Pre-transplant co-infusion of donor-adipose tissue derived mesenchymal stem cells and hematopoietic stem cells may help in achieving tolerance in living donor renal transplantation

Transplantation tolerance is still a Utopian dream for many transplanters. Mesenchymal stem cells (MSC) have shown immuno-modulatory and tolerogenic effects in experimental models. We present a 29-year-old male with end stage renal disease (ESRD) who was transplanted with HLA 4/6 matched kidney from 51-year-old father in June 2010 preceded by co-infusion of donor-adipose tissue derived mesenchymal stem cells (AD-MSC) and bone marrow derived hematopoietic stem cells (BM-HSC) under non-myeloablative conditioning for deleting rejecting T and B-cells. He has maintained fairly stable graft function with serum creatinine (SCr) between 1.5 and 1.8?mg/dL at 3 years post-transplant with absence of donor specific antibodies (DSA), normal protocol graft biopsy, and peripheral T-regulatory cell levels (pTregs) (CD127^low/?CD25^highCD4⁺) of 4.57% on zero immunosuppression since 6 months.     

Novel PEGylated Basal Insulin LY2605541 Has a Preferential Hepatic Effect on Glucose Metabolism

The impact of the novel basal insulin LY2605541 (LY) on hepatic and nonhepatic glucose uptake (non-HGU) was evaluated. Conscious dogs underwent euglycemic clamps with tracer and hepatic balance measurements. Clamp period infusions were peripheral venous regular insulin (0.1 nmol ⋅ kg⁻¹ ⋅ h⁻¹ [control], n = 6) or LY (bolus [nmol/kg], continuous [nmol ⋅ kg⁻¹ ⋅ h⁻¹]: 0.5, 0.5 [n = 6]; 0.375, 0.375 [n = 5]; 0.25, 0.25 [n = 4]), somatostatin, and glucose, as well as intraportal glucagon (basal). During the clamp, the dogs switched from net hepatic glucose output to uptake (rates reached 2.1 ± 1.2, 0.9 ± 2.1, 8.6 ± 2.3, and 6.0 ± 1.1 µmol ⋅ kg⁻¹ ⋅ min⁻¹ within 5 h in control, LY_0.25, LY_0.375, and LY_0.5, respectively). Non-HGU in LY increased less than in control; the ratio of change from basal in non-HGU to change in net hepatic glucose balance, calculated when glucose infusion rates (GIRs) were ~20 µmol ⋅ kg^-1 ⋅ min⁻¹ in all groups, was higher in control (1.17 ± 0.38) versus LY_0.25 (0.39 ± 0.33), LY_0.375 (−0.01 ± 0.13), and LY_0.5 (−0.09 ± 0.07). Likewise, the change from baseline in glucose R_d-to-R_a ratio was greatest in control (1.4 ± 0.3 vs. 0.6 ± 0.4, 0.5 ± 0.2, and 0.6 ± 0.2 in LY_0.25, LY_0.375, and LY_0.5, respectively). In contrast to exogenously administered human insulin, LY demonstrated preferential hepatic effects, similar to endogenously secreted insulin. Therefore, the analog might reduce complications associated with current insulin therapy.     

Percutaneous Nephrolithotomy in Autosomal Dominant Polycystic Kidney Disease: Is it Different from Percutaneous Nephrolithotomy in Normal Kidney?

Objectives

Nephrolithiasis has been reported in 20-28% of patients, of whom 50% are symptomatic for stone disease and 20% require definite urologic intervention. The management of nephrolithiasis includes oral alkali dissolution therapy, extracorporeal shock wave lithotripsy and surgical treatment. In such patients, percutaneous nephrolithotomy (PNL) as a method of stone treatment has been reported in few cases with limited experience. The aim of this study is to present our experience of PNL in autosomal dominant polycystic kidney disease (ADPKD) and assessing the outcome results.

Material and Methods

From 2002 to 2011, 22 patients (26 renal units) suffering from ADPKD with stone were managed by PNL. Demographic characteristics, operative parameters and postoperative complications were recorded and analysed.

Result

The overall success rate of PNL was 82.1% and PNL with extracorporeal shock wave lithotripsy for clinically significant residual fragments was 92.85% respectively. The hematuria required blood transfusion (n = 9), postoperative fever due to cyst infection (n = 4) and paralytic ileus (n = 3) were recorded.

Conclusion

The PNL in ADPKD PNL is safe and effective but have more postoperative complications such as bleeding requiring transfusions, fever due to cyst infection and paralytic ileus.Key Words: Percutaneous nephrolithotomy, Nephrolithiasis, Autosomal dominant polycystic kidney disease     

Postoperative apnea, respiratory strategies, and pathogenesis mechanisms: a review

Recovery from anesthesia is ideally routine and uneventful. After extubation, the recovering postoperative patient ought to breathe without supportive care or additional oxygenation. It has been demonstrated in previous studies that postoperative pulmonary complications are clinically relevant in terms of mortality, morbidity, and length of hospital stay. Compromised postoperative ventilation can be described as the condition in which the postoperative patient does not have satisfactory spontaneous ventilation support and adequate oxygenation. Causes of impaired ventilation, oxygenation, and airway maintenance can be mechanical, hemodynamic, and pharmacologic. This review describes prevalence and differential diagnosis, including co-morbidities of postoperative apnea. The physiological mechanisms of breathing and prolonged postoperative apnea are also reviewed; these mechanisms include influences from the brainstem, the cerebral cortex, and chemoreceptors in the carotid and aortic body. Causes of prolonged postoperative apnea and management are also discussed.     

Short-term outcome analysis of total pelvic reconstruction with mesh: the vaginal approach

PURPOSE: We describe our experience with transvaginal total pelvic reconstruction using a mesh with 4-point fixation for patients with genitourinary prolapse with or without stress urinary incontinence. MATERIALS AND METHODS: A total of 29 consecutive patients who underwent sacrospinous fixation using mesh material since March 1999 for genitourinary prolapse were analyzed retrospectively. In all patients defect specific repair was done, including hysterectomy (in 13). For isolated vault prolapse a rectangular mesh was interposed between the peritoneum and vaginal vault, with each corner anchored to the sacrospinous ligament using a suture-capturing device. For vault prolapse associated with anterior vaginal wall prolapse an "H" shaped, 1-piece sling was used to support both entities. Additionally, posterior and perineal repairs were done through separate incisions if needed. RESULTS: Of the 29 patients 19 (65.5%), 7 (26.92%) and 11 (39.29%) had associated symptoms of stress urinary incontinence, urgency and frequency, respectively, and 79.31% had associated anterior and 44.8% had associated posterior prolapse. Average operative time was 175.6 minutes, blood loss was 340 cc and hospital stay was 2.46 days. Early adverse events following the procedure were perineal pain, vaginal discharge and irritative voiding symptoms. At 6 month followup (mean 25.14 months) mild constipation and dyspareunia were encountered in a small subset of patients. Two patients (6.89%) have genital prolapse recurrence and none has reported erosion or nonhealing to date. CONCLUSIONS: Transvaginal technique of 4-point vaginal vault fixation using mesh is a safe and effective procedure at 2 years.     

Isolated mediastinal lymphangioma herniating through the intercostal space

Lymphangiomas are congenital malformations of the lymphatic system, and 90% have manifested by the end of the second year of life. While 75% of these are located in the cervical region, only 2% to 3% are associated with an intrathoracic extension. An isolated mediastinal lymphangioma without a cervical component is an uncommon occurrence. Presented here is an isolated mediastinal lymphangioma that herniated through the intercostal space to present as a cystic mass in the parasternal region, which has not been reported so far.     

Ostomy and pregnancy

Pregnancy in a woman with ostomy poses significant concern in its management. A search for literature addressing this problem revealed minimal information. Questionnaires on this subject were sent to all of the members of the American Society of Colon and Rectal Surgeons, and the replies received from them were analyzed by the computer. Attempts were made to answer questions regarding stoma complications, recurrence of disease during pregnancy, type of childbirth (vaginal or cesarean), special needs during pregnancy, and any recurring problems with subsequent pregnancies. Read at the meeting of the American Society of Colon and Rectal Surgeons, San Diego, California, May 5 to 10, 1985.     

Enumeration of lactotropes and somatotropes among male and female pituitary cells in culture: evidence in favor of a mammosomatotrope subpopulation in the rat

The hemolytic plaque assay technique can be used to detect specific hormone release from single pituitary cells. Using antisera raised against murine GH or rat PRL, we have enumerated the active lactotropes and somatotropes from male and female rat pituitary glands. These studies reveal sex-related differences in the number of cells exporting GH and PRL among anterior pituitary cells in culture. In the presence of human GH-releasing factor (hGRF), the mean percentage of GH cells was 53% in males and 30% in females (P less than 0.005). The mean percentage of PRL cells was 15% in males and 39% in females (P less than 0.008). These values were not significantly altered when hGRF was omitted. The sum of GH and PRL cells identified in separate plaque assays significantly exceeds the number obtained when GH and PRL cells were determined concurrently with a simultaneous plaque assay for both hormones. This difference is dependent on the presence of hGRF, since there was no difference when hGRF was omitted. These data identify the mammosomatotrope in numbers lower than previous reports. By this approach, the mammosomatotrope subpopulation numbers about 5% of all cells in culture. In summary, we demonstrate a sex-related difference in the number of cells exporting GH or PRL among pituitary cells in culture. This difference corresponds with and may underly sex-related differences in the responsiveness of GH and PRL secretion from the pituitary gland. Furthermore, a minor subpopulation of normal pituitary cells appears capable of simultaneous secretion of both GH and PRL.     

High Gleason grade carcinoma at a positive surgical margin predicts biochemical failure after radical prostatectomy and may guide adjuvant radiotherapy

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Only 30–35% of patients with positive surgical margins after radical prostatectomy develop recurrent disease. Adjuvant radiotherapy reduces the rate of biochemical relapse or metastasis and improves overall survival after radical prostatectomy. Various pathological factors, such as location and extent of positive margins, have been proposed as possible prognostic factors in men with margin‐positive prostate cancer, however, the recent International Society of Urological Pathology consensus meeting in Boston noted that there is limited data on the significance of Gleason grade of the carcinoma at a positive margin. The present study shows that the presence of high grade prostate cancer, i.e. Gleason pattern 4 or 5, at a positive surgical margin is an independent predictor of biochemical recurrence after radical prostatectomy. Moreover, patients with lower grade carcinoma at the margin have a similar prognosis to men with negative margins. Hence, assessment of Gleason grade at the site of positive margin may aid optimal selection of patients for adjuvant radiotherapy.

OBJECTIVE

• ? To establish predictors of biochemical recurrence by analysing the pathological characteristics of positive surgical margins (PSMs), including Gleason grade of the carcinoma at the involved margin.

PATIENTS AND METHODS

• ? Clinicopathological and outcome data on 940 patients who underwent radical prostatectomy (RP) between 1997 and 2003 were collected.
• ? Of these, 285 (30.3%) patients with PSMs were identified for pathological review, including assessment of location of margin, linear extent, number of PSMs, plane of margin and Gleason grade (3 vs 4 or 5) at the margin.

RESULTS

• ? At a median follow‐up of 82 months, the biochemical recurrence rate of the PSM cohort was 29%.
• ? On univariate analysis, the presence of Gleason grade 4 or 5 at the margin (34.4% of cases) was significantly associated with biochemical recurrence (hazard ratio [HR] 2.80, 95% confidence interval [CI]= 1.82–4.32, P < 0.001) compared with the presence of Gleason grade 3.
• ? Linear extent of margin involvement was also associated with recurrence (P= 0.009).
• ? Single vs multiple margin involvement, location, and plane of the involved margin were not significant predictors of recurrence.
• ? On multivariate analysis, Gleason grade 4 or 5 at the margin remained an independent predictor of recurrence (HR 2.14, 95% CI = 1.29–4.03, P= 0.003).

CONCLUSION

• ? The Gleason grade at the site of a PSM identifies patients at increased risk of biochemical recurrence and should aid stratification of patients for adjuvant radiation therapy.