Publications by authors named "Christian von Buchwald"

218 Publications

[Head and neck ultrasound examination].

Ugeskr Laeger 2021 Feb;183(7)

Head and neck ultrasound examination is increasingly used as point-of-care imaging among clinicians from different specialities to improve the diagnostic workup and perform ultrasound-guided interventions. Ultrasound can provide immediate information about morphology and anatomic relation of lumps and bumps of the neck and guide treatment of various lesions varying from patients with putative head and neck cancer to patients with acute neck abscess. This review describes the principles of a systematic head and neck ultrasound examination and the most common pathologies diagnoses with benefit by ultrasound.
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February 2021

Manuscript title: the maxillary swing approach - the first Scandinavian experience.

Acta Otolaryngol 2021 Feb 27:1-12. Epub 2021 Feb 27.

Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Background: The maxillary swing approach was introduced three decades ago in the head and neck field providing optimal surgical exposure for tumors in the nasopharyngeal and/or the retromaxillary space.

Objectives: To report the clinical experience, patient surgical morbidity and survival outcomes following the introduction of the maxillary swing approach in Denmark.

Material And Methods: A retrospective study including patients who underwent the maxillary swing approach from January 2012 - January 2020. Baseline and perioperative data, pathology, postoperative morbidity and survival outcomes were registered.

Results: Sixteen patients were included of which 15 had a malignant tumor with different histology, while one patient had a benign tumor. Most commonly reported short-term morbidity were trismus, cheek hypoesthesia, nasopalatal fistula, lacrimation and nasal stenosis (<3 months postoperatively) improving markedly at 12 months follow-up. For patients with malignant tumors, the 5-year overall survival and recurrence-free survival rates were 60% and 66.7%, respectively.

Conclusions And Significance: The maxillary swing approach was safely implemented by a multidisciplinary team at a high-volume centralized head and neck cancer center in Denmark. The procedure may be considered for salvage surgery of recurrent nasopharyngeal carcinomas and selected malignant and benign tumors located in the nasopharynx and/or retromaxillary space inaccessible by other surgical modalities.
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http://dx.doi.org/10.1080/00016489.2021.1884746DOI Listing
February 2021

Incidence and survival of salivary gland cancer in children and young adults in Denmark: A nation-wide study for the period 1990-2015.

Int J Pediatr Otorhinolaryngol 2021 Feb 1;143:110637. Epub 2021 Feb 1.

Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Denmark.

Objectives: The aim of this study was to evaluate incidence and survival of children and young adults with salivary gland cancer (SGC) in Denmark during the period 1990-2015.

Method: We included all patients aged 0-24 years registered with primary SGC in the Danish Cancer Registry, the Danish Pathology Data Bank, or the DAHANCA database during 1990-2015. Patients were divided in two age-groups: children (0-17 years) and young adults (18-24 years). Incidence rates, overall survival (OS), and recurrence free survival (RFS) was evaluated in relation to age-group, sex, tumor location, tumor histology, and T-, N-, and M-classification.

Results: A total of 70 SGC patients between 0 and 24 years (67% female, n = 47) were included. Thirty-six were children at time of diagnosis, and 34 were young adults. The incidence was higher among young adults compared to children (0.29 vs. 0.11 per 100.000) and showed no significant change during the study period. There were no differences in the distribution of sex, tumor location, or tumor histology between children and young adults. The total 5 and 15-year survival rates were 97.1% and 91.7% for OS, and 97.1% and 83.1% for RFS. The survival rates showed no significant differences according to age-groups, sex, tumor location, or tumor histology. Patients diagnosed in stage T4 had significantly worse OS and RFS.

Conclusion: The incidence of SGC among children and young adults in Denmark was low and stable in the period 1990-2015. The overall survival was very high, demonstrating the excellent prognosis for children and young adults with SGC.
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http://dx.doi.org/10.1016/j.ijporl.2021.110637DOI Listing
February 2021

COVID-19 infection rate among tertiary referral center otorhinolaryngology healthcare workers.

Eur Arch Otorhinolaryngol 2021 Feb 5. Epub 2021 Feb 5.

Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.

Importance: Otorhinolaryngology is considered one of the medical specialties with a high risk for exposure to corona disease 2019 (COVID-19). Uncontrolled transmission in a hospital department poses a risk to both healthcare workers (HCWs) and patients.

Objective: To monitor SARS-CoV-2 incidence, transmission, and antibody development among HCWs to identify high risk procedures, pathways, and work areas within the department.

Methods: Prospective cohort study of HCWs using repetitive oro- and nasopharygeal swab samples, antibody tests, and self-reported symptoms questionnaires at a tertiary referral center in Copenhagen, Denmark.

Results: 347/361 (96%) HCWs participated. Seven (1.9%) were positive on swab tests and none had symptoms. Fifteen (4.2%) developed antibodies. Only one case of potential transmission between HCWs was identified. Infection rates were low and no procedures or areas within the department were identified as exposing HCWs to a higher risk.

Conclusions And Relevance: Adherence to the surveillance program was high. The low incidence among HCW during the first wave of the COVID-19 pandemic may reflect local transmission and infection control precautions, as well as a low infectious burden in the Danish society.
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http://dx.doi.org/10.1007/s00405-021-06615-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862982PMC
February 2021

The impact and prevalence of SARS-CoV-2 in patients with head and neck cancer and acute upper airway infection in a tertiary otorhinolaryngology referral center in Denmark.

Eur Arch Otorhinolaryngol 2021 Jan 3. Epub 2021 Jan 3.

Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark.

Purpose: To determine the prevalence of SARS-CoV-2 at a Danish tertiary referral otorhinolaryngology clinic during the first wave of the COVID-19 pandemic among patients with suspected acute upper airway infection (UAI) and patients operated for head and neck cancer (HNC), respectively. To monitor changes in the number of patient encounters for acute UAI and the number of referrals for the workup of HNC.

Trial Registration: NCT-04356560 (Clinicaltrials.gov).

Methods: Prospective enrolled case series of all patients with suspected acute UAI (n = 88) and of patients undergoing surgery for HNC (n = 96), respectively, from March 23rd to May 5th, 2020, at a public tertiary referral otorhinolaryngology clinic in Denmark. SARS-CoV-2 was diagnosed with nasopharyngeal and oropharyngeal swabbing. Patients with suspected acute UAI had symptoms and definitive diagnoses registered in a database. Trends in the number of referrals and patient encounters were retrieved from an electronic patient journal system and analyzed retrospectively.

Results: Eighty-eight patients with acute UAI were enrolled including 55 men and 34 women, median age of 31 years (range: 10 months to 82 years). One patient (1.1%) tested positive. Among 96 patients operated for HNC, zero tested positive. The number of referrals for HNC workup, and patient encounters for peritonsillar abscesses, decreased markedly in the first 3 weeks.

Conclusion: The prevalence of SARS-CoV-2 during the first 6 weeks of the first wave was minimal among patients with acute UAI and zero among patients operated for HNC. The decrease in referrals for the workup of HNC may increase time to treatment initiation and patient morbidity.
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http://dx.doi.org/10.1007/s00405-020-06514-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778690PMC
January 2021

Impact of time to treatment initiation for patients with oral cavity squamous cell carcinoma: a population-based, retrospective study.

Acta Oncol 2020 Dec 26:1-6. Epub 2020 Dec 26.

Department of Otorhinolaryngology, Head and Neck Surgery, and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Background: The increasing incidence of oral cavity squamous cell carcinoma (OSCC) is challenging the capacity to treat patients efficiently. The aim of this study was to evaluate the impact of time to treatment initiation (TTI) on overall survival (OS) and recurrence free survival (RFS) for patients with primary OSCC.

Material And Methods: All patients with primary OSCC treated with curative intent at Rigshospitalet in the period 2000-2014 with known date of diagnosis and treatment initiation were included. Correlation analyses between TTI and Charlson comorbidity index (CCI), UICC stage, and year of diagnosis were performed in addition to uni- and multivariate Cox proportional hazard regression analyses. Further, interaction analysis of TTI and UICC stage were conducted.

Results: Eight hundred and sixty-two patients (64% men) with a median age at diagnosis of 62 years (range: 28-95 years) were included. The median TTI was 31 days (range: 2-137 days). Correlation analyses showed correlations between TTI and CCI, TTI and UICC stage, and TTI and year of diagnosis (rho = -0.10, -value = <.01; rho = 0.16, -value = <.001; rho = -0.47 -value = <.001). Univariate analyses showed a statistically significant increase in hazard ratio for both OS and RFS with a five-day increase in TTI (HR = 1.05, 95%CI: 1.02-1.07 and HR = 1.04, 95%CI: 1.02-1.07). However, when adjusting for age, sex, smoking, UICC stage, tumor sublocation, CCI, and year of diagnosis in a multivariate analysis, the increase in HR with TTI was not statistically significant. There was no statistically significant interaction between TTI and UICC stage.

Conclusion: Survival of OSCC patients decreased with increasing TTI, yet not statistically significant in multivariate analysis. There was no difference in the effect of TTI between patients diagnosed in low or advanced stages.
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http://dx.doi.org/10.1080/0284186X.2020.1863462DOI Listing
December 2020

Correction to: Major driver mutations are shared between sinonasal intestinal-type adenocarcinoma and the morphologically identical colorectal adenocarcinoma.

J Cancer Res Clin Oncol 2020 Dec 8. Epub 2020 Dec 8.

Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark.

In the original article, the reference Hwang et al. 2019 is incorrect.
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http://dx.doi.org/10.1007/s00432-020-03473-7DOI Listing
December 2020

Long-term quality of life & functional outcomes after treatment of oropharyngeal cancer.

Cancer Med 2021 Jan 4;10(2):483-495. Epub 2020 Dec 4.

Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Functional and QoL outcomes were compared longitudinally in a cohort of patients treated for oropharyngeal squamous cell carcinoma (OPSCC) with primary transoral robotic surgery (TORS) or radiotherapy (RT). Forty-four patients undergoing primary TORS (n = 31) or RT (n = 13) for any stage OPSCC were included. Only low-stage disease was treated with TORS. Functional outcomes were: salivary flow rate, image-based swallowing function, and a self-reported 10-point scale comparing current swallowing function to baseline (CvB scale). QoL was assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30), Head & Neck Module (EORTC QLQ-HN35), and MD Anderson Dysphagia Inventory (MDADI). Shoulder impairment was assessed with Neck Dissection Impairment Index (NDII) and Oxford Shoulder Score (OSS). In the RT group, salivary flow rates had significantly declined at 12-month follow-up, with the biggest declines in QoL subscale scores recorded in the RT group for dry mouth and sticky saliva. Swallowing function on imaging studies was overall good, with no severe dysphagia within 1 year although, both treatment groups showed significant deterioration relative to baseline at the 12-month follow-up with increased DIGEST scores and pharyngeal retention. Shoulder impairment was rare at 1 year in both groups. A comprehensive examination of this cohort treated for OPSCC showed overall good functional and QoL outcomes 1 year after treatment. However, persistent impairment was seen in both groups with regards to swallowing function. In the TORS group, at 12-months follow-up, the QoL questionnaires showed worse scores in only one subscale (sticky saliva).
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http://dx.doi.org/10.1002/cam4.3599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877346PMC
January 2021

Penetrating Orbital Sphenoid Sinus Trauma with a Wooden Stick: A Challenging Case Report.

Case Rep Ophthalmol 2020 Sep-Dec;11(3):540-545. Epub 2020 Oct 29.

Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

Transorbital and intra-sphenoidal traumas are relatively uncommon, can be challenging to manage, and are associated with a high risk of complications and potentially fatal outcome. Transorbital and intra-sphenoidal trauma pose a medical challenge due to close relationship to delicate and critical anatomical structures, such as the globe, optic nerve, the ophthalmic internal carotid arteries, and central nervous system. Rapid admission to a level 1 trauma center with a high surgical expertise level is essential to ensure the best possible treatment and outcome. We present a case of a 75-year-old man who had a severe orbital trauma, where a wooden foreign object penetrated the orbit into the sphenoid sinus without penetrating its posterior wall. This case is important because of the rare trauma presentation with a wooden foreign object, which can easily be missed on computed tomography. The case also illustrates the importance of close collaboration between ophthalmologists and rhinologists when challenged with severe orbital sphenoid sinus trauma.
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http://dx.doi.org/10.1159/000510019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670381PMC
October 2020

Lymphoma of the Sublingual Gland: Clinical, Morphological, Histopathological, and Genetic Characterization.

Front Surg 2020 6;7:581105. Epub 2020 Nov 6.

Department of Ophthalmology, Rigshospitalet-Glostrup, Glostrup, Denmark.

Lymphoma of the sublingual gland is rare, representing 1% of all salivary gland lymphomas. In this case report, we present three new cases and compare them to previously published cases, with the aim of characterizing the clinical, morphological, histopathological, and genetic features of this type of malignancy. We provide a clinical description of three cases along with a characterization of the microscopic features, including morphology, and immunohistochemistry. In addition, we analysed possible cytogenetic rearrangements with the use of fluorescence hybridization (FISH). Case 1: A 61-year-old male presenting with a painless swelling of the floor of the mouth diagnosed as extranodal marginal zone lymphoma (EMZL) of the left sublingual gland. The patient is alive with no evidence of disease after his fourth treatment regimen following several relapses. Case 2: A 68-year-old female with a prior history of mantle cell lymphoma (MCL) presenting with a tender swelling of the left sublingual gland as well as the right submandibular gland. The lesions were diagnosed as relapsing MCL. The patient died of unrelated causes after 18 months of treatment. Case 3: A 75-year-old female presenting with a swelling of the floor of the mouth diagnosed as follicular lymphoma (FL) of the left sublingual gland. The patient received chemotherapy along with radiotherapy and was still alive 10 years after the diagnosis. The three cases of sublingual gland lymphomas presented in this case report resemble lymphomas of other major salivary glands. The clinician should be aware of this type of malignancy and that the clinical presentation may not differ from benign lesions or other more common malignancies in this location.
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http://dx.doi.org/10.3389/fsurg.2020.581105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677352PMC
November 2020

Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers : A Randomized Controlled Trial.

Ann Intern Med 2020 Nov 18. Epub 2020 Nov 18.

Herlev & Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark (J.B.N., P.B.N., K.F., R.H., J.H.K., K.I.).

Background: Observational evidence suggests that mask wearing mitigates transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is uncertain if this observed association arises through protection of uninfected wearers (protective effect), via reduced transmission from infected mask wearers (source control), or both.

Objective: To assess whether recommending surgical mask use outside the home reduces wearers' risk for SARS-CoV-2 infection in a setting where masks were uncommon and not among recommended public health measures.

Design: Randomized controlled trial (DANMASK-19 [Danish Study to Assess Face Masks for the Protection Against COVID-19 Infection]). (ClinicalTrials.gov: NCT04337541).

Setting: Denmark, April and May 2020.

Participants: Adults spending more than 3 hours per day outside the home without occupational mask use.

Intervention: Encouragement to follow social distancing measures for coronavirus disease 2019, plus either no mask recommendation or a recommendation to wear a mask when outside the home among other persons together with a supply of 50 surgical masks and instructions for proper use.

Measurements: The primary outcome was SARS-CoV-2 infection in the mask wearer at 1 month by antibody testing, polymerase chain reaction (PCR), or hospital diagnosis. The secondary outcome was PCR positivity for other respiratory viruses.

Results: A total of 3030 participants were randomly assigned to the recommendation to wear masks, and 2994 were assigned to control; 4862 completed the study. Infection with SARS-CoV-2 occurred in 42 participants recommended masks (1.8%) and 53 control participants (2.1%). The between-group difference was -0.3 percentage point (95% CI, -1.2 to 0.4 percentage point;  = 0.38) (odds ratio, 0.82 [CI, 0.54 to 1.23];  = 0.33). Multiple imputation accounting for loss to follow-up yielded similar results. Although the difference observed was not statistically significant, the 95% CIs are compatible with a 46% reduction to a 23% increase in infection.

Limitation: Inconclusive results, missing data, variable adherence, patient-reported findings on home tests, no blinding, and no assessment of whether masks could decrease disease transmission from mask wearers to others.

Conclusion: The recommendation to wear surgical masks to supplement other public health measures did not reduce the SARS-CoV-2 infection rate among wearers by more than 50% in a community with modest infection rates, some degree of social distancing, and uncommon general mask use. The data were compatible with lesser degrees of self-protection.

Primary Funding Source: The Salling Foundations.
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http://dx.doi.org/10.7326/M20-6817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707213PMC
November 2020

The molecular profile of mucosal melanoma.

Melanoma Res 2020 12;30(6):533-542

Eye Pathology Section, Department of Pathology.

Herein, we wanted to explore the molecular landscape of mucosal melanoma from different sites and identify potential molecular targets for future therapy. Mucosal melanomas (N = 40) from different sites (conjunctiva, sinonasal cavity, rectum, and vagina) were investigated. Targeted next-generation sequencing along with Nanostring gene expression profiling was performed. Genetically, conjunctival melanoma was characterized by BRAF-V600E (30%) and NF1 mutations (17%). Mucosal melanomas at nonsun-exposed sites harbored alterations in NRAS, KIT, NF1, along with atypical BRAF mutations. When comparing the gene expression profile of conjunctival melanoma and nonsun-exposed mucosal melanoma, 41 genes were found to be significantly deregulated. Programmed death-ligand 1 (PD-L1) presented a significant sixfold upregulation in conjunctival melanoma compared to the other mucosal melanomas. While melanomas of the sinonasal cavity, vagina, and rectum are molecularly similar, conjunctival melanoma is characterized by a higher frequency of BRAF-V600E mutations and differential expression of several genes involved in the immune response.
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http://dx.doi.org/10.1097/CMR.0000000000000686DOI Listing
December 2020

Autologous fibrin sealant co-delivered with antibiotics is a robust method for topical antibiotic treatment after sinus surgery.

Acta Otolaryngol 2021 Feb 6;141(2):181-186. Epub 2020 Nov 6.

Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Denmark.

Background: Most patients with cystic fibrosis have the risk of pathogenic bacteria being exchanged between their sinuses and lungs.

Aims: A method for topical application of antibiotics where the antibiotics persist for a long period of time is needed.

Material And Methods: Ten patients with cystic fibrosis and bacterial sinusitis were included. Autologous platelet rich fibrin was mixed with an antibiotic solution and sprayed onto the mucosa at the end of an endoscopic sinus surgery; Colistin, a Ciprofloxacin-Colistin combination or Tobramycin was used. The antibiotic concentration was measured in the sinonasal mucus four, seven and 13 days after surgery.

Results: Nine patients had in their nose/sinuses at the time of surgery; in eight of these was not detected by culture at the final visit. In the majority of the ten included patients the antibiotics were continuously released for more than 7 days. No severe side effects were seen.

Conclusions: Autologous platelet rich fibrin co-delivered with antibiotics is a feasible method for topical antibiotic treatment in supplementary to sinus surgery.

Significance: We expect that this treatment is successful for eradication of sinonasal bacterial infections in immunosuppressed patients suffering from recalcitrant sinus infections. The efficacy should be evaluated in randomized controlled trials.
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http://dx.doi.org/10.1080/00016489.2020.1841909DOI Listing
February 2021

Days alive and out of hospital after treatment for oropharyngeal squamous cell carcinoma with primary transoral robotic surgery or radiotherapy - a prospective cohort study.

Acta Otolaryngol 2021 Feb 5;141(2):193-196. Epub 2020 Nov 5.

Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Copenhagen University Hospital Copenhagen, Rigshospitalet, Denmark.

Background: With the rising incidence of oropharyngeal squamous cell cancer, there is a need to assess the burden of treatment.

Aims/objectives: This study assessed 'days alive and out of hospital' (DAOH) in a cohort of patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with either transoral robotic surgery (TORS) or radiotherapy (RT).

Material And Methods: A prospective cohort study conducted between May 2017-June 2019. Primary outcome was DAOH in the first 30 days after treatment (DAOH). The secondary outcome was DAOH.

Results: Forty-four patients were included, 31 treated with TORS and 13 with RT. Patients treated with TORS had a median DAOH of 25 (IQR 22.8-26) including a required four-day postoperative stay- and a median DAOH of 168 (IQR 163-171.3). In contrast, patients treated with RT had a median DAOH of 30 (IQR 26-30) and a DAOH of 143 days (IQR 135.5-149).

Conclusions And Significance: DAOH has not been examined in oropharyngeal cancer before. We found, patients overall spent 92.5% of the first 180 days alive and out of hospital. Patients treated with TORS had high DAOH, which remained high in DAOH, while patients treated with RT with reduced DAOH, had reduced DAOH calling for further large-scale studies.
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http://dx.doi.org/10.1080/00016489.2020.1836395DOI Listing
February 2021

Days alive and out of hospital a validated patient-centred outcome to be used for patients undergoing transoral robotic surgery: protocol and perspectives.

Acta Otolaryngol 2021 Jan 27;141(1):95-98. Epub 2020 Oct 27.

Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Rigshospitalet, Copenhagen, Denmark.

Background: Days Alive and Out of Hospital (DAOH) has been validated as a suitable clinical trial outcome. It can be used as a proxy for surgical quality and reflects both procedure specific morbidity and mortality.

Aims/objectives: We propose DAOH as a supplement to established patient-related and objective outcomes, since it adds information on health care burden. Two upcoming studies incorporating DAOH are planned and will report DAOH for patients undergoing transoral robotic surgery.

Methods: Firstly, a multicentre national prospective cohort study investigating DAOH with a 1-year follow-up after TORS is planned. Secondly a retrospective study of DAOH with a 1-year follow-up period will be performed using our institute's, the largest TORS center in Scandinavia, transoral robotic surgery (TORS) database. The database consists of more than 250 patients with more than 300 procedures performed between 2013 and 2018.

Conclusion And Significance: The planned studies of DAOH may, when applied to TORS, contribute to a better interpretation of post-treatment morbidity and provide a basis for further interventional studies to enhance recovery, perioperative optimization, and serve as a comparison tool between treatment modalities.
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http://dx.doi.org/10.1080/00016489.2020.1814964DOI Listing
January 2021

The impact of comorbidities on survival in oral cancer patients: a population-based, case-control study.

Acta Oncol 2021 Feb 24;60(2):173-179. Epub 2020 Oct 24.

Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Background: Comorbidities have shown to highly influence the outcome and risk of death of head and neck cancer patients. The purpose of this study was to examine the comorbidities among oral cavity squamous cell carcinoma (OSCC) patients, and to investigate the impact of comorbidities on overall survival (OS) and recurrence free survival (RFS).

Methods: Patients diagnosed with OSCC in Eastern Denmark in the period 2000-2014 and treated with curative intend were included. Patients data were linked to the Danish National Patients Register to identify comorbidities based on the Charlson Comorbidity Index (CCI) at the time of diagnosis and five years after diagnosis. Each patient was age-and sex-matched in a 1:10 ratio with an age and sex matched reference group.

Results: A total of 1,183 patients and 11,830 controls were included. Overall this study found comorbidities to be more common among OSCC compared to the reference group both at the time of diagnosis and five years after. The 5-year OS among patients with a CCI score of zero, one, two, and three or above was 60%, 44%, 41%, and 40%, respectively. Similarly, the multivariate cox-regression analysis showed that patients with increasing CCI score also had an increasing risk of death compared to patients with no comorbidities.

Conclusion: OSCC patients had significantly higher comorbidity burden at diagnosis and risk of developing additional comorbidities after diagnosis compared to the reference population. Survival outcomes decreased significantly with higher CCI.
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http://dx.doi.org/10.1080/0284186X.2020.1836393DOI Listing
February 2021

Incidence of head and neck cancer in adolescents and young adults: a Danish nationwide study from 1978-2014.

Acta Oncol 2020 Oct 15:1-4. Epub 2020 Oct 15.

Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

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http://dx.doi.org/10.1080/0284186X.2020.1828618DOI Listing
October 2020

Major driver mutations are shared between sinonasal intestinal-type adenocarcinoma and the morphologically identical colorectal adenocarcinoma.

J Cancer Res Clin Oncol 2020 Oct 13. Epub 2020 Oct 13.

Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark.

Purpose: The purpose of our study was to compare genomic changes in sinonasal intestinal-type adenocarcinoma (sITAC) and colorectal adenocarcinoma (CRC), as they are histomorphologically indistinguishable. This can cause diagnostic difficulties as sinonasal tumours initially diagnosed as sITAC may represent metastasis from CRC, a frequent cancer. Previous studies have not uncovered the underlying mechanism behind the histomorphological resemblance.

Methods/patients: Tissue samples from all consecutive patients with sITAC at our facility (20 patients) were compared to samples from 20 patients with CRC as well as samples from 2 patients with both CRC and sinonasal tumours. DNA sequencing was performed using Illumina TruSight Oncology 500 panel consisting of 523 cancer-associated genes. Frequent mutations were inspected manually using the Integrative Genomics Viewer.

Results: Several well-known cancer-associated genes were mutated in the CRC group, but also in the sinonasal ITAC group. These genes included APC mutated in 65% of the CRC group and 37% of the sinonasal ITAC group, and TP53 mutated in 65% of CRC samples and 58% of ITAC samples. These shared mutations may explain the histomorphological similarities. Successful DNA sequencing was performed on the colorectal sample from one of the two patients with both CRC and sinonasal tumour. Comparing mutations in these samples from one patient we have shown that the sinonasal tumour in all probability was a CRC metastasis.

Conclusion: We have identified several genetic similarities between sITAC and CRC. This discovery brings us closer to understanding mechanisms behind the development of sITAC-and hopefully in the future targeted therapy.
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http://dx.doi.org/10.1007/s00432-020-03421-5DOI Listing
October 2020

Long-term health and socioeconomic outcome of obstructive sleep apnea in children and adolescents.

Sleep Med 2020 11 24;75:441-447. Epub 2020 Aug 24.

Danish Center for Social Science Research (VIVE), Copenhagen, Denmark.

Background: There is limited information about the long-term outcome of obstructive sleep apnea (OSA) diagnosed in children and adolescents for educational and social factors. Here, we estimate the long-term socioeconomic outcome and health care costs of OSA.

Methods: The historical case-control cohort study included Danish individuals with OSA diagnosed in childhood or adolescence between 1994 and 2015. Health care costs and socioeconomic data were obtained from nationwide administrative and health registers. A total of 5419 were diagnosed during this period; of these we traced 1004 patients who we compared with 4085 controls (mean index age, 10.2 years; Standard Deviation (SD), 5.6 years) until the age of 20 years. Controls were matched for age, gender, and residency.

Results: Comparing the OSA patient and control groups at age 20 years we found: 1) lower parental educational level; 2) significantly lower educational level also after adjustment for parental educational level; 3) lower school grade-point averages; 4) lower employment rate and lower income, which was not fully compensated when transfer payments were considered; and 5) patients' initial health care costs were higher due to higher morbidity. Patients showed higher mortality rates than controls (Hazard Ratio (HR) = 7.63, 95% CI = 4.87-11.95, P < 0.001).

Conclusions: OSA in children and adolescent is associated with a significant influence on morbidity, mortality, educational level, grading, social outcome, and welfare consequences.
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http://dx.doi.org/10.1016/j.sleep.2020.08.017DOI Listing
November 2020

New Validated Method for Measuring Fat Graft Retention in the Breast with MRI.

Plast Reconstr Surg Glob Open 2020 Aug 17;8(8):e3052. Epub 2020 Aug 17.

Department of Plastic Surgery and Burns, Rigshospitalet, Copenhagen, Denmark.

In this study, we present a new method for measuring fat graft volume retention in the breast based on magnetic resonance imaging scans and a validation study to assess its accuracy and precision. The method was validated by 4 observers using the magnetic resonance imaging scans of 14 patients undergoing breast augmentation with fat grafting. The method was translated into software and was used to measure the change in breast volume from a preoperative scan to a postoperative scan recorded within 3 hours after the surgery, which was compared with the injected fat graft volume. The new method measured the injected fat graft volumes with an average systematic overestimation of 6.3% (SD, 10.5). The median interobserver variation was <7%. We propose that this new method can be a good alternative to previous techniques for clinical research purposes. The software can be made available upon request free of charge for use on the MeVisLab platform.
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http://dx.doi.org/10.1097/GOX.0000000000003052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489734PMC
August 2020

Sequelae of Major Trauma Patients with Maxillofacial Fractures.

Ann Otol Rhinol Laryngol 2020 Sep 16:3489420958732. Epub 2020 Sep 16.

Trauma Centre and Department of Anesthesia, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Objectives: Sequelae after maxillofacial fractures are frequent and may affect the patient's quality of life. This study examined sequelae associated with maxillofacial fractures of severely traumatized patients focusing mainly on nerve injuries.

Methods: A retrospective study including trauma patients with relevant facial fractures admitted to our Trauma Center in the period 2011-2016. Presence of posttraumatic maxillofacial sequelae was identified by examining the medical records of the included patients. Focusing on facial sensory deficits and facial nerve paralysis, but also comprising data on diplopia, blindness, malocclusion, trismus, eye globe malposition, flattening of the malar, facial contour changes, and wound infections.

Results: Two-hundred-seventy-five severely traumatized patients were included, comprising 201 men (73%), with a median age of 40 years and ISS of 20. 163 (59%) patients only had assessments within 3 months from trauma of which 79 patients (48.5%) had facial complications at initial examination, mostly malocclusion and trismus. Most patients in this group had no or only minor sequelae at their last clinical assessment, mainly being sensory deficits. 112 (41%) patients had assessments both within and beyond 3 months of which 73 patients (65.2%) had facial complications at initial examination, while 91 patients (81%) had reported sequelae within 3 months decreasing to 47 patients (42%) at their last clinical assessment beyond 3 months from trauma, mostly sensory deficits. An improvement of most sequelae was observed.

Conclusion: Objective sequelae were found to be quite common after maxillofacial fractures in severely traumatized patients, especially sensory deficits. However, most of the addressed sequelae seemed to improve over time.
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http://dx.doi.org/10.1177/0003489420958732DOI Listing
September 2020

Self-Collected versus Healthcare Worker-Collected Swabs in the Diagnosis of Severe Acute Respiratory Syndrome Coronavirus 2.

Diagnostics (Basel) 2020 Sep 9;10(9). Epub 2020 Sep 9.

Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark.

The aim of this study was to compare the sensitivity of self-collected versus healthcare worker (HCW)-collected swabs for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing. Symptomatic individuals referred for SARS-CoV-2 testing were invited to provide mobile-phone video-instructed self-collected oropharyngeal and nasal samples followed by a HCW-collected oropharyngeal sample. All samples were sent for analysis to the same microbiology laboratory, and the number of SARS-CoV-2-positive participants in the two tests was compared. A total of 109 participants were included, and 19 participants had SARS-CoV-2-positive results. The diagnostic sensitivity of the self-collected and HCW-collected swabs was 84.2% and 89.5%, respectively, with an acceptable agreement, Cohens kappa 0.82, < 0.001. Further, results from a questionnaire answered by the participants found that loss of smell as a self-reported symptom was a strong predictor for a SARS-CoV-2-positive test. In conclusion, we found that self-collected oropharyngeal and nasal swabs for SARS-CoV-2 testing can be reliable compared to HCW-collected oropharyngeal samples.
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http://dx.doi.org/10.3390/diagnostics10090678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554687PMC
September 2020

Mesenchymal Stem Cell Therapy for Osteoradionecrosis of the Mandible: a Systematic Review of Preclinical and Human Studies.

Stem Cell Rev Rep 2020 12;16(6):1208-1221

Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Background: Osteoradionecrosis (ORN) of the mandible is a severe complication of radiotherapy for head and neck cancer and is arduously difficult to manage. Current treatment options carry risks with some patients remaining incurable. Mesenchymal stromal/stem cell (MSC) therapy has shown promising results supporting osteogenesis and regeneration of radiotherapy-damaged tissues. The aim of this study was to systematically review the literature on the safety and efficacy of MSCs in treating ORN.

Methods: A systematic search was performed on MEDLINE, Embase, Cochranes Library online databases, and clinicaltrials.gov to identify preclinical and clinical studies examining the effect of MSCs on osseous healing of ORN. The preclinical studies were assessed according to the SYRCLEs guidelines and risk of bias tool.

Results: Six studies (n = 142) from 5 countries were eligible for analysis. Of these four were preclinical studies and two clinical case studies. Preclinical studies found MSC treatment to be safe, demonstrating bone restorative effects and improved soft tissue regeneration. In the clinical cases, healing of bone and soft tissue was reported with no serious adverse events.

Conclusion: The evidence from the included studies suggests that MSCs may have beneficial regenerative effects on the healing of ORN. None of the studies reported adverse events with the use of MSCs. More carefully controlled studies with well-identified cells are however needed to demonstrate the efficacy of MSCs in a clinical setting. Graphical abstract.
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http://dx.doi.org/10.1007/s12015-020-10034-5DOI Listing
December 2020

Chronic rhinosinusitis in COPD: A prevalent but unrecognized comorbidity impacting health related quality of life.

Respir Med 2020 09 12;171:106092. Epub 2020 Aug 12.

Department of Otorhinolaryngology - Head and Neck Surgery and Audiology, Copenhagen University Hospital, Rigshospitalet, Denmark.

Introduction: Unified airway disease where upper respiratory tract inflammation including chronic rhinosinusitis (CRS) affects lower airway disease is known from asthma, bronchiectasis, cystic fibrosis and primary ciliary dyskinesia but little is known about CRS and health related quality of life in COPD. We investigate firstly, the prevalence of CRS in COPD. Secondly the impact of CRS on HRQoL. Thirdly, risk factors for CRS in COPD.

Methods: cross-sectional study of CRS in 222 COPD patients from 2017 to 2019 according to EPOS2012/2020 and GOLD2019 criteria. Patients completed the COPD assessment test (CAT), Medical Research Council dyspnea scale and Sinonasal outcome test 22 (SNOT22) and questions on CRS symptoms. They then had a physical examination including flexible nasal endoscopy, CT-sinus scan and HRCT-thorax.

Results: 22.5% of COPD patients had CRS and 82% of these were undiagnosed prior to the study. HRQoL (CAT, SNOT22 and the SNOT22-nasal symptom subscore) was significantly worse in COPD patients with CRS compared with those without CRS and healthy controls. Multiple logistic regression analysis suggests that the most likely candidate for having CRS was a male COPD patient who actively smoked, took inhaled steroids, had a high CAT and SNOT22_nasal symptom subscore.

Discussion: the largest clinical study of CRS in COPD and the only study diagnosing CRS according to EPOS and GOLD. This study supports unified airway disease in COPD. The SNOT22_nasal symptoms subscore is recommended as a standard questionnaire for COPD patients and patients at risk should be referred to an otorhinolaryngologist.
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http://dx.doi.org/10.1016/j.rmed.2020.106092DOI Listing
September 2020

Face masks for the prevention of COVID-19 - Rationale and design of the randomised controlled trial DANMASK-19.

Dan Med J 2020 Aug 18;67(9). Epub 2020 Aug 18.

Introduction: The coronavirus disease 19 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), progresses globally, and means to reduce the transmission are needed. In the community, the use of face masks is increasing world-wide, but documentation for the efficacy of this remedy is lacking. This trial investigates whether the use of face masks in the community will reduce wearers' risk of SARS-CoV-2 infection.

Methods: This study will be a two-arm, unblinded, randomised controlled trial. We will include adults (>18 years of age) without prior confirmed COVID-19 or symptoms suggestive of COVID-19, who spend more than three hours per day outside the home with exposure to other people. A total of 6,000 participants are randomly assigned 1:1 to use face masks or not for a 30-day period during the pandemic. Participants will perform self-testing; quick test for SARS-CoV-2 antibodies (immunoglobulin M (IgM) and immunoglobulin G (IgG)) (the Livzon lateral flow test) and oropharyngeal/nasal swabs for viral detection using polymerase chain reaction (PCR). The primary endpoint following the 30-day study period is the difference in the number of SARS-CoV-2-infected individuals between the two study groups as assessed by a positive nasopharyngeal swap, a positive antibody test or a hospital-based diagnosis of SARS-CoV-2 infection.

Conclusions: We will study whether a face mask protects the wearer of the mask against SARS-CoV-2 infection. The findings are expected to apply to the present pandemic and to future viral outbreaks and to provide evidence for authority recommendations across the world.

Funding: This study was funded by Salling Fondene.

Trial Registration: ClinicalTrials.gov Identifier: NCT04337541.
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August 2020

Clinical Features and Disease Course of Primary Angioedema Patients in a Tertiary Care Hospital.

J Asthma Allergy 2020 17;13:225-236. Epub 2020 Jul 17.

Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.

Purpose: To give a better understanding of primary AE, the clinical characteristics and the possible therapeutic approaches.

Background: Angioedema (AE) is a non-pitting, non-itching swelling of skin or mucosa. The symptom can become life-threatening if located in the airways. Primary (monosymptomatic) AE is a manifestation of several different diseases and the diagnosis is not always straight-forward. The aetiological and pathophysiological factors of primary AE are not completely clarified. There is a need for further investigation.

Patients And Methods: This was a retrospective cohort study of patients referred to an outpatient dermatology clinic in a tertiary care hospital for clinical assessment due to primary AE in the period from 1996 to 2014.

Results: A total of 315 patients were identified with primary AE. The most frequent subtype was idiopathic AE (42.5%) and the second most common was angiotensin-converting enzymeinhibitor (ACEi)-induced AE (31.1%). Three patients were diagnosed with hereditary AE and one patient was diagnosed with acquired C1-inhibitor deficiency. At least 107 (34.0%) patients had established histaminergic AE. More than 1/3 of the patients were treated in an emergency room or hospitalized due to AE. A 98.1% of patients had experienced AE in the head and neck area. Seven patients were in the need of acute airway intervention. Six of these had ACEi-induced AE. Female sex and smoking were found to be risk factors for developing AE.

Conclusion: The most frequent diagnoses were histaminergic-, non-histaminergic idiopathic AE and ACEi-induced AE, whereas complement C1-inhibitor deficiency was rare. Histaminergic AE made up a substantial group of patients with primary AE. Even though there are different pathophysiological causes of AE, many cases have overlapping clinical manifestations, which make diagnosis and treatment difficult.
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http://dx.doi.org/10.2147/JAA.S245161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373665PMC
July 2020

Low-dose aspirin use and risk of head and neck cancer-A Danish nationwide case-control study.

Br J Clin Pharmacol 2021 Mar 14;87(3):1561-1567. Epub 2020 Aug 14.

Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.

Results concerning a potential preventive effect of aspirin on head and neck cancer (HNC) are conflicting. We examined the association between low-dose aspirin use and HNC risk overall and by degree of human papillomavirus association in a nested case-control study using nationwide registries. Cases (n = 12 389) were all Danish residents diagnosed with primary HNC (2000-2015). Age- and sex-matched population controls (n = 185 835) were selected by risk-set-sampling. Using conditional logistic regression, we estimated multivariable-adjusted odds ratios and 95% confidence intervals for HNC associated with low-dose aspirin use (≥2 prescriptions). No association was observed between low-dose aspirin ever-use and overall HNC (odds ratio: 1.03, 95% confidence interval: 0.97-1.10). Estimates remained neutral according to patterns of use. Low-dose aspirin use appeared to slightly decrease HNC risk among the eldest (71-84 y), independently of human papillomavirus association, while slightly increase HNC risk among younger age groups (30-60, 61-70 y), driven by an increased risk of oral cancer. However, no consistent patterns in risk estimates were found according to duration and consistency of low-dose aspirin use in the age-stratified analyses.
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http://dx.doi.org/10.1111/bcp.14502DOI Listing
March 2021

Design and validation of a cross-specialty simulation-based training course in basic robotic surgical skills.

Int J Med Robot 2020 Oct 19;16(5):1-10. Epub 2020 Aug 19.

Department of Otorhinolaryngology, Head & Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Background: The aim of this study was to design and validate a cross-specialty basic robotic surgical skills training program on the RobotiX Mentor virtual reality simulator.

Methods: A Delphi panel reached consensus on six modules to include in the training program. Validity evidence was collected according to Messick's framework with three performances in each simulator module by 11 experienced robotic surgeons and 11 residents without robotic surgical experience.

Results: For five of the six modules, a compound metrics-based score could significantly discriminate between the performances of novices and experienced robotic surgeons. Pass/fail levels were established, resulting in very few novices passing in their first attempt.

Conclusions: This validated course can be used for structured simulation-based basic robotic surgical skills training within a mastery learning framework where the individual trainee can practice each module until they achieve proficiency and can continue training on other modalities and more specific to their specialty.
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http://dx.doi.org/10.1002/rcs.2138DOI Listing
October 2020

Outcome in patients with isolated regional recurrence after primary radiotherapy for head and neck cancer.

Head Neck 2020 Nov 18;42(11):3161-3170. Epub 2020 Jul 18.

Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Background: Isolated regional recurrences following head-neck squamous-cell carcinomas (HNSCC) are often accessible for curatively intended salvage treatment. Factors prognostic for outcome were investigated in a large cohort of HNSCC patients.

Methods: In total, 1811 patients receiving curatively intended radiotherapy from 2007 to 2017 were reviewed and isolated cervical nodal recurrences were identified. Factors associated with survival and second recurrence were investigated using univariate and multivariate analyses.

Results: Isolated regional recurrence was seen in 95/1811 (5.2%) patients. Eighty of 95 patients (84%) received salvage surgery. Two-year survival after isolated regional recurrence was 40%. Overall survival (OS) and time to second recurrence were associated with resection status of the salvage surgery and presence of extranodal spread (ENS), while p16-positive oropharyngeal squamous-cell carcinoma (OPSCC) was associated with better OS.

Conclusion: Long-term survival after regional recurrence in HNSCC is possible. p16-positive OPSCC, complete salvage surgery, and lack of ENS are associated with better outcome.
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http://dx.doi.org/10.1002/hed.26361DOI Listing
November 2020

Development of depression in patients with oral cavity cancer: a systematic review.

Acta Otolaryngol 2020 Oct 9;140(10):876-881. Epub 2020 Jul 9.

Department of Otorhinolaryngology, Head and Neck Surgery, and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Background: The incidence of oral cancer is approximately 300,000 patients annually. A cancer diagnosis and treatment affect both physical and mental issues.

Objectives: The aim of this systematic review was to examine the development of depression in patients who have been treated for oral squamous cell carcinoma (OSCC).

Material And Methods: PubMed and EMBASE were systematically searched for studies addressing depression among patients treated for OSCC and published within the past ten years.

Results: We identified three studies comprising 528 patients (range: 75-349), primarily men (66-83%), treated for OSCC from Europe and India. Tumour stage, treatment modality, and scales used to evaluate depressive symptoms varied in the studies. The European studies showed that 28% of the patients experienced depressive symptoms on the Hospital Anxiety and Depression Scale (HADS) and a mean of 8.0 on depression in the Brief Symptom Inventory (BSI). The Indian study showed a significant increase ( Value < .001) from moderate to severe depressive symptoms on the Depression, Anxiety, and Stress Scale-21 (DASS-21). This systematic review showed that OSCC patients are at risk of developing depressive symptoms after treatment, though severity of symptoms varied. This knowledge could preferably be implemented in future follow-up regimes.
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http://dx.doi.org/10.1080/00016489.2020.1778785DOI Listing
October 2020