuvant chemotherapy, although its use has increased in more recent years. Age was one of the most important determinants of chemotherapy use, which may explain higher rates in nonwhite and uninsured. In addition to patient characteristics, race, gender and socioeconomic factors influence chemotherapy use. These findings have important implications for healthcare reform.

Fondaparinux for Management of Heparin-induced Thrombocytopenia after Cardiovascular Intervention: A Systematic Review.

OBJECTIVES: The efficacy and safety of fondaparinux, an emerging therapeutic option for heparin-induced thrombocytopenia (HIT), remain unclear in cardiac surgery patients with HIT. METHODS: Using several search criteria, we reviewed all cases of fondaparinux use in patients who developed HIT after any cardiovascular intervention and were indexed in MEDLINE by August 2014. Based on pre-specified criteria, cases were divided into confirmed HIT, probable HIT and possible HIT. The outcome of fondaparinux use in each group was compared using Chi-square test. RESULTS: Of 43 total cases, 22 had confirmed HIT and 21 had possible HIT. Valve replacement or repair (39%) and heart transplant or ventricular assist device placement (21%) were the most common preceding cardiovascular interventions. Creatinine clearance <30 ml was present in 27% and 52% of confirmed and possible HIT respectively. Overall the risk of new thrombosis and bleeding with fondaparinux were 4.6% and 7% respectively, without any differences in the two subgroups. The majority (86%) of cases improved clinically; of the remainder patients, similar percentage of cases with possible HIT and confirmed HIT died (24% vs. 5%; p= 0.102). None of the deaths were attributed to HIT or complications of bleeding. CONCLUSION: Within the limitations of this study, the risk of thrombosis and bleeding with fondaparinux use in cardiac surgery patients with HIT are low and largely comparable to outcomes reported in literature with other agents.

Systemic therapy in stage IV pancreatic cancer: a population-based analysis using the National Cancer Data Base.

BACKGROUND: Pancreatic cancer accounts for approximately 7% of all cancer deaths. More than half of all pancreatic cancers are stage IV at diagnosis, where systemic chemotherapy is used with the goal of life prolongation as well as palliation. The patient characteristics and health system factors that drive the use of systemic therapy are unknown. METHOD: This is a retrospective study of stage IV pancreatic cancer patients (n = 140,210) diagnosed between 2000 and 2011 in the NCDB. NCDB contains approximately 70% of new cancer diagnosis from more than 1500 accredited cancer programs in the United States and Puerto Rico. Chi-squared test was used to determine any differences in characteristics of patients who did or did not receive systemic therapy. RESULTS: Our study demonstrated that only 49.1% of stage IV pancreatic cancer patients received systemic therapy. The use of systemic therapy is significantly lower in female, African American/Hispanic, patients older than 40 years, those without insurance or with Medicare and Medicaid, higher Charlson Comorbidity Score, poor economic and educational status and in nonacademic centers. CONCLUSIONS: This is the largest study to evaluate the determinants of systemic therapy use in stage IV pancreatic cancer. The use of systemic therapy was significantly lower in patients older than 40 years, lower educational status, nonprivate insurance and with higher Charlson Comorbidity Scores. In addition, the use of systemic therapy was lower with female sex, African Americans/Hispanic, and lower socio-economic status. Understanding the barriers in the use of systemic therapy as well as appropriate utilization of systemic therapy can both optimize cancer care.

Differentiating malignant hypertension-induced thrombotic microangiopathy from thrombotic thrombocytopenic purpura.

OBJECTIVES: Malignant hypertension can cause thrombotic microangiopathy (TMA) and the overall presentation may mimic thrombotic thrombocytopenic purpura (TTP). This presents a dilemma of whether or not to initiate plasma exchange. The objective of the study was to determine the clinical and laboratory manifestations of malignant hypertension-induced TMA, and its outcomes. METHODS: Using several search terms, we reviewed English language articles on malignant hypertension-induced TMA, indexed in MEDLINE by 31 December 2013. We also report a new case. All these cases were analyzed using descriptive statistics. RESULTS: A total of 19 patients, with 10 males, had a median age of 38 years at diagnosis; 58% had a history of hypertension. Mean arterial pressure at presentation was 159 mmHg (range 123-190 mmHg). All had prominent renal dysfunction (mean creatinine of 5.2 mg/dl, range 1.7-13 mg/dl) but relatively modest thrombocytopenia (mean platelet count of 60 × 103/µl, range 12-131 × 10(3)/µl). Reported cases (n = 9) mostly had preserved ADAMTS-13 activity (mean 64%, range 18-96%). Following blood pressure control, the majority had improvement in presenting symptoms (100%) and platelet counts (84%); however, only 58% had significant improvement in creatinine. More than half (53%) needed hemodialysis. One patient died of cardiac arrest during pacemaker insertion. CONCLUSION: Prior history of hypertension, high mean arterial pressure, significant renal impairment but relatively modest thrombocytopenia and lack of severe ADAMTS-13 deficiency (activity <10%) at diagnosis are clues to diagnose malignant hypertension-induced TMA. Patients with malignant hypertension respond well to antihypertensive agents and have favorable nonrenal outcomes.