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Despite the high prevalence and economic burden of chronic kidney disease (CKD) in the United States, federal funding for kidney-related research, prevention, and education activities under the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) remains substantially lower compared to other chronic diseases. More federal support is needed to promote critical research that will expand knowledge of kidney health and disease, develop new and effective therapies, and reduce health disparities. In 2021, the National Kidney Foundation (NKF) convened 2 Research Roundtables (preclinical and clinical research), comprising nephrology leaders from prominent US academic institutions and the pharmaceutical industry, key bodies with expertise in research, and including individuals with CKD and their caregivers and kidney donors. The goal of these roundtables was to identify priorities for preclinical and clinical kidney-related research. The research priorities identified by the Research Roundtables and presented in this position statement outline attainable opportunities for groundbreaking and critically needed innovations that will benefit patients with kidney disease in the next 5-10 years. Research priorities fall within 4 preclinical science themes (expand data science capability, define kidney disease mechanisms and utilize genetic tools to identify new therapeutic targets, develop better models of human disease, and test cell-specific drug delivery systems and utilize gene editing) and 3 clinical science themes (expand number and inclusivity of clinical trials, develop and test interventions to reduce health disparities, and support implementation science). These priorities in kidney-related research, if supported by additional funding by federal agencies, will increase our understanding of the development and progression of kidney disease among diverse populations, attract additional industry investment, and lead to new and more personalized treatments.

This chapter summarizes primary care principles for recognizing psychologically traumatized patients and engaging them in treatment. Psychological trauma is a psychiatric injury that occurs in response to severely stressful events and can become chronic if not treated. Trauma-informed clinicians understand how psychological trauma changes how people feel, think, and behave. Recognizing and engaging a psychologically traumatized patient for diagnosis and treatment is one of the most satisfying clinical experiences in primary care, opening doors for both patient and provider. While posttraumatic stress disorder (PTSD) is a common psychiatric disorder, the condition tends to be under-recognized. PTSD recognition is challenging owing to stigma, the variety of presentations, the non-specific nature, and range of severity of PTSD symptoms, and high co-occurrence with other conditions. Patients can be reluctant to seek care, disclose traumatizing events, or remember events. PTSD is more prevalent in people with addictions, chronic physical health conditions, chronic pain, medically unexplained symptoms, other psychiatric disorders, and occupations such as military and public safety personnel. Fourteen diverse case examples demonstrate some of the many faces of PTSD in adults. Barriers and facilitators to recognizing PTSD in primary care and targeted use of screening tools are discussed.

Kidney disease is an important US public health problem because it affects over 37 million Americans, and Medicare expenditures for patients with chronic kidney disease now alone exceed $130 billion annually. Kidney disease is characterized by strong racial, ethnic, and socioeconomic disparities, and reducing kidney disease incidence will positively impact US health disparities. Due to the aging of the US population and an unabated obesity epidemic, the number of patients receiving treatment for kidney failure is anticipated to increase, which will escalate kidney disease health expenditures. The historical and current investment in kidney-related research via the National Institute of Diabetes and Digestive and Kidney Diseases has severely lagged behind ongoing expenditures for kidney disease care. Increasing research investment will identify, develop, and increase implementation of interventions to slow kidney disease progression, reduce incidence of kidney failure, enhance survival, and improve quality of life. This perspective states the urgent reasons why increasing investment in kidney-related research is important for US public health. The National Kidney Foundation and the American Society of Nephrology are working together to advocate for increased funding for the National Institute of Diabetes and Digestive and Kidney Diseases. The long-term goal is to reduce the burden of kidney disease in the US population and improve the quality of life of patients living with kidney disease.

Objectives/Hypothesis To characterize the frequency and nature of readmissions to free standing pediatric hospitals after otolaryngologic procedures. Study Design Retrospective national database analysis. Methods Using the Pediatric Health Information Systems database, we examined 30-day inpatient readmissions in children less than 18 years old who underwent otolaryngology procedures between January 1, 2009, and December 31, 2011. Univariate and multivariate logistic regression analyses accounting for correlated structure of the data identified factors related to readmission rate. Reasons for readmission and the postoperative day at which readmission occurred were also examined. Results In the 24-month study period, a total of 493,507 procedures were performed, resulting in 11,574 (2.3%) 30-day readmissions. Readmission rates varied significantly based on the type of procedure, patient age, and presence of chronic medical condition(s). Direct surgical complications accounted for 3,432 (29.7%) of all readmissions; and 4,729 (40.9%) of all readmissions occurred following tonsil and adenoid surgery. Conclusion Readmissions after pediatric otolaryngologic surgery are relatively uncommon. These readmission rates vary directly with the type of procedure performed, as well as patient level factors (i.e., patient age, ethnicity, and the presence of other medical comorbidities). These data demonstrate that if readmission rates are to be used as a quality measure in pediatric otolaryngology procedures, complex risk adjustment of patient level variables will be necessary to accurately compare outcomes between different hospitals. Level of Evidence 2c. Laryngoscope, 2015

To test the possibility that chronic mild stress (CMS) might be unreliable in producing its often-intended outcome (i.e., decreased preference for sucrose, hypothesized to represent depression-relevant anhedonia) because it is typically applied to "normal" rats, a CMS procedure was applied to rats that may possess genetic susceptibility to affective disorders, having had been selectively-bred to show behavior indicative of such disorders. These rat lines were: Hyperactive (HYPER) rats, which show characteristics of bipolar disorder, Swim-test Susceptible (SUS) and Swim-test Resistant (RES) rats, being susceptible or resistant to effects of stress in the swim test, Swim High-active (SwHi) and Swim Low-active (SwLo) rats, which innately show high or low activity in the swim test. These selectively-bred lines were compared to normal, non-selectively bred (NS) rats. During CMS, HYPER rats, both females and males, as well as RES and SwHi rats, showed reduced consumption of a palatable 2% sucrose solution, and reduced preference for sucrose (vs. water) in comparison to non-stressed rats (no CMS) of the same lines. In contrast, CMS produced no decrease in sucrose consumption or in preference for sucrose in normal NS rats, and actually a caused a slight increase in sucrose consumption and preference in male NS rats. Other measures that indicate depression - food intake and motor activity in the home cage - were also assessed. SwLo and SwHi showed greater sensitivity to having their home-cage ambulatory activity reduced by CMS than did NS rats, but no other such differences relative to NS rats were seen for these other measures; thus, changes in sucrose intake or preference could not be explained by a change in caloric intake. These results suggest that the genetic attributes of animals can influence the outcome of CMS, and that the application of CMS to normal, non-selected rats may account, at least in part, for the unreliability of CMS in decreasing consumption of palatable substances and decreasing preference for such substances.

This study was conducted to evaluate whether preoperative magnetic resonance imaging (MRI) measurements of the cross-sectional area and length of the semitendinosus tendon correlated with graft diameter. The goal of the study was to identify tendons at risk for requiring graft augmentation. The records of 140 consecutive patients undergoing anterior cruciate ligament (ACL) reconstruction between 2013 and 2016 were examined retrospectively. The study included 39 patients who underwent all-inside ACL reconstruction with a semitendinosus autograft. A single researcher used preoperative MRI scans to measure the cross-sectional area and length of the semitendinosus tendon. Graft cross-sectional area was correlated with semitendinosus tendon cross-sectional area with Pear-son's coefficients of 0.50 (95% confidence interval [CI], 0.21–0.70; P =.0013) and 0.59 (95% CI, 0.34–0.76; P =.0001) when measured under 2× and 4× magnification, respectively. In addition, MRI measurements of semitendinosus tendon length were correlated with both intraoperatively measured tendon length ( r =0.75; 95% CI, 0.40–0.91; P =.0008) and graft diameter ( r =0.43; 95% CI, 0.14–0.66; P =.0058). Average semitendinosus tendon cross-sectional area was 3.10 mm 2 (95% CI, 0.53–5.67; P =.024) greater and semitendinosus tendon length was 14.05 mm (95% CI, 1.25–26.85; P =.035) greater in cases that did not require graft augmentation. Semitendinosus tendons with cross-sectional area of less than 13.2 mm 2 or length of less than 81 mm are most likely to require graft augmentation. In addition, MRI measurements of the length and cross-sectional area of the semitendinosus tendon are significantly correlated with ACL graft diameter and could help to identify patients who may require graft augmentation. [ Orthopedics. 2017; 40(4):e617–e622.]

Cancer-associated fibroblasts (CAFs) are a major cancer-promoting component in the tumor microenvironment (TME). The dynamic role of human CAFs in cancer progression has been ill-defined because human CAFs lack a unique marker needed for a cell-specific, promoter-driven knockout model. Here, we developed an engineered human CAF cell line with an inducible suicide gene to enable selective in vivo elimination of human CAFs at different stages of xenograft tumor development, effectively circumventing the challenge of targeting a cell-specific marker. Suicide-engineered CAFs were highly sensitive to apoptosis induction in vitro and in vivo by the addition of a simple small molecule inducer. Selection of timepoints for targeted CAF apoptosis in vivo during the progression of a human breast cancer xenograft model was guided by a bi-phasic host cytokine response that peaked at early timepoints after tumor implantation. Remarkably, we observed that the selective apoptosis of CAFs at these early timepoints did not affect primary tumor growth, but instead increased the presence of tumor-associated macrophages and the metastatic spread of breast cancer cells to the lung and bone. The study revealed a dynamic relationship between CAFs and cancer metastasis that has counter-intuitive ramifications for CAF-targeted therapy.

Objectives/Hypothesis: Recurrent respiratory papillomatosis (RRP) is a benign disease characterized by recurrent lesions in the airway. The prevalence and degree of dysplasia that is present in the natural course of RRP is not well established. Adjuvant therapies, such as cidofovir, have been tried with the goal of decreasing the interval between repeat surgical treatments, the mainstay of therapy. Although, the off-label use of cidofovir to treat RRP has been common, there have been concerns regarding carcinogenic transformation following the use of cidofovir. This study aims to explore the association between increasing degree of papilloma dysplasia and the use of cidofovir in the context of the natural progression of dysplasia in RRP. Study Design: Retrospective case series. Methods: Demographic data and surgical history were obtained through chart reviews for this retrospective case series of 13 patients with RRP who had histopathologic biopsies done before and after exposure to cidofovir. Pathologic data collected over 10 years from serial excisions at the University of Iowa Hospitals were reviewed by a single pathologist, and the highest degree of dysplasia was noted per excision time. Results: Of the 176 specimens collected in these 13 patients with serial papilloma biopsies, 5.7% had no dysplasia, 57.4% had mild dysplasia (grade 1), 28.4% had moderate dysplasia (grade 2), and 8.5% had severe dysplasia (grade 3). A comparison of each patient's multiple biopsies across time suggested that the dysplastic grade was worse in two patients, better in four patients, and virtually unchanged in seven patients. There was no clear-cut pattern between the use of cidofovir and the degree of dysplasia over time. Conclusions: These results strongly suggest that intralesional cidofovir therapy does not correlate with worsening dysplastic progression. Dysplasia is relatively common in the setting of RRP; however, the prognostic significance of this finding is unknown. Additional research is needed to delineate the natural progression of dysplasia and its clinical significance in RRP, as well as the efficacy of cidofovir.

An infant with a ventricular septal defect; Vertebral anomalies, Anal atresia, Cardiac anomalies, Tracho Esophageal fistula (TEF), Renal anomalies, Limb anomalies syndrome; and tracheal stenosis with a bridging bronchus underwent repair of the ventricular septal defect and trachea-bronchial reconstruction at age 11 months. Herein we describe our surgical approach to resection of the bridging bronchus and a technique using a modified end-to-end tracheal anastomosis for the correction of this complex anomaly.

IntroductionLactate measurement has been used to identify critical medical illness and initiate early treatment strategies. The prehospital environment offers an opportunity for very early identification of critical illness and commencement of care.HypothesisThe investigators hypothesized that point-of-care lactate measurement in the prehospital aeromedical environment would: (1) identify medical patients with high mortality; (2) influence fluid, transfusion, and intubation; and (3) increase early central venous catheter (CVC) placement.MethodsCritically ill, medical, nontrauma patients who were transported from September 2007 through February 2009 by University of Massachusetts (UMass) Memorial LifeFlight, a university-based emergency medical helicopter service, were eligible for enrollment. Patients were prospectively randomized to receive a fingerstick whole-blood lactate measurement on an alternate-day schedule. Flight crews were not blinded to results. Flight crews were asked to inform the receiving attending physician of the results. The primary endpoint was the ability of a high, prehospital lactate value [> 4 millimoles per liter (mmol/L)] to identify mortality. Secondary endpoints included differences in post-transport fluid, transfusion, and intubation, and decrease in time to central venous catheter (CVC) placement. Categorical variables were compared between groups by Fisher's Exact Test, and continuous variables were compared by t-test.ResultsPatients (N = 59) were well matched for age, gender, and acuity. In the lactate cohort (n = 20), mean lactate was 7 mmol/L [Standard error of the mean, SEM = 1]. Initial analysis revealed that prehospital lactate levels of ≥4 mmol/L did show a trend toward higher mortality with an odds ratio of 2.1 (95% CI, 0.3-13.8). Secondary endpoints did not show a statistically significant change in management between the lactate and non lactate groups. There was a trend toward decreased time to post-transport CVC in the non lactate faction.ConclusionPrehospital aeromedical point-of-care lactate measurement levels ≥4 mmol/L may help stratify mortality. Further investigation is needed, as this is a small, limited study. The initial analysis did not find a significant change in post-transport management.MullenM, CerriG, MurrayR, TalbotA, SanseverinoA, McCahillP, MangoldsV, VolturoJ, DarlingC, RestucciaM. Use of point-of-care lactate in the prehospital aeromedical environment. Prehosp Disaster Med. 2014;29(1):1-4.

We present a case of temporary cochlear nerve dysfunction due to endocochlear inflammation with subsequent recovery. Retrospective case review at a pediatric tertiary care hospital. A nine-year-old male presented seven years post-cochlear implantation with an electrode array extruded into the external auditory canal. Upon exploration in the operating room, turbid perilymph from the scala tympani was discovered. A new electrode array was implanted. The patient had no discernible neural response telemetry (NRT) responses or auditory perception immediately following the procedure. Continuous but varying stimulation was continued postoperatively. Two months after implantation, he began having some auditory awareness; subsequent mapping resulted in the activation of a limited number of channels. Nine months following reimplantation, NRT demonstrated responses in three channels. Additionally, functional gain testing revealed sound awareness levels in the mild-hearing-loss range and the patient was able to detect and repeat all six Ling sounds. Continuous cochlear nerve stimulation at various levels may aid in function recovery after endocochlear inflammation.

Results: Nineteen manifested anterior webs during treatment, whereas six were successfully treated with mitomycin c without developing a web. 84% demonstrated resolution of the AGW. Conversely three patients developed new web formation following application of mitomycin C, all of which were subsequently cleared. Only one patient was recalcitrant to therapy and required surgical lysis with keel placement. No patients developed laryngeal cancer during our study period.

We sought to identify which patients with an apparent life-threatening event require infectious evaluation through an analysis of infants aged ≤12 months brought to an emergency department with an apparent life-threatening event. Among the 533 children evaluated, there were no cases of meningitis, 1 case of bacteremia, 17 cases of urinary tract infection, 22 cases of bacterial pneumonia, 22 cases of respiratory syncytial virus, and 2 cases of influenza virus identified in respiratory specimens.