Association of high miR-27a, miR-206, and miR-214 expression with poor patient prognosis and increased chemoresistance in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) represents the most aggressive breast cancer subtype, associated with early metastasis and recurrence as well as poor patient outcome. TNBC does not or weakly respond to hormonal or HER2-targeted therapies. Therefore, there is a strong need to identify other potential molecular targets for TNBC therapy. Micro-RNAs play important roles in the post-transcriptional regulation of gene expression. Thus, micro-RNAs, displaying an association between elevated expression and poor patient prognosis, may represent candidates for such novel tumor targets. In the present study, we evaluated the prognostic impact of miR-27a, miR-206, and miR-214 in TNBC via qPCR in tumor tissue (n=146). In univariate Cox regression analysis, elevated expression of all three analyzed micro-RNAs was significantly associated with shortened disease-free survival (hazard ratio [HR] for miR-27a: 1.85, P=0.038; miR-206: 1.83, P=0.041; miR-214: 2.06, P=0.012). In multivariable analysis, the micro-RNAs remained independent biomarkers for disease-free survival (HR for miR-27a: 1.99, P=0.033; miR-206: 2.14, P=0.018; miR-214: 2.01, P=0.026). Furthermore, our results suggest that elevated levels of these micro-RNAs are linked to enhanced resistance to chemotherapy. Based on the association of high expression levels with shortened patient survival and increased chemoresistance, miR-27a, miR-206, and miR-214 may represent novel molecular targets for TNBC.

Objective gustatory and olfactory dysfunction in COVID-19 patients: a prospective cross-sectional study.

PURPOSE: To determine the prevalence of objective gustatory (GD) and olfactory (OD) dysfunction in COVID-19 patients. METHODS: This is a prospective, cross-sectional study of 51 COVID-19 positive patients diagnosed using RT-PCR-based testing. Of these study participants, 41 reported having present GD and OD at the time of enrollment and ten patients were without symptomatic OD and GD. All participants were objectively tested for OD by Brief Smell Identification Test (BSIT) and for GD by Burghart taste strip test, which were mailed to the participants. The subjective presence and severity of COVID-19 symptoms of smell loss, loss of taste, nasal obstruction, rhinorrhea/mucus production, fever, cough and shortness of breath were also assessed. RESULTS: Of the 41 patients with GD and OD, only 25.6% (10/39; p ≤ 0.0001) objectively presented GD and 39.1% (16/41; p ≤ 0.0001) OD at the time of their subjective dysfunction. Regarding GD, 23.1% (9/39) suffered from total hypogeusia, 2.6% (1/39) from ageusia. A significant loss of sour (33.3% (13/39)) and salty taste (17.9% (7/39)) could be recognized. Only 10.3% (4/39) showed a reduction in sweet and bitter taste. Concerning OD, 9.8% (4/41) showed a deficit relative to younger age in the BSIT and 29.3% (12/41) results abnormal relative to age. CONCLUSION: Subjective and objective findings in GD and OD differ significantly. Most patients suffering from objective dysgeusia present a deficit in sour and salty taste. TRIAL REGISTRATION NUMBER: DRKS00021516; 22/04/2020.

Mood, Anxiety and Olfactory Dysfunction in COVID-19: Evidence of Central Nervous System Involvement?

OBJECTIVE: The objective of this study was to determine the burden of depressed mood and anxiety in COVID-19, and associated disease characteristics. MATERIALS AND METHODS: This is a prospective, cross-sectional study of 114 COVID-19 positive patients diagnosed using RT-PCR-based testing over a 6-week period. The two-item Patient Health Questionnaire (PHQ-2) and the two-item Generalized Anxiety Disorder questionnaire (GAD-2) were used to measure depressed mood and anxiety level, respectively, at enrollment and for participants' baseline, pre-COVID-19 state. Severity of smell loss, loss of taste, nasal obstruction, rhinorrhea/mucus production, fever, cough, and shortness of breath (SOB) during COVID-19 were assessed. RESULTS: PHQ-2 and GAD-2 significantly (P < .001) increased from baseline to enrollment. PHQ-2 was associated with smell loss (adjusted incidence rate ratio [aIRR] = 1.40, 95% CI, 1.10-1.78, P = .006), age (aIRR = 1.02, 95% CI, 1.01-1.04, P = .006), and baseline PHQ-2 score (aIRR = 1.39, 95% CI, 1.09-1.76, P = .007). GAD-2 score was associated with smell loss (aIRR = 1.29, 95% CI, 1.02-1.62, P = .035), age (aIRR = 1.02, 95% CI, 1.01-1.04, P = .025) and baseline GAD-2 score (aIRR = 1.55, 95% CI, 1.24-1.93, P < .001). Loss of taste also exhibited similar associations with PHQ-2 and GAD-2. PHQ-2 and GAD-2 scores were not associated with severities of any other symptoms during the COVID-19 course. CONCLUSIONS: Despite the occurrence of symptoms-such as SOB-associated with severe manifestations of COVID-19, only the severities of smell and taste loss were associated with depressed mood and anxiety. These results may raise the novel possibility of emotional disturbance as a CNS manifestation of COVID-19 given trans-olfactory tract penetration of the central nervous system (CNS) by coronaviruses. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:2520-2525, 2020.

Olfactory Dysfunction and Sinonasal Symptomatology in COVID-19: Prevalence, Severity, Timing, and Associated Characteristics.

OBJECTIVE: Olfactory dysfunction (OD)-hyposmia or anosmia-is a symptom of coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We sought to better determine prevalence, severity, and timing of OD in COVID-19 relative to other sinonasal and pulmonary symptoms. STUDY DESIGN: Prospective, cross-sectional. SETTING: Regional/cantonal hospital. SUBJECTS: In total, 103 patients diagnosed with COVID-19 with reverse transcription polymerase chain reaction (RT-PCR)-based testing. METHODS: All patients testing positive for COVID-19 at Kantonsspital Aarau over a 6-week period were approached. Timing and severity (at its worst, on scale of 0 [none], 1 [mild], 2 [moderate], and 3 [severe]) of OD, loss of taste, nasal obstruction, rhinorrhea/mucus production, fever, cough and shortness of breath (SOB) were assessed for each patient. RESULTS: Prevalence of OD was 61.2%, and severity of OD was strongly correlated with severity of loss of taste experienced (ρ = 0.87, P < .001). OD was experienced on the first day of COVID-19 by 8.7% and overall occurred at median infection day 3 (mean, 3.4; range, 0-12). Most experiencing OD reported anosmia, and mean severity of all with OD was moderate to severe (mean [SD], 2.7 [0.6]). Nasal obstruction (49.5%) and rhinorrhea (35.0%) were frequently reported but not correlated with OD. SOB was more severe in patients with OD. OD was associated negatively with older age (OR, 0.96; 95% CI, 0.93-0.99; P = .007) and positively with female sex (OR, 2.46; 95% CI, 0.98-6.19; P = .056). CONCLUSIONS: OD is highly prevalent during COVID-19, occurring early and severely, often in conjunction with loss of taste. OD is associated negatively with older age and positively with female sex. Patients with OD may also experience more severe SOB.