Repair of Limb Ischemia Is Dependent on Hematopoietic Stem Cell Specific-SHP-1 Regulation of TGF-ß1.

BACKGROUND: Hematopoietic stem cell (HSC) therapy has shown promise for tissue regeneration after ischemia. Therefore, there is a need to understand mechanisms underlying endogenous HSCs activation in response to ischemic stress and coordination of angiogenesis and repair. SHP-1 plays important roles in HSC quiescence and differentiation by regulation of TGF-ß1 signaling. TGF-ß1 promotes angiogenesis by stimulating stem cells to secrete growth factors to initiate the formation of blood vessels and later aid in their maturation. We propose that SHP-1 responds to ischemia stress in HSC and progenitor cells (HSPC) via regulation of TGF-ß1. METHODS: A mouse hind limb ischemia model was used. Local blood perfusion in the limbs was determined using laser doppler perfusion imaging. The number of positive blood vessels per square millimeter, as well as blood vessel diameter (µm) and area (µm2), were calculated. Hematopoietic cells were analyzed using flow cytometry. The bone marrow transplantation assay was performed to measure HSC reconstitution. RESULTS: After femoral artery ligation, TGF-ß1 was initially decreased in the bone marrow by day 3 of ischemia, followed by an increase on day 7. This pattern was opposite to that in the peripheral blood, which is concordant with the response of HSC to ischemic stress. In contrast, SHP-1 deficiency in HSC is associated with irreversible activation of HSPCs in the bone marrow and increased circulating HSPCs in peripheral blood following limb ischemia. In addition, there was augmented auto-induction of TGF-ß1 and sustained inactivation of SHP-1-Smad2 signaling, which impacted TGF-ß1 expression in HSPCs in circulation. Importantly, restoration of normal T GF-ß1 oscillations helped in the recovery of limb repair and function. CONCLUSIONS: HSPC-SHP-1-mediated regulation of TGF-ß1 in both bone marrow and peripheral blood is required for a normal response to ischemic stress.

Randomized Controlled Trial of Single-dose Perioperative Pregabalin in Ureteroscopy.

PURPOSE: Ureteroscopy is a commonly performed procedure, with postoperative pain that can lead to revisits and opioid prescribing. Perioperative gabapentinoids have shown promise in decreasing pain and opioid use. We hypothesized that single-dose perioperative pregabalin would be safe and efficacious for decreasing pain after ureteroscopy. MATERIALS AND METHODS: This was an Institutional Review Board-approved and registered blinded, placebo-controlled trial conducted at a single institution. Patients undergoing ureteroscopy without histories that would limit use of opioids, gabapentinoids, and nonsteroidal medications were enrolled. Either 300 mg pregabalin or placebo was administered 1 hour before ureteroscopy. Pain was assessed using a visual analogue scale before administration and 1 hour after surgery. Clinical factors, pain scores, a proxy for cognition, patient satisfaction, and opioid prescribing were assessed in the first 30 postoperative days. RESULTS: A total of 118 patients were enrolled over a 2-year period. Patients who received pregabalin were younger than those who received placebo (median of 44 years vs 57). Postoperative pain scores were higher in those who received pregabalin (3.7 vs 2.0, P = .004), a finding that remained statistically significant when accounting for patient age and preoperative pain scores. There was no difference in the measure of cognition or in reports of adverse events. CONCLUSIONS: In this trial evaluating the efficacy of single-dose perioperative pregabalin in ureteroscopy, pregabalin did not decrease postoperative pain when compared to placebo. Urologists should not routinely use this adjunctive medication in ureteroscopy, as it is unlikely to provide benefit.

Characteristics, Comorbidities, and Outcomes in a Multicenter Registry of Patients With Human Immunodeficiency Virus and Coronavirus Disease 2019.

BACKGROUND: People living with human immunodeficiency virus (HIV) may have numerous risk factors for acquiring coronavirus disease 2019 (COVID-19) and developing severe outcomes, but current data are conflicting. METHODS: Health-care providers enrolled consecutively, by nonrandom sampling, people living with HIV (PWH) with lab-confirmed COVID-19, diagnosed at their facilities between 1 April and 1 July 2020. Deidentified data were entered into an electronic Research Electronic Data Capture (REDCap) system. The primary endpoint was a severe outcome, defined as a composite endpoint of intensive care unit (ICU) admission, mechanical ventilation, or death. The secondary outcome was the need for hospitalization. RESULTS: There were 286 patients included; the mean age was 51.4 years (standard deviation, 14.4), 25.9% were female, and 75.4% were African American or Hispanic. Most patients (94.3%) were on antiretroviral therapy, 88.7% had HIV virologic suppression, and 80.8% had comorbidities. Within 30 days of testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 164 (57.3%) patients were hospitalized, and 47 (16.5%) required ICU admission. Mortality rates were 9.4% (27/286) overall, 16.5% (27/164) among those hospitalized, and 51.5% (24/47) among those admitted to an ICU. The primary composite endpoint occurred in 17.5% (50/286) of all patients and 30.5% (50/164) of hospitalized patients. Older age, chronic lung disease, and hypertension were associated with severe outcomes. A lower CD4 count (<200 cells/mm3) was associated with the primary and secondary endpoints. There were no associations between the ART regimen or lack of viral suppression and the predefined outcomes. CONCLUSIONS: Severe clinical outcomes occurred commonly in PWH with COVID-19. The risks for poor outcomes were higher in those with comorbidities and lower CD4 cell counts, despite HIV viral suppression. CLINICAL TRIALS REGISTRATION: NCT04333953.

The deep medial femoral sulcus sign: does it exist?

OBJECTIVE: To determine the normal depth of the medial femoral sulcus on lateral radiographs of the knee and determine if abnormal deepening of the medial femoral sulcus exists as a radiographic indicator of intra-articular knee abnormalities. MATERIALS AND METHODS: A retrospective search was performed over a period of 10 years to identify all individuals with a bone contusion of the anterior medial femoral condyle at MR imaging. Study patients had documented acute knee injuries and radiographs 6 weeks or less prior to their MR. A control group had normal MR exams and radiographs 6 weeks or less prior to their MR. Two fellowship-trained musculoskeletal radiologists independently measured the depth of the medial femoral sulcus on lateral radiographs blinded to control or study individuals. RESULTS: The study group consisted of 76 patients (57 men, 19 women; age range, 18-50 years; mean age, 27 years) and 92 control patients (33 men, 59 women; age range, 18-46 years; mean age 26 years). Sulcus depth was (0-2.3 mm reader 1 and 0-1.7 mm reader 2 for controls; 0-2.2 mm reader1 and 0-1.8 mm reader 2 for study patients). No significant difference in sulcus depth was identified between the control and study groups. Inter-reader agreement was very strong. The most common cause of injury in the study group was motor vehicle accidents followed by hyperextension and twisting injuries of the knee. CONCLUSION: The normal medial femoral sulcus ranges in depth from 0 to 2.3 mm. Although impaction of the sulcus does occur following knee injuries, the sulcus does not deepen.

Proton pump inhibitors are associated with increased risk of development of chronic kidney disease.

BACKGROUND: Acute interstitial nephritis secondary to proton pump inhibitors (PPIs) frequently goes undiagnosed due to its subacute clinical presentation, which may later present as chronic kidney disease (CKD). We investigated the association of PPI use with the development of CKD and death. METHODS: Two separate retrospective case-control study designs were employed with a prospective logistic regression analysis of data to evaluate the association of development of CKD and death with PPI use. The population included 99,269 patients who were seen in primary care VISN2 clinics from 4/2001 until 4/2008. For evaluation of the CKD outcome, 22,807 with preexisting CKD at the first observation in Veterans Affairs Health Care Upstate New York (VISN2) network data system were excluded. Data obtained included use of PPI (Yes/No), demographics, laboratory data, pre-PPI comorbidity variables. RESULTS: A total of 19,311/76,462 patients developed CKD. Of those who developed CKD 24.4 % were on PPI. Patients receiving PPI were less likely to have vascular disease, COPD, cancer and diabetes. Of the total of 99,269 patients analyzed for mortality outcome, 11,758 died. A prospective logistic analysis of case-control data showed higher odds for development of CKD (OR 1.10 95 % CI 1.05-1.16) and mortality (OR 1.76, 95 % CI 1.67-1.84) among patients taking PPIs versus those not on PPIs. CONCLUSIONS: Use of proton pump inhibitors is associated with increased risk of development of CKD and death. With the large number of patients being treated with proton pump inhibitors, healthcare providers need to be better educated about the potential side effects of these medications.

Prevalence of various comorbidities among veterans with chronic kidney disease and its comparison with other datasets.

Chronic kidney disease (CKD) has a complicated interrelationship with various comorbidities. The purpose of this study was to describe the prevalence of various comorbidities among veterans with CKD and compare it with other datasets like Kidney Early Evaluation Program (KEEP), National Health and Nutrition Examination Survey (NHANES) and Medicare. Patients who had at least one outpatient visit in year 2007 (1 January 2007 to 31 December 2007) were included in the study (n = 75,787). Glomerular filtration rate (eGFR) was estimated by the Modification of Diet in Renal Disease (MDRD) study equation. CKD prevalence was calculated based on one or two serum creatinine values at least 3 months apart. Demographic data were obtained including age, gender, race, weight, height and body mass index (BMI). The prevalence of various comorbidities was also collected based on ICD 9 codes from the problem list. The prevalence of CKD among veterans was 47.3%, much higher than estimated in the US population. Patients with CKD were more likely to have any vascular disease (36.89% vs. 14.87%), diabetes (34.18% vs. 17.83%), hypertension (86.65% vs. 57.56%), and cancer (18.69% vs. 9.23%). Irrespective of age, the prevalence of vascular disease was much higher among veterans with CKD. The prevalence of coronary artery disease, peripheral vascular disease, and cancer was much higher among elderly veterans with CKD as compared to other datasets. CKD is a growing endemic associated with a high frequency of concomitant chronic illnesses. Public health resources should be applied for early recognition and risk modification of CKD.

Developing and Psychometric Testing a Health Care Transition Service Measure in the National Survey of Children's Health.

OBJECTIVE: Access to health care transition (HCT) services has been included in national surveys for 20 years. While dozens of studies have assessed HCT, no study has examined the model fit of the HCT questions or psychometric properties of the measure. We utilized National Survey of Children's Health (NSCH) data to develop and test a comprehensive HCT measure. METHODS: We utilized NSCH data (2016-19) to examine the model fit of 9 HCT questions. The new measure's psychometric properties were assessed by comparing it to theoretically similar and divergent variables including receiving care coordination/help, shared-decision making, satisfaction with communication, preventative dental care, and volunteer experience. RESULTS: An exploratory factor analysis and item culling yielded 8 items addressing 3 subscales. A confirmatory factor analysis on separate data confirmed the identified subscales. A dichotomous and continuous scale was created with subscales including Guidance Toward Independence, Adequate Clinic Visit, and Continuity of Care Discussions. Model fit was excellent with an Eigenvalue of 1.08% and 89% variance explained in exploratory factor analysis and a Goodness of Fit index of 0.97 in confirmatory factor analysis. Examination of initial reliability and content and criterion validity indicated high reliability and validity for the scale and subscales. CONCLUSIONS: This was the first study to examine the psychometric properties of the HCT measure in the NSCH. The HCT measure identified in this study assesses providers' use of care plans, promotion of independence, clinic visit quality, and transfer assistance. This measure will be a useful tool in clinics, intervention development, and research for adolescents with and without special health care needs.retain-->.

Renal function, calcium regulation, and time to hospitalization of patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease is associated with disruption of the endocrine system that distorts the balance between calcitriol, calcium, phosphate and parathyroid hormone in the calcium regulation system. This can lead to calcification of the arterial tree and increased risk of cardiovascular disease and death. In this study we develop a health metric, based on biomarkers involved in the calcium regulation system, for use in identifying patients at high risk for future high-cost complications. METHODS: This study is a retrospective observational study involving a secondary analysis of data from the kidney disease registry of a regional managed care organization. Chronic kidney disease patients in the registry from November 2007 through November 2011 with a complete set of observations of estimated glomerular filtration rate, calcitriol, albumin, free calcium, phosphate, and parathyroid hormone were included in the study (n = 284). Weibull regression model was used to identify the most significant lab tests in predicting "waiting time to hospitalization". A multivariate linear path model was then constructed to investigate direct and indirect effects of the biomarkers on this outcome. RESULTS: The results showed negative significant direct effects of phosphate and parathyroid hormone on "waiting time to hospitalization". Base on this result, the risk of hospitalization increases 16.8% for each 0.55 mg/dl increase in phosphate level and 13.5% for each 0.467 increase in the natural logarithm of parathyroid hormone. Positive indirect effects of calcitriol surrogate (calcidiol), free calcium, albumin and estimated glomerular filtration rate were observed but were relatively small in magnitude. CONCLUSION: Variables involved in the calcium regulation system should be included in future efforts to develop a quality of care index for Chronic Kidney disease patients.

Right inferior frontal gyrus theta-burst stimulation reduces smoking behaviors and strengthens fronto-striatal-limbic resting-state functional connectivity: a randomized crossover trial.

Introduction: Functional and anatomical irregularities in the right inferior frontal gyrus (rIFG), a ventrolateral prefrontal region that mediates top-down inhibitory control over prepotent behavioral responding, are implicated in the ongoing maintenance of nicotine dependence (ND). However, there is little research on the effects of neuromodulation of the rIFG on smoking behavior, inhibitory control, and resting-state functional connectivity (rsFC) among individuals with ND. Methods: In this double-blind, crossover, theta-burst stimulation (TBS) study, adults with ND (N = 31; female: n = 15) completed a baseline session and were then randomized to two counterbalanced sessions of functionally neuronavigated TBS to the rIFG: continuous TBS (cTBS) on 1 day and intermittent TBS (iTBS) on another. Differences in cigarette cravings, smoking, and fronto-striatal-limbic rsFC were assessed. Results: Relative to baseline, cTBS significantly reduced appetitive and withdrawal cravings immediately after treatment. The effects of cTBS on withdrawal craving persisted for 24 h, as well as produced a reduction in smoking. Furthermore, cTBS significantly strengthened rsFC between the rIFG pars opercularis and subcallosal cingulate (fronto-striatal circuit), and between the rIFG pars opercularis and the right posterior parahippocampal gyrus (fronto-limbic circuit). At post-24 h, cTBS-induced increase in fronto-striatal rsFC was significantly associated with less appetitive craving, while the increase in fronto-limbic rsFC was significantly associated with less withdrawal craving and smoking. Discussion: These findings warrant further investigation into the potential value of rIFG cTBS to attenuate smoking behavior among individuals with ND.

Within State Variability of Antimicrobial Susceptibility: Missouri as an Archetype to Assess Guidelines for Antimicrobial Prophylaxis for Transurethral Procedures.

OBJECTIVE: To evaluate variability among hospitals in susceptibility of common uropathogens to antimicrobial agents frequently used in transurethral procedures in order to examine whether state-based guidelines might be more appropriate than national prophylactic guidelines. METHODS: Hospital-level antibiograms were requested from all hospitals throughout the state of Missouri. We studied Escherichia coli, Klebsiella, and Proteus sensitivities to evaluate common guideline recommended antimicrobials including trimethoprim sulfamethoxazole (TMP-SMX), third-generation cephalosporins, cefazolin, penicillin combinations, gentamicin, and fluoroquinolones. We evaluated variability and association between hospital characteristics and antimicrobial sensitivities. RESULTS: Data was requested from 81 hospitals across the state and 38 provided the requested data (47% response rate). Susceptibility was highest for third-generation cephalosporins for E. coli (mean of 94%), Proteus (96%), and Klebsiella (96%). Gentamicin also had high susceptibility for the bacteria studied; 94% for E. coli and 96% for Klebsiella. Current first line recommended agents showed more modest coverage for E. coli (cefazolin 84%, TMP-SMX 78%), Proteus (cefazolin 82%, TMP-SMX 71%), and Klebsiella (cefazolin 90%, TMP-SMX 89%). CONCLUSION: Post transurethral procedure infections are common. Rates can be limited with appropriate prophylaxis. Deciding on empirical coverage must take into account local resistance patterns. There is substantial variability among and within states in antimicrobial susceptibility for common uropathogens. When selecting antimicrobial prophylaxis, urologists should consider local- rather than state- or nation-level antibiograms, given the considerable variability. Future studies should consider the merits of very-broad spectrum prophylaxis and the potential role of molecular urinary pathogen (and pathogen-resistance) testing when selecting an optimal regimen.

Holistic Assessment of Quality of Life Predicts Survival in Older Patients with Bladder Cancer.

OBJECTIVE: To determine if clustering methods can use a holistic assessment of health-related quality-of-life after bladder cancer diagnosis to predict survival outcomes independent of clinical characteristics. In the United States, an estimated 81,180 cases of bladder cancer will be diagnosed in 2022. We aim to help address the knowledge gap concerning the impact of patient functional status on outcomes. MATERIALS AND METHODS: This is a cross-sectional, retrospective cohort study of patients in the End Results-Medicare Health Outcomes Survey Registry. Age and 36-Item Short Form Survey (SF-36) responses were used as K-means inputs to identify homogenous clusters of older patients with bladder cancer. We analyzed the association between the identified clusters, patient and disease characteristics, and outcomes. We used Cox proportional hazard regression to compare overall survival. RESULTS: We identified 5 homogenous clusters that exhibited differences in patient characteristics and survival. There was no significant difference in cancer stage or surgery type among the clusters. The Cox proportional hazard regression demonstrated significant associations of cluster with gender, age, education, marital status, smoking status, type of surgery, and cancer stage on overall survival. Cluster independently predicted overall survival. CONCLUSION: Using unsupervised machine learning, we identified clusters of patients with bladder cancer who had similar mental and physical function scores. Cluster grouping suggests that patients' mental and physical function may not be based on disease or treatment. There are significant survival differences between all clusters, demonstrating that a holistic assessment of patient-reported health-related quality-of-life has the potential to predict survival and possible modifiable risk factors in older patients with bladder cancer.

Improving Perceptual Speech Ratings: The Effects of Auditory Training on Judgments of Dysarthric Speech.

PURPOSE: Auditory training has been shown to reduce rater variability in perceptual voice assessment. Because rater variability is also a central issue in the auditory-perceptual assessment of dysarthria, this study sought to determine if training produces a meaningful change in rater reliability, criterion validity, and scaling magnitude of four features: overall speech impairment, articulatory imprecision, monotony, and slow rate. METHOD: Forty-four nonexperts randomized to training and nontraining listener groups completed a pretest and posttest. Only the former group underwent auditory training between pre- and posttests. For both testing and training, listeners rated samples from speakers with amyotrophic lateral sclerosis (ALS), speakers with Parkinson's disease (PD), and neurologically healthy control speakers using separate visual analog scales (VASs) for each of the four features. Intraclass correlation coefficients were used to compare inter- and intrarater reliability between pre- and posttest for both listener groups. For criterion validity, severity ratings from the two nonexpert listener groups were compared to those of two experienced listeners for all four features. To determine changes in scaling magnitude, raw VAS scores for each feature were compared from pre- to posttest within the two nonexpert listener groups. Scaling changes were also compared between the two listener groups for the pre- and posttest conditions. RESULTS AND CONCLUSIONS: In the training group, a meaningful improvement in interrater reliability was observed for some features in all three speaker groups, but not in the nontraining group. In contrast, for intrarater reliability, in the nontraining group, a meaningful improvement was observed for many features in all three speaker groups, but only for PD monotony and slow rate in the training group. All ratings from the nonexpert listeners were valid except for monotony. Raw VAS scores did not meaningfully change from pre- to posttest for any of the features, but there was a trend toward lower scores posttraining, mainly for the ALS samples. Modifications to the auditory training paradigm to further improve reliability and validity, along with future goals for optimizing training, are discussed.

Development and Initial Evaluation of Web-Based Cognitive Behavioral Therapy for Insomnia in Rural Family Caregivers of People With Dementia (NiteCAPP): Mixed Methods Study.

BACKGROUND: Informal caregivers of people with dementia frequently experience chronic insomnia, contributing to stress and poor health outcomes. Rural caregivers are particularly vulnerable but have limited access to cognitive behavioral therapy for insomnia (CBT-I), a recommended frontline treatment for chronic insomnia. Web-based delivery promises to improve insomnia, particularly for rural caregivers who have limited access to traditional in-person treatments. Our team translated an efficacious 4-session standard CBT-I content protocol into digital format to create NiteCAPP. OBJECTIVE: This study aimed to (1) adapt NiteCAPP for dementia caregivers to create NiteCAPP CARES, a tailored digital format with standard CBT-I content plus caregiver-focused modifications; (2) conduct usability testing and evaluate acceptability of NiteCAPP CARES' content and features; and (3) pilot-test the adapted intervention to evaluate feasibility and preliminary effects on sleep and related health outcomes. METHODS: We followed Medical Research Council recommendations for evaluating complex medical interventions to explore user needs and adapt and validate content using a stepwise approach: (1) a rural dementia caregiver (n=5) and primary care provider (n=5) advisory panel gave feedback that was used to adapt NiteCAPP; (2) caregiver (n=5) and primary care provider (n=7) focus groups reviewed the newly adapted NiteCAPP CARES and provided feedback that guided further adaptations; and (3) NiteCAPP CARES was pilot-tested in caregivers (n=5) for feasibility and to establish preliminary effects. Self-report usability measures were collected following intervention. Before and after treatment, 14 daily electronic sleep diaries and questionnaires were collected to evaluate arousal, health, mood, burden, subjective cognition, and interpersonal processes. RESULTS: The stepped approach provided user and expert feedback on satisfaction, usefulness, and content, resulting in a new digital CBT-I tailored for rural dementia caregivers: NiteCAPP CARES. The advisory panel recommended streamlining content, eliminating jargon, and including caregiver-focused content. Focus groups gave NiteCAPP CARES high usefulness ratings (mean score 4.4, SD 0.79, scored from 1=least to 5=most favorable; score range 4.2-4.8). Multiple features were evaluated positively, including the intervention's comprehensive and engaging information, caregiver focus, good layout, easy-to-access intervention material, and easy-to-understand sleep graphs. Suggestions for improvement included the provision of day and night viewing options, collapsible text, font size options, tabbed access to videos, and a glossary of terms. Pilot-test users rated usefulness (mean score 4.3, SD 0.83; range 4.1-4.5) and satisfaction (mean score 8.4, SD 1.41, scored from 1=least to 10=most satisfied; range 7.4-9.0) highly. Preliminary effects on caregiver sleep, arousal, health, mood, burden, cognition, and interpersonal processes (all P<.05) were promising. CONCLUSIONS: Adaptations made to standard digital CBT-I created a feasible, tailored digital intervention for rural dementia caregivers. Important next steps include further examination of feasibility and efficacy in a randomized controlled trial with an active control condition, a multisite effectiveness trial, and eventual broad dissemination. TRIAL REGISTRATION: ClinicalTrials.gov NCT04632628; https://clinicaltrials.gov/ct2/show/NCT04632628.

Effectiveness of Standard Margin Stereotactic Radiosurgery Dose to Brain Metastases.

BACKGROUND: This study aims to assess efficacy of a 15-Gy margin dose in terms with the hypothesis that efficacy will be comparable with historical controls with fewer radiation-related side effects. METHODS: Patients who received single-fraction stereotactic radiosurgery (SRS) for metastatic brain tumors (prescribed 1500 cGy with 2-mm planning tumor volume) at the University of Missouri Hospital between 2004 and 2018 with at least 3 months of follow-up were retrospectively reviewed. Demographics, lesion dimensions, concurrent therapy, and treatment history before SRS were assessed. Outcomes included local control, distant control, radiation-related changes, survival, repeat SRS or whole-brain radiation therapy, and side effects. Data from the literature were pooled for a meta-analysis. RESULTS: A total of 142 patients had at least 3 months of follow-up data available. The 12-month actual local control rate among these patients was 92% per tumor. The overall intracranial control rate was 66.9% per patient. Radiation-related side effects occurred in 32.4% of patients (n = 46), with some patients having more than 1 side effect. Radiation-related radiographic changes occurred in 48 lesions (10.6%) in 37 patients (26%). Pathologically confirmed radiation necrosis occurred in 19 lesions (4%) and in 18 patients (12.6%). Local and distant control rates for this population was comparable with historical controls. Side effects in the literature are inconsistently reported, so rigorous comparative analysis is not possible. CONCLUSIONS: A single-fraction radiosurgery margin dose of 15 Gy to the planning tumor volume can effectively provide local control and distant control and is comparable with historical controls, which use 18-25 Gy, with a good toxicity profile.

Phase I single center trial of ketogenic diet for adults with traumatic brain injury.

BACKGROUND: Traumatic Brain injury (TBI) is a major cause of mortality and morbidity in the United States. Ketogenic diet (KD) has been shown to have neuroprotective effects in acute brain injury, but limited data about its use in adult TBI patients is available. The objective of this study is to investigate the feasibility and safety of ketogenic diet (KD) for adult TBI patients in the Neuroscience Intensive Care Unit (NSICU). METHODS: TBI patients admitted to NSICU between June 2019 to March 2021 were enrolled in this single-center, open label, single-arm prospective intervention study. The primary feasibility outcome was achievement of ketosis (detection and maintenance of serum beta-hydroxybutyrate (BOB) levels above normal); secondary outcomes included laboratory and clinical adverse effects related to KD. RESULTS: 10 adults with TBI with Abbreviated Injury Score (AIS)-Head ≥3 and ventriculostomy catheter to monitor intracranial pressure met inclusion/exclusion criteria and were placed on KD. Mean age was 47 years, and all patients were male. Eight out of 10 patients achieved ketosis within mean 2.2 days. KD was initiated within 8-33 h (average 23 h) of hospital admission. No clinical adverse effects were noted, 2 patients developed hypertriglyceridemia and 1 patient developed hypoglycemia. Serum glucose showed a decreasing trend in most patients. CONCLUSIONS: This pilot study shows that KD is feasible in the management of TBI patients. A randomized controlled trial (RCT) is justified to further understand the optimal serum BOB levels, dose and duration of KD in TBI and its effect on the outcome. CLINICALTRIALS. GOV IDENTIFIER: NCT03982602, Registered 06/11/2019, https://clinicaltrials.gov/ct2/show/NCT03982602?term=brain+injury&cond=ketogenic+diet&draw=2&rank=3.

Antimicrobial Selection for Transurethral Procedures Across the United States: A State-by-State Antibiogram Evaluation.

OBJECTIVE: To evaluate optimal regimens for perioperative antimicrobial prophylaxis in transurethral procedures by examining antimicrobial susceptibility patterns in the United States. MATERIALS AND METHODS: Through several methods, we attempted to attain an antibiogram for each state. We focused on microbes known to cause infections after transurethral surgeries and antibiotics referred to in current or prior recommendations and compared susceptibility rates across states using Kruskal Walis tests and the Dwass, Steel, Critchlow-Fligner tests. We also examined susceptibility to (non-ceftazidime) third generation cephalosporins. RESULTS: Data is included from 40 states. For each microbe studied, there was significant variability in sensitivity to antibiotics studied. Current first line recommendations for antimicrobial prophylaxis include first generation cephalosporins with 82%, 80%, and 87% mean coverage for E coli, Proteus, and Klebsiella respectively and trimethoprim-sulfamethoxazole with 74%, 80%, and 93% coverage, respectively. Susceptibility to aminoglycosides is 91%, 92%, and 96%, respectively and to third generation cephalosporin, it is 92%, 99%, and 94%. CONCLUSION: Current first line recommended antimicrobials for prophylaxis in transurethral procedures provide overall poor predicted coverage based on our database of antibiograms. Alternatives exist that have higher predicted susceptibility, though clinical significance of this and risk of resultant antimicrobial resistance is unknown. Urologists should consider local patterns when selecting antimicrobial prophylaxis for their patients.