According to the 'Faint Young Sun' paradox, during the late Archaean eon a Sun approximately 20% dimmer warmed the early Earth such that it had liquid water and a clement climate. Explanations for ...this phenomenon have invoked a denser atmosphere that provided warmth by nitrogen pressure broadening or enhanced greenhouse gas concentrations. Such solutions are allowed by geochemical studies and numerical investigations that place approximate concentration limits on Archaean atmospheric gases, including methane, carbon dioxide and oxygen. But no field data constraining ground-level air density and barometric pressure have been reported, leaving the plausibility of these various hypotheses in doubt. Here we show that raindrop imprints in tuffs of the Ventersdorp Supergroup, South Africa, constrain surface air density 2.7 billion years ago to less than twice modern levels. We interpret the raindrop fossils using experiments in which water droplets of known size fall at terminal velocity into fresh and weathered volcanic ash, thus defining a relationship between imprint size and raindrop impact momentum. Fragmentation following raindrop flattening limits raindrop size to a maximum value independent of air density, whereas raindrop terminal velocity varies as the inverse of the square root of air density. If the Archaean raindrops reached the modern maximum measured size, air density must have been less than 2.3 kg m(-3), compared to today's 1.2 kg m(-3), but because such drops rarely occur, air density was more probably below 1.3 kg m(-3). The upper estimate for air density renders the pressure broadening explanation possible, but it is improbable under the likely lower estimates. Our results also disallow the extreme CO(2) levels required for hot Archaean climates.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Introduction
Cardiotoxicity, manifest by reduced left ventricular ejection fraction (LVEF), is the most common reason for the premature discontinuation of trastuzumab. While permissive ...cardiotoxicity (where mild cardiotoxicity is accepted to enable ongoing trastuzumab) has been shown feasible, the longer-term outcomes are unknown. We aimed to study the intermediate-term clinical outcomes of patients who underwent permissive cardiotoxicity.
Materials and Methods
We performed a retrospective cohort study of patients referred to the cardio-oncology service at McMaster University from 2016 to 2021 for LV dysfunction following trastuzumab administration.
Results
Fifty-one patients underwent permissive cardiotoxicity. The median (25th-75th percentile) follow-up time from cardiotoxicity onset was 3 years (1.3-4 years). Forty-seven (92%) patients completed trastuzumab; 3 (6%) developed severe LV dysfunction or clinical heart failure (HF) while on trastuzumab and prematurely discontinued therapy. One discontinued trastuzumab by patient choice. At final follow-up after therapy completion, 7 (14%) patients still had mild cardiotoxicity, including 2 who had clinical heart failure and stopped trastuzumab early. Among those with recovered LV function, 50% had normalized LVEF or GLS by 6 and 3 months, respectively, after initial cardiotoxicity. There was no difference in characteristics between those who did or did not recover their LV function.
Conclusions
Among patients exposed to permissive trastuzumab cardiotoxicity for HER2-positive breast cancer, 6% were unable to complete planned trastuzumab due to severe LV dysfunction or clinical HF. Although most patients recover their LV function after trastuzumab discontinuation or completion, 14% still have persistent cardiotoxicity by 3-year follow-up.
This article reports oncological and cardiac outcomes of 51 patients with HER2-positive breast cancer who developed mild cardiac dysfunction after trastuzumab administration, and pursued a strategy of permissive cardiotoxicity.
Background
Treatment of human papillomavirus‐related oropharyngeal squamous cell carcinoma (HPVOPC) results in unprecedented high survival rates but possibly unnecessary toxicity. We hypothesized ...that upfront surgery and neck dissection followed by reduced‐dose adjuvant therapy for early and intermediate HPVOPC would ultimately result in equivalent progression‐free survival (PFS) and overall survival while reducing toxicity.
Methods
This study was a nonrandomized phase II trial for early‐stage HPVOPC treated with transoral robotic surgery (TORS) followed by reduced‐dose radiotherapy. Patients with previously untreated p16‐positive HPVOPC and <20 pack years’ smoking history were enrolled. After robotic surgery, patients were assigned to group 1 (no poor risk features; surveillance), group 2 (intermediate pathologic risk factors perineural invasion, lymphovascular invasion; 50‐Gy radiotherapy), or group 3 (poor prognostic pathologic factors extranodal extension ENE, more than three positive lymph nodes and positive margin; concurrent 56‐Gy chemoradiotherapy with weekly cisplatin).
Results
Fifty‐four patients were evaluable; there were 25 in group 1, 15 in group 2, and 14 in group 3. Median follow‐up was 43.9 months (9.6–75.8). Disease‐specific survival was 98.1%, and PFS was 90.7%. PFS probability via Kaplan‐Meier was 91.3% for group 1, 86.7% for group 2, and 93.3% for group 3. There were five locoregional failures (LRFs), including one distant metastasis and one contralateral second primary. Average time to LRF was 18.9 months (9.6–59.0); four LRFs were successfully salvaged, and the patients remain disease free (11.0–42.7 months); one subject remains alive with disease.
Conclusion
The results indicate that upfront surgery with neck dissection with reduced‐dose radiation for T1–2, N1 stage (by the eighth edition American Joint Committee on Cancer staging manual) HPVOPC results in favorable survival with excellent function in this population. These results support radiation dose reduction after TORS as a de‐escalation strategy in HPVOPC.
Implications for Practice
Transoral robotic surgery can provide a safe platform for de‐escalation in carefully selected patients with early‐stage human papillomavirus‐related oropharyngeal cancer. In this clinical trial, disease‐specific survival was 100%, over 90% of the cohort had a reduction of therapy from standard of care with excellent functional results, and the five patients with observed locoregional failures were successfully salvaged.
Treatment of human papillomavirus‐related oropharyngeal squamous cell carcinoma results in high survival rates but unnecessary toxicity. The SIRS trial investigated the use of transoral robotic surgery with selective neck dissection, followed by reduced‐dose adjuvant therapy, to reduce toxicity and maintain overall and progression‐free survival rates.
Human epidermal growth factor receptor 2 (HER2) overexpressing malignancies, including breast and gastro-esophageal, are associated with a poor prognosis. The cardiotoxicity of trastuzumab, a ...HER2-targeting monoclonal antibody, is well established. However, the cardiotoxic effect of pertuzumab, another HER2-directed therapy, is less well documented. The objective of this systematic review and meta-analysis was to determine the risk of cardiac events in patients with HER2-positive cancer who are receiving pertuzumab.
We performed a systematic review of phase 2 and 3 randomized controlled trials in which the addition of pertuzumab to other standard therapies in patients with stage I-IV HER2-positive cancer was evaluated, and cardiac adverse effects reported. We searched MEDLINE (1946-2020), Embase (1974-2020), and CENTRAL. Two independent reviewers assessed the risk of bias and extracted the data. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated from the pooled data using the inverse variance method and random-effects models.
Eight randomized controlled trials (8420 patients) were included: 1 was gastro-esophageal; 7 were breast cancer trials. Participants’ median age ranged from 49 to 61.5 years. All participants received trastuzumab and chemotherapy in addition to pertuzumab or placebo. Compared with placebo, pertuzumab increased the risk of clinical heart failure (HF; RR 95% CI: 1.97 1.05-3.70; I2 = 0%). However, pertuzumab had no demonstrable effect on asymptomatic/minimally symptomatic left ventricular systolic dysfunction (RR 95% CI: 1.19 0.89-1.61; I2 = 19%).
Pertuzumab increases the risk of clinical HF, but not asymptomatic/minimally symptomatic left ventricular systolic dysfunction, in HER2-positive cancer patients. Further research into the mechanisms underlying pertuzumab-related HF is needed to understand its clinical spectrum of cardiotoxicity.
Les tumeurs malignes qui surexpriment le récepteur 2 du facteur de croissance épidermique humain (HER2, de l’anglais Human epidermal growth factor receptor 2), notamment le cancer du sein et le cancer de la jonction gastro-œsophagienne, sont associées à un mauvais pronostic. La cardiotoxicité du trastuzumab, un anticorps monoclonal qui vise le HER2, est bien établie. Toutefois, les effets cardiotoxiques du pertuzumab, un autre traitement qui vise le HER2, sont moins bien démontrés. L’objectif de cette revue systématique et de cette méta-analyse était de déterminer le risque d’événements cardiaques chez les patients atteints d’un cancer HER2 positif qui prennent du pertuzumab.
Nous avons réalisé une revue systématique d’essais comparatifs à répartition aléatoire de phase 2 et de phase 3 lors desquels nous avons évalué l’ajout du pertuzumab à d’autres traitements standards chez les patients atteints d’un cancer HER2 positif de stades I-IV, et signalé les effets indésirables sur le cœur. Nous avons fait des recherches dans MEDLINE (1946-2020), Embase (1974-2020) et CENTRAL. Deux examinateurs indépendants ont évalué le risque de biais et extrait les données. Les données groupées ont permis de calculer les intervalles de confiance (IC) à 95 % des risques relatifs (RR) au moyen de la méthode de la variance inverse et des modèles à effets aléatoires.
Nous avons inclus huit essais contrôlés randomisés (8420 patients), soit un qui portait sur le cancer de la jonction gastro-œsophagienne, et sept sur le cancer du sein. L’âge médian des participants se situait entre 49 à 61,5 ans. Tous les participants ont pris le trastuzumab et ont suivi une chimiothérapie en plus de la prise du pertuzumab ou du placebo. Comparativement au placebo, le pertuzumab a fait augmenter le risque de manifestations cliniques de l’insuffisance cardiaque (IC) (RR IC à 95 % : 1,97 1,05-3,70; I2 = 0 %). Toutefois, le pertuzumab n’a démontré aucun effet sur la dysfonction systolique du ventricule gauche asymptomatique/minimalement symptomatique (RR IC à 95 % : 1,19 0,89-1,61; I2 = 19 %).
Le pertuzumab fait augmenter le risque de manifestations cliniques de l’IC, mais pais la dysfonction systolique du ventricule gauche asymptomatique/minimalement symptomatique, chez les patients atteints d’un cancer HER2 positif. Des recherches plus approfondies sur les mécanismes sous-jacents à l’IC liée au pertuzumab sont nécessaires pour comprendre son spectre de manifestations cliniques de cardiotoxicité.
The purpose of this study was to determine the incidence of sinonasal anatomic variants and to assess their relation to sinonasal mucosal disease.
A retrospective evaluation of 192 sinus CT ...examinations of patients with a clinical history of rhinosinusitis was conducted. The CT scans were evaluated for the presence of several anatomic variants of the sinonasal cavities, and the prevalence of each variant was calculated. Prevalences of all sinonasal anatomic variants were compared between patients who had minimal to no apparent imaging evidence of rhinosinusitis and those who had radiologic evidence of clinically significant rhinosinusitis.
The most common normal variants were nasal septal deviation, Agger nasi cells, and extension of the sphenoid sinuses into the posterior nasal septum. We found no statistically significant difference in the prevalence of any of the studied anatomic variants between patients with minimal and those with clinically significant paranasal sinus or nasal cavity disease.
Analysis of every routine CT scan of the paranasal sinuses obtained for sinusitis or rhinitis for the presence of different anatomic variants is of questionable value unless surgery is planned.
A Rare Case of a Nasopharyngeal Mass Rodrigues, Marta Gomes; Laitman, Benjamin M; Som, Peter M
JAMA otolaryngology-- head & neck surgery,
02/2019, Letnik:
145, Številka:
2
Journal Article
To correlate positron emission tomography (PET) standard uptake value (SUV) with pathologic specimen size in patients with head-and-neck cancers.
Eighteen patients with Stage II-IVB head-and-neck ...cancer with 27 tumors who underwent PET and computed tomography (CT) imaging of the head and neck followed by surgical resection were selected for this study. Various SUV thresholds were examined, including the software default (SUV(def)), narrowing the window by 1 standard deviation (SD) of the maximum (SUV-1SD), and SUV cutoff values of 2.5 or greater (SUV2.5) and 40% or greater maximum (SUV40). Volumetric pathologic data were available for 12 patients. Tumor volumes based on pathologic examination (gold standard), CT, SUV(def), SUV-1SD, SUV2.5, and SUV40 were analyzed.
PET identified five tumors not seen on CT. The sensitivity of PET for identifying primary tumors was 94% (17 of 18). The Sensitivity of PET for staging the neck was 90% (9 of 10), whereas the specificity was 78% (7 of 9). The SUV2.5 method was most likely to overestimate tumor volume, whereas SUV(def) and SUV-1SD were most likely to underestimate tumor volume.
The PET scan provides more accurate staging of primary tumors and nodal metastases for patients with advanced head-and-neck cancer than CT alone. Compared with the gold standard, significant variability exists in volumes obtained by using various SUV thresholds. A combination of clinical, CT, and PET data should continue to be used for optimal treatment planning. The SUV40 method appears to offer the best compromise between accuracy and reducing the risk of underestimating tumor extent.
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