Impact of Cochlear Dose on Hearing Preservation Following Stereotactic Radiosurgery in Treatment of Vestibular Schwannomas: A Multi-Center Study.

OBJECTIVE: Stereotactic radiosurgery (SRS) is a well-established treatment for vestibular schwannomas (VS). Hearing loss remains a main morbidity of VS and its treatments, including SRS. The effects of radiation parameters of SRS on hearing remain unknown. The goal of this study is to determine the effect of tumor volume, patient demographics, pretreatment hearing status, cochlear radiation dose, total tumor radiation dose, fractionation, and other radiotherapy parameters on hearing deterioration. METHODS: Multicenter retrospective analysis of 611 patients who underwent SRS for VS from 1990-2020 and had pre- and post-treatment audiograms. RESULTS: Pure tone averages (PTAs) increased and word recognition scores (WRSs) decreased in treated ears at 12-60 months while remaining stable in untreated ears. Higher baseline PTA, higher tumor radiation dose, higher maximum cochlear dose, and usage of single fraction resulted in higher post radiation PTA; WRS was only predicted by baseline WRS and age. Higher baseline PTA, single fraction treatment, higher tumor radiation dose, and higher maximum cochlear dose resulted in a faster deterioration in PTA. Below a maximum cochlear dose of 3 Gy, there were no statistically significant changes in PTA or WRS. CONCLUSIONS: Decline of hearing at one year in VS patients after SRS is directly related to maximum cochlear dose, single versus 3-fraction treatment, total tumor radiation dose, and baseline hearing level. The maximum safe cochlear dose for hearingtbrowd preservation at one year is 3 Gy, and the use of 3 fractions instead of one fraction was better at preserving hearing.

Association of Hyperchloremia and Acute Kidney Injury in Patients With Traumatic Brain Injury.

INTRODUCTION: Hypertonic saline is often used to treat patients with traumatic brain injury. It carries the undesired side effect of hyperchloremia, which has been linked to acute kidney injury (AKI). We sought to evaluate the relationship of hyperchloremia and AKI in this population and whether the absolute exposure to hyperchloremia, including maximal hyperchloremia and duration of hyperchloremia were associated with AKI. METHODS: A retrospective study of severe traumatic brain injury patients who received hypertonic saline at a single academic institution. Demographics, head abbreviated injury scale, development of hyperchloremia (Cl ≥ 115), duration of hyperchloremia, highest chloride level, duration of hypertonic saline use, admission GFR, and administration of nephrotoxic medications were abstracted. The outcome of interest was the association between renal function and hyperchloremia. RESULTS: A total of 123 patients were included in the study. Multivariable logistic regression analysis demonstrated that only duration of hyperchloremia (p = 0.014) and GFR on admission (p = 0.004) were independently associated with development of AKI. The number of days of hypertonic saline infusion (p = 0.79) without the persistence of hyperchloremia and highest serum chloride levels (p = 0.23) were not predictive of AKI development. DISCUSSION: In patients with traumatic brain injury, admission GFR and prolonged hyperchloremia rather than the highest chloride level or the duration of hypertonic saline infusion were associated with the development of AKI.

Comparison of the causes of death and wounding patterns in urban firearm-related violence and civilian public mass shooting events.

BACKGROUND: There are no reports comparing wounding pattern in urban and public mass shooting events (CPMS). Because CPMS receive greater media coverage, there is a connation that the nature of wounding is more grave than daily urban gun violence. We hypothesize that the mechanism of death following urban gunshot wounds (GSWs) is the same as has been reported following CPMS. METHODS: Autopsy reports of all firearm-related deaths in Washington, DC were reviewed from January 1, 2016, to December 31, 2017. Demographic data, firearm type, number and anatomic location of GSWs, and organ(s) injured were abstracted. The organ injury resulting in death was noted. The results were compared with a previously published study of 19 CPMS events involving 213 victims. RESULTS: One hundred eighty-six urban autopsy reports were reviewed. There were 171 (92%) homicides and 13 (7%) suicides. Handguns were implicated in 180 (97%) events. One hundred eight (59%) gunshots were to the chest/upper back, 85 (46%) to the head, 77 (42%) to an extremity, and 71 (38%) to the abdomen/lower back. The leading mechanisms of death in both urban firearm violence and CPMS were injury to the brain, lung parenchyma, and heart. Fatal brain injury was more common in CPMS events as compared with urban events involving a handgun. CONCLUSION: There is little difference in wounding pattern between urban and CPMS firearm events. Based on the organs injured, rapid point of wounding care and transport to a trauma center remain the best options for mitigating death following all GSW events. LEVEL OF EVIDENCE: Epidemiological, level IV.

Transmitral Septal Myectomy for Hypertrophic Obstructive Cardiomyopathy.

BACKGROUND: Intrinsic abnormalities of the mitral valve are common in patients with hypertrophic cardiomyopathy and may need to be addressed at operation. METHODS: Consecutive patients undergoing transmitral septal myectomy were retrospectively reviewed. The ventricular septum was exposed through a left atriotomy, and the anterior leaflet of the mitral valve was detached from its annulus. An extended myectomy was performed to the base of the papillary muscles. After myectomy, the anterior leaflet was reattached and concomitant mitral valve repair or replacement was performed. In some cases, we performed a modified anterolateral commissural closure suture, which served to reposition the lateral aspect of the anterior leaflet out of the left ventricular outflow tract ("curtain stitch"). RESULTS: Twenty patients who underwent this procedure were identified (70% women; mean age 63 years). Mitral regurgitation was moderate in 55% and severe in 40%. Preoperative peak left ventricular outflow tract gradient was 92 ± 43 mm Hg. Mitral valve repair (n = 11) or replacement (n = 9) was performed. Predischarge transthoracic echocardiography demonstrated a left ventricular outflow tract gradient of 10 ± 5 mm Hg. There was no operative mortality. Follow-up was 100% complete and averaged 22 ± 25 months. No patient required reoperation, and there was no recurrence of left ventricular outflow tract obstruction or mitral regurgitation greater than mild. CONCLUSIONS: Potential advantages of transmitral myectomy include a panoramic view of the septum and mitral subvalvular apparatus and the ability to simultaneously address mitral valve pathology. Consideration should be given to using the transmitral approach to septal myectomy as the preferred approach for the surgical treatment of hypertrophic cardiomyopathy.

Early Operation in Patients With Mitral Valve Infective Endocarditis and Acute Stroke Is Safe.

BACKGROUND: To determine if preoperative embolic stroke is associated with an increased risk of postoperative stroke among patients undergoing early operation for mitral valve (MV) infective endocarditis (IE), we compared outcomes among patients presenting with and without acute stroke. METHODS: From 2003 to 2015, 243 consecutive patients underwent surgery for active MV IE. Patients were categorized into 2 groups: 72% (174 of 243 patients) with no preoperative acute stroke (clinical, radiographic or both) and 28% (69 of 243 patients) with stroke. Both preoperative and postoperative strokes were confirmed in all patients with brain computed tomography or magnetic resonance imaging and comprehensive examination by a neurologist. RESULTS: Among patients presenting with stroke, 33% (23 of 69 patients) were asymptomatic and had only positive imaging findings. The median time from admission to operation was 5 days. The overall rate of new postoperative stroke was 4% (10 of 243 patients). The rate of postoperative stroke was not different between the 2 groups: 4% (7 of 174 patients) among patients with no preoperative stroke and 4% (3 of 69 patients) with stroke (p = 0.9). One patient developed a hemorrhagic conversion of an acute infarct. Operative mortality was 7% (13 of 174 patients) among patients with no preoperative stroke and 7% (5 of 69 patients) among patients with stroke (p = 0.9). CONCLUSIONS: MV surgery for IE and acute stroke can be performed early with a low risk of postoperative neurologic complications. When indicated, surgical intervention for MV IE complicated by acute stroke should not be delayed.

Undersized Rigid Nonplanar Annuloplasty: The Key to Effective and Durable Repair of Functional Tricuspid Regurgitation.

BACKGROUND: Previous clinical experiences have demonstrated high early and late recurrence rates after repair of functional tricuspid regurgitation (TR). We investigated the results of functional TR repair with undersized rigid nonplanar annuloplasty rings. METHODS: From January 2007 to December 2013, 216 consecutive patients with moderate or greater functional TR were treated with undersized (size 26 mm or 28 mm) rigid nonplanar annuloplasty rings. RESULTS: The mean age was 69 ± 13 years. There was a previous history of cardiac operation in 25% (54 of 216 patients). Tricuspid regurgitation was graded as severe in 47% (102 of 216) and moderate in 53% (114 of 216). Concomitant operations included mitral valve procedures in 92% (198 of 216), coronary artery bypass grafting in 21% (45 of 216), aortic valve procedures in 9% (20 of 216), and cryomaze procedures in 35% (76 of 216). Size 26 mm rings were used in 38% of patients (81 of 216), and size 28 mm in 62% (135 of 216). The perioperative mortality rate was 6% (14 of 216). On predischarge echocardiography, TR grade was none or mild in 94% (176 of 187 patients), moderate in 4% (7 of 187), and severe in 2% (4 of 187). At a mean follow-up of 33.0 ± 24.0 months, TR grade was none or mild in 81% of patients (130 of 160), moderate in 16% (26 of 160), and severe in 2% (4 of 160). There were no reoperations for recurrent TR, and no patients have had tricuspid stenosis or annuloplasty ring dehiscence. CONCLUSIONS: Treatment of functional TR with undersized (26 mm or 28 mm) nonplanar rigid annuloplasty rings is safe and highly effective, with a near absence of recurrent severe TR at midterm follow-up.

NKX3.1 is regulated by protein kinase CK2 in prostate tumor cells.

Diminished expression of NKX3.1 is associated with prostate cancer progression in humans, and in mice, loss of nkx3.1 leads to epithelial cell proliferation and altered gene expression patterns. The NKX3.1 amino acid sequence includes multiple potential phosphoacceptor sites for protein kinase CK2. To investigate posttranslational regulation of NKX3.1, phosphorylation of NKX3.1 by CK2 was studied. In vitro kinase assays followed by mass spectrometric analyses demonstrated that CK2 phosphorylated recombinant NKX3.1 on Thr89 and Thr93. Blocking CK2 activity in LNCaP cells with apigenin or 5,6-dichlorobenzimidazole riboside led to a rapid decrease in NKX3.1 accumulation that was rescued by proteasome inhibition. Replacing Thr89 and Thr93 with alanines decreased NKX3.1 stability in vivo. Small interfering RNA knockdown of CK2alpha' but not CK2alpha also led to a decrease in NKX3.1 steady-state level. In-gel kinase assays and Western blot analyses using fractionated extracts of LNCaP cells demonstrated that free CK2alpha' could phosphorylate recombinant human and mouse NKX3.1, whereas CK2alpha' liberated from the holoenzyme could not. These data establish CK2 as a regulator of NKX3.1 in prostate tumor cells and provide evidence for functionally distinct pools of CK2alpha' in LNCaP cells.