Bladder Augmentation (Enterocystoplasty): the Current State of a Historic Operation.

PURPOSE OF REVIEW: The goal of this paper was to evaluate the current use of enterocystoplasty, a historical operation for bladder dysfunction but with continued and increasing modern relevance. RECENT FINDINGS: Since the advent of third line neuromodulation techniques for neurogenic and idiopathic overactive bladder (OAB), the usage of enterocystoplasty has decreased. However, this procedure continues to be utilized in pediatric urology patients and the most refractory OAB patients. Adult urologist should be familiar with this operative technique in an effort to manage pediatric patients transitioning to adulthood. Minimally invasive techniques for this surgical procedure have been described with very limited outcome data. It is important for all urologists to be familiar with enterocystoplasty, both technically and with the unique needs of these patients postoperatively. Further studies evaluating the outcomes of this procedure in idiopathic overactive bladder patients and efforts to standardize recommendations for neurogenic bladder patients will help guide care in the future.

Nonsurgical management of photoaversive ocular and systemic loiasis in Michigan.

Objective: Ocular loasis refers to ocular conditions such as pain and redness caused by the movement of the Loa loa nematode through the subconjuctival space of the eye. It is a tropical disease that is very rarely seen in North America. We report the case of a 32-year-old male who was recently diagnosed with ocular loasis in the Midwestern region of the United States. Methods: He presented to the emergency department with left eye pain after seeing a "worm in his eye" the previous night. He had emigrated from Cameroon 7 years prior. Anterior segment examination revealed a translucent, motile worm in the subconjunctival space of his left eye. Results: Prior to the patient's scheduled follow-up for surgical removal of the worm, it migrated into the lower eyelid subdermal space. Serum testing confirmed the presence of Loa loa microfilariae at a concentration of >17,000 mf/mL. Conclusion: The patient was treated at the National Institute of Health (NIH) with pheresis followed by diethylcarbamazine and reported symptomatic improvement 1 month after treatment. This case report demonstrates the importance of being able to recognize and properly manage vector-borne parasites in nonendemic areas due to increased travel and climate change.

Prognostic value of changes in neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) for patients with cervical cancer undergoing definitive chemoradiotherapy (dCRT).

BACKGROUND: Peripheral NLR, PLR, and LMR have prognostic value in various malignancies as they are surrogates for inflammation. Recent studies have identified NLR, PLR, and LMR correlate with patient outcomes in cervical cancer patients however there remains uncertainty regarding the optimal time point for assessing these markers. METHODS: We retrospectively reviewed cervical cancer patients underoing definitive chemoradiation therapy (dCRT). NLR, PLR, and LMR values were identified before, during, and after dCRT and both relative and absolute changes in these values were calculated and compared with patient outcmoes. RESULTS: Ninety-nine patients who met the includsion criteria were identified. NLR values before, during, and after dCRT correlated with progression free survival (PFS) and overall survival (OS). In addition, increasing NLR after treatment was associated with worse PFS and OS. LMR before and after treatment had a positive correlation with PFS however increasing LMR during dCRT was found to have a negative correlation with PFS and OS. CONCLUSIONS: NLR serves as a prognostic indicator irrespective of timing with response to dCRT. While higher LMR before treatment was a positive prognostic indicator, increasing LMR was found to negatively correlate with PFS and OS.

Outcomes of Intradetrusor Onabotulinum Toxin A Therapy in Overactive Bladder Refractory to Sacral Neuromodulation.

PURPOSE: Intradetrusor onabotulinum toxin A (BTXA) and sacral neuromodulation (SNM) are effective third-line therapies for overactive bladder (OAB). We aimed to measure the outcomes of BTXA for treatment of OAB refractory to initial SNM and identify patient characteristics associated with these outcomes. METHODS: This retrospective cohort study included patients who failed to respond to initial SNM treatment for OAB and subsequently received BTXA at a single provider's clinic between January 2013 and December 2016. Treatment successes were defined as patients willing to continue BTXA or who found symptom relief whereas treatment failures discontinued BTXA due to adverse effects or lack of symptom relief. Symptoms and patient-reported outcomes on validated questionnaires were compared before the initial BTXA trial to 2 months after the last BTXA treatment. The SNM failure BTXA groups were also compared to BTXA SNM naïve groups. RESULTS: Of 18 patients who received BTXA after failed SNM treatment, 7 (39%) achieved treatment success. Successfully treated patients demonstrated decreased urinary frequency from a median 11 voids/day pre-BTXA to 8 voids/day with BTXA (P=0.042). Patients whose treatment failed reported increased complaints of a weak urinary stream (P=0.03) and higher frequency of straining to urinate (P=0.016) than the successful treatment group pre-BTXA. Compared to BTXA patients without prior SNM, the odds of failing BTXA after initial SNM were 3.6 times higher (P=0.016). CONCLUSION: BTXA appears effective for OAB refractory to SNM, although the success rate is lower compared to BTXA patients without SNM exposure.

Author Correction: Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Atomic-level evidence for packing and positional amyloid polymorphism by segment from TDP-43 RRM2.

Proteins in the fibrous amyloid state are a major hallmark of neurodegenerative disease. Understanding the multiple conformations, or polymorphs, of amyloid proteins at the molecular level is a challenge of amyloid research. Here, we detail the wide range of polymorphs formed by a segment of human TAR DNA-binding protein 43 (TDP-43) as a model for the polymorphic capabilities of pathological amyloid aggregation. Using X-ray diffraction, microelectron diffraction (MicroED) and single-particle cryo-EM, we show that the 247DLIIKGISVHI257 segment from the second RNA-recognition motif (RRM2) forms an array of amyloid polymorphs. These associations include seven distinct interfaces displaying five different symmetry classes of steric zippers. Additionally, we find that this segment can adopt three different backbone conformations that contribute to its polymorphic capabilities. The polymorphic nature of this segment illustrates at the molecular level how amyloid proteins can form diverse fibril structures.

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of ß-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible ß-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation.