Tumors with mismatch repair deficiency (MMR-d) are characterized by sequence alterations in microsatellites and can accumulate thousands of mutations. This high mutational burden renders tumors ...immunogenic and sensitive to programmed cell death-1 (PD-1) immune checkpoint inhibitors. Yet, despite their tumor immunogenicity, patients with MMR-deficient tumors experience highly variable responses, and roughly half are refractory to treatment. We present experimental and clinical evidence showing that the degree of microsatellite instability (MSI) and resultant mutational load, in part, underlies the variable response to PD-1 blockade immunotherapy in MMR-d human and mouse tumors. The extent of response is particularly associated with the accumulation of insertion-deletion (indel) mutational load. This study provides a rationale for the genome-wide characterization of MSI intensity and mutational load to better profile responses to anti-PD-1 immunotherapy across MMR-deficient human cancers.
The aim of this study was to report the safety, efficacy, and early results of tracheostomy in patients with COVID-19 and determine whether differences exist between percutaneous and open methods.
...Prolonged respiratory failure is common in symptomatic patients with COVID-19, the disease process caused by infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Tracheostomy, although posing potential risk to the operative team and other healthcare workers, may be beneficial for safe weaning of sedation and ventilator support. However, short- and long-term outcomes remain largely unknown.
A prospectively collected database of patients with COVID-19 undergoing tracheostomy at a major medical center in New York City between April 4 and April 30, 2020 was reviewed. The primary endpoint was need for continued mechanical ventilation. Secondary outcomes included complication rates, sedation weaning, and need for intensive care unit (ICU) level of care. Patient characteristics, perioperative conditions, and outcomes between percutaneous and open groups were analyzed.
During the study period, 67 consecutive patients underwent tracheostomy, including 48 males and 19 females with a median age of 66 years interquartile range (IQR) 52-72. Two surgeons alternated techniques, with 35 tracheostomies performed percutaneously and 32 via an open approach. The median time from intubation to tracheostomy was 23 days (IQR 20-26). At a median follow-up of 26 days, 52 patients (78%) no longer required mechanical ventilation and 58 patients (87%) were off continuous sedation. Five patients (7.5%) died of systemic causes. There were 11 total complications (16%) in 10 patients, most of which involved minor bleeding. There were no significant differences in outcomes between percutaneous and open methods.
Tracheostomy under apneic conditions by either percutaneous or open technique can be safely performed in patients with respiratory failure due to COVID-19. Tracheostomy facilitated weaning from continuous intravenous sedation and mechanical ventilation. Continued follow-up of these patients to ascertain long-term outcome data is ongoing.
A population of appropriately selected patients does not respond, or does not achieve cure, with hypoglossal nerve stimulation (HGNS). We describe the case of nonresponder whose obstructive sleep ...apnea (OSA) resolved with the addition of chin strap. After initial placement and titration of HGNS implant, follow‐up sleep study demonstrated persistent moderate OSA. Drug‐induced sleep endoscopy demonstrated supraglottic collapse with activate neurostimulation. With mouth closure and change of stimulation settings to unipolar from bipolar, the airway collapse and desaturations improved. The follow‐up polysomnogram with (HGNS) therapy and chin strap demonstrated resolution of sleep apnea. Laryngoscope, 128:1727–1729, 2018
Vestibular schwannomas are the most common tumor of the cerebellopontine angle. The history of their management has driven advances in imaging, lateral skull base surgery, as well as radiosurgery. ...With these advances, a shift has occurred from life-saving treatment for late-stage disease to quality of life focused management of smaller tumors. The complicated treatment paradigms involving observation, stereotactic radiosurgery and surgery require close communication between the treatment and neuroradiology teams.
Objectives
To evaluate the feasibility of using Calcium Hydroxylapatite (CaHA) to augment the tongue base for patients with swallowing impairment due to tongue base atrophy.
Methods
A fresh human ...cadaver was obtained through the institution's body donation program and baseline lateral fluoroscopic images were obtained. A total of 2 mL of CaHA (Prolaryn Plus) were injected into three sites of the base of tongue under flexible endoscopic guidance with a 22G, 1.5‐inch needle (Monoject, Cardinal Health). Post‐lateral fluoroscopic images were obtained and pharyngeal area (cm2) and tongue base to pharyngeal wall distance (cm) was measured pre‐ and postinjection using SwallowTail fluoroscopic measurement software (Belldev Medical).
Results
The procedure was easily performed and the CaHA flowed easily into the cadaveric tongue without evidence of extrusion. The pre‐procedural pharyngeal area decreased from 24.36 to 23.14 cm after augmentation. The base of tongue to pharyngeal wall distance decreased from 2.21 to 1.32 cm after augmentation.
Conclusion
Tongue base augmentation with CaHA may be a feasible adjuvant therapy for the management of swallowing impairment secondary to tongue base atrophy. Further investigation is necessary to evaluate the clinical safety and efficacy.
Level of Evidence
4
This study evaluates the feasibility of using Calcium Hydroxylapatite (CaHA) to augment the tongue base for patients with swallowing impairment due to tongue base atrophy. A fresh human cadaver was utilized for this study. Our results show this method may be a feasible adjuvant therapy for the management of swallowing impairment secondary to tongue base atrophy.
An anterior glottic web is an abnormal fusion of the anterior aspect of the membranous vocal folds. Noncongenital glottic webs are usually iatrogenic from intubation or laryngeal surgery. We present ...six adult patients whose initial in‐office diagnoses were consistent with “idiopathic” benign anterior glottic webs as determined by three laryngologists (a.m.k., j.m.b., m.j.p.). Further evaluation revealed the diagnoses of laryngeal squamous cell carcinoma in all cases. The high risk of malignancy in cases of idiopathic anterior glottic web necessitates biopsy for tissue diagnosis of all such lesions.
Laryngoscope, 129:2118–2120, 2019
Weak or absent peristalsis of the esophageal musculature is a common finding in ambulatory patients suffering from dysphagia and frequently associated with gastroesophageal reflux. There is currently ...no pharmacologic intervention that reliably improves esophageal contractility in patients suffering from various esophageal motility disorders. Our objective was to evaluate the acute effects of pyridostigmine on high-resolution manometry parameters in patients suffering from dysphagia with evidence of esophageal dysmotility. Pyridostigmine is an acetylcholinesterase inhibitor which increases effective concentrations of acetylcholine at the neuromuscular junction of both striated and smooth muscle cells. We conducted a prospective crossover study of five patients with dysphagia and proven esophageal dysmotility. Three patients had baseline ineffective esophageal motility and two had achalasia. Patients underwent pharyngeal and esophageal manometry before and after pyridostigmine administration. The median distal contractile integral (DCI), a marker of esophageal contractile vigor, was significantly higher post pyridostigmine administration 3001 (1950.3–3703.2) mmHg × s × cm compared to pre-pyridostigmine DCI of 1229.9 (956.2–2100) mmHg × s × cm;
P
< 0.001. Pre-pyridostigmine 18/25 (72%) of the patient’s swallows was peristaltic compared to 25/25 (100%) post-pyridostigmine;
P
< 0.005. No other pharyngeal or esophageal high-resolution manometry parameter differed significantly after pyridostigmine administration. The results of this pilot study demonstrate that pyridostigmine acutely improves esophageal contractile vigor in patients suffering from dysphagia with esophageal dysmotility. Further investigation with larger sample size, longer follow-up, side effect profile, and patient-reported outcome measures is still needed to determine the clinical usefulness of pyridostigmine in specific disorders of esophageal motility.
Neuro-otologists rely on the expertise and judgment of a skilled neuroradiologist to identify radiographic abnormalities in the complicated regional anatomy of the temporal bone and middle and ...posterior fossa, and more importantly, to alert the surgeon to potential operative pitfalls. This article highlights some of the common otologic surgical procedures that stress this important dynamic. The surgical perspective on quick and effective clinical decision-making pearls to keep in mind during a thorough radiographic analysis of the ear and lateral skull base is presented.
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