Extremely High Body Mass Index is not a Contraindication to Laparoscopic Gastric Bypass

Background: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) is an effective operation for morbidly obese patients who have failed conservative weight loss treatments. It is currently indicated for patients with BMI >40 kg/m² or >35 with significant co-morbidities. Controversy exists whether there is an upper limit to BMI beyond which this operation should not be performed. Methods: Between April 1999 and February 2001, 82 patients (19 male, 63 female) underwent LRYGBP. Average age was 43.6, and average BMI was 56 kg/m². These patients were divided into those with BMI <60 and those with BMI ≥60 kg/m². Results:There were 61 patients with BMI <60 and 21 patients with BMI ≥60. The groups were similar in age, gender, distribution or incidence of co-morbid conditions (diabetes, coronary artery disease, hypertension, sleep apnea, asthma) between the groups. The BMI ≥60 group had a significantly longer length of stay (6.6 days vs 5.3 days, P <0.05), and only 1 patient (BMI 85) developed an anastomotic leak and died. 2 patients in this group (BMI 62 and 73) developed small bowel obstruction requiring lysis of adhesions. 1 patient in the BMI <60 group developed a gastrojejunal stricture requiring balloon dilatation. Conclusion: While patients with a BMI ≥60 are at higher risk for postoperative complications, they are also at higher risk from continued extreme obesity. In our series, 85% of these patients had an uneventful postoperative course and began shedding excess weight. BMI ≥60 should not be a contraindication for LRYGBP.     

Prevalence and immunohistochemical findings of subclinical kidney allograft rejection and its association with graft outcome

Subclinical acute rejection (SAR) occurs in about 30% of stable renal transplant patients and may be a risk factor for a poor allograft outcome. In the present study, the prevalence and clinical features of subclinical rejection, and the expression of immune activation markers in surveillance graft biopsies were assessed and correlated with late graft outcomes. Protocol biopsies were obtained at 2 and 12 months post-transplant in 32 and 26 patients, respectively, with stable renal function. The Banff 1997 criteria were used for histological diagnosis. Graft function and survival and proteinuria were assessed during the 36 months of follow-up. Immunohistochemical evaluation of cell subpopulations and immunoactivation markers were performed on protocol biopsies. The prevalence of SAR at 2 months and of chronic allograft nephropathy (CAN) at 12 months in representative biopsies was 55 and 50%, respectively. Patients with SAR presented mononuclear cell infiltration with an increased expression of CD3, CD4, CD68, IL-2R and granzyme B. Kidney graft function was significantly worse in patients with SAR at 2 months who had chronic rejection on biopsy at 12 months, but SAR was not associated with a worse graft function, greater proteinuria or a lower graft survival in 3 yr of follow-up. In conclusion, we found an elevated prevalence of SAR at 2 months after transplantation with an increased expression of activation markers. Although an association of SAR with poor graft outcome was not observed, our results suggest that SAR is an immunologically active process and underscore the importance of protocol biopsies in the surveillance of transplanted kidneys.     

ERα signaling regulates MMP3 expression to induce FasL cleavage and osteoclast apoptosis

The benefits of estrogens on bone health are well established; how estrogens signal to regulate bone formation and resorption is less well understood. We show here that 17β‐estradiol (E2)‐induced apoptosis of bone‐resorbing osteoclasts is mediated by cleavage and solubilization of osteoblast‐expressed Fas ligand (FasL). U2OS‐ERα osteoblast‐like cells expressing an EGFP‐tagged FasL at the C‐terminus showed decreased fluorescence after E2 treatment, indicative of a cleavage event. Treatment of U2OS‐ERα cultures with a specific MMP3 inhibitor in the presence of E2 blocked FasL cleavage and showed an increase in the number of EGFP‐FasL⁺ cells. siRNA experiments successfully knocked down MMP3 expression and restored full‐length FasL to basal levels. E2 treatment of both human and murine primary osteoblasts showed upregulation of MMP3 mRNA expression, and calvarial organ cultures showed increased expression of MMP3 protein and colocalization with the osteoblast‐specific RUNX2 after E2 treatment. In addition, osteoblast cell cultures derived from ERαKO mice showed decreased expression of MMP3 but not MMP7 and ADAM10, two known FasL proteases, demonstrating that ERα signaling regulates MMP3. Also, conditioned media of E2‐treated calvarial osteoblasts showed an approximate sixfold increase in the concentration of soluble FasL, indicating extensive cleavage, and soluble FasL concentrations were reduced in the presence of a specific MMP3 inhibitor. Finally, to show the role of soluble FasL in osteoclast apoptosis, human osteoclasts were cocultured with MC3T3 osteoblasts. Both a specific MMP3 inhibitor and an MMP inhibitor cocktail preserved osteoclast differentiation and survival in the presence of E2 and demonstrate the necessity of MMP3 for E2‐induced osteoclast apoptosis. These experiments further define the molecular mechanism of estrogen's bone‐protective effects by inducing osteoclast apoptosis through upregulation of MMP3 and FasL cleavage. © 2013 American Society for Bone and Mineral Research     

Glycation in Parkinson's disease and Alzheimer's disease

Glycation is a spontaneous age‐dependent posttranslational modification that can impact the structure and function of several proteins. Interestingly, glycation can be detected at the periphery of Lewy bodies in the brain in Parkinson's disease. Moreover, α‐synuclein can be glycated, at least under experimental conditions. In Alzheimer's disease, glycation of amyloid β peptide exacerbates its toxicity and contributes to neurodegeneration. Recent studies establish diabetes mellitus as a risk factor for several neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. However, the mechanisms underlying this connection remain unclear. We hypothesize that hyperglycemia might play an important role in the development of these disorders, possibly by also inducing protein glycation and thereby dysfunction, aggregation, and deposition. Here, we explore protein glycation as a common player in Parkinson's and Alzheimer's diseases and propose it may constitute a novel target for the development of strategies for neuroprotective therapeutic interventions. © 2016 International Parkinson and Movement Disorder Society     

Impact of genetic polymorphisms on tacrolimus pharmacokinetics and the clinical outcome of renal transplantation

We retrospectively examined the association of polymorphisms in the CYP3A, CYP2J2, CYP2C8, and ABCB1 genes with pharmacokinetic (PKs) and pharmacodynamic (PDs) parameters of tacrolimus in 103 renal transplant recipients for a period of 1 year. CYP3A5 expressers had lower predose concentrations (C(0) )/dose and higher dose requirements than nonexpressers throughout the study. Among CYP3A5*1 carriers, those also carrying the CYP3A4*1B allele showed the lowest C(0) /dose, as compared with CYP3A4*1/CYP3A5*3 carriers (54.28±26.45, 59.12±24.00, 62.43±41.12, and 57.01±17.34 vs. 112.37± 76.60, 123.21±59.57, 163.34±76.23, and 183.07±107.82 at 1 week, 1 month, 5 months, and 1 year after transplantation). In addition, CYP3A4*1B/CYP3A5*1 carriers showed significantly lower dose-corrected exposure than CYP3A4*1/CYP3A5*1 carriers 1 year after transplantation (57.01±17.34 vs. 100.09±24.78; P=0.016). Only the ABCB1 TGC (3435-2677-1236) haplotype showed a consistent association with PDs (nephrotoxicity; OR=4.73; CI: 1.3-16.7; P=0.02). Our findings indicate that the CYP3A4*1B-CYP3A5*1 haplotype may have a more profound impact in tacrolimus PKs than the CYP3A5*1 allele. This study does not support a critical role of the CYP450 or ABCB1 single nucleotide polymorphisms in the occurrence of toxicity or acute rejection in renal transplant recipients treated with tacrolimus.     

Posterior approach (Kraske procedure) for surgical treatment of presacral tumors

Presacral tumors are rare,but can comprise a great variety of histological types.Congenital tumors are the most common.Once the diagnosis is established,surgical resection is essential because of the potential for malignancy or infection.Previous biopsy is not necessary or may be even harmful.To decide the best surgical approach(abdominal,sacral or combined) an individual and multidisciplinary analysis must be carried out.We report three cases of cystic presacral masses in which a posterior approach(Kraske procedure) enabled complete resection,the only way to decrease local recurrence.All patients had a satisfactory recovery.A brief overview of retrorectal tumors is presented,focusing on classification,clinical presentation,diagnosis and surgical management.     

Radical cystectomy with orthotopic neobladder reconstruction following prior radical prostatectomy

Purpose

To review the perioperative and follow-up outcomes of patients undergoing radical cystectomy with orthotopic neobladder reconstruction for bladder cancer after prior radical prostatectomy (RP) for prostate cancer.

Methods

A retrospective review of more than 1,900 patients treated with radical cystectomy at USC between 1990 and 2011 was conducted. Fifty-six patients were identified who were previously treated with RP for prostate cancer. Twenty-four of these patients (43?%) underwent orthotopic neobladder reconstruction. Perioperative data and follow-up including postoperative continence were analyzed.

Results

The median age at cystectomy for these 24 patients was 68?years (range 55?C89). The types of neobladder reconstruction were Kock neobladder in 3, Sigmoid reservoir in 1, Studer neobladder in 12, and T-pouch ileal neobladder in 8 patients. There were no major intraoperative complications. Of 19 patients eligible for evaluation of post-cystectomy urinary control, 11 patients (57.9?%) with good continence (0?C1 pad/day) after RP regained preoperative level of urinary control after cystectomy within 1?year. The continence rate of 13 post-RP patients with good continence was 84.6?%. Among the 4 patients who received adjuvant radiotherapy after RP, 1 regained good continence. One with poor continence after prostatectomy had an artificial urethral sphincter (AUS) placed 2?months after cystectomy, and 2 with fair and poor continence after prostatectomy had an AUS placed at the time of cystectomy.

Conclusions

Patients undergoing radical cystectomy after prior RP pose a challenge to urologists. Those who are continent post-RP have a fair chance of regaining good urinary control with neobladder reconstruction. Adjuvant radiotherapy for prostate cancer may have a negative impact on continence with neobladder reconstruction.     

Image noise-based dose adaptation in dynamic volume CT of the heart: dose and image quality optimisation in comparison with BMI-based dose adaptation

Objectives

To compare the image quality and radiation dose using image-noise (IN)-based determination of X-ray tube settings compared with a body mass index (BMI)-based protocol during CT coronary angiography (CTCA).

Methods

Two hundred consecutive patients referred for CTCA to our institution were divided into two groups: BMI-based, 100 patients had CTCA with the X-ray tube current adjusted to the patient’s BMI while maintaining a fixed tube potential of 120 kV; IN-based, 100 patients underwent imaging with the X-ray tube current and voltage adjusted to the IN measured within the mid-left ventricle on a pre-acquisition trans-axial image. Two independent cardiac radiologists performed blinded image quality assessment with quantification of the IN and signal-to-noise ratio (SNR) from the mid-LV and qualitative assessment using a three-point score. Radiation dose (CTDI and DLP) was recorded from the console.

Results

Results showed: IN (HU): BMI-based, 30.1?±?9.9; IN-based, 33.1?±?6.7; 32 % variation reduction (P?=?0.001); SNR: BMI-based, 18.6?±?7.1; IN-based, 15.4?±?3.7; 48 % variation reduction (P?<?0.0001). Visual scores: BMI-based, 2.3?±?0.6; IN-based, 2.2?±?0.5 (P?=?0.54). Radiation dose: CTDI (mGy), BMI-based, 22.68?±?8.9; IN-based, 17.16?±?7.6; 24.3 % reduction (P?<?0.001); DLP (mGy.cm), BMI-based, 309.3?±?127.5; IN-based, 230.6?±?105.5; 25.4 % reduction (P?<?0.001).

Conclusions

Image-noise-based stratification of X-ray tube parameters for CTCA results in 32 % improvement in image quality and 25 % reduction in radiation dose compared with a BMI-based protocol.

Key Points

? Image quality and radiation dose are closely related in CT coronary angiography. ? So too are the image quality, radiation dose and body mass index (BMI). ? An image-noise-based CTCA protocol reduces the radiation dose by 25 %. ? It improves inter-patient image homogeneity by 32 %.     

Single versus sequential fine-needle aspiration biopsy in the management of thyroid nodular disease.

Fine-needle aspiration biopsy (FNAB) is considered a safe, reliable and cost-effective means of selecting thyroid nodules with risk for malignancy. However, there are limitations of this method including false positive/negative and "nondiagnostic" results that may be reduced by repeating FNAB. OBJECTIVE: To evaluate accuracy, sensitivity, specificity and costs of sequential FNAB in the management of thyroid nodular disease. METHODS: Charts of all patients who underwent thyroidectomy at a university teaching hospital in Toronto from 1998 to 2000 were reviewed. FNAB reports of "suspicious for malignancy," "follicular lesion" and "cellular atypia" were considered to be positive. Data were analyzed with chi2 and z tests. RESULTS: There were 268 patients (225 women and 43 men; age range 18-89 yr; mean age 47 yr) who underwent a total of 449 FNABs (mean 1.7 FNABs/patient) within a year before thyroidectomy. Accuracy (63.8%), sensitivity (73.8%) and specificity (69%) were determined for single FNABs. Sequential FNAB increased the accuracy of method by 22.6%, sensitivity by 13.8% and specificity by 6.2%, with reduction of false positive/negative results by 14.2% and "nondiagnostic" results by 100%. However, the costs of sequential cytology per patient were 70% higher than single FNAB. CONCLUSIONS: Multiple FNABs are unpleasant for patients, but useful in the selection for treatment of patients with thyroid nodular diseases. Although sequential FNAB increases the costs of method, the improvement of precision of FNAB may imply a reduction in overall health-care costs.