T-Cell Acute Lymphoblastic Leukemia-Current Concepts in Molecular Biology and Management.

T-cell acute lymphoblastic leukemia (T-ALL) is an uncommon, yet aggressive leukemia that accounts for approximately one-fourth of acute lymphoblastic leukemia (ALL) cases. CDKN2A/CDKN2B and NOTCH1 are the most common mutated genes in T-ALL. Children and young adults are treated with pediatric intensive regimens and have superior outcomes compared to older adults. In children and young adults, Nelarabine added to frontline chemotherapy improves outcomes and end of consolidation measurable residual disease has emerged as the most valuable prognostic marker. While outcomes for de-novo disease are steadily improving, patients with relapsed and refractory T-ALL fare poorly. Newer targeted therapies are being studied in large clinical trials and have the potential to further improve outcomes. The role of allogeneic stem cell transplant (HSCT) is evolving due to the increased use of pediatric-inspired regimens and MRD monitoring. In this review we will discuss the biology, treatment, and outcomes in pediatric and adult T-ALL.

Metastatic Malignant Paraganglioma Presenting as a Neck Mass Treated with Radiolabeled Somatostatin Analog.

Paragangliomas are rare neuroendocrine tumors that arise from chromaffin-containing tissue. Surgical resection and/or radiation are used for locoregional disease, and reduction of tumor burden with systemic therapy is reserved for metastatic disease. Iobenguane I-131, somatostatin analog (octreotide), and Sunitinib are noncytotoxic options for treatment, while cyclophosphamide, vincristine, and dacarbazine (CVD) and temozolomide are often used as initial chemotherapy options as studies have shown that they offer some tumor response. However, there are no randomized clinical trials demonstrating prolonged survival with the use of chemotherapeutics in metastatic cases. Investigation of alternative therapies that provide survival benefit is thus necessary. We present a case of a 69-year-old female with metastatic malignant paraganglioma presenting as a left parapharyngeal neck mass, which metastasized after surgery, requiring radiation therapy for bony metastasis who was treated with a radioisotope somatostatin analog for disease progression.

How Should We Assess Pain: Do Patients Prefer a Quantitative or Qualitative Scale? A Study of Patient Preferences.

BACKGROUND: Pain perception is a subjective experience and is influenced by a variety of factors. Pain assessment tools, included the numeric pain rating scale (NRS) and the visual analog scale (VAS). A VAS qualitative (VASQ) scale asks patients their current pain level along a continuum of "Good Day," "Average Day," or "Bad Day." We had patients complete both scales and asked them their preference and reason for their choice. METHODS: We identified patients 18 years of age and older, seen by Palliative medicine at Geisinger, who had cancer-associated pain of at least one-month duration. Patients filled out the study questionnaire composed of 2 questions. Characteristics of patients who preferred the VASQ were compared to those who preferred the NRS using a 2-sample t tests or Wilcoxon rank-sum tests and Pearson χ2 or Fisher exact tests. The relationship between the NRS and the VASQ used the Pearson correlation coefficient. RESULTS: One hundred forty-six patients completed the questionnaire, 52.1% were female; 63.7% preferred the NRS, 31.5% preferred the VASQ. Patients who preferred the NRS reported a higher NRS rating than patients who preferred the VASQ (mean NRS rating of 6.0 compared to 5.3) but the difference was not statistically significant (P = .1531). Visual analog scale qualitative ratings were higher among patients who preferred the NRS, but the difference was not statistically different (mean rating of 5.2 vs 4.8, P = .3669). CONCLUSION: Patients preferred the NRS over VASQ for pain assessment. Patients tend to rate their pain at a higher level when using NRS compared to VASQ.

Myelodysplastic Syndrome with Transfusion Dependence Treated with Venetoclax.

Myelodysplastic syndromes are characterized by ineffective hematopoiesis in one or more lineages of the bone marrow. They are a group of heterogeneous clonal stem cell malignancies with a high risk to progress to acute myeloid leukemia. Currently, there are no curative FDA-approved medications for myelodysplastic syndromes. Hematopoietic cell transplantation is potentially the only curative option; however, treatment is often unavailable due to age and comorbidities. Hypomethylating agents, azacitidine and decitabine, and the immunomodulatory agent, lenalidomide, are the only FDA approved medications for the treatment of MDS, all of which are noncurative. Venetoclax, an inhibitor of the antiapoptotic protein BCL-2 used to treat chronic lymphocytic leukemia, is currently being evaluated in clinical trials as a monotherapy in high-risk myelodysplastic syndromes/acute myeloid leukemia. We present a patient with transfusion-dependent myelodysplastic syndromes refractory to the current standard of care treatment not a candidate for hematopoietic cell transplantation who responded well to monotherapy treatment with venetoclax and has since remained transfusion-independent.

Opioid-Related Sleep-Disordered Breathing: An Update for Clinicians.

Opioids are an effective treatment for patients with intractable pain. Long-term administration of opioids for pain relief is being delivered by an increasing number of medical providers in the United States including primary care physicians and nonspecialists. One common complication of chronic opioid use is sleep-disordered breathing which can result in various morbidities as well as an increase in all-cause mortality. It is important for providers to understand the relationship between opioids and sleep-disordered breathing as well as methods to improve diagnosis and strategies for treatment. This review aims to update clinicians on the mechanism, diagnosis, and treatment of opioid-related sleep-disordered breathing in order to improve the quality of care for patients with chronic pain.

Cancer-Related Fatigue: Perception of Effort or Task Failure?

CONTEXT: Patient's rating of perceived effort (RPE) is used to assess central fatigue. Cancer-related fatigue (CRF) is believed to be of central origin. The increased RPE with a motor task, such as the Finger-Tapping Test (FTT), can easily be measured in the clinical setting. OBJECTIVES: To correlate the FTT, RPE and the Brief Fatigue Inventory (BFI) rated fatigue severity in patients with cancer. METHODS: Subjective fatigue was assessed in adult patients with cancer by the BFI. Participants performed a modified FTT with the index finger of the dominant hand: 15 seconds × 2, 30 seconds × 2, and 60 seconds × 2 with 1 minute of rest between each time trial. Rating of perceived effort at the end of task was measured by the Borg 10 scale. EXCLUSIONS: Brain metastasis, history of brain radiation, Parkinson disease, Huntington Chorea, multiple sclerosis, delirium, and depression. Pearson correlation coefficients were used to describe the relationships between BFI, FTT, and Borg 10 scale. RESULTS: Thirty patients participated. Mean age was 56.2. Sixteen were females (53.3%). The mean BFI mean was 4.1, median 4.4. Tapping rate did not correlate with fatigue severity. The RPE correlated with the mean BFI: r s 0.438, P = .0155. These correlations persisted after adjustment for age. CONCLUSION: An increased RPE in the absence of task failure suggests that the origin of CRF is central. The performance of an FTT with RPE helps to improve our understanding of fatigue in the clinical setting.

Pulmonary Haemosiderosis Secondary to Hereditary Haemochromatosis; a Case Report.

Introduction: Hereditary haemochromatosis (HH) is an autosomal recessive disease of increased intestinal absorption of iron, leading to accumulation in tissues which may progress to organ damage, most commonly in the liver. Iron deposition in the liver can lead to cirrhosis and hepatocellular carcinoma. Other common manifestations of haemochromatosis include diabetes, bronzing of the skin, arthropathy and cardiomyopathy. Here, we describe a case of pulmonary haemosiderosis secondary to HH. Case Description: A 49-year-old male with no medical history or family history of iron overload presented with fatigue, shortness of breath and chest pain after a recent finding of elevated ferritin. The patient was found to have biallelic C282Y mutations of the human homeostatic iron regulator protein (HFE) protein and after further workup with laboratory tests and imaging was diagnosed with HH with secondary pulmonary haemosiderosis. The patient is receiving twice weekly phlebotomies and has had an overall improvement in his symptoms. Practical Implications: The presentation of haemochromatosis can vary widely depending on the severity of iron overload and the presence of conditions that predispose organ dysfunction. Pulmonary haemosiderosis is a very rare manifestation of HH. This report illustrates the various manifestations of this disease and provides insight into this rare presentation to improve the diagnosis of this disease.

Prostate cancer leading to monoclonal gammopathy of undetermined significance: A case report.

Prostate cancer is one of the most common cancer types, affecting millions of individuals worldwide. The present study reported two cases of metastatic prostate cancer presenting with newly diagnosed monoclonal gammopathy of undetermined significance (MGUS). To the best of our knowledge, prostate cancer leading to MGUS has not been documented previously. MGUS is generally thought to be benign and has been demonstrated to convert into multiple myeloma (MM), as well as other lymphoproliferative disorders. Due to the high mortality rate associated with MM, further studies are required to confirm and clarify the association between prostate cancer and MGUS. Additionally, patients can be counseled on the requirement for follow up studies following a diagnosis of prostate cancer.

Mixed Adenocarcinoid Tumor Presenting as Acute Appendicitis.

Mixed adenocarcinoid tumors are not uncommon neoplasms of appendix. The clinical presentation of these tumors is often similar to that of acute appendicitis or may present as asymptomatic. These tumors are found incidentally during histopathological examination of the resected appendix following appendectomy or other abdominal procedures. Mixed adenocarcinoids usually behave as adenocarcinomas with rapid metastasis, so prognosis depends upon how aggressive the tumor behaves. The present study reports a case of a 53-year-old male who presented with abdominal pain and fever for 1 day and underwent successful appendectomy and recovered later. Subsequently, a mixed adenocarcinoma with carcinoid features of the appendix was diagnosed by histopathological examination. Follow-up examination of the patient in 3 months revealed metastasis of carcinoma to the peritoneum with adenocarcinoma features.

Normal Pressure Hydrocephalus in a Human Immunodeficiency Virus Type 1 Patient.

Normal pressure hydrocephalus (NPH) is a relatively common disease of adulthood characterized by a typical combination of clinical and radiological findings. In this report, we discuss a 54-year-old female presenting with symptoms suggestive of NPH and found to have a history of human immunodeficiency virus (HIV) type 1. She was not treated as she was in denial state and developed NPH as a possible complication. In the literature, there has only been one reported case of HIV type 2 causing NPH; however, no relationship has been properly documented with HIV type 1. These findings bring about a question on whether NPH is associated or a complication of HIV with awareness of this association. Earlier screening of HIV can be done in patients presenting with such symptoms, thus to prevent further progression of its complications.

Pericardial Metastasis Induced Tamponade from Urothelial Carcinoma: A Rare Entity.

Urothelial carcinoma in a few cases may result in cardiac metastasis. A rare presentation of this condition is its diagnosis as a result of cardiac tamponade. Tamponade is an unusual entity as a result of urothelial carcinoma and has only been reported in four cases. There have also been only a total of fifteen cases of cardiac metastasis from this form of malignancy. It is through this discussion that we emphasize the importance of early detection and monitoring of cardiac symptoms with the implementation of echocardiogram imaging. Although not feasible in all patients it may be considered in those presenting with cardiac and pulmonary symptoms. In this case we discuss the presentation of a 71-year-old gentleman with a history of urothelial carcinoma after cystectomy and while on chemotherapy presented with new onset atrial fibrillation and later was diagnosed with cardiac tamponade as a result of malignant metastasis.

Thoracic Actinomycosis: A Rare Occurrence.

Actinomyces israelii is a branching anaerobic bacilli microorganism that can be identified as normal flora throughout various portions of the human alimentary canal. It is crucial to establish a diagnosis as treatment will vary depending on the clinical form of the disease. We report a case of a 78-year-old man who initially presented with an acute onset of respiratory distress displayed contrast leakage on computed tomography from the site of a previously inserted esophageal stent for an unsuccessful surgical repair of an esophageal rupture. In addition to the contrast leakage, the presence of a bronchopulmonary fistula imaging prompted the need for further investigation. Our patient was empirically treated with antibiotics and obtained blood cultures, which returned positive A. israelii.

Cocaine-Induced Delayed Myocardial Infarction Complicated by Apical Thrombus.

It is well demonstrated in the literature that cocaine use has been well linked to the formation of various forms of acute and chronic cardiovascular problems including but not limited to acute coronary syndromes. However, cocaine has been commonly associated with coronary vasospasms and less commonly with myocardial infarction and the formation of atrial thrombus. Through this case presentation, we illustrate the findings of a 35-year-old gentleman with history of cocaine use presenting with acute coronary syndrome and complicated by thrombus formation. Furthermore, through this report, we illustrate in a patient with no other risk factors and at a young age, how chronic cocaine use or even a history of usage may result in complications even weeks after its consumption.

A Rare Case of Myelodysplastic Syndrome with Refractory Thrombocytopenia.

Myelodysplastic syndromes (MDS) represent a variety of clonal abnormalities, possibly preleukemic and display numerous phenotypic manifestations. Specific mutations carry high morbidity and mortality rates due to cell line dysplasia. MDS commonly presents with symptoms related to anemia, and approximately two-thirds will develop thrombocytopenia, a rare, but potentially lethal complication that increases complexity in treatment and morbidity, and may be due to unique genetic mutations leading to refractory thrombocytopenia, ultimately leading to an overall reduction in survival. Careful identification and monitoring of this patient subdivision can significantly reduce morbidity and mortality, and potential identification of specific gene mutations and advances in treatment options will hopefully provide guidance on detecting at-risk patients in the future. We present a case of a man with MDS-U (karyotype 46, XY, del (20) (q11.2q13.3) (20) with no detected JAK2 V617F mutation), who in despite of appropriate evidenced based treatment, continued to exhibit refractory thrombocytopenia.

Emphysematous Cystitis: A Rare Disease of Genito-Urinary System.

CONTEXT: Emphysematous cystitis (EC) is a rare infection of the urinary tract that results in gas production in the bladder. It is more common in diabetic and female patients, and can be associated with more serious complications, including pyelonephritis. CASE REPORT: We describe a case of recurrent bacterial cystitis caused by Escherichia coli (E. coli). An incidental finding in our patient of pneumaturia on computed tomography (CT) scan prompted further work-up. Differential diagnoses for pneumaturia include infection, trauma, and fistula, most commonly colovesicular. The patient history ruled out trauma and CT scanning ruled out a fistula; culture of the urine then showed a bacterial load greater than 100,000 E. coli/mL. The patient was then diagnosed with EC. She was treated with ceftriaxone and released in stable condition. CONCLUSION: The literature was scarce when it came to diagnoses of EC based on bacterial load. We present this case to increase health care providers' awareness of recurrent EC with a urine culture bacterial load greater than 100,000 E. coli/mL.

Hypertriglyceridemia-Induced Pancreatitis: Choice of Treatment.

Severe hypertriglyceridemia is one of the many yet rare risk factors associated with acute pancreatitis. The level of triglycerides plays a crucial role in determining the method and duration of treatment. As with the treatment of other causes of acute pancreatitis, bowel rest, intravenous fluids, and supportive care play a crucial role. However, depending on the degree of hypertriglyceridemia, the role of other treatment options may need to be implemented. There are no set established guidelines for the management of hypertriglyceridemia-induced pancreatitis, but the role of insulin, heparin, and plasmapheresis has been studied and successfully used in its management. We report the case a 44-year-old female with clinical acute pancreatitis secondary to hypertriglyceridemia who was successfully managed with the addition of intravenous insulin.

Abdominal Tuberculosis: An Immigrant's Disease in the United States.

BACKGROUND: Abdominal tuberculosis (TB) is an uncommon condition in the United States (US) except for patients with human immunodeficiency virus (HIV). An increasing number of cases have been reported in western countries amongst immigrants. It is important to be aware of the data and clinical characteristics in the immigrant population. AIMS: The purpose of this study is to determine the epidemiologic characteristics of abdominal TB among immigrants in the US and to review the clinical presentations of abdominal TB with a focus particularly on unusual features. MATERIALS AND METHODS: In a community teaching hospital in New Jersey, patients diagnosed with abdominal TB were examined and included in this report. All nine patients were immigrants from countries with high prevalence of TB and a majority had resided in the US for at least 5 years. None had clinical evidence of HIV and those that were tested were not found to be positive for HIV. Initial examination, diagnostic workup, and response to therapy were all pertinent to the management and diagnosis of these patients. RESULTS: Three patients had atypical clinical presentations with normal chest X-rays and either negative or unknown tuberculin tests leading to delayed diagnosis and inappropriate therapy in at least one patient. With antituberculous therapy, all except for one patient had satisfactory outcomes. Immigrant patients with a diagnosis of abdominal TB had no evidence of HIV infection or other associated conditions in contrast to native-born individuals. CONCLUSION: Atypical presentations may cause diagnostic difficulties. Failure to perform appropriate tests may lead to inappropriate therapy with adverse outcomes. Although there is a decline in the number of TB cases in the US and screening for latent pulmonary infection in foreigners has been implemented effectively, the diagnosis of abdominal TB continues to be under diagnosed.

Effect of Atorvastatin and Pioglitazone on Plasma Levels of Adhesion Molecules in Non-Diabetic Patients With Hypertension or Stable Angina or Both.

BACKGROUND: It was to study the effect of atorvastatin, pioglitazone and their combination on plasma levels of adhesion molecules in patients with hypertension or stable angina or both. METHODS: It was an open-label, randomized parallel-group study. Forty-five atorvastatin-naive patients with hypertension or stable angina or both, were randomized to receive either atorvastatin (19 patients; 10 mg OD for 12 weeks) or pioglitazone (26 patients; 30 mg OD for 12 weeks). Another group of 30 patients who were already on atorvastatin were put on add-on pioglitazone therapy (pioglitazone (15 mg OD) + atorvastatin (10 mg OD) for 12 weeks). Plasma high-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were measured at baseline and after 12 weeks of therapy. RESULTS: Atorvastatin monotherapy significantly reduced plasma sICAM-1, but pioglitazone monotherapy did not produce any significant effect. Addition of pioglitazone in patients already receiving atorvastatin also significantly reduced plasma sICAM-1 level. However, there was no significant change in plasma hsCRP and sVCAM-1 levels in any of the groups after 12 weeks of therapy. CONCLUSION: There is therapeutic advantage of combining pioglitazone and atorvastatin on plasma sICAM-1 levels.

A New Early Finding of Moyamoya-Like Phenomena.

Moyamoya disease (MMD) primarily causes constriction of internal carotid artery, but it is known to extend to the middle and anterior cerebral arteries. Some of the symptoms caused by MMD include transient ischemic attack (TIA) and seizures. The etiology of MMD from Graves' disease (GD) is mostly caused by thyrotoxicosis, but our finding of leukocytosis indicates a new finding that may help physicians prepare for the pending outcome of MMD from GD with leukocytosis. A 26-year-old Hispanic woman with a significant past medical history of GD and hypertension presented to the emergency department complaining of cough and shortness of breath for the past 5 days. During the patient's stay in the hospital, the patient suddenly developed numbness of the right arm with subsequent right arm weakness 10 minutes later. The head CT showed no acute intercranial hemorrhage, but MRA showed right intracranial internal carotid artery stenosis, with marked focal stenosis along the proximal supraclinoid segment, moderate stenosis along its distal supraclinoid segment with marked stenosis along the origin of the right A1 segment. It was therefore believed to be moyamoya-like phenomena. We discuss an atypical presentation that led to moyamoya-like phenomena which we believe has not been described before. We believe that presentation of idiopathic leukocytosis may have triggered the cerebral stenosis.