DAA‐based antiviral treatment of patients with chronic hepatitis C in the pre‐ and postkidney transplantation setting

DAA‐based regimens for chronic hepatitis C infection encourage treatment of “difficult‐to‐treat” cohorts. This study investigated efficacy and safety of DAA‐based regimens in HCV patients on dialysis or postkidney or liver/kidney transplantation. Twenty‐five patients treated with DAA combinations were evaluated: 10 were on dialysis (eight: hemodialysis, two: peritoneal dialysis), eight were kidney transplant recipients, and seven were liver/kidney transplant recipients. Except for one patient treated with daclatasvir ([DCV]/60 mg/QD)/simeprevir ([SMV]/150 mg/QD), the others received sofosbuvir‐based regimens ([SOF];400 mg/QD) combined with SMV:eight, DCV:13 or either ledipasvir ([LDV]90 mg/QD), ribavirin ([RBV];weight based) or pegylated interferon/RBV. HCV‐RNA was determined by Abbott RealTime (LLOQ]:12 IU/ml) or Roche AmpliPrep/COBAS TaqMan assay (LLOQ:15 IU/ml); treatment response evaluated every 4 weeks, at the end of treatment, and 4 and 12 weeks thereafter. Twenty‐four (96%) patients achieved SVR 12/24 (ITT‐analysis). Mean treatment duration was 15.1 ± 5.1 weeks (±SD), and two patients terminated prematurely – both reached SVR12. Six patients were hospitalized due to complications of underlying disease. One patient achieved SVR24 but was re‐infected (week 27). Kidney function remained stable; serum creatinine increased in only one patient – SOF was reduced to 400 mg/48 h. Treatment with DAA combinations in renally impaired HCV patients is highly effective and well tolerated. These findings call for further controlled trials and data from real‐life cohorts.     

Preferred and Energetically Optimal Transition Speeds During Backward Human Locomotion

Some aspects of backward locomotion are similar to forward locomotion, while other aspects are not related to their forward counterpart. The backward preferred transition speed (BPTS) has never been directly compared to the energetically optimal transition speed (EOTS), nor has it been compared to the preferred transition speed (PTS) during forward locomotion. The purpose of this study was to determine whether the BPTS occurs at the EOTS, and to examine the relationship between the backward and forward preferred gait transition speeds. The preferred backward and forward transition speeds of 12 healthy, young subjects (7 males, 5 females) were determined after subjects were familiarized with forward and backward treadmill locomotion. On a subsequent day, subjects walked backward at speeds of 70, 80, 90, 100, and 110% of the BPTS and ran backward at speeds of 60, 75, 90, 100, and 120% of the BPTS while VO₂ and RPE data were collected. After subtracting standing VO₂, exercise VO₂ was normalized to body mass and speed. For each subject, energy-speed curves for walking and running were fit to the normalized data points. The intersection of these curves was defined as the EOTS which was compared to the BPTS using a paired t-test (p < 0.05). RPE and VO₂ at the BPTS were also compared between walking and running conditions, and the correlation between BPTS and PTS was calculated. The EOTS (1.85 ± 0.09 m·s^-1) was significantly greater than the BPTS (1.63 ± 0.11 m·s^-1). Even though RPE was equal for walking and running at the BPTS, VO₂ was significantly greater when running. There was a strong correlation (r = 0.82) between the BPTS and the PTS. Similar to forward locomotion, the determinants of the BPTS must include factors other than metabolic energy. The gait transition during backward locomotion exhibits several similarities to its forward counterpart.

Key Points

• The backward preferred transition speed (1.63 ± 0.11 m·s^-1) was significantly less than the energetically optimal transition speed (1.85 ± 0.09 m·s^-1), similar to what is observed during forward locomotion.
• RPE was equal for walking and running at the backward preferred transition speed.
• There was a strong correlation (r = 0.82) between the backward and forward preferred transition speeds.
• Similar to forward locomotion, the determinants of the BPTS must include factors other than metabolic energy.

Key Words: Running, walking, gait transition, preferred transition speed     

Mini-open thoracoscopically assisted thoracotomy versus video-assisted thoracoscopic surgery for anterior release in thoracic scoliosis and kyphosis: a comparison of operative and radiographic results

BACKGROUND CONTEXT: Combining anterior release and interbody fusion with posterior instrumented fusion is an accepted treatment for severe rigid spinal deformity. Video-assisted thoracoscopic surgery (VATS) and mini-open thoracoscopically assisted thoracotomy (MOTA) are two minimally invasive approaches to the thoracic spine. Both reduce surgical trauma, improve cosmesis and provide effective exposure for release and fusion. Published data and the authors' surgical experience have demonstrated that both techniques are equivalent in degree of release to traditional open thoracotomy, but no comparison between these two minimally invasive alternatives has been published to our knowledge. PURPOSE: This study compared MOTA and VATS under the hypothesis that both result in similar corrections and comparable operative parameters when used in conjunction with posterior instrumented fusion. STUDY DESIGN/SETTING: Retrospective chart review of consecutive case series by two surgeons. PATIENT SAMPLE: Twenty-one (13 female, 8 male) patients underwent MOTA and 24 patients (17 female, 7 male) underwent VATS for anterior release, discectomy and fusion prior to posterior instrumented fusion. OUTCOME MEASURES: Outcomes were measured at a minimum of 1-year follow-up and included radiographic Cobb measurements and operative parameters. METHODS: The indications for surgery included rigid and severe scoliosis or thoracic kyphosis. Data collection included preoperative demographics, number of levels released, primary curve correction, operative time and blood loss. Data were normalized per number of levels released anteriorly. Statistical analysis of results was done using a two-sample t test assuming equal variances with two-tail p values less than .05. RESULTS: More anterior levels were operated on average in the VATS group (6.33 vs. 4.38 levels). Curve correction per anterior level released was similar in both groups (8.7 and 8.8 degrees/level for MOTA and VATS, respectively). There was a significant difference in operative time with MOTA averaging 131.7 minutes and VATS averaging 162.8 minutes. However, a comparison of the operative time per anterior level operated, approached statistical significance in favor of VATS (33.0 vs. 28.4 minutes, p=.08). There was no significant difference in estimated blood loss during the anterior portion of the surgeries. There was a trend toward decreased blood loss per operated level favoring VATS (68.4 vs. 38.9 cc, p=.09). CONCLUSIONS: Both approaches resulted in corrections that compare favorably with open thoracotomy. We suggest that a factor in choosing between these two minimally invasive techniques is the number of thoracic levels requiring release. For four levels or less, MOTA provides an excellent alternative to standard thoracotomy. For five or more levels, VATS provides for excellent exposure of additional levels with the advantages of less operative time and blood loss per operated level.     

Multivisceral transplantation for diffuse portomesenteric thrombosis in a patient with life-threatening esophagogastroduodenal bleeding

Portal vein thrombosis is the most common cause of portal hypertension in noncirrhotic patients. Variceal bleeding is difficult to treat in these patients, especially those with prehepatic diffuse portal mesenteric thrombosis. In a patient with refractory esophagogastroduodenal variceal bleeding as a result of diffuse portomesenteric thrombosis and portal hypertension, life-threatening bleeding was unresponsive to endoscopic therapy and other surgical procedures. A multivisceral transplant was performed. It was curative and also lifesaving. There is only one report in the literature mentioning multivisceral transplantation for a patient with life-threatening esophagogastroduodenal bleeding; however that patient had protein C deficiency. Our patient had normal liver and intestinal function tests and no signs of hypercoagulable disease. We believe that multivisceral transplantation should be considered as a treatment option for patients with diffuse mesenteric thrombosis, even in the absence of liver and intestinal failure, when other treatment options for variceal bleeding have failed, particularly in a younger patient with a relatively good nutritional status before transplantation.     

Bone repair following bone grafting hydroxyapatite guided bone regeneration and infra-red laser photobiomodulation: a histological study in a rodent model

The aim of the investigation was to assess histologically the effect of laser photobiomodulation (LPBM) on a repair of defects surgically created in the femurs of rats. Forty-five Wistar rats were divided into four groups: group I (control); group II (LPBM); group III (hydroxyapatite guided bone regeneration; HA GBR); group IV (HA GBR LPBM). The animals in the irradiated groups were subjected to the first irradiation immediately after surgery, and it was repeated every day for 2 weeks. The animals were killed 15 days, 21 days and 30 days after surgery. When the groups irradiated with implant and membrane were compared, it was observed that the repair of the defects submitted to LPBM was also processed faster, starting from the 15th day. At the 30th day, the level of repair of the defects was similar in the irradiated groups and those not irradiated. New bone formation was seen inside the cavity, probably by the osteoconduction of the implant, and, in the irradiated groups, this new bone formation was incremental. The present preliminary data seem to suggest that LPMB therapy might have a positive effect upon early wound healing of bone defects treated with a combination of HA and GBR.     

A 16-year clinical experience with intermittent androgen deprivation for prostate cancer: oncological results

Objective  

To present oncological results with intermittent androgen deprivation (IAD) in a single center.     

Androgen and estrogen receptors in the human corpus cavernosum penis: immunohistochemical and cell culture results

Despite the central and peripheral effects of androgens on the nervous system, the local effects of androgens in the corpus cavernosum penis and their importance for erectile function is still unclear. In this study corpus cavernosum biopsies of eight adult potent patients, aged 19–63 years, undergoing penile deviation surgery (group A) and 12 patients undergoing male-to-female transsexual surgery (group B) were immunostained for nuclear androgen and estrogen-alpha receptors. Additionally, primary corpus cavernosum endothelial cell cultures were obtained from six transsexual patients and exposed to testosterone, dihydrotestosterone, estradiol and progesterone likewise for 7 days. Total cell count was performed and cell metabolic activity was measured by a tetrazolium salt-based assay. Androgen and estrogen-alpha receptors were detected in stromal as well as in endothelial cells. Of all cell nuclei, 74.9% (SD 16.4) in group A and 63.5% (SD 17.1) in group B were positively stained for androgen receptors. The respective percentage of estrogen receptors was 11% (SD 9.5) and 21.2% (SD 12.6). An age-dependent difference in receptor distribution was not observed in either group. In the cell culture system only cultures exposed to testosterone and dihydrotestosterone showed a dose-dependent increase of cell metabolic activity compared to the cultures supplemented with estradiol and progesterone. The significant and age-independent high androgen and low estrogen-alpha receptor distribution found in both groups suggests a possible peripheral effect of androgens at the level of the corpus cavernosum penis in adult humans. This is supported by the observed effect of testosterone and dihydrotestosterone on cell count and endothelial cell metabolism in our cell culture system. The role of estrogens remains unclear.     

High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats

OBJECT: Ibuprofen is an antiinflammatory drug that disrupts leukocyte-endothelial cell interactions by limiting expression of endothelial adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), also known as CD54. The authors hypothesized that ibuprofen could reduce the size of the infarct associated with transient focal ischemia by inhibition of ICAM-1 expression, and they evaluated its effects in rats treated with middle cerebral artery (MCA) occlusion. Ibuprofen treatment was compared with mild systemic hypothermia, which is known to be neuroprotective and is commonly used during neurosurgical procedures. METHODS: The maximum ibuprofen dose (240 mg/kg/day) that could be tolerated with no systemic toxicity was established in the initial experiments. In the efficacy experiment, rats were pretreated with vehicle, ibuprofen, or hypothermia (33 degrees C) prior to 2 hours of MCA occlusion; then their brains were harvested at 24 hours of reperfusion for histological studies. End-ischemic cerebral blood flow (CBF) was evaluated using [14C]iodoantipyrine autoradiography in additional cohorts. Expression of ICAM-1 within ischemic compared with nonischemic caudate nucleus and putamen (striatum) or cortex was evaluated using immunohistochemical studies. Compared with vehicle treatment, ibuprofen produced a 46.2% reduction (p = 0.01) in striatal infarcts, which was comparable to hypothermia (48.7% reduction, p = 0.02). Ibuprofen did not alter end-ischemic CBF in any region studied, and the ibuprofen treatment group had the lowest proportion of animals with marked ICAM-1 staining. CONCLUSIONS: Ibuprofen given in maximum tolerated doses reduces the striatal infarct size after focal cerebral ischemia. The neuroprotective mechanism does not work through preservation of intraischemic CBF and is consistent with inhibition of ICAM-1 expression; however, at the doses used in this study, other effects of ibuprofen on platelet and endothelial function are possible.     

Circulating alloreactive T cells correlate with graft function in longstanding renal transplant recipients

Monitoring for alloreactive memory T cells after organ transplantation may allow individualization of immunosuppression. Two pathways of T cell allorecognition have been implicated in chronic graft dysfunction: Direct (recipient T cells respond to donor peptides presented by donor antigen-presenting cells) and indirect (donor peptides are processed and presented by recipient antigen-presenting cells). Previous studies have assessed these alloresponses only during the first 2 yr after kidney transplantation,so this study correlated the presence of circulating donor-reactive memory/effector T cells, primed by both pathways, in 34 longstanding living-donor renal transplant recipients using the highly sensitive IFN-gamma Elispot assay. Remarkably, 59% of patients had directly primed donor-reactive T cells, and their presence correlated directly with serum creatinine (P = 0.001) and inversely with estimated GFR (P = 0.042). Multivariate analysis revealed that hyporesponsiveness of direct, donor-specific T cells was the only variable that significantly correlated with graft function and that antidonor indirect alloreactivity was the only variable that significantly correlated with proteinuria. Interestingly, when both allorecognition pathways were considered together, patients with undetectable direct alloreactivity had better longterm graft function, independent of allosensitization by the indirect pathway. In conclusion, circulating donor-specific alloreactive T cells primed by both pathways are detectable long after transplantation and are associated with graft injury. Assessment of alloreactive memory/effector T cells might be helpful to tailor individual immunosuppression regimens for transplant recipients in the future.     

Endoscopic Dilation with Savary-Gilliard Bougies of Stomal Strictures After Laparosocopic Gastric Bypass in Morbidly Obese Patients

Background Anastomotic strictures after bariatric surgery are a frequent complication that requires endoscopic management, but the optimal technique for dilation remains to be determined. The aim of this study was to evaluate the safety and efficacy of dilation with Savary–Gilliard bougies (SGB) in morbidly obese patients treated with laparoscopic Roux-en-Y gastric bypass (RYGBP). Patients and Methods Retrospective review of prospectively collected data from a series of 474 consecutive patients with laparoscopic bariatric surgery. Four-hundred twenty four of these patients (90%) underwent a laparoscopic RYGBP. A total of 24 patients were referred for anastomotic stricture dilation with SGB from January 1998 to December 2006. Results A total of 24/424 patients (6%) developed a stricture that was successfully dilated with SGB. Patients were 17 females (71%) and seven males (29%) with a mean age of 41 ± 11 years (range 24–63) and a mean BMI of 48 ± 6 (range 40–69). The time between RYGBP and the appearance of stricture-related symptoms ranged from 29 to 154 days (mean, 69 days). The mean number of dilations was 1.6 ± 0.6. The majority of patients required one (n = 11; 46%) or two (n = 12; 50%) dilations and only one patient required three dilations. During the initial dilation, a final diameter of 11 ± 1.7 mm (range 7–12.8 mm) was achieved. In all cases, there was complete resolution of symptoms. There were no complications. Conclusions Dilation with SGB is an effective, safe, and durable method for managing anastomotic strictures after laparoscopic RYGBP. Presented at the 12th World Congress of the International Federation for the Surgery of Obesity, Porto, Portugal, September 7, 2007.