The obstruction of renal vein outflow often causes renal vein hypertension, and this hypertension can lead to formation of collateral vessels and tributaries to compensate for outflow.1 There is no ...single known cause for renal vein entrapment, although contributing factors are thought to include an acute SMA-aorta angle, abnormal SMA branching, or an abnormally low origin of the SMA.2 The actual incidence of nutcracker syndrome is also unknown; most published data seem to be in the form of small case series or case reports. ...there are no existing diagnostic criteria for this condition, so a high index of suspicion is needed for diagnosis. ...the ureter was anastomosed to the bladder with running polydiaxanone suture over a 12 x 7-mm double- j ureteral stent. Pushpa Neppala B.S. University of California San Diego School of Medicine La Jolla, California Harrison S. Chau, M.D. Divya Sood M.D. Department of Surgery University of California, San Diego La Jolla, California Jennifer Berumen, M.D. Kristin L. Mekeel, M.D. Division ofTransplantation and Hepatobiliary Surgery Department of Surgery University of California, San Diego La Jolla, California Author Contributions: Pushpa Neppala: study design, article drafting, and critical review of the manuscript.
Ureter obstruction is a highly prevalent event during embryonic development and is a major cause of pediatric kidney disease. We have previously reported that ureteric bud-specific ablation of the ...gene expressing the exocyst subunit EXOC5 in late murine gestation results in failure of urothelial stratification, cell death and complete ureter obstruction. However, the mechanistic connection between disrupted exocyst activity, urothelial cell death and subsequent ureter obstruction was unclear. Here, we report that inhibited urothelial stratification does not drive cell death during ureter development. Instead, we demonstrate that the exocyst plays a critical role in autophagy in urothelial cells, and that disruption of autophagy activates a urothelial NF-κB stress response. Impaired autophagy first provokes canonical NF-κB activity, which is progressively followed by increasing levels of non-canonical NF-κB activity and cell death if the stress remains unresolved. Furthermore, we demonstrate that ureter obstructions can be completely rescued in Exoc5 conditional knockout mice by administering a single dose of the pan-caspase inhibitor z-VAD-FMK at embryonic day 16.5 prior to urothelial cell death. Taken together, ablation of Exoc5 disrupts autophagic stress response and activates progressive NF-κB signaling, which promotes obstructive uropathy.
Ultrasonography for trauma is a widely used tool in the initial evaluation of trauma patients with complete ultrasonography of trauma (CUST) demonstrating equivalence to computed tomography (CT) for ...detecting clinically significant abdominal hemorrhage. Initial reports demonstrated high sensitivity of CUST for the bedside diagnosis of pneumothorax. We hypothesized that the sensitivity of CUST would be greater than initial supine chest radiograph (CXR) for detecting pneumothorax.
A retrospective analysis of patients diagnosed with pneumothorax from 2018 through 2020 at a Level I trauma center was performed. Patients included had routine supine CXR and CUST performed prior to intervention as well as confirmatory CT imaging. All CUST were performed during the initial evaluation in the trauma bay by a registered sonographer. All imaging was evaluated by an attending radiologist. Subgroup analysis was performed after excluding occult pneumothorax. Immediate tube thoracostomy was defined as tube placement with confirmatory CXR within 8 hours of admission.
There were 568 patients screened with a diagnosis of pneumothorax, identifying 362 patients with a confirmed pneumothorax in addition to CXR, CUST, and confirmatory CT imaging. The population was 83% male, had a mean age of 45 years, with 85% presenting due to blunt trauma. Sensitivity of CXR for detecting pneumothorax was 43%, while the sensitivity of CUST was 35%. After removal of occult pneumothorax (n = 171), CXR was 78% sensitive, while CUST was 65% sensitive (p < 0.01). In this subgroup, CUST had a false-negative rate of 36% (n = 62). Of those patients with a false-negative CUST, 50% (n = 31) underwent tube thoracostomy, with 85% requiring immediate placement.
Complete ultrasonography of trauma performed on initial trauma evaluation had lower sensitivity than CXR for identification of pneumothorax including clinically significant pneumothorax requiring tube thoracostomy. Using CUST as the primary imaging modality in the initial evaluation of chest trauma should be considered with caution.
Diagnostic Test study, Level IV.
Acute viral infection generates lineage-committed T helper 1 (Th1) and T follicular helper (Tfh) memory cells that recall their lineage-specific functions following secondary challenge with virus. ...However, the lineage commitment of effector and memory T helper cells
in vivo
following protein vaccination is poorly understood. In this study, we analyzed effector and memory CD4+ T cell differentiation in mice (
Mus musculus
) following adjuvanted glycoprotein immunization compared to acute lymphocytic choriomeningitis virus (LCMV) infection. Glycoprotein immunization induced CXCR5- non-Tfh effector and memory CD4+ T cells that surprisingly had not undergone polarization toward any particular T helper cell lineage but had undergone memory differentiation. However, upon challenge with virus, these T helper lineage-nonpolarized memory CD4+ T cells were able to generate Th1 secondary effector cells, demonstrating their lineage plasticity. In addition, Tfh and memory Tfh cells were generated in response to protein immunization, and these cells differed from infection-induced Tfh cells by their lack of the transcription factor Tbet. Rechallenge experiments demonstrated that viral infection, but not protein immunization, during either the primary or secondary immune response, restricts the recall of Bcl6 expression and the generation of germinal center Tfh cells. Together, these data demonstrate that protein immunization generates a combination of nonpolarized memory cells that are highly plastic and memory Tfh cells that can undergo further Th1-like modulation during a secondary response to viral infection.
Abstract
Acute viral infection generates lineage-committed T helper 1 (Th1) and T follicular helper (Tfh) memory cells that recall their lineage-specific functions following secondary challenge with ...virus. However, the lineage commitment of effector and memory T helper cells in vivo following protein vaccination is poorly understood. In this study, we analyzed effector and memory CD4+ T cell differentiation following adjuvanted glycoprotein immunization compared to acute lymphocytic choriomeningitis virus (LCMV) infection. Glycoprotein immunization-induced CXCR5-non-Tfh effector and memory CD4+ T cells that surprisingly had not undergone polarization toward any particular T helper cell lineage but had undergone memory differentiation. However, upon challenge with virus, these T helper lineage-nonpolarized memory CD4+ T cells were able to generate Th1 secondary effector cells, demonstrating their lineage plasticity. In addition, Tfh and memory Tfh cells were generated in response to protein immunization, and these cells differed from infection-induced Tfh cells by their lack of the transcription factor Tbet. Rechallenge experiments demonstrated that viral infection, but not protein immunization, during either the primary or secondary immune response, restricts the recall of Bcl6 expression and the generation of germinal center Tfh cells. Together, these data demonstrate that protein immunization generates a combination of nonpolarized memory cells that are highly plastic and memory Tfh cells that can undergo further Th1-like modulation during a secondary response to viral infection.
Breast cancer mortality after ductal carcinoma in situ is rare, making it difficult to predict which patients are at risk and to identify whether risk factors for this outcome are the same as those ...for invasive recurrence. We aimed to identify whether risk factors for invasive recurrences are similar to those for breast cancer death after a diagnosis of pure ductal carcinoma in situ.
The Surveillance, Epidemiology, and End Results Program was queried for female patients diagnosed with pure ductal carcinoma in situ. Cumulative incidence was estimated by treatment group using competing risks. Competing risks regression was then performed for the development of in-breast invasive recurrence with competing risks of breast and non–breast cancer death. Competing risks regression was then again performed for development of breast cancer mortality with the competing risk of non–breast cancer death.
A total of 29,515 patients were identified. Of them, 164 patients suffered breast cancer mortality without an intervening invasive recurrence, and 44 suffered breast cancer mortality after an invasive in-breast recurrence. On competing risks analysis for invasive in-breast recurrence, significant factors included lesion size >5 cm (hazard ratio = 1.59, 95% confidence interval 1.24–2.04, P < .001), diffuse disease (hazard ratio = 0.0005, 95% confidence interval 0.0003–0.0007, P < .001), other race (hazard ratio = 1.29, 95% confidence interval 1.10–1.52, P = .002), Black race (hazard ratio = 1.21, 95% confidence interval 1.01–1.46, P = .04), age at diagnosis (hazard ratio = 0.99, confidence interval 0.98–1.00, P = .02), low-grade disease (hazard ratio = 0.79, 95% confidence interval 0.64–0.96, P = .02), lumpectomy with radiation (hazard ratio = 0.67, 95% confidence interval 0.58-0.77, P < .001), and mastectomy (hazard ratio = 0.36, 95% confidence interval 0.30–0.44, P < .001). Significant factors for breast cancer mortality included age at diagnosis (hazard ratio = 1.04, 95% confidence interval 1.03–1.05, P < .001), Black race (hazard ratio = 2.88, 95% confidence interval 2.08–3.99, P < .001), diffuse disease (hazard ratio = 6.02, 95% confidence interval 1.39–26.07, P = .02), lumpectomy with radiation (hazard ratio = 0.51, 95% confidence interval 0.36–0.72, P < .001), and mastectomy (hazard ratio = 0.60, 95% confidence interval 0.50–0.92, P = .02).
Our results suggested that risk factors for in-breast invasive recurrence after a diagnosis of pure ductal carcinoma in situ differ from risk factors for breast cancer mortality and development of metastatic recurrence. In-breast invasive recurrence is not the only consideration for breast cancer specific mortality in ductal carcinoma in situ patients.
Adherence to opioid prescribing protocols after operations remains challenging despite published guidelines. Integration of these guidelines with the electronic health record could potentially ...improve their adoption. We hypothesize that implementing an electronic health record order set containing prepopulated tablet quantities tailored to surgical procedures based on published guidelines will decrease postoperative opioid prescription.
We conducted a 12-month prepost intervention study on adult patients who underwent appendectomy, cholecystectomy, inguinal or umbilical hernia repair, thyroidectomy, or parathyroidectomy at a single institution. An electronic health record order set was developed with prepopulated opioid tablet quantities reflecting the upper limit of published recommendations. The primary endpoint was change in morphine milligram equivalent prescribed postintervention and was analyzed using linear regression adjusting for age, race, procedure, and prescriber training level. Secondary endpoints were emergency department visits for pain-related issues and opioid refill rates.
We identified 524 patients (mean age = 53, 51% male) in our baseline cohort and 433 patients (mean age = 52, 58% male) in our postintervention group. The mean morphine milligram equivalent prescribed was 62.6 and 50.4 for the preintervention and postintervention cohorts, respectively (P = .049). Thyroidectomies and parathyroidectomies achieved the largest decrease after intervention, which decreased to 42.6 morphine milligram equivalent from 79.7 morphine milligram equivalent preintervention (P < .001). Refill rate was 1.6% postintervention compared to 3.1% preintervention (P = .20), and emergency department visit for pain control rate was 0.2% post intervention and 2.5% preintervention (P = .005).
An electronic health record tailored order set based on prescription guidelines is a safe, effective, and scalable intervention for decreasing opioid prescriptions after operations.
