Outcomes of Kidney Transplantation in Patients That Underwent Bariatric Surgery: A Systematic Review and Meta-analysis.

The impact of bariatric surgery (BS) on kidney transplantation (KT) outcomes in patients with obesity remains controversial. We systematically searched MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials for studies reporting outcomes of KT recipients that underwent prior BS. Common/random effects meta-analyses were performed to obtain summary ratios of the postoperative outcomes. Eighteen eligible studies involving 315 patients were identified. Sleeve gastrectomy was the most common BS type (65.7%) followed by Roux-en-Y gastric bypass (27.6%) and gastric banding (4.4%). Across studies that provided the data, the %excess weight loss from BS to KT was 62.79% (95% confidence interval [CI], 52.01-73.56; range, 46.2%-80.3%). The rates of delayed graft function and acute rejection were 16% (95% CI, 7%-28%) and 16% (95% CI, 11%-23%) in 14 and 11 studies that provided this data, respectively. The rates of wound, urinary, and vascular complications following KT were 5% (95% CI, 0%-13%),19% (95% CI, 2%-42%), and 2% (95% CI, 0%-5%), in 12, 9, and 11 studies that provided this data, respectively. Follow-up time after KT was reported in 11 studies (61.1%) and ranged from 16 mo to >5 y. Graft loss was reported in 14 studies with an average of 3% (95% CI, 1%-6%). Four studies that included a comparator group of patients with obesity who did not undergo BS before KT showed comparable outcomes between the groups. We conclude that currently there is a paucity of robust evidence to suggest that pretransplant BS has a major effect on post-KT outcomes. High-quality studies are needed to fully evaluate the impact of BS on KT outcomes.

Current Approaches to Diagnosis and Treatment of Ductal Carcinoma In Situ and Future Directions.

The presentation and treatment of ductal carcinoma in situ (DCIS) has changed substantially over the years. While previously an incidental pathologic finding in more advanced, palpable tumors, the institution of screening mammography has repositioned this disease entity as one largely diagnosed as a non-palpable lesion, often prior to any invasive disease. As DCIS is a precursor to invasive carcinoma, evolution in the approach to treatment has followed in the footsteps of that for invasive disease, including breast conservation therapy, adjuvant radiation, and use of antihormonal therapy. Survival outcomes for DCIS are very high and more recent literature has investigated tailoring therapeutic approaches to avoid overtreatment. Two important areas of ongoing clinical debate concerning overtreatment include use of preoperative MRI and the role of adjuvant radiation. The heterogeneity of the disease makes it difficult to differentiate lesions that would benefit from more aggressive treatment from those in which overtreatment could be avoided. Clinical characteristics, such as histologic appearance, age at diagnosis, and margin status at tumor excision have been established as moderate predictors of disease recurrence, but none has provided strong enough evidence as to guide consensus decisions on adjuvant therapy. Continuing research seeks to define the genetic and molecular characteristics that can predict disease course and serve as the potential targets for novel therapeutic agents. While several markers have shown promise in differentiating tumor aggressiveness, there is still much to be discovered about the precise mechanisms of disease progression and how this can be applied clinically to optimize treatment.

Feasibility and advantage of adding (131)I-MIBG to (90)Y-DOTATOC for treatment of patients with advanced stage neuroendocrine tumors.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) is an effective form of treatment for patients with metastatic neuroendocrine tumors (NETs). However, delivering sufficient radiation dose to the tumor to result in a high percentage of long-term tumor remissions remains challenging because of the limits imposed on administered activity levels by radiation damage to normal tissues. The goal of this study was to evaluate the dosimetric advantages of adding (131)I meta-iodobenzylguanidine ((131)I-MIBG) to (90)Y DOTA Phe1-Tyr3-octreotide ((90)Y-DOTATOC) in patients with advanced stage midgut NETs. METHODS: Ten patients were imaged simultaneously with (131)I-MIBG and (111)In-pentetreotide (as a surrogate for (90)Y-DOTATOC) on days 1, 2, and 3 post-administration. Blood samples were obtained at the same time points. Using dosimetry measures from this data and our previously published methodology for calculating optimal combined administered activity levels for therapy, we determined the amount of (131)I-MIBG that could be added to (90)Y-DOTATOC without exceeding normal organ dose limits (marrow and kidneys) along with the expected increase in associated tumor dose, if any. RESULTS: We found that a median value of 34.6 GBq of (131)I-MIBG could be safely added to (90)Y-DOTATOC (delivered over multiple cycles) by reducing the maximum total deliverable (90)Y-DOTATOC by a median value of 24.5%. Taking this treatment approach, we found that there would be a median increase in deliverable tumor dose of 4,046 cGy in six of the ten subjects. Of note, there were a small number of metastases that were positive for only one or the other of these radiopharmaceuticals within the same subject. CONCLUSIONS: We conclude that approximately half of the patients with midgut NETs that are eligible for PRRT could reasonably be expected to benefit from the addition of (131)I-MIBG to (90)Y-DOTATOC.

A functional role for TorsinA in herpes simplex virus 1 nuclear egress.

Herpes simplex virus 1 (HSV-1) capsids leave the nucleus by a process of envelopment and de-envelopment at the nuclear envelope (NE) that is accompanied by structural alterations of the NE. As capsids translocate across the NE, transient primary enveloped virions form in the perinuclear space. Here, we provide evidence that torsinA (TA), a ubiquitously expressed ATPase, has a role in HSV-1 nuclear egress. TA resides within the lumen of the endoplasmic reticulum (ER)/NE and functions in maintaining normal NE architecture. We show that perturbation of TA normal function by overexpressing torsinA wild type (TAwt) inhibits HSV-1 production. Ultrastructural analysis of infected cells overexpressing TAwt revealed reduced levels of surface virions in addition to accumulation of novel, double-membrane structures called virus-like vesicles (VLVs). Although mainly found in the cytoplasm, VLVs resemble primary virions in their size, by the appearance of the inner membrane, and by the presence of pUL34, a structural component of primary virions. Collectively, our data suggest a model in which interference of TA normal function by overexpression impairs de-envelopment of the primary virions leading to their accumulation in a cytoplasmic membrane compartment. This implies novel functions for TA at the NE.