Volatile elements have a fundamental role in the evolution of planets. But how budgets of volatiles were set in planets, and the nature and extent of volatile-depletion of planetary bodies during the ...earliest stages of Solar System formation remain poorly understood. The Moon is considered to be volatile-depleted and so it has been predicted that volatile loss should have fractionated stable isotopes of moderately volatile elements. One such element, zinc, exhibits strong isotopic fractionation during volatilization in planetary rocks, but is hardly fractionated during terrestrial igneous processes, making it a powerful tracer of the volatile histories of planets. Here we present high-precision zinc isotopic and abundance data which show that lunar magmatic rocks are enriched in the heavy isotopes of zinc and have lower zinc concentrations than terrestrial or Martian igneous rocks. Conversely, Earth and Mars have broadly chondritic zinc isotopic compositions. We show that these variations represent large-scale evaporation of zinc, most probably in the aftermath of the Moon-forming event, rather than small-scale evaporation processes during volcanism. Our results therefore represent evidence for volatile depletion of the Moon through evaporation, and are consistent with a giant impact origin for the Earth and Moon.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To determine whether injection laryngoplasty within 6 months following the onset of unilateral vocal fold paralysis (UVFP) decreases the rate of permanent thyroplasty in adults.
Data ...Sources
Search strategies created by a medical librarian were implemented in multiple online research databases.
Review Methods
Inclusion and exclusion criteria were designed to capture randomized clinical trials and cohort studies examining adults with UVFP who received injection laryngoplasty early in the course of treatment, within 6 months of onset, or who were observed. The primary outcome was the rate of thyroplasty. The Newcastle‐Ottawa scale was used to assess quality of included cohort studies. Random effects meta‐analysis was used to calculate an overall relative risk (RR). Heterogeneity was evaluated with the I2 statistic.
Results
The search strategy resulted in 1,177 studies, of which four cohort studies remained for meta‐analysis after applying inclusion and exclusion criteria. All studies were rated as 9 of 9 on the Newcastle‐Ottawa scale. Meta‐analysis of 275 patients with UVFP revealed that the overall pooled RR of undergoing thyroplasty in those receiving an early injection was 0.25 (95% confidence interval 0.14–0.45) compared to conservative management (late or no injection). The I2 overall was 62.4%.
Conclusion
Otolaryngologists should offer injection laryngoplasty to patients with a diagnosis of UVFP within 6 months of diagnosis (recommendation based on grade C evidence with a preponderance of benefit over harm). Laryngoscope, 128:935–940, 2018
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
3.
A practical guide to understanding Kaplan-Meier curves Rich, Jason T; Neely, J Gail; Paniello, Randal C ...
Otolaryngology and head and neck surgery/Otolaryngology--head and neck surgery,
September 2010, Volume:
143, Issue:
3
Journal Article
Peer reviewed
Open access
In 1958, Edward L. Kaplan and Paul Meier collaborated to publish a seminal paper on how to deal with incomplete observations. Subsequently, the Kaplan-Meier curves and estimates of survival data have ...become a familiar way of dealing with differing survival times (times-to-event), especially when not all the subjects continue in the study. "Survival" times need not relate to actual survival with death being the event; the "event" may be any event of interest. Kaplan-Meier analyses are also used in nonmedical disciplines. The purpose of this article is to explain how Kaplan-Meier curves are generated and analyzed. Throughout this article, we will discuss Kaplan-Meier estimates in the context of "survival" before the event of interest. Two small groups of hypothetical data are used as examples in order for the reader to clearly see how the process works. These examples also illustrate the crucially important point that comparative analysis depends upon the whole curve and not upon isolated points.
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FZAB, GEOZS, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBJE, SBMB, UL, UM, UPUK
Introduction
Patients with bilateral vocal fold paralysis (BVFP) experience airway obstruction because of loss of abductor function of posterior cricoarytenoid (PCA) muscles. We previously reported ...that implantation of autologous muscle progenitor (stem) cells into thyroarytenoid muscles during reinnervation resulted in improved adductor function. In this study, that same approach was applied to treating PCA muscles in a canine model of BVFP.
Design
Animal study.
Methods
Two canines underwent baseline measures of glottal resistance (GR), then complete transection and suture repair of both recurrent laryngeal nerves. Muscle stem cells were isolated from skeletal muscle and cultured. Two months later, GR was measured, and then 107 stem cells were implanted into one PCA muscle of each animal. After four more months, GR and glottal opening force (GOF) were measured and the muscles were harvested for histologic study. One control dog underwent the same procedures without stem cell implantation, for comparison.
Results
GR increased by 21%–25% over baseline at 2 months, but after stem cell implantation, improved to 10%–14% over baseline at 6 months. PCA muscle strength, as determined by GOF, was 61%–65% on control sides (no stem cells), and 78%–83% on treated sides (with stem cells). Histology confirmed survival of stem cells and a 50% higher rate of innervation of motor endplates in the stem cell treated sides.
Conclusion
Autologous muscle progenitor (stem) cells show promise as a potential new therapy for patients with bilateral vocal fold paralysis. Additional studies are needed to determine the optimal number of cells, timing of implantation, and other variables before launching a clinical trial.
Level of Evidence
NA (animal study) Laryngoscope, 134:324–328, 2024
Adult autologous muscle stem cells were implanted into one posterior cricoarytenoid (PCA) muscle of each canine after bilateral recurrent laryngeal nerve transection and re‐anastomosis. At 6 months post‐implantation, glottal resistance was reduced by 20% compared with non‐implanted controls, PCA muscle strength was increased by 17%, and motor endplate innervation increased by 50% compared with controls. Muscle stem cell implantation may offer a less invasive treatment option for patients with bilateral vocal fold paralysis and allow decannulation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objectives/Hypothesis
When the recurrent laryngeal nerve (RLN) is injured, functional recovery may be limited by the number of axons that regrow across the site of injury, and by the proportions of ...these axons that reinnervate the antagonistic muscle (synkinesis). This process was investigated in a computer model of RLN recovery.
Study Design
Computer simulation.
Methods
The developed computer program accepted as inputs: number of RLN axons; proportions of axons originally innervating adductor versus abductor, fraction of axons transected, fraction of axons that grow back, and width of 1 standard deviation about the mean. The program employed random sampling from a normal distribution to model various degrees of recovery, using random numbers to assign each axon to the correct muscle, an incorrect muscle, or no recovery. Each simulation was run 1,000×, and the mean, highest, and lowest degrees of synkinesis were determined.
Results
More severe injuries were associated with greater degrees of synkinesis. Extremes of synkinesis were possible but were rare. One example result, for a 50% injury with a 50% recovery rate, found: in the adductor muscles, 74.8% of axons will be innervated, of which 49.2% are the original uninjured axons, 19.4% are recovered adductor axons, and 6.2% are misdirected abductor axons. In the posterior cricoarytenoid (PCA), these values were 75.7%, 50.8%, 6.1%, and 18.8%, respectively. Results of many such simulations are plotted.
Conclusions
Laryngeal synkinesis can be simulated based on known anatomic ratios and estimated recovery rates. The PCA is invariably much more affected by synkinetic reinnervation than are the adductor muscles.
Level of Evidence
NA Laryngoscope, 126:1600–1605, 2016
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Enstatite meteorites include the undifferentiated enstatite chondrites and the differentiated enstatite achondrites (aubrites). They are the most reduced group of all meteorites. The oxygen isotope ...compositions of both enstatite chondrites and aubrites plot along the terrestrial mass fractionation line, which suggests some genetic links between these meteorites and the Earth as well.
For this study, we measured the Zn isotopic composition of 25 samples from the following groups: aubrites (main group and Shallowater), EL chondrites, EH chondrites and Happy Canyon (impact-melt breccia). We also analyzed the Zn isotopic composition and elemental abundance in separated phases (metal, silicates, and sulfides) of the EH4, EL3, and EL6 chondrites. The different groups of meteorites are isotopically distinct and give the following values (‰): aubrite main group (−7.08
<
δ
66Zn
<
−0.37); EH3 chondrites (0.15
<
δ
66Zn
<
0.31); EH4 chondrites (0.15
<
δ
66Zn
<
0.27); EH5 chondrites (δ
66Zn
=
0.27
±
0.09;
n
=
1); EL3 chondrites (0.01
<
δ
66Zn
<
0.63); the Shallowater aubrite (1.48
<
δ
66Zn
<
2.36); EL6 chondrites (2.26
<
δ
66Zn
<
7.35); and the impact-melt enstatite chondrite Happy Canyon (δ
66Zn
=
0.37).
The aubrite Peña Blanca Spring (δ
66Zn
=
−7.04‰) and the EL6 North West Forrest (δ
66Zn
=
7.35‰) are the isotopically lightest and heaviest samples, respectively, known so far in the Solar System. In comparison, the range of Zn isotopic composition of chondrites and terrestrial samples (−1.5
<
δ
66Zn
<
1‰) is much smaller (
Luck et al., 2005; Herzog et al., 2009).
EH and EL3 chondrites have the same Zn isotopic composition as the Earth, which is another example of the isotopic similarity between Earth and enstatite chondrites. The Zn isotopic composition and abundance strongly support that the origin of the volatile element depletion between EL3 and EL6 chondrites is due to volatilization, probably during thermal metamorphism. Aubrites show strong elemental depletion in Zn compared to both EH and EL chondrites and they are enriched in light isotopes (δ
66Zn down to −7.04‰). This is the opposite of what would be expected if Zn elemental depletion was due to evaporation, assuming the aubrites started with an enstatite chondrite-like Zn isotopic composition. Evaporation is therefore not responsible for volatile loss from aubrites. On Earth, Zn isotopes fractionate very little during igneous processes, while differentiated meteorites show only minimal Zn isotopic variability. It is therefore very unlikely that igneous processes can account for the large isotopic fractionation of Zn in aubrites. Condensation of an isotopically light vapor best explains Zn depletion and isotopically light Zn in these puzzling rocks. Mass balance suggests that this isotopically light vapor carries Zn lost by the EL6 parent body during thermal metamorphism and that aubrites evolved from an EL6-like parent body. Finally, Zn isotopes suggest that Shallowater and aubrites originate from distinct parent bodies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objectives/Hypothesis
A new treatment for acute unilateral vocal‐fold paralysis (UVFP) was proposed in which a drug is injected into the posterior cricoarytenoid muscle (PCA) shortly after nerve ...injury, before the degree of natural recovery is known, to prevent antagonistic synkinetic reinnervation. This concept was tested in a series of canine experiments using vincristine as the blocking agent.
Study Design
Animal experiments.
Methods
Laryngeal adductor function was measured at baseline and at 6 months following experimental recurrent laryngeal nerve (RLN) injuries, including complete transection, crush injury, and cautery. In the treatment animals, the PCA was injected with vincristine at the time of RLN injury.
Results
Adductor function in the vincristine‐treated hemilarynges was significantly improved compared with injury‐matched noninjected controls (total n = 43). Transection/repair controls recovered 56.1% of original adductor strength; vincristine‐treated hemilarynges recovered to 73.1% (P = 0.002). Cautery injuries also improved with vincristine block (60.7% vs. 88.7%; P = 0.031). Crush injuries recovered well even without vincristine (104.8% vs. 111.2%; P = 0.35).
Conclusion
These findings support a new paradigm of early, preemptive blockade of the antagonist muscle (PCA) to improve ultimate net adductor strength, which could potentially improve functional recovery in many UVFP patients and avoid the need for medialization procedures. Possible clinical aspects of this new approach are discussed.
Level of Evidence
N/A. Laryngoscope, 125:655–660, 2015
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Pembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result ...in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)-unrelated HNSCC.
Neoadjuvant pembrolizumab (200 mg) was administered and followed 2 to 3 weeks later by surgical tumor ablation. Postoperative (chemo)radiation was planned. Patients with high-risk pathology (positive margins and/or extranodal extension) received adjuvant pembrolizumab. pTR was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (<10%), pTR-1 (10%-49%), and pTR-2 (≥50%). Coprimary endpoints were pTR-2 among all patients and 1-year relapse rate in patients with high-risk pathology (historical: 35%). Correlations of baseline PD-L1 and T-cell infiltration with pTR were assessed. Tumor clonal dynamics were evaluated (ClinicalTrials.gov NCT02296684).
Thirty-six patients enrolled. After neoadjuvant pembrolizumab, serious (grades 3-4) adverse events and unexpected surgical delays/complications did not occur. pTR-2 occurred in eight patients (22%), and pTR-1 in eight other patients (22%). One-year relapse rate among 18 patients with high-risk pathology was 16.7% (95% confidence interval, 3.6%-41.4%). pTR ≥10% correlated with baseline tumor PD-L1, immune infiltrate, and IFNγ activity. Matched samples showed upregulation of inhibitory checkpoints in patients with pTR-0 and confirmed clonal loss in some patients.
Among patients with locally advanced, HPV-unrelated HNSCC, pembrolizumab was safe, and any pathologic response was observed in 44% of patients with 0% pathologic complete responses. The 1-year relapse rate in patients with high-risk pathology was lower than historical.
Purpose:
Vocal fold medialization laryngoplasty (ML) and laryngeal reinnervation (LR) as treatments for unilateral vocal fold paralysis (UVFP) were compared in a multicenter, prospective, randomized ...clinical trial.
Methods:
Previously untreated patients with UVFP were randomized to undergo either ML or LR. Voice results were compared pretreatment and at 6 and 12 months posttreatment using perceptual ratings by untrained listeners (RUL), blinded speech pathologist GRBAS scores, and voice‐related quality of life (VRQOL) scores. Other secondary data included maximum phonation time (MPT), cepstral analysis, and electromyography (EMG) findings.
Results:
Twenty‐four patients from nine sites completed the study, 12 in each group. There were no significant intergroup differences in pretreatment variables. At 12 months, both study groups showed significant improvement in RUL, total GRBAS (grade, roughness, breathiness, asthenia, and strain) scores, and VRQOL scores, but no significant differences were found between the two groups. However, patient age significantly affected the LR, but not the ML, group results. The age less than 52 LR subgroup had significantly (P < .05) better scores than the age more than 52 LR subgroup, and had better RUL and GRBAS scores than the age less than 52 ML subgroup. The age more than 52 ML subgroup results were significantly better than the age more than 52 LR subgroup. The secondary data generally followed the primary data, except that the MPTs for the ML patients were significantly longer than for the LR patients.
Conclusions:
ML and LR are both effective surgical options for patients with UVFP. Laryngeal reinnervation should be considered in younger patients, whereas medialization laryngoplasty should be favored in older patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The validity of sentinel lymph node biopsy (SLNB) for T1 or T2, clinically N0, oral cancer was tested by correlation of sentinel node pathologic status with that of nodes within the completion neck ...dissection.
This prospective, cooperative group trial involved 25 institutions over a 3-year period. One hundred forty patients with invasive oral cancers, stage T1 and T2, N0 including 95 cancers of the tongue, 26 of the floor of mouth, and 19 other oral cancers were studied. The study excluded lesions with diameter smaller than 6 mm or minimal invasion. Imaging was used to exclude nonpalpable gross nodal disease. Patients underwent injection of the lesion with (99m)Tc-sulfur colloid, nuclear imaging, narrow-exposure SLNB, and completion selective neck dissection. The major end point was the negative-predictive value (NPV) of SLNB.
In the 106 SLNBs, which were found to be pathologically and clinically node-negative by routine hematoxylin and eosin stain, 100 patients were found to have no other pathologically positive nodes, corresponding to a NPV of 94%. With additional sectioning and immunohistochemistry, NPV was improved to 96%. In the forty patients with proven cervical metastases, the true-positive rate was 90.2% and was superior for tongue tumors relative to floor of mouth. For T1 lesions, metastases were correctly identified in 100%.
For T1 or T2 N0 oral squamous cell carcinoma, SLNB with step sectioning and immunohistochemistry, performed by surgeons of mixed experience levels, correctly predicted a pathologically negative neck in 96% of patients (NPV, 96%).
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