Sustained HBs seroconversion during lamivudine and adefovir dipivoxil combination therapy for lamivudine failure

We describe the case of a patient with chronic hepatitis B who became resistant to lamivudine and was treated successfully with adefovir dipivoxil in addition to lamivudine. Lamivudine resistance was associated with the selection of a L180M+M204V polymerase mutant. After the addition of adefovir dipivoxil, serum HBV DNA levels dropped by more than 4log(10), which was followed by HBsAg clearance after 22 months of combination therapy. Moreover, anti-HBs antibody titers rose above 1000 mIU/mL after 32 months of the new treatment regimen. In parallel, HBV DNA declined below 100 copies/mL by a quantitative real time PCR assay. Analysis of intrahepatic viral DNA showed a significant decline of total HBV DNA and cccDNA which was accompanied by a decrease of the number of infected cells expressing viral antigens below the detection limit of immunostaining. In parallel, liver histology analysis showed an improvement in both the activity index and fibrosis score. This report suggests that in patients who previously failed lamivudine therapy, proactive antiviral treatment may lead to a beneficial virological and clinical effect.     

Predictors of hepatitis B surface antigen loss,relapse and retreatment after discontinuation of effective oral antiviral therapy in noncirrhotic HBeAg‐negative chronic hepatitis B

Reliable predictors of outcomes after treatment discontinuation in HBeAg‐negative chronic hepatitis B (CHB) patients have not been established. We investigated the role of hepatitis B surface antigen (HBsAg), interferon‐inducible protein‐10 (IP10) and hepatitis B core‐related antigen (HBcrAg) serum levels as predictors of HBsAg loss, relapse and retreatment in noncirrhotic HBeAg‐negative CHB patients who discontinued long‐term antiviral therapy. All HBsAg‐positive (n = 57) patients of the prospective DARING‐B study were included and followed monthly for 3 months, every 2/3 months until month‐12 and every 3/6 months thereafter. HBsAg, IP10 and HBcrAg levels were measured by enzyme immunoassays, and SCALE‐B score was calculated. Twelve patients achieved HBsAg loss before retreatment with 18‐month cumulative incidence of 25%. Independent predictors of HBsAg loss were baseline HBsAg and month‐1 IP10 levels. Of 10 patients with baseline HBsAg ≤100 IU/mL, 70% cleared HBsAg and 10% required retreatment. Of 23 patients with baseline HBsAg >1000 IU/mL, 4% cleared HBsAg and 43% required retreatment. Of 24 patients with intermediate baseline HBsAg (100‐1000 IU/mL), 17% cleared HBsAg and 21% required retreatment; in this subgroup, month‐1 IP10 was significantly associated with HBsAg loss, which occurred in 30% and 7% of cases with IP10 >150 and ≤150 pg/mL, respectively. Baseline HBcrAg was undetectable in all patients who cleared HBsAg and was associated with retreatment. SCALE‐B was associated with HBsAg loss but not with relapse or retreatment. In conclusion, HBsAg, IP10 and HBcrAg serum levels can be useful for the decisions and management of treatment discontinuation in noncirrhotic Caucasian patients with HBeAg‐negative CHB.     

Coaptation/elevation role of the middle deltoid muscle fibers: a static biomechanical pilot study using shoulder MRI

Purpose

It is generally recognized that the middle deltoid muscle fibers (MDMF) have an elevating effect on the humeral head at small abduction angles. These forces are normally counterbalanced by the coaptation effect of the rotator cuff (RC) muscles to maintain shoulder stability. With RC tears, this balance may be jeopardized leading to shoulder dysfunction. Conversely, not all patients with RC tears develop shoulder dysfunction. The purpose of this study was to investigate the coaptation/elevation forces (CEF) ratio of the MDMF in RC tears subjects and in volunteers, using magnetic resonance imaging (MRI).

Methods

Magnetic resonance imaging images in 10 subjects with RC tears and in five volunteers were used to build a three-dimensional model of the shoulder. The CEF ratio of the MDMF was estimated by representing the glenohumeral joint as a pulley.

Results

The CEF ratio increased from the posterior to the anterior fibers of the MDMF.The median and interquartile range (IQR) of the CEF ratios of the posterior-third, middle-third, anterior-third and anterior-surface segments of the deltoid were: 0.16 (IQR = 0.23), 0.61 (IQR = 0.4), 1.42 (IQR = 0.41), 1.94 (IQR = 0.56) in subjects, and 0.06 (IQR = 0.24), 0.45 (IQR = 0.28), 1.32 (IQR = 1.01), 1.49 (IQR = 0.39) in volunteers. In the subjects, the CEF ratio of the anterior-surface segment was greater than all other segments (P ≤ 0.03).

Conclusions

The CEF ratio of the MDMF increased from its posterior segment to its anterior segment, indicating a greater stabilizing effect of the anterior segment both in RC tears subjects and in volunteers. Strengthening of the anterior fibers of the MDMF could potentially improve shoulder function in subjects with RC tears.     

Does the force level modulate the cortical activity during isometric contractions after a cervical spinal cord injury?

ObjectiveThis study investigated the effects of a cervical spinal cord injury (SCI) on the modulation of cortical desynchronization (ERD) during isometric contractions at different force levels.MethodsFor 8 able-bodied (AB) and 6 cervical SCI participants, the net joint moment and electroencephalographic activities were recorded during isometric contractions of the right elbow in flexion and in extension at 3 force levels, that is, during intact and altered muscle contractions for SCI participants. The mean net moment and ～20 Hz ERD from C3 electroencephalographic electrode were compared between AB and SCI participants.ResultsIn flexion, that is, during intact contractions for all participants, the mean net moment and the ERD increased with the required force level. In extension, that is, during altered contractions, the mean net moment increased for 3 SCI participants while it was almost zero for 3 other SCI participants. The associated ERD increased with the required force level for all participants.ConclusionThe cortical desynchronization was modulated by the intent to modulate the force level rather than the actual modulation of the force production.SignificanceThese results provide a better understanding of the modulation of the cortical desynchronization following SCI. Potential applications could include the control of neuroprostheses.     

The impact of lymph node status and features on oncological outcomes in urothelial carcinoma of the upper urinary tract (UTUC) treated by nephroureterectomy

Purpose

Prognostic impact of lymphadenectomy during radical nephroureterectomy (RNU) for urothelial carcinoma of the upper urinary tract (UTUC) is controversial. Our aim was to assess the impact of lymph node status (LNS) on survival in patients treated by RNU.

Methods

In our multi-institutional, retrospective database, 714 patients with non-metastatic UTUC had undergone RNU between 1995 and 2010. LNS was tested as prognostic factor for survivals through univariate and multivariable Cox regression analysis.

Results

Median age was 70 years [interquartile range (IQR), 60–75] with median follow-up of 27 months (IQR, 10–50). Overall, lymphadenectomy was performed in 254 patients (35.5 %). Among these patients, 204 (80 %) had negative lymph nodes (pN0) and 50 (20 %) had positive lymph nodes (pN1/2). The 5-year cancer-specific survival (CSS) was 81 % [95 % confidence interval (CI), 73–88 %] for pN0 patients, 85 % (95 % CI, 80–90 %) for pNx patients and 47 % (95 % CI, 24–69 %) for pN1/2 patients (p < 0.001). Metastasis-free survival (MFS) and overall survival (OS) rates were significantly lower in pN1/2 patients than in pN0 and pNx patients (p < 0.05). On multivariable analysis, LNS did not appear as an independent prognostic factor for CSS, OS or MFS (p > 0.05). In case of lymph node involvement, extra-nodal extension was marginally associated with worse CSS (log rank p = 0.07). The retrospective design was the main limitation.

Conclusion

LNS is helpful for survival stratification in patients treated with RNU for UTUC. However, LNS did not appear as an independent predictor of survival in this retrospective series and needs to be investigated in a large multicentre, prospective evaluation.