Mitochondrial DNA Copy Number, a Damage-Associated Molecular Pattern Molecule, Can Predict Pancreatic Necrosis and Is Correlated with the Severity of Acute Pancreatitis.

BACKGROUND: Mitochondrial DNA (mtDNA) is a damage-associated molecular pattern molecule that can trigger an immune-inflammatory response during pancreatic necrosis (PN). AIM: To evaluate the role of mtDNA in the detection of PN and severe acute pancreatitis (SAP). METHODS: The present study included 40 AP patients and 30 controls. AP patients were grouped into mild AP (MAP, n = 15), moderately severe AP (MSAP, n = 17), and SAP (n = 8). Also, the SAP + MSAP group, n = 25, was compared to MAP. AP patients were divided into NAP (n = 7) and non-necrotizing AP (n = 33). The mtDNA copy number, IL-6, and STAT3 expression levels were measured using quantitative real-time PCR. RESULTS: The mtDNA, IL-6, and STAT3 levels were significantly higher in AP patients than in controls and in the SAP + MSAP than in the MAP. However, the SAP had non-significantly higher levels of mtDNA, STAT3, and IL-6 levels than the MSAP and statistically significant mtDNA, STAT3, and IL-6 when compared to the MAP. mtDNA, IL-6, and STAT3 showed significantly higher levels in NAP compared with non-necrotizing AP. mtDNA was positively correlated with STAT3, IL-6, CRP, APACHE, and CT severity index (CTSI) and negatively correlated with albumin. In the receiver operating curve (ROC), mtDNA was the most significant independent predictor of PN and MAP vs. SAP + MSAP. IL-6 and mtDNA + CRP had higher diagnostic abilities for SIRS and high CTSI. CONCLUSIONS: mtDNA could enhance the prediction of NAP; however, its diagnostic ability of SAP needs further study.

Predictors of therapeutic failure among patients with acute brucellosis treated by dual therapy with doxycycline-rifampin.

OBJECTIVE: To determine the frequency of therapeutic failure among patients with acute and subacute brucellosis and to explore the predictors of failure. METHODS: The study included 213 consecutive, naïve patients with acute and subacute brucellosis. All participants underwent clinical evaluation, chest radiography, stool microscopic examination and interferon-gamma release assay. Patients received the WHO-recommended therapy of doxycycline 200 mg/day and rifampin 900 mg/day, for 6 weeks. RESULTS: Mean age of the study population was 39.8 ± 12.2 years; 64.8% of them were males. The therapeutic failure rate was 16.4%. Adverse effects were reported by 13.1%. Multivariate analysis of factors associated with therapeutic failure revealed latent tuberculosis infection (LTBI) (OR 3.1, 95% CI, 1.9-24.6, P: 0.009), ascariasis (OR 2.6, 95% CI 1.5-17.9, P: 0.012), and the use of acid suppressive therapy (OR 2.1, 95% CI 1.2-19.5, P: 0.037) as the predictors of therapeutic failure. CONCLUSIONS: The prevalence of therapeutic failure among the Egyptian patients with acute/subacute brucellosis is increasing. Predictors of therapeutic failure are LTBI, ascariasis, and the use of acid suppressive therapy.

Role of vitamin D deficiency as a risk factor for infections in cirrhotic patients.

BACKGROUND: Vitamin D plays a role in innate and acquired immunity. The risk for bacterial infections is increased in cirrhotic patients due to low levels of vitamin D. This study aimed to determine serum 25-(OH) vitamin D levels among cirrhotic patients in the presence and absence of infections and correlate this level with liver disease severity. METHODS: This cross-sectional analytic study recruited 87 hospitalised cirrhotic patients who were divided into the following groups: group with evidence of infection (45 cases) and group without infection (42 cases). Urine analysis, ascetic fluid study and chest X-rays were performed to find the site of infection. Serum 25-(OH) vitamin D was also measured. RESULTS: Vitamin D levels were lower in the cirrhotic with infection group than in the cirrhotic without infection group (17.3 ± 2.5 vs. 41.1 ± 3.1, respectively) (P-value < 0.001). Approximately 71.4% cirrhotic patients without infection had sufficient vitamin D levels, while 60% of cirrhotic patients with infection had insufficient vitamin D levels, and 28.9% had vitamin D deficiency (P-value < 0.001). Spontaneous bacterial peritonitis was the most common infection (62.2%). The cutoff point of vitamin D levels for cirrhotic patients with infection was 21 ng/mL. CONCLUSION: Vitamin D deficiency was found to be an independent predictor of infection in cirrhotic patients suggesting that vitamin D supplementation may be useful in these patients. No significant correlations were found between the vitamin D level and the Child-Pugh class and MELD score among the infected group and non-infected group.

Diagnostic validity of flow cytometry vs manual counting of polymorphonuclear leukocytes in spontaneous bacterial peritonitis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is frequently occurring infection among patients with liver cirrhosis, defined by polymorphonuclear (PMN) leukocytic count ≥250 cell/mm3 with or without a positive ascitic fluid (AF) bacterial culture. So, this study aimed to investigate the diagnostic value of flow cytometry versus manual counting of ascitic fluid PMNL in cirrhotic patients, with clinical suspicion of SBP. METHODS: A hospital-based cross-sectional study was carried out on 320 cirrhotic patients with clinical suspicion of SBP. Abdominal paracentesis was performed in all cases for microscopic manual and flow cytometry counting of PMNL. Anti-HLA-DR, anti-CD15, anti-CD16, and anti-CD45 monoclonal antibodies were used for flow cytometry method. RESULTS: Flow cytometric PMNL count had 100% sensitivity and specificity, while manual PMNL count had a sensitivity of 65.52% and specificity of 90% with significant difference (P value < .05). CONCLUSION: Flow cytometry is more reliable rapid method for PMNL counting, than the manual method that is less accurate and time-consuming in diagnosing clinically suspected SBP.

Long-term recurrence of neoplasia and Barrett's epithelium after complete endoscopic resection.

BACKGROUND: Current endoscopic therapy for neoplastic Barrett's oesophagus (BO) consists of complete resection/ablation of all Barrett's tissue including neoplastic lesions. Recurrence seems to be frequent after thermal therapy, such as radiofrequency ablation. OBJECTIVE: To analyse long-term recurrence of neoplasia and BO after successful widespread endoscopic mucosal resection (EMR). DESIGN: In a retrospective analysis, all patients undergoing widespread EMR of neoplastic BO between 2002 and 2007 at two referral centres were followed for at least 3 years after completion of endotherapy. Recurrence was diagnosed if neoplasia and/or BO were detected following previous successful complete removal, defined as at least two negative endoscopies and biopsies. RESULTS: Ninety patients undergoing widespread EMR were included (mean age 63 years; 82 male), 58% of whom underwent additional thermal ablation for minor residual disease. Complete eradication of neoplasia and Barrett's tissue was achieved in 90% of patients. On further follow-up (mean 64.8 months), recurrence of neoplastic and non-neoplastic BO was found in 6.2% and 39.5%, respectively. Recurring neoplasia (3 adenocarcinomas, 1 low-grade and 1 high-grade dysplasia) were found after a median of 44 months (range 38-85) and could be retreated endoscopically. In a multivariate analysis, Barrett's length was the only factor significantly associated with recurrence (OR 2.73). CONCLUSIONS: Even after seemingly complete endoscopic resection, recurrence of BO is frequent and independent of additional thermal therapy. Due to the possibility of neoplasia recurrence even after long disease-free intervals, follow-up should be extended beyond 5 years.

Subsquamous extension of intestinal metaplasia is detected in 98% of cases of neoplastic Barrett's esophagus.

BACKGROUND & AIMS: Subsquamous intestinal metaplasia (SSIM) has been observed after endotherapy in patients with neoplastic Barrett's esophagus (BE). However, it is not clear whether SSIM occurs in untreated patients. Incompletely eradicated SSIM could provide a source of recurrent disease. We assessed its prevalence in a large cohort of patients who had not received endoscopic therapy. METHODS: Two experienced pathologists analyzed 138 samples of 506 resection specimens found to contain squamous epithelium from 110 patients with neoplastic BE treated by widespread endoscopic mucosal resection (92 men; mean age, 66 years). The maximum extent of SSIM was measured. RESULTS: Of the 138 samples analyzed, 124 (89.9%) were found to contain SSIM from 108 of the 110 patients (98.2%). The mean length of SSIM was 3.3 mm (range, 0.2-9.6 mm; 25% ≥ 5 mm); SSIM length correlated with BE length (P < .05). In 83 of 138 samples (60.1%), the SSIM consisted partially or entirely of neoplasias of different grades, with a mean subsquamous extension of 3.3 mm; the extension correlated with grade of neoplasia (P = .0001). CONCLUSIONS: Most patients with BE with neoplasia (of all grades) have subsquamous extension of intestinal metaplasia, including subsquamous extension of lesions at the squamocolumnar junction. Therefore, biopsy and resection of neoplastic BE should extend at least 1 cm into the squamous epithelium.