Risk factors associated with renal lithiasis during uricosuric treatment of hyperuricemia in patients with Gout

Objective

To find factors associated with the development of renal colic during uricosuric therapy.

Methods

We performed a prospective cohort followup study of patients with gout and no previous history of kidney stones who had been treated with uricosurics. Clearance of creatinine and urate, 24‐hour urinary uric acid (UA), undissociated urinary UA concentration, 24‐hour undissociated urinary UA, and pH and urine sediment were obtained. Cox proportional hazards regression analysis was used to identify variables associated with renal colic as the outcome. The rate of renal colic was compared with that of control patients receiving allopurinol who had no previous history of renal stones.

Results

We analyzed a 784 patient‐year exposure from 216 patients: 206 with renal underexcretion of UA and 10 with normal excretion. There were 21 clinical events. Two variables showed increased risk hazard for developing lithiasis: clearance of UA at baseline and undissociated urinary UA concentration during followup. When only patients with underexcretion of UA were included in the analysis, undissociated urinary UA during followup remained the only statistically significant variable. Patients who showed an undissociated UA concentration <20 mg/dl did not show an increase in the rate of lithiasis or events compared with patients receiving allopurinol.

Conclusion

Clearance of UA at baseline may be useful for selecting patients suitable for uricosuric treatment. The estimation of the concentration of undissociated urinary UA is useful for evaluating the risk of lithiasis during followup.     

Gastric tonometry versus cardiac index as resuscitation goals in septic shock: a multicenter, randomized, controlled trial

Introduction  

Resuscitation goals for septic shock remain controversial. Despite the normalization of systemic hemodynamic variables, tissue hypoperfusion can still persist. Indeed, lactate or oxygen venous saturation may be difficult to interpret. Our hypothesis was that a gastric intramucosal pH-guided resuscitation protocol might improve the outcome of septic shock compared with a standard approach aimed at normalizing systemic parameters such as cardiac index (CI).     

CT-guided fine-needle aspiration in vertebral osteomyelitis: true usefulness of a common practice

Computed tomography (CT)-guided biopsy of the spine is considered a safe, accurate, and relatively inexpensive examination technique. Our purpose was to determine the diagnostic accuracy of CT-guided biopsies exclusively for vertebral osteomyelitis. A retrospective study was performed from a consecutive series of 72 patients with confirmed vertebral osteomyelitis with 46 CT-guided biopsies performed in 40 patients. Biopsy specimens were sent for bacteriologic and cytologic analysis. An adequate specimen for microbiologic examination was not obtained in one case and not enough sample for additional pathologic examination in 17 cases. The mean age of patients was 58 years, with a range of 1–88 years, including 24 men and 16 women. The level of spinal biopsy was thoracic in 18 (40%) and lumbar in 28 (60%). The analysis revealed the infection agent in 20 cases (43% sensitivity). Diagnostic rates obtained in patients with previous antibiotic treatment were significantly lower (23% vs. 60%, p = 0.013). Computed tomography-guided fine-needle aspiration biopsy is an important tool in the diagnostic evaluation of vertebral osteomyelitis. However, this technique yields a lower diagnostic rate than previously reported biopsy of neoplastic vertebral lesions, especially if performed in patients with previous antibiotic treatment.     

Morphologic and clinical effects of subretinal injection of indocyanine green and infracyanine green in rabbits.

PURPOSE: The aim of this study was to determine the effects of subretinal injection of indocyanine green (ICG), infracyanine (IfCG), and balanced salt solution (BSS) in rabbits. METHODS: Ten (10) animals were subjected to a subretinal injection of 0.05% ICG (279 mOsm), 0.5% IfCG (276 mOsm), and BSS (300 mOsm) used as a control. Animals were examined at 6, 12, and 24 h and 14 days following the surgical procedure by indirect binocular ophthalmoscopy, fluorescein angiography (FA), and light and transmission electron microscopy. RESULTS: The subretinal injection of ICG caused damage to all retinal layers and retinal pigment epithelium (RPE) during the entire follow-up. Subretinal injection of IfCG resulted in abnormalities of the photoreceptor outer segments (POSs) during the entire follow-up; however, abnormalities of the photoreceptor inner segments (PISs) and outer nuclear layer (ONL) were observed only 24 h and 14 days after surgery; no RPE damage was observed. FA showed that window defects were more prominent in the subretinal ICG bleb position than the IfCG-related area. BSS caused only abnormalities of the POS layer and no RPE alterations. CONCLUSIONS: Subretinal injection of 0.05% ICG results in more significant retinal damage than 0.5% IfCG. In this model, iodine-free IfCG demonstrates a safer profile than a tenfold lower concentration of ICG, which contains iodine in its composition.     

Cadherin-catenin adhesion system and mucin expression: a comparison between young and older patients with gastric carcinoma

BACKGROUND: Young patients are thought to develop gastric carcinomas with a molecular genetic profile that is distinct from that of gastric carcinomas occurring at a later age. The aim of this study was to compare the clinicopathological features and expression patterns of the markers E-cadherin and beta-catenin, and mucins (MUC1, MUC2, MUC5AC, and MUC6) in young and older patients. METHODS: The clinicopathological features and overall survival data of 62 young patients (age 40 years). A tissue microarray method and immunohistochemistry were used in order to analyze marker expression in paraffin-embedded tissue blocks obtained from both groups. RESULTS: The young group presented a higher percentage of diffuse-type tumors in comparison to the older group (P<0.01). The rates of positivity for E-cadherin and beta-catenin membranous expression patterns and mucin (MUC2, MUC5AC and MUC6) positivity were higher in the young group (P<0.01). Although young patients showed a lower frequency of alterations in marker expression and had significantly better survival rates than the older patients, neither age nor the marker expression pattern were found to be independent prognostic factors of survival. Only stage, tumor size, and tumor location persisted as prognostic factors for patients with gastric cancer. CONCLUSION: Biological markers of cellular adhesion and gastric differentiation were differently expressed in young and older patients. Our findings support the hypothesis that young patients develop carcinomas with a different genetic pathway compared to the pathway of tumors occurring at a later age, and we suggest further investigations to assess the prognostic relevance of the markers to specific subgroups.     

Molecular Analysis of a Multistep Lung Cancer Model Induced by Chronic Inflammation Reveals Epigenetic Regulation of p16 and Activation of the DNA Damage Response Pathway

The molecular hallmarks of inflammation-mediated lung carcinogenesis have not been fully clarified, mainly due to the scarcity of appropriate animal models. We have used a silica-induced multistep lung carcinogenesis model driven by chronic inflammation to study the evolution of molecular markers and genetic alterations. We analyzed markers of DNA damage response (DDR), proliferative stress, and telomeric stress: γ-H2AX, p16, p53, and TERT. Lung cancer-related epigenetic and genetic alterations, including promoter hypermethylation status of p16(CDKN2A), APC, CDH13, Rassf1, and Nore1A, as well as mutations of Tp53, epidermal growth factor receptor, K-ras, N-ras, and c-H-ras, have been also studied. Our results showed DDR pathway activation in preneoplastic lesions, in association with inducible nitric oxide synthase and p53 induction. p16 was also induced in early tumorigenic progression and was inactivated in bronchiolar dysplasias and tumors. Remarkably, lack of mutations of Ras and epidermal growth factor receptor, and a very low frequency of Tp53 mutations suggest that they are not required for tumorigenesis in this model. In contrast, epigenetic alterations in p16(CDKN2A), CDH13, and APC, but not in Rassf1 and Nore1A, were clearly observed. These data suggest the existence of a specific molecular signature of inflammation-driven lung carcinogenesis that shares some, but not all, of the molecular landmarks of chemically induced lung cancer.