PROPOSED REVISION OF THE AMERICAN ASSOCIATION FOR SURGERY OF TRAUMA RENAL TRAUMA ORGAN INJURY SCALE: SECONDARY ANALYSIS OF THE MULTI-INSTITUTIONAL GENITOURINARY TRAUMA STUDY.

BACKGROUND: This study updates the American Association for Surgery of Trauma (AAST) Organ Injury Scale (OIS) for renal trauma using evidence-based criteria for bleeding control intervention. METHODS: This was a secondary analysis of a multi-center retrospective study including patients with high grade renal trauma from 7 Level-1 trauma centers from 2013-2018. All eligible patients were assigned new renal trauma grades based on revised criteria. The primary outcome used to measure injury severity was intervention for renal bleeding. Secondary outcomes included intervention for urinary extravasation, units of packed red blood cells (PRBCs) transfused within 24 hours, and mortality. To test the revised grading system, we performed mixed effect logistic regression adjusted for multiple baseline demographic and trauma covariates. We determined the area under the receiver-operator curve (AUC) to assess accuracy of predicting bleeding interventions from the revised grading system and compared this to 2018 AAST organ injury scale. RESULTS: based on the 2018 OIS grading system, we included 549 patients with AAST Grade III-V injuries and CT scans (III: 52% (n = 284), IV: 45% (n = 249), and V: 3% (n = 16)). Among these patients, 89% experienced blunt injury (n = 491) and 12% (n = 64) underwent intervention for bleeding. After applying the revised grading criteria, 60% (n = 329) of patients were downgraded and 4% (n = 23) were upgraded; 2.8% (n = 7) downgraded from grade V to IV, and 69.5% (n = 173) downgraded from IV to III. The revised renal trauma grading system demonstrated improved predictive ability for bleeding interventions (2018 AUC = 0.805, revised AUC = 0.883; p = 0.001) and number of units of PRBCs transfused. When we removed urinary injury from the revised system, there was no difference in its predictive ability for renal hemorrhage intervention. CONCLUSIONS: A revised renal trauma grading system better delineates the need for hemostatic interventions than the current AAST OIS renal trauma grading system. LEVEL OF EVIDENCE: II.

Abnormalities in microbiota/butyrate/FFAR3 signaling in aging gut impair brain function.

Aging-related abnormalities in gut microbiota are associated with cognitive decline, depression, and anxiety, but underlying mechanisms remain unstudied. Here, our study demonstrated that transplanting old gut microbiota to young mice induced inflammation in the gut and brain coupled with cognitive decline, depression, and anxiety. We observed diminished mucin formation and increased gut permeability ("leaky gut") with a reduction in beneficial metabolites like butyrate because of decline in butyrate-producing bacteria in the aged gut microbiota. This led to suppressed expression of butyrate receptors, free fatty acid receptors 2 and 3 (FFAR2/3). Administering butyrate alleviated inflammation, restored mucin expression and gut barriers, and corrected brain dysfunction. Furthermore, young mice with intestine-specific loss of FFAR2/3 exhibited gut and brain abnormalities akin to those in older mice. Our results demonstrate that reduced butyrate-producing bacteria in aged gut microbiota result in low butyrate levels and reduced FFAR2/3 signaling, leading to suppressed mucin formation that increases gut permeability, inflammation, and brain abnormalities. These findings underscore the significance of butyrate-FFAR2/3 agonism as a potential strategy to mitigate aged gut microbiota-induced detrimental effects on gut and brain health in older adults.

Geroprotective potential of microbiome modulators in the Caenorhabditis elegans model.

Aging is associated with cellular and physiological changes, which significantly reduce the quality of life and increase the risk for disease. Geroprotectors improve lifespan and slow the progression of detrimental aging-related changes such as immune system senescence, mitochondrial dysfunction, and dysregulated nutrient sensing and metabolism. Emerging evidence suggests that gut microbiota dysbiosis is a hallmark of aging-related diseases and microbiome modulators, such as probiotics (live bacteria) or postbiotics (non-viable bacteria/bacterial byproducts) may be promising geroprotectors. However, because they are strain-specific, the geroprotective effects of probiotics and postbiotics remain poorly understood and understudied. Drosophila melanogaster, Caenorhabditis elegans, and rodents are well-validated preclinical models for studying lifespan and the role of probiotics and/or postbiotics, but each have their limitations, including cost and their translation to human aging biology. C. elegans is an excellent model for large-scale screening to determine the geroprotective potential of drugs or probiotics/postbiotics due to its short lifecycle, easy maintenance, low cost, and homology to humans. The purpose of this article is to review the geroprotective effects of microbiome modulators and their future scope, using C. elegans as a model. The proposed geroprotective mechanisms of these probiotics and postbiotics include delaying immune system senescence, preventing or reducing mitochondrial dysfunction, and regulating food intake (dietary restriction) and metabolism. More studies are warranted to understand the geroprotective potential of probiotics and postbiotics, as well as other microbiome modulators, like prebiotics and fermented foods, and use them to develop effective therapeutics to extend lifespan and reduce the risk of debilitating aging-related diseases.

Poor Oral Health Linked with Higher Risk of Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease characterized by cognitive and behavioral changes in older adults. Emerging evidence suggests poor oral health is associated with AD, but there is a lack of large-scale clinical studies demonstrating this link. Herein, we used the TriNetX database to generate clinical cohorts and assess the risk of AD and survival among >30 million de-identified subjects with normal oral health (n = 31,418,814) and poor oral health (n = 1,232,751). There was a greater than two-fold increase in AD risk in the poor oral health cohort compared to the normal oral health group (risk ratio (RR): 2.363, (95% confidence interval: 2.326, 2.401)). To reduce potential bias, we performed retrospective propensity score matching for age, gender, and multiple laboratory measures. After matching, the cohorts had no significant differences in survival probability. Furthermore, when comparing multiple oral conditions, diseases related to tooth loss were the most significant risk factor for AD (RR: 3.186, (95% CI: 3.007, 3.376)). Our results suggest that oral health may be important in AD risk, regardless of age, gender, or laboratory measures. However, more large-scale cohort studies are necessary to validate these findings and further evaluate links between oral health and AD.

Robot-Assisted Repair of Bladder Rupture following Penile Ring Entrapment.

Penile rings have been used to help sustain erection and enhance sexual pleasure for centuries. Constriction of the penis reduces the outflow of blood from the cavernosal tissue. However, if left for an extended time period, a condition called penile ring entrapment can occur. This may result in severe edema, gangrene, necrosis, and even penile amputation. Penile ring entrapment is a very rare condition; complete urinary obstruction with concomitant bladder rupture as a result renders this case even more extraordinary. We discuss our experience in the management of a 64-year-old man, who presented with altered mental status and inability to urinate, found to have penile ring entrapment and intraperitoneal bladder rupture. Removal of the constricting ring was performed in the ED, and bladder injury and penile necrosis were subsequently repaired with robot-assisted laparoscopic cystorrhaphy, penectomy, and perineal urethrostomy.

Distinct inflammatory Th17 subsets emerge in autoimmunity and infection.

Th17 cells play a critical role in both tissue homeostasis and inflammation during clearance of infections as well as autoimmune and inflammatory disorders. Despite numerous efforts to distinguish the homeostatic and inflammatory roles of Th17 cells, the mechanism underlying the divergent functions of inflammatory Th17 cells remains poorly understood. In this study, we demonstrate that the inflammatory Th17 cells involved in autoimmune colitis and those activated during colitogenic infection are distinguishable populations characterized by their differential responses to the pharmacological molecule, clofazimine (CLF). Unlike existing Th17 inhibitors, CLF selectively inhibits proautoimmune Th17 cells while preserving the functional state of infection-elicited Th17 cells partially by reducing the enzyme ALDH1L2. Overall, our study identifies two distinct subsets within the inflammatory Th17 compartment with distinct regulatory mechanisms. Furthermore, we highlight the feasibility to develop disease-promoting Th17 selective inhibitor for treating autoimmune diseases.

Grade V renal trauma management: results from the multi-institutional genito-urinary trauma study.

PURPOSE: To investigate management trends for American Association for the Surgery of Trauma (AAST) grade V renal trauma with focus on non-operative management. METHODS: We used prospectively collected data as part of the Multi-institutional Genito-Urinary Trauma Study (MiGUTS). We included patients with grade V renal trauma according to the AAST Injury Scoring Scale 2018 update. All cases submitted by participating centers with radiology images available were independently reviewed to confirm renal trauma grade. Management was classified as expectant, conservative (minimally invasive, endoscopic or percutaneous procedures), or operative (renal-related surgery). RESULTS: Eighty patients were included, 25 of whom had complete imaging and had independent confirmation of AAST grade V renal trauma. Median age was 35 years (Interquartile range (IQR) 25-50) and 23 (92%) had blunt trauma. Ten patients (40%) were managed operatively with nephrectomy. Conservative management was used in nine patients (36%) of which six received angioembolization and three had a stent or drainage tube placed. Expectant management was followed in six (24%) patients. Transfusion requirements were progressively higher with groups requiring more aggressive treatment, and injury characteristics differed significantly across management groups in terms of hematoma size and laceration size. Vascular contrast extravasation was more likely in operatively managed patients though a statistically significant association was not found. CONCLUSION: Successful use of nonoperative management for grade V injuries is used for a substantial subset of patients. Lower transfusion requirement and less severe injury radiologic phenotype appear to be important characteristics delineating this group.

Genital infection from Monkeypox virus requiring surgical debridement and scrotoplasty in an immunocompromised patient.

Background: Mpox is a zoonotic viral disease transmitted by close contact with infected individuals, contacting or eating infected animals, and now, sexual contact. The main treatment option for infected individuals is supportive care as no FDA-approved treatment exists. Case presentation: A 33-year-old male with HIV who contracted Mpox who developed a large painful genital ulcer with overlying eschar. He required surgical debridement of the penile ulcer followed by scrotoplasty. Conclusion: While local wound care plus antibiotics may be effective at managing some genital lesions, Urologists should consider surgical debridement with delayed reconstruction for progressive, non-healing wounds in these individuals.

A multicenter prospective cohort study of endoscopic urethral realignment versus suprapubic cystostomy after complete pelvic fracture urethral injury.

BACKGROUND: Pelvic fracture urethral injury (PFUI) occurs in up to 10% of pelvic fractures. There is mixed evidence supporting early endoscopic urethral realignment (EUR) over suprapubic tube (SPT) placement and delayed urethroplasty. Some studies show decreased urethral obstruction with EUR, while others show few differences. We hypothesized that EUR would reduce the rate of urethral obstruction after PFUI. METHODS: Twenty-six US medical centers contributed patients following either an EUR or SPT protocol from 2015 to 2020. If retrograde cystoscopic catheter placement failed, patients were included and underwent either EUR or SPT placement based on their institution's assigned treatment arm. Endoscopic urethral realignment involved simultaneous antegrade/retrograde cystoscopy to place a catheter across the urethral injury. The primary endpoint was development of urethral obstruction. Fisher's exact test was used to analyze the relationship between PFUI management and development of urethral obstruction. RESULTS: There were 106 patients with PFUI; 69 (65%) had complete urethral disruption and failure of catheter placement with retrograde cystoscopy. Of the 69 patients, there were 37 (54%) and 32 (46%) in the EUR and SPT arms, respectively. Mean age was 37.0 years (SD, 16.3 years) years, and mean follow-up was 463 days (SD, 280 days) from injury. In the EUR arm, 36 patients (97%) developed urethral obstruction compared with 30 patients (94%) in the SPT arm ( p = 0.471). Urethroplasty was performed in 31 (87%) and 29 patients (91%) in the EUR and SPT arms, respectively ( p = 0.784). CONCLUSION: In this prospective multi-institutional study of PFUI, EUR was not associated with a lower rate of urethral obstruction or need for urethroplasty when compared with SPT placement. Given the potential risk of EUR worsening injuries, clinicians should consider SPT placement as initial treatment for PFUI when simple retrograde cystoscopy is not successful in placement of a urethral catheter. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

The Outcomes of Pelvic Fracture Urethral Injuries Stratified by Urethral Injury Severity: A Prospective Multi-institutional Genitourinary Trauma Study (MiGUTS).

OBJECTIVE: To determine patient outcomes across a range of pelvic fracture urethral injury (PFUI) severity. PFUI is a devastating consequence of a pelvic fracture. No study has stratified PFUI outcomes based on severity of the urethral distraction injury. METHODS: Adult male patients with blunt-trauma-related PFUI were followed prospectively for a minimum of six months at 27 US medical centers from 2015-2020. Patients underwent retrograde cystourethroscopy and retrograde urethrography to determine injury severity and were categorized into three groups: (1) major urethral distraction, (2) minor urethral distraction, and (3) partial urethral injury. Major distraction vs minor distraction was determined by the ability to pass a cystoscope retrograde into the bladder. Simple statistics summarized differences between groups. Multi-variable analyses determined odds ratios for obstruction and urethroplasty controlling for urethral injury type, age, and Injury Severity Score. RESULTS: There were 99 patients included, 72(72%) patients had major, 13(13%) had minor, and 14(14%) had partial urethral injuries. The rate of urethral obstruction differed in patients with major (95.8%), minor (84.6%), and partial injuries (50%) (P < 0.001). Urethroplasty was performed in 90% of major, 66.7% of minor, and 35.7% of partial injuries (P < 0.001). CONCLUSION: In PFUI, a spectrum of severity exists that influences outcomes. While major and minor distraction injuries are associated with a higher risk of developing urethral obstruction and need for urethroplasty, up to 50% of partial PFUI will result in obstruction, and as such need to be closely followed.

Activation of Microbiota Sensing - Free Fatty Acid Receptor 2 Signaling Ameliorates Amyloid-ß Induced Neurotoxicity by Modulating Proteolysis-Senescence Axis.

Multiple emerging evidence indicates that the gut microbiota contributes to the pathology of Alzheimer's disease (AD)-a debilitating public health problem in older adults. However, strategies to beneficially modulate gut microbiota and its sensing signaling pathways remain largely unknown. Here, we screened, validated, and established the agonists of free fatty acid receptor 2 (FFAR2) signaling, which senses beneficial signals from short chain fatty acids (SCFAs) produced by microbiota. The abundance of SCFAs, is often low in the gut of older adults with AD. We demonstrated that inhibition of FFAR2 signaling increases amyloid-beta (Aß) stimulated neuronal toxicity. Thus, we screened FFAR2 agonists using an in-silico library of more than 144,000 natural compounds and selected 15 of them based on binding with FFAR2-agonist active sites. Fenchol (a natural compound commonly present in basil) was recognized as a potential FFAR2 stimulator in neuronal cells and demonstrated protective effects against Aß-stimulated neurodegeneration in an FFAR2-dependent manner. In addition, Fenchol reduced AD-like phenotypes, such as Aß-accumulation, and impaired chemotaxis behavior in Caenorhabditis (C.) elegans and mice models, by increasing Aß-clearance via the promotion of proteolysis and reduced senescence in neuronal cells. These results suggest that the inhibition of FFAR2 signaling promotes Aß-induced neurodegeneration, while the activation of FFAR2 by Fenchol ameliorates these abnormalities by promoting proteolytic Aß-clearance and reducing cellular senescence. Thus, stimulation of FFAR2 signaling by Fenchol as a natural compound can be a therapeutic approach to ameliorate AD pathology.

Nephrectomy After High-Grade Renal Trauma is Associated With Higher Mortality: Results From the Multi-Institutional Genitourinary Trauma Study (MiGUTS).

OBJECTIVE: To test the hypothesis that undergoing nephrectomy after high-grade renal trauma is associated with higher mortality rates. METHODS: We gathered data from 21 Level-1 trauma centers through the Multi-institutional Genito-Urinary Trauma Study. Patients with high-grade renal trauma were included. We assessed the association between nephrectomy and mortality in all patients and in subgroups of patients after excluding those who died within 24 hours of hospital arrival and those with GCS≤8. We controlled for age, injury severity score (ISS), shock (systolic blood pressure <90 mmHg), and Glasgow Coma Scale (GCS). RESULTS: A total of 1181 high-grade renal trauma patients were included. Median age was 31 and trauma mechanism was blunt in 78%. Injuries were graded as III, IV, and V in 55%, 34%, and 11%, respectively. There were 96 (8%) mortalities and 129 (11%) nephrectomies. Mortality was higher in the nephrectomy group (21.7% vs 6.5%, P <.001). Those who died were older, had higher ISS, lower GCS, and higher rates of shock. After adjusting for patient and injury characteristics nephrectomy was still associated with higher risk of death (RR: 2.12, 95% CI: 1.26-2.55). CONCLUSION: Nephrectomy was associated with higher mortality in the acute trauma setting even when controlling for shock, overall injury severity, and head injury. These results may have implications in decision making in acute trauma management for patients not in extremis from renal hemorrhage.

A Newly Developed Synbiotic Yogurt Prevents Diabetes by Improving the Microbiome-Intestine-Pancreas Axis.

The prevalence of type 2 diabetes mellitus (T2D) is increasing worldwide, and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of T2D, while microbiome modulators may be beneficial for T2D prevention. However, microbiome modulators that are effective, safe, affordable, and able to be administered daily are not yet available. Based on our previous pro- and prebiotic studies, we developed a novel synbiotic yogurt comprised of human-origin probiotics and plant-based prebiotics and investigated its impact on diet- and streptozotocin-induced T2D in mice. We compared the effects of our synbiotic yogurt to those of a commercially available yogurt (control yogurt). Interestingly, we found that the feeding of the synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls. Surprisingly, the control yogurt exacerbated diabetes progression. Synbiotic yogurt beneficially modulated the gut microbiota composition compared to milk, while the control yogurt negatively modulated it by significantly increasing the abundance of detrimental bacteria such as Proteobacteria and Enterobacteriaceae. In addition, the synbiotic yogurt protected pancreatic islet morphology compared to the milk control, while the control yogurt demonstrated worse effects on islets. These results suggest that our newly developed synbiotic yogurt protects against diabetes in mice and can be used as a therapeutic to prevent diabetes progression.

Low Interrater Reliability of Videourodynamic Diagnosis of Detrusor External Sphincter Dyssynergia.

OBJECTIVES: Complex bladder dysfunction requires urodynamic testing, often under fluoroscopy termed videourodynamic study (VUDS), to assist the diagnosis and management. Videourodynamic study is an objective tool with high interrater reliability (IRR) for identifying detrusor overactivity. However, IRR has not been validated with disorders associated with neurogenic bladder (NGB). We aim to investigate the IRR of VUDS to diagnose detrusor external sphincter dyssynergia (DESD) among NGB patients and hypothesize a high IRR to DESD diagnosis on VUDS. METHODS: Videourodynamics tracings with fluoroscopic images were rated either positive or negative for evidence of DESD by 4 raters (2 neurourologists, neurourology fellow, and urology postgraduate year 2 resident), in patients who underwent VUDS from 2013 to 2017. The study population had known NGB without previous bladder reconstruction. The IRR was determined using percent agreement and κ values. RESULTS: The experts had a percent agreement of 82.1% (κ = 0.26). Expert 1 and expert 2 had a percent agreement of 63.6% (κ = 0.1497) and 68.9% (κ = 0.2967), respectively, when compared with the fellow. Sensitivity and specificity ranged from 28% to 75% and 64% to 93%, respectively. The negative predictive values ranged from 90% to 95%. CONCLUSIONS: The IRR to diagnose DESD on VUDS was much lower than expected, even among experts, and was likely multifactorial and partially owing to lack of clinical context and lack of standardized VUDS interpretation of the electromyogram. A high negative predictive value was found among all participants. Further research is needed to evaluate factors contributing to the low reproducibility of DESD diagnosis on VUDS.

Current Management of Extraperitoneal Bladder Injuries: Results from the Multi-Institutional Genito-Urinary Trauma Study (MiGUTS).

PURPOSE: We studied the current management trends for extraperitoneal bladder injuries and evaluated the use of operative repair versus catheter drainage, and the associated complications with each approach. MATERIALS AND METHODS: We prospectively collected data on bladder trauma from 20 level 1 trauma centers across the United States from 2013 to 2018. We excluded patients with intraperitoneal bladder injury and those who died within 24 hours of hospital arrival. We separated patients with extraperitoneal bladder injuries into 2 groups (catheter drainage vs operative repair) based on their initial management within the first 4 days and compared the rates of bladder injury related complications among them. Regression analyses were used to identify potential predictors of complications. RESULTS: From 323 bladder injuries we included 157 patients with extraperitoneal bladder injuries. Concomitant injuries occurred in 139 (88%) patients with pelvic fracture seen in 79%. Sixty-seven patients (43%) initially underwent operative repair for their extraperitoneal bladder injuries. The 3 most common reasons for operative repair were severity of injury or bladder neck injury (40%), injury found during laparotomy (39%) and concern for pelvic hardware contamination (28%). Significant complications were identified in 23% and 19% of the catheter drainage and operative repair groups, respectively (p=0.55). The only statistically significant predictor for complications was bladder neck or urethral injury (RR 2.69, 95% 1.21-5.97, p=0.01). CONCLUSIONS: In this large multi-institutional cohort, 43% of patients underwent surgical repair for initial management of extraperitoneal bladder injuries. We found no significant difference in complications between the initial management strategies of catheter drainage and operative repair. The most significant predictor for complications was concomitant urethral or bladder neck injury.

The American Association for the Surgery of Trauma renal injury grading scale: Implications of the 2018 revisions for injury reclassification and predicting bleeding interventions.

BACKGROUND: In 2018, the American Association for the Surgery of Trauma (AAST) published revisions to the renal injury grading system to reflect the increased reliance on computed tomography scans and non-operative management of high-grade renal trauma (HGRT). We aimed to evaluate how these revisions will change the grading of HGRT and if it outperforms the original 1989 grading in predicting bleeding control interventions. METHODS: Data on HGRT were collected from 14 Level-1 trauma centers from 2014 to 2017. Patients with initial computed tomography scans were included. Two radiologists reviewed the scans to regrade the injuries according to the 1989 and 2018 AAST grading systems. Descriptive statistics were used to assess grade reclassifications. Mixed-effect multivariable logistic regression was used to measure the predictive ability of each grading system. The areas under the curves were compared. RESULTS: Of the 322 injuries included, 27.0% were upgraded, 3.4% were downgraded, and 69.5% remained unchanged. Of the injuries graded as III or lower using the 1989 AAST, 33.5% were upgraded to grade IV using the 2018 AAST. Of the grade V injuries, 58.8% were downgraded using the 2018 AAST. There was no statistically significant difference in the overall areas under the curves between the 2018 and 1989 AAST grading system for predicting bleeding interventions (0.72 vs. 0.68, p = 0.34). CONCLUSION: About one third of the injuries previously classified as grade III will be upgraded to grade IV using the 2018 AAST, which adds to the heterogeneity of grade IV injuries. Although the 2018 AAST grading provides more anatomic details on injury patterns and includes important radiologic findings, it did not outperform the 1989 AAST grading in predicting bleeding interventions. LEVEL OF EVIDENCE: Prognostic and Epidemiological Study, level III.

The associations between initial radiographic findings and interventions for renal hemorrhage after high-grade renal trauma: Results from the Multi-Institutional Genitourinary Trauma Study.

BACKGROUND: Indications for intervention after high-grade renal trauma (HGRT) remain poorly defined. Certain radiographic findings can be used to guide the management of HGRT. We aimed to assess the associations between initial radiographic findings and interventions for hemorrhage after HGRT and to determine hematoma and laceration sizes predicting interventions. METHODS: The Genitourinary Trauma Study is a multicenter study including HGRT patients from 14 Level I trauma centers from 2014 to 2017. Admission computed tomography scans were categorized based on multiple variables, including vascular contrast extravasation (VCE), hematoma rim distance (HRD), and size of the deepest laceration. Renal bleeding interventions included angioembolization, surgical packing, renorrhaphy, partial nephrectomy, and nephrectomy. Mixed-effect Poisson regression was used to assess the associations. Receiver operating characteristic analysis was used to define optimal cutoffs for HRD and laceration size. RESULTS: In the 326 patients, injury mechanism was blunt in 81%. Forty-seven (14%) patients underwent 51 bleeding interventions, including 19 renal angioembolizations, 16 nephrectomies, and 16 other procedures. In univariable analysis, presence of VCE was associated with a 5.9-fold increase in risk of interventions, and each centimeter increase in HRD was associated with 30% increase in risk of bleeding interventions. An HRD of 3.5 cm or greater and renal laceration depth of 2.5 cm or greater were most predictive of interventions. In multivariable models, VCE and HRD were significantly associated with bleeding interventions. CONCLUSION: Our findings support the importance of certain radiographic findings in prediction of bleeding interventions after HGRT. These factors can be used as adjuncts to renal injury grading to guide clinical decision making. LEVEL OF EVIDENCE: Prognostic and Epidemiological Study, Level III and Therapeutic/Care Management, Level IV.

Probiotics and Prebiotics for the Amelioration of Type 1 Diabetes: Present and Future Perspectives.

Type 1-diabetes (T1D) is an autoimmune disease characterized by immune-mediated destruction of pancreatic beta (ß)-cells. Genetic and environmental interactions play an important role in immune system malfunction by priming an aggressive adaptive immune response against ß-cells. The microbes inhabiting the human intestine closely interact with the enteric mucosal immune system. Gut microbiota colonization and immune system maturation occur in parallel during early years of life; hence, perturbations in the gut microbiota can impair the functions of immune cells and vice-versa. Abnormal gut microbiota perturbations (dysbiosis) are often detected in T1D subjects, particularly those diagnosed as multiple-autoantibody-positive as a result of an aggressive and adverse immunoresponse. The pathogenesis of T1D involves activation of self-reactive T-cells, resulting in the destruction of ß-cells by CD8⁺ T-lymphocytes. It is also becoming clear that gut microbes interact closely with T-cells. The amelioration of gut dysbiosis using specific probiotics and prebiotics has been found to be associated with decline in the autoimmune response (with diminished inflammation) and gut integrity (through increased expression of tight-junction proteins in the intestinal epithelium). This review discusses the potential interactions between gut microbiota and immune mechanisms that are involved in the progression of T1D and contemplates the potential effects and prospects of gut microbiota modulators, including probiotic and prebiotic interventions, in the amelioration of T1D pathology, in both human and animal models.

A nomogram predicting the need for bleeding interventions after high-grade renal trauma: Results from the American Association for the Surgery of Trauma Multi-institutional Genito-Urinary Trauma Study (MiGUTS).

BACKGROUND: The management of high-grade renal trauma (HGRT) and the indications for intervention are not well defined. The American Association for the Surgery of Trauma (AAST) renal grading does not incorporate some important clinical and radiologic variables associated with increased risk of interventions. We aimed to use data from a multi-institutional contemporary cohort to develop a nomogram predicting risk of interventions for bleeding after HGRT. METHODS: From 2014 to 2017, data on adult HGRT (AAST grades III-V) were collected from 14 level 1 trauma centers. Patients with both clinical and radiologic data were included. Data were gathered on demographics, injury characteristics, management, and outcomes. Clinical and radiologic parameters, obtained after trauma evaluation, were used to predict renal bleeding interventions. We developed a prediction model by applying backward model selection to a logistic regression model and built a nomogram using the selected model. RESULTS: A total of 326 patients met the inclusion criteria. Mechanism of injury was blunt in 81%. Median age and injury severity score were 28 years and 22, respectively. Injuries were reported as AAST grades III (60%), IV (33%), and V (7%). Overall, 47 (14%) underwent interventions for bleeding control including 19 renal angioembolizations, 16 nephrectomies, and 12 other procedures. Of the variables included in the nomogram, a hematoma size of 12 cm contributed the most points, followed by penetrating trauma mechanism, vascular contrast extravasation, pararenal hematoma extension, concomitant injuries, and shock. The area under the receiver operating characteristic curve was 0.83 (95% confidence interval, 0.81-0.85). CONCLUSION: We developed a nomogram that integrates multiple clinical and radiologic factors readily available upon assessment of patients with HGRT and can provide predicted probability for bleeding interventions. This nomogram may help in guiding appropriate management of HGRT and decreasing unnecessary interventions. LEVEL OF EVIDENCE: Prognostic and epidemiological study, level III.

Optimal timing of delayed excretory phase computed tomography scan for diagnosis of urinary extravasation after high-grade renal trauma.

BACKGROUND: Excretory phase computed tomography (CT) scan is used for diagnosis of renal collecting system injuries and accurate grading of high-grade renal trauma. However, optimal timing of the excretory phase is not well established. We hypothesized that there is an association between excretory phase timing and diagnosis of urinary extravasation and aimed to identify the optimal excretory phase timing for diagnosis of urinary extravasation. METHODS: The Genito-Urinary Trauma Study collected data on high-grade renal trauma (grades III-V) from 14 Level I trauma centers between 2014 and 2017. The time between portal venous and excretory phases at initial CT scans was recorded. Poisson regression was used to measure the association between excretory phase timing and diagnosis of urinary extravasation. Predictive receiver operating characteristic analysis was used to identify a cutoff point optimizing detection of urinary extravasation. RESULTS: Overall, 326 patients were included; 245 (75%) had excretory phase CT scans for review either initially (n = 212) or only at their follow-up (n = 33). At initial CT with excretory phase, 46 (22%) of 212 patients were diagnosed with urinary extravasation. Median time between portal venous and excretory phases was 4 minutes (interquartile range, 4-7 minutes). Time of initial excretory phase was significantly greater in those diagnosed with urinary extravasation. Increased time to excretory phase was positively associated with finding urinary extravasation at the initial CT scan after controlling for multiple factors (risk ratio per minute, 1.15; 95% confidence interval, 1.09-1.22; p < 0.001). The optimal delay for detection of urinary extravasation was 9 minutes. CONCLUSION: Timing of the excretory phase is a significant factor in accurate diagnosis of renal collecting system injury. A 9-minute delay between the early and excretory phases optimized detection of urinary extravasation. LEVEL OF EVIDENCE: Diagnostic tests/criteria study, level III.