Reply to Theodorou et al. Comment on "Umemoto et al. Management of Migraine-Associated Vestibulocochlear Disorders. Audiol. Res. 2023, 13, 528-545".

We thank the authors for their insightful and thoughtful commentary on our recent publication [...].

Medical Therapies to Conquer Surgical Diseases: Gallstone Disease May Be the Next Frontier.

Over the past half century, diseases that were predominantly treated surgically have transitioned to less invasive medical therapies. Such diseases that are now effectively treated with medicine are (1) peptic ulcer disease (PUD), (2) coronary artery disease (CAD), and (3) gastrointestinal stromal tumors (GISTs). Likewise, gallstone disease may soon follow this trend. Currently, the gold standard treatment of symptomatic gallstones is laparoscopic cholecystectomies. Though one of the most common surgeries in the United States, certain cases of acute and gangrenous cholecystitis can be some of the most difficult surgeries to perform. Advancements in neutrophil extracellular trap (NET) inhibitor medical therapies will alter gallstone disease management and the mainstream role of surgical interventions. This focus on less invasive therapies will greatly impact the quality of patient care, financial obligations, and even resident training opportunities.

A Novel Technique of Reduction Meatoplasty for Correction of Very Large Meatus from a Previous Canal Wall-Down Mastoidectomy.

OBJECTIVE: To evaluate the efficacy of reduction meatoplasty, a novel technique aiming to improve the usage of molded hearing aids and ear plugs in patients undergoing mastoid obliteration of a previous canal wall-down (CWD) mastoidectomy, complicated with a very large meatus. PATIENTS: Twenty-six patients from a tertiary care neurotology clinic with a very large meatus from a previous CWD mastoidectomy, who were unable to use molded hearing aids or ear plugs for water protection. INTERVENTION: Reduction meatoplasty after mastoid obliteration (cartilage strips and bone pate) of the CWD mastoidectomy. The procedure involves removing a wedge of skin and underlying soft tissue superiorly in the meatus. MAIN OUTCOME MEASURES: Reduction in meatus size, enabling usage of hearing aids and ear plugs. RESULTS: Twenty-six patients underwent mastoid obliteration and reduction meatoplasty to reduce meatus size. Patients were followed up for an average of 22 months postoperation. After operation, the meatus size was significantly reduced in all patients, enabling usage of over-the-counter ear plugs. In addition, all six patients with hearing aids could use standard occlusive hearing aid domes without requiring molded hearing aids. No patients showed symptoms of chronic infection in the mastoid cavity during the follow-up period. CONCLUSIONS: Results of reduction meatoplasty showed significant improvements in functionality of the external auditory meatus, indicating that this technique is effective in reducing meatus size and improving the normal meatal anatomy after mastoid obliteration.

Water, a powerful tool in surgery.

Inflammation of the gallbladder, also known as acute cholecystitis, may be caused by infection and inflammation of the gallbladder wall due to bile stasis, with or without gallstones. It is one of the most common surgical procedures that are performed laparoscopically. Gangrenous gallbladders are one of the most difficult conditions to treat clinically and surgically, being the cause of many medical malpractice litigations. Gangrenous gallbladders constitute 15% of all laparoscopic surgeries, with the cost of these surgeries being approximately $48,000, compared to other laparoscopic gallbladder surgeries being around $7,000. Dr. Dinesh Vyas and his team have worked together to develop the novel HydroLap, which is a tool that utilizes hydrodissection technology during laparoscopic cholecystectomies to remove the delicate, dead tissue while preserving the healthy tissue of surrounding structures. This decade-long journey began in the operating room and resulted in an innovation that is awaiting Food and Drug Administration (FDA) approval for use in 2023.

Management of Migraine-Associated Vestibulocochlear Disorders.

Migraine is a chronic neurological disorder that frequently coexists with different vestibular and cochlear symptoms (sudden hearing loss, tinnitus, otalgia, aural fullness, hyperacusis, dizziness, imbalance, and vertigo) and disorders (recurrent benign positional vertigo, persistent postural perceptual dizziness, mal de debarquement, and Menière's disease). Despite evidence of an epidemiological association and similar pathophysiology between migraine and these vestibulocochlear disorders, patients suffering from migraine-related symptoms are usually underdiagnosed and undertreated. Current migraine treatment options have shown success in treating vestibulocochlear symptoms. Lifestyle and dietary modifications (reducing stress, restful sleep, avoiding migraine dietary triggers, and avoiding starvation and dehydration) and supplements (vitamin B2 and magnesium) offer effective first-line treatments. Treatment with migraine prophylactic medications such as tricyclic antidepressants (e.g., nortriptyline), anticonvulsants (e.g., topiramate), and calcium channel blockers (e.g., verapamil) is implemented when lifestyle and dietary modifications are not sufficient in improving a patient's symptoms. We have included an algorithm that outlines a suggested approach for addressing these symptoms, taking into account our clinical observations. Greater recognition and understanding of migraine and its related vestibular and cochlear symptoms are needed to ensure the appropriate diagnosis and treatment of affected patients.

National Survey of Sharps Injuries Incidence Amongst Healthcare Workers in the United States.

Purpose: Reporting sharps injuries is crucial for healthcare worker occupational safety. However, these incidents are often underreported, thus posing potentially dangerous working environments. Previous small and limited studies have quantified this underreporting in specific groups of healthcare workers. This study aims to expand on these studies by further quantifying sharps injury incidences through a national study, thus better understanding healthcare reporting behaviors and the reasons for underreporting. Patients and Methods: This is a national, multi-center, cross-sectional study conducted via an online anonymous survey distributed through email among United States attending physicians, fellows, residents, medical students, and nurses of all specialties (ie, surgery, medicine, pediatrics). Data analysis used descriptive statistics and regressive modeling with significance defined as p<0.05. Results: Of over 3000 surveys emailed, 460 (15.3%) healthcare workers responded. The most vulnerable cohort to report sharps injuries were medical students (0.87 injuries per year ±0.69, n=92) and Postgraduate Year (PGY) 1 (0.67±0.81, n=71), PGY2 (0.86±-0.82, n=48), and PGY3 (0.92±0.8, n=45) resident physicians. Healthcare workers in surgical fields reported significantly higher likelihoods (odds ratio=4.61, p<0.001, 95% confidence interval 2.83-7.26) of sharps injuries. Medical students reported sharps injuries the least (40%) and nurses reported sharps injuries the most frequently (71%). The three most common reasons for not reporting sharps injuries included (1) healthcare workers perceiving low infection risk based on patient medical history, (2) fear of peer perception, and (3) belief of lack of reporting utility or that reporting is inconsequential. Conclusion: Medical students and physicians early in training, especially those in surgical fields, are more vulnerable to sharps injuries, but are less likely to report, while nurses are the most likely to report. Dedicated sharps training, education to reduce stigma around injury, and implementing a simplified reporting process may help encourage reporting as well as consistency in reporting, leading to improved workplace safety.

Novel Application of Hydrodissection in Laparoscopic Cholecystectomy for Gangrenous Gallbladders.

INTRODUCTION: Laparoscopic cholecystectomy (LC) for gangrenous gallbladders (GGBs) can be challenging and represent a significant number of LC cases, necessitating more efficacious surgical techniques. Currently, the standard treatment for GGBs is blunt dissection which can have high iatrogenic complication rates. To our knowledge, this is the first large retrospective study conducted on the novel application of hydrodissection (HD) in LCs for GGBs. METHODS: In this retrospective study of 386 LCs, data were collected for patient demographics, medical comorbidities, operating time (OT), anesthesia time (AT), length of stay (LOS), estimated blood loss, conversion to open procedures, 30-day readmissions, and mortality. Patients were categorized into four groups: (1) Vyas employing HD for GGBs (VHG), (2) non-Vyas group of five surgeons not employing HD for GGBs (NVG), (3) Vyas treating non-GGBs, and (4) non-Vyas group of five surgeons treating non-GGBs. Control groups were age-matched and sex-matched. Statistical analysis used descriptive statistics, Mann-Whitney U testing, and chi-squared testing (α = 0.05). RESULTS: This study demonstrated significantly decreased (P < 0.05) OT (P = 0.001), AT (P < 0.001), LOS (P = 0.015), and conversion to open procedures (P = 0.047) between the VHG and NVG groups, with HD reducing OT by 35.5% compared to blunt dissection. This study did not demonstrate significantly decreased (P > 0.05) estimated blood loss (P = 0.185) and 30-day readmissions (P = 0.531) between the VHG and NVG groups, but they were trending toward significant. There were no mortalities in this study. CONCLUSIONS: HD is associated with improved surgical outcomes of LCs for GGBs demonstrated by reduced OT, AT, LOS, and conversion to open procedures. Further multi-institutional studies are needed to validate HD implementation and further dissemination.

Hydrodissection in Laparoscopic Cholecystectomies for Gangrenous Gallbladders.

To improve the quality of patient care for cholecystectomies for gangrenous gallbladders, multiple innovations have been introduced including laparoscopic and robotic surgery. However, laparoscopic cholecystectomies for gangrenous gallbladders performed by blunt dissection still represents one of the most technically challenging general surgery procedures, with a high rate of iatrogenic complications and suboptimal measures for key surgical parameters such as length of stay, operating time, and blood loss. For this reason, the novel use of surgical techniques such as hydrodissection, which involves the expulsion of normal saline streams at a predetermined pressure, for cholecystectomies for gangrenous gallbladders are of utmost importance. In this manuscript, we explore the application of hydrodissection in cholecystectomies for gangrenous gallbladders.

Procedure room innovation during the COVID-19 crisis: Protecting healthcare workers while learning from history.

The impact of the recent pandemic on healthcare workers highlights the need to improve the working environment in hospitals. This is especially true in procedural rooms such as the operating and delivery rooms, which inherently require extended exposure to the virus, allows no social distancing, and generates aerosolized virus into the room through the use of the equipment. While reviewing the history of the development of the current Heating, Ventilation, and Air Conditioning Systems (HVAC), we identified inadequacies in the architecture and regulations of the system that resulted in insufficient protection during the current pandemic. Thus, we worked with building/facilities management, the operating room and nursing staff, and learned from research on airplane cabin air circulation to modify HVAC systems to address this issue. The modification includes calculating and implementing appropriate air changes per hour of the HVAC system. Modifying the existing system allows sufficient exchange of air within the procedure room to reduce the amount of exposure to viruses which results in safer working environments for healthcare workers. In the future, there will continue to be more pandemics, thus it is important to start creating safer working environments now, such as revisiting the hospital architecture and HVAC system, so that they can be improved upon and so that we are more prepared for the future.

Evidence for DNA-mediated nuclear compartmentalization distinct from phase separation.

RNA Polymerase II (Pol II) and transcription factors form concentrated hubs in cells via multivalent protein-protein interactions, often mediated by proteins with intrinsically disordered regions. During Herpes Simplex Virus infection, viral replication compartments (RCs) efficiently enrich host Pol II into membraneless domains, reminiscent of liquid-liquid phase separation. Despite sharing several properties with phase-separated condensates, we show that RCs operate via a distinct mechanism wherein unrestricted nonspecific protein-DNA interactions efficiently outcompete host chromatin, profoundly influencing the way DNA-binding proteins explore RCs. We find that the viral genome remains largely nucleosome-free, and this increase in accessibility allows Pol II and other DNA-binding proteins to repeatedly visit nearby DNA binding sites. This anisotropic behavior creates local accumulations of protein factors despite their unrestricted diffusion across RC boundaries. Our results reveal underappreciated consequences of nonspecific DNA binding in shaping gene activity, and suggest additional roles for chromatin in modulating nuclear function and organization.

Evaluating the Utility of Canine Mdr1 Knockout Madin-Darby Canine Kidney I Cells in Permeability Screening and Efflux Substrate Determination.

Permeability assays are commonly conducted with Madin-Darby canine kidney (MDCK) cells to predict the intestinal absorption of small-molecule drug candidates. In addition, MDCK cells transfected to overexpress efflux transporters are often used to identify substrates. However, MDCK cells exhibit endogenous efflux activity for a significant proportion of experimental compounds, potentially leading to the underestimation of permeability and confounded findings in transport studies. The goal of this study was to evaluate canine Mdr1 knockout MDCK (gMDCKI) cells in permeability screening and human MDR1 substrate determination in a drug discovery setting. The gMDCKI cells were established by CRISPR-Cas9-mediated knockout of the canine Mdr1 gene in MDCKI wildtype (wt) cells. A comparison of efflux ratios (ER) between MDCKI wt and gMDCKI showed that out of 135 compounds tested, 38% showed efflux activity in MDCKI wt, while no significant efflux was observed in gMDCKI cells. Apparent permeability (Papp) from apical-to-basolateral (A-to-B) and basolateral-to-apical were near unity in gMDCKI cells, which approximated passive permeability, and 17% of compounds demonstrated increases in their Papp A-to-B values. Overexpression of human MDR1 in gMDCKI (gMDCKI-MDR1) cells enabled substrate determination without the contribution of endogenous efflux, and the assay was able to deconvolute ambiguous results from MDCKI-MDR1 and identify species differences in substrate specificity. An analysis of 395 and 474 compounds in gMDCKI and gMDCKI-MDR1, respectively, suggested physicochemical properties that were associated with low permeability correlated with MDR1 recognition. Poorly permeable compounds and MDR1 substrates were more likely to be large, flexible, and more capable of forming external hydrogen bonds. On the basis of our evaluation, we concluded that gMDCKI is a better cell line for permeability screening and efflux substrate determination than the MDCK wt cell line.