Adjuvant Reirradiation With Proton Therapy in Head and Neck Squamous Cell Carcinoma.

Purpose: For patients with head and neck squamous cell carcinoma (HNSCC), locoregional failure and second primary tumors are common indications for adjuvant reirradiation (re-RT). Given an absence of clear consensus on the role of adjuvant re-RT, we sought to assess histopathologic risk factors of patients with HNSCC and their resulting outcomes after adjuvant re-RT with proton therapy. Methods and Materials: We conducted a retrospective analysis of patients with HNSCC who underwent salvage surgery at our institution followed by adjuvant re-RT with proton therapy over 1.5 years. All included patients received prior radiation therapy. The Kaplan-Meier method was used to evaluate locoregional recurrence-free survival and overall survival. Results: The cohort included 22 patients, with disease subsites, including oropharynx, oral cavity, hypopharynx, larynx, and nasopharynx. Depending on adverse pathologic features, adjuvant re-RT to 66 Gy (32% of cohort) or 60 Gy (68%), with (59%) or without (41%) concurrent systemic therapy was administered. The majority (86%) completed re-RT with no reported treatment delay; 3 patients experienced grade ≥3 acute Common Terminology Criteria for Adverse Events toxicity and no patient required enteral feeding tube placement during re-RT. Median follow-up was 21.0 months (IQR, 11.7-25.2 months). Five patients had biopsy-proven disease recurrences a median of 5.9 months (IQR, 3.8-9.7 months) after re-RT. Locoregional recurrence-free survival was 95.2%, 70.2%, 64.8% at 6, 12, and 24 months, respectively. OS was 100%, 79.2%, and 79.2% at 6, 12, and 24 months, respectively. Four patients had osteoradionecrosis on imaging a median of 13.2 months (IQR, 8.7-17.4 months) after re-RT, with 2 requiring surgical intervention. Conclusions: Adjuvant re-RT for patients with HNSCC was well-tolerated and offered reasonable local control in this high-risk cohort but appears to be associated with a risk of osteoradionecrosis. Additional study and longer follow-up could help define optimal patient management in this patient population.

Noninvasive Treatment of Venous Pulsatile Tinnitus with an Internal Jugular Vein Compression Collar.

OBJECTIVE: The study was conducted to evaluate the safety and efficacy of mild internal jugular (IJV) compression via an FDA approved compression collar for symptomatic treatment of venous pulsatile tinnitus. METHODS: This is a prospective study that recruited 20 adult patients with venous pulsatile tinnitus. Participants completed the Tinnitus Handicap Inventory (THI), were fitted with the collar, and rated symptom intensity on a 10-point tinnitus intensity scale before and during collar use. Once weekly for 4 weeks, they answered a survey quantifying days used, average tinnitus intensity before and after wearing the collar each day of use, and any safety concerns. Lastly, they completed an exit interview. The primary outcome was symptomatic relief, with secondary outcomes of safety, effect of treatment setting, effect of time, and quality of life assessed via nonparametric testing. RESULTS: 18 participants completed the study, and 276 paired daily before use/during use intensity scores were submitted. The median symptom intensity without the collar was 6 (IQR 4, 7), whereas with the collar it was 3 (IQR 2, 5), for a median symptomatic relief of 50%. The collar had a significant effect in reducing symptom intensity (p < 0.0001) and burden of illness via the THI (p < 0.0001). There was no effect of setting, frequency, or time on symptomatic relief with the collar. There were no adverse safety events reported aside from minor discomfort upon initial application. CONCLUSIONS: Venous compression collars offer acute symptom relief for patients with venous pulsatile tinnitus. Further study is needed to assess safety and efficacy of longitudinal use. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3342-3348, 2024.

Does the clopidogrel CYP2C19 genotype assay predict postprocedure stenosis in cerebral aneurysms treated with a flow diverter?

OBJECTIVE: Flow diverters have emerged as a popular modality for treating cerebral aneurysms but require dual antiplatelet therapy (DAPT) after placement. Clopidogrel is a common choice but is a prodrug that some patients may not convert into an active metabolite. The CYP2C19 genotype assay is used to predict activation speed; however, limited data exist showcasing whether this genotype accurately predicts postprocedure complications after flow diversion treatment of cerebral aneurysms. Therefore, the authors sought to characterize whether CYP2C19 genotype correlated with the development of postprocedure intimal hyperplasia (stenosis) after flow diverter placement. METHODS: Medical records were reviewed for patients who underwent flow diverter treatment of cerebral aneurysm at a single academic institution between January 1, 2012, and May 31, 2020. Patient demographics and comorbidities were reviewed alongside CYP2C19 genotype assay, DAPT regimen, and postprocedure angiogram data. Stenosis was defined based on review of angiogram data by two independent physicians. RESULTS: In this review of 120 unique cerebral aneurysms, 102 received DAPT with clopidogrel and 18 received DAPT with an alternative agent. Stenosis was present on 3-month follow-up angiogram for 35/102 (34.3%) aneurysms receiving DAPT with clopidogrel and in 11/18 (61.1%) aneurysms receiving an alternative DAPT regimen (p = 0.031). The CYP2C19 genotype did not correlate with postprocedure stenosis (p = 0.35). CONCLUSIONS: Clopidogrel was a significantly more effective DAPT agent for preventing stenosis when compared to nonclopidogrel DAPT regimens. The clopidogrel CYP2C19 genotype did not predict postprocedure stenosis in this cohort of 120 cerebral aneurysms treated with a flow diverter.

Linked disturbance in the temperate forest: Earthworms, deer, and canopy gaps.

Despite the large body of theory concerning multiple disturbances, relatively few attempts have been made to test the theoretical assumptions of how and if disturbances interact. Of particular importance is whether disturbance events are linked, as this can influence the probability and intensity of ecological change. Disturbances are linked when one disturbance event increases or decreases the likelihood or extent of another. To this end, we used two long-term, multi-disturbance experiments in northern Wisconsin to determine whether earthworm invasion is linked to canopy gap creation and white-tailed deer browsing. These three disturbances are common and influential within North American temperate forests, making any interactions among them particularly important to understand. We expected both deer and canopy gaps to favor invasive earthworms, particularly species that live close to or on the soil surface. However, we found only partial support of our hypotheses, as both deer exclosures and canopy gaps decreased earthworms in each experiment. Further, earthworm density increased the most over time in areas far from the gap center and in areas with deer present. Deer exclosures primarily decreased Aporrectodea and Lumbricus species, while gaps decreased Dendrobaena and Lumbricus species. Our findings show that earthworm invasion is linked to deer presence and gap-creating disturbances, which provides new insight in multiple disturbance theory, aboveground-belowground dynamics, and temperate forest management.

Cumulative Radiation Exposure in Aneurysmal Subarachnoid Hemorrhage: A Single-Institution Analysis.

OBJECTIVE: Diagnosis and management of aneurysmal subarachnoid hemorrhage (aSAH) depend heavily on imaging modalities that repeatedly expose patients to ionizing radiation. There is limited literature on cumulative radiation exposure in this patient population, which is a problem compounded by wide variation among institutions. The present study quantifies the cumulative cranial exposure to ionizing radiation resulting from diagnostic medical imaging and medical procedures during initial hospitalization for ruptured aSAH at a single academic institution and estimates the risk of future adverse events related to radiation injury. METHODS: We performed a retrospective observational study of adults who presented to our institution during a nearly 3-year period with acute-onset aSAH, which was confirmed with diagnostic imaging, and had the aneurysm treated with either surgical clip ligation or endovascular embolization. RESULTS: A total of 131 patients met the inclusion criteria. Eighty-eight patients (67%) were treated with endovascular embolization and 43 (32%) were treated with clip ligation. We found the average radiation dose to the head during the incident hospitalization for aSAH to be 4.40 Gy (95% confidence interval, 3.91-4.89). Angiography and interventional radiology procedures accounted for most of this exposure. CONCLUSIONS: Most patients were exposed to levels of ionizing radiation that put them at considerable risk of deterministic radiation injury. Providers should be aware of the potential consequences of acute and long-term radiation exposure in this patient population, so they can monitor and counsel individuals accordingly and take steps to safely limit radiation exposure during aSAH management.

Toll-Dorsal signaling regulates the spatiotemporal dynamics of yolk granule tubulation during Drosophila cleavage.

The Toll-Dorsal signaling pathway controls dorsal-ventral (DV) patterning in early Drosophila embryos, which defines specific cell fates along the DV axis and controls morphogenetic behavior of cells during gastrulation and beyond. The extent by which DV patterning information regulates subcellular organization in pre-gastrulation embryos remains unclear. We find that during Drosophila cleavage, the late endosome marker Rab7 is increasingly recruited to the yolk granules and promotes the formation of dynamic membrane tubules. The biogenesis of yolk granule tubules is positively regulated by active Rab7 and its effector complex HOPS, but negatively regulated by the Rab7 effector retromer. The occurrence of tubules is strongly biased towards the ventral side of the embryo, which we show is controlled by the Toll-Dorsal signaling pathway. Our work provides the first evidence for the formation and regulation of yolk granule tubulation in oviparous embryos and elucidates an unexpected role of Toll-Dorsal signaling in regulating this process.

Neonatal Hydrocephalus Treatment with Ultrasmall Valve Implantation.

OBJECTIVE: Neonatal hydrocephalus remains a difficult condition to manage, due to high failure rates among all management strategies. Neurosurgeons commonly manage hydrocephalus with ventriculoperitoneal shunt (VPS) implantation, and valves of variable sizes and profiles are available for implantation. This study examines primary ventricular shunt valve implantation complication rates based on valve profiles in pediatric patients with hydrocephalus. METHODS: This study retrospectively reviews pediatric patients younger than 1 year of age who underwent ventricular shunt placement at a single institution from January 2001 to January 2017. Patients were classified by valve profile and categorized as either ultrasmall valves or regular-sized valves. Time until complication and type of complication were studied. RESULTS: A total of 156 patients met the inclusion criteria. Forty-eight (31%) patients received an ultrasmall shunt valve, while 108 patients received a regular valve. On average, patients undergoing ultrasmall valve placement were younger (2.1 months) than patients undergoing placement of regular valves (3.1 months) (P = 0.03). The overall complication rate within 2 years of VPS placement was 37.5% in patients with the ultrasmall valve and 41.7% in the regular valve population. There was no difference in 1-year shunt survival rate between the 2 cohorts. CONCLUSION: Our review did not find a significant difference in complication rates between ultrasmall and regular valves in patients under 1 year of age. However, the etiology of shunt malfunction did differ between the groups. This work further supports evidence suggesting a surgeon's preference for shunt hardware alone does not significantly impact outcome.

Simultaneous DNA amplification and detection using a pH-sensing semiconductor system.

We developed an integrated chip for real-time amplification and detection of nucleic acid using pH-sensing complementary metal-oxide semiconductor (CMOS) technology. Here we show an amplification-coupled detection method for directly measuring released hydrogen ions during nucleotide incorporation rather than relying on indirect measurements such as fluorescent dyes. This is a label-free, non-optical, real-time method for detecting and quantifying target sequences by monitoring pH signatures of native amplification chemistries. The chip has ion-sensitive field effect transistor (ISFET) sensors, temperature sensors, resistive heating, signal processing and control circuitry all integrated to create a full system-on-chip platform. We evaluated the platform using two amplification strategies: PCR and isothermal amplification. Using this platform, we genotyped and discriminated unique single-nucleotide polymorphism (SNP) variants of the cytochrome P450 family from crude human saliva. We anticipate this semiconductor technology will enable the creation of devices for cost-effective, portable and scalable real-time nucleic acid analysis.