Potential limitations of diagnostic standard codes to distinguish polycythemia vera and secondary erythrocytosis.

Red cell overproduction is seen in polycythemia vera (PV), a bone marrow myeloproliferative neoplasm characterized by trilinear cell proliferation (WBC, platelets), as well as in secondary erythrocytosis (SE), a group of heterogeneous disorders characterized by elevated EPO gene transcription. We aimed to verify the concordance of the International Classification of Diseases (ICD) code-based diagnosis of "polycythemia" or "erythrocytosis" with the true clinical diagnosis of these conditions. We retrospectively reviewed the electronic medical records (January 1, 2005, to December 31, 2016) of adult patients with ICD codes of polycythemia and/or erythrocytosis who had testing done for the presence of the JAK2V617F mutation. We verified the accuracy of the ICD code-based diagnoses by meticulous chart review and established whether these patients fulfilled the criteria by the evaluating physician for PV or SE and according to the World Health Organization 2016 diagnostic guidelines. The reliability of ICD coding was calculated using Cohen's kappa. We identified and chart reviewed a total of 578 patient records. Remarkably, 11% of the patients had concurrent diagnosis codes for PV and SE and were unable to be classified appropriately without individual chart review. The ICD code-based diagnostic system led to misidentification in an important fraction of cases. This represents a problem for the detection of PV or SE cases by ICD-based registries and their derived studies. Research based exclusively on ICD codes could have a potential impact on patient care and public health, and limitations must be weighed when research findings are conveyed.

Diagnostic Performance of Erythropoietin Levels in Polycythemia Vera: Experience at a Comprehensive Cancer Center.

INTRODUCTION: Considering the evolving diagnostic criteria of polycythemia vera (PV), we analyzed the utility of serum erythropoietin (EPO) as a predictive marker for differentiating polycythemia vera (PV) from other etiologies of erythrocytosis. PATIENTS AND METHODS: We conducted a retrospective study after a review of electronical medical records from January 2005 to December 2016 with diagnosis of erythrocytosis using International Classification of Disease-specific codes. To evaluate the diagnostic performance of EPO levels and JAK2-V617F mutation, we constructed a receiver-operated characteristic curve of sensitivity versus 1-specificity for serum EPO levels and JAK2-V617F mutation as predictive markers for differentiating PV from other causes of erythrocytosis. RESULTS: We surveyed 577 patients with erythrocytosis. Median patient age was 59.2 years, 57.72% (n = 329) were male, 86.3% (n = 491) were white, and only 3.3% (n = 19) were African American. A total of 80.88% (n = 351) of those diagnosed with PV had a JAK2-V617F mutation compared to only 1.47% (n = 2) whose primary diagnosis was secondary polycythemia. When comparing JAK2-V617 mutation to the EPO level, the area under the curve of JAK2-V617 (0.8970) was statistically larger than that of EPO test (0.6765). Therefore, the PV diagnostic methodology using JAK2-V617 is better than the EPO test. An EPO level of < 2 mIU/mL was > 99% specific to predict PV but was only 12% sensitive. CONCLUSION: In the appropriate clinical setting, cytogenetic and molecular studies such as JAK2 mutation status prevail as the most useful tools for PV case identification. The use of isolated EPO to screen patients with erythrocytosis is not a good diagnostic approach.

Adjuvant Ipilimumab in High-Risk Uveal Melanoma.

Uveal melanoma is a common intraocular malignant tumor that is uniformly fatal once metastatic. No effective adjuvant therapy currently exists to reduce the risk of distant metastasis after definitive treatment of the primary lesion. Immunotherapy has been used effectively in the adjuvant setting in locally advanced cutaneous melanoma. We performed a Phase I/II clinical trial of adjuvant ipilimumab in high-risk primary uveal melanoma with distant metastasis-free survival (DMFS) as the primary objective. A total of 10 patients with genomically high-risk disease were treated: three at a dose of 3 mg/kg and seven at 10 mg/kg. Two of the seven patients at the higher dose had to discontinue therapy secondary to grade 3 toxicity. At 36 months follow-up, 80% of patients had no evidence of distant disease (95% CI, 58.7⁻100). With recent advancements in CTLA-4 inhibition, PD-1 inhibition, and combined checkpoint blockade, immunotherapy is a promising avenue of treatment in uveal melanoma. Further clinical trials are needed to elucidate the role of immunotherapy in the adjuvant setting.

Etiology and complications of thrombocytopenia in hospitalized medical patients.

To determine incidence, risk factors, hematologic complications, and prognostic significance of thrombocytopenia in the general medicine population, we performed a single-institutional, retrospective study of all adult patients admitted to a general medical ward from January 1st, 2014 to December 31st, 2014 with hospital-acquired thrombocytopenia. Those with moderate thrombocytopenia, defined as a platelet count nadir of <100 × 10^9/L and/or a >50% relative decline, were compared to those with less severe thrombocytopenia. Of the 7420 patients admitted, 465 (6.3%) developed hospital-acquired thrombocytopenia. Infection and moderate thrombocytopenia were present in 56 and 23%, respectively. Severe sepsis and antibiotic use were both associated with moderate thrombocytopenia, and proton pump inhibitor use was statistically significant in both univariate and multivariate analysis. Hematologic complications were more frequent with moderate thrombocytopenia, including frequency of HIT testing and red blood cell transfusions. Outcome metrics including transfer to an intensive care unit (OR 6.78), death during admission (OR 6.85), and length of stay (10.6 vs. 5.1 days) were all associated with moderate thrombocytopenia. Thrombocytopenia is associated with poor prognosis, and the association between moderate thrombocytopenia and proton pump inhibitor use is relatively novel and should be validated in prospective studies.

Thrombocytopenia in hospitalized patients with severe clostridium difficile infection.

Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhea and colitis. The incidence and prognostic significance of thrombocytopenia as related to mode of acquisition (hospital vs. community), NAP1/027 strain, and disease severity has not been examined. We performed a single-institution retrospective analysis of all adult inpatients from 2013 to 2014 diagnosed with CDI during their hospitalization to document the incidence/prevalence of thrombocytopenia and associated outcomes. Severe disease was defined by a composite endpoint of inpatient death, death within 30 days of discharge, presence of septic shock, or need for colectomy during hospitalization. Of the 533 patients diagnosed with CDI, moderate thrombocytopenia (platelet count <100 × 109/L at time of CDI diagnosis) was present in 15 % of the total cohort and incident thrombocytopenia developed in 3 % of patients after admission. Thrombocytopenia was more common in hospital-acquired disease and associated with increased length of stay, but was not associated with treatment failure. Those with moderate thrombocytopenia were more likely to have severe disease, after controlling for white blood cell count, albumin, and creatinine. Moderate thrombocytopenia is associated with poor prognosis and is a potential risk stratification tool for severe CDI.

Diagnosis of Capnocytophaga canimorsus Sepsis by Whole-Genome Next-Generation Sequencing.

We report the case of a 60-year-old man with septic shock due to Capnocytophaga canimorsus that was diagnosed in 24 hours by a novel whole-genome next-generation sequencing assay. This technology shows great promise in identifying fastidious pathogens, and, if validated, it has profound implications for infectious disease diagnosis.

Neuro-Behçet's disease: an unusual cause of headache.

Neuro-Behçet's disease (NBD) is a potentially fatal complication of Behçet's disease (BD) that can sometimes masquerade as a primary neoplasm, aseptic meningitis or multiple sclerosis. Headache in patients with BD may portend onset of NBD, but the majority of headache in BD is benign. Clinicians who are unaware of the specific neurological manifestations of systemic inflammatory disorders like BD may fail to consider the possibility of serious intracranial pathology. We illustrate these challenges with the case of a 50-year-old woman with a history of BD who presented with headache in the absence of initial focal neurological deficits. The diagnosis of NBD was missed on multiple occasions before the correct diagnosis was made. We describe the etiology of headache in BD, the specific neurological manifestations of BD that suggest NBD, and the utility of routine neurological exams for BD patients with chronic headache. We further discuss the appropriate use of neuroimaging for headache in BD, and we recommend consideration of NBD as a diagnosis for headache in patients suspected of having an underlying systemic disease.