New onset vesicovaginal fistula after transurethral collagen injection in women who underwent cystectomy and orthotopic neobladder creation: presentation and definitive treatment

PURPOSE: We present our experience with collagen injection for treating urinary incontinence after cystectomy and orthotopic bladder substitution in women. We discuss the efficacy of collagen injection, specific complications and subsequent definitive therapy. MATERIALS AND METHODS: We performed cystectomy and orthotopic bladder substitution in 2 women for muscle invasive transitional cell carcinoma of the bladder. In each case new onset stress urinary incontinence developed after surgery that was refractory to conservative therapy. Intrinsic sphincter deficiency was diagnosed in each patient by video urodynamic studies. Initial treatment involved transurethral collagen injections but subsequent intervention was required due to resultant complications and primary therapy inefficacy. RESULTS: Collagen (3.5 cc per session) was injected in 1 case at 2 treatment sessions and in the other at 3. Incontinence symptoms did not significantly improve in either patient and a new onset vesicovaginal fistula developed 2 days and 1 month after collagen injection, respectively. Subsequently in each case 1-stage transvaginal primary fistula repair was done in multiple layers with a pubovaginal sling procedure. Six months after repair there has been no recurrent fistula and the women remain hypercontinent, requiring intermittent self-catheterization. They are satisfied with their eventual lower tract function and overall outcome. CONCLUSIONS: Collagen injection for type 3 stress urinary incontinence after cystectomy and orthotopic bladder replacement in women may not be as effective and innocuous as in patients with a native bladder. Initial treatment with a pubovaginal sling procedure should be considered.     

Monoclonal antibodies to human platelet glycoprotein IIb beta that initiate distinct platelet responses

Hybridomas secreting monoclonal antibodies (MoAbs) to human platelet membrane glycoprotein IIb (GPIIb) were prepared by fusing cells of a mouse myeloma line to spleen cells from a BALB/c mouse immunized with purified GPIIb. Six of the hybridomas secreted MoAbs that recognized epitopes on the 23,000-dalton, disulfide-linked subunit of GPIIb, GPIIb beta. All six of these MoAbs agglutinated platelets in the absence of calcium. The agglutination titers of three of the MoAbs, however, were enhanced between 2 and 6 log2 dilutions when titrated in the presence of mmol/L of calcium. The enhancement in titer was the result of MoAb- induced platelet activation followed by platelet aggregation, a reaction that could also be initiated by the monovalent Fab fragments prepared from one of the MoAbs. The MoAbs did not significantly agglutinate platelets from patients with Glanzmann's thrombasthenia, confirming biochemical evidence that there is a paucity of GPIIb beta in the membranes of these cells. Our results show that MoAbs to epitopes on GPIIb beta initiate distinct platelet responses; therefore, they should be useful for studying the ways in which regions of surface glycoproteins are involved in platelet-platelet interactions. In addition, these reagents may prove of value in diagnosing and typing patients with Glanzmann's thrombasthenia.     

Proteomics and transcriptomics of peripheral nerve tissue and cells unravel new aspects of the human Schwann cell repair phenotype

The remarkable feature of Schwann cells (SCs) to transform into a repair phenotype turned the spotlight on this powerful cell type. SCs provide the regenerative environment for axonal re‐growth after peripheral nerve injury (PNI) and play a vital role in differentiation of neuroblastic tumors into a benign subtype of neuroblastoma, a tumor originating from neural crest‐derived neuroblasts. Hence, understanding their mode‐of‐action is of utmost interest for new approaches in regenerative medicine, but also for neuroblastoma therapy. However, literature on human SCs is scarce and it is unknown to which extent human SC cultures reflect the SC repair phenotype developing after PNI in patients. We performed high‐resolution proteome profiling and RNA‐sequencing on highly enriched human SC and fibroblast cultures, control and ex vivo degenerated nerve explants to identify novel molecules and functional processes active in repair SCs. In fact, we found cultured SCs and degenerated nerves to share a similar repair SC‐associated expression signature, including the upregulation of JUN, as well as two prominent functions, i.e., myelin debris clearance and antigen presentation via MHCII. In addition to myelin degradation, cultured SCs were capable of actively taking up cell‐extrinsic components in functional phagocytosis and co‐cultivation assays. Moreover, in cultured SCs and degenerated nerve tissue MHCII was upregulated at the cellular level along with high expression of chemoattractants and co‐inhibitory rather than ‐stimulatory molecules. These results demonstrate human SC cultures to execute an inherent program of nerve repair and support two novel repair SC functions, debris clearance via phagocytosis‐related mechanisms and type II immune‐regulation. GLIA 2016;64:2133–2153     

Studies on murine thyroiditis: new insights from organ flow cytometry.

The pathogenesis of autoimmune diseases is frequently studied in murine models, in which disease outcome is traditionally assessed by light microscopy. To determine whether digital imaging improves reliability of the histopathologic assessment, and whether flow cytometry is applicable directly on the murine thyroid, we studied 395 CBA/J mice 3 weeks after thyroglobulin immunization, and 192 nonimmunized CBA/J mice. Digital imaging significantly improved reliability of the histopathological assessment (r = 0.988, 95% confidence interval: 0.980-0.992, p < 0.0001), and flow cytometry on the murine thyroid could be performed successfully. We also found that normal thyroids contained a higher than expected number of hematopoietic cells in the interstitium. We suggest that digital imaging offers a better means of estimating disease outcome, and that flow cytometry performed at the target organ levels reflects the autoimmune pathogenesis more closely than when performed on peripheral lymphoid organs. These methods should also be applicable to other organ systems targeted by autoimmune attack, such as heart, exocrine, and other endocrine glands.     

Use of half‐normal saline irrigant with cooled radiofrequency ablation within the great cardiac vein to ablate premature ventricular contractions arising from the left ventricular summit

A 62‐year‐old man was referred to our institution for high‐density, symptomatic premature ventricular contractions (PVCs) with resultant decrease in left ventricular (LV) function having failed prior ablation attempts. Successful, durable ablation of the patient's mid‐myocardial PVC arising from the LV summit region was achieved through the proximal great cardiac vein with ablation depth augmented by use of half‐normal saline irrigant. Though standard ablation of ventricular arrhythmias using normal saline irrigation from the coronary venous system has been well‐reported, this may be of limited value in addressing mid‐myocardial sites of origin. This novel case describes the safe use of cooled radiofrequency ablation with use of half‐normal saline irrigant from the distal coronary sinus as an option to address complex sites of PVC origin such as the LV summit.