BackgroundIn 2011, The Infectious Diseases Society of America released a clinical practice guideline (CPG) that recommended short-course antibiotic therapy and avoidance of fluoroquinolones for uncomplicated urinary tract infections (UTIs). Recommendations from this CPG were rapidly disseminated to clinicians via review articles, UpToDate, and the Centers for Disease Control and Prevention website; however, it is unclear if this CPG had an impact on national antibiotic prescribing practices.MethodsWe performed a retrospective cohort study of outpatient and emergency department visits within a commercial insurance database between January 1, 2009, and December 31, 2013. We included nonpregnant women aged 18–44 years who had an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code for a UTI with a concurrent antibiotic prescription. We performed interrupted time series analyses to determine the impact of the CPG on the appropriateness of the antibiotic agent and duration.ResultsWe identified 654 432 women diagnosed with UTI. The patient population was young (mean age, 31 years) and had few comorbidities. Fluoroquinolones, nonfirstline agents, were the most commonly prescribed antibiotic class both before and after release of the guidelines (45% vs 42%). Wide variation was observed in the duration of treatment, with >75% of prescriptions written for nonrecommended treatment durations. The CPG had minimal impact on antibiotic prescribing behavior by providers.ConclusionsInappropriate antibiotic prescribing is common for the treatment of UTIs. The CPG was not associated with a clinically meaningful change in national antibiotic prescribing practices for UTIs. Further interventions are necessary to improve outpatient antibiotic prescribing for UTIs.

Congenital heart defects are the most common types of birth defects in humans. Children with congenital heart defects frequently require heart valve replacement with an implant. Unfortunately, conventional heart valve implants do not grow. Therefore, these children are committed to serial re-operations for successively larger implant exchanges. Partial heart transplantation is a new and innovative approach to deliver growing heart valve implants. However, the transplant biology of partial heart transplant grafts remains unexplored. This is a critical barrier for clinical translation. Therefore, we investigated the cellular viability of partial heart transplants in cold storage. Histology and immunohistochemistry revealed no morphological differences in heart valves after 6, 24, or 48 h of cold storage. Moreover, immunohistochemistry showed that the marker for apoptosis activated caspase 3 and the marker for cell division Ki67 remained unchanged after 48 h of cold storage. Finally, quantification of fluorescing resorufin showed no statistically significant decrease in cellular metabolic activity in heart valves after 48 h of cold storage. We conclude that partial heart transplants remain viable after 48 h of cold storage. These findings represent the first step toward translating partial heart transplantation from the bench to the bedside because they have direct clinical implications for the procurement logistics of this new type of transplant.

Background: Limited donor availability and evolution in procurement techniques have renewed interest in heart transplantation (HT) with donation after circulatory death (DCD). The aim of this study is to evaluate outcomes of HT using DCD in the United States. Methods: The United Network for Organ Sharing registry was used to identify adult HT recipients from 2019 to 2021. Recipients were stratified between DCD and donation after brain death. Propensity-score matching was performed. Cox proportional hazards was used to identify independent predictors of 1-year mortality. Kaplan-Meier analysis was used to estimate 1-year survival. Results: Of 7496 HTs, 229 DCD and 7267 donation after brain death recipients were analyzed. The frequency of DCD HT increased from 0.2% of all HT in 2019 to 6.4% in 2021 ( P <0.001), and the number of centers performing DCD HT increased from 3 of 120 centers to 20 of 121 centers ( P <0.001). DCD donors were more likely to be younger, male, and White. After propensity matching, 1-year survival was 92.5% for DCD versus 90.3% for donation after brain death (hazard ratio, 0.80 [95% CI, 0.44–1.43]; P =0.44). Among DCD HTs, increasing recipient age and waitlist time predicted 1-year mortality on univariable analysis. Conclusions: Rates of DCD HT in the United States are increasing. This practice appears safe and feasible as mortality outcomes are comparable to donation after brain death. Although this study represents early adopting centers, outcomes of the experience for DCD HT in the United States is consistent with existing international data and encourages broader utilization of this practice.

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Immune privilege is an evolutionary adaptation that protects vital tissues with limited regenerative capacity from collateral damage by the immune response. Classical examples include the anterior chamber of the eye and the brain. More recently, the placenta, testes and articular cartilage were found to have similar immune privilege. What all of these tissues have in common is their vital function for evolutionary fitness and a limited regenerative capacity. Immune privilege is clinically relevant, because corneal transplantation and meniscal transplantation do not require immunosuppression. The heart valves also serve a vital function and have limited regenerative capacity after damage. Moreover, experimental and clinical evidence from heart valve transplantation suggests that the heart valves are spared from alloimmune injury. Here we review this evidence and propose the concept of heart valves as immune privileged sites. This concept has important clinical implications for heart valve transplantation.

We describe the endovascular exclusion and surgical resection of an intralobar pulmonary sequestration supplied by an aneurysmal feeding vessel from the aorta. Pulmonary sequestration is a rare congenital anomaly, and the presence of an aneurysmal feeding vessel is even rarer. The possibility of life-threatening hemorrhage resulting from failure to control these aberrant vessels has led many to pursue preoperative embolization. The anatomy in the patient described here was not deemed suitable for embolization, and we thus elected to pursue a novel approach. This case also demonstrates the diagnostic utility of magnetic resonance imaging for delineating the vasculature of pulmonary sequestrations when contrast-enhanced computed tomography is contraindicated.

Complement is known to play a role in ischemia and reperfusion injury (IRI). A general paradigm is that complement is activated by self‐reactive natural IgM antibodies (nAbs), after they engage postischemic neoepitopes. However, a role for nAbs in lung transplantation (LTx) has not been explored. Using mouse models of LTx, we investigated the role of two postischemic neoepitopes, modified annexin IV (B4) and a subset of phospholipids (C2), in LTx. Antibody deficient Rag1‐/‐ recipient mice were protected from LTx IRI. Reconstitution with either B4 or C2nAb restored IRI, with C2 significantly more effective than B4 nAb. Based on these information, we developed/characterized a novel complement inhibitor composed of single‐chain antibody (scFv) derived from the C2 nAb linked to Crry (C2scFv‐Crry), a murine inhibitor of C3 activation. Using an allogeneic LTx, in which recipients contain a full nAb repertoire, C2scFv‐Crry targeted to the LTx, inhibited IRI, and delayed acute rejection. Finally, we demonstrate the expression of the C2 neoepitope in human donor lungs, highlighting the translational potential of this approach.

Background: The treatment of neonates with unrepairable heart valve dysfunction remains an unsolved problem because there are no growing heart valve replacements. Heart valve transplantation is a potential approach to deliver growing heart valve replacements. Therefore, we retrospectively analysed the semilunar valve function of orthotopic heart transplants during rejection episodes. Methods: We included children who underwent orthotopic heart transplantation at our institution and experienced at least one episode of rejection between 1/1/2010 and 1/1/2020. Semilunar valve function was analysed using echocardiography at baseline, during rejection and approximately 3 months after rejection. Results: Included were a total of 31 episodes of rejection. All patients had either no (27) or trivial (4) aortic insufficiency prior to rejection. One patient developed mild aortic insufficiency during a rejection episode (P = 0.73), and all patients had either no (21) or trivial (7) aortic insufficiency at follow-up (P = 0.40). All patients had mild or less pulmonary insufficiency prior to rejection, which did not significantly change during (P = 0.40) or following rejection (P = 0.35). Similarly, compared to maximum pressure gradients across the valves at baseline, which were trivial, there was no appreciable change in the gradient across the aortic valve during (P = 0.50) or following rejection (P = 0.42), nor was there any meaningful change in the gradient across the pulmonary valve during (P = 0.55) or following rejection (P = 0.91). Conclusions: This study demonstrated that there was no echocardiographic evidence of change in semilunar valve function during episodes of rejection in patient with heart transplants. These findings indicate that heart valve transplants require lower levels of immune suppression than orthotopic heart transplants and provide partial foundational evidence to justify future research that will determine whether heart valve transplantation may deliver growing heart valve replacements for children.