A toolbox of different approaches to analyze and present PRO-CTCAE data in oncology studies.

BACKGROUND: The patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is used to assess symptomatic adverse events in oncology trials. Currently, no standard for PRO-CTCAE analysis exists. METHODS: Key methods of descriptive analysis and longitudinal modeling using PRO-CTCAE data from an oncology clinical trial, DRiving Excellence in Approaches to Multiple Myeloma-2 (DREAMM-2), a phase II trial of belantamab mafodotin in multiple myeloma (NCT03525678), were explored. Descriptive methods included maximum postbaseline ratings, mean change over time, ratings above a predefined cutoff, line graphs, and stacked bar charts to illustrate patient-reported adverse events at one timepoint or dynamics over time. Analysis methods involving modeling over time included toxicity over time (ToxT) (repeated measurement model, time-to-event, area under the curve analyses), generalized estimating equations (GEE), and ordinal log-linear models (OLLMs). RESULTS: Visualizations of PRO-CTCAE data highlighted different aspects of the data. Selection of the appropriate visualization will depend on the audience and message to be conveyed. Consistent results were obtained by all modeling approaches; no difference was found between dose groups of the DREAMM-2 study in any PRO-CTCAE item by the ToxT approach or the more sophisticated GEE and OLLM methods. Interpretation of GEE results was the most challenging. OLLM supported the interval nature of the PRO-CTCAE response scale in the DREAMM-2 study. All modeling approaches account for multiple testing (driven by the number of items). CONCLUSIONS: Descriptive analyses and longitudinal modeling approaches are complementary approaches to presenting PRO-CTCAE data. In modeling, the ToxT approach may be a good compromise compared with more sophisticated analyses.

An alphavirus replicon-based vaccine expressing a stabilized Spike antigen induces protective immunity and prevents transmission of SARS-CoV-2 between cats.

Early in the SARS-CoV-2 pandemic concerns were raised regarding infection of new animal hosts and the effect on viral epidemiology. Infection of other animals could be detrimental by causing clinical disease, allowing further mutations, and bares the risk for the establishment of a non-human reservoir. Cats were the first reported animals susceptible to natural and experimental infection with SARS-CoV-2. Given the concerns these findings raised, and the close contact between humans and cats, we aimed to develop a vaccine candidate that could reduce SARS-CoV-2 infection and in addition to prevent spread among cats. Here we report that a Replicon Particle (RP) vaccine based on Venezuelan equine encephalitis virus, known to be safe and efficacious in a variety of animal species, could induce neutralizing antibody responses in guinea pigs and cats. The design of the SARS-CoV-2 spike immunogen was critical in developing a strong neutralizing antibody response. Vaccination of cats was able to induce high neutralizing antibody responses, effective also against the SARS-CoV-2 B.1.1.7 variant. Interestingly, in contrast to control animals, the infectious virus could not be detected in oropharyngeal or nasal swabs of vaccinated cats after SARS-CoV-2 challenge. Correspondingly, the challenged control cats spread the virus to in-contact cats whereas the vaccinated cats did not transmit the virus. The results show that the RP vaccine induces protective immunity preventing SARS-CoV-2 infection and transmission. These data suggest that this RP vaccine could be a multi-species vaccine useful to prevent infection and spread to and between animals should that approach be required.

Effect of Surgical Setting on Cost and Hospital Reported Outcomes for Single-Level Anterior Cervical Discectomy and Fusion.

BACKGROUND: Hospitals seek to reduce costs and improve patient outcomes by decreasing length of stay (LOS), 30-day all-cause readmissions, and preventable complications. We evaluated hospital-reported outcome measures for elective single-level anterior cervical discectomy and fusions (ACDFs) between tertiary (TH) and community hospitals (CH) to determine location-based differences in complications, LOS, and overall costs. METHODS: Patients undergoing elective single-level ACDF in a 1-year period were retrospectively reviewed from a physician-driven database from a single medical system consisting of 1 TH and 4 CHs. Adult patients who underwent elective single-level ACDF were included. Patients with trauma, tumor, prior cervical surgery, and infection were excluded. Outcomes measures included all-cause 30-day readmissions, preventable complications, LOS, and hospital costs. RESULTS: A total of 301 patients (60 TH, 241 CH) were included. CHs had longer LOS (1.25 ± 0.50 versus 1.08 ± 0.28 days, P = .01). There were no differences in complication and readmission rates between hospital settings. CH, orthopaedic subspecialty, female sex, and myelopathy were predictors for longer LOS. Overall, costs at the TH were significantly higher than at CHs ($17 171 versus $11 737; Δ$ = 5434 ± 3996; P < .0001). For CHs, the total costs of drugs, rooms, supplies, and therapy were significantly higher than at the TH. TH status, orthopaedic subspecialty, and myelopathy were associated with higher costs. CONCLUSION: Patients undergoing single-level ACDFs at CHs had longer LOS, but similar complications and readmission rates as those at the TH. However, cost of ACDF was 1.5 times greater in the TH. To improve patient outcomes, optimize value, and reduce hospital costs, modifiable factors for elective ACDFs should be evaluated. LEVEL OF EVIDENCE: 3.

Effect of Surgical Setting on Hospital-Reported Outcomes for Elective Lumbar Spinal Procedures: Tertiary Versus Community Hospitals.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: As hospital compensation becomes increasingly dependent on pay-for-performance and bundled payment compensation models, hospitals seek to reduce costs and increase quality. To our knowledge, no reported data compare these measures between hospital settings for elective lumbar procedures. The study compares hospital-reported outcomes and costs for elective lumbar procedures performed at a tertiary hospital (TH) versus community hospitals (CH) within a single health care system. METHODS: Retrospective review of a physician-maintained, prospectively collected database consisting of 1 TH and 4 CH for 3 common lumbar surgeries from 2015 to 2016. Patients undergoing primary elective microdiscectomy for disc herniation, laminectomy for spinal stenosis, and laminectomy with fusion for degenerative spondylolisthesis were included. Patients were excluded for traumatic, infectious, or malignant pathology. Comparing hospital settings, outcomes included length of stay (LOS), rates of 30-day readmissions, potentially preventable complications (PPC), and discharge to rehabilitation facility, and hospital costs. RESULTS: A total of 892 patients (n = 217 microdiscectomies, n = 302 laminectomies, and n = 373 laminectomy fusions) were included. The TH served a younger patient population with fewer comorbid conditions and a higher proportion of African Americans. The TH performed more decompressions (P < .001) per level fused; the CH performed more interbody fusions (P = .007). Cost of performing microdiscectomy (P < .001) and laminectomy (P = .014) was significantly higher at the TH, but there was no significant difference for laminectomy with fusion. In a multivariable stepwise linear regression analysis, the TH was significantly more expensive for single-level microdiscectomy (P < .001) and laminectomy with single-level fusion (P < .001), but trended toward significance for laminectomy without fusion (P = .052). No difference existed for PPC or readmissions rate. Patients undergoing laminectomy without fusion were discharged to a facility more often at the TH (P = .019). CONCLUSIONS: We provide hospital-reported outcomes between a TH and CH. Significant differences in patient characteristics and surgical practices exist between surgical settings. Despite minimal differences in hospital-reported outcomes, the TH was significantly more expensive.

Design and characterization of a nanopore-coupled polymerase for single-molecule DNA sequencing by synthesis on an electrode array.

Scalable, high-throughput DNA sequencing is a prerequisite for precision medicine and biomedical research. Recently, we presented a nanopore-based sequencing-by-synthesis (Nanopore-SBS) approach, which used a set of nucleotides with polymer tags that allow discrimination of the nucleotides in a biological nanopore. Here, we designed and covalently coupled a DNA polymerase to an α-hemolysin (αHL) heptamer using the SpyCatcher/SpyTag conjugation approach. These porin-polymerase conjugates were inserted into lipid bilayers on a complementary metal oxide semiconductor (CMOS)-based electrode array for high-throughput electrical recording of DNA synthesis. The designed nanopore construct successfully detected the capture of tagged nucleotides complementary to a DNA base on a provided template. We measured over 200 tagged-nucleotide signals for each of the four bases and developed a classification method to uniquely distinguish them from each other and background signals. The probability of falsely identifying a background event as a true capture event was less than 1.2%. In the presence of all four tagged nucleotides, we observed sequential additions in real time during polymerase-catalyzed DNA synthesis. Single-polymerase coupling to a nanopore, in combination with the Nanopore-SBS approach, can provide the foundation for a low-cost, single-molecule, electronic DNA-sequencing platform.

Real-time single-molecule electronic DNA sequencing by synthesis using polymer-tagged nucleotides on a nanopore array.

DNA sequencing by synthesis (SBS) offers a robust platform to decipher nucleic acid sequences. Recently, we reported a single-molecule nanopore-based SBS strategy that accurately distinguishes four bases by electronically detecting and differentiating four different polymer tags attached to the 5'-phosphate of the nucleotides during their incorporation into a growing DNA strand catalyzed by DNA polymerase. Further developing this approach, we report here the use of nucleotides tagged at the terminal phosphate with oligonucleotide-based polymers to perform nanopore SBS on an α-hemolysin nanopore array platform. We designed and synthesized several polymer-tagged nucleotides using tags that produce different electrical current blockade levels and verified they are active substrates for DNA polymerase. A highly processive DNA polymerase was conjugated to the nanopore, and the conjugates were complexed with primer/template DNA and inserted into lipid bilayers over individually addressable electrodes of the nanopore chip. When an incoming complementary-tagged nucleotide forms a tight ternary complex with the primer/template and polymerase, the tag enters the pore, and the current blockade level is measured. The levels displayed by the four nucleotides tagged with four different polymers captured in the nanopore in such ternary complexes were clearly distinguishable and sequence-specific, enabling continuous sequence determination during the polymerase reaction. Thus, real-time single-molecule electronic DNA sequencing data with single-base resolution were obtained. The use of these polymer-tagged nucleotides, combined with polymerase tethering to nanopores and multiplexed nanopore sensors, should lead to new high-throughput sequencing methods.

Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia.

PURPOSE: New treatments are needed for patients with fludarabine- and alemtuzumab-refractory (FA-ref) chronic lymphocytic leukemia (CLL) or patients with fludarabine-refractory CLL with bulky (> 5 cm) lymphadenopathy (BF-ref) who are less suitable for alemtuzumab treatment; these groups have poor outcomes with available salvage regimens. Ofatumumab (HuMax-CD20) is a human monoclonal antibody targeting a distinct small-loop epitope on the CD20 molecule. We conducted an international clinical study to evaluate the efficacy and safety of ofatumumab in patients with FA-ref and BF-ref CLL. PATIENTS AND METHODS: Patients received eight weekly infusions of ofatumumab followed by four monthly infusions during a 24-week period (dose 1 = 300 mg; doses 2 to 12 = 2,000 mg); response by an independent review committee (1996 National Cancer Institute Working Group criteria) was assessed every 4 weeks until week 24 and then every 3 months until month 24. RESULTS: This planned interim analysis included 138 treated patients with FA-ref (n = 59) and BF-ref (n = 79) CLL. The overall response rates (primary end point) were 58% [corrected] and 47% in the FA-ref and BF-ref groups, respectively. Complete resolution of constitutional symptoms and improved performance status occurred in 57% and 48% of patients, respectively. Median progression-free survival and overall survival times were 5.7 and 13.7 months in the FA-ref group, respectively, and 5.9 and 15.4 months in the BF-ref group, respectively. The most common adverse events during treatment were infusion reactions and infections, which were primarily grade 1 or 2 events. Hematologic events during treatment included anemia and neutropenia. CONCLUSION: Ofatumumab is an active, well-tolerated treatment providing clear clinical improvements for fludarabine-refractory patients with very poor-prognosis CLL.

Assuring optimal physiologic craniocervical alignment and avoidance of swallowing-related complications after occipitocervical fusion by preoperative halo vest placement.

STUDY DESIGN: A retrospective review. OBJECTIVE: To assess the utility of preoperative halo immobilization in the avoidance of swallowing complications-associated occipitocervical fixation. SUMMARY OF BACKGROUND DATA: The craniocervical region is commonly affected by a number of pathologic processes. Fixation of the upper cervical spine to the occiput provides an excellent means of treating these conditions. Occipitocervical fixation, however, is associated with a number of potential complications. One under-reported postoperative complication is the swallowing difficulty that some patients experience. Another is the overall patient dissatisfaction with postoperative head position. One means that the authors have used to avoid these complications is the use of preoperative halo vest fixation. METHODS: In this article, we report our experience with preoperative halo vest immobilization for occipitocervical fusion in 12 consecutive patients over a 5-month period and its effect on postoperative complications. We also report our experience with the index case of this series in which the patient required operative revision because of severe postoperative dysphagia and stridor after an occipitocervical fusion. RESULTS: All patients achieved satisfactory postoperative head position using the preoperative halo immobilization technique. One patient experienced transient dysphagia, which did not require intervention. No patients experienced any complications related to the placement of the halo vest itself. CONCLUSIONS: Preoperative halo immobilization allows patients, who are going to have their head permanently fixed in a particular position, to determine if they are able to tolerate the new head position. This allows the surgeon to adjust the head position before permanently locking the patient in the position, if necessary. We, therefore, advocate the use of preoperative halo immobilization as a means of assuring physiologic craniocervical neutrality and the avoidance of the resultant complications.

High-efficiency microarray printer using fused-silica capillary tube printing pins.

We describe a contact printing approach for microarrays that uses fused-silica capillary tubes with tapered tips for printing pins and a pressure/vacuum system to control pin loading, printing, and cleaning. The printing process is insensitive to variable environmental factors such as humidity, and the small diameter of the pins allows routine printing from 1536 well source plates. Pin load capacity, 0.2 microL in the current system, is adjustable by controlling pin length. More than 2000 spots can be printed per 0.2-microL pin load (<100 pl/spot), and densities of >12,000 spots/cm(2) are readily achievable. Solutions with a wide range of viscosities and chemical properties can be printed. The system can print tens of thousands of different solutions at high speed, due to the ability to use large numbers of pins simultaneously, and can produce a large number of replicate arrays since all of the solution picked up by the pins is available for deposition.

Demonstration of passive protection in neonatal calves against colibacillosis following immunization of pregnant heifers at 3 months of gestation.

Enterotoxigenic Escherichia coli is one of the primary etiologic agents for diarrhea in neonatal calves. Immunization of dams can provide passive protection in neonatal calves; antibodies transferred through colostrum block colonization of bacteria, thereby preventing disease. In this study, healthy pregnant heifers were vaccinated at approximately 3 months of gestation with either a polyvalent oil-adjuvanted vaccine containing inactivated coronavirus, rotavirus, E. coli K99 subunit antigen, and Clostridium perfringens b and e toxoid or normal saline as a placebo. Calves were allowed to nurse immediately after birth, were orally challenged with virulent heterologous enterotoxigenic E. coli at 1 day of age, and were observed for clinical signs of scours for 10 days. Signs of severe scours were noted in 75% of control calves and 28.6% of vaccinates, and the severity of scours was significantly higher (P = .0382) in the control group. The mortality rate was significantly higher (P = .0007) in the control group (80%) than in the vaccinate group (14%). These findings indicate that the vaccination of pregnant heifers at as early as 3 months of gestation (6 months before calving) provides passive protection in neonatal calves against colibacillosis.

Analytical validation and biological evaluation of a high molecular-weight adiponectin ELISA.

BACKGROUND: Of the 3 circulating multimeric forms of adiponectin, the high-molecular-weight (HMW) form, as measured by size-exclusion and/or immunoblotting techniques, is a better index of insulin sensitivity for monitoring health and disease than is total adiponectin. We aimed to develop a simple ELISA to measure HMW adiponectin. METHODS: We pretreated serum or plasma samples with digestion solution containing proteinase K (Millipore, ESDS). HMW (Millipore, EZHMWA-64K) and total adiponectin (Millipore, EZHADP-61K) concentrations were measured in treated and untreated samples, respectively, from 108 individuals and from 20 morbidly obese patients before and at 1, 3, 6, and 12 months after gastric-bypass surgery. RESULTS: The ELISA has a dynamic range of 3-200 microg/L and a detection limit of 0.8 microg/L. Intraassay and interassay CVs were <4% and <10%, respectively. Sample-dilution curves paralleled the calibration curves. Fast protein liquid chromatography profiles of the proteinase K-treated samples revealed predominantly HMW adiponectin. Values for HMW adiponectin produced with this method are comparable with those obtained with Western blot analysis (y = 0.77x - 0.15; r = 0.96; n = 56). Body mass index (BMI)- and sex-related changes were more pronounced for HMW adiponectin and percentage of HMW adiponectin than for total adiponectin. HMW and total adiponectin increased after bypass surgery, but changes in HMW adiponectin were more pronounced and preceded changes in total adiponectin. CONCLUSION: This simple, rapid ELISA for HMW adiponectin recognizes the HMW isoform, produces results closely correlated with those obtained with Western blotting, and appears to better distinguish BMI-, sex-, and weight loss-associated differences than assays for total adiponectin.

Comparison of the mucosal immune response in dogs vaccinated with either an intranasal avirulent live culture or a subcutaneous antigen extract vaccine of Bordetella bronchiseptica.

Healthy dogs with low antibody titer to Bordetella bronchiseptica were vaccinated intranasally with an avirulent live vaccine, subcutaneously with an antigen extract vaccine, or subcutaneously and intranasally with a placebo. Intranasally vaccinated dogs developed B. bronchiseptica-specific IgA titers in nasal secretions that remained at high levels until the end of the study; dogs vaccinated subcutaneously with the antigen extract or placebo did not develop measurable antigen-specific IgA titers in nasal secretions. Dogs were challenged with virulent live B. bronchiseptica 63 days after vaccination. Intranasally vaccinated dogs had significantly lower cough scores (P < or =.0058) and shed significantly fewer challenge organisms (P <.0001) than dogs in either of the other groups. Cough scores of subcutaneously vaccinated dogs were not significantly different from placebo-vaccinated dogs.

Array comparative genomic hybridization in patients with congenital diaphragmatic hernia: mapping of four CDH-critical regions and sequencing of candidate genes at 15q26.1-15q26.2.

Congenital diaphragmatic hernia (CDH) is a common birth defect with a high mortality and morbidity. There have been few studies that have assessed copy number changes in CDH. We present array comparative genomic hybridization data for 29 CDH patients to identify and map chromosome aberrations in this disease. Three patients with 15q26.1-15q26.2 deletions had heterogeneous breakpoints that overlapped with the critical 4 Mb region previously delineated for CDH, confirming 15q26.1-15q26.2 as a critical region for CDH. The three other most compelling CDH-critical regions for genomic deletions based on these data and a literature review are located at chromosomes 8p23.1, 4p16.3-4pter, and 1q41-1q42.1. Based on these recurrent deletions at 15q26.1-15q26.2, we hypothesized that loss-of-function mutations in a gene or genes from this region could cause CDH and sequenced six candidate genes from this region in more than 100 patients with CDH. For three of these genes (CHD2, ARRDC4, and RGMA), we identified missense changes and that were not identified in normal controls; however, none of these alterations appeared unambiguously causal with CDH. These data suggest that CDH caused by chromosome deletions at 15q26.2 may arise because of a contiguous gene deletion syndrome or may have a multifactorial etiology. In addition, there is evidence for substantial genetic heterogeneity in CDH and diaphragmatic hernias can be non-penetrant in patients who have deletions involving CDH-critical regions.

Surgical management of spinal metastases: analysis of prognostic factors during a 10-year experience.

OBJECT: Refinement of surgical techniques, especially anterior approaches, for the management of spinal metastases has improved patient outcomes, despite the fact that a complete analysis of the prognostic factors that would inform patient selection has not been undertaken. The authors sought to identify such prognostic factors for neurological outcome and life expectancy in patients with spinal metastases. METHODS: The authors used Kaplan-Meier techniques, log-rank comparisons, and a multivariate model stratified by tumor type to identify prognostic factors for duration of ability to walk and survival in patients who underwent surgical treatment for spinal metastases during a decade when all current treatment options were available. Preoperatively, 53 (87%) of the 61 patients in the study population suffered neurological symptoms (for example, weakness) and 52 (85%) were ambulatory. Postoperatively, 59 (97%) were ambulatory. Most patients who survived 6 months (81%) remained ambulatory, as did 66% of those alive at 1.6 years. The median postoperative survival was 10 months. The risk factors for loss of ambulation were preoperative loss of ambulatory ability, recurrent or persistent disease after primary radiotherapy of the operative site, a procedure other than corpectomy, and tumor type other than breast cancer. Prognostic factors for reduced survival were surgical intervention extending over two or more spinal segments, recurrent or persistent disease after primary radiotherapy involving the operative site, diagnosis other than breast cancer, and a cervical spinal procedure. CONCLUSIONS: The results of this analysis allowed the authors to create a simple prognostic factor scoring system that can be applied to individual patients. The positive experience derived from this study supports an expanded role for the surgical treatment of metastatic spinal disease.

Factors associated with response to lamivudine: Retrospective study in a tertiary care clinic serving patients with chronic hepatitis B.

BACKGROUND AND AIMS: Chronic hepatitis B (CHB) is an important cause of end stage liver disease and hepatocellular carcinoma. Controlled clinical trials indicate treatment with lamivudine results in positive clinical responses. The study goal was to determine if the response to lamivudine treatment (HBeAg loss, HBV DNA loss and alanine aminotransferase [ALT] reduction) differs according to pretherapy (pre-tx) ALT levels. METHODS: This was a retrospective review of medical record data. All CHB patients at all stages of disease (including cirrhotic) with more than two visits to the clinic were included in the study (n = 719). Kaplan-Meier survival and Cox proportional hazards were estimated. RESULTS: Of the total 719 HBsAg (+) patients, 317 were treated with lamivudine 150 mg or 100 mg daily. Among HBeAg positive patients, at 3 years, Kaplan-Meier estimates of the loss of HBeAg were 40%, 57% and 61% for pre-tx ALT < upper limit of normal (ULN), 1-2 x ULN and >2 x ULN, respectively. Similar results of HBV-DNA loss were seen in HBeAg negative patients. CONCLUSIONS: In this setting, we observed that pre-tx ALT levels were not associated with response to lamivudine, but that lower platelet count and female sex in HBeAg (+) patients were important predictive factors of a favorable response to lamivudine therapy.

Ovarian cancer in women with prior hysterectomy.

OBJECTIVE: To determine the proportion of women with ovarian cancer treated at our institution who may have had their disease prevented if oophorectomy had been performed during prior hysterectomy. MATERIALS AND METHODS: One hundred twelve women with ovarian cancer treated at our institution were identified through records in our Gynecologic Oncology office. We identified 19 women (17%) who had undergone prior hysterectomy without bilateral oophorectomy (Group 1). We compared age at cancer diagnosis, stage of disease, and cell type between these women and the 93 without prior hysterectomy (Group 2). RESULTS: The mean age at hysterectomy for women in Group 1 was 33.8+/-5.9 years (range 21-44 years). There were 7 women over the age of 35 years, 3 of whom were over the age of 40 years at time of hysterectomy. Overall, 17.0% of ovarian cancer cases theoretically could have been prevented if bilateral oophorectomy had been performed at the time of hysterectomy. However, this drops to only 2.7% if oophorectomy was limited to women over 40 years. CONCLUSION: Women in our study who underwent prior hysterectomy did so at a relatively young age. This limited the impact prophylactic oophorectomy could have had on ovarian cancer prevention in our population.

Determinants of early mortality in patients with decompensated chronic hepatitis B treated with antiviral therapy.

BACKGROUND & AIMS: Chronic hepatitis B is a leading cause of death worldwide. To identify patients who might require urgent liver transplantation despite antiviral therapy, we investigated the determinants of early mortality in a large cohort of patients with decompensated chronic hepatitis B treated with lamivudine. METHODS: One hundred fifty-four North American patients with decompensated chronic hepatitis B received lamivudine for a median of 16 months. Univariate and multivariate Cox regression modeling was used to develop a model of 6-month mortality. RESULTS: A biphasic survival pattern was observed, with most deaths occurring within the first 6 months of treatment (25 of 32, 78%) because of complications of liver failure. The estimated actuarial 3-year survival of patients who survived at least 6 months was 88% on continued treatment. In multivariate modeling, elevated pretreatment serum bilirubin and creatinine levels as well as the presence of detectable hepatitis B virus (HBV) DNA (by the bDNA assay) pretreatment were significantly associated with 6-month mortality. An equation approximating the probability of early mortality was developed from these variables. CONCLUSIONS: Our data demonstrate a distinct alteration in the slope of the survival curve after 6 months of lamivudine treatment for decompensated chronic hepatitis B. An equation consisting of 3 widely available pretreatment laboratory parameters was developed that can be used to predict the likelihood of early death in patients receiving lamivudine for decompensated chronic hepatitis B. These observations may help identify patients who can be stabilized with suppressive antiviral therapy vs. those who require urgent liver transplantation.