Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Δευτέρα 22 Φεβρουαρίου 2021

Long‐term neck and shoulder function among survivors of oropharyngeal squamous cell carcinoma treated with chemoradiation as assessed with the neck dissection impairment index

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Abstract

Background

Of interest is the long‐term neck and shoulder impairment of patients treated with primary chemoradiotherapy (CRT). This is important for counseling patients regarding treatment decisions when discussing primary CRT.

Methods

A cross‐sectional study to identify factors that contribute to neck and shoulder dysfunction in patients treated with primary CRT. We utilized the neck dissection impairment index (NDII). Eighty‐seven patients treated between 2003 and 2010, who were free of disease, responded; 24 of these 87 underwent post‐CRT neck dissection. Mean interval since completion of CRT was over 5 years (62.7 months). Mean age, 63.5 years, male:female 75:12.

Results

Mean NDII score was 87.4 (SD 22.1, range 5–100). Multiple linear regression revealed worse NDII scores for patients with larger pre‐CRT gross tumor nodal volume (GTVnodal), controlled for age, sex, body mass index (BMI), and the presence of neck dissection (p = 0.02). There were significant associations with increasing GTVnodal and "low" scores for components of the NDII that assessed neck pain (p = 0.02), neck stiffness (p = 0.01), lifting heavy objects (p = 0.02), reaching overhead (p = 0.02), and ability to do work (p = 0.02). Physical therapy (PT) was evaluated as an "anchor" but it was prescribed "as needed." Regression revealed participation in PT was associated with higher GTVnodal, lower BMI, presence of neck dissection, and female sex (p = 0.00007).

Conclusion

GTVnodal was an independent predictor of neck and shoulder impairment. High GTVnodal was associated with increased pain and stiffness, and increased difficulty lifting heavy objects, reaching overhead, overall ability to perform work‐related tasks and was associated with participation in post‐treatment PT.

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A sprayable Acid-Oxidizing solution containing hypochlorous acid (AOS2020) efficiently and safely inactivates SARS-Cov-2: a new potential solution for upper respiratory tract hygiene.

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A sprayable Acid-Oxidizing solution containing hypochlorous acid (AOS2020) efficiently and safely inactivates SARS-Cov-2: a new potential solution for upper respiratory tract hygiene.

Eur Arch Otorhinolaryngol. 2021 Feb 11;:

Authors: Giarratana N, Rajan B, Kamala K, Mendenhall M, Reiner G

Abstract
INTRODUCTION: To eliminate the COVID-19 pandemic, the transmission of the virus SARS-CoV-2 among the population needs to be blocked and/or at least reduced. Upper respiratory tract viral loads are highest in the early stages of the disease, and high loads are associated with higher mortality rates. This study aims to evaluate the virucidal efficacy of AOS2020, a novel sprayable Acid-Oxidizing solution containing pure and stable hypochlorous acid (HClO), on human coronavirus SARS-Cov-2 in vitro, and the tolerability profile on nasal and oral mucosa suggesting to be a potential solution for upper respiratory hygiene.
METHOD: Virucidal assays and intranasal and oral irritation tests were undertaken in accordance with relevant national and international guidance and methods.
RESULTS: In pre-clinical tests, the AOS2020, showed > 99.8% virucidal efficacy in < 1 min against SARS-Cov-2. The safety profile testing on both the nasal and oral mucosa indicates that AOS2020 is non-irritant.
CONCLUSION: These initial results indicate that this product has the potential treatment to reduce viral load in the upper respiratory tract.

PMID: 33575830 [PubMed - as supplied by publisher]

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Association of Mast Cell Burden and TIM-3 Expression with Recalcitrant Chronic Rhinosinusitis with Nasal Polyps.

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Association of Mast Cell Burden and TIM-3 Expression with Recalcitrant Chronic Rhinosinusitis with Nasal Polyps.

Ann Otol Rhinol Laryngol. 2021 Feb 12;:3489421995038

Authors: Belsky MA, Corredera E, Banerjee H, Moore J, Wang L, Kane LP, Lee SE

Abstract
OBJECTIVES: Previous work showed that higher polyp mast cell load correlated with worse postoperative endoscopic appearance in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Polyp epithelial mast cells showed increased expression of T-cell/transmembrane immunoglobulin and mucin domain protein 3 (TIM-3), a receptor that promotes mast cell activation and cytokine production. In this study, CRSwNP patients were followed post-operatively to investigate whether mast cell burden or TIM-3 expression among mast cells can predict recalcitrant disease.
METHODS: Nasal polyp specimens were obtained via functional endoscopic sinus surgery (FESS) and separated into epithelial and stromal layers via enzymatic digestion. Mast cells and TIM-3-expressing mast cells were identified via flow cytometry. Mann-Whitney U tests and Cox proportional hazard models assessed whether mast cell burden and TIM-3 expression were associated with clinical outcomes, including earlier recurrence of polypoid edema and need for treatment with steroids.
RESULTS: Twenty-three patients with CRSwNP were studied and followed for 6 months after undergoing FESS. Higher mast cell levels were associated with earlier recurrence of polypoid edema: epithelial HR = 1.283 (P = .02), stromal HR = 1.103 (P = .02). Percent of mast cells expressing TIM-3 in epithelial or stromal layers was not significantly associated with earlier recurrence of polypoid edema. Mast cell burden and TIM-3+ expression were not significantly associated with need for future treatment with steroids post-FESS.
CONCLUSIONS: Mast cell load in polyp epithelium and stroma may predict a more refractory postoperative course for CRSwNP patients. The role of TIM-3 in the chronic inflammatory state seen in CRSwNP remains unclear.

PMID: 33576238 [PubMed - as supplied by publisher]

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Mycoplasma pneumoniae pneumonia with pulmonary embolism: A study on pediatric cases in Jilin province of China.

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Mycoplasma pneumoniae pneumonia with pulmonary embolism: A study on pediatric cases in Jilin province of China.

Exp Ther Med. 2021 Mar;21(3):201

Authors: Sheng CQ, Yang CF, Ao Y, Zhao ZY, Li YM

Abstract
Mycoplasma is one of the most common pathogens causing community-acquired pneumonia in pediatric patients. In recent years, the number of refractory or severe cases with drug resistance has been gradually increasing and cases that developed embolism after Mycoplasma pneumoniae (M. pneumoniae) infection have been reported. The present study retrospectively analyzed the clinical features, diagnosis and treatment of M. pneumoniae pneumonia (MPP) combined with pulmonary embolism (PE) in a series of 7 cases encountered between January 1st, 2016 to August 1st, 2019 at the Department of Pediatric Intensive Care Unit of The First Hospital of Jilin University (Changchun, China). Combined with relevant Chinese and international studies published during the last two decades, a comprehensive analysis was performed. All of the pediatric patients of the present study had fever, cough and dyspnea respiratory symptoms at onset and the disease progressed rapidly. Thereafter, PE was confirmed by a series of examinations. Pulmonary CT indicated patchy inflammations and significantly elevated D-dimer levels, accompanied by positive anticardiolipin antibodies. Furthermore, a filling defect in the pulmonary artery branch was observed on CT pulmonary angiography (CTPA) examination. In 2 cases, the condition was improved with anti-infection and anticoagulation treatment with low-molecular-weight heparin and warfarin, respectively, and the pulmonary embolism disappeared after 3-4 months. A total of 5 cases, who were not responsive to the drug treatment, underwent surgical resection. During the operation, the local tissues were determined to be infarcted and the pathological diagnosis was consistent with pulmonary infarction. Among the 5 cases, 2 died of Acute Respiratory Distress Syndrome at 3-8 days after the operation. The remaining patients underwent 6-12 months of follow-up and respiratory rehabilitation and their quality of life is now good. In conclusion, compared with he althy individuals, pediatric patients with critical MPP have an elevated risk of embolism. It is necessary to be vigilant regarding whether MMP is combined with PE and perform timely CTPA examination. Early detection, early treatment and surgical intervention (if necessary) may significantly reduce the risk of mortality and disability.

PMID: 33574906 [PubMed]

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HSP60 participates in the anti-glioma effects of curcumin.

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HSP60 participates in the anti-glioma effects of curcumin.

Exp Ther Med. 2021 Mar;21(3):204

Authors: Bi F, Wang J, Zheng X, Xiao J, Zhi C, Gu J, Zhang Y, Li J, Miao Z, Wang Y, Li Y

Abstract
The chaperone protein heat shock protein 60 (HSP60) is considered a tumor promoter in several types of primary human tumors, where it orchestrates a broad range of survival programs. Curcumin (CCM) is well-established to exhibit several anticancer properties with an excellent safety profile. Our previous study showed that CCM suppresses extracellular HSP60 expression, which is typically released by activated microglia, and acts as an inflammatory factor by binding to Toll-like receptor 4 (TLR-4) on the cell membrane. The present study assessed whether CCM exerted its anti-neuroglioma effects on U87 cells via inhibition of HSP60/TLR-4 signaling, similar to that in microglia. The results demonstrated that CCM significantly inhibited the viability and invasive capacity of neuroglioma U87 cells as evidenced by a Cell Counting Kit-8 assay. Western blotting and ELISA results showed that CCM decreased the expression of HSP60 and its transcriptional factor, heat shock factor 1, and r educed HSP60 release. Accordingly, TLR-4, as the target of HSP60, and its downstream signaling proteins myeloid differentiation primary response 88 (MYD88), NF-κB, inducible nitric oxide synthase and cytokines IL-1β and IL-6 were downregulated by CCM. The expression levels of apoptotic factors associated with NF-κB activation, including TNF-α and caspase-3 were increased in U87 cells by CCM treatment, while p53 expression, a tumor suppressor, was shown to be decreased. Based on the results of the present study, CCM may exert its anti-tumor effects in U87 cells by inhibiting the HSP60/TLR-4/MYD88/NF-κB pathway and inducing tumor cell apoptosis. Thus, CCM may be used as a potential therapy for the clinical treatment of neuroglioma.

PMID: 33574907 [PubMed]

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Dexpanthenol reduces fibrosis and aids repair following nerve laceration and neurorrhaphy.

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Dexpanthenol reduces fibrosis and aids repair following nerve laceration and neurorrhaphy.

Exp Ther Med. 2021 Mar;21(3):207

Authors: Karahan G, Kaya H, Eyceyurt RS, Erdogan MA, Yigitturk G, Erbas O

Abstract
The aim of the present study was to investigate the effect of dexpanthenol on nerve healing following neurorrhaphy in lacerated peripheral nerves. A total of 30 mature Sprague Dawley rats were used. Surgical sciatic nerve dissection and repair was performed on an experimental group of 20 rats. The remaining 10 rats were designated as the control group. The experimental group was divided into 2 subgroups. The surgery + saline group (SSLE; n=10) was given 1 ml/kg 0.9% sodium chloride saline intraperitoneally. The surgery + dexpanthenol group (SDPL; n=10) rats were given 500 mg/kg/day dexpanthenol intraperitoneally. Histological evaluation of the sciatic nerve tissue revealed that the fibrosis score was significantly lower in the SDPL group than in the SSLE group (P<0.001). Electrophysiological evaluation of compound muscle action potential (CMAP) indicated that the CMAP level in the SDPL group was significantly higher than that of the SSLE group (P<0.001), and the CMAP la tency period was lower in the SDPL group compared with the SSLE group (P<0.001). In addition, the SDPL group malondialdehyde level was significantly lower than that of the SSLE group (P<0.001). Functional evaluation with an inclined plane test revealed a significant difference between the SSLE (39.6±5.5˚) and SDPL (79.1±6.93˚) groups (P<0.001). Dexpanthenol was observed to have a positive effect on nerve tissue repaired with neurorrhaphy in a rat sciatic model of laceration-type injuries similar to those frequently encountered in the clinic.

PMID: 33574908 [PubMed]

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NOD-like receptor X1, tumor necrosis factor receptor-associated factor 6 and NF-κB are associated with clinicopathological characteristics in gastric cancer.

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NOD-like receptor X1, tumor necrosis factor receptor-associated factor 6 and NF-κB are associated with clinicopathological characteristics in gastric cancer.

Exp Ther Med. 2021 Mar;21(3):208

Authors: Fan Z, Pan J, Wang H, Zhang Y

Abstract
Gastric cancer (GC) is a common cancer worldwide and its precise mechanism is largely unknown. The aim of the present study was to evaluate the expression levels of NOD-like receptor X1 (NLRX1), tumor necrosis factor receptor-associated factor 6 (TRAF6) and NF-κB in GC and normal gastric tissue samples to determine the association with the clinicopathological features of GC. GC and adjacent normal gastric tissues from 60 patients with GC were analyzed using immunohistochemistry and western blotting analysis. In addition, the association between NLRX1, TRAF6 and NF-κB expression levels were investigated by Spearman's correlation analysis. The results revealed that NLRX1 protein expression levels were downregulated in the GC tissues compared with the normal gastric tissues (P<0.05). Conversely, TRAF6 and NF-κB protein expression levels were upregulated in the GC tissues compared with the normal gastric tissues (P<0.05). A significant difference was identified between G C patients with high and low expression levels of each protein in the tumor size, vascular invasion, neural invasion, lymph node metastasis, differentiation, gross stage and clinical stage. In addition, a negative correlation was observed between NLRX1 and TRAF6, and NLRX1 and NF-κB expression levels, while a positive correlation was observed between TRAF6 and NF-κB expression levels. In conclusion, NLRX1 expression levels were discovered to be downregulated in GC tissues. The expression levels of NLRX1, TRAF6 and NF-κB were also significantly associated with the clinicopathological characteristics of GC, and the aforementioned results indicated that NLRX1 may be a biomarker in assessing GC.

PMID: 33574909 [PubMed]

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Umbilical cord-derived mesenchymal stem cells exert anti-fibrotic action on hypertrophic scar-derived fibroblasts in co-culture by inhibiting the activation of the TGF β1/Smad3 pathway.

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Umbilical cord-derived mesenchymal stem cells exert anti-fibrotic action on hypertrophic scar-derived fibroblasts in co-culture by inhibiting the activation of the TGF β1/Smad3 pathway.

Exp Ther Med. 2021 Mar;21(3):210

Authors: Meng X, Gao X, Chen X, Yu J

Abstract
A hypertrophic scar (HS) is a severe fibrotic skin disease that causes disfigurement and deformity. It occurs after deep cutaneous injury and presents a major clinical challenge. The present study aimed to evaluate the effects of umbilical cord-derived mesenchymal stem cells (UCMSCs) on hypertrophic scar fibroblasts (HSFs), one of the main effector cells for HS formation, in a co-culture system and to investigate the potential underlying molecular mechanism. Cultured HSFs were divided into control and co-culture groups. The proliferation ability of HSFs was evaluated using cell counting kit-8 and the percentage of Ki67-positive fibroblasts was assessed by immunofluorescence. The apoptosis of HSFs was determined using a TUNEL assay and by assessing the expression of capase-3 via western blotting. A scratch wound healing assay was employed to examine the migration of HSFs. The expression levels of HS-associated genes (collagen type Iα 2 chain, collagen type IIIα 1 chain and a ctin α 2 smooth muscle) and proteins (collagen I, collagen III and α-smooth muscle actin) were measured by reverse transcription-quantitative PCR (RT-qPCR) and western blotting, respectively, to assess the pro-fibrotic phenotype of HSFs. The modulation of the transforming growth factor β1 (TGF β1)/Smad3 pathway in HSFs was evaluated by measuring the protein levels of TGF β1, Smad3 and phosphorylated Smad3 using western blotting, and the mRNA levels of TGFβ1 and several other target genes (cellular communication network factor 2, metalloproteinase inhibitor 1 and periostin) were measured by RT-qPCR. The proliferative and migratory ability of co-cultured HSFs was suppressed compared with controls, and no significant difference in apoptosis was observed between the two groups. The pro-fibrotic phenotype of co-cultured HSFs was inhibited due to a decline in expression levels of HS-associated genes and proteins. Furthermore, co-culture with UCMSCs inhibited the activation of the TG F β1/Smad3 pathway. In conclusion, the present study indicated that UCMSCs may exert an anti-fibrotic action on HSFs in co-culture through inhibition of the TGF β1/Smad3 pathway, which suggests a potential use for UCMSCs in HS therapy.

PMID: 33574910 [PubMed]

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A systematic review and meta-analysis of minimally invasive vs. standard percutaneous nephrolithotomy in the surgical management of renal stones.

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A systematic review and meta-analysis of minimally invasive vs. standard percutaneous nephrolithotomy in the surgical management of renal stones.

Exp Ther Med. 2021 Mar;21(3):213

Authors: Jiao B, Luo Z, Huang T, Zhang G, Yu J

Abstract
The present study aimed to assess current evidence on the effectiveness and safety of minimally invasive vs. standard percutaneous nephrolithotomy (PCNL) in the management of renal stones. A systematic search of electronic databases, which included PubMed, EMBASE and the Cochrane Library up to May 2019 was performed. Using Review Manager statistical software (version 5.3), primary outcomes, including stone-free rates (SFRs), were evaluated. Meanwhile, analysis was also performed to compare secondary outcomes, such as peri- and postoperative complications and operative data. Fourteen studies involving 1,611 patients with renal stones were analyzed based on the inclusion criteria. On the basis of the present analysis, mini percutaneous nephrolithotomy (MPCNL) was proven to have non-inferior clinical efficacy with respect to the SFR compared with PCNL [odds ratio (OR)=1.10; 95% confidence interval (CI), 0.84-1.44; P=0.48]. In addition, the meta-analysis showed that MPCNL had a s ignificantly lower hemoglobin decrease [mean difference (MD)=-0.68; 95% CI, -1.05 to -0.31; P=0.0003] and fewer blood transfusions (OR=0.36; 95% CI, 0.18-0.71; P=0.003) compared with PCNL. Moreover, the MPCNL group had a shorter inpatient stay (MD=-0.81; 95% CI, -1.55 to -0.08; P=0.03) compared with the PCNL group. However, the overall evidence was insufficient to suggest a statistically significant difference in the adverse event profile for MPCNL compared with PCNL. The present meta-analysis indicates that MPCNL is an effective method for treating renal stones. Compared with PCNL, MPCNL not only has similarly high SFRs but is also associated with less blood loss, fewer blood transfusions, more favorable recovery time and shorter inpatient stays. However, the findings of the present study should be further confirmed by well-designed prospective randomized controlled trials with a larger patient series.

PMID: 33574911 [PubMed]

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Insulin-like growth factor-1 improves postoperative cognitive dysfunction following splenectomy in aged rats.

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Insulin-like growth factor-1 improves postoperative cognitive dysfunction following splenectomy in aged rats.

Exp Ther Med. 2021 Mar;21(3):215

Authors: Wang B, Lin X, Zhou J, Xie C, Li C, Dong R, Zhang G, Sun X, Wang M, Bi Y

Abstract
Postoperative cognitive dysfunction (POCD) is a serious complication following anesthesia and operations in aged patients undergoing surgical intervention. It is characterized by temporary or permanent cognitive decline, memory impairment and deterioration in language comprehension and social adaption ability. Therefore, the development of POCD prevention and treatment tools has become an area of interest. The current study assessed the therapeutic effects of insulin-like growth factor-1 (IGF-1) on POCD in aged rats and explored the underlying mechanisms. Model rats underwent splenectomy under 1.5-2% isoflurane and mechanical ventilation. IGF-1 (50 µg/kg) was diluted in normal saline and administered by abdominal hypodermic injection daily from the operation to day 7 post-operation. Following splenectomy, the animals showed marked cognitive impairment as determined by the Morris water maze test. Hippocampal protein levels of amyloid precursor protein (APP), β-site APP-cleav ing enzyme-1 (BACE-1), amyloid-β (Aβ), capase3, Bax and Bcl-2 were assessed by immunoblotting. Neuronal apoptosis in the hippocampus was analyzed using a TUNEL assay. The results demonstrated that the levels of APP, BACE-1, Aβ, caspase3 and Bax were increased following splenectomy, while the levels of Bcl2 were reduced at days 1, 3 and 7 post-operation in aged rats. However, IGF-1 downregulated APP, BACE-1, Aβ, capase3 and Bax, and upregulated Bcl2 at these time points following splenectomy. TUNEL staining revealed that administration of IGF-1 significantly reduced neuronal apoptosis in the hippocampal CA1 region following splenectomy. These results indicated that IGF-1 decreased Aβ-protein production and inhibited neuronal apoptosis in the hippocampus following splenectomy, subsequently alleviating POCD.

PMID: 33574912 [PubMed]

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Efficacy and tolerability of sitagliptin and metformin compared with insulin as an initial therapy for newly diagnosed diabetic patients with severe hyperglycaemia.

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Efficacy and tolerability of sitagliptin and metformin compared with insulin as an initial therapy for newly diagnosed diabetic patients with severe hyperglycaemia.

Exp Ther Med. 2021 Mar;21(3):217

Authors: He M, Deng M, Wang J, Fan P, Wang Y, Zhao X, He Y, Shi B, Sui J

Abstract
The safety and efficacy of dipeptidyl peptidase-4 inhibitors in patients newly diagnosed type 2 diabetes mellitus (T2DM) with severe hyperglycaemia have remained to be sufficiently demonstrated. The aim of the present study was to determine whether sitagliptin combined with metformin as an initial treatment had non-inferior outcomes with regards to glycaemic remission and β-cell function recovery to those of standard insulin therapy in this patient group. A prospective observational study was performed comparing the effects of sitagliptin combined with metformin and insulin therapy in a real-world clinical setting. A total of 168 participants were enrolled and received sitagliptin combined with metformin (Sig) or insulin (Ins) for almost 4 weeks. In addition, each group was further stratified into three subgroups, according to glycosylated haemoglobin (HbA1c) levels (<10, 10-12 and >12%). The primary outcomes were β-cell function and changes in fasting plasma glucose (FPG) and HbA1c at the 3-month follow-up. Both insulin and sitagliptin combined with metformin reduced hyperglycaemia and achieved similar glycaemic outcomes, and no significant differences in FPG and HbA1c levels were obtained. No significant changes were observed in β-cell function concomitant with the glucose-lowering effects of the treatments. Of note, participants in the Ins group exhibited weight gain, whereas those in the Sig group had weight loss, with significant differences becoming evident after 1 month, particularly in the HbA1c <10% subgroup. As compared with insulin injection, early treatment with sitagliptin combined with metformin in newly diagnosed patients with T2DM and severe hyperglycaemia produced non-inferior outcomes with regards to glycaemic remission. Therefore, combination of sitagliptin and metformin may be a viable initial treatment option for patients who prefer an alternative to insulin injection. This study was registered with ClinicalTrials.gov un der no. NCT03180281.

PMID: 33574913 [PubMed]

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