S,R(+/-)-3,4-methylenedioxymethamphetamine (SR-MDMA) is an amphetamine derivative with prosocial and putative therapeutic effects. Ongoing clinical trials are investigating it as a treatment for post-traumatic stress disorder (PTSD) and other conditions. However, its potential for adverse effects such as hyperthermia and neurotoxicity may limit its clinical viability. We investigated the hypothesis that one of the two enantiomers of SR-MDMA, R-MDMA, would retain the prosocial and therapeutic effects but with fewer adverse effects. Using male Swiss Webster and C57BL/6 mice, the prosocial effects of R-MDMA were measured using a social interaction test, and the therapeutic-like effects were assessed using a Pavlovian fear conditioning and extinction paradigm relevant to PTSD. Locomotor activity and body temperature were tracked after administration, and neurotoxicity was evaluated post-mortem. R-MDMA significantly increased murine social interaction and facilitated extinction of conditioned freezing. Yet, unlike racemic MDMA, it did not increase locomotor activity, produce signs of neurotoxicity, or increase body temperature. A key pharmacological difference between R-MDMA and racemic MDMA is that R-MDMA has much lower potency as a dopamine releaser. Pretreatment with a selective dopamine D1 receptor antagonist prevented SR-MDMA-induced hyperthermia, suggesting that differential dopamine signaling may explain some of the observed differences between the treatments. Together, these results indicate that the prosocial and therapeutic effects of SR-MDMA may be separable from the stimulant, thermogenic, and potential neurotoxic effects. To what extent these findings translate to humans will require further investigation, but these data suggest that R-MDMA could be a more viable therapeutic option for the treatment of PTSD and other disorders for which SR-MDMA is currently being investigated.

Introduction Frequent right AQ4ventricular pacing (≥40%) with a transvenous pacemaker (TVP) is associated with the risk of pacing‐induced cardiomyopathy (PICM). Leadless pacemakers (LPs) have distinct physical and mechanical differences from TVP. The risk of PICM with LP is not known. To identify incidence, predictors, and long‐term outcomes of PICM in LP and TVP patients. Methods The study comprised all pacemaker‐dependent patients with LP or TVP who had left ventricular ejection fraction (LVEF) of ≥50 from 2014 to 2019. The incidence of PICM (≥10% LVEF drop) was assessed with an echocardiogram. Predictors for PICM were identified using multivariate analysis. Long‐term outcomes after cardiac resynchronization (CRT) were assessed in both groups. Results A total of 131 patients with TVP and 67 with LP comprised the study. All patients in the TVP group and the majority in the LP group underwent atrioventricular node ablation. The mean follow‐up duration in TVP and LP groups was 592 ± 549 and 817 ± 600 days, respectively. A total of 18 (13.7%) patients in TVP and 2 (3%) in LP developed PICM after a median duration of 254 (interquartile range: 470) days. The incidence of PICM was significantly higher with TVP compared with LP (p = .02). TVP as pacing modality was a positive (odds ratio [OR]: 1.07) while age was negative (OR: 0.94) predictor for PICM on multivariable analysis. Both patients in LP and all except two in the TVP group responded to CRT. Conclusion Incidence of PICM is significantly lower with LP compared with TVP in pacemaker‐dependent patients. Age and TVP as pacing modality were predictors for PICM.

Background: Recent reports have investigated the nascent role of induction chemotherapy for sinonasal undifferentiated carcinoma (SNUC). The goal of this study was to ascertain trends in treatment pattern changes for SNUC at a single institution and design a treatment algorithm utilized at our institution. Methods: Retrospective chart analysis of 21 cases of SNUC from 2010 to 2018. Results: Of 21 patients in this cohort, 18 (85.7%) presented with T4 disease, 7 (33.3%) presented with nodal disease, and 3 (14.3%) presented with distant metastasis. Since 2016, patients have been managed by induction chemotherapy followed by concurrent chemoradiation. To this point, patients treated with TPF induction chemotherapy followed by concurrent chemoradiation show no evidence of disease; however, the average follow up time is 16.8 months. Conclusions: The multimodality treatment for SNUC continues to evolve, as highlighted by this study, toward increased use of induction chemotherapy followed by chemoradiotherapy.

Cardiac resynchronization therapy (CRT) is an effective and well-established therapy for patients suffering with heart failure, left ventricular (LV) systolic dysfunction (ejection fraction ≤35%), and electrical dyssynchrony, demonstrated by a surface QRS duration of ≥120 ms. Patients undergoing treatment with CRT have shown significant improvement in functional class, quality of life, LV ejection fraction, exercise capacity, hemodynamics, and reverse remodeling of LV, and ultimately, morbidity and mortality. However, 30%–40% of patients who receive a CRT device may not show improvement, and they are termed as non responders. The nonresponders have a poor prognosis; several methods have been developed to try to enhance response to CRT. Echocardiography-guided optimization of CRT has not resulted in significant clinical benefit, since it is done at rest with the patient in supine position. An ideal optimization strategy would provide continuous monitoring and adjustment of device pacing to provide maximal cardiac resynchronization, under a multitude of physiologic states. Intrinsic activation of the right ventricle (RV) with paced activation of the RV, even in the setting of biventricular (BiV) pacing, may result in an adverse effect on cardiac performance. With this physiology, the use of LV-only pacing may be preferred and may enhance CRT. Adaptive CRT is a novel device-based algorithm that was designed to achieve patient-specific adjustment in CRT so as to provide appropriate BiV pacing or LV-only pacing. This article will review the goals of CRT optimization, and implementation and outcomes associated with adaptive CRT.

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Graphical abstract Additive manufacturing, or 3-Dimensional (3-D) Printing, is built with technology that utilizes layering techniques to build 3-D structures. Today, its use in medicine includes tissue and organ engineering, creation of prosthetics, the manufacturing of anatomical models for preoperative planning, education with high-fidelity simulations, and the production of surgical guides. Traditionally, these 3-D prints have been manufactured by commercial vendors. However, there are various limitations in the adaptability of these vendors to program-specific needs. Therefore, the implementation of a point-of-care in-house 3-D modeling and printing workflow that allows for customization of 3-D model production is desired. In this manuscript, we detail the process of additive manufacturing within the scope of medicine, focusing on the individual components to create a centralized in-house point-of-care manufacturing workflow. Finally, we highlight a myriad of clinical examples to demonstrate the impact that additive manufacturing brings to the field of medicine.

In patients undergoing laparotomy, as many as 10% develop ventral hernias, and the risk increases with each additional repair. 1 One of the most important goals of hernia repair is achieving reliable and durable reconstruction. However, hernia repairs have 10-year recurrence rates as high as 54%. 2,3 Using mesh to reinforce each reconstruction during repair has been consistently shown to reduce the risk of recurrence by as much as 50%. [4][5][6] In addition, obtaining musculofascial reapproximation has been shown to reduce the risk of hernia recurrence compared to bridged repairs. 7 Therefore, mesh-reinforced primary repair is the standard for ventral hernias. 8,9 Synthetic mesh repair is frequently used for tissue reinforcement to help decrease recurrence rates, and the optimal position for placement is Background: Mesh repair has been demonstrated to be superior to suture alone in ventral hernia repair. In a previous short-term pilot study, the authors found lower postoperative narcotic requirements with self-adhering mesh. The aim of this study was to follow-up on that pilot study, using long-term data. Methods: This is a retrospective review of a prospectively collected database. All patients who underwent ventral hernia repair with retrorectus mesh and who had at least a 12-month follow-up were reviewed. Comparisons were performed between patients who received self-adhering mesh and those who received transfascially sutured mesh, using matched-pair analysis, examining perioperative outcomes, surgical-site occurrences, and hernia recurrence/bulge. Results: Forty-two patients were included in the study, with 21 patients undergoing repair with transfascially sutured mesh and 21 patients receiving self-adhering mesh. Average length of follow-up was 1078 days. There were no significant differences between the two groups in baseline characteristics. Patients receiving self-adhering mesh had significantly shorter surgery, and a shorter hospital length of stay. They also had a tendency toward lower narcotic requirements. There were no significant differences in the rate of surgical-site occurrences, hernia recurrences, or bulge between the two groups. Conclusions: This long-term study shows that self-adhering mesh in ventral hernia repair results in similar long-term outcomes to transfascially sutured mesh, with shorter surgery, shorter length of stay, and a tendency toward improved pain control. These findings mirror the known advantages of self-adhering mesh in inguinal hernia repair. Further research is needed to study the incidence of chronic pain and the cost-effectiveness of self-adhering mesh.

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