Pediatric Trauma Recidivism: A Statewide Risk Factor Analysis of the Maryland Health Services Cost Review Commission (HSCRC).

BACKGROUND: National estimates suggest pediatric trauma recidivism is uncommon but are limited by short follow up and narrow ascertainment. We aimed to quantify the long-term frequency of trauma recidivism in a statewide pediatric population and identify risk factors for re-injury. METHODS: The Maryland Health Services Cost Review Commission Dataset was queried for 0-19-year-old patients with emergency department or inpatient encounters for traumatic injuries between 2013 and 2019. We measured trauma recidivism by identifying patients with any subsequent presentation for a new traumatic injury. Univariate and multivariable regressions were used to estimate associations of patient and injury characteristics with any recidivism and inpatient recidivism. RESULTS: Of 574,472 patients with at least one injury encounter, 29.6% experienced trauma recidivism. Age ≤2 years, public insurance, and self-inflicted injuries were associated with recidivism regardless of index treatment setting. Of those with index emergency department presentations 0.06% represented with an injury requiring inpatient admission; unique risk factors for ED-to-inpatient recidivism were age >10 years (aOR 1.61), cyclist (aOR 1.31) or burn (aOR 1.39) mechanisms, child abuse (aOR 1.27), and assault (aOR 1.43). Among patients with at least one inpatient encounter, 6.3% experienced another inpatient trauma admission, 3.4% of which were fatal. Unique risk factors for inpatient-to-inpatient recidivism were firearm (aOR 2.48) and motor vehicle/transportation (aOR 1.62) mechanisms of injury (all p < 0.05). CONCLUSIONS: Pediatric trauma recidivism is more common and morbid than previously estimated, and risk factors for repeat injury differ by treatment setting. Demographic and injury characteristics may help develop and target setting-specific interventions. LEVEL OF EVIDENCE: III (Retrospective Comparative Study).

BLM overexpression as a predictive biomarker for CHK1 inhibitor response in PARP inhibitor-resistant BRCA-mutant ovarian cancer.

Poly(ADP-ribose) polymerase inhibitors (PARPis) have changed the treatment paradigm in breast cancer gene (BRCA)-mutant high-grade serous ovarian carcinoma (HGSC). However, most patients eventually develop resistance to PARPis, highlighting an unmet need for improved therapeutic strategies. Using high-throughput drug screens, we identified ataxia telangiectasia and rad3-related protein/checkpoint kinase 1 (CHK1) pathway inhibitors as cytotoxic and further validated the activity of the CHK1 inhibitor (CHK1i) prexasertib in PARPi-sensitive and -resistant BRCA-mutant HGSC cells and xenograft mouse models. CHK1i monotherapy induced DNA damage, apoptosis, and tumor size reduction. We then conducted a phase 2 study (NCT02203513) of prexasertib in patients with BRCA-mutant HGSC. The treatment was well tolerated but yielded an objective response rate of 6% (1 of 17; one partial response) in patients with previous PARPi treatment. Exploratory biomarker analyses revealed that replication stress and fork stabilization were associated with clinical benefit to CHK1i. In particular, overexpression of Bloom syndrome RecQ helicase (BLM) and cyclin E1 (CCNE1) overexpression or copy number gain/amplification were seen in patients who derived durable benefit from CHK1i. BRCA reversion mutation in previously PARPi-treated BRCA-mutant patients was not associated with resistance to CHK1i. Our findings suggest that replication fork-related genes should be further evaluated as biomarkers for CHK1i sensitivity in patients with BRCA-mutant HGSC.

Krukenberg tumor in pregnancy: a rare case and review of the literature.

Krukenberg's tumor diagnosed in pregnancy is an uncommon situation that raises both diagnosis and medical management issues. We performed a review of the existing literature regarding this pathology, diagnostic means and therapeutic approaches, motivated by a case in our own practice. A 35-year-old primigravida was diagnosed with an adnexal mass during the first trimester prenatal ultrasound. Ultrasound revealed a 10 cm right adnexal mass with multiple septae, richly vascularized, whose presence and characteristics were confirmed by magnetic resonance imaging. Due to the progressively increasing tumor size, laparoscopy was performed with right adnexectomy and peritoneal biopsies. Histopathology diagnosed a metastatic ovarian tumor from a mucinous colorectal adenocarcinoma. After delivery the patient was further investigated and diagnosed with sigmoid cancer. Even though ovarian cancer in pregnancy is rare, adnexal ultrasound is mandatory when scanning during the first trimester to rule out the presence of associated fallopian or ovarian masses.

Recent advancements of antiangiogenic combination therapies in ovarian cancer.

Ovarian cancer is a deadly malignancy with a growing therapeutic armamentarium, though achieving sustained benefit in the clinic remains largely elusive. Through biomarker and genetic analysis, several pathways of resistance and sensitivity to commonly used therapeutics have been identified, expanding the potential of identifying unique drug combinations and indicating new directions for improving clinical outcomes. Here, we review the mechanisms of angiogenic response and antiangiogenic therapy in ovarian cancer, as well as the interactions it exhibits with the immune and DNA damage response pathways. We discuss results from clinical trials examining the combinations of antiangiogenics, PARP inhibitors, and immune checkpoint inhibitors are also discussed, as well as several ongoing trials.

Assessing the diagnostic accuracy for pleomorphic adenoma and Warthin tumor by employing the Milan System for Reporting Salivary Gland Cytopathology: An international, multi-institutional study.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has established distinct diagnostic categories for reporting cytopathological findings, and each is associated with a defined risk of malignancy (ROM). However, the ROM is applied at the overall category level and is not specific for particular morphological entities within a category. Here, the diagnostic performance of the MSRSGC for pleomorphic adenoma (PA) and Warthin tumor (WT) is reported. METHODS: The pathology archives of 11 institutions from 4 countries were retrospectively searched to identify all salivary gland fine-needle aspiration (FNA) biopsies with a differential or definitive diagnosis of PA or WT and all resection specimens with a diagnosis of PA or WT; only paired cases were included. All FNA diagnoses were retrospectively classified according to the MSRSGC. RESULTS: A total of 1250 cases met the inclusion criteria, and they included 898 PA cases and 352 WT cases. The ROM in the benign neoplasm category was 3.0% and 1.3% for cases with a differential or definitive diagnosis of PA and WT, respectively. The ROM in the salivary gland neoplasm with uncertain malignant potential (SUMP) category was 2.7% and 18.8% for PA and WT, respectively (P = .0277). The diagnostic accuracy for PA and WT was 95.1% and 96.1%, respectively. CONCLUSIONS: The diagnostic accuracy for PA and WT on FNA is high. Furthermore, these findings highlight the difference in the ROMs associated with 2 specific differential diagnoses in the SUMP category: basaloid neoplasms and oncocytoid neoplasms.

Adenoid cystic carcinoma cytology: Salivary gland and nonsalivary gland.

OBJECTIVES: Adenoid cystic carcinoma (ACCA) is an uncommon primary malignancy of salivary glands and rarely nonsalivary tissue. This study aims to evaluate the diagnostic accuracy of ACCA on fine needle aspiration (FNA) material and the associated challenges. METHODS: A search on electronic pathology database from 2006 to 2016 at The Johns Hopkins Hospital found 83 cytology specimens diagnosed as ACCA, 49 with histology follow-up. RESULTS: Fifty-two females and 31 males were found ranging from 37 to 95 years old (mean 62.5). The tumor size was 1 to 11.5 cm (mean 3.4). FNAs were performed on 46 salivary glands (54.88%), 12 head and neck masses (14.45%), 9 lymph nodes (10.84%), 9 tracheas/lungs (10.84%), 4 vaginal/perineum/gluteal masses (4.82%), and one for each kidney, liver and abdominal/pelvic mass (1.21%). 83 FNA diagnoses revealed 3 nondiagnostics (3.61%), 20 neoplasms with unspecified features (24.10%), 30 basaloid neoplasms (36.14%), 18 ACCA (21.69%), and 12 other malignancies (14.46%). The accuracy of FNA in diagnosis of ACCA comparing to histologic follow-up in 49 cases was 87.5% sensitivity, 66.67% specificity, with 92.11% positive predictive value and 54.55% negative predictive value. The most common mimicker was pleomorphic adenoma. CONCLUSION: ACCA can be diagnosed not only in the salivary gland FNAs, but also respiratory tract, intra-abdominal, kidney, and gynecologic regions. FNA is a preferred technique to assess mass lesions. However, a diagnosis of ACCA on FNA material should be rendered with caution since there are benign and malignant neoplasms with overlapping features. Awareness of prior medical history and ancillary studies can improve the diagnosis.

Phase II trial of bevacizumab and sorafenib in recurrent ovarian cancer patients with or without prior-bevacizumab treatment.

OBJECTIVE: To examine whether blocking multiple points of the angiogenesis pathway by addition of sorafenib, a multi-kinase inhibitor against VEGFR2/3, Raf, c-Kit, and PDGFR, to bevacizumab would yield clinical activity in ovarian cancer (OvCa). METHODS: This phase II study tested bevacizumab plus sorafenib in two cohorts; bevacizumab-naïve and bevacizumab-exposed patients. Bevacizumab (5 mg/kg IV every 2 weeks) was given with sorafenib 200 mg bid 5 days-on/2 days-off. The primary objective was response rate using a Simon two-stage optimal design. Progression-free survival (PFS) and toxicity were the secondary endpoints. Exploratory correlative studies included plasma cytokine concentrations, tissue proteomics and dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI). RESULTS: Between March 2007 and August 2012, 54 women were enrolled, 41 bevacizumab-naive and 13 bevacizumab-prior, with median 5 (2-9) and 6 (5-9) prior systemic therapies, respectively. Nine of 35 (26%) evaluable bevacizumab-naive patients attained partial responses (PR), and 18 had stable disease (SD) ≥ 4 months. No responses were seen in the bevacizumab-prior group and 7 (54%) patients had SD ≥ 4 months, including one exceptional responder with SD of 27 months. The overall median PFS was 5.5 months (95%CI: 4.0-6.8 months). Treatment-related grade 3/4 adverse events (≥5%) included hypertension (17/54 [31%]; grade 3 in 16 patients and grade 4 in one patient) and venous thrombosis or pulmonary embolism (5/54 [9%]; grade 3 in 4 patients and grade 4 in one patient). Pretreatment low IL8 concentration was associated with PFS ≥ 4 months (p = .031). CONCLUSIONS: The bevacizumab and sorafenib combination did not meet the pre-specified primary endpoint although some clinical activity was seen in heavily-pretreated bevacizumab-naive OvCa patients with platinum-resistant disease. Anticipated class toxicities required close monitoring and dose modifications.

Self-reported and clinical periodontal conditions in a group of Eastern European postpartum women.

Periodontitis is a highly prevalent condition leading to a continuous destruction of tooth-supporting tissues. It increases the risk for various systemic diseases and adverse pregnancy outcomes. Therefore, screening for periodontitis is important. Screening measures can range from self-reported symptoms to clinical full-mouth periodontal examination. The hypothesis of our study was that self-reported parameters and clinical definition perform equally well in identifying periodontitis patients. The aim of this study was to develop, validate its internal consistency, and evaluate a self-reported instrument against periodontal clinical evaluation for diagnosis of periodontitis in a group of postpartum women, as well as to describe their periodontal status and the risk factors associated with periodontal disease. A cross-sectional study on postpartum women was conducted in a tertiary university hospital, from April 2018 to March 2019. Sociodemographic and behavioral data, periodontal clinical parameters, and self-reported periodontal perception were collected. A 16-item questionnaire was developed to obtain information about perceived periodontal alterations and oral hygiene habits. The utility of the questionnaire was tested against a periodontal diagnosis based on a full-mouth periodontal examination. The questionnaire was applied in 215 postpartum women aged 29.16±5.54 years (mean age (y) ± standard deviation) having the following periodontal status: 16 individuals without periodontal disease (7.44%), 32 individuals with gingivitis (14.88%), 19 individuals with mild periodontitis (8.84%), 132 individuals with moderate periodontitis (61.39%), and 16 individuals with severe periodontitis (7.44%). A significant association was observed between oral hygiene score, smoking status, and periodontal conditions (p<0.05). A significant association between the self-reported items related to "gum swelling", "halitosis", "previous periodontal diagnosis" and "previous periodontal treatment" with clinical periodontitis have been identified (p<0.05). Using self-reported questionnaires for detection of periodontal disease was ineffective in our studied population, since self-reported parameters and clinical definition do not appear to perform equally in identifying periodontitis cases. Clinical periodontal examination remains the gold standard for screening. Periodontitis was frequent in our group and the severity was significantly associated with the oral hygiene score and smoking. These results underline the necessity for periodontal clinical examination during pregnancy.

Clinical outcomes of prexasertib monotherapy in recurrent BRCA wild-type high-grade serous ovarian cancer involve innate and adaptive immune responses.

BACKGROUND: Preclinical data suggest cell cycle checkpoint blockade may induce an immunostimulatory tumor microenvironment. However, it remains elusive whether immunomodulation occurs in the clinical setting. To test this, we used blood and fresh tissue samples collected at baseline and post therapy from a phase II trial of the cell cycle checkpoint 1 inhibitor (CHK1i) prexasertib in recurrent ovarian cancer. METHODS: Paired blood samples and fresh core biopsies, taken before treatment was started at baseline (cycle 1 day 1 (C1D1)) and post second dose on day 15 of cycle 1 (C1D15), were collected. To evaluate changes in the immune responses after treatment, multiparametric flow cytometry for DNA damage markers and immune cell subsets was performed on paired blood samples. RNA sequencing (RNAseq) of paired core biopsies was also analyzed. Archival tissue immune microenvironment was evaluated with immunohistochemistry. All correlative study statistical analyses used two-sided significance with a cut-off of p=0.05. RESULTS: Flow cytometric analysis showed significantly increased γ-H2AX staining after CHK1i treatment, accompanied by increased monocyte populations, suggestive of an activated innate immune response (median 31.6% vs 45.6%, p=0.005). Increased expressions of immunocompetence marker HLA-DR (Human Leukocyte Antigen DR antigen) on monocytes and of TBK1, a marker of STING (stimulator of interferon genes) pathway activation, in biopsies were associated with improved progression-free survival (PFS) (9.25 vs 3.5 months, p=0.019; 9 vs 3 months, p=0.003, respectively). Computational analysis of RNAseq data indicated increased infiltration of tumor niches by naïve B-cells and resting memory T-cells, suggestive of a possibly activated adaptive immune response, and greater T-reg infiltration after treatment correlated with worse PFS (9.25 vs 3.5 months, p=0.007). An immunosuppressive adaptive immune response, perhaps compensatory, was also observed on flow cytometry, including lymphodepletion of total peripheral CD4+ and CD8+T cells after CHK1i and an increase in the proportion of T-regs among these T-cells. Additionally, there was a trend of improved PFS with greater tumor-infiltrating lymphocytes (TILs) in archival tissues (13.7 months >30% TILs vs 5.5 months ≤30% TILs, p=0.05). CONCLUSION: Our study demonstrates that a favorable clinical response in high-grade serous ovarian carcinoma patients treated with CHK1i is possibly associated with enhanced innate and adaptive immunity, requiring further mechanistic studies. It is supportive of current efforts for a clinical development strategy for therapeutic combinations with immunotherapy in ovarian cancer.

Risk of malignancy associated with cytomorphology subtypes in the salivary gland neoplasm of uncertain malignant potential (SUMP) category in the Milan System: A bi-institutional study.

BACKGROUND: Salivary gland neoplasm of uncertain malignant potential (SUMP) is a diagnostic category in the Milan System for Reporting Salivary Gland Cytopathology. The objective of this study was to assess the risk of neoplasm (RON) and the risk of malignancy (ROM) in SUMP cases by evaluating them based on their prominent cytomorphology. METHODS: The pathology databases were searched for cases of fine-needle aspiration-diagnosed SUMP at The Johns Hopkins Hospital and Northwestern University from 2013 to 2018. Only cytopathology cases diagnosed as SUMP that had available surgical follow-up were included. RESULTS: Sixty-five patients with SUMP were identified, including 31 men and 34 women who ranged in age from 15 to 87 years (mean age, 55.2 years). Sixty-five cases had histologic follow-up, including 13 (20%) with basaloid features, 13 (20%) with oncocytic features, and 39 (60%) with unspecified features. No cases with clear cell features were found. Overall, the RON in the SUMP category was 95.4% (62 of 65 cases), and the ROM was 33.8% (22 of 65 cases). The RON in SUMPs with basaloid, oncocytic, and unspecified subtypes was 92.3%, 100%, and 94.9%, respectively, whereas the ROM was 38.5%, 7.7%, and 41%, respectively. The most common benign neoplasm was pleomorphic adenoma (23.1%), whereas mucoepidermoid carcinoma (9.2%) was the most common malignant neoplasm. CONCLUSIONS: This study shows that the ROM differs significantly based on cytomorphology subtypes, whereas the overall ROM is approximately the same as the target rate in the Milan System for Reporting Salivary Gland Cytopathology. Moreover, the RON remains high in the SUMP category among different cytomorphology subtypes. Adequate sampling, immunohistochemical staining, and familiarity with metaplastic and reactive changes may improve the diagnosis.

Mucoepidermoid carcinoma, acinic cell carcinoma, and adenoid cystic carcinoma on fine-needle aspiration biopsy and The Milan System: an international multi-institutional study.

BACKGROUND: We evaluated the diagnostic accuracy (DA), risk of neoplasm (RON), and risk of malignancy (ROM) for the commonly encountered malignant salivary gland tumors mucoepidermoid carcinoma (MECa), acinic cell carcinoma (ACCa), and adenoid cystic carcinoma (ADCa) applying The Milan System for Reporting Salivary Gland Cytology (MSRSGC). MATERIALS AND METHODS: The cytology archives from 2007 to 2017 of 9 academic institutions were searched for salivary gland FNAs for the following key words mentioned either in the principal and/or differential diagnosis: MEC, ACCa, and ADCa. The original cytology diagnosis was retrospectively classified according to the MSRSGC. Patient demographics, biopsy site, and available surgical follow-up were recorded. The final analysis included only cases with surgical follow-up. RESULTS: A total of 212 salivary gland FNAs were included. Based on retrospective reclassification according to MSRSGC, 97 of 212 (46%) FNA cases carried a diagnosis of malignancy specific for either MECa, ACCa, or ADCa. In the remaining 115 cases, 24 of 212 (11%) were reclassified as suspicious for malignancy (SM) and 91 of 212 (43%) as salivary gland neoplasm of uncertain malignant potential (SUMP). The DA for MECa, ACCa, and ADCa was 78.7%, 75% and 89%, respectively. The RON was 100% for all 3 tumors and the ROM was 93.6% for MECa, 96.8% for ACCa, and 94.4% for ADCa. CONCLUSIONS: The DA of 78.7% for MECa, 75% for ACCa, and 89% for ADCa is reasonable in FNA specimens. Although the management of definitive cases of malignancy remains unchanged, the MSRSGC provides a ROM for SM and SUMP categories, which can improve patient management.

Silencing Prion Protein in HT29 Human Colorectal Cancer Cells Enhances Anticancer Response to Fucoidan.

BACKGROUND: The putative functions of the cellular prion protein (PrP(c)) are believed to be associated with cell signaling, differentiation, survival, and cancer progression. With respect to cancer development and progression, elevations and mutations of PrP(c) expression have been shown to increase the risk for malignancy and metastasis in breast and colorectal cancer. Since both natural supplements and direct regulation of PrP(c) expression contribute to inhibition of cancer progression and growth, we hypothesized that knockdown of PrP(c) could lead to an enhanced synergic effect on the inhibition of cancer growth by fucoidan. MATERIALS AND METHODS: PrP(c) expression was suppressed in HT29 human colon cancer cells by utilizing small-interfering RNA (si-PRNP), and cells were subsequently used to study the antiproliferative and anticancer effects of fucoidan treatment of HT29 human colon cancer cells. RESULTS: Fucoidan treatment significantly inhibited growth and reduced cyclin and cyclin-dependent kinase (CDK) expression in HT29 colon cancer cells. Furthermore, silencing PrP(c) expression with si-PRNP amplified the fucoidan-induced changes in cell proliferation, apoptosis, and migration. Intraperitoneal injection of si-PRNP with fucoidan reduced proliferation and tumor volume in Balb/c nude mice. This enhanced antitumor efficacy was associated with decreased angiogenesis. CONCLUSION: Combination of fucoidan with silencing of PrP(c) has a synergic effect on the inhibition of HT29 colon cancer cell growth. Furthermore, we provide evidence for the therapeutic application of PrP(c) silencing with other anticancer drugs for cancer.

Noninvasive assessment of liver steatosis using ultrasound methods.

Hepatic steatosis is a condition frequently encountered in clinical practice, with potential progression towards chirrhosis and hepatocellular carcinoma. Ultrasonography (US) is one of the noninvasive imaging techniques used in the diagnosis of steatosis. We will review the US diagnostic criteria, the US performance in the diagnosis and grading of hepatic steatosis, the US steatosis models, but also its limitations in the diagnosis of steatosis. In addition, we will discuss 2 modern methods of assessing hepatic steatosis using ultrasounds, namely the computerized processing of data forming the US image and the controlled attenuation parameter measured with unidimensional transient elastography.

Defective entry into mitosis 1 (Dim1) negatively regulates osteoclastogenesis by inhibiting the expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1).

Bone remodeling is a continuous process of osteoblastic bone formation and osteoclastic bone resorption to maintain normal bone mass. NFATc1 is the master regulator of osteoclastogensis and transcriptionally activated by c-Fos and NF-κB in response to receptor activator of NF-κB ligand (RANKL) treatment. Defective entry into mitosis 1 (Dim1) is a nuclear protein that is implicated in pre-mRNA splicing and cell cycle progression, but the possible role of Dim1 in regulating other cellular processes remains unknown. Here, we demonstrate that Dim1 attenuates RANKL-induced osteoclastogenesis by targeting NFATc1 signaling pathway. Expression levels of Dim1 and NFATc1 are significantly increased during the formation of multinucleated osteoclasts. RNAi-mediated knockdown of Dim1 markedly enhances the expression of NFATc1 and its target genes, leading to the increase of RANKL-induced osteoclastogenesis in bone marrow-derived macrophages. Conversely, ectopic expression of Dim1 decreases RANKL-induced osteoclast differentiation by silencing NFATc1 and its target genes, further linking Dim1 to the dynamic regulation of osteoclastogenesis. Consistent with this notion, ChIP and interaction studies show that Dim1 directly associates with c-Fos and prevents c-Fos from binding to the NFATc1 promoter, resulting in targeted inactivation of the NFATc1 gene. Therefore, our studies reveal an unrecognized role for Dim1 as a master modulator of osteoclast differentiation, as well as the molecular mechanism underlying its repressive action toward osteoclastogensis.

Cystatin C as a marker of residual renal function during continuous hemodiafiltration.

BACKGROUND: The level of residual renal function (RRF) has an important impact on follow-up in critically ill patients with renal failure. There is currently no clear marker of RRF. METHODS: Cystatin C (cysC) concentrations were measured before and during the first 48 h of CVVHDF in 33 mechanically ventilated patients suffering from renal failure. Samples were drawn both from the ports proximal and distal to the filter. Each of the two control groups consisted of 10 patients. RESULTS: The levels of cysC were significantly higher in the group where diuresis (Vu) remained low or decreased after 48 h of treatment (n = 21, Vu median 380 (80-935) ml/24 h, cysC range 4.44-3.42 mg/l) than in the group where Vu increased to the level of 1.5 ml.kg(-1).h(-1) or higher after 48 h of treatment (n = 12, Vu 4,570 (4,000-5,130) ml/24 h, cysC 3.17-2.46 mg/l, p < 0.01). Creatinine clearance taken before treatment was not different between the groups. Significant correlation between cysC levels and Vu was found (r = -0.44, p < 0.0001). CysC levels were significantly higher in non-survivors than in survivors (3.54 +/- 1.38 vs. 3.07 +/- 1.24, p < 0.03). CONCLUSION: The levels of cysC are inversely related to Vu. High levels of cysC are associated with low residual diuresis, longer duration of CVVHDF and higher intensive care unit mortality in patients treated with CVVHDF.

Relationship between natriuretic peptides and residual diuresis during continuous hemodiafiltration.

BACKGROUND: The reasons for the decrease or increase of urine output following the start of continuous venovenous hemodiafiltration (CVVHDF) have not yet been explained sufficiently. The renoprotective properties of natriuretic peptides were described. METHODS: The levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured in 23 mechanically ventilated patients before and during the first 48 h of CVVHDF. Samples were drawn both from the ports proximal and distal to the filter. The results were compared between the group where daily diuresis (Vu) remained low or decreased and the group where diuresis increased to the level of 1.5 ml x kg(-1) x h(-1) or higher after 48 h of treatment. Left ventricular dysfunction (LVD) was defined as LV ejection fraction below 40%. A control group consisted of 10 patients exposed to abdominal surgery. RESULTS: The average AVdiff (%) of ANP and BNP on filter were insignificant. Patients with increasing diuresis (n = 12) had significantly lower levels of both ANP (p < 0.001) and BNP (p < 0.005) than the patients with decreasing diuresis (n = 11). Significant correlations were revealed for ANP and Vu (p < 0.01) and for BNP and Vu (p < 0.05). The levels of both peptides were grossly elevated in comparison to controls and were predictive of survival. The differences between cardiac and non-cardiac patients were significant both for ANP and for BNP. CONCLUSIONS: The elimination of ANP and BNP by the CVVHDF is negligible. The levels of natriuretic peptides are inversely related to Vu and predict survival. ANP and BNP levels correlate with left ventricular function even during acute renal failure and CVVHDF.