Myeloproliferative Neoplasms: Contemporary Review and Molecular Landscape.

Myelofibrosis (MF), Myeloproliferative neoplasms (MPNs), and MDS/MPN overlap syndromes have a broad range of clinical presentations and molecular abnormalities, making their diagnosis and classification complex. This paper reviews molecular aberration, epigenetic modifications, chromosomal anomalies, and their interactions with cellular and other immune mechanisms in the manifestations of these disease spectra, clinical features, classification, and treatment modalities. The advent of new-generation sequencing has broadened the understanding of the genetic factors involved. However, while great strides have been made in the pharmacological treatment of these diseases, treatment of advanced disease remains hematopoietic stem cell transplant.

A Case Report of Refractory Diffuse Alveolar Hemorrhage as a Complication of Antiphospholipid Syndrome and Review of Its Management.

Diffuse alveolar hemorrhage is a rare complication of antiphospholipid syndrome with high mortality rates. Early diagnosis and treatment with steroids and immunosuppressive agents, along with the achievement of hemostasis and hemodynamic stability, is critical to improving outcomes. This case demonstrates the complexity of managing refractory diffuse alveolar hemorrhage in a 48-year-old woman with antiphospholipid syndrome requiring treatment with high-dose corticosteroids, rituximab, and cyclophosphamide.

Peripheral T-Cell Lymphoma in a Patient Previously Diagnosed With Sarcoidosis.

Sarcoidosis is a multisystem disorder characterized by granulomatous inflammation on histopathological evaluation. Diagnosis of sarcoidosis requires thorough elimination of malignancy and alternative causes of noncaseating granulomatous inflammation. Sarcoidosis and several subtypes of lymphoma have similar clinical presentations and can potentially have similar histopathological findings. Patients with a histopathology-confirmed diagnosis of sarcoidosis are at higher risk of developing malignancies. In this report, we present a case of a 64-year-old male diagnosed with sarcoidosis 2 years before presenting to the emergency department with a 4-month history of generalized weakness, cough, and very high fever. After a thorough workup involving cervical lymph node biopsy and bone marrow biopsy, he was diagnosed with peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS). Due to the patient's current lymphoma diagnosis and features noted on pathology, a retrospective review of the prior biopsy specimen was performed, finding similar hematopathological features on both initial lymph node biopsy diagnosing sarcoidosis and current biopsies diagnosing lymphoma. Given these findings, our patient likely had early manifestation of PTCL misdiagnosed as sarcoidosis. In summary, lymphoma should be considered in all patients with suspected sarcoidosis, especially those who do not respond to treatment or who present with persistent hematological abnormalities.

Leukemic stem cells and advances in hematopoietic stem cell transplantation for acute myeloid leukemia: a narrative review of clinical trials.

Objective: The purpose of this literature review is to summarize and provide a brief overview of our current understanding of acute myeloid leukemia (AML) and the role of stem cell transplantation (SCT) in its management. Background: AML is a malignant hematological disorder that is characterized by the uncontrolled proliferation of myeloid blood cells. This disease has been associated with various risk factors such as ionizing radiation, cigarette smoke, pesticides/herbicides, and chemotherapy. SCT remains the most beneficial treatment for medically fit AML patients due to superior survival outcomes. Methods: A thorough search was conducted on PubMed, Scopus, ClinicalTrials.gov, Embase and Web of Science using related keywords. Current articles on the uses of stem cell therapy in AML patients were selected. Conclusions: Long term exposure to ionizing radiation and other harmful substances such as benzene, cigarette smoke and chemotherapeutic drugs plays an important role in AML carcinogenesis. Mutations in certain genes (e.g., ASXL1, RUNX1, KIT, TP53, BCR-ABL1) seem to accelerate the process as they affect normal cellular proliferation and cell death. These events may give rise to a small subpopulation of leukemic stem cells (LSC) which continuously sustain tumor development and growth. Patients who are deemed to be medically "fit" should receive an allogenic hematopoietic stem cell transplantation (allo-HSCT) due to improved overall survival (OS) (~50%) and decreased relapsed risk (32% vs. 59%). Several studies have revealed that the medically "unfit" may benefit from more conventional agents such as azacytidine, decitabine, venetoclax or sorafenib.

Cholangiocarcinoma: a review of the literature and future directions in therapy.

Cholangiocarcinomas (CCA) are a group of rare cancers with an incidence of about 1.26 per 100,000 people. The disease reflects one of three different subtypes: intrahepatic, perihilar or hilar and distal cholangiocarcinoma. The preferred modality of definitive therapy is surgical resection with or without adjuvant therapy, however the majority of patients with this disease do not present at an early stage. Some efforts to improve survival rates have come in the form of offering neoadjuvant therapy prior to surgical resection or liver transplantation. Some new protocols are in the process of development for neoadjuvant therapy. Despite advancements in locally advanced or borderline resectable lesions, most patient present at an advanced stage. The mainstay of treatment for advanced stage disease is chemotherapy regardless of location. The mainstay of treatment in fit patients is the combination of gemcitabine and cisplatin. The addition of nab-paclitaxel to this backbone is currently being evaluated in phase III trial. In addition, the role of targeted therapy is currently being studied extensively through multiple different mutational pathways including isocitrate dehydrogenase-1 (IDH1), fibroblast growth factor receptor (FGFR), epidermal growth factor receptor (EGFR) and ERBB2 (HER2/neu). CCA remains a significant challenge in medicine, however recent studies have shown that there is significant interest in advancing therapy in the form of neoadjuvant, adjuvant and palliative intent treatment.

A Case of Myeloid Sarcoma following Allogeneic HSCT Presenting as Localized Hip Pain.

Myeloid sarcoma is a rare variant of acute myeloid leukemia (AML) which presents as an extramedullary soft tissue mass. Due to the rarity of this disease, along with nonspecific presenting symptoms, diagnosis can be delayed or missed without a high index of suspicion. In this case, we discuss a patient diagnosed with AML relapse in the form of myeloid sarcoma two years after allogeneic hematopoietic stem cell transplant (alloHSCT) for myelodysplastic syndrome (MDS) with the initial presentation for back pain misdiagnosed as spinal stenosis. This case report aims to help healthcare providers in recognizing the early signs and symptoms of this disorder as well as provide information in regards to treatment options and risk assessment.

Rare side effect of adjuvant ipilimumab after surgical resection of melanoma: Guillain-Barré syndrome.

Guillain-Barré syndrome is a life-threatening neurological disorder that presents with rapid ascending paralysis and areflexia. Guillain-Barré syndrome is traditionally associated with infections from a gastrointestinal or respiratory tract source. We report the case of a 71-year-old man with melanoma who was treated with ipilimumab as adjuvant immunotherapy and subsequently developed Guillain-Barré syndrome. The diagnosis was made clinically through physical exam findings. He was successfully treated with a combination of intravenous immunoglobulin therapy and corticosteroids.

A Review of Autologous Stem Cell Transplantation in Lymphoma.

PURPOSE OF REVIEW: Chemotherapy remains the first-line therapy for aggressive lymphomas. However, 20-30% of patients with non-Hodgkin lymphoma (NHL) and 15% with Hodgkin lymphoma (HL) recur after initial therapy. We want to explore the role of high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) for these patients. RECENT FINDINGS: There is some utility of upfront consolidation for-high risk/high-grade B-cell lymphoma, mantle cell lymphoma, and T-cell lymphoma, but there is no role of similar intervention for HL. New conditioning regimens are being investigated which have demonstrated an improved safety profile without compromising the myeloablative efficiency for relapsed or refractory HL. Salvage chemotherapy followed by HDT and rescue autologous stem cell transplant remains the standard of care for relapsed/refractory lymphoma. The role of novel agents to improve disease-related parameters remains to be elucidated in frontline induction, disease salvage, and high-dose consolidation or in the maintenance setting.

Man's best friend: How humans can develop Dirofilaria immitis infections.

Canine heartworm, Dirofilaria immitis, is a nematode parasite that infects dogs by way of mosquito bite. Rarely, humans play accidental hosts to this parasite and are not a suitable environment for the nematode to live. As the parasite dies in the pulmonary vessels it embolizes the vessels causing infarction and eventual nodule formation in the lungs. In the right clinical context, a nodule can be considered malignant prompting invasive tissue sampling. We describe a case of a 48-year-old man who was found to have multiple asymptomatic scattered pulmonary nodules during imaging workup for an insulinoma. Fine needle biopsy of the largest nodule revealed a necrotic granuloma, lab testing and culture ruled out fungal and bacterial causes. Clinically, this picture was consistent with D. immitis infection.

Kytococcus schroeteri Bacteremia in a Patient with Hairy Cell Leukemia: A Case Report and Review of the Literature.

The Kytococcus genus formerly belonged to Micrococcus. The first report of a Kytococcus schroeteri infection was in 2002 in a patient diagnosed with endocarditis. We report a case of central line associated Kytococcus schroeteri bacteremia in a patient with underlying Hairy Cell Leukemia. Kytococcus schroeteri is an emerging infection in the neutropenic population and in patients with implanted artificial tissue. It is thought to be a commensal bacterium of the skin; however, attempts to culture the bacteria remain unsuccessful. There have been a total of 5 cases (including ours) of K. schroeteri bacteremia in patients with hematologic malignancies and neutropenia and only 18 documented cases in any population. Four of the cases of bacteria in neutropenic patients have been fatal, but early detection and treatment could make a difference in clinical outcomes.

Mycobacterium avium-intracellulare brain abscesses in an HIV-infected patient.

The Mycobacterium avium-intracellulare complex (MAC) is an uncommon cause of brain abscesses even in patients with acquired immunodeficiency syndrome (AIDS). We present a case of a multiple MAC brain abscesses, confirmed by brain biopsy and culture, in a patient with AIDS. The patient's initial symptoms were weakness, confusion and headaches. The patient was initially treated for toxoplasmosis and pyogenic bacterial brain abscesses with no resolution. Following treatment for MAC the patient's abscesses resolved.

Mnemonic strategy training improves memory for object location associations in both healthy elderly and patients with amnestic mild cognitive impairment: a randomized, single-blind study.

OBJECTIVE: To evaluate the efficacy of mnemonic strategy training versus a matched-exposure control condition and to examine the relationship between training-related gains, neuropsychological abilities, and medial temporal lobe volumetrics in patients with amnestic mild cognitive impairment (aMCI) and age-matched healthy controls. METHOD: Twenty-three of 45 screened healthy controls and 29 of 42 screened patients with aMCI were randomized to mnemonic strategy or matched-exposure groups. Groups were run in parallel, with participants blind to the other intervention. All participants completed five sessions within 2 weeks. Memory testing for object-location associations (OLAs) was performed during sessions one and five and at a 1-month follow-up. During Sessions 2-4, participants received either mnemonic strategy training or a matched number of exposures with corrective feedback for a total of 45 OLAs. Structural magnetic resonance imaging was performed in most participants, and medial temporal lobe volumetrics were acquired. RESULTS: Twenty-one healthy controls and 28 patients with aMCI were included in data analysis. Mnemonic strategy training was significantly more beneficial than matched exposure immediately after training, p = .006, partial η2 = .16, and at 1 month, p < .001, partial η2 = .35, regardless of diagnostic group (healthy group or aMCI group). Although patients with aMCI demonstrated gains comparable to the healthy control groups, their overall performance generally remained reduced. Mnemonic strategy-related improvement was correlated positively with baseline memory and executive functioning and negatively with inferior lateral ventricle volume in patients with aMCI; no significant relationships were evident in matched-exposure patients. CONCLUSION: Mnemonic strategies effectively improve memory for specific content for at least 1 month in patients with aMCI.

Where did I put that? Patients with amnestic mild cognitive impairment demonstrate widespread reductions in activity during the encoding of ecologically relevant object-location associations.

Remembering the location of objects in the environment is both important in everyday life and difficult for patients with amnestic mild cognitive impairment (aMCI), a clinical precursor to Alzheimer's disease. To test the hypothesis that memory impairment for object location in aMCI reflects hippocampal dysfunction, we used an event-related functional magnetic resonance imaging paradigm to compare patients with aMCI and healthy elderly controls (HEC) as they encoded 90 ecologically relevant object-location associations (OLAs). Two additional OLAs, repeated a total of 45 times, served as control stimuli. Memory for these OLAs was assessed following a 1-h delay. The groups were well matched on demographics and brain volumetrics. Behaviorally, HEC remembered significantly more OLAs than did aMCI patients. Activity differences were assessed by contrasting activation for successfully encoded Novel stimuli vs. Repeated stimuli. The HEC demonstrated activity within object-related (ventral visual stream), spatial location-related (dorsal visual stream), and feature binding-related cortical regions (hippocampus and other memory-related regions) as well as in frontal cortex and associated subcortical structures. Activity in most of these regions correlated with memory test performance. Although the aMCI patients demonstrated a similar activation pattern, the HEC showed significantly greater activity within each of these regions. Memory test performance in aMCI patients, in contrast to the HEC, was correlated with activity in regions involved in sensorimotor processing. We conclude that aMCI patients demonstrate widespread cerebral dysfunction, not limited to the hippocampus, and rely on encoding-related mechanisms that differ substantially from healthy individuals.