A Pilot Study of Short-course Nivolumab and Low-dose Ipilimumab for Adjuvant Treatment of Melanoma: Brown University Oncology Research Group Trial, BrUOG 324.

BACKGROUND: Combined cytotoxic T-lymphocyte-associated antigen 4 and programmed death 1 inhibitor blockade is a promising strategy in advanced melanoma and other solid tumors. This pilot study assessed the safety and toxicity of nivolumab plus low-dose ipilimumab in patients with high-risk completely resected melanoma. PATIENTS AND METHODS: Patients received ipilimumab, 1 mg/kg every 6 weeks, and nivolumab, 3 mg/kg every 2 weeks, for a total of 24 weeks (4 cycles). The primary objective was to assess the toxicity of the combined regimen. RESULTS: Twenty-one patients with resected melanoma were enrolled. One patient was stage IIC, 16 patients were stage III and 4 patients had resected stage 4 disease. Ten of 21 (48%) had grade 3 treatment-related toxicities but there was no grade 4 or grade 5 toxicities. The rate of grade 3 nonhematologic toxicities exceeded the toxicity limits defined by the study. Fifteen of 21 patients (71%) completed all 4 cycles of therapy. The median follow-up is 41 months. The 2-year recurrence-free survival is 85.7% and the 2-year overall survival is 90.5%. CONCLUSION: A 6-month course of nivolumab and low-dose ipilimumab may be a promising adjuvant treatment for patients with resected melanoma. Further studies of this regimen are indicated.

Immune checkpoint inhibitors in malignancies with mismatch repair deficiency: a review of the state of the current knowledge.

The use of immune checkpoint inhibitors to treat malignant tumors with microsatellite instability is an emerging new modality. This is based on the observations that these tumors may have a high mutation rate-thus a potential source of tumor-specific neoantigens-and harbor infiltrating cytotoxic T cells in response, suggesting that they may be particularly susceptible to immune checkpoint therapy. PUBMED and ASCO library were systematically reviewed to identify all relevant data that involved the use of immune checkpoint inhibitors in the treatment of cancers with microsatellite instability. The manual search retrieved a total of 3 relevant articles and 1 abstract published between 2015 and 2016. A total of 61 patients with colorectal, 3 with ampullary/cholangiocarcinoma, 2 with endometrial carcinomas, 3 with small bowel cancers, 2 with glioblastoma multiforme, and 1 with bladder cancer with reported efficacy results were reviewed. All the patients had stage IV cancer and were treated with immune checkpoint inhibitors until progression of disease or intolerable side effects emerged. The range of objective response rate was 25-71%. Responses were also durable with progression-free survival at 20 weeks of around 67-78% and to 46% at 1 year. The use of immune checkpoint inhibitors is effective in cancers that express microsatellite instability.

Telephone-based anticoagulation management in the homebound setting: a retrospective observational study.

BACKGROUND: Anticoagulation management is currently performed through anticoagulation clinics or self-managed with or without the help of medical services. Homebound patients are a unique population that cannot utilize anticoagulation clinics or self-testing. Telephone-based anticoagulation management could be an alternative to the traditional methods of monitoring warfarin in this subgroup. The objective of this retrospective, observational study is to investigate the feasibility of warfarin management in homebound patients. METHODS: This study was performed through the use of telephone-based adjustments of warfarin dose based on an international normalized ratio (INR) result. Four hundred forty-eight homebound patients referred to the anticoagulation clinic at Staten Island University Hospital were visited at home by a phlebotomist; a blood sample was drawn for initial laboratory testing. A nurse practitioner then called the patient or designated person to relay the INR result and to direct dosage adjustment. INR results and dosage changes were entered into an electronic medical record and analyzed statistically. RESULTS: The mean percentage of INR values in range was 58.39%. The mean time when the INR was in the therapeutic range was 62.75%. The percent of patients who were therapeutically controlled decreased as the number of medications increased. The complication rate was 4% per patient year, with an equal distribution between bleeding and clotting. These values compared favorably to other studies in which monitoring was performed through anticoagulation clinics or self-monitoring. The cost per visit at our anticoagulation clinic was found to be approximately $300 compared with $82 when utilizing our homebound service. CONCLUSION: Telephone-based management of warfarin therapy in the homebound setting is feasible. It can lower the cost of health care expenditures compared to other modalities of anticoagulation management.

Bifocal Presentation of Primary Testicular Extranasal NK/T-Cell Lymphoma: A Case Report and Review of the Literature.

Introduction. Testicular lymphoma is an aggressive disease with a very poor prognosis. Nasal-type natural killer/T-cell lymphoma (NKTCL-N) in particular is very uncommon and has a rapidly progressive, fatal course. Case Report. We report a case of primary NKTCL-N of the testis in a 38-years-old Middle Eastern man. The patient had a history of primary right testicular tumor diagnosed at an outside institution as a seminoma and treated with orchiectomy followed by chemo/radiation. On admission, the patient had an enormous nasal granuloma with blood workup showing pancytopenia and elevated liver function tests due to active hepatitis B infection. CT scan of the sinuses showed a very large soft tissue mass, and PET scan showed splenomegaly with multiple lymph node masses in the pelvis and the chest areas. Bone marrow and nasal tumor biopsies as well as review of the slides from the initial orchiectomy were all in favor of NKTCL-N lymphoma. The patient was treated with CHOD based combination chemotherapy and responded dramatically to the first two cycles but passed away from fulminant hepatitis B infection. Conclusion. Despite all known treatments of NKTCL-N lymphoma of the testes, this disease has a very poor prognosis and invariably follows an aggressive clinical course.

Relationship between platelet count and hemodialysis membranes.

BACKGROUND: One factor associated with poor outcomes in hemodialysis patients is exposure to a foreign membrane. Older membranes are very bioincompatible and increase complement activation, cause leukocytosis by activating circulating factors, which sequesters leukocytes in the lungs, and activates platelets. Recently, newer membranes have been developed that were designed to be more biocompatible. We tested if the different "optiflux" hemodialysis membranes had different effects on platelet levels. METHODS: Ninety-nine maintenance hemodialysis patients with no known systemic or hematologic diseases affecting their platelets had blood drawn immediately prior to, 90 minutes into, and immediately following their first hemodialysis session of the week. All patients were dialyzed using a Fresenius Medical Care Optiflux polysulfone membrane F160, F180, or F200 (polysulfone synthetic dialyzer membranes, 1.6 m(2), 1.8 m(2), and 2.0 m(2) surface area, respectively, electron beam sterilized). Platelet counts were measured from each sample by analysis using a CBC analyzer. RESULTS: The average age of the patients was 62.7 years; 36 were female and 63 were male. The mean platelet count pre, mid, and post dialysis was 193 (standard deviation ±74.86), 191 (standard deviation ±74.67), and 197 (standard deviation ±79.34) thousand/mm3, respectively, with no statistical differences. CONCLUSION: Newer membranes have no significant effect on platelet count. This suggests that they are, in fact, more biocompatible than their predecessors and may explain their association with increased survival.

Effects of proton pump inhibitors and electrolyte disturbances on arrhythmias.

Several case reports have been written regarding the relationship between the use of proton pump inhibitors (PPI) and hypomagnesemia. Some of these reported cases have electrocardiogram abnormalities where electrolytes deficiencies were the contributing factor for these events. This study investigates the correlation between different arrhythmias and the use of PPI and hypomagnesaemia incidence. Four-hundred and twenty-one patients admitted to the critical care unit with unstable angina, non-ST elevation myocardial infarction, and ST-elevation myocardial infarction were included in this study. One-hundred and eighty-four patients (43.8%) received PPI and 237 patients (51.16%) did not, magnesium levels were low (<1.8 mg/dL) in 95 patients (22.5%), and 167 patients (39.6%) developed arrhythmias. The P-values for the regression coefficient association for the use of PPI and the level of magnesium were P = 1.31e(-29) and P = 8e(-102), respectively. The P-values indicate that there is a statistically significant association between the PPI use, magnesium levels, and the occurrence of cardiovascular events, with a strong correlation factor of 0.817. Patients receiving PPIs should be followed closely for magnesium deficiency, especially if they experience acute cardiovascular events, because this may contribute to worsening arrhythmias and further complications.

The value of the pretreatment albumin/globulin ratio in predicting the long-term survival in colorectal cancer.

BACKGROUND: Low serum albumin was found as a predictor of long-term mortality in colorectal cancer (CRC) patients. Our aim was to evaluate the value of the pretreatment albumin/globulin ratio (AGR) to predict the long-term mortality in CRC patients. METHODS: Patients were included if they had comprehensive metabolic panel (CMP) before treatment (surgery or chemotherapy). The albumin/globulin ratio, routinely reported in CMP, is calculated [AGR = Albumin/(Total protein - Albumin)]. Patients were divided into three equal tertiles according to their pretreatment AGR. The primary outcome was cancer-related mortality, which was obtained from our cancer registry database. RESULTS: A total of 534 consecutive CRC patients had pretreatment CMP. The 1st AGR tertile had a significant higher 4-year mortality compared to the second and third AGR tertiles (42 vs. 19 and 7 %, p < 0.0001 according to Fisher's exact two-tailed test). In the multivariate model, AGR remained an independent predictor of survival with 75 % decrease in mortality among the highest AGR tertile in comparison to the lowest AGR tertile, p < 0.0001. In the subset of 234 patients with normal serum albumin (albumin of >3.5 g/dl), serum AGR continues to be an independent predictor of cancer-related mortality with an adjusted hazard ratio of the third tertile compared to the first tertile equal to 0.05 (95 % confidence interval 0.01-0.33, p = 0.002). CONCLUSION: Low AGR was a strong independent predictor of long-term cancer-specific survival among colorectal cancer patients. Additionally, among the patients with normal albumin (>3.5 g/dl), patients with lower globulins but higher albumin and AGR levels had better survival.

Community-Acquired Methicillin-Resistant Staphylococcus aureus Prostatic Abscess Presenting as Acute Urinary Retention: A Case Report and Review of the Literature.

Background. Community-associated MRSA (CA-MRSA) strains have emerged as a substantial cause of infection in individuals without exposure to the healthcare system. Prostatic abscess is an uncommon disease. To date, there are only 6 published reports of a prostatic abscess secondary to CA-MRSA. Case Description. A 52-year-old diabetic Caucasian presented to the emergency department with severe lower abdominal pain of few hours duration, urinary frequency, and dribbling over the last 3 weeks. Physical examination was remarkable for an enlarged nontender prostate. A urine analysis showed pyuria while urine cultures grew CA-MRSA. Computed tomography of the abdomen and pelvis showed multiple prostate abscesses and a thickened urinary bladder wall. A TURP was performed by the urology team and pathology showed severe acute and chronic prostatitis with abscess formation and necrotic tissue. Our treatment regimen included IV vancomycin followed by oral trimethoprim/sulfamethoxazole and rifampin. Eradication of CA-MRSA was confirmed by follow-up cultures 2 months following discharge. Conclusion. This case illustrates the successful identification, diagnosis, and prompt treatment of a prostatic abscess secondary to CA-MRSA in a diabetic patient without recent hospitalization. Early treatment with antibiotics and transurethral resection of the prostate abscess led to a shortened hospital stay and decreased morbidity.

Measuring visceral and hepatic fat in clinical practice and clinical research.

OBJECTIVE: To review how visceral and hepatic fat are measured in clinical practice and clinical research. METHODS: We examine different methods employed to assess visceral and hepatic fat in the literature. RESULTS: Fat in the human body is located in 2 main compartments: subcutaneous and visceral, which also includes liver fat. Visceral and liver fats are associated with the metabolic complications of obesity like hypertension, diabetes, and atherosclerosis. Therefore, there is a need to detect those fats early in life before the development of cardiometabolic syndrome (CMS). Many modalities have been proposed to measure visceral and liver fat. Indirect measurements can be done through waist circumference (WC), dual-energy X-ray absorptiometry (DEXA), ultrasound, and bioelectric impedance, whereas direct methods include computed tomography (CT) and magnetic resonance imaging (MRI). An ideal measurement method should be noninvasive, reliable, suitable for all body sizes, widely available, cost and time effective, show low variability, and have no or limited radiation exposure. CONCLUSION: Measuring visceral and liver fat is not a straightforward procedure in clinical practice or research; several variables may affect measure accuracy and validity.