Bone Density and Microarchitecture: Relationship Between Hand, Peripheral, and Axial Skeletal Sites Assessed by HR-pQCT and DXA in Rheumatoid Arthritis

We assessed the relationship of bone density and microarchitecture between hand, peripheral, and axial skeletal sites using high-resolution peripheral quantitative computed tomography (HR-pQCT) and dual-energy X-ray absorptiometry (DXA) in patients with rheumatoid arthritis (RA) and which factors influence these parameters. This was a cross-sectional study of 100 female patients (53.4?±?9.3?years) with RA. HR-pQCT scans at distal radius and the second metacarpal head were performed to assess cortical and trabecular volumetric bone mineral density (vBMD) and microarchitecture. DXA scans at the hip, lumbar spine, and ultradistal radius were performed to assess areal BMD. There was significant correlation in vBMD and microarchitectural parameters between the second metacarpal head and distal radius (r?=?0.201?0.628). Areal BMD at the axial skeleton was moderately associated with vBMD at the peripheral sites (r?=?0.354–0.558). Factors related to disease severity/chronicity significantly correlated with vBMD and microarchitecture at the distal radius and the second metacarpal head. Factors related to disease activity were more likely to correlate with vBMD and microarchitecture at the second metacarpal head but not those at the distal radius. HR-pQCT is a promising technique that is capable of providing detailed quantitative assessment of disease-associated periarticular bone loss at both cortical and trabecular bone compartments in patients with RA. Future longitudinal studies will be needed to investigate whether assessment by HR-pQCT can be used as a marker of disease activity and a predictor of disease progression in RA.     

Nerve sparing can preserve orgasmic function in most men after robotic-assisted laparoscopic radical prostatectomy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Orgasm has a major influence on patients’ satisfaction with the overall sexual experience, and alternations in orgasm are associated with significant reductions in emotional and physical satisfaction, which in turn may lead to sexual avoidance behaviour, disharmonious relationships and relationship breakdowns. Studies have found a reduction in orgasmic function after retropublic radical prostatectomy. While open radical prostatectomy inevitably damages some pelvic neuronal circuitry, which will thus impact on orgasmic responses, there is a paucity of data investigating the effect on robotic assisted radical prostatectomy on this. To our knowledge this study represents the largest analysis of orgasmic function in the robotic prostatectomy literature, and therefore would be of value to surgeons in counseling candidates for RALP about orgasmic outcomes. In our series, young men (age ≤60 years) and those who underwent bilateral nerve sparing approaches had a better recovery of their premorbid orgasmic function when compared to older men or men with no nerve sparing.

OBJECTIVE

• ? To investigate orgasmic outcomes in patients undergoing robotic‐assisted laparoscopic radical prostatectomy (RALP) and the effects of age and nerve sparing on these outcomes.

PATIENTS AND METHODS

• ? Between January 2005 and June 2007, 708 patients underwent RALP at our institution.
• ? We analysed postoperative potency and orgasmic outcomes in the 408 men, of the 708, who were potent, able to achieve orgasm preoperatively and available for follow‐up.

RESULTS

• ? Of men aged ≤60 years, 88.4% (198/224) were able to achieve orgasm postoperatively in comparison to 82.6% (152/184) of older men (P < 0.001).
• ? Of patients who received bilateral nerve sparing (BNS) during surgery, 273/301 (90.7%) were able to achieve orgasm postoperatively compared with 46/56 (82.1%) patients who received unilateral nerve sparing and 31/51 (60.8%) men who received non‐nerve‐sparing surgery (P < 0.001).
• ? In men ≤60 years who also underwent BNS, decreased sensation of orgasm was present in 3.2% of men, and postoperative orgasmic rates were significantly better than men ≤60 years who underwent unilateral or no nerve sparing (92.9% vs 83.3% vs 65.4%, respectively; P < 0.001).
• ? Potency rates were also significantly higher in men ≤60 years and in those who underwent BNS.

CONCLUSIONS

• ? Age and nerve sparing influence recovery of orgasm and erectile function after RALP.
• ? Men ≤60 years old and those who undergo BNS are most likely to maintain normal sexual function.

     

Cross sectional survey on the concerns and anxiety of patients waiting for organ transplants

Aim: We aimed to gain an understanding of patient concerns while on a transplantation waiting list in areas with long transplant waiting time. Methods: The study population comprised patients with organ failure on the transplant waiting list in Hong Kong. They were invited to complete a questionnaire survey. Demographic data and waiting time were collected. Respondents rated their chance of getting transplanted, their subjective concerns and feelings, level of happiness and support received. Results: A total of 442 patients on the waiting list for kidney, liver, lung and heart‐lung transplants completed the questionnaire survey. The majority of patients (93.0%) were waiting for kidney transplantation. More than half of the respondents (63.3%) had been waiting for more than 3 years. Patients with longer transplant waiting times had lower self‐estimated chance of receiving a transplant (P = 0.004). Self‐estimated chance of getting transplanted was positively associated with the happiness score (P < 0.0001). Issues of most concerns to the patients waiting for organ transplants were: inconvenience of therapy (48.2%), disease progression (47.9%), burden to family (59.5%) and financial difficulties (52.3%). More female patients on the waiting list (50.0% vs 25.7% in male) reported concerns about suffering associated with the illnesses. 21.7% of patients considered the level of support received inadequate. Conclusions: Our patients had long waiting time for transplantation, which is associated with a lower perceived chance of getting a transplant. Attention to more psychosocial support to these patients waiting for organ transplant is important. Promoting and improving organ donation would be the ultimate way to help these patients.     

Functional quality of life following open valve surgery in high-risk octogenarians

Abstract Aim: The aim of this study was to determine the midterm functional quality of life in octogenarians after open valvular surgery. Methods: One hundred and eighty‐five consecutive patients above age 80 had valvular surgery with or without coronary artery bypass grafting (CABG). Using the Karnofsky Performance score and Barthel Index, patients were evaluated for functional autonomy, living disposition, and leisure activity by a single telephone interview. Subgroup analysis was performed on the 49 cases of isolated aortic valve replacement (AVR). Results: Mean age of octogenarians undergoing valvular surgery was 82.7 years (range 80 to 92 years). Actuarial survival at one and three years was 71% and 59%, respectively, for the entire group, compared to 84% and 71%, respectively, for isolated AVRs. After a mean follow‐up of 38 months there were 110 survivors (59.5%). Among survivors, 66% were autonomous, 26% semiautonomous, and 8% deemed dependent. Seventy‐two percent were living at home, 19% in a residence, and 9% in a supervised nursing facility. Over 90% of patients pursued leisure activities in the social, cognitive, and physical domains. Conclusions: Valvular surgery in high‐risk octogenarians, can be performed with acceptable mortality rates, and provide patients with functional autonomy and an excellent quality of life. (J Card Surg 2012;27:408‐414)     

Impact of a multidisciplinary trauma team on the outcome of acute subdural haematoma

IntroductionTo review the outcome of patients with post-traumatic acute subdural haematoma (ASDH) before and after the establishment of a hospital trauma team at a designated trauma centre.MethodA retrospective analysis was conducted on 82 consecutive patients who underwent surgery for post-traumatic ASDH. The ‘PRE’ and ‘POST’ groups included patients admitted before and after the establishment of a hospital trauma team, respectively.Injury severity was assessed by the admission Glasgow coma score, imaging findings, and the revised trauma score. Clinical outcome measures were the hospital length of stay and the Glasgow outcome score (GOS) upon hospital discharge.ResultsThe overall mortality rate was 53.7%. No significant difference was found between the PRE and POST groups. The mean length of hospital stay was also comparable between the two groups. The functional status of those who survived acute hospital care was significantly better in the POST group. Good outcome (GOS of 4 or 5) was achieved in 66.7% of the survivors in the POST group, compared with 25.0% in the PRE group (p = 0.024).ConclusionPost-traumatic ASDH carried a poor prognosis. The mortality rate and hospital length of stay of patients were not found to be reduced after the establishment of a hospital trauma team. The latter, however, was associated with significantly better functional outcome amongst survivors. Although causality cannot be established due to the multitude of factors which may have affected patient outcome, our findings nonetheless provide further support for the introduction of a multidisciplinary hospital trauma team for the optimal care of trauma patients.     

Pseudotyped adeno‐associated viral vector tropism and transduction efficiencies in murine wound healing

Cell specific gene transfer and sustained transgene expression are goals of cutaneous gene therapy for tissue repair and regeneration. Adeno‐associated virus serotype 2 (AAV2/2) mediated gene transfer to the skin results in stable transgene expression in the muscle fascicles of the panniculus carnosus in mice, with minimal gene transfer to the dermal or epidermal elements. We hypothesized that pseudotyped AAV vectors may have a unique and characteristic tropism and transduction efficiency profile for specific cells in the cutaneous wounds. We compared transduction efficiencies of cells in the epidermis, cells in the dermis, and the fascicles of the panniculus carnosus by AAV2/2 and three pseudotyped AAV vectors, AAV2/5, AAV2/7, and AAV2/8 in a murine excisional wound model. AAV2/5 and AAV2/8 result in significantly enhanced transduction of cells both in the epidermis and the dermis compared to AAV2/2. AAV2/5 transduces both the basilar and supra‐basilar keratinocytes. In contrast, AAV2/8 transduces mainly supra‐basilar keratinocytes. Both AAV2/7 and AAV2/8 result in more efficient gene transfer to the muscular panniculus carnosus compared to AAV2/2. The capsid of the different pseudotyped AAV vectors produces distinct tropism and efficiency profiles in the murine wound healing model. Both AAV2/5 and AAV2/8 administration result in significantly enhanced gene transfer. To further characterize cell specific transduction and tropism profiles of the AAV pseudotyped vectors, we performed in vitro experiments using human and mouse primary dermal fibroblasts. Our data demonstrate that pseudotyping strategy confers a differential transduction of dermal fibroblasts, with higher transduction of both human and murine cells by AAV2/5 and AAV2/8 at early and later time points. At later time points, AAV2/2 demonstrates increased transduction. Interestingly, AAV2/8 appears to be more efficacious in transducing human cells as compared to AAV2/5. The pseudotype‐specific pattern of transduction and tropism observed both in vivo and in vitro suggests that choice of AAV vectors should be based on the desired target cell and the timing of transgene expression in wound healing for gene transfer therapy in dermal wounds.     

Laparoscopic live donor nephrectomy: Current practice and results of renal transplantation

Objective: In 2009, 1659 patients with end‐stage renal failure in Hong Kong were waiting for a renal transplant. The overall number of renal transplants carried out locally remains low, with an even lower number being live donor donations. Yet, live donor kidney transplantation yields results that are consistently superior to those of deceased donor kidney transplantation, and laparoscopic donor nephrectomy (LDN) is increasingly accepted worldwide as a safe and preferred surgical option. We aim to evaluate the outcome of LDN in our setting, and to compare with that of deceased donors in this retrospective review. Patients and Methods: A total of 12 patients received LDN over the study period of 2006–2009. Standard left transperitoneal LDN was carried out. Grafts including three with double vessels were prepared using the bench technique. The postoperative outcomes up to 1 year for both the donors and the recipients were studied. Contemporary results for the 47 deceased donor kidneys were studied and compared. Results: All donors had an eventful recovery. The operating time was 225.0 ± 67.4 min. The hospital stay was 5.6 ± 2.3 days. The recipient outcomes including hospital stay and creatinine levels at discharge and 1 year were 11 days, 121 umol/L and 116 umol/L, respectively. Specifically, no ureteric stricture or graft loss was noted at the 1‐year follow up. Recipient complications included haematoma (1 patient), renal artery stenosis (1 patient) and redo of vascular anastomosis (1 patient). In contrast, the deceased donor graft recipients had a hospital stay of 11 days, and creatinine levels of 205 umol/L on discharge and 205 umol/L at 1 year, respectively. The delayed graft function rates for the live donor and deceased donors group were 0% and 14.9%, whereas the 1‐year graft survival rates were 100% and 87.2% respectively. Conclusion: The results showed that the donor morbidity rate was low, as reflected by the short hospital stay. Also, the overall parameters of recipients were good. In particular, no ureteric stricture was noted, and graft survival was 100% at 1 year. Living donor kidney transplant program using the laparoscopic technique is a viable option to improve the pool of kidneys for transplantation.     

Differential anterior prefrontal activation during the recognition stage of a spatial working memory task

Neuroimaging studies commonly show widespread activations in the prefrontal cortex during various forms of working memory and long-term memory tasks. However, the anterior prefrontal cortex (aPFC, Brodmann area 10) has been mainly associated with retrieval in episodic memory, and its role in working memory is less clear. We conducted an event-related functional magnetic resonance imaging study to examine brain activations in relation to recognition in a spatial delayed-recognition task. Similar to the results from previous findings, several frontal areas were strongly activated during the recognition phase of the task, including the aPFC, the lateral PFC and the anterior cingulate cortex. Although the aPFC was more active during the recognition phase, it was also active during the delay phase of the spatial working memory task. In addition, the aPFC showed greater activity in response to negative probes (non-targets) than to positive probes (targets). While our analyses focused on examining signal changes in the aPFC, other prefrontal regions showed similar effects and none of the areas were more active in response to the positive probes than to the negative probes. Our findings support the conclusion that the aPFC is involved in working memory and particularly in processes that distinguish target and non-target stimuli during recognition.     

Promoter hyper-methylation of calcium binding proteins S100A6 and S100A2 in human prostate cancer

BACKGROUND: S100A6 and S100A2 are members of the S100 family of calcium binding proteins, which are down regulated in prostate cancer, however the molecular mechanism(s) underlying their loss of expression is unknown. METHODS: The promoter and exon 1 region of the S100A6 and S100A2 genes was sequenced in bisulfite modified DNA from non-malignant, benign prostatic hyperplasia (BPH), malignant and metastatic prostate tissues and in cell lines. Immunohistochemistry was performed to correlate S100A2 expression with methylation status. RESULTS: S100A6 methylation was absent or occurred at isolated sites in 14/14 cases of non-malignant epithelium and 5/5 cases of BPH tissues, whereas methylation was seen in 14/27 (52%) cases of prostatic cancer (P<0.0001), 2/2 cases of metastatic cancer and in the CWR22 prostatic cancer xenograft. Critical CpG sites within the S100A2 promoter were methylated in LNCaP, LNCaP-LN3, and CWR22 cells but not in Du145, PC3 or BPH45 cells. In tissues, S100A2 methylation was seen in 32/34 (94%) cases of adenocarcinoma and 5/5 cases of metastatic cancer. However, S100A2 methylation was also seen in 9/12 (75%) cases of non-malignant tissues and in 5/5 cases of BPH. Immunostaining, showed absent S100A2 expression all 41 cases of prostatic cancer, whereas staining was seen in the basal cells of non-malignant epithelium. CONCLUSIONS: Loss of S100A6 and S100A2 proteins is frequent in human prostatic cancer. A major mechanism underlying the loss of S100A6 expression appears to involve promoter hyper-methylation. However, mechanisms other than methylation of the known promoter are involved in silencing S100A2 in the prostate.