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Reliability and toxicity of bevacizumab for neurofibromatosis type 2-related vestibular schwannomas: A systematic review and meta-analysis

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Publication date: November–December 2021

Source: American Journal of Otolaryngology, Volume 42, Issue 6

Author(s): Jianwei Shi, Dafeng Lu, Ruxin Gu, Huaping Sun, Li Yu, Ruihan Pan, Yansong Zhang

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Temporal determinants of tumour response to neoadjuvant rectal radiotherapy

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by Kendrick Koo, Rachel Ward, Ryan L. Smith, Jeremy Ruben, Peter W. G. Carne, Hany Elsaleh

Introduction

In locally advanced rectal cancer, longer delay to surgery after neoadjuvant radiotherapy increases the likelihood of histopathological tumour response. Chronomodulated radiotherapy in rectal cancer has recently been reported as a factor increasing tumour response to neoadjuvant treatment in patients having earlier surgery, with patients receiving a larger proportion of afternoon treatments showing improved response. This paper aims to replicate this work by exploring the impact of these two temporal factors, independently and in combination, on histopathological tumour response in rectal cancer patients.

Methods

A retrospective review of all patients with rectal adenocarcinoma who received long course (≥24 fractions) neoadjuvant radiotherapy with or without chemotherapy at a tertiary referral centre was conducted. Delay to surgery and radiotherapy treatment time were correlated to clinicopathologic characteristics with a particular focus on tumour regression grade. A review of the literature and meta-analysis were also conducted to ascertain the impact of time to surgery from preoperative radiotherapy on tumour regression.

Results

From a cohort of 367 patients, 197 patients met the inclusion criteria. Complete pathologic response (AJCC regression grade 0) was seen in 46 (23%) patients with a further 44 patients (22%) having at most small groups of residual cells (AJCC regression grade 1). Median time to surgery was 63 days, and no statistically significant difference was seen in tumour regression between patients having early or late surgery. There was a non-significant trend towards a larger proportion of morning treatments in patients with grade 0 or 1 regression (p = 0.077). There was no difference in tumour regression when composite groups of the two temporal variables were analysed. Visualisation of data from 39 reviewed papers (describing 27379 patients) demonstrated a plateau of response to neoadjuvant radiotherapy after approximately 60 days, and a meta-analysis found improved complete pathologic response in patients having later surgery.

Conclusions

There was no observed benefit of chronomodulated radiotherapy in our cohort of rectal cancer patients. Review of the literature and meta-analysis confirms the benefit of delayed surgery, with a plateau in complete response rates at approximately 60-days between completion of radiotherapy and surgery. In our cohort, time to surgery for the majority of our patients lay along this plateau and this may be a more dominant factor in determining response to neoadjuvant therapy, obscuring any effects of chronomodulation on tumour response. We would recommend surgery be performed between 8 and 11 weeks after completion of neoadjuvant radiotherapy in patients with locally advanced rectal cancer.

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Videofluoroscopic Swallow Study in Diagnostics of H-Type Tracheoesophageal Fistula in Children

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Ear Nose Throat J. 2021 Jun 30:1455613211021580. doi: 10.1177/01455613211021580. Online ahead of print.

ABSTRACT

Esophageal atresia remains one of the most challenging congenital anomalies of the newborn. It can occur with or without tracheoesophageal fistula (TEF), and to date, there are still no universally recommended diagnostic procedures. The so-called H-type TEF is that without esophageal atresia, and its prevalence is lower than 5% of all TEFs. We present a case repor t of a newborn with regurgitation, vomiting, feeding problems, dyspnea, and repeated aspiration bronchopneumonia. A wide range of diagnostics procedures had been performed with negative results until we used videofluoroscopy, which revealed the H-type TEF and allowed appropriate treatment of the patient.

PMID:34189975 | DOI:10.1177/01455613211021580

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Maxillary Sinus Vascular Malformation or Metastatic Renal Cell Carcinoma: The Importance of Differential Diagnosis

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Abstract

Epistaxis is a common presenting complain with varied differentials. Our case is of epistaxis due to maxillary sinus vascular malformation which could be managed with embolization and endoscopic excision. Histopathologically, the lesion had features of metastatic renal cell carcinoma (RCC). A RCC metastatic lesion masquerading as a maxillary sinus vascular malformation (VM) has been extremely rare in published literature. We present this interesting case of maxillary sinus VM and also briefly review the relevant literature.

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Non-acid reflux and sleep apnea: the importance of drug induced sleep endoscopy

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Published: 30 June 2021
Non-acid reflux and sleep apnea: the importance of drug induced sleep endoscopy
Carlos O'Connor-Reina, Jose Maria Ignacio Garcia, Peter Baptista, Maria Teresa Garcia-Iriarte, Carlos Casado Alba, Monica Perona, Paz Francisca Borrmann, Laura Rodriguez Alcala & Guillermo Plaza
Journal of Otolaryngology - Head & Neck Surgery volume 50, Article number: 42 (2021) Cite this article

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Abstract
Background
We present the first case of a patient with obstructive sleep apnea syndrome (OSA), where drug induced sleep endoscopy was helpful to suspect a non-acid reflux disease and showed an improvement in a swollen epiglottis after treatment. Patient ameliorated significantly his disease only with medical therapy.

Case presentation
A 54-year-old man without significant anatomical findings with obstructive sleep apnea syndrome and non-acid gastroesophageal reflux disease (GERD) disease whose Apnea- hypopnea index (AHI) was significantly reduced with the intake of 500 mg of sodium alginate twice a day for 6 months. Conventional digestive tests such as esophagoscopy and simple- and double-channel 24-h pH-metry suggested mild GERD. Conventional proton-pump inhibitor treatment with pantoprazole (40 mg daily) was started without any improvement in his sleep. Multichannel intraluminal 24-h impedanciometry indicated the presence of severe pathological GER of gaseous origin. The patient's AHI decreased from 25.3 at baseline to 8 after treatment with sodium alginate. A drug-induced sleep endoscopy study showed the changes before and after this treatment and was helpful for the diagnosis.

Conclusions
Thus, medical treatment can be a therapeutic option in some patients with OSA. Multichannel 24-h impedanciometry should be performed when nonacid GERD is suspected.

Background
Gastroesophageal reflux disease (GERD) can be categorized as acid and non-acid types. Non-acid reflux is defined as GERD episodes resulting in an esophageal pH drop to ~ 4.0. It is associated with refractory reflux symptoms in GERD with proton-pump inhibitor (PPI) failure and other extraesophageal symptoms, including coughing [1]. A laryngopharyngeal reflux (LPR) is defined as GERD reaching the laryngopharynx. It is supposed to cause inflammation in the airway and lead to respiratory symptoms. The exact role of reflux in the pathogenesis of obstructive sleep apnea syndrome (OSA) is still unclear, especially for non-acid reflux and LPR [2]. We present the first documented case of a patient with OSA where the epiglottis inflammatory changes after using gastric mucosal protector have been documented with a drug-induced sleep endoscopy (DISE) and correlated with a significant improvement in his apnea-hypopnea index (AHI).

Case presentation
A 54-year-old man was referred from our Department of Pulmonology to our Department of Otorhinolaryngology complaining of continuous positive airway pressure (CPAP) device intolerance. He was not able to use it more than 3 h per night, despite changing masks and improving humidity. He only takes tadalafil 20 mg for erectile dysfunction and showed no other comorbidities. His wife did not complain about his snoring. His main concern was a sensation of suffocation during the night, as well as when lying on his back. His body mass index (BMI) was 23.1 m/kg2. Laboratory polysomnography (PSG) showed 299 snore events per hour, an AHI of 25.3, a saturated oxygen level (Sat O2) minimum of 74%, and an oxygen desaturation index (ODI) of 20.2. Awake rhinofibrolaryngoscopy did not show any anatomical findings that explained the CPAP intolerance showing an epiglottis with normal shape and appearance. In this case, our clinical protocol established the recommendation to perform a DISE. It was done following the European position paper protocol using the VOTE classification in the operating room, starting with the patient in supine position. For sedation, 2% propofol syringe infusion pump with target-controlled infusion (TCI) was used, with a target concentration of 2 ng/ml if progressive increases were requiered: 0.2–0.5 ng / ml. Sedation level was monitored using bispectral index (BIS) (BIS Quatro®. Covidien ILc. MA. USA). When the patient was asleep and actively snoring (BIS between 70 and 50), video-flexible endoscopy (TGH Endoscopia. MACHIDA ENT-30PIII. Spain) was used to assess the upper airway to visualize the site of collapse in real time and recording equipment. During DISE, the head was first turned to the right, then to the left and, finally, the mandibular advance maneuver was performed. The findings were observed for a minimum of two cycles in each segment and for each maneuver.

DISE was done without adverse incident and revealed significant swelling of the epiglottis (Supplementary Video 1). A severely obstructed airway surrounded by fluid compatible with LPR was found (Fig. 1A). The VOTE classification [3] was V1O1T1E2AP, which improved with the Esmarch maneuver.

Fig. 1
figure1
Epiglottis showing changes before (A) and after (B) 6 months of treatment with 500 mg sodium alginate daily

Full size image
Additional file 1: Video S1. Drug-induced sleep endoscopy showing active GER with a swelling epiglottis blocking the airway.

With this diagnosis, the patient was offered a mandibular advancement device, but rejected it for economic reasons. He was referred to our Department of Gastroenterology. A PPI, pantoprazole (40 mg daily), was prescribed. Conventional esophagoscopy and single-channel pH-metry confirmed grade A esophagitis with mild GERD. Two-channel 24-h pH-metry indicated excellent suppression of gastric acid production with the PPI. Patient was recommended to avoid heavy meals for dinner and to raise the head of the bed for sleeping. The patient continued taking pantoprazole for 3 months but without improvement in his sleep symptoms, so he stopped the PPI treatment. During this time, he asked us to perform an epiglottectomy, but we rejected this option because non-acid reflux had not been discounted. Multichannel impedanciometry with 24-h pH-metry was performed and indicated severe alkaline GERD, mainly of gaseous origin (Fig. 2). Non-acid reflux therapy was started with sodium alginate (500  mg twice daily), and his sleep symptoms improved. After 6 months, a control PSG was performed. The AHI had decreased to 8, the Sat O2 min had improved to 87%, and the ODI had declined to 7.7 and snore events decline to 48 per hour. There was no change in his BMI. We performed a new DISE to evaluate the anatomical changes and this showed complete normality, with a VOTE classification of V1O1T1EO (Fig. 1B; Supplementary Video 2).

Fig. 2
figure2
Multichannel impedanciometry (Z1-Z6) 24 h recording with multiple episodes of GER due to non acid reflux (gas). Ph1 showed peaks of non acid reflux (Ph > 4). Channels Z1 to Z6 showed the chapters where there is an increase of the impedance due to gas

Full size image
Additional file 2: Video S2. After 6 months of therapy with 500 mg sodium alginate daily. The epiglottis had recovered its normal shape.

Treatment with CPAP devices may aggravate airway obstruction in patients with a collapsed epiglottis [4]. Surgery in these cases could be an option [5], but it is always essential to evaluate the reason for collapse. In our case, the initial findings suggested a potential association with GERD, and DISE was mandatory for a complete evaluation [6]. A conventional ENT examination did not show any pathological findings of the epiglottis that were visualized during DISE.

Discussion
There is great controversy on the possible link between GERD and OSA [7,8,9]. Some authors have considered that these diseases lack significant association, especially when non-acid GERD is diagnosed [2],. while other authors have shown such relation, especially after multichannel intraluminal impedance pH testing is done [10,11,12].

However there are few studies published about this matter, because the gold standard procedure to diagnose non-acid reflux, is the multichannel intraluminal impedance ph testing and this is expensive, invasive and not well tolerated in all the patients [13].

A recent metanalysis [14] has shown an overall incidence of 45,2% of LPR positivity in OSA patients. However, up to date, there are two studies [2, 15] published focused only in the association between nonacid reflux and sleep disordered breathing who concluded that there is no association between non-acid reflux and OSA. Both studies were prospective case control studies, and they presented a statistical significant difference between BMI, in the OSA and non OSA group. According to Halum et al., in obese patients, the correlation with GERD is also quite clear, but the association with LPR alone is not [16]. We believe BMI can act as a confounding variable that could affect the results of association and prediction of LPR in OSA. Our patient had a normal BMI.

Multichannel impedance pH monitoring enables the quantification of acid and non-acid GERD episodes and contact time and also allows the investigators to distinguish liquid-, gaseous-, and mixed-type GERD [17, 18]. It should be done when reflux symptoms remain after prolonged PPI treatment [2, 11]. It may help understanding persistent cough in patients having OSA and GERD [2, 19]

There is no established formal therapy for patients with non-acid GERD. Treatment is usually based on weight loss, lifestyle changes, having small meals, tobacco and alcohol withdrawal, avoiding late dinners, and elevation of the head during bed rest. Prokinetics such as metoclopramide and domperidone, or mucoprotective agents have been shown to be helpful [17, 18]. Therapy with baclofen has also been suggested to improve the tone of the lower esophageal sphincter [18]. Our patient is now stable after taking sodium alginate 500 mg twice a day, and he is currently considering a laparoscopic Nissen fundoplication procedure to be done.

Alginate–antacid formulations may protect from both acid and non-acid gastro-oesophageal reflux [19]. They have proven efficacy for reducing symptoms in GERD, both as and as add-on therapy for patients experiencing breakthrough symptoms with PPIs [20]. Alginate–antacids have a unique mode of action, creating a viscous antacid gel matrix that can form a physical barrier in the proximal stomach that suppresses reflux events. Alginate–antacids also bind pepsin and bile, potentially removing them from the refluxate. This may contribute to the mucosal protection provided by alginates because pepsin is known to damage oesophageal and laryngopharyngeal mucosa even in weakly acidic reflux (pH 5–6) [21].

This is the first reported case documented with DISE where non-acid-type GERD was demonstrated as the primary cause of airway obstruction. We have shown that the epiglottis has reduced its swelling and the AHI has improved significantly after 6 months of medical therapy with alginate. There are countless other potential explanations for the differences between the two sleep studies and the two DISE studies [22, 23]. However, all of them were exhaustively excluded although retrospectively these factors could be confounding ones: there were no concurrent URTI, the patient does not smoke nor is vaping nor in alcohol use. Environmental exposures, allergies, non-allergic rhinitis, fatigue status, hydration level, and other possible confounding factors were carefully excluded [24]. Finally, positional OSA was also excluded, and tongue weakness or glosoptopsis were also excluded.

This novel case presents an interesting theory that deserves attention and may warrant the design of future studies on the association of OSA and GERD, especially when PPI are not effective and non-acid reflux is suspected.

We understand the limited level of evidence of a case report, but this case can orientate the diagnosis in those patients where, despite proper use of PPIs, symptoms remained.

Conclusions
Thus, non-acid GERD can be a potential cause of OSA in some patients. Medical treatment should be considered before surgery and DISE should be performed in cases where CPAP adaption has failed.

Availability of data and materials
Not applicable.

Abbreviations
AHI:
Apnea-hypopnea index

BMI:
Body mass index

CPAP:
Continuous positive airway pressure

DISE:
Drug-induced sleep endoscopy

ENT:
Ear, nose, and throat

GERD:
Gastroesophageal reflux

LPR:
Laryngopharyngeal reflux

ODI:
Oxygen desaturation index

OSA:
Obstructive sleep apnea syndrome

PPI:
Proton-pump inhibitor

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Acknowledgements
Not applicable.

Funding
Not applicable.

Author information
Affiliations
Otorhinolaryngology Department, Hospital Quiron Salud Marbella, Marbella, Spain

Carlos O'Connor-Reina & Laura Rodriguez Alcala

Otorhinolaryngology Department, Hospital Quiron Salud Campo de Gibraltar, Cádiz, Spain

Carlos O'Connor-Reina

Pulmonology Department, Hospital Quiron Salud Marbella, Marbella, Spain

Jose Maria Ignacio Garcia

Pulmonology Department, Hospital Quiron Salud Campo de Gibraltar, Cádiz, Spain

Jose Maria Ignacio Garcia

Otorhinolaryngology Department, Clinica Universitaria de Navarra, Pamplona, Spain

Peter Baptista

Otorhinolaryngology Department, Hospital Universitario de Valme, Sevilla, Spain

Maria Teresa Garcia-Iriarte

Clinica Universitaria de Navarra, School of Medicine, Pamplona, Spain

Carlos Casado Alba

Digestive Department, Hospital Quironsalud Marbella, Marbella, Spain

Monica Perona

Phonoaudiology Unit. Otorhinolaryngology Department Hospital Universitario Italiano Buenos Aires, Buenos Aires, Argentina

Paz Francisca Borrmann

Otorhinolaryngology Department, Hospital Universitario de Fuenlabrada & Hospital Sanitas la Zarzuela. Universidad Rey Juan Carlos, Madrid, Spain

Guillermo Plaza

Contributions
All authors contribute equally in this manuscript. The author(s) read and approved the final manuscript.

Corresponding author
Correspondence to Carlos O'Connor-Reina.

Ethics declarations
Ethics approval and consent to participate
Consent from the patient was obtained in all the tests in this case report.

Consent for publication
Provided.

Competing interests
Dr. C O'Connor-Reina declares no conflict of interest.

J. Ignacio Garcia declares no conflict of interest.

P. Baptista Jardin declares no conflict of interest.

Mt Garcia Iriarte declares no conflict of interest.

C. Casado Alba declares no conflict of interest.

M. Perona declares no conflict of interest.

PF. Borrmann declares no conflict of interest.

L. Rodriguez Alcala declares no conflict of interest.

G. Plaza declares no conflict of interest.

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O'Connor-Reina, C., Garcia, J.M.I., Baptista, P. et al. Non-acid reflux and sleep apnea: the importance of drug induced sleep endoscopy. J of Otolaryngol - Head & Neck Surg 50, 42 (2021). https://doi.org/10.1186/s40463-021-00526-w

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Received
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30 June 2021

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Keywords
Obstructive sleep apnea
Nonacid reflux disease
Multichannel impedanciometry
Epiglottis
Continuous positive airway pressure
Drug-induced sleep endoscopy
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J Neurol Surg B Skull Base
DOI: 10.1055/s-0041-1731033

Objective The aim of this study is to measure the average corpus callosum (CC) volume of healthy Turkish humans and to analyze the effects of gender and age on volumes, including the genu, truncus, and splenium parts of the CC. Patients and Methods Magnetic resonance imaging brain scans were obtained from 301 healthy male and female subjects, aged 11 to 84 years. The median age was 42 years (min–max: 11–82) in females and 49 years (min–max: 12–84) in males. Corpus callosum and its parts were calculated by using MRICloud. CC volumes of each subject were compared with those of the age and gender groups. Results All volumes of the CC were significantly higher in males than females. All left volumes except BCC were significantly higher than the right volumes in both males and females. The oldest two age groups (50–69 and 70–84 years) were found to have higher bilateral CC volumes, and bilateral BCC volumes were also higher than in the other two age groups (11–29 and 30–49 years). Conclusion The results suggest that compared with females/males, females have a faster decline in the volume of all volumes of the CC. We think that quantitative structural magnetic resonance data of the brain is vital in understanding human brain function and development.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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Decompression of the geniculate ganglion and labyrinthine segments of the facial nerve through a middle cranial fossa approach using an ultrasonic surgical system: an anatomic study

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Eur Arch Otorhinolaryngol. 2021 Jun 30. doi: 10.1007/s00405-021-06966-4. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study is to evaluate the feasibility and the safety of a novel, alternative method for bone tissue management in facial nerve decompression by a middle cranial fossa approach. Several applications of Piezosurgery technology have been described, and the technique has recently been extended to otologic surgery. The piezoelectric device is a bone dissector which, using micro-vibration, preserves the anatomic integrity of soft tissue thanks to a selective action on mineralized tissue.

METHODS: An anatomic dissection study was conducted on fresh-frozen adult cadaveric heads. Facial nerve decompression was performed by a middle cranial fossa approach in all specimens using the piezoelectric device under a surgical 3D exoscope visualization. After the procedures, the temporal bones were examined for evidence of any injury to the facial nerve or the cochleovestibular organs.

RESULTS: In all cases, it was possible to perform a safe dissection of the greater petrosal superficial nerve, the geniculate ganglion, and the labyrinthine tract of the facial nerve. No cases of semicircular canal, cochlea, or nerve damage were observed. All of the dissections were carried out with the ultrasonic device without the necessity to replace it with an otological drill.

CONCLUSION: From this preliminary study, surgical decompression of the facial nerve via the middle cranial fossa approach using Piezosurgery seems to be a safe and feasible procedure. Further cadaveric training is recommended before intraoperative use, and a wider case series is required to make a comparison with conventional devices.

PMID:34191113 | DOI:10.1007/s00405-021-06966-4

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Predictive Value of a Prognostic Model Based on Lymphocyte-to-Monocyte Ratio Before Radioiodine Therapy for Recurrence of Papillary Thyroid Carcinoma

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Technol Cancer Res Treat. 2021 Jan-Dec;20:15330338211027910. doi: 10.1177/15330338211027910.

ABSTRACT

BACKGROUND: The aim of this study was to investigate the predictive value of a prognostic model based on the lymphocyte-to-monocyte ratio (LMR) before radioiodine treatment for the recurrence of papillary thyroid carcinoma (PTC).

METHODS: Clinicopathological data of 441 patients with papillary thyroid cancer were collected retrospectively. The Receiver operating characteristi c (ROC) was used to determine the optimal cut-off value for predicting PTC recurrence by LMR before radioiodine treatment. Recurrence was the endpoint of the study, and survival was estimated by the Kaplan-Meier method, and any differences in survival were evaluated with a stratified log-rank test. Univariate and multifactorial analyses were performed using Cox proportional-hazards models to identify risk factors associated with PTC recurrence.

RESULTS: The ROC curve showed that the best cut-off value of LMR before radioiodine treatment to predict recurrence in patients with PTC was 6.61, with a sensitivity of 54.1%, a specificity of 73%, and an area under the curve of 0.628. The recurrence rate was significantly higher in the low LMR group (16%) than in the high LMR group (5%) (P = 0.001, χ2 = 12.005). Multifactorial analysis showed that LMR < 6.61 (P = 0.006; HR = 2.508) and risk stratification (high risk) (P = 0.000; HR = 5.076) before ra dioiodine treatment were independent risk factors predicting recurrence in patients with PTC. Patients with preoperative LMR < 6.61 and high risk stratification had the lowest recurrence-free survival rate and the shortest recurrence-free survival time.

CONCLUSIONS: The LMR-based prognostic model before radioactive iodine treatment is valuable for early prediction of PTC recurrence and it can be used in clinical practice as a supplement to risk stratification and applied in combination to help screen out patients with poorer prognosis early.

PMID:34191658 | DOI:10.1177/153303382110 27910

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