Longitudinal changes of the laboratory data of chronic hepatitis C patients with sustained virological response on long-term follow-up

There is no study that follows up longitudinal changes in laboratory data of patients with C-viral chronic liver disease (C-CLD) who achieved sustained virological esponse (SVR) with interferon treatment in a long-term study. We investigated the laboratory data in a long-term retrospective cohort study of 581 patients with C-CLD who underwent liver biopsy between January 1986 and December 2005. 467 were treated with interferon and 207 of these patients achieved SVR with follow-up periods of 8.36 ± 5.13 years. Alanine aminotransferase (ALT) levels, albumin levels, platelet counts, and the aspartate aminotransferase (AST)-to-platelet ratio index (APRI) values were serially examined during the follow-up period. None of the 207 patients with SVR exhibited hepatitis C virus (HCV) RNA positivity more than 6 months after the end of IFN treatment. Platelet counts and albumin levels increased only in those with eradication of HCV. APRI values decreased more in patients with SVR than in those with nonsustained virological responses (non-SVR). Patients who achieved SVR and had fibrosis stage 0-1 and 2-4 at enrolment had platelet counts that longitudinally increased by 2.81 ± 3.95 and 5.49 ± 4.53 × 10(3) /μL during the 10-year follow-up period, respectively. Albumin levels continuously increased during the first 2 years by 0.15 ± 0.31 and 0.33 ± 0.37 in fibrosis stage 0-1 and 2-4, respectively and then plateaued. ALT levels decreased rapidly one year after the start of treatment by 110.3 ± 140.0 and 100.5 ± 123.4 in fibrosis 0-1 and 2-4, respectively. HCV RNA negativity persisted in all patients with SVR, and laboratory data including APRI longitudinally improved during the long-term follow-up period.     

Cervical Lymph Node Dissection for Clinically Submucosal Carcinoma of the Thoracic Esophagus

Background

The purposes of this study were to clarify the risk factors for supraclavicular lymph node (SCLN) metastasis and the survival benefit from cervical lymph node (LN) dissections in patients with clinically submucosal (cT1b) carcinoma of the thoracic esophagus.

Methods

A total of 86 patients with this disease who underwent esophagectomy with 3-field lymph node dissection were retrospectively reviewed. Multivariate logistic regression and Cox proportional hazard model were used to identify the independent risk factors for SCLN metastasis and prognostic factors, respectively. An index calculated by multiplying the frequency of metastasis at nodal basin and the 5-year overall survival rate of patients with metastasis at that basin were used to assess the therapeutic outcomes.

Results

A total of 40 patients (47 %) were found to have pathological LN metastasis. Also, 13 patients (15 %) had cervical LN metastasis: 6 and 7 with carcinoma of the upper and mid-thoracic esophagus, respectively. SCLN metastasis was found in 6 patients (7 %); however, there was no independent risk factor for SCLN metastasis. The 5-year overall survival rate was 72.5 %. Cervical LN metastasis was an independent prognostic factor (p = .04; odds ratio 2.55; 95 % confidence interval 1.03–6.31); however, there was no significant difference in survival between patients with SCLN metastasis and those without (p = .06). The calculated index of estimated benefit from cervical LN dissections was 6.9, following upper mediastinal LN of 15.6 and perigastric LN of 8.3.

Conclusions

We could not identify risk factors to predict SCLN metastasis. Cervical LN dissection should not be omitted in patients with cT1b carcinoma, especially of the upper and mid-thoracic esophagus.     

COX‐1‐dependent prostaglandin D2 in microglia contributes to neuropathic pain via DP2 receptor in spinal neurons

Cyclooxygenase (COX) enzyme synthesizes prostaglandins (PGs) from arachidonic acid and exists as two major isozymes, COX‐1 and COX‐2. The crucial role of prostaglandins in the pathogenesis of inflammatory pain in peripheral tissue and the spinal cord has been established; however its expression dynamics after peripheral nerve injury and its role in neuropathic pain are not clear. In this study, we examined the detailed expression patterns of genes for COX, PGD2 and thromboxane A2 synthases and their receptors in the spinal cord. Furthermore, we explored the altered gene expression of these molecules using the spared nerve injury (SNI) model. We also examined whether these molecules have a role in the development or maintenance of neuropathic pain. We found a number of interesting results in this study, the first was that COX‐1 was constitutively expressed in the spinal cord and up‐regulated in microglia located in laminae I‐II after nerve injury. Second, COX‐2 mRNA expression was induced in blood vessels after nerve injury. Third, TXA2 synthase and hematopoietic PGD synthase mRNAs were dramatically increased in the microglia after nerve injury. Finally, we found that intrathecal injection of a COX‐1 inhibitor and DP2 receptor antagonist significantly attenuated the mechanical allodynia. Our findings indicate that PGD2 produced by microglia is COX‐1 dependent, and that neurons in the spinal cord can receive PGD2 from microglia following peripheral nerve injury. We believe that PGD2 signaling via DP2 signaling pathway from microglia to neurons is one of the triggering factors for mechanical allodynia in this neuropathic pain model.     

Estimation of daily protein intake based on spot urine urea nitrogen concentration in chronic kidney disease patients

Background

Determination of daily protein intake in the management of chronic kidney disease (CKD) requires precision. Inaccuracies in recording dietary intake occur, and estimation from total urea excretion presents hurdles owing to the difficulty of collecting whole urine for 24 h. Spot urine has been used for measuring daily sodium intake and urinary protein excretion.

Methods

In this cross-sectional study, we investigated whether urea nitrogen (UN) concentration in spot urine can be used to predict daily protein intake instead of the 24-h urine collection in 193 Japanese CKD patients (Stages G1–G5). After patient randomization into 2 datasets for the development and validation of models, bootstrapping was used to develop protein intake estimation models.

Results

The parameters for the candidate multivariate regression models were male gender, age, body mass index (BMI), diabetes mellitus, dyslipidemia, proteinuria, estimated glomerular filtration rate, serum albumin level, spot urinary UN and creatinine level, and spot urinary UN/creatinine levels. The final model contained BMI and spot urinary UN level. The final model was selected because of the higher correlation between the predicted and measured protein intakes r = 0.558 (95 % confidence interval 0.400, 0.683), and the smaller distribution of the difference between the measured and predicted protein intakes than those of the other models.

Conclusion

The results suggest that UN concentration in spot urine may be used to estimate daily protein intake and that a prediction formula would be useful for nutritional control in CKD patients.