Nevin Manimala

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2022 Jan;36(1):8-13. doi: 10.13201/j.issn.2096-7993.2022.01.002.

ABSTRACT

Objective:The purpose of this study was to compare the olfactory function examination results of patients with post-viral olfactory dysfunction（PVOD） in different prognostic groups and analyze prognostic factors, especially the influence of olfactory bulb volume（OBV） on prognosis, so as to provide objective basis for clinical diagnosis and treatment. Methods:After approval by the hospital ethics committee, the patients with PVOD admitted to Beijing Anzhen Hospital’s outpatient department from January 2019 to December 2019 were followed up for at least 1 year. These patients completed the Sniffin’ Sticks test and MRI examination of the olfactory pathway before treatment. According to the results of the Sniffin’ Sticks test after 1 year follow-up（threshold-discrimination-identification（TDI） score of the patients was increased at least 6 points）, the patients were divided into two groups as the improvement group and the non-improvement group. The prognostic factors of PVOD patients were preliminarily determined by comparing the differences of various factors and the results of olfactory function examination between the two groups. Results:In this study, 47 patients with PVOD were included, with the smell improvement rate was 53.2%. Compared with the improvement group, the patients in the non-improvement group had longer duration, poorer initial olfactory function, higher olfactory threshold, and poorer olfactory discrimination and recognition ability（All P<0.01）. There was no statistical difference in terms of gender, age, allergic rhinitis and smoking between the two groups（All P>0.05）.The OBV of the non-improvement group was （59.48±23.92） mm³, which was significantly lower than that in the improvement group（[92.77±14.35]mm³, P<0.001）. Multiple logistic regression analysis showed that prognostic factors included course of disease（OR 0.677, 95%CI 0.461-0.993, P=0.046）, initial T value（OR 263.806, 95%CI 1.028-67 675.884, P=0.049） and OBV（OR 1.160, 95%CI 1.002-1.343, P=0.047）. The area under the receiver operating characteristic curve（ROC curve） of OBV was 0.888（0.797-0.979, P<0.001）. The correct diagnostic index of OBV≥78.50 mm³was used to determine the prognosis of olfactory function, with a specificity of 0.818 and a sensitivity of 0.840. The ROC curve analysis showed that the area under the ROC curve of duration was 0.822（0.703-0.940, P<0.001）. The correct diagnostic index of the duration ≤6 months was used to determine the prognosis of olfactory function, with a specificity of 0.727 and a sensitivity of 0.800. The area of T score was 0.793（0.662-0.924, P=0.001）. T score ≥1.25 was used as the correct diagnostic index to determine the prognosis of olfactory function. The specificity and sensitivity were 0.818 and 0.680, respectively. Conclusion:The prognosis of olfactory function in PVOD patients is related to the course of disease, the degree of olfactory loss and OBV. Those with no improvement in olfactory function have a longer disease course, aggravated olfactory damage and reduced OBV than those with improved olfactory function. The factors of Duration ≤6 months, T value ≥1.25 and OBV≥78.50 mm³suggested better prognosis, and the results of objective olfactory examination have greater value in evaluating the prognosis of olfactory function.

PMID:34979611 | DOI:10.13201/j.issn.2096-7993.2022.01.002

Infect Chemother. 2021 Dec;53(4):767-775. doi: 10.3947/ic.2021.0125.

ABSTRACT

BACKGROUND: Neutralizing antibody cocktail therapy, REGN-COV2, is promising in preventing a severe form of coronavirus disease 2019 (COVID-19), but its effectiveness in Japan has not been fully investigated.

MATERIALS AND METHODS: To evaluate the effectiveness of REGN-COV2, clinical data of 20 patients with COVID-19 who received REGN-COV2 was compared with the control by matching age and sex. The primary outcome was the time from the onset to defervescence, the duration of hospitalization, and oxygen requirement. A sensitivity analysis using Bayesian analysis was also conducted.

RESULTS: The time to defervescence was significantly shorter in the treatment group (5.25 vs. 7.95 days, P = 0.02), and so was the duration of hospitalization (7.115 vs. 11.45, P = 0.0009). However, the oxygen therapy requirement did not differ between the two groups (15% vs. 35%, P = 0.27). For Bayesian analysis, the median posterior probability of the time to defervescence since the symptom onset on the REGN-COV2 group was 5.28 days [95% credible interval (CrI): 4.28 – 6.31 days], compared with the control of 7.99 days (95% CrI: 6.81 – 9.24 days). The posterior probability of the duration of the hospitalization on the REGN-COV2 group was 7.17 days (95% CrI: 5.99 – 8.24 days), compared with the control of 11.54 days (95% CrI: 10.28 – 13.14 days). The posterior probability of the oxygen requirement on the REGN-COV2 group was 18% (95% CrI: 3 – 33%), compared with the control of 36% (95% CrI: 16 – 54%).

CONCLUSION: REGN-COV2 may be effective in early defervescence and shorter hospitalization. Its effectiveness for preventing a severe form of infection needs to be evaluated by further studies.

PMID:34979607 | DOI:10.3947/ic.2021.0125

J Breast Cancer. 2021 Dec;24(6):504-519. doi: 10.4048/jbc.2021.24.e53.

ABSTRACT

PURPOSE: We aimed to investigate whether obtaining a higher level of education was causally associated with lower breast cancer risk and to identify the causal mechanism linking them.

METHODS: The main data analysis used publicly available summary-level data from 2 large genome-wide association study consortia. Mendelian randomization (MR) analysis used 65 genetic variants derived from the Social Science Genetic Association Consortium as instrumental variables for years of schooling. The outcomes from the Breast Cancer Association Consortium (BCAC) were the overall breast cancer risk (122,977 cases/105,974 controls in women) and the two subtypes: estrogen receptor (ER)-positive breast cancer and ER-negative breast cancer. Fixed and random effects inverse variance weighted methods were used to estimate the causal effects, along with other additional MR methods for sensitivity analyses.

RESULTS: Results showed that each additional standard deviation of 4.2 years of education was causally associated with a 27% lower risk of ER-negative breast cancer (odds ratio, 0.73; 95% confidence interval, 0.64-0.84; p-value < 0.001). This finding was consistent with the results of the sensitivity analyses. Physical activities can help improve the protective effect of education against breast cancer, with relatively large mediation proportions. Education increases the risk of ER-positive breast cancer due to alterations in high-density lipoprotein level, triglyceride level, height, waist-to-hip ratio, body mass index, and smoking status, with relative medium mediation proportions. Other mediators including low-density lipoprotein, hip circumference, number of cigarettes smoked per day, time spent performing light physical activity, and performing vigorous physical activity for > 10 minutes explain a small part of the causal effect of education on the risk of developing breast cancer, and their mediation proportion is approximately 1%.

CONCLUSION: A low level of education is a causal risk factor in the development of breast cancer as it is associated with poor lipid profile, obesity, smoking, and types of physical activity.

PMID:34979597 | DOI:10.4048/jbc.2021.24.e53

J Breast Cancer. 2021 Dec;24(6):491-503. doi: 10.4048/jbc.2021.24.e55.

ABSTRACT

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the rates of screening, case identification, and referral for cancer diagnosis. We investigated the diagnosis and surgery status of breast cancer before and after the COVID-19 pandemic at a multi-institutional level.

METHODS: We collected breast cancer data from the clinical data warehouse which contained the medical records of patients from six academic institutions in South Korea. Patients were divided into two groups: February to April (period A) and May to July (period B). The data from the two groups were then compared against the same periods in 2019 and 2020. The primary objective was to investigate the differences in breast cancer stages before and after the COVID-19 pandemic.

RESULTS: Among 3,038 patients, there was a 9.9% reduction in the number of diagnoses in 2020. This decrease was more significant during period A than period B. The breast cancer stage was not statistically different in period A (p = 0.115), but it was in period B (p = 0.001). In the subset analysis according to age, there was a statistical difference between 2019 and 2020 in period B for patients under the age of 65 years (p = 0.002), but no difference was observed in the other groups.

CONCLUSION: The number of breast cancer cases declined during the pandemic, and the staging distribution has changed after the pandemic peak.

PMID:34979596 | DOI:10.4048/jbc.2021.24.e55

J Knee Surg. 2022 Jan 3. doi: 10.1055/s-0041-1740926. Online ahead of print.

ABSTRACT

BACKGROUND: The use and the optimal timing of tourniquet during primary total knee arthroplasty (TKA) is controversial. Most previous studies failed to show clinically significant differences in different strategies. The aim of this study was to determine how three strategies of tourniquet application affect the outcome in TKA patients.

METHODS: This was a prospective randomized controlled study. Patients who undergo TKA were randomized into one of the three groups (1:1:1 ratio): tourniquet inflated from skin incision to cement hardening, tourniquet from cement application to hardening, and tourniquet from skin incision to skin closure. The perioperative blood loss, limb swelling, and complications were recorded. The level of hemoglobin, hematocrit, C-reactive protein (CRP), interleukin (IL)-6, creatine kinase (CK), and lactate dehydrogenase (LDH) were determined. Patients’ thigh and TKA wound pain, Knee Society knee score (KSKS) and Knee Society functional assessment (KSFA) scores, and rehabilitation parameters were evaluated.

RESULTS: A total of 90 patients were enrolled. The baseline characteristics were comparable. We only found significant difference in the intraoperative blood loss (skin to cement: 58.7 ± 36.1 mL, cement-only: 147.8 ± 107.9 mL, skin to skin: 16.3 ± 13.1 mL, p < 0.0001). There were no statistical differences in postoperative drainage, thigh/knee circumference, change of hemoglobin/hematocrit, CRP, IL-6, CK, and LDH on day 1 to day 4 after surgery. The thigh/TKA wound Visual Analogue Scale scores, KSKS score, KSFA score, and rehabilitation parameters were not significantly different at up to 6-month follow-up. No thromboembolic events were noted.

CONCLUSION: Our results revealed that there was no best tourniquet strategy in TKA. Different tourniquet methods can be utilized based on surgeon preference without affecting outcomes.

PMID:34979585 | DOI:10.1055/s-0041-1740926

J Knee Surg. 2022 Jan 3. doi: 10.1055/s-0041-1741000. Online ahead of print.

ABSTRACT

Selection of appropriate candidates for simultaneous bilateral total knee arthroplasty (si-BTKA) is crucial for minimizing postoperative complications. The aim of this study was to develop a scoring system for identifying patients who may be appropriate for si-BTKA. Patients who underwent si-BTKA were identified in the National Surgical Quality Improvement Program database. Patients who experienced a major 30-day complication were identified as high-risk patients for si-BTKA who potentially would have benefitted from staged bilateral total knee arthroplasty. Major complications included deep wound infection, pneumonia, renal insufficiency or failure, cerebrovascular accident, cardiac arrest, myocardial infarction, pulmonary embolism, sepsis, or death. The predictive model was trained using randomly split 70% of the dataset and validated on the remaining 30%. The scoring system was compared against the American Society of Anesthesiologists (ASA) score, the Charlson Comorbidity Index (CCI), and legacy risk-stratification measures, using area under the curve (AUC) statistic. Total 4,630 patients undergoing si-BTKA were included in our cohort. In our model, patients are assigned points based on the following risk factors: +1 for age ≥ 75, +2 for age ≥ 82, +1 for body mass index (BMI) ≥ 34, +2 for BMI ≥ 42, +1 for hypertension requiring medication, +1 for pulmonary disease (chronic obstructive pulmonary disease or dyspnea), and +3 for end-stage renal disease. The scoring system exhibited an AUC of 0.816, which was significantly higher than the AUC of ASA (0.545; p < 0.001) and CCI (0.599; p < 0.001). The BTK Safety Score developed and validated in our study can be used by surgeons and perioperative teams to risk stratify patients undergoing si-BTKA. Future work is needed to assess this scoring system’s ability to predict long-term functional outcomes.

PMID:34979584 | DOI:10.1055/s-0041-1741000

J Gerontol A Biol Sci Med Sci. 2022 Jan 3:glab386. doi: 10.1093/gerona/glab386. Online ahead of print.

ABSTRACT

Increased mechanistic insight into the pathogenesis of knee osteoarthritis (KOA) is needed to develop efficacious disease-modifying treatments. Though age-related pathogenic mechanisms are most relevant to the majority of clinically-presenting KOA, the bulk of our mechanistic understanding of KOA has been derived using surgically induced post-traumatic OA (PTOA) models. Here, we took an integrated approach of meta-analysis and multi-omics data analysis to elucidate pathogenic mechanisms of age-related KOA in mice. Protein-level data were integrated with transcriptomic profiling to reveal inflammation, autophagy, and cellular senescence as primary hallmarks of age-related KOA. Importantly, the molecular profiles of cartilage aging were unique from those observed following PTOA, with less than 3% overlap between the two models. At the nexus of the three aging hallmarks, Advanced Glycation End-Product (AGE)/Receptor for AGE emerged as the most statistically robust pathway associated with age-related KOA. This pathway was further supported by analysis of mass spectrometry data. Notably, the change in AGE-RAGE signaling over time was exclusively observed in male mice, suggesting sexual dimorphism in the pathogenesis of age-induced KOA in murine models. Collectively, these findings implicate dysregulation of AGE-RAGE signaling as a sex-dependent driver of age-related KOA.

PMID:34979545 | DOI:10.1093/gerona/glab386

PLoS Negl Trop Dis. 2022 Jan 3;16(1):e0010020. doi: 10.1371/journal.pntd.0010020. eCollection 2022 Jan.

ABSTRACT

BACKGROUND: The Old world Alphavirus, Middelburg virus (MIDV), is not well known and although a few cases associated with animal illness have previously been described from Southern Africa, there has been no investigation into the association of the virus with human illness. The current study aimed to investigate possible association of MIDV infection with febrile or neurological manifestations in hospitalized or symptomatic patients fromGauteng, South Africa.

METHODS: This study is a descriptive retrospective and prospective laboratory based study. Archived cerebrospinal fluid (CSF) samples submitted to the National Health Laboratory Service (NHLS), Tshwane Academic division for viral investigation from public sector hospitals in Gauteng as well as EDTA (ethylenediaminetetraacetic acid) whole blood samples from ad hoc cases of veterinary students, presenting with neurological and febrile illness, were selected and screened for the presence of alphaviruses using real-time reverse transcription(rtRT) PCR.Virus isolations from rtRT-PCR positive samples were conducted in Vero cell culture and used to obtain full genome sequences. Basic descriptive statistical analysis was conducted using EpiInfo.

RESULTS: MIDV was detected by rtRT-PCR in 3/187 retrospective CSF specimens obtained from the NHLS from hospitalised patients in the Tshwane region of Gauteng and 1/2 EDTA samples submitted in the same year (2017) from ad hoc query arbovirus cases from veterinary students from the Faculty of Veterinary Science University of Pretoria.Full genome sequences were obtained for virus isolates from two cases; one from an EDTA whole blood sample (ad hoc case) and another from a CSF sample (NHLS sample).Two of the four Middelburg virus positive cases,for which clinical information was available, had other comorbidities or infections at the time of infection.

CONCLUSION: Detection of MIDV in CSF of patients with neurological manifestations suggests that the virus should be investigated as a human pathogen with the potential of causing or contributing to neurological signs in children and adults.

PMID:34979534 | DOI:10.1371/journal.pntd.0010020

Dermatology. 2022 Jan 3:1-9. doi: 10.1159/000520592. Online ahead of print.

ABSTRACT

BACKGROUND: Skin self-examination (SSE) is widely promoted for the detection of suspicious pigmented lesions. However, determining screening accuracy is essential to appraising the usefulness of SSE.

OBJECTIVES: The aim of this work was to pool estimates from studies of SSE diagnostic accuracy in the detection of suspicious pigmented lesions.

METHODS: This study was registered with PROSPERO (CRD42021246356) and conducted in accordance with PRISMA-DTA guidelines. A systematic search of Medline (PubMed) EMBASE, CINAHL, and The Cochrane Library was conducted to identify relevant studies. We included studies that examined the accuracy of SSE, either whole-body or site-specific, for detecting change in individual pigmented lesions or detecting an atypical naevus. A univariate random-effects model, based on logit-transformed data, was used to calculate a summary diagnostic odds ratio (DOR) as well as pooled sensitivity and specificity. Cochran’s Q test and the I2 statistic were calculated to assess heterogeneity. A proportional hazards model was used to calculate the area under the curve (AUC) and plot the summary receiver operator characteristic curve. We used the Quality Assessment of Diagnostic Accuracy Studies-2 tool to grade study quality.

RESULTS: We identified 757 studies, of which 3 met inclusion criteria for quantitative synthesis. The pooled sensitivity and specificity based on 553 included participants was 59 and 82%, respectively. The summary DOR was 5.88 and the AUC was 0.71. There were some concerns regarding risk of bias in all 3 studies.

CONCLUSIONS: SSE can detect suspicious pigmented lesions with reasonable sensitivity and relatively high specificity, with the AUC suggesting acceptable discriminatory ability.

PMID:34979506 | DOI:10.1159/000520592

ORL J Otorhinolaryngol Relat Spec. 2022 Jan 3:1-9. doi: 10.1159/000519575. Online ahead of print.

ABSTRACT

BACKGROUND: Allergic rhinitis (AR) is characterized by an inflammatory reaction. High mobility group box 1 (HMGB1) protein and interleukin (IL)-33 are damage-associated molecular pattern molecules and have many characteristics similar to pro-inflammatory cytokines. However, the role of IL-33 and HMGB1 in AR remains unclear. The aim of this study is to explore the role of HMGB1 and IL-33 in AR.

METHODS: Twenty patients with AR (AR group) and 10 normal controls (normal group) were enrolled in this study. HMGB1 and IL-33 expression were analyzed by immunohistochemistry in epithelial cells of the inferior turbinate mucosa samples. Then, the human nasal mucosa epithelial cells (HNECs) were cultured in vitro, and the house dust mite allergen (Derp1) was used to stimulate the cells. Quantitative real-time PCR and ELISA assay were performed to detect HMGB1 and IL-33 expression in HNECs.

RESULTS: The expression of HMGB1 and IL-33 in the nasal mucosa was higher in the AR group than in the normal group, with a statistically significant difference (p < 0.05). In HNECs of AR, the expression of both HMGB1 and IL-33 in stimulated groups was higher than that in non-stimulated groups. The differences were statistically significant (p < 0.05). In addition, they increased gradually with the prolonging time and the concentration of the added Derp1.

CONCLUSIONS: The expression of HMGB1 and IL-33 were both increased in AR. HMGB1 and IL-33 may have a close relationship in AR.

PMID:34979505 | DOI:10.1159/000519575