Treatment of infants with ureteropelvic junction obstruction: findings from the PURSUIT network

International Urology and Nephrology - Studies based on administrative databases show that infant pyeloplasty is associated with minority race/ethnicity but lack clinical data that may influence...     

A review of burn symptoms and potential novel neural targets for non-invasive brain stimulation for treatment of burn sequelae

Burn survivors experience myriad associated symptoms such as pain, pruritus, fatigue, impaired motor strength, post-traumatic stress, depression, anxiety, and sleep disturbance. Many of these symptoms are common and remain chronic, despite current standard of care. One potential novel intervention to target these post burn symptoms is transcranial direct current stimulation (tDCS). tDCS is a non-invasive brain stimulation (NIBS) technique that modulates neural excitability of a specific target or neural network. The aim of this work is to review the neural circuits of the aforementioned clinical sequelae associated with burn injuries and to provide a scientific rationale for specific NIBS targets that can potentially treat these conditions. We ran a systematic review, following the PRISMA statement, of tDCS effects on burn symptoms. Only three studies matched our criteria. One was a feasibility study assessing cortical plasticity in chronic neuropathic pain following burn injury, one looked at the effects of tDCS to reduce pain anxiety during burn wound care, and one assessed the effects of tDCS to manage pain and pruritus in burn survivors. Current literature on NIBS in burn remains limited, only a few trials have been conducted. Based on our review and results in other populations suffering from similar symptoms as patients with burn injuries, three main areas were selected: the prefrontal region, the parietal area and the motor cortex. Based on the importance of the prefrontal cortex in the emotional component of pain and its implication in various psychosocial symptoms, targeting this region may represent the most promising target. Our review of the neural circuitry involved in post burn symptoms and suggested targeted areas for stimulation provide a spring board for future study initiatives.     

Variation in acute fluid resuscitation among pediatric burn centers

BackgroundAccurate resuscitation of pediatric patients with large thermal injury is critical to achieving optimal outcomes. The goal of this project was to describe the degree of variability in resuscitation guidelines among pediatric burn centers and the impact on fluid estimates.MethodsFive pediatric burn centers in the Pediatric Injury Quality Improvement Collaborative (PIQIC) contributed data from patients with ≥15% total body surface area (TBSA) burns treated from 2014 to 2018. Each center's resuscitation guidelines and guidelines from the American Burn Association were used to calculate estimated 24-h fluid requirements and compare these values to the actual fluid received.ResultsDifferences in the TBSA burn at which fluid resuscitation was initiated, coefficients related to the Parkland formula, criteria to initiate dextrose containing fluids, and urine output goals were observed. Three of the five centers’ resuscitation guidelines produced statistically significant lower mean fluid estimates when compared with the actual mean fluid received for all patients across centers (4.53 versus 6.35 ml/kg/% TBSA, p < 0.001), (4.90 versus 6.35 ml/kg/TBSA, p = 0.002) and (3.38 versus 6.35 ml/kg/TBSA, p < 0.0001).ConclusionsThis variation in practice patterns led to statistically significant differences in fluid estimates. One center chose to modify its resuscitation guidelines at the conclusion of this study.     

Mortality After Revision Total Hip Arthroplasty

BackgroundIn counseling patients about the complications of revision total hip arthroplasty (revTHA), it is imperative that mortality be considered. The actual mortality rate by indication of revision is ill-defined. The purpose of this study is to determine the mortality rate after revTHA.MethodsAn institutional database identified 596 patients who had undergone revTHA between 2012 and 2018. Medical records, national, state, and local death indexes were queried for mortality status and indication for revTHA. For survivors, the last clinical visit date was used for censoring in the mortality analysis. Mortality rates were calculated for all clinical patients and then by specific indication for revision.ResultsThe overall 2-year mortality rate following revTHA was 19.5 deaths per 1000 or 1 in 51 patients. Patients presenting with a periprosthetic fracture had a significantly higher 2-year mortality rate of 74.5 deaths per 1000 or 1 in 13 patients (P < .001), while an indication of dislocation or instability had a slightly higher 2-year mortality rate of 50.3 per 1000 (1 in 20) but this difference was not significant (P = .531). Other indications such as mechanical loosening or infection did not have a significantly different mortality rate.ConclusionThe overall 2-year mortality rate following revTHA was 19.5 deaths per 1000 which was largely attributed to patients with a periprosthetic fracture (74.5 per 1000) with other indications not significantly impacting mortality. Mortality rates and specific rates by indication for revision should be considered when counseling patients prior to revTHA.     

Outcomes following adoption of a standardized protocol for abscess drain management in pediatric appendicitis

Background/purposeThough evidence-based clinical pathways for the diagnosis and treatment of pediatric appendicitis have been established, protocols guiding management of percutaneous abscess drains are lacking. We hypothesized a drain management protocol utilizing drain output and clinical factors instead of fluoroscopic drain studies would reduce interventional radiologic procedures without adversely impacting clinical outcomes.MethodsA standardized protocol was uniformly adopted at a tertiary-care children's hospital in April 2016. A retrospective chart review included all cases of appendicitis requiring abscess drainage by interventional radiology three years pre- and postprotocol implementation.ResultsFifty-eight patients (preprotocol = 39, postprotocol = 19) underwent percutaneous abscess drainage, of whom 52 (preprotocol = 34, postprotocol = 18) required a drain. Baseline demographics and clinical presentation were similar across groups. Following protocol implementation, total number of IR procedures decreased from 2.4 to 1.3 per patient (p = 0.004). There was no significant difference in the number of postprocedure diagnostic imaging studies, readmissions, or inpatient days, and there was a trend towards a decrease in number of drain days (10.7 to 5.7, p = 0.067).ConclusionA standardized protocol for management of abscess drains for complicated appendicitis reduced the number of IR procedures without a negative impact on clinical outcomes or increase in alternative imaging studies. This approach may decrease radiation exposure, anesthetic administration, and resource utilization.Type of studyTreatment study (retrospective comparative study).Level of evidenceLevel III.     

Gli1 Defines a Subset of Fibro-adipogenic Progenitors that Promote Skeletal Muscle Regeneration With Less Fat Accumulation

Skeletal muscle has remarkable regenerative ability after injury. Mesenchymal fibro-adipogenic progenitors (FAPs) are necessary, active participants during this repair process, but the molecular signatures of these cells and their functional relevance remain largely unexplored. Here, using a lineage tracing mouse model (Gli1-CreER Tomato), we demonstrate that Gli1 marks a small subset of muscle-resident FAPs with elevated Hedgehog (Hh) signaling. Upon notexin muscle injury, these cells preferentially and rapidly expanded within FAPs. Ablation of Gli1+ cells using a DTA mouse model drastically reduced fibroblastic colony-forming unit (CFU-F) colonies generated by muscle cells and impaired muscle repair at 28 days. Pharmacologic manipulation revealed that Gli1+ FAPs rely on Hh signaling to increase the size of regenerating myofiber. Sorted Gli1+ FAPs displayed superior clonogenicity and reduced adipogenic differentiation ability in culture compared to sorted Gli1− FAPs. In a glycerol injury model, Gli1+ FAPs were less likely to give rise to muscle adipocytes compared to other FAPs. Further cell ablation and Hh activator/inhibitor treatments demonstrated their dual actions in enhancing myogenesis and reducing adipogenesis after injury. Examining single-cell RNA-sequencing dataset of FAPs from normal mice indicated that Gli1+ FAPs with increased Hh signaling provide trophic signals to myogenic cells while restrict their own adipogenic differentiation. Collectively, our findings identified a subpopulation of FAPs that play an essential role in skeletal muscle repair. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Osteoblasts Generate Testosterone From DHEA and Activate Androgen Signaling in Prostate Cancer Cells

Bone metastasis is a complication of prostate cancer in up to 90% of men afflicted with advanced disease. Therapies that reduce androgen exposure remain at the forefront of treatment. However, most prostate cancers transition to a state whereby reducing testicular androgen action becomes ineffective. A common mechanism of this transition is intratumoral production of testosterone (T) using the adrenal androgen precursor dehydroepiandrosterone (DHEA) through enzymatic conversion by 3β- and 17β-hydroxysteroid dehydrogenases (3βHSD and 17βHSD). Given the ability of prostate cancer to form blastic metastases in bone, we hypothesized that osteoblasts might be a source of androgen synthesis. RNA expression analyses of murine osteoblasts and human bone confirmed that at least one 3βHSD and 17βHSD enzyme isoform was expressed, suggesting that osteoblasts are capable of generating androgens from adrenal DHEA. Murine osteoblasts were treated with 100 nM and 1 μM DHEA or vehicle control. Conditioned media from these osteoblasts were assayed for intermediate and active androgens by liquid chromatography–tandem mass spectrometry. As DHEA was consumed, the androgen intermediates androstenediol and androstenedione were generated and subsequently converted to T. Conditioned media of DHEA-treated osteoblasts increased androgen receptor (AR) signaling, prostate-specific antigen (PSA) production, and cell numbers of the androgen-sensitive prostate cancer cell lines C4-2B and LNCaP. DHEA did not induce AR signaling in osteoblasts despite AR expression in this cell type. We describe an unreported function of osteoblasts as a source of T that is especially relevant during androgen-responsive metastatic prostate cancer invasion into bone. © 2021 American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.     

Survival Outcomes for Metaplastic Breast Cancer Differ by Histologic Subtype

Background

Metaplastic breast carcinoma (MBC) is a rare, aggressive subtype of breast cancer associated with poorer overall survival than other triple-negative breast cancers. This study sought to compare survival outcomes among histologic subtypes of MBC with those of non-metaplastic triple-negative breast cancer.

Methods

Clinicopathologic and treatment data for all patients with non-metastatic, pure MBC undergoing surgery from 1995 to 2017 and for a large cohort of patients with other types of triple-negative breast cancer during that period were collected from an institutional database. The MBC tumors were classified as having squamous, spindle, heterologous mesenchymal, or mixed histology. Survival outcomes were compared using the Kaplan-Meier method.

Results

Of 132 MBC patients, those with heterologous mesenchymal MBC (n?=?45) had the best 5-year overall and breast cancer-specific survival (BCSS, 88%; 95% confidence interval [CI], 0.78–0.99), whereas those with squamous MBC had the worst survival (BCSS, 56%; 95% CI, 0.32–0.79). Overall survival, BCSS, and recurrence-free survival were worse for the patients with MBC than for the patients who had non-MBC triple-negative breast cancer, with a clinicopathologically adjusted recurrence hazard ratio of 2.4 (95% CI, 1.6–3.3; p?<?0.001). Of the 10 MBC patients who received neoadjuvant chemotherapy, 4 progressed while receiving treatment, and 3 had no response.

Conclusions

Metaplastic breast carcinoma is associated with worse survival than other triple-negative breast cancers. The heterologous mesenchymal subtype is associated with the best survival, whereas the squamous subtype is associated with the worst survival. These data call for research to identify therapies tailored to MBC’s unique biology.