Non-ischemia Cardiomyopathy and Polycythemia Secondary to Anabolic-Androgenic Steroid Use.

Athletes and bodybuilders use anabolic-androgenic steroids (AAS) to increase muscle mass and enhance performance. Its use is widespread among competitive athletes in order to enhance athletic performances. However, the use of AAS has been linked to many deleterious adverse effects, including cardiomyopathy and polycythemia. We present the case of a young man in his late 20s who presented with uncontrolled hypertension and elevated hemoglobin. He was found to have a reduced left ventricular ejection fraction of 20-25%. Further workup showed dilated cardiomyopathy and low normal erythropoietin (EPO) levels. Evaluation for polycythemia vera was negative, and there was no evidence of ischemic cardiomyopathy. The patient later admitted to using injected AAS for professional bodybuilding. The coexistence of both these conditions can be challenging to diagnose and treat. While primary and secondary polycythemia can lead to hyperviscosity and result in ischemic cardiomyopathy from coronary occlusion, anabolic steroids can directly result in cardiomyopathy and polycythemia. This case points to the importance of identifying cardiomyopathy and polycythemia from illicit drug use, which can often be missed, and the workups needed to identify the etiology.

AIMS65, Glasgow-Blatchford bleeding score and modified Glasgow-Blatchford bleeding score in predicting outcomes of upper gastrointestinal bleeding: An accuracy and calibration study.

BACKGROUND: Albumin, international normalized ratio (INR), mental status, systolic blood pressure, age >65 years (AIMS65), Glasgow-Blatchford bleeding score (GBS) and modified GBS (mGBS) are three pre-endoscopy scoring systems used in the risk stratification of upper gastrointestinal bleeding (UGIB). The utility of such scoring systems in a population is estimated by their accuracy and calibration in the population. We aimed at validating and comparing the accuracy of the three scoring systems in predicting clinical outcomes including in-hospital mortality, need for blood transfusion, endoscopic treatment and rebleeding risk. METHOD: We conducted a single-center, retrospective cohort study on patients with UGIB at a tertiary care center in India over 12 months. Clinical and laboratory data was collected from all patients admitted with UGIB. All patients were risk stratified using AIMS65, GBS and mGBS. The clinical outcome examined were: in-hospital mortality, requirement of blood transfusion, need for endoscopic treatment and rebleeding during hospital stay. The area under receiver-operating curve (AUROC) was calculated to assess the performance and calibration curves (Hosmer-Lemeshow goodness of fit curve) were plotted to examine how accurately the model describes the data of all three scoring systems. RESULTS: Total 260 patients were included in the study, of which 236 (90.8%) were males. As many as 144 (55.4%) patients required blood transfusion and 64 (30.8%) required endoscopic treatment. While the incidence of rebleeding was 7.7%, in hospital mortality was 15.4%. Of 208 who underwent endoscopy, the most common causes identified were varices (49%) and gastritis (18.2%), followed by ulcer (11%), Mallory-Weiss tear (8.1%), portal hypertensive gastropathy (6.7%), malignancy (4.8%) and esophageal candidiasis (1.9%). The median AIMS65 score was 1, GBS 7 and mGBS 6. The area under curve (AUROC) for AIMS65, GBS and mGBS was (0.77, 0.73,0.70), (0.75, 0.82,0.83), (0.56, 0.58,0.83), (0.81, 0.94,0.53) for in-hospital mortality, blood transfusion requirement, endoscopic treatment and rebleeding prediction, respectively. CONCLUSION: GBS and mGBS are superior to AIMS65 in predicting the requirement of blood transfusion and rebleeding risk, whereas in-hospital mortality was better predicted by AIMS 65. Both scores performed poorly in predicting the need of endoscopic treatment. An AIMS65 of 0,1 and a GBS of ≤ 1 are not associated with significant adverse events. A poor calibration of the scores in our population points to the lack of generalizability of these scoring systems.

Neoadjuvant Versus Adjuvant Chemotherapy for Resectable Metastatic Colon Cancer in Non-academic and Academic Programs.

BACKGROUND: Overall survival advantage of chemotherapy before versus after metastasectomy of liver or lung lesion is not clear for colon cancer with synchronous liver or lung metastasis. MATERIALS AND METHODS: Adults 20 years or older with primary colon cancer and single organ metastatic disease either in the liver or lung at diagnosis were identified between 2010 and 2015 through the National Cancer Database (NCDB). Patients were categorized into 2 cohorts: pre-operative/peri-operative chemotherapy (neoadjuvant -[NAC]) or post-operative chemotherapy (adjuvant [AC]). Survivals and factors associated with were compared between the 2 groups. RESULTS: A total of 3038 patients with colon cancer with liver or lung metastases were identified. The percentage of patients receiving NAC had steadily increased from 12.29% to 28.31%, mostly in academic programs. On multivariate analysis, patients who received NAC had an overall survival advantage in the non-academic setting whereas no advantage is seen in the patients treated in the academic settings. The median overall survival for patients receiving NAC and AC was 47.24 months and 38.08 months, respectively. Factors associated with overall survival advantage in NAC patients treated in non-academic programs included age 20-49 years, CEA value of >30, right-sided colon primary, liver metastasis, and clear resection margins. CONCLUSIONS: Metastatic colon cancer with single organ liver or lung lesions benefits from neoadjuvant chemotherapy, especially in -non-academic settings. The overall survival advantage in this setting has not been shown before.

Case report: Uridine triacetate in the management of delayed onset 5-fluorouracil toxicity: A case report and review of literature.

5-fluorouracil (5FU) and capecitabine are fluoropyrimidine anti-neoplastic drugs commonly used in the treatment of different types of cancer. Hereditary dihydropyrimdine deaminase (DPD), thymidylate synthase mutations and drug overdose may lead to life-threatening toxicities. Uridine triacetate (UTA) is an emergency treatment for overdoses and early onset, severe or life-threatening toxicities from fluoropyrimidines. It is approved for use in adults and children within 96 h of last fluoropyrimidine administration. We present the case of a 64-year-old male treated with 5-FU and oxaliplatin as adjuvant systemic therapy for stage IIIA rectal cancer who developed delayed central nervous system toxicity 18 days after initiating chemotherapy. He had rapidly worsening encephalopathy and ataxia. Laboratory workups, MRI brain and EEG were negative. He was started on UTA with concerns of 5-FU toxicity due to the life-threatening nature of his condition even beyond the recommended 96-h time cut-off. He had rapid improvement in clinical status and resolution of encephalopathy. DPD deficiency testing later resulted as heterozygous for IVS14+1G>A allele indicating enzyme deficiency. This report demonstrates the importance of identifying delayed side effects with fluoropyrimidine therapy and potential treatment for reversing these effects. We also did an extensive literature review and obtained reports from the uridine triacetate clinical trials on patients receiving UTA after the 96-h cut-off. Based on our experience and previous published reports, a patient developing life-threatening delayed 5-FU toxicity should also be considered for UTA on a case-by-case basis.

Epidemiology and Determinants of Survival for Primary Intestinal Non-Hodgkin Lymphoma: A Population-Based Study.

Background: Gastrointestinal tract is the most common site of extranodal non-Hodgkin lymphoma (EN-NHL). Most of the published data have been on gastric NHL with limited studies on primary intestinal non-Hodgkin lymphoma (PI-NHL) considering rare incidence. We performed epidemiological and survival analysis for PI-NHL from the Surveillance, Epidemiology, and End Results (SEER) 18 database. Methods: A total of 9,143 PI-NHL cases of age ≥ 18 years were identified from the SEER 18 database for the period 2000 - 2015. Totally, 8,568 patients were included for survival analysis. Cause-specific survival (CSS) and overall survival (OS) analysis were done for PI-NHL and PI-diffuse large B-cell lymphoma (PI-DLBCL) using sex, age of onset, treatment, histology, stage, and year of diagnosis. Survival analysis was done by using Cox proportional hazard model and Kaplan-Meier plot with log-rank test. Results: The percentage of PI-NHL of all the intestinal cancers and EN-NHL were 1.35%, and 10.52%, respectively. The age-adjusted incidence was 0.9145/100,000 population for the study population. PI-NHL was more common among patients aged ≥ 60 years, male and non-Hispanics Whites. Majority of patients were diagnosed at stage 1 and 2 (74%), and DLBCL (44.8%) was the most common histology. Overall median survival was 111 (95% confidence interval (CI): 105 - 117) months. In OS analysis, significant increased risk of mortality was seen with T-cell NHLs vs. DLBCL (hazard ratio (HR): 2.56), patients aged ≥ 60 vs. < 60 years (HR: 2.87), stage 4 vs. stage 1 (HR: 1.93), male vs. female (HR: 1.17), with best outcome seen in patient treated with combination of chemotherapy and surgery vs. none (HR: 0.45). Similar results were seen in CSS and for PI-DLBCL as well. Significant improvement in outcomes was observed for PI-DLBCL patients receiving chemotherapy with/without surgery. Conclusions: Findings from our large, population-based study reveal PI-NHL is a rare type of intestinal malignancy with significant difference in survival based on histological and epidemiological characteristics.

A Case of Undiagnosed Functional Gonadotroph Adenoma Leading to Ovarian Hyperstimulation Syndrome.

A functional gonadotroph adenoma is a very rare endocrinopathy, and only a few cases have been reported in the literature. We present a case of a woman in her early 50s with a past medical history of recurrent ovarian cysts who developed bilateral hemianopsia and was referred to the endocrinology clinic after a magnetic resonance imaging (MRI) identified a pituitary mass. Anterior pituitary hormone workup confirmed hypersecretion of follicle-stimulating hormone (FSH), which suggested ovarian hyperstimulation syndrome (OHSS) as the etiology of recurrent ovarian cysts. The patient underwent transsphenoidal resection of the pituitary tumor with improvement in visual symptoms. Our case illustrates that functional gonadotroph adenoma can be a potential cause of OHSS apart from the setting of assisted reproductive technology and hence warranting a meticulous endocrine evaluation to rule out this rare disease.

Late onset of pituitary apoplexy following gonadotropin-releasing hormone agonist for prostate cancer treatment.

Pituitary apoplexy (PA) is a clinical condition characterised by a sudden increase in pituitary gland volume secondary to ischaemia and/or necrosis. Most cases occur in non-functioning pituitary adenoma but can also occur in functioning adenoma. Certain predisposing factors can result in PA and the use of gonadotropin-releasing hormone (GnRH) agonists for prostate cancer (PCa) is one such condition. Once diagnosed, both surgical and conservative management has been used for the treatment of PA. We present a case of a man in his late 50s who developed PA following treatment of PCa with leuprolide. His symptoms developed insidiously and he presented 6 months after symptom onset. Anterior pituitary hormone workup along with pituitary MRI confirmed the diagnosis of PA and patient was subsequently treated with adequate replacement of pituitary hormone with significant improvement in his symptoms. It is very important to keep a high index of suspicion for PA, especially among elderly patients receiving GnRH agonist treatment for PCa.

An Update on the Management of Mixed Neuroendocrine-Non-neuroendocrine Neoplasms (MiNEN).

OPINION STATEMENT: The classification of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) is evolving, and no clear management guidelines are currently available. However, recent studies provide insight into factors affecting outcomes and could help develop treatment decisions for patients with these rare malignancies. The majority of MiNENs have a poorly differentiated neuroendocrine carcinoma (NEC) component which is associated with an aggressive clinical course and poor outcomes. Due to the paucity of clinical trials, strategies adopted in gastrointestinal cancers and NECs are used to manage MiNENs. It is also to be noted that the thoracic neuroendocrine neoplasm WHO 2021 classification does not recognize MiNEN terminology but suggests an equivalent terminology called "combined neuroendocrine non neuroendocrine neoplasm." Surgical management is appropriate in early-stage disease with a low threshold for addition of adjuvant chemotherapy. Multimodality treatment with chemotherapy offers a survival benefit in advanced disease or when surgical resection is not possible without significant morbidity. Chemotherapy should be directed at the more aggressive component which is often the NEC component. In addition, molecular testing should be employed to evaluate patients for enrollment in clinical trials and other targeted treatments. Being a rare disease with retrospective studies and case series providing the majority of data on treatment selection, it is essential to include more granular details of pathology (e.g., Ki-67, mitotic index, percentage of each component, staging information) and treatment modalities (e.g., type and duration, rationale, radiologic response, survival outcomes) in future studies to make systematic reviews possible and help derive meaningful conclusions.

External Validation of a Clinical Score for Patients With Neuroendocrine Tumors Under Consideration for Peptide Receptor Radionuclide Therapy.

Importance: Despite the benefit of peptide receptor radionuclide therapy (PRRT) for patients with well-differentiated neuroendocrine tumors (WD NETs), no clinical metric to anticipate benefit from the therapy for individual patients has been previously defined. Objective: To assess whether the prognostic ability of the clinical score (CS) could be validated in an external cohort of patients with WD NETs. Design, Setting, and Participants: This multicenter cohort study's analysis included patients with WD NETs who were under consideration for peptide receptor radionuclide therapy (PRRT) with lutetium-177 (177Lu)-dotatate between March 1, 2016, and March 17, 2020. The original cohort included patients from Vanderbilt-Ingram Cancer Center. The validation cohort included patients from Ochsner Medical Center, Markey Cancer Center, and Rush Medical Center. Patients with paragangliomas, pheochromocytomas and neuroblastomas were excluded. Statistical analysis was performed from June to November 2021. Exposures: PRRT with 177Lu-dotatate or alternate therapies such as everolimus, sunitinib, or capecitabine plus temozolomide. Main Outcomes and Measures: The primary outcome was progression-free survival (PFS) and was estimated by the Kaplan-Meier method; a Cox proportional-hazards model adjusting for primary tumor site, tumor grade, and number of PRRT doses administered was used to analyze association between CS and outcomes. Results: A total of 126 patients (median age [IQR] age: 63.6 [52.9-70.7] years; 64 male individuals) were included in the validation cohort, and the combined cohort (validation and original cohorts combined) had a total of 248 patients (median [IQR] patient age: 63.3 [53.3-70.3] years; 126 male individuals). In the validation cohort, on multivariable analysis, for each 2-point increase in CS, PFS decreased significantly (hazard ratio, 2.61; 95% CI, 1.64-4.16). After finding an association of the CS with PFS in the validation cohort, the original and validation cohorts were combined into the cohort for this analysis. On multivariable analysis, for each 2-point increase in CS, PFS decreased significantly (hazard ratio, 2.52; 95% CI, 1.89-3.36). Conclusions and Relevance: Increases in CS were associated with worsening PFS in the validation cohort, validating findings from the original cohort. These findings suggest that the CS, to our knowledge, represents the first clinical metric to estimate anticipated benefit from PRRT for patients with WD NETs and may be a clinical tool for patients being considered for PRRT.

Case report: A case of classic hairy cell leukemia with CNS involvement treated with vemurafenib.

Hairy cell leukemia (HCL) is a rare mature B-cell lymphoproliferative disorder and most often presents as classic hairy cell leukemia. This entity is characterized by an indolent course and the presence of the BRAF V600E mutation. We report the case of an 80-year-old man with a history of classical hairy cell leukemia who presented with fatigue, dizziness, shortness of breath, blurring of vision, and headache. His initial diagnosis was 9 years prior, and he received treatments with cladribine, pentostatin, and rituximab. The workup showed an elevated white blood cell count with atypical lymphocytes, anemia, and thrombocytopenia. A peripheral blood smear confirmed HCL relapse, and a magnetic resonance imaging (MRI) of the brain showed diffuse, nonenhancing masses in the supratentorial and infratentorial regions of the brain. He was initiated on treatment with vemurafenib, with improvements in his white blood cell count and a recovery of his platelet count and hemoglobin. A repeat MRI of the brain after 3 months showed complete resolution of the lesions. Vemurafenib was discontinued after 6 months, with bone marrow biopsy showing no evidence of residual hairy cell leukemia. There have only been limited reports of HCL involvement in the central nervous system in the literature. Due to the rarity of the condition, it is not clear which treatments can be effective for intracranial disease control. Our report shows the successful use of vemurafenib, resulting in complete remission of relapsed HCL with CNS involvement.

Androgen Receptor Signaling in Prostate Cancer and Therapeutic Strategies.

Understanding of the molecular mechanisms of prostate cancer has led to development of therapeutic strategies targeting androgen receptor (AR). These androgen-receptor signaling inhibitors (ARSI) include androgen synthesis inhibitor-abiraterone and androgen receptor antagonists-enzalutamide, apalutamide, and darolutamide. Although these medications provide significant improvement in survival among men with prostate cancer, drug resistance develops in nearly all patients with time. This could be through androgen-dependent or androgen-independent mechanisms. Even weaker signals and non-canonical steroid ligands can activate AR in the presence of truncated AR-splice variants, AR overexpression, or activating mutations in AR. AR splice variant, AR-V7 is the most studied among these and is not targeted by available ARSIs. Non-androgen receptor dependent resistance mechanisms are mediated by activation of an alternative signaling pathway when AR is inhibited. DNA repair pathway, PI3K/AKT/mTOR pathway, BRAF-MAPK and Wnt signaling pathway and activation by glucocorticoid receptors can restore downstream signaling in prostate cancer by alternative proteins. Multiple clinical trials are underway exploring therapeutic strategies to overcome these resistance mechanisms.

Adjuvant therapy for lung neuroendocrine neoplasms.

Pulmonary neuroendocrine neoplasms (NENs) represent a minority of lung cancers and vary from slower growing pulmonary carcinoid (PC) tumors to aggressive small cell lung cancer (SCLC). While SCLC can account for up to 15% of lung cancer, PCs are uncommon and represent about 2% of lung cancers. Surgical resection is the standard of care for early-stage PCs and should also be considered in early stage large cell neuroendocrine carcinoma (LCNEC) and SCLC. Adjuvant treatment is generally accepted for aggressive LCNEC and SCLC, however, less well established for PCs. Guidelines admit a lack of trials to support a high-level recommendation for adjuvant therapy. This manuscript will discuss the role for adjuvant therapy in NENs and review the available literature.

Pituitary apoplexy induced by gonadotropin-releasing hormone (GnRH) agonist administration for treatment of prostate cancer: a systematic review.

OBJECTIVE: We aimed to review of literature on the clinical presentation, management and outcomes of pituitary apoplexy following gonadotrophic release hormone (GnRH) agonist administration for the treatment of prostate cancer. METHODS: We used PRISMA guidelines for our systematic review and included all English language original articles on pituitary apoplexy following GnRH agonist administration among prostate cancer patients from Jan 1, 1995 to Dec 31, 2020. Data on patient demographics, prostate cancer type, Gleason score at diagnosis, history of pituitary adenoma, clinical presentation, GnRH agonist, interval to pituitary apoplexy, laboratory evaluation at admission, radiologic findings, treatment of pituitary apoplexy, time to surgery if performed, pathology findings, and clinical/hormonal outcomes were collected and analyzed. RESULTS: Twenty-one patients with pituitary apoplexy met our inclusion criteria. The mean age of patients was 70 (60-83) years. Leuprolide was the most common used GnRH agonist, used in 61.9% of patients. Median duration to symptom onset was 5 h (few minutes to 6 months). Headache was reported by all patients followed by ophthalmoplegia (85.7%) and nausea/vomiting (71.4%). Three patients had blindness at presentation. Only 8 cases reported complete anterior pituitary hormone evaluation on presentation and the most common endocrine abnormality was FSH elevation. Tumor size was described only in 15 cases and the mean tumor size was 26.26 mm (18-48 mm). Suprasellar extension was the most common imaging finding seen in 7 patients. 71.4% of patients underwent pituitary surgery, while 23.8% were managed conservatively. Interval between symptoms onset to pituitary surgery was 7 days (1-90 days). Gonadotroph adenoma was most common histopathologic finding. Clinical resolution was comparable, while endocrine outcomes were variable among patients with conservative vs surgical management. CONCLUSION: Although the use of GnRH agonists is relatively safe, it can rarely lead to pituitary apoplexy especially in patients with pre-existing pituitary adenoma. Physicians should be aware of this complication as it can be life threatening. A multidisciplinary team approach is recommended in treating individuals with pituitary apoplexy.

Real world clinicopathologic observations of patients with metastatic solid tumors receiving immune checkpoint inhibitor therapy: Analysis from Kentucky Cancer Registry.

The state of Kentucky has the highest cancer incidence and mortality in the United States. High-risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution. Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure was 78.3% and 14.5%, respectively. TP53 (62.3%), CDKN1B/2A (40.5%), NOTCH and PIK3 (33.3%) were the most common alterations in tumors. 67.4% were PDL1 positive and 59.4% had intermediate-high tumor mutational burden (TMB). Median TMB (12.6) was twofold to fourfold compared to clinical trials. The prevalence of mutations associated with smoking, homologous recombinant repair and PIK3/AKT/mTOR pathway mutations was higher compared to historic cohorts. PDL1 expression had no significant effect on radiologic response, but PFS improvement in patients with tumors expressing PDL1 trended toward statistical significance (median 18 vs. 40 weeks. HR = 1.43. 95%CI 0.93, 4.46). Median PFS was higher in the high-TMB cohort compared to low-intermediate TMB (median not reached vs. 26 weeks; HR = 0.37. 95%CI 0.13, 1.05). A statistically significant improvement in PFS was observed in the PIK3 mutated cohort (median 123 vs. 23 weeks. HR = 2.51. 95%CI 1.23, 5.14). This was independent of tumor mutational burden (TMB) status or PDL1 expression status. PIK3 mutants had a higher overall response rate than the wild type (69.6% vs. 43.5%, OR 0.34; p = 0.045). The results should prompt further evaluation of these potential biomarkers and more widespread real-world data publications which might help determine biomarkers that could benefit specific populations.

Reversal of warfarin-coagulopathy: How to improve plasma transfusion practice in a community hospital setting?

BACKGROUND: Plasma is often given inappropriately to reverse warfarin-induced coagulopathy, wasting health-care resources and exposing the patients to transfusion-associated risks. AIMS: The clinical practice at our institution was evaluated in order to reduce the number of unnecessary plasma transfusions. MATERIALS AND METHODS: Retrospective audit of plasma transfusions was done (July 2014 to June 2015). DESIGN: To improve the clinical practice, a two-prong strategy was implemented: (1) in-service was given to clinicians on the warfarin-reversal guidelines and (2) for a 30-day period, plasma orders were placed on the approval list of the Transfusion Medicine Service. RESULTS: Of the 729 units of plasma, 189 (26% of total) were given for the reversal of warfarin-induced coagulopathy. The medical charts of these patients were reviewed: 46 units of plasma (~25%) were given inappropriately (e.g., patients with minimally elevated international normalized ratio, no evidence of bleeding, and no surgery within 24 h). To check the effectiveness of our intervention, two audits of plasma transfusions were done. During the first audit (January 1-February 29, 2016), 24 patients received plasma to reverse warfarin-coagulopathy. Medical chart review revealed that the vast majority of plasma orders (96.66%) followed the guidelines. A second audit was carried out a year later (January 1-March 31, 2017): during this 3-month period, 47 patients were transfused with plasma for warfarin reversal with a 94% adherence to the guidelines. CONCLUSION: We conclude that plasma transfusion practices may be improved by a combination of education and active enforcement of warfarin reversal guidelines.

Fever of Unknown Origin as a Sole Presentation of Subacute Thyroiditis in an Elderly Patient: A Case Report with Literature Review.

An 80-year-old Caucasian male presented with fever of 3-week duration. Outpatient workup for infectious etiologies was negative and due to persistent fever, he was hospitalized for further evaluation of fever of unknown origin (FUO). Physical examination and laboratory studies remained unremarkable; however a follow-up CT scan of chest, abdomen, and pelvis with contrast done to rule out malignancy as an underlying cause of FUO revealed heterogeneous thyroid gland with surrounding hazy changes suggestive of thyroiditis. Thyroid function tests confirmed the diagnosis of subacute thyroiditis. The patient was started on prednisone with good response in his symptoms and was eventually discharged to home. The importance of our case lies in the fact that diagnosing subacute thyroiditis in the absence of classical symptoms of neck pain can be challenging and a physician should have a very high index of suspicion especially in an elderly patient where FUO can be the sole presentation.

Cardiovascular effects of Hodgkin's lymphoma: a review of literature.

Hodgkin's lymphoma (HL) constitutes 0.6% of all the cancers diagnosed worldwide and 10% of all lymphomas. Ten-year survival rate for HL is estimated to be 80% and cardiovascular death is the prevalent cause for a non-malignant death among these HL survivors. We are reviewing the cardiovascular morbidities associated with Hodgkin's lymphoma from the available literature. We performed a systematic review of all articles published from January 1, 1960 to October 1, 2016 on the MEDLINE database using PubMed search engine. Key factors in the diagnosis and management of these conditions are discussed in individual sections.

Systemic Amyloidosis and Cardiac Autonomic Neuropathy Associated with Waldenstrom's Macroglobulinemia.

A 73-year-old male with long-standing Waldenstrom's macroglobulinemia complicated with systemic amyloidosis presented with a witnessed syncopal episode. He had complaints of orthostatic dizziness and palpitations for few months. Orthostatic hypotension and peripheral neuropathy were demonstrated on physical examination. EKG, 24-hour Holter monitoring, and 2D echocardiogram were unremarkable. MRI of the brain ruled out stroke. Patients with amyloidosis can develop cardiovascular disease through amyloid cardiomyopathy, small vessel disease, conduction defects, pericardial effusion, or autonomic denervation. After ruling out other life-threatening causes, Ewing's battery of tests was done to rule out cardiac autonomic neuropathy. Two heart rate tests and one blood pressure test were abnormal which indicated severe cardiac autonomic neuropathy. Cardiac autonomic neuropathy can mask symptoms of acute coronary syndrome and hence early diagnosis using the simple bedside maneuver is beneficial. The test is also important for prognostication. Absence of augmentation of cardiac output from inadequate autonomic stimulation will lead to postural hypotension, exercise intolerance, and tachycardia. There may be no change in heart rate with Valsalva or deep breathing both of which increase parasympathetic tone. As the condition progresses, it may result in cardiac denervation which can result in silent myocardial infarction, syncope, and sudden death.