Inpatient Infliximab Biosimilar Cost-Savings: Cost Analysis of Inpatient Treatment with Originator Infliximab (Remicade™) versus Biosimilar Infliximab (Renflexis™) for Acute Severe Ulcerative Colitis.

INTRODUCTION: Infliximab (IFX) is a standard, inpatient salvage therapy for the treatment of refractory acute severe ulcerative colitis (ASUC). Remicade™ is the originator IFX. Its biosimilar Renflexis™ offers a reduced cost structure. We performed a cost-minimization analysis to compare costs with Remicade™ and Renflexis™ for the inpatient treatment of ASUC. METHODS: Retrospective clinical and financial data were obtained from 34 inpatients with refractory ASUC who received Renflexis™ (n = 17) or Remicade™ (n = 17) between 2019 and 2021. Clinical data included admission and discharge laboratory values. Financial data included a decision support drug cost (DSDC), constituting the total cost associated with inpatient IFX administration, and total inpatient cost of care. The following equation generated a ratio (rDSDC) representing the percentage of drug cost (or DSDC) of the total inpatient cost of care, after controlling for IFX dose and length of stay: [DSDC of IFX/Number of Units of IFX] ÷ [Total Inpatient Cost of Care/Length of Stay in Days]. Median and non-parametric Wilcoxon ranked sum test were used for analyzing patient demographics, clinical, and financial data. RESULTS: No differences were found in baseline or discharge clinical parameters. The median unadjusted ratio of DSDC to total inpatient cost of care was 0.387 versus 0.241 in the Remicade™ versus Renflexis™ groups (p = 0.0025), respectively, representing an absolute difference of ∼14%. Median adjusted rDSDC were 0.04 versus 0.024 in the Remicade™ versus Renflexis™ groups, respectively, representing a relative cost reduction of ∼40% (p = 0.0001). DISCUSSION: The unadjusted absolute cost reduction and adjusted relative cost reduction were, respectively, 14% and 40% in the Renflexis™ group as compared to Remicade™, when treating inpatient ASUC. Our calculation included median DSDC as a percentage of the total inpatient cost of care, controlling for IFX dose and length of stay. This reduced cost structure promotes use of Renflexis™ for ASUC inpatients and may reduce costs systemically.

Extramedullary Waldenström macroglobulinemia.

Disease assessment in Waldenstrom Macroglobulinemia (WM) is dependent on the percent involvement of B-cell neoplasm in the bone marrow and IgM paraprotein in the serum. A subset of patients also demonstrates extramedullary involvement, which is infrequently examined. The role of extramedullary involvement in the diagnosis and prognosis of WM is poorly understood. The purpose of this study is to report the characteristics of WM patients with extramedullary disease (EMD). Nine hundred and eight-five patients with WM were evaluated at one academic center and the presence of EMD was assessed in these patients. Forty-three (4.4%) patients were identified to have EMD. Nine (21%) patients presented with involvement at WM diagnosis, while 34 (79%) developed EMD post-therapy for WM. Most frequent EMD sites involved were pulmonary (30%), soft tissue (21%), cerebrospinal fluid (23%), renal (8%), and bone (9%). The median overall survival at 10 years was 79% (95% CI: 57-90%). This is the first study to describe the clinical characteristics, response and overall survival in patients with extramedullary WM. Further studies to define the molecular characteristics of this entity and mechanisms of its development are warranted.

A rare case of polyarthritis panniculitis and pancreatitis.

Extra pancreatic manifestations of pancreatitis are rare, with a prevalence of 2-3%. One such rare manifestation is the triad of joint pain (polyarthritis), tender skin lesions (panniculitis), and pancreatic inflammation (pancreatitis), known as PPP. The pathogenesis of this phenomenon is not fully understood but is believed to involve lipolysis by pancreatic enzymes at lipid-rich skin and joint sites. PPP primarily affects middle-aged males with a history of alcohol use disorder. Diagnosis can be challenging due to the absence of typical abdominal symptoms. Delayed diagnosis may significantly worsen outcomes. Supportive therapy is the mainstay, but resolution requires addressing the underlying pancreatic abnormality. We present a case of a patient with a history of alcohol use disorder and recurrent acute pancreatitis who developed joint pain and skin rash. Extensive work-up ruled out other causes, and imaging and biopsy confirmed the diagnosis of PPP. Symptomatic management and treatment of the underlying pancreatic abnormality led to complete resolution of symptoms. Our case serves to raise awareness of this rare but potentially fatal syndrome.

Hepatic hydrothorax is not associated with increased complications or poor survival after liver transplantation.

BACKGROUND: Hepatic hydrothorax (HH) is associated with a poor prognosis. Liver transplant (LT) is the best treatment modality. We aim to assess post-LT morbidity and mortality in patients with cirrhosis and HH. RESEARCH DESIGN AND METHODS: Adult patients with cirrhosis, who underwent LT at our institution from 2015 to 2020, were retrospectively reviewed. Baseline data was obtained at the time of LT. Patients were followed from baseline until the last follow-up or death. Censoring occurred at the time of the last follow-up or death, whichever occurred earlier. Cumulative incidence of outcomes was determined by the Kaplan-Meier method. Short-term post-operative complications were compared between both groups as well. RESULTS: 428 patients had a LT, of which 72 (16.8%) had HH. Most of the baseline characteristics were similar between patients with and without HH; however, patients in the HH group had a higher proportion of pre-operative history of ascites and hepatic encephalopathy. Pre-operative HH was not significantly associated with post-LT mortality (Hazard ratio 1.12, 95% confidence interval 0.54-2.32; P-value 0.76). Patients had similar short-term post-operative complications between both groups. CONCLUSIONS: LT is an excellent therapeutic option for patients with cirrhosis and HH, with excellent long-term survival without increased morbidity.

Nosocomial spontaneous bacterial peritonitis is associated with high mortality - a systematic review and meta-analysis.

INTRODUCTION: It is unclear if Nosocomial Spontaneous Bacteria Peritonitis (NSBP) is associated with higher mortality compared with community acquired spontaneous bacterial peritonitis. METHODS: Database search from inception to May 2022 was conducted. The databases included MEDLINE, EMBASE, Cochrane registry of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. Inclusion criteria were as follows: adult patients, age >18 years, with a diagnosis of NSBP. Pooled estimates of mortality were calculated following the restricted maximum likelihood method. The mortality rate between NSBP and CA-SBP was reported as odds ratio (OR) and 95% confidence interval (CI). Data synthesis was obtained using random effects meta-analysis. Heterogeneity was reported as I2. RESULTS: A total of 482 unique titles were screened. Twenty-two articles were included. A total of 2,145 patients with NSBP were included. Patients were followed for a median of 90 days. The pooled mortality rate of NSBP was 52.51% (95% CI 42.77-62.06%; I2 83.72%). Seven studies compared the mortality outcome of patients with NSBP and CA-SBP. NSBP was significantly associated with a higher rate of mortality (OR 2.78, 95% CI 1.87-4.11; I2 36.00%). CONCLUSION: NSBP was associated with higher mortality rate compared to CA-SBP, which could be due to a higher rate of resistance organisms.

Progression Risk Stratification of Asymptomatic Waldenström Macroglobulinemia.

BACKGROUND: Waldenström macroglobulinemia (WM) is preceded by asymptomatic WM (AWM), for which the risk of progression to overt disease is not well defined. METHODS: We studied 439 patients with AWM, who were diagnosed and observed at Dana-Farber Cancer Institute between 1992 and 2014. RESULTS: During the 23-year study period, with a median follow-up of 7.8 years, 317 patients progressed to symptomatic WM (72%). Immunoglobulin M 4,500 mg/dL or greater, bone marrow lymphoplasmacytic infiltration 70% or greater, ß2-microglobulin 4.0 mg/dL or greater, and albumin 3.5 g/dL or less were all identified as independent predictors of disease progression. To assess progression risk in patients with AWM, we trained and cross-validated a proportional hazards model using bone marrow infiltration, immunoglobulin M, albumin, and beta-2 microglobulin values as continuous measures. The model divided the cohort into three distinct risk groups: a high-risk group with a median time to progression (TTP) of 1.8 years, an intermediate-risk group with a median TTP of 4.8 years, and a low-risk group with a median TTP of 9.3 years. We validated this model in two external cohorts, demonstrating robustness and generalizability. For clinical applicability, we made the model available as a Web page application ( www.awmrisk.com ). By combining two cohorts, we were powered to identify wild type MYD88 as an independent predictor of progression (hazard ratio, 2.7). CONCLUSION: This classification system is positioned to inform patient monitoring and care and, for the first time to our knowledge, to identify patients with high-risk AWM who may need closer follow-up or benefit from early intervention.

Mortality and serum sodium: do patients die from or with hyponatremia?

BACKGROUND AND OBJECTIVES: Severe hyponatremia (<120 mEq/L) in hospitalized patients has a high mortality rate. We hypothesized that underlying diseases causing hyponatremia attribute to mortality rather than hyponatremia itself. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The relationship between mortality and serum sodium (sNa) was examined in 45,693 patients admitted to a single community teaching hospital between January 1996 and December 2007. We conducted a comprehensive retrospective review of the medical records of 53 patients who died after developing sNa <120 mEq/L before or after admission and of 32 patients who survived after developing sNa <110 mEq/L. RESULTS: Mortality rates tended to increase as the sNa fell from 134 to 120 mEq/L, rising above 10% for patients with sNa of 120 to 124 mEq/L. However, below sNa of 120 mEq/L, the trend reversed, such that the mortality rate progressively decreased as sNa fell. More than two thirds of patients who died after sNa <120 mEq/L had at least two additional acute severe progressive illnesses, most commonly sepsis and multiorgan failure. Three deaths (5.6%) in 12 years could plausibly be related to adverse consequences of hyponatremia, and one (1.8% of the fatal cases and 0.15% of all patients with sNa <120 mEq/L) was from cerebral edema. Most patients who survived with sNa <110 mEq/L had medication-induced hyponatremia. Severe underlying illnesses were uncommon in this group. CONCLUSIONS: The nature of underlying illness rather than the severity of hyponatremia best explains mortality associated with hyponatremia. Neurologic complications from hyponatremia are uncommon among patients who die with hyponatremia.

Hypertonic saline for hyponatremia: risk of inadvertent overcorrection.

BACKGROUND AND OBJECTIVES: Data regarding dosage-response relationships for using hypertonic saline in treatment of hyponatremia are extremely limited. Objectives of this study were to assess adherence to previously published guidelines (limiting correction to <12 mEq/L per d and <18 mEq/L per 48 h) in treating hyponatremia with hypertonic saline and to determine the predictive accuracy of the Adrogué-Madias formula. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: A retrospective review was conducted of all 62 adult, hyponatremic patients who were treated with hypertonic saline during 5 yr at a 528-bed, acute care, teaching hospital. RESULTS: Median infusion rate was 0.38 ml/kg per h, increasing serum sodium concentration by 0.47 +/- 0.05 mEq/L per h, 7.1 +/- 0.6 mEq/L per 24 h, and 11.3 +/- 0.7 mEq/L per 48 h. In 11.3% of cases, the increase was >12 mEq/L per 24 h and in 9.7% was >18 mEq/L per 48 h. No patient's rate was corrected by >25 mEq/L per 48 h. Among patients with serum sodium <120 mEq/L, the observed increase in sodium exceeded the rise predicted by the Adrogué-Madias formula in 74.2%; the average correction in overcorrectors was 2.4 times the predicted. Inadvertent overcorrection was due to documented water diuresis in 40% of cases. CONCLUSIONS: The Adrogué-Madias formula underestimates increase in sodium concentration after hypertonic saline therapy. Unrecognized hypovolemia and other reversible causes of water retention pose a risk for inadvertent overcorrection. Hypertonic saline should be infused at rates lower than those predicted by formulas with close monitoring of serum sodium and urine output.

Prevalence and penetrance of HFE mutations in 4865 unselected primary care patients.

Two HFE gene mutations, C282Y and H63D, underlie the vast majority of cases of hereditary hemochromatosis. We performed a cross-sectional primary care-based study to determine the allele frequency of the C282Y and H63D mutations and the penetrance of each of the affected genotypes defined by their presence. Patients had previously undergone transferrin saturation (TS) testing. A total of 4865 unselected frozen serum samples were analyzed to determine serum ferritin (SF) levels. Genomic DNA isolated from these samples was analyzed for the C282Y and H63D HFE mutations. Homozygotes for each mutation and compound heterozygotes were evaluated to determine clinical penetrance. The allele frequency of C282Y was 0.0507 among Caucasian and 0.0067 among African Americans; that of H63D was 0.1512 and 0.0263, respectively. TS was > or =55% in 83% of individuals with C282Y/C282Y, 14.5% of C282Y/H63D, and 5% of H63D/H63D; SF was > or =300 microG/L in 42, 9, and 5% of these genotypes, respectively. None of the 12 C282Y homozygotes had cardiac dysfunction or hepatic cirrhosis. Only 9/129 (7%) individuals with the genotypes C282Y/H63D or H63D/H63D had a SF > or =300 microG/L; many had explanations other than iron overload that accounted for this increase. Thus, the prevalence of the common HFE mutations is the same in our population as previously described. TS screening would detect most C282Y homozygotes but not the other two genotypes. The penetrance of C282Y/C282Y is significant. The biochemical penetrance of H63D/H63D and C282Y/H63D is modest and the clinical penetrance is low.