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When should elective neck dissection be performed in maxillary gingival and alveolar squamous cell carcinoma with a cN0 neck? A systematic review

Tang L, Leung YY

Int J Oral Maxillofac Surg, 2016 Nov;45(11):1358-1365.
PMID: 27289248 DOI: 10.1016/j.ijom.2016.05.021

The purpose of this systematic review was to answer the clinical question "When should elective neck dissection be performed in maxillary gingival and alveolar squamous cell carcinoma with a cN0 neck?" A systematic review, designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, was conducted by two independent reviewers with three rounds of search and evaluation. Ten studies with 506 patients were included in the final review. The overall risk of cervical metastasis was 23.2% for those who did not receive an elective neck dissection (END), which was 3.4 times higher than that in the END group (6.8%). The 5-year survival rate was higher in those who had an END (80.3%) when compared to those who did not receive an END (67.4%). Overall, 14.1% of the cases with cN0 maxillary squamous cell carcinoma (SCC) presented with positive node(s) in pathological specimens after END. The risk of occult cervical metastasis in a cN0 maxillary SCC case with pathological stage pT1, pT2, pT3, and pT4 was 11.1%, 12.1%, 20%, and 36.1%, respectively. It is therefore concluded that END is recommended in patients with cN0 maxillary SCC, especially in stage T3 or T4 cases.
A systematic review of the associations, mediators and moderators of life satisfaction, positive affect and happiness in near-centenarians and centenarians

Cheng A, Leung Y, Brodaty H

Aging Ment Health, 2022 Apr;26(4):651-666.
PMID: 33645362 DOI: 10.1080/13607863.2021.1891197

OBJECTIVE: Results from studies investigating life satisfaction, positive affect and happiness of near-centenarians (95+) and centenarians are inconsistent. This is the first systematic review to summarise the extant literature on the subjective well-being of this unique age group.
METHOD: Seven electronic databases (PubMed, MEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science and the Cochrane database for systematic reviews) were systematically searched. Subjective well-being was defined as life satisfaction, positive affect and happiness. A narrative synthesis of relevant articles was undertaken.
RESULTS: Of 28 studies eligible for inclusion in this review, 20 predominantly examined life satisfaction, 11 positive affect and 4 happiness. Sex and other demographic variables were not significant predictors of subjective well-being. In contrast, greater perceived health was significantly associated with higher levels of life satisfaction and positive affect. Fatigue and visual impairment were significantly correlated with lower levels of life satisfaction and positive affect. However, there was considerable heterogeneity in the findings on physical, cognitive and social associations, mediators and moderators.
CONCLUSION: The large discrepancy of results in the literature may be explained by methodological differences between studies. Centenarian research needs a clearer definition of life satisfaction, positive affect and happiness as their operationalisation is inconsistent. An international consortium of centenarian studies could facilitate cross-cultural comparisons on subjective well-being. Future research should be directed towards interventions that promote subjective well-being in the oldest-old.
Does the use of amoxicillin/amoxicillin-clavulanic acid in third molar surgery reduce the risk of postoperative infection? A systematic review with meta-analysis

Menon RK, Gopinath D, Li KY, Leung YY, Botelho MG

Int J Oral Maxillofac Surg, 2019 Feb;48(2):263-273.
PMID: 30145064 DOI: 10.1016/j.ijom.2018.08.002

The objectives of this systematic review were to investigate the efficacy of amoxicillin/amoxicillin-clavulanic acid for reducing the risk of postoperative infection after third molar surgery and to evaluate the adverse outcomes in these patients, as well as in healthy volunteers. A systematic search of four databases was performed on May 26, 2017. Eleven studies qualified for the qualitative analysis and eight were found suitable for meta-analysis. The results suggest that both amoxicillin-clavulanic acid and amoxicillin significantly reduce the risk of infection after third molar extraction (overall relative risk (RR) 0.25, P<0.001). However, with the exclusion of randomized controlled trials with a split-mouth design (due to an inadequate crossover period after antibiotic treatment), only amoxicillin-clavulanic acid was found to be effective (RR 0.21, P<0.001). The risk of adverse effects was significantly higher in the amoxicillin-clavulanic acid group (RR=4.12, P=0.023) than in the amoxicillin group (RR 1.57, P=0.405). In conclusion, amoxicillin-clavulanic acid and amoxicillin may significantly reduce the risk of infection after third molar extraction. However, their use in third molar surgery should be viewed with caution, as recent clinical trials on healthy volunteers have shown evidence of the negative impact of amoxicillin use on bacterial diversity and antibiotic resistance.
Bone regeneration at the distal aspect of the adjacent second molar after lower third molar coronectomy: a long-term analysis

Leung YY, Yeung AWK, Ismail IN, Wong NSM

Int J Oral Maxillofac Surg, 2020 Oct;49(10):1360-1366.
PMID: 32340909 DOI: 10.1016/j.ijom.2020.03.016

A residual bone defect at the distal aspect of the adjacent second molar may occur after total removal of the lower third molar. Lower third molar coronectomy has been proved to be a safe alternative to total removal, but the extent of bone regeneration at the adjacent tooth after coronectomy is not well reported. The aim of this prospective study was to investigate the long-term bone regeneration at the distal aspect of the adjacent second molar after lower third molar coronectomy. Preoperative and postoperative cone beam computed tomography scans were measured to assess bone regeneration at the distobuccal (DB), mid-distal (MD), and distolingual (DL) aspects of the lower second molar. Forty-eight coronectomies in 37 patients (23 female) with a mean±standard deviation age of 29.1±7.2 years were assessed. The mean follow-up was 93.2±8.7 months. The mean bone level increase at DB, MD, and DL aspects was 3.2±1.6mm, 3.5±1.5mm, and 3.2±1.6mm, respectively; the bone levels were significantly higher than the preoperative measurements (P<0.001). Age and impaction patterns were not factors affecting bone regeneration. Based on this study, it appears that coronectomy of the lower third molar brings favourable bone regeneration at the distal aspect of the adjacent second molar.
Fulltext Long-term impact of oral surgery with or without amoxicillin on the oral microbiome-A prospective cohort study

Menon RK, Gomez A, Brandt BW, Leung YY, Gopinath D, Watt RM, et al.

Sci Rep, 2019 12 10;9(1):18761.
PMID: 31822712 DOI: 10.1038/s41598-019-55056-3

Routine postoperative antibiotic prophylaxis is not recommended for third molar extractions. However, amoxicillin still continues to be used customarily in several clinical practices worldwide to prevent infections. A prospective cohort study was conducted in cohorts who underwent third molar extractions with (group EA, n = 20) or without (group E, n = 20) amoxicillin (250 mg three times daily for 5 days). Further, a control group without amoxicillin and extractions (group C, n = 17) was included. Salivary samples were collected at baseline, 1-, 2-, 3-, 4-weeks and 3 months to assess the bacterial shift and antibiotic resistance gene changes employing 16S rRNA gene sequencing (Illumina-Miseq) and quantitative polymerase chain reaction. A further 6-month follow-up was performed for groups E and EA. Seven operational taxonomic units reported a significant change from baseline to 3 months for group EA (adjusted p 0.05). In conclusion, the salivary microbiome is resilient to an antibiotic challenge by a low-dose regimen of amoxicillin. Further studies evaluating the effect of routinely used higher dose regimens of amoxicillin on gram-negative bacteria and antibiotic resistance genes are warranted.
Lymph node metastasis of primary endometrial cancers: Associated proteins revealed by MALDI imaging

Mittal P, Klingler-Hoffmann M, Arentz G, Winderbaum L, Lokman NA, Zhang C, et al.

Proteomics, 2016 06;16(11-12):1793-801.
PMID: 27061135 DOI: 10.1002/pmic.201500455

Metastasis is a crucial step of malignant progression and is the primary cause of death from endometrial cancer. However, clinicians presently face the challenge that conventional surgical-pathological variables, such as tumour size, depth of myometrial invasion, histological grade, lymphovascular space invasion or radiological imaging are unable to predict with accuracy if the primary tumour has metastasized. In the current retrospective study, we have used primary tumour samples of endometrial cancer patients diagnosed with (n = 16) and without (n = 27) lymph node metastasis to identify potential discriminators. Using peptide matrix assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI), we have identified m/z values which can classify 88% of all tumours correctly. The top discriminative m/z values were identified using a combination of in situ sequencing and LC-MS/MS from digested tumour samples. Two of the proteins identified, plectin and α-Actin-2, were used for validation studies using LC-MS/MS data independent analysis (DIA) and immunohistochemistry. In summary, MALDI-MSI has the potential to identify discriminators of metastasis using primary tumour samples.
Annexin A2 and alpha actinin 4 expression correlates with metastatic potential of primary endometrial cancer

Mittal P, Klingler-Hoffmann M, Arentz G, Winderbaum L, Kaur G, Anderson L, et al.

Biochim Biophys Acta Proteins Proteom, 2017 Jul;1865(7):846-857.
PMID: 27784647 DOI: 10.1016/j.bbapap.2016.10.010

The prediction of lymph node metastasis using clinic-pathological data and molecular information from endometrial cancers lacks accuracy and is therefore currently not routinely used in patient management. Consequently, although only a small percentage of patients with endometrial cancers suffer from metastasis, the majority undergo radical surgery including removal of pelvic lymph nodes. Upon analysis of publically available data and published research, we compiled a list of 60 proteins having the potential to display differential abundance between primary endometrial cancers with versus those without lymph node metastasis. Using data dependent acquisition LC-ESI-MS/MS we were able to detect 23 of these proteins in endometrial cancers, and using data independent LC-ESI-MS/MS the differential abundance of five of those proteins was observed. The localization of the differentially expressed proteins, was visualized using peptide MALDI MSI in whole tissue sections as well as tissue microarrays of 43 patients. The proteins identified were further validated by immunohistochemistry. Our data indicate that annexin A2 protein level is upregulated, whereas annexin A1 and α actinin 4 expression are downregulated in tumours with lymph node metastasis compared to those without lymphatic spread. Moreover, our analysis confirmed the potential of these markers, to be included in a statistical model for prediction of lymph node metastasis. The predictive model using highly ranked m/z values identified by MALDI MSI showed significantly higher predictive accuracy than the model using immunohistochemistry data. In summary, using publicly available data and complementary proteomics approaches, we were able to improve the prediction model for lymph node metastasis in EC.
Incorporating connectivity into conservation planning for the optimal representation of multiple species and ecosystem services

Williams SH, Scriven SA, Burslem DFRP, Hill JK, Reynolds G, Agama AL, et al.

Conserv Biol, 2020 08;34(4):934-942.
PMID: 31840279 DOI: 10.1111/cobi.13450

Conservation planning tends to focus on protecting species' ranges or landscape connectivity but seldom both-particularly in the case of diverse taxonomic assemblages and multiple planning goals. Therefore, information on potential trade-offs between maintaining landscape connectivity and achieving other conservation objectives is lacking. We developed an optimization approach to prioritize the maximal protection of species' ranges, ecosystem types, and forest carbon stocks, while also including habitat connectivity for range-shifting species and dispersal corridors to link protected area. We applied our approach to Sabah, Malaysia, where the state government mandated an increase in protected-area coverage of approximately 305,000 ha but did not specify where new protected areas should be. Compared with a conservation planning approach that did not incorporate the 2 connectivity features, our approach increased the protection of dispersal corridors and elevational connectivity by 13% and 21%, respectively. Coverage of vertebrate and plant species' ranges and forest types were the same whether connectivity was included or excluded. Our approach protected 2% less forest carbon and 3% less butterfly range than when connectivity features were not included. Hence, the inclusion of connectivity into conservation planning can generate large increases in the protection of landscape connectivity with minimal loss of representation of other conservation targets.
Fulltext APOE ε4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline

Makkar SR, Lipnicki DM, Crawford JD, Kochan NA, Castro-Costa E, Lima-Costa MF, et al.

J Gerontol A Biol Sci Med Sci, 2020 09 25;75(10):1863-1873.
PMID: 32396611 DOI: 10.1093/gerona/glaa116

We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.