An Hspa8 variant is a shocking modifier of spinal muscular atrophy in mice.

In this issue of Neuron, Kim et al.1 show that an Hspa8 variant modifies disease phenotypes in a mouse model of spinal muscular atrophy. Hspa8 facilitates the correct folding of proteins, enhances SNARE assembly, and influences SMN2 splicing.

Cardiac surgery during the COVID-19 sine wave: Preparation once, preparation twice. A view from Houston.

The novel coronavirus disease (COVID-19) pandemic has created major challenges and disruptions to hospitals throughout the world, with profound implications for cardiac surgery and cardiac surgeons. In this review, we highlight the hospital and cardiac surgical experience at Baylor St. Luke's Medical Center in the Texas Medical Center in Houston, Texas as of mid-July 2020. Our local experience has consisted of a spring surge (early March to early May), followed by a relative flattening and then a summer surge (early June to present day), similar to a sine wave. Throughout the entire pandemic, our simultaneous medical priorities have been treating the growing number of patients with COVID-19 while continuing to provide needed care for those without COVID-19. The current situation will be the "new normal" until a vaccine becomes available. It will be vital to stay attuned to epidemiologists, public health officials, and infection control experts, because what they see today, the intensive care units will see tomorrow. The lessons we have learned are outlined in this review but can be summarized most succinctly: preparation. We must prepare in advance, stockpile supplies and personal protective equipment, have rapid and vigorous testing protocols in place, utilize technology (eg, online meetings, videoconference "office visits"), and encourage hospital-wide and community protective efforts (social distancing, mask wearing, hand hygiene). Hopefully, the lessons learned through this challenging experience will prepare us for the next time.

Donor and transplant candidate selection for solid organ transplantation during the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus responsible for a worldwide pandemic has forced drastic changes in medical practice in an alarmingly short period of time. Caregivers must modify their strategies as well as optimize the utilization of resources to ensure public and patient safety. For organ transplantation, in particular, the loss of lifesaving organs for transplantation could lead to increased waitlist mortality. The priority is to select uninfected donors to transplant uninfected recipients while maintaining safety for health care systems in the backdrop of a virulent pandemic. We do not yet have a standard approach to evaluating donors and recipients with possible SARS-CoV-2 infection. Our current communication shares a protocol for donor and transplant recipient selection during the coronavirus disease 2019 (COVID-19) pandemic to continue lifesaving solid organ transplantation for heart, lung, liver, and kidney recipients. The initial results using this protocol are presented here and meant to encourage dialogue between providers, offering ideas to improve safety in solid organ transplantation with limited health care resources. This protocol was created utilizing the guidelines of various organizations and from the clinical experience of the authors and will continue to evolve as more is understood about SARS-CoV-2 and how it affects organ donors and transplant recipients.

A programmed wave of uridylation-primed mRNA degradation is essential for meiotic progression and mammalian spermatogenesis.

Several developmental stages of spermatogenesis are transcriptionally quiescent which presents major challenges associated with the regulation of gene expression. Here we identify that the zygotene to pachytene transition is not only associated with the resumption of transcription but also a wave of programmed mRNA degradation that is essential for meiotic progression. We explored whether terminal uridydyl transferase 4- (TUT4-) or TUT7-mediated 3' mRNA uridylation contributes to this wave of mRNA degradation during pachynema. Indeed, both TUT4 and TUT7 are expressed throughout most of spermatogenesis, however, loss of either TUT4 or TUT7 does not have any major impact upon spermatogenesis. Combined TUT4 and TUT7 (TUT4/7) deficiency results in embryonic growth defects, while conditional gene targeting revealed an essential role for TUT4/7 in pachytene progression. Loss of TUT4/7 results in the reduction of miRNA, piRNA and mRNA 3' uridylation. Although this reduction does not greatly alter miRNA or piRNA expression, TUT4/7-mediated uridylation is required for the clearance of many zygotene-expressed transcripts in pachytene cells. We find that TUT4/7-regulated transcripts in pachytene spermatocytes are characterized by having long 3' UTRs with length-adjusted enrichment for AU-rich elements. We also observed these features in TUT4/7-regulated maternal transcripts whose dosage was recently shown to be essential for sculpting a functional maternal transcriptome and meiosis. Therefore, mRNA 3' uridylation is a critical determinant of both male and female germline transcriptomes. In conclusion, we have identified a novel requirement for 3' uridylation-programmed zygotene mRNA clearance in pachytene spermatocytes that is essential for male meiotic progression.

Anesthetic Management of Laser Lead Extraction for Cardiovascular Implantable Electronic Devices.

Cardiovascular implantable electronic devices (CIEDs) play a significant role in the modern management of cardiovascular disease. CIEDs include implantable pacemakers (PMs), implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices. These devices improve the quality of life of their recipients and help reduce the incidence of sudden cardiac death. Traditionally, CIEDs have been reliant on the use of transvenous endocardial leads to directly connect with the heart. Over time, these endovascular leads may become endothelialized rendering removal extremely difficult. As the indications for CIEDs expands and with the continuing evolution of these devices, the number of patients requiring explantation for device recall, malfunction, and infection continues to increase. In this manuscript, we review the most common CIEDs, the indications and process of lead removal/device explantation, potential complications associated with the procedure and the anesthetic management of these patients.

Anesthetic Management of Patients Undergoing Percutaneous Endocardial and Epicardial Left Atrial Appendage Occlusion.

Atrial fibrillation is the most common cardiac arrhythmia in adults affecting almost 6 million adults in the United States. The 2 most common comorbidities associated with atrial fibrillation are heart failure and thromboembolic events. Heart failure symptoms may be treated with rate control, antiarrhythmic medications or by catheter ablation. Unfortunately, despite optimal medical management, thromboembolic events still occur. Recently, there has been a great deal of interest and innovation in finding an alternative to chronic anticoagulation. Several percutaneous left atrial appendage occlusion devices have been developed over recent years, some of which have proven to be noninferior to anticoagulation in preventing strokes in atrial fibrillation patients. The 2 most widely used left atrial appendage occlusion devices are the WATCHMAN (Atritech Inc, Plymouth, MN, USA) and the LARIAT (SentreHEART, Palo Alto, CA, USA) devices. After a detailed description of the procedures, the anesthetic considerations of each procedure and management of specific adverse events are discussed within this review.

Anesthetic Management in Radiofrequency Catheter Ablation of Ventricular Tachycardia.

Radiofrequency catheter ablation is increasingly being used to treat patients who have ventricular tachycardia, and anesthesiologists frequently manage their perioperative care. This narrative review is intended to familiarize anesthesiologists with preprocedural, intraprocedural, and postprocedural implications of this ablation. Ventricular tachycardia typically arises from structural heart disease, most often from scar tissue after myocardial infarction. Many patients thus affected will benefit from radiofrequency catheter ablation in the electrophysiology laboratory to ablate the foci of arrhythmogenesis. The pathophysiology of ventricular tachycardia is complex, as are the technical aspects of mapping and ablating these arrhythmias. Patients often have substantial comorbidities and tenuous hemodynamic status, necessitating pharmacologic and mechanical cardiopulmonary support. General anesthesia and monitored anesthesia care, when used for sedation during ablation, can lead to drug interactions and side effects in the presence of ventricular tachycardia, so anesthesiologists should also be aware of potential perioperative complications. We discuss variables that can help anesthesiologists safely guide patients through the challenges of radiofrequency catheter ablation of ventricular tachycardia.

Early detection of a cavopulmonary tumor embolus with the use of transesophageal echocardiography.

Pulmonary tumor embolization from renal cell carcinoma is associated with severe cardiopulmonary morbidity and high perioperative mortality rates. We report the case of a 71-year-old woman who presented with right-sided abdominal pain. Magnetic resonance images revealed a mass originating from the upper pole of the right kidney and extending into the infrahepatic portion of the inferior vena cava. Transesophageal echocardiography was continuously used to monitor the mass during intended radical nephrectomy and tumor resection. When the right kidney was mobilized, intracaval thrombus detached and migrated to the patient's right atrium, causing severe hemodynamic instability. After emergent sternotomy and during the initiation of cardiopulmonary bypass, the mass was no longer echocardiographically detectable in the heart; it was soon removed completely from the left pulmonary artery. The mass was a renal cell carcinoma. We recommend the use of transesophageal echocardiography as an efficient diagnostic tool in the early detection of pulmonary tumor embolization during the resection of renal cell carcinoma that involves the inferior vena cava.

Perioperative management of lower extremity revascularization.

Patients presenting for lower extremity revascularization often have multiple systemic comorbidities, making them high-risk surgical candidates. Neuraxial anesthesia and general anesthesia are equivocal in their effect on perioperative cardiac morbidity and improved graft patency. Postoperative epidural analgesia may improve perioperative cardiac morbidity. Systemic antithrombotic and anticoagulation therapy is common among this patient population and may affect anesthetic techniques.

Contributions of anesthesiology to the surgical treatment of cerebrovascular disease: the role of Arthur S. Keats, M.D.

Increased tolerance to cerebral ischemia produced by general anesthesia during temporary carotid occlusion. By B. A. Wells, A. S. Keats, and D. A. Cooley. Surgery 1963; 54:216-23. Local anesthesia with little or no preoperative sedation is currently recommended as the anesthetic of choice for temporary carotid occlusion during carotid endarterectomy. Purported advantages include minimal circulatory and respiratory changes from the local anesthetic, and constant verbal contact can be maintained with the patient so that neurologic changes are promptly recognized. However, local anesthesia may not be satisfactory in uncooperative or semiconscious patients. We therefore undertook a trial of general anesthesia in 56 consecutive patients undergoing carotid endarterectomy. Patients were induced in standardized fashion using intravenous thiopental (100-400 mg), atropine (0.2 mg), and succinylcholine (40-80 mg). Cyclopropane, along with deliberate hypercapnia and hypertension, was used for anesthesia maintenance. All patients tolerated carotid occlusion for periods of up to 30 min during general anesthesia without shunt, bypass, or hypothermia. Except for one patient, electroencephalogram evidence of cerebral ischemia was not apparent during occlusion, and no patient suffered postoperative neurologic sequela. Twenty percent of patients who had their carotid arteries occluded preoperatively for 30-60 s without general anesthesia suffered convulsions. These data suggest that general anesthesia increased the tolerance to cerebral ischemia. Potential mechanisms involved might include: 1) decreased cerebral metabolic rate for oxygen; 2) increased cerebral blood flow from hypercapnia; 3) increased arterial oxygen tension; and 4) recruitment of new routes of collateral circulation.