To be or not to be a case of heparin resistance.

Heparin resistance can be defined as high doses of unfractionated heparin (UFH), greater than 35,000 IU/day, required to raise the activated partial thromboplastin time (aPTT) and activated coagulation time (ACT) to within therapeutically desired ranges or the impossibility of doing so. The most common pathology responsible is the deficiency of anti-thrombin III (ATIII) deficiency. Other clinically relevant conditions that can present with heparin resistance are congenital deficiencies; use of high doses of heparin during extracorporeal circulation, use of asparaginase therapy and disseminated intravascular coagulation (DIC). Most of these conditions effect the ATIII levels. Patients are typically identified in an acute phase, when determination of the cause of resistance is challenging. We present a case where a patient presented with suspected heparin resistance in an acute phase of sickness, where timely intervention was able to prevent a potentially fatal situation. Abbreviations: Neuroendocrine tumors (NETs), World health Organization (WHO), Radiation therapy (RT).

A case of madness resulting in a fortunate outcome; case report of a psychotic break as a result of cortisol secreting thymic neuroendocrine thymic tumor.

Representing a mere 2-5% of the total thymic malignancies and 0.4% of total carcinoid tumors, primary thymic neuroendocrine tumors (NETs) are the zebras of the thymic neoplasms. They were initially characterized as 'epithelial thymomas'; later, the term carcinoid tumors was coined by Rosai and Higa. These tumors are highly unpredictable in their presentation and prognosis. Coupled with variable clinical presentation, rare pathologic diagnosis and absence of diagnostic and prognostic parameters, it is a challenge for both patients and clinicians. Treatment entails local definitive therapy, symptom control and systemic chemoradiation given either pre or post operatively based on staging and resectability. We hereby report a peculiar case of psychosis that likely resulted from one such rare tumor.

Survival trends among patients with metastatic melanoma in the pretargeted and the post-targeted era: a US population-based study.

In 2011, ipilimumab was approved by the US Food and Drug Administration (FDA) for metastatic melanoma. Since its approval, numerous targeted therapies have been approved by the FDA. Population-based studies assessing the survival benefit from these agents are lacking. We therefore carried out this study to compare the 1-year, 2-year, and median overall survival (OS) among metastatic melanoma patients in pretargeted and post-targeted eras. This is a retrospective study that utilized the Surveillance, Epidemiology, and End Results (SEER-18) database, version 8.3.4 (22 March 2017). The patient groups were defined as the pretargeted era (2004-2010) and the post-targeted era (2011-2014) as ipilimumab was approved by the FDA in 2011. The database comprised of 5471 patients (3314 in the pretargeted era and 2157 in the post-targeted era). OS in the post-targeted era was found to be significantly better compared with the pretargeted era by Kaplan-Meier curve (1-year OS: 38.9 vs. 36.8%, 2-year OS: 28.3 vs. 23.5%, and median survival: 8 vs. 7 months, P=0.001 by the log-rank test). The survival was significantly better in the post-targeted era compared with the pretargeted era on multivariate analysis using a Cox proportional hazard model after adjusting for age, sex, race, and metasectomy status (adjusted hazard ratio of 0.889, 95% CI: of 0.832-0.951, P=0.001). There is significant survival benefit in metastatic melanoma patients since the introduction of immune checkpoint-blocking agents.

Analysis of Efficacy and Tolerability of Bruton Tyrosine Kinase Inhibitor Ibrutinib in Various B-cell Malignancies in the General Community: A Single-center Experience.

BACKGROUND: Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), is a novel drug that has shown significant efficacy and survival benefit for treatment of various B-cell malignancies. The primary objective of the present study was to investigate the efficacy of ibrutinib therapy in various B-cell malignancies in the general community. The secondary objectives included studying the adverse effects, ibrutinib-induced peripheral lymphocytosis, and effect on immunoglobulin levels. PATIENTS AND METHODS: The present study was a retrospective observational cohort analysis conducted at Abington Jefferson Health. The clinical response was determined from the hematologist's assessment and evaluated independently using the response criteria for each B-cell malignancy. Adverse effects were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The Wilcoxon signed-rank test was used to compare immunoglobulin levels before and after ibrutinib. Forty five patients with B-cell malignancies and receiving ibrutinib therapy were eligible. RESULTS: The median age was 73 years (range, 49-96 years), and 84.4% of the patients had received ≥ 1 previous therapy. The best overall response rate of all cohorts combined was 63.8%. The greatest overall response rate was observed in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (76.1%), followed by those with Waldenström macroglobulinemia (75%). Of the 45 patients, 88.9% experienced adverse effects. Antiplatelet activity of ibrutinib was most commonly observed (30.5%). Of note, 5 patients (11%) developed new-onset atrial fibrillation after drug initiation. Peripheral lymphocytosis after drug initiation was observed in most patients, with a peak level at 1 month (median lymphocyte count, 2.7 × 103 cells/µL). Although the IgG levels at 3, 6, and 12 months had decreased (P = .01 for all) compared with the levels before ibrutinib, the IgA levels had not increased at 3, 6, 12, and 24 months (P = .6, P = .5, P = .3, and P = .9, respectively). CONCLUSION: Ibrutinib is a highly effective and tolerable drug for B-cell malignancies in the general community. In contrast to the previously reported rate of 5% to 7%, we observed a higher rate (11%) of atrial fibrillation, which might have resulted from the smaller sample size in the present study and the multiple comorbidities. Nonetheless, this treatment-limiting side effect requires further elucidation. Paradoxical lymphocytosis at the outset of therapy was a common and benign finding. In conjunction with the reported trials, the IgG levels decreased in the first year of continued therapy. However, the IgA levels did not increase, even after 2 years of therapy.

The tell-tale heart: A case of recurrent vulvar carcinoma with cardiac metastasis and review of literature.

A 50-year-old female was diagnosed with vulvar cancer treated with left partial vulvectomy and bilateral lymphadenectomy. Ten months after her surgery, she presented with increased labial swelling, pain and discharge. Biopsy confirmed recurrence of squamous cell vulvar carcinoma. Incidentally, on restaging radiographic scans, she was found to have a large right ventricular mass which, after surgical debulking, was shown to be a squamous cell cancer of vulvar origin. She was commenced on chemotherapy with carboplatin and paclitaxel along with concurrent radiation therapy. Restaging PET scan showed persistent metastatic disease. She was switched to Cisplatin/Taxol after having hypersensitivity reaction to Carboplatin. She received 5 cycles with progression of disease in the follow up scans. She then received Nivolumab for 2 cycles. The patient then opted for comfort directed care given worsening functional status and progression of disease on repeat imaging. Secondary cardiac tumors are very rare and not extensively studied in oncology. Therefore, optimal management is not entirely clear. It is extremely rare for vulvar cancer to metastasize to the heart and only two cases have been reported in the literature. However, vulvar cancer metastasizing to the right ventricular cavity and endocardium has not been described before. We believe that this is the first ever such reported case.

Casual or Causal? Two Unique Cases of Hodgkin's Lymphoma: A Case Report and Literature Review.

BACKGROUND Immunosuppressive diseases and therapies have long been connected to risk of malignancies, especially lymphoma. With some diseases and drugs, the association is well established but the data is mostly anecdotal because of the rarity of the situation. CASE REPORT We present 2 rare cases. The first patient had psoriasis, was on etanercept, and developed Hodgkin's lymphoma. This case is rare because psoriasis and etanercept do not usually cause lymphoma, and if they do, it is predominantly Epstein-Barr virus-positive non-Hodgkin's lymphoma. The second patient had acquired immune deficiency syndrome (AIDS) and developed Hodgkin's lymphoma while on highly active antiretroviral therapy (HAART). This case is rare because AIDS mostly causes Kaposi's sarcoma or non-Hodgkin's lymphoma due to immunosuppression, but whether it is AIDS or HAART therapy that leads to development of Hodgkin's lymphoma in these patients is not clear. CONCLUSIONS Immunosuppression seems to be the primary culprit leading to lymphomas in these cases. The exact mechanism is still not completely understood.

Continuous diphenhydramine infusion and imatinib for KIT-D816V-negative mast cell activation syndrome: a case report.

BACKGROUND: We present the first full case report of the treatment of mast cell activation syndrome with continuous diphenhydramine infusion, which resulted in the improvement of anaphylactic reactions and a decrease in hospital readmission. Furthermore, the patient received imatinib in the absence of the KIT-D816V mutation, which led to further improvement of quality of life. Currently, we are trying to wean this patient off diphenhydramine; if successful, this attempt will represent the first reported case. CASE PRESENTATION: An 18-year-old white girl presented with a flare of mast cell activation syndrome and received epinephrine and steroids. She had failed multiple previous therapies, and her quality of life was affected due to two to three flares/week. She was started on continuous diphenhydramine infusion and imatinib, which led to a decrease in hospital admissions and marked improvement in her quality of life. CONCLUSIONS: Continuous diphenhydramine infusion can provide promising outcomes following the failure of intermittent antihistamine dosing in patients with severe mast cell activation syndrome. Initiating continuous diphenhydramine infusion may be helpful in an intensive care setting when the patient is particularly prone to anaphylaxis and/or the resources needed to manage anaphylaxis are not available outside the intensive care unit. Furthermore, imatinib provides benefits in KIT-D816V-negative mast cell disorders due to other unknown mutations.

Guillain-Barré syndrome occurring synchronously with systemic lupus erythematosus as initial manifestation treated successfully with low-dose cyclophosphamide.

Systemic lupus erythematous (SLE) is frequently encountered in clinical practice; a widespread immunological response can involve any organ system, sometimes leading to rare and diagnostically challenging presentations. We describe a 38-year-old female who presented with symmetric numbness and tingling of the hands and feet, and cervical pain. Imaging studies were not diagnostic of any serious underlying pathology. The patient developed ascending paresis involving lower extremities and cranial muscles (dysphagia and facial weakness). Guillain-Barré syndrome (GBS) was diagnosed on the basis of electromyography and lumbar puncture showing albuminocytologic dissociation. Intravenous immunoglobulins (IVIG) were administered for 5 days. Supported by anti-dsDNA antibody, oral ulcers, proteinuria of 0.7 g in 24 h, and neurological manifestation, she was diagnosed with lupus. After completion of IVIG, she received pulse-dose corticosteroids and one dose of low-dose cyclophosphamide. Her neurological symptoms improved and she had complete neurological recovery several months after her initial presentation. Literature search provides evidence of co-occurrence of lupus and GBS occurring mostly later in the course of the disease. However, GBS as initial manifestation of SLE is exceedingly rare and less understood. The association of GBS with lupus is important to recognize for rapid initiation of appropriate therapy and for consideration of immunosuppressive therapy which may affect the outcome.