Prognostic impact of FOXF1 polymorphisms in gastric cancer patients.

A recent genome-wide association study identified seven single-nucleotide polymorphisms (SNPs) in region 16q24, near the Forkhead box-F1 (FOXF1) gene, which confer susceptibility to esophageal adenocarcinoma. We examined whether these SNPs are associated with clinical outcomes in gastric cancer (GC) patients in Japan and the United States. A total of 362 patients were included in this study: 151 Japanese GC patients treated with first-line S1 plus CDDP (training cohort) and 211 GC patients from Los Angeles County (LAC; validation cohort). Genomic DNA was isolated from whole blood or tumor tissue and analyzed by PCR-based direct DNA sequencing. Cox proportional hazard regression analyses were used to assess relationships between FOXF1 SNPs and progression-free survival (PFS) and overall survival (OS). FOXF1 rs3950627 was significantly associated with survival in both the training and validation cohorts. Japanese patients with the C/C genotype had a longer PFS (median 8.2 vs 5.3 months, hazard ratio (HR) 1.44, P=0.037) and OS (median 16.4 vs 12.2 months, HR 1.44, P=0.043) compared to patients with any A allele. Similarly, LAC patients with the C/C genotype had improved OS (3.9 vs 2.3 years, HR 1.5, P=0.022). Subgroup analyses showed these associations were specific to male patients and primary tumor subsite. Our findings suggest that FOXF1 rs3950627 might be a promising prognostic marker in GC patients.

Utility of Tolvaptan in the Perioperative Management of Severe Hyponatremia During Liver Transplantation: A Case Report.

Severe hyponatremia can complicate the pretransplantation management of patients with decompensated cirrhosis while they await liver transplantation. Before the liver transplant, it is critical to correct severe hyponatremia to an appropriate level to reduce the risks of perioperative complications such as central pontine myelinolysis, cerebral edema, and seizures. Vasopressin receptor antagonists, and in particular tolvaptan, offer a therapeutic modality that can correct severe refractory hyponatremia in a timely and predictable manner before liver transplantation. In this case report, we describe a patient with decompensated cirrhosis and severe hyponatremia in whom administration of tolvaptan led to an optimal correction of preoperative severe hyponatremia and allowed for successful liver transplantation with no associated postoperative complications. In light of the increasing pretransplantation disease severity and higher risk of severe hyponatremia, the use of tolvaptan in the pretransplant period may gain increasing importance as a therapeutic intervention for maintaining peritransplant sodium homeostasis.

Comparison of Post-Liver Transplantation Outcomes in Portopulmonary Hypertension and Pulmonary Venous Hypertension: A Single-Center Experience.

BACKGROUND: In potential liver transplant candidates, pulmonary vascular diseases, including portopulmonary hypertension (PoPH) and pulmonary venous hypertension (PVH), can be associated with high morbidity and mortality. Although there are clear guidelines regarding management and transplant listing criteria for patients with PoPH, the listing criteria for PVH are not well defined. OBJECTIVE: The aim of this study was to describe and compare the perioperative and postoperative morbidity and mortality associated with PoPH and PVH in patients undergoing liver transplantation. METHODS: We conducted a retrospective observational study of all patients referred for liver transplantation to our center between 2005 and 2015 who underwent a right heart catheterization (RHC) for screening for pulmonary hypertension as suggested by initial echocardiography. Based on the RHC data, the patients were grouped into no pulmonary hypertension (No PH), PoPH, and PVH categories. In patients who underwent liver transplantation, we recorded vital status intraoperatively and at 30 days and 1-year post-transplant, and we recorded the incidence of postoperative cardiopulmonary and renal complications. RESULTS: Of the 134 patients who underwent RHC as part of the initial transplant evaluation, 50 patients were successfully transplanted. There was 1 intraoperative death in the PoPH group. No significant difference in mortality was noted between the No PH, PoPH, and PVH groups intraoperatively and 30 days after liver transplantation. At 1 year, the survival rates were 100%, 69.2%, and 94.1% in the No PH, PoPH, and PVH groups, respectively. With respect to cardiopulmonary and renal complications, no statistically significant difference was noted among the groups, though there was a trend toward increased post-transplant reversible pulmonary complications in the PVH group. CONCLUSION: Our findings suggest that the post-transplant outcomes of patients with PoPH and PVH are similar. In light of the growing recognition of diastolic dysfunction and cirrhotic cardiomyopathy in decompensated cirrhotic patients at the time of transplant, the issue of pulmonary hypertension related to PVH will gain increasing importance as we assess these patients for transplantation. Therefore, future studies are needed to define evidence based guidelines to determine candidacy for liver transplantation in the context of PVH.

Genetic variants associated with colorectal brain metastases susceptibility and survival.

Colorectal brain metastases (BM) are rare (1-2%) and a late-stage disease manifestation. Molecular mechanisms for BM development are not well understood. We tested whether variants within genes involved in overcoming the blood-brain barrier (BBB) are associated with BM susceptibility and survival in patients with BM. Germline single-nucleotide polymorphisms (SNPs, n=17) in seven genes (CXCR4, MMP9, ST6GALNAC5, ITGAV, ITGB1, ITGB3, KLF4) were analyzed from germline DNA in patients with resected BM (n=70) or no clinical evidence of BM after at least 24 months from diagnosis (control group, n=45). SNPs were evaluated for association with BM susceptibility and overall survival (OS) from BM diagnosis. ST6GALNAC5 rs17368584 and ITGB3 rs3809865 were significantly associated with BM susceptibility. In multivariable analysis adjusted for patient characteristics, KLF4 rs2236599, ITGAV rs10171481, ST6GALNAC5 rs1883778, CXCR4 rs2680880 and ITGB3 rs5918 were significant for OS. This study shows for the first time that variants within genes involved in breaching the BBB are associated with BM susceptibility and survival. These findings warrant further validation to develop better screening guidelines and to identify novel therapy targets for patients with BM.

Estrogen receptor-beta genetic variations and overall survival in patients with locally advanced gastric cancer.

Estrogen has been shown not only to reduce the incidence of colorectal cancer but also gastric cancer (GC). Polymorphisms in estrogen receptor ß gene, ESR2, correlate with colorectal cancer survival. To better understand the role of ESR2 in GC, genomic DNA extracted from 169 Japanese patients and 172 patients from Los Angeles County (LAC) was analyzed for association of overall survival (OS) with three ESR2 polymorphisms, which are of biological significance using multivariable Cox proportional hazard regression. ESR2 rs1271572 (C>A) and rs3020443 (T>G) had univariate and multivariable associations with OS in the Japanese cohort, whereas the C allele of ESR2 rs2978381 (T>C) predicted favorable OS in the Japanese cohort but worse OS in the LAC cohort. The interaction term of the ESR2 rs2978381 and cohort group reached statistical significance. Our study provides evidence that genetic variations in ESR2 gene are significantly associated with survival in patients with locally advanced GC.

Genetic variations in immunomodulatory pathways to predict survival in patients with locoregional gastric cancer.

Immunomodulator-targeting therapies are under development in gastric cancer (GC). However, the role of genes modulating anti-tumor immunity in GC remains poorly understood. We investigated the association of variations in genes involved in immunomodulatory pathways with overall survival (OS) in locoregional GC patients. Extracted genomic DNA was analyzed for 35 functional single-nucleotide polymorphisms in genes, PDCD1, CD274, CTLA4, FOXP3, LAG3, ADORA2A, NT5E and IDO1, in 162 Japanese patients as discovery set and 277 US patients as validation set. The C allele of PDCD1 rs10204525 had univariate and multivariable associations with shorter OS in Japanese cohort (P=0.015, P=0.043, respectively). In US cohort the C allele predicted worse OS (P=0.007). Univariate and multivariable analyses revealed IDO1 rs9657182 associated with OS in the Japanese cohort; moreover, the association was confirmed in the US cohort. Genetic predisposition of the host in the immunomodulators may serve as a prognostic biomarker in patients with locoregional GC.

CXCR4 polymorphism predicts progression-free survival in metastatic colorectal cancer patients treated with first-line bevacizumab-based chemotherapy.

We analyzed associations between CXCR4/CXCL12 single-nucleotide polymorphisms and outcomes in metastatic colorectal cancer (mCRC) patients who underwent first-line bevacizumab-based chemotherapy. A total of 874 patients were included in this study: 144 treated with bevacizumab and FOLFOX or XELOX (training cohort), 653 treated with bevacizumab and FOLFIRI or FOLFOXIRI (validation cohort A or B) and 77 treated with cetuximab- and oxaliplatin-based regimens (control cohort). One CXCR4 polymorphism (rs2228014) and two CXCL12 polymorphisms (rs1801157 and rs3740085) were analyzed by PCR-based direct sequencing. Patients with a C/C genotype had a prolonged progression-free survival (PFS) compared with those with any T allele (P=0.030) in the training cohort. Similarly, patients with the C/C genotype had a superior PFS in the validation cohorts, but not in the control cohort. Our findings suggest that a common genetic variant, CXCR4 rs2228014, could predict PFS and may guide therapeutic decisions in mCRC patients receiving first-line bevacizumab-based chemotherapy.

GW627368X inhibits proliferation and induces apoptosis in cervical cancer by interfering with EP4/EGFR interactive signaling.

PGE2, the major product of cyclooxygenases implicated in carcinogenesis, is significantly upregulated in cervical cancer. PGE2 via prostanoid receptor EP4 stimulates proliferation and motility while inhibiting apoptosis and immune surveillance. It promotes angiogenesis by stimulating the production of pro-angiogenic factors. The present study demonstrates GW627368X, a highly selective competitive EP4 antagonist, which hinders cervical cancer progression by inhibiting EP4/epithelial growth factor receptor (EGFR) interactive signaling. GW627368X reduced protein kinase A (PKA) phosphorylation which in turn leads to decreased cAMP response element-binding protein (CREB) activation. Decreased PKA phosphorylation also directly enhanced Bax activity and in part reduced glycogen synthase kinase 3 (GSK3)ß phosphorylation. Owing to the interactive signaling between EP4 and EGFR, GW627368X lowered EGFR phosphorylation in turn reducing Akt, mitogen-activated protein kinase (MAPK) and GSK3ß activity significantly. Sublethal dose of GW627368X was found to reduce the nuclear translocation of ß-catenin in a time dependent manner along with time-dependent decrease in cytoplasmic as well as whole-cell ß-catenin. Decreased CREB and ß-catenin transcriptional activity restricts the aberrant transcription of key genes like EP4, cyclooxygenase (COX)-2, vascular endothelial growth factor and c-myc, which ultimately control cell survival, proliferation and angiogenesis. Reduced activity of EGFR resulted in enhanced expression of 15-hydroxyprostaglandin dehydrogenase increasing PGE2 degradation thereby blocking a positive feedback loop. In xenograft model, dose-dependent decrease in cancer proliferation was observed characterized by reduction in tumor mass and volume and a marked decrease in Ki67 expression. A diminished CD31 specific staining signified decreased tumor angiogenesis. Reduced expression of pAkt, pMAPK, pEGFR and COX-2 validated in vitro results. GW627368X therefore effectively inhibits tumor survival, motility, proliferation and angiogenesis by blocking EP4/EGFR interactive signaling. EP4 is a potent therapeutic target in cervical cancer and can be explored in combination with conventional therapies to attain superior outcomes and to overcome complications associated with organ toxicities, therapeutic resistance and disease relapse.

Variations in genes regulating tumor-associated macrophages (TAMs) to predict outcomes of bevacizumab-based treatment in patients with metastatic colorectal cancer: results from TRIBE and FIRE3 trials.

BACKGROUND: Tumor-associated macrophages (TAMs) with the M2-like phenotype are regulated by mainly NF-kB pathway including TBK1, which can influence tumor progression by secretion of proangiogenic factors such as vascular endothelial growth factor. The CCL2/CCR2 axis, histidine-rich glycoprotein (HRG), and placenta growth factor (PIGF) play a critical role in the polarization of M1/M2 phenotypes and the recruitment of TAMs to tumor microenvironment. We therefore hypothesized that variations in genes involved in regulating TAMs may predict clinical outcomes of bevacizumab treatment in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: We analyzed genomic DNA extracted from samples of patients receiving bevacizumab plus FOLFIRI as a first-line treatment using PCR-based direct sequencing. Twelve functional single-nucleotide polymorphisms in eight genes (CCL2, CCR2, HRG, PIGF, NFKB1, TBK1, CCL18, and IRF3) were tested for associations with clinical outcomes in a discovery cohort of 228 participants in TRIBE trial (NCT00719797), then validated in 248 KRAS exon2 (KRAS) wild-type participants in FIRE3 trial (NCT00433927). FIRE3-cetuximab cohort served as a negative control. RESULTS: TBK1 rs7486100 was significantly associated with overall survival in 95 KRAS wild-type patients of TRIBE cohort in univariate analysis and had a strong trend in multivariable analysis; furthermore, the association of the T allele was observed for progression-free survival (PFS) in both univariate and multivariable analyses in FIRE3-bevacizumab but not cetuximab cohort. CCL2 rs4586, CCL18 rs14304, and IRF3 rs2304205 had univariate and multivariable correlations with PFS in KRAS mutant patients of the TRIBE cohort, whereas they had no correlations in KRAS wild-type patients of the TRIBE cohort. No association was seen in control cohort. CONCLUSIONS: Our study demonstrates for the first time that variations in genes regulating TAMs-related functions are significantly associated with clinical outcomes in mCRC patients treated with bevacizumab-containing chemotherapy. These results also suggest that some TAM-related gene variations may predict outcomes of bevacizumab treatment in KRAS status-dependent manner.

Variations in genes involved in dormancy associated with outcome in patients with resected colorectal liver metastases.

BACKGROUND: Tumor dormancy has been described as a state of hibernation. Dormancy can be switched to proliferation by different pathways, which may play a critical role in tumor recurrence. In this study, we investigated genetic variations within genes involved in tumor dormancy and their association with recurrence and outcome in patients with colorectal liver metastases (CLM) who underwent neoadjuvant bevacizumab-based chemotherapy. PATIENTS AND METHODS: Genomic DNA was extracted from resected CLM (FFPE) from 149 patients. Single-nucleotide polymorphisms (SNPs) in 14 genes associated with dormancy were analyzed by direct Sanger DNA sequencing and evaluated for response, recurrence-free survival (RFS), overall survival (OS) and recurrence patterns. RESULTS: NME1 rs34214448 C>A was significantly associated with RFS in univariable analysis (P = 0.039) and with intrahepatic recurrence (P = 0.014). NOTCH3 rs1044009 T>C and CD44 rs8193 C>T showed a significant difference in 3-year OS rates (P = 0.004 and P = 0.042, respectively). With respect to radiological response, CD44 rs8193 C>T variant genotypes were associated with a significantly higher response rate (P = 0.033). Recursive partitioning analyses revealed that Dll4 rs12441495 C>G, NME1 rs34214448 C>A and NOTCH3 rs1044009 T>C were the dominant SNPs predicting histological response, RFS and OS, respectively. CONCLUSION: Our data suggest that gene variations within genes involved in tumor dormancy pathways are associated with response and outcome in patients with resected CLM. These data may lead to new and more effective treatment strategies targeting tumor dormancy.

Catalyzing the Critical Path Initiative: FDA's progress in drug development activities.

The US Food and Drug Administration (FDA) has directed considerable effort towards modernizing its regulatory processes over the past decade to address the challenges in the drug development sector. Through partnerships and input from stakeholders, multiple initiatives are under way, many projects have been launched, several have resulted in tangible results, and many are ongoing and under discussion. We are learning that collaborative efforts can better inform and leverage existing knowledge, that the challenges of data sharing and intellectual property can be overcome, and that there is wide interest in partnering to address key public health regulatory science issues. It is crucial that we continue to build on these initial efforts to facilitate drug development.

Association of variants in genes encoding for macrophage-related functions with clinical outcome in patients with locoregional gastric cancer.

BACKGROUND: Nuclear factor-kappaB (NF-κB) and CCL2/CCR2 chemokine axis play a central role in tumor progression such as stimulation of angiogenesis, acceleration of tumor invasion and migration, and suppression of innate immunosurveillance in the macrophage-related functions. There have been few reports regarding association of the macrophage function-related genes with the clinical outcome in gastric cancer. We hypothesized that variants in genes encoding for NF-κB and CCL2/CCR2 axis may predict prognosis in gastric cancer and tested whether the functional single-nucleotide polymorphisms (SNPs) will be associated with clinical outcome in patients with gastric cancer across two independent groups. PATIENTS AND METHODS: This study enrolled two cohorts which consisted of 160 Japanese patients and 104 US patients with locoregional gastric cancer. Genomic DNA was analyzed for association of 11 SNPs in NFKB1, RELA, CCL2, and CCR2 with clinical outcome using PCR-based direct DNA sequencing. RESULTS: The univariable analysis showed four SNPs had significant association with clinical outcome in the Japanese cohort, NFKB1 rs230510 remained significant upon multivariable analysis. The patients with the A allele of the NFKB1 rs230510 had significantly longer overall survival (OS) compared with those with the T/T genotype in both the Japanese and US cohort in the univariable analysis. In contrast, genotypes with the T allele of CCL2 rs4586 were significantly associated with shorter OS compared with the C/C genotype in the US cohort [hazard ratio (HR) 2.43; P = 0.015] but longer OS in the Japanese cohort (HR 0.58; P = 0.021), resulting in the statistically significant opposite impact on OS (P = 0.001). CONCLUSIONS: Our study provides the first evidence that the NFKB1 rs230510 and CCL2 rs4586 are significantly associated with the clinical outcome in patients with locoregional gastric cancer. These results also suggest that the genetic predisposition of the host may dictate the immune-related component of the tumor for progression in gastric cancer.

High tuberculosis prevalence in children exposed at home to drug-resistant tuberculosis.

SETTING: Urban Karachi, Pakistan. OBJECTIVE: To describe the yield of a contact investigation protocol implemented among children living with drug-resistant tuberculosis (DR-TB) patients. DESIGN: We implemented a contact investigation protocol in households of DR-TB patients treated at the Indus Hospital, Karachi, between January 2008 and April 2011. This included a detailed history and physical examination, tuberculin skin test, chest radiograph, smear microscopy and culture of sputum or gastric aspirate specimens, and drug susceptibility testing. Treatment supporters who visited DR-TB patients at home referred all child contacts for baseline evaluation and performed monthly assessments. We evaluated two age groups: 1) children aged <5 years, and 2) those aged 5-14 years. RESULTS: Among 133 children aged <15 years in 40 households, 40.4% (51/125) were moderately to severely underweight (weight-for-age Z-score <-2). Overall, 7.5% (10/133) had TB disease. This proportion was 6.5% (2/31) in those aged <5 years and 7.8% (8/102) in those aged 5-14 years. Seven (7/10) were smear-positive, and 4/10 had culture-confirmed multidrug-resistant Mycobacterium tuberculosis CONCLUSION: We detected a high prevalence of TB in children who live with DR-TB patients, regardless of the age of the child. Child contacts of DR-TB patients are a high-yield population for detecting TB cases.

Immunostaining for the α3 isoform of the Na+/K+-ATPase is selective for functionally identified muscle spindle afferents in vivo.

Muscle spindle afferent (MSA) neurons can show rapid and sustained firing. Immunostaining for the α3 isoform of the Na(+)/K(+)-ATPase (α3) in some large dorsal root ganglion (DRG) neurons and large intrafusal fibres suggested α3 expression in MSAs (Dobretsov et al. 2003), but not whether α3-immunoreactive DRG neuronal somata were exclusively MSAs. We found that neuronal somata with high α3 immunointensity were neurofilament-rich, suggesting they have A-fibres; we therefore focussed on A-fibre neurons to determine the sensory properties of α3-immunoreactive neurons. We examined α3 immunointensity in 78 dye-injected DRG neurons whose conduction velocities and hindlimb sensory receptive fields were determined in vivo. A dense perimeter or ring of staining in a subpopulation of neurons was clearly overlying the soma membrane and not within satellite cells. Neurons with clear α3 rings (n = 23) were all MSAs (types I and II); all MSAs had darkly stained α3 rings, that tended to be darker in MSA1 than MSA2 units. Of 52 non-MSA A-fibre neurons including nociceptive and cutaneous low-threshold mechanoreceptive (LTM) neurons, 50 had no discernable ring, while 2 (Aα/ß cutaneous LTMs) had weakly stained rings. Three of three C-nociceptors had no rings. MSAs with strong ring immunostaining also showed the strongest cytoplasmic staining. These findings suggest that α3 ring staining is a selective marker for MSAs. The α3 isoform of the Na(+)/K(+)-ATPase has previously been shown to be activated by higher Na(+) levels and to have greater affinity for ATP than the α1 isoform (in all DRG neurons). The high α3 levels in MSAs may enable the greater dynamic firing range in MSAs.

Multiple myeloma--presenting as acute kidney injury.

BACKGROUND: Multiple myeloma (MM) is a commonly encountered hematological malignancy with significant renal involvement and often presents as renal failure. The aim of the present study is to analyze clinical spectrum of acute renal failure (ARF) in patients with MM. MATERIAL AND METHODS: We analyzed 26 (males 24; females 2) patients of multiple myeloma who were referred for evaluation of ARF between July 1994 - June 2007. The referral diagnosis did not include MM in majority 23 (88%) of the patients. Multiple myeloma was diagnosed by at least two of the four features; (1) lytic bone lesions, (2) serum or urine monoclonal peak, (3) Bence Jones proteinuria and (4) more than 20% plama cells in marrow aspirate. RESULTS: Multiple myeloma contributes 1.93% of total ARF cases (26/1342) over a period of thirteen years. Mean age of patients was 59.3 +/- 7.4 years. The clinical manifestations of myeloma included; anemia (100%), Bence Jones proteinuria (80%), "M" peak in serum electrophoresis (69%), lytic bone lesions (62%), "M" peak in urine electrophoresis (54%), body pain (58%), plasma cells more than 20% in bone marrow aspirate (38%). Oliguric ARF was seen in 73% patients. The precipitating factors of ARF identified were; hypercalcemia (31%); infection (23%); volume depletion (19%); and NSAIDs in (15%). Dialysis support was needed in 77% of the patients because of severe renal failure at presentation with mean serum creatinine of 9.05 +/- 2.84 mg%. Seventeen patients completed chemotherapy, seven last to follow up and two patients died. Ten (38.5%) patients had complete recovery of renal function; three patients had partial recovery and off dialysis and four patients remained dialysis dependent. Remission of myeloma was achieved in nine of seventeen patients treated with chemotherapy Renal biopsy finding in nine patients revealed-cast nephropathy in (4), amyloidosis in (3), proliferative glomerulonephritis in (1) and cast nephropathy with chronic interstitial nephritis and plasma cell infiltration in one patient. CONCLUSION: Acute reversible renal failure is a common complication in MM, multiple myeloma should be considered as cause a cause of unexplained ARF in middle aged and elderly patients.

Local Ca2+ influx through CRAC channels activates temporally and spatially distinct cellular responses.

Ca(2+) entry through store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels controls a disparate array of key cellular responses. In this review, recent work will be described that shows local Ca(2+) influx through CRAC channels has important spatial and temporal consequences on cell function. A localized Ca(2+) rise below the plasma membrane activates, within tens of seconds, catabolic enzymes resulting in the generation of the intracellular messenger arachidonic acid and the paracrine pro-inflammatory molecule LTC(4). In addition, local Ca(2+) entry can activate gene expression, which develops over tens of minutes. Local Ca(2+) influx through CRAC channels therefore has far-reaching consequences on intra- and intercellular communication.

An unusual case of Acanthamoeba peritonitis in a malnourished patient on continuous ambulatory peritoneal dialysis (CAPD).

An unusual case of peritonitis in a 61-year-old patient is reported where culture for bacteria and fungi were negative. Acanthamoeba was isolated and the patient was treated with Ceftazidine, Cefazolin, Levofloxacin, Fluconazole and Rifampicin with regular haemodialytic support. The patient was completely cured of the infection and continuous ambulatory peritoneal dialysis (CAPD) fluid became clear after 2 weeks of treatment. Diagnosis and treatment of Acanthamoeba infections are difficult due to the rarity of the infections, lack of familiarity of most clinicians with disease syndromes, and limitations of therapeutics options. Even an experienced microbiologist can easily mistake the amoebae in ascitic fluid for peritoneal macrophages or lymphocytes.

High prevalence of malnutrition and inflammation in undialyzed patients with chronic renal failure in developing countries: a single center experience from eastern India.

BACKGROUND: Malnutrition is common in patients with chronic renal failure (CRF), and its prevalence before the initiation of dialysis is poorly characterized in these patients in developing countries. There is a paucity of data on the quantification of malnutrition and inflammation in undialyzed patients of CRF from India. This study analyzed the prevalence and causes of malnutrition in patients with CRF before the initiation of dialysis treatment. MATERIAL AND METHODS: In the present study, assessments of nutritional and inflammatory status were carried out in patients with CRF. Serum albumin, body mass index (BMI), triceps skin fold thickness (TST), mid-arm muscle circumference (MAMC), and subjective global assessment (SGA) scoring were used for assessment of nutritional parameters. Serum C-reactive protein and serum ferritin level were used to assess the inflammatory state of the patient. RESULTS: Two hundred and three (146 male, 57 female) patients with CRF were included in the study from August 2004 to April 2006. Overall, the prevalence of malnutrition was 65% (131/203). The age of malnourished patients (93 male, 38 female) ranged from 11-82, with mean age of 52 +/- 12.68 years. The mean serum total protein and albumin were also significantly lower in patients with malnutrition in comparison to non malnourished cases (5.50 +/- 0.40 gm/dL vs. 5.74 +/- 0.38 gm/dL; p < 0.05, and 3.18 +/- 0.58 gm/dL vs. 3.68 +/- 0.55 gm/dL; p < 0.05). The C-reactive protein and serum ferritin were significantly elevated in the malnourished group as compared to non-malnourished patients (63% vs. 33%; p < 0.05, and 301.2 +/- 127.1 mg/dL vs. 212.7 +/- 124.9 mg/dL; p < 0.05). CONCLUSION: Thus, malnutrition was common in patients with CRF before the commencement of dialysis. These data indicate that an emphasis should be placed on the assessment and prevention or correction of malnutrition in patients with CRF because of its documented adverse effect on the outcome on maintenance dialysis.