Neuromonitoring during Endovascular Thoracoabdominal Aortic Aneurysm Repair: A Systematic Review.

BACKGROUND: Spinal cord ischemia (SCI) is a potentially devastating complication of thoracic endovascular aortic repair (TEVAR) and fenestrated-branched endovascular aortic repair (F-BEVAR). The aim of this systematic review was to evaluate the efficacy of neuromonitoring modalities to mitigate the risk of SCI during TEVAR and F-BEVAR procedures. METHODS: Following the PRISMA guidelines, we conducted a detailed literature search of databases including PubMed, MEDLINE via Ovid, Embase, Scopus, and Cochrane CENTRAL, from 1998 to the present. Inclusion criteria were original research articles examining neuromonitoring during TEVAR and F-BEVAR. The primary outcome was the incidence of SCI, while the secondary outcome included early mortality. The quality of studies was assessed using the Newcastle-Ottawa Scale. RESULTS: From 1,450 identified articles, 11 met inclusion criteria, encompassing data from 1,069 patients. Neuromonitoring modalities included motor-evoked potentials (MEPs), somatosensory evoked potentials (SSEPs), and near-infrared spectroscopy. The combination of MEPs and SSEPs was most commonly used, with 93% sensitivity and 96% specificity for detecting SCI risks. SCI incidence ranged from 3.8 to 17.3%, with permanent deficits occurring in 2.7-5.8% of cases. In-hospital mortality ranged from 0.4 to 8%. Risk factors for SCI were identified, including operation duration and extent of aortic coverage. CONCLUSIONS: Neuromonitoring with MEPs and SSEPs appears to be effective in detecting perioperative SCI risk during TEVAR and F-BEVAR. However, discrepancies between neuromonitoring changes and actual SCI outcomes suggest the need for cautious interpretation. While the incidence of SCI remains variable, identified risk factors may guide clinical decisions, particularly in high-risk procedures. Future research should focus on prospective studies and randomized controlled trials to validate these findings and improve SCI prevention strategies in TEVAR and F-BEVAR.

Frozen Elephant Trunk Procedure for Acute Type a Aortic Dissection: Analysis of Distal Aortic Remodeling According to the Society for Vascular Surgery (SVS)/Society of Thoracic Surgeons (STS) Reporting Standard.

BACKGROUND: To investigate impact of frozen elephant trunk (FET) on long-term distal aortic remodeling in acute A aortic dissection (AAD) according to the latest recommended standards from the Society for Vascular Surgery (SVS)/Society of Thoracic Surgeons (STS). METHODS: Clinical data and imaging of patients who underwent FET to treat acute AAD over the last 8 years were retrospectively reviewed. Patients were included if a pre and postoperative computed angio tomographies at least 30 days from surgery was available for comparison. Contrasted postprocessed imaging were analyzed with Aquarius iNtuition (TeraRecon Inc., Foster City, CA, USA) to analyze long-term positive aortic remodeling, false lumen thrombosis, and aortic expansion according to the SVS or STS recommendations. Secondary endpoints were the rate of in-hospital and long-term mortality, spinal cord ischemia (SCI), and aortic-related reinterventions. RESULTS: Out of 75 patients who underwent FET for type A AAD, n = 41 (54.6%) were included. Significant positive aortic remodeling was reported in Ishimaru zone 1-4 but not in visceral or infrarenal aorta (P < 0.001), and the overall rate of false lumen thrombosis was 95.1% (n = 39). Aortic expansion rates were as follows: 4.9% in zones 1-4, 8.3% in zones 5-6, and 15% in zone 7. The rates of in-hospital mortality and long-term mortality were 7.3% (n = 3) and 9.7% (n = 4), respectively. At a median follow-up of 11 months (range 1-141, reintervention rate was 17.1%. CONCLUSIONS: We report positive aortic remodeling of the distal thoracic aorta in patients who underwent FET for acute AAD according to the SVS or STS reporting standards. The positive effect on the distal aorta is limited to the thoracic segments but not in the visceral aorta.

Aortic Outcome after Implementation of a Treatment Strategy for Type B Aortic Dissection Involving the Aortic Arch.

OBJECTIVE: To evaluate the outcomes achieved after implementing a treatment strategy for non-A non-B (NANB) (B 1-2 D according to the latest consensus document of the Society of Vascular Surgery (SVS) and Society of Thoracic Surgeons (STS) acute aortic dissection (AAD)). METHODS: This retrospective observational study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. All cases of NANB AAD (B 1-2 D) treated at our institution between January 2016 and December 2022 were reviewed. Morbidity, mortality, aortic-related reintervention, and remodeling were analyzed. RESULTS: Among 519 cases of acute aortic syndrome, n = 22 (4.2%) patients presented with NANB AAD (B 1-2 D) (n = 16,72.7% men, mean age 61.5 years+/14.7). Eleven cases were managed with best medical treatment (BMT) alone. Among them, one patient (9.1%) died suddenly 2 days after diagnosis for aortic rupture. Frozen elephant trunk procedure (FET) was required in the remaining 11 patients: 7 (31.8%) needed emergent operation for risks of impending aortic rupture or retrograde aortic dissection extension, and 4 (26.7%) underwent delayed surgery within a month from initial presentation. Overall, in-hospital mortality was 9.1% with both FET and BMT. At a median follow-up of 40 months (range 2 days-200 months) no other deaths occurred. A statistically significant differences in the rate of false lumen thrombosis (100% vs 55.5%, P = 0.033), and a significant positive aortic remodeling in zone 3 (P < 0.001) and 4 (P = 0.038) were reported in operated versus medically managed patients. CONCLUSIONS: The best treatment for NANB is not established. We advocate for medical stabilization with an operative approach that favors open surgery in the acute post dissection period, promotes aortic remodeling, and carries acceptable risk in centers where FET is performed routinely.

Age-Related Effects on MSC Immunomodulation, Macrophage Polarization, Apoptosis, and Bone Regeneration Correlate with IL-38 Expression.

Mesenchymal stem cells (MSCs) are known to promote tissue regeneration and suppress excessive inflammation caused by infection or trauma. Reported evidence indicates that various factors influence the expression of MSCs' endogenous immunomodulatory properties. However, the detailed interactions of MSCs with macrophages, which are key cells involved in tissue repair, and their regulatory mechanisms are not completely understood. We herein investigated how age-related immunomodulatory impairment of MSCs alters the interaction of MSCs with macrophages during bone healing using young (5-week old) and aged (50-week old) mice. To clarify the relationship between inflammatory macrophages (M1) and MSCs, their spatiotemporal localization at the bone healing site was investigated by immunostaining, and possible regulatory mechanisms were analyzed in vitro co-cultures. Histomorphometric analysis revealed an accumulation of M1 and a decrease in MSC number at the healing site in aged mice, which showed a delayed bone healing. In in vitro co-cultures, MSCs induced M1 apoptosis through cell-to-cell contact but suppressed the gene expression of pro-inflammatory cytokines by soluble factors secreted in the culture supernatant. Interestingly, interleukin 38 (Il-38) expression was up-regulated in M1 after co-culture with MSCs. IL-38 suppressed the gene expression of inflammatory cytokines in M1 and promoted the expression of genes associated with M1 polarization to anti-inflammatory macrophages (M2). IL-38 also had an inhibitory effect on M1 apoptosis. These results suggest that MSCs may induce M1 apoptosis, suppress inflammatory cytokine production by M1, and induce their polarization toward M2. Nevertheless, in aged conditions, the decreased number and immunomodulatory function of MSCs could be associated with a delayed M1 clearance (i.e., apoptosis and/or polarization) and consequent delayed resolution of the inflammatory phase. Furthermore, M1-derived IL-38 may be associated with immunoregulation in the tissue regeneration site.

Preoperative B-Type Natriuretic Peptides to Predict Postoperative Atrial Fibrillation in Cardiac Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Post-operative atrial fibrillation (AF) is the most common complication following cardiac surgery. There has been extensive exploration of clinical variables, imaging, and biomarkers to predict its occurrence after cardiac surgery. In this study, we examine the emerging biomarkers B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) to assess their pre-operative values and correlations with the occurrence of post-operative AF in patients undergoing cardiac surgery. METHODS: A comprehensive literature search was conducted using PubMed, EMBASE, MEDLINE via Ovid, ClinicalTrials.Gov, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify studies published until March 2023. The studies were included if they reported pre-operative BNP or NT-proBNP values and the development of post-operative AF in cardiac surgery patients. Subsequently, data were extracted, and a meta-analysis was performed using Review Manager 5.4 4 (The Cochrane Collaboration, 2020) and SPSS version 28 (IBM Corp, Armonk, NY, USA) to assess the difference between pre-operative BNP and NT-proBNP levels between patients with post-operative AF (AF group) and those without (No-AF group) using a random-effect model. Further analysis was performed in three subgroups: isolated coronary artery bypass grafting, isolated valve, and combined/mixed surgery group. RESULT: A total of 20 studies, including 9,079 participants were identified and included in the systematic review and meta-analysis. Pre-operative BNP levels were reported in 11 studies, and NT-proBNP levels were reported in 10 studies, of which one study reported both BNP and NT-proBNP levels. There is an overall significant difference between pre-operative levels of BNP (p=0.03, I2=95%) and NT-proBNP (p<0.001, I2=65%) when compared between AF and No-AF groups. Nonetheless, subgroup analysis showed there is no significant difference in pre-operative BNP levels, except in isolated valve surgery (p<0.001), whereas all subgroups showed significantly different pre-operative levels of NT-proBNP. CONCLUSIONS: Elevated levels of both BNP and NT-proBNP were observed in patients who developed post-operative AF after undergoing cardiac surgery. In particular, pre-operative NT-proBNP levels were elevated in all patients irrespective of the type of surgical procedure, but elevated pre-operative BNP was only seen in valve surgery patients. These findings suggest the potential usefulness of NT-proBNP as a promising biomarker for predicting the occurrence of post-operative AF following cardiac surgery.

Risk factors for metachronous colorectal cancer and advanced neoplasia following primary colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Identifying risk factors for metachronous colorectal cancer (CRC) and metachronous advanced neoplasia could be useful for guiding surveillance. We conducted a systematic review and meta-analysis to investigate risk factors for metachronous CRC and advanced neoplasia. METHODS: Searches were conducted in MEDLINE, Embase, Web of Science and Cochrane Central Registry of Controlled Trials for articles (searching period: 1945 to Feburary, 2021) that reported the results of an association between any factor and metachronous advanced neoplasia or metachronous CRC. There were no restrictions on the publication date or language. Random effects models were fitted to estimate the combined association between the risk factors and metachronous CRC or advanced neoplasia. The Risk of Bias In Non-Randomised Studies of Interventions tool (ROBINS-I) was used to assess the risk of bias of included studies. RESULTS: In total, 22 observational studies with 625,208 participants were included in the systematic review and meta-analysis. Of these, 13 studies investigated risk factors for metachronous CRC and 9 for advanced neoplasia. The risks of metachronous CRC or advanced neoplasia were higher if the first CRC was diagnosed in the presence of a synchronous advanced lesion (pooled risk ratio (RR) from 3 studies: 3.61, 95% confidence interval (CI): 1.44-9.05; and pooled RR from 8 studies: 2.77, 95% CI: 2.23-3.43, respectively). The risk of metachronous CRC was lower, but the risk of metachronous advanced neoplasia was higher if the first CRC was distal (compared with proximal) (pooled RR from 3 studies: 0.48, 95% CI: 0.23-0.98; and pooled RR from 2 studies: 2.99, 95% CI: 1.60-5.58 respectively). The risk of metachronous advanced neoplasia increased with age (pooled RR from 3 studies: 1.07 per year of age, 95% CI: 1.03-1.11). There was no evidence that any lifestyle risk factors studied were associated with the risk of metachronous CRC or advanced neoplasia. CONCLUSIONS: The identified risk factors for metachronous CRC and advanced neoplasia might be useful to tailor the existing surveillance guidelines after the first CRC. There were potential limitations due to possible misclassification of the outcome, confounding and risk of bias, and the findings cannot be generalised to high-risk genetic syndrome cases.

Surgical and endovascular treatment of late postcoarctation repair aortic aneurysms: Results from an international multicenter study.

OBJECTIVE: The formation of postaortic coarctation aneurysms (pCoAA) is well-described in the literature and carries a significant risk of rupture and death. Treatment strategies include open surgical, hybrid, and endovascular repair, depending on the clinical presentation, risk assessment, and anatomy. The aim of this study was to report the early and midterm results of open surgical and endovascular repair of pCoAA. METHODS: This is an international multicenter retrospective study including patients who underwent open surgical or endovascular repair for pCoAA between 2000 and 2021 at 14 highly specialized academic cardiovascular centers. The preoperative, intraoperative, and postoperative data were recorded and analyzed. RESULTS: A total of 74 patients (46 male; median age, 44 years; interquartile range [IQR], 35-53 years) underwent pCoAA repair. All patients had previously undergone surgical repair of aortic coarctation at a median age of 11 years for the index procedure (IQR, 7-17 years). The most common first surgical correction was synthetic patch aortoplasty in 48 patients, followed by graft interposition in 11. The median pCoAA diameter was 54 mm (IQR, 44-63 mm). The median time from the aortic coarctation repair to the pCoAA diagnosis was 33 years (IQR, 25-40 years). A total of 33 patients had symptoms at presentation, including thoracic or back pain in 8 patients. Open surgical repair was performed in 28 patients, including four frozen elephant trunk procedures and one Bentall. The remaining 46 patients underwent endovascular repair of the pCoAA. Two in-hospital deaths were observed (one frozen elephant trunk and one endovascular). After a median follow-up of 50 months (IQR, 14-127 months), there were a total of seven reinterventions. CONCLUSIONS: This international multicenter study demonstrates that patients with pCoAA can be safely treated with either open surgical or endovascular interventions. Because the median time between the coarctation repair and the aneurysm formation was more than 30 years, life-long surveillance of these patients is warranted.

A comparison of malaria prevention behaviours, care-seeking practices and barriers between malaria at-risk worksite migrant workers and villagers in Northern Shan State, Myanmar-a mixed method study.

BACKGROUND: Migrant populations are at an increased risk of exposure to malaria due to their nature of work and seasonal migration. This study aimed to compare malaria prevention behaviours and care-seeking practices among worksite migrant workers and villagers in the malaria-at-risk areas of Eastern Myanmar close to the China border. METHODS: A mixed method study was conducted in March 2019. The malaria-at-risk worksites in the four targeted townships, and villages located the nearest to these worksites were approached. Key stakeholders, such as worksite managers and village leaders, were interviewed. RESULTS: A total of 23 worksites, which employed 880 migrants and 447 locals, and 20 villages, which were homes for 621 migrants and 9731 locals, were successfully interviewed. Regarding malaria prevention behaviours, sleeping under a bed net was common among both worksites (74%) and villages (85%). In contrast, insecticide-treated nets/long-lasting insecticidal nets (ITN/LLIN) usage was much lower in the worksites than in the villages (39% vs 80%). Regarding care-seeking practices for febrile illness, self-medication was a popular choice for both worksite workers and villagers owing to the easy availability of western medicine. Moreover, local-belief-driven traditional practices were more common among villagers. For occasions in which fever was not relieved, both would seek health care from rural health centres, private clinics, or public hospitals. As for barriers, villagers mostly cited language barriers, which often lead to misunderstanding between health providers and them. In contrast, most of the worksites cited logistics issues as they were in remote areas with devastated road conditions and the routes to formal health facilities were not secure due to frequent armed conflicts. CONCLUSION: This study demonstrated that site-workers and villagers had different malaria prevention behaviours and care-seeking practices even though they resided in the same geographic area. Hence, it is important to recognize such differences for more effective intervention approaches.

Identities and HIV-Related Risk Behaviors Among Transgender Women in Myanmar: Perspectives from Transgender Women and Service Providers.

In Myanmar, transgender women (TGW) have historically been grouped into the men who have sex with men (MSM) population in program and surveillance data. There is no direct translation for the term transgender in Myanmar language, and there are no data on HIV prevalence or HIV-related risk behaviors among TGW. Therefore, this study aimed to explore how TGW identify and express themselves in Myanmar and their HIV-related risk behaviors. This qualitative study consisted of 11 key informant interviews with service providers and 20 in-depth interviews with TGW participants in Yangon in 2017. All participants said that TGW in Myanmar were assigned male at birth, but none identified as men; they all self-identified as women or another gender, such as trans. Such identity emerged from an internal sense of being a woman or an alternative gender. In addition, many participants reported that TGW changed their appearance through changes in clothing or mannerisms. TGW are particularly vulnerable to violence: Often reported during transition, transgender women were exposed to transphobia, violence and discrimination from their family, relatives or workplace. Many participants reported TGW being the receptive partner during sex and engaged in high-risk sexual behaviors, such as sex with multiple partners, group sex, and condomless sex. Our findings can help to define this population in the Myanmar context and assess needs for health services.

Novel mammogram-based measures improve breast cancer risk prediction beyond an established mammographic density measure.

Mammograms contain information that predicts breast cancer risk. We developed two novel mammogram-based breast cancer risk measures based on image brightness (Cirrocumulus) and texture (Cirrus). Their risk prediction when fitted together, and with an established measure of conventional mammographic density (Cumulus), is not known. We used three studies consisting of: 168 interval cases and 498 matched controls; 422 screen-detected cases and 1197 matched controls; and 354 younger-diagnosis cases and 944 controls frequency-matched for age at mammogram. We conducted conditional and unconditional logistic regression analyses of individually- and frequency-matched studies, respectively. We estimated measure-specific risk gradients as the change in odds per standard deviation of controls after adjusting for age and body mass index (OPERA) and calculated the area under the receiver operating characteristic curve (AUC). For interval, screen-detected and younger-diagnosis cancer risks, the best fitting models (OPERAs [95% confidence intervals]) involved: Cumulus (1.81 [1.41-2.31]) and Cirrus (1.72 [1.38-2.14]); Cirrus (1.49 [1.32-1.67]) and Cirrocumulus (1.16 [1.03 to 1.31]); and Cirrus (1.70 [1.48 to 1.94]) and Cirrocumulus (1.46 [1.27-1.68]), respectively. The AUCs were: 0.73 [0.68-0.77], 0.63 [0.60-0.66], and 0.72 [0.69-0.75], respectively. Combined, our new mammogram-based measures have twice the risk gradient for screen-detected and younger-diagnosis breast cancer (P ≤ 10-12 ), have at least the same discriminatory power as the current polygenic risk score, and are more correlated with causal factors than conventional mammographic density. Discovering more information about breast cancer risk from mammograms could help enable risk-based personalised breast screening.

Elephant Endotheliotropic Herpesvirus Hemorrhagic Disease in Asian Elephant Calves in Logging Camps, Myanmar.

In recent years, an alarming number of cases of lethal acute hemorrhagic disease have occurred in Asian elephant calves raised in logging camps in Myanmar. To determine whether these deaths were associated with infection by elephant endotheliotropic herpesvirus (EEHV), we conducted diagnostic PCR subtype DNA sequencing analysis on necropsy tissue samples collected from 3 locations. We found that EEHV DNA from 7 PCR loci was present at high levels in all 3 calves and was the same EEHV1A virus type that has been described in North America, Europe, and other parts of Asia. However, when analyzed over 5,610 bp, the strains showed major differences from each other and from all previously characterized EEHV1A strains. We conclude that these 3 elephant calves in Myanmar died from the same herpesvirus disease that has afflicted young Asian elephants in other countries over the past 20 years.

Interval breast cancer risk associations with breast density, family history and breast tissue aging.

Interval breast cancers (those diagnosed between recommended mammography screens) generally have poorer outcomes and are more common among women with dense breasts. We aimed to develop a risk model for interval breast cancer. We conducted a nested case-control study within the Melbourne Collaborative Cohort Study involving 168 interval breast cancer patients and 498 matched control subjects. We measured breast density using the CUMULUS software. We recorded first-degree family history by questionnaire, measured body mass index (BMI) and calculated age-adjusted breast tissue aging, a novel measure of exposure to estrogen and progesterone based on the Pike model. We fitted conditional logistic regression to estimate odds ratio (OR) or odds ratio per adjusted standard deviation (OPERA) and calculated the area under the receiver operating characteristic curve (AUC). The stronger risk associations were for unadjusted percent breast density (OPERA = 1.99; AUC = 0.66), more so after adjusting for age and BMI (OPERA = 2.26; AUC = 0.70), and for family history (OR = 2.70; AUC = 0.56). When the latter two factors and their multiplicative interactions with age-adjusted breast tissue aging (p = 0.01 and 0.02, respectively) were fitted, the AUC was 0.73 (95% CI 0.69-0.77), equivalent to a ninefold interquartile risk ratio. In summary, compared with using dense breasts alone, risk discrimination for interval breast cancers could be doubled by instead using breast density, BMI, family history and hormonal exposure. This would also give women with dense breasts, and their physicians, more information about the major consequence of having dense breasts-an increased risk of developing an interval breast cancer.

Comparison of point transect distance and traditional acoustic point-count sampling of hoolock gibbons in Htamanthi Wildlife Sanctuary, Myanmar.

Effective conservation demands more accurate and reliable methods of survey and monitoring of populations. Surveys of gibbon populations have relied mostly on mapping of groups in "listening areas" using acoustical point-count data. Traditional methods of estimating density in have usually used counts of gibbon groups within fixed-radius areas or areas bounded by terrain barriers to sound transmission, and have not accounted for possible decline in detectability with distance. In this study we sampled the eastern hoolock gibbon (Hoolock leucogenys) population in Htamanthi Wildlife Sanctuary (WS), Myanmar, using two methods: the traditional point-count method with fixed-radius listening areas, and a newer method using point-transect Distance analysis from a sample point established in the center of each listening point array. The basic data were obtained by triangulating on singing groups from four LPs for 4 days, in 10 randomly selected sample areas within the sanctuary. The point transect method gave an average density of 3.13 groups km-2 , higher than the estimates of group density within fixed-radius areas without correction for detectability. A new method of analysis of singing probability per day (p[1]) gave an estimate of 0.547. Htamanthi WS is an important conservation area containing an estimated 7000 (95% confidence interval: 5000-10,000) hoolock groups. Surveys at Htamanthi WS and locations in the Hukaung Valley suggest that the extensive evergreen forests in northern Myanmar have the capacity to support 2-4 (average about 3) groups of hoolock gibbons per km2 , but most forests in its range have yet to be surveyed.

Aging-Affected MSC Functions and Severity of Periodontal Tissue Destruction in a Ligature-Induced Mouse Periodontitis Model.

Mesenchymal stem cells (MSCs) are known to play important roles in the repair of lost or damaged tissues and immunotolerance. On the other hand, aging is known to impair MSC function. However, little is currently known about how aged MSCs affect the host response to the local inflammatory condition and tissue deterioration in periodontitis, which is a progressive destructive disease of the periodontal tissue potentially leading to multiple tooth loss. In this study, we examined the relationship between aging-induced impairment of MSC function and the severity of periodontal tissue destruction associated with the decrease in host immunomodulatory response using a ligature-induced periodontitis model in young and aged mice. The results of micro computerized tomography (micro-CT) and histological analysis revealed a more severe bone loss associated with increased osteoclast activity in aged (50-week-old) mice compared to young (5-week-old) mice. Immunostaining analysis revealed that, in aged mice, the accumulation of inflammatory T and B cells was higher, whereas the percentage of platelet-derived growth factor receptor α (PDGFRα)+ MSCs, which are known to modulate the apoptosis of T cells, was significantly lower than in young mice. In vitro analysis of MSC function showed that the expression of surface antigen markers for MSCs (Sca-1, CD90, CD146), colony formation, migration, and osteogenic differentiation of aged MSCs were significantly declined compared to those of young MSCs. Moreover, a significantly higher proportion of aged MSCs were positive for the senescence-associated ß galactosidase activity. Importantly, aged MSCs presented a decreased expression of FAS-L, which was associated with a lower immunomodulatory property of aged MSCs to induce T cell apoptosis in co-cultures compared with young MSCs. In summary, this is the first study showing that aging-induced impairment of MSC function, including immunomodulatory response, is potentially correlated with progressive periodontal tissue deterioration.

Predicting interval and screen-detected breast cancers from mammographic density defined by different brightness thresholds.

BACKGROUND: Case-control studies show that mammographic density is a better risk factor when defined at higher than conventional pixel-brightness thresholds. We asked if this applied to interval and/or screen-detected cancers. METHOD: We conducted a nested case-control study within the prospective Melbourne Collaborative Cohort Study including 168 women with interval and 422 with screen-detected breast cancers, and 498 and 1197 matched controls, respectively. We measured absolute and percent mammographic density using the Cumulus software at the conventional threshold (Cumulus) and two increasingly higher thresholds (Altocumulus and Cirrocumulus, respectively). Measures were transformed and adjusted for age and body mass index (BMI). Using conditional logistic regression and adjusting for BMI by age at mammogram, we estimated risk discrimination by the odds ratio per adjusted standard deviation (OPERA), calculated the area under the receiver operating characteristic curve (AUC) and compared nested models using the likelihood ratio criterion and models with the same number of parameters using the difference in Bayesian information criterion (ΔBIC). RESULTS: For interval cancer, there was very strong evidence that the association was best predicted by Cumulus as a percentage (OPERA = 2.33 (95% confidence interval (CI) 1.85-2.92); all ΔBIC > 14), and the association with BMI was independent of age at mammogram. After adjusting for percent Cumulus, no other measure was associated with risk (all P > 0.1). For screen-detected cancer, however, the associations were strongest for the absolute and percent Cirrocumulus measures (all ΔBIC > 6), and after adjusting for Cirrocumulus, no other measure was associated with risk (all P > 0.07). CONCLUSION: The amount of brighter areas is the best mammogram-based measure of screen-detected breast cancer risk, while the percentage of the breast covered by white or bright areas is the best mammogram-based measure of interval breast cancer risk, irrespective of BMI. Therefore, there are different features of mammographic images that give clinically important information about different outcomes.

Breast Cancer Risk Associations with Digital Mammographic Density by Pixel Brightness Threshold and Mammographic System.

Purpose To compare three mammographic density measures defined by different pixel intensity thresholds as predictors of breast cancer risk for two different digital mammographic systems. Materials and Methods The Korean Breast Cancer Study included 398 women with invasive breast cancer and 737 control participants matched for age at mammography (±1 year), examination date, mammographic system, and menopausal status. Mammographic density was measured by using the automated Laboratory for Individualized Breast Radiodensity Assessment (LIBRA) software and the semiautomated Cumulus software at the conventional threshold (Cumulus) and at increasingly higher thresholds (Altocumulus and Cirrocumulus, respectively). Measures were Box-Cox-transformed and adjusted for age, body mass index, and menopausal status. Conditional logistic regression was used to estimate risk associations. For calculation of measures of predictive value, the change in odds per standard deviation (OPERA) and the area under the receiver operating characteristic curve (AUC) were used. Results For dense area, with use of the direct conversion system the OPERAs were 1.72 (95% confidence interval [CI]: 1.38, 2.15) for LIBRA, 1.58 (95% CI: 1.27, 1.97) for Cumulus, 2.04 (95% CI: 1.60, 2.59) for Altocumulus, and 3.48 (95% CI: 2.45, 4.47) for Cirrocumulus (P < .001). The corresponding AUCs were 0.70, 0.69, 0.76, and 0.89, respectively. With use of the indirect conversion system, the corresponding OPERAs were 1.50 (95% CI: 1.28, 1.76), 1.36 (95% CI: 1.16, 1.59), 1.40 (95% CI: 1.19, 1.64), and 1.47 (95% CI: 1.25, 1.73) (P < .001) and the AUCs were 0.64, 0.60, 0.61, and 0.63, respectively. Conclusion It is possible that mammographic density defined by higher pixel thresholds could capture more risk-predicting information with use of a direct conversion mammographic system; the mammographically bright, rather than white, regions are etiologically important. © RSNA, 2017.

Understanding malaria treatment-seeking preferences within the public sector amongst mobile/migrant workers in a malaria elimination scenario: a mixed-methods study.

BACKGROUND: Migration flows and the emerging resistance to artemisinin-based combination therapy in the Greater Mekong Sub-region (GMS) create programmatic challenges to meeting the AD 2030 malaria elimination target in Myanmar. The National Malaria Control Programme (NMCP) targeted migrant workers based mainly on the stability of their worksites (categories 1: permanent work-setting; categories 2 and 3: less stable work-settings). This study aims to assess the migration patterns, malaria treatment-seeking preferences, and challenges encountered by mobile/migrant workers at remote sites in a malaria-elimination setting. METHODS: A mixed-methods explanatory sequential study retrospectively analysed the secondary data acquired through migrant mapping surveys (2013-2015) in six endemic regions (n = 9603). A multivariate logistic regression model was used to ascertain the contributing factors. A qualitative strand (2016-2017) was added by conducting five focus-group discussions (n = 50) and five in-depth interviews with migrant workers from less stable worksites in Shwegyin Township, Bago Region. The contiguous approach was used to integrate quantitative and qualitative findings. RESULTS: Among others, migrant workers from Bago Region were significantly more likely to report the duration of stay ≥ 12 months (63% vs. 49%) and high seasonal mobility (40% vs. 35%). Particularly in less stable settings, a very low proportion of migrant workers (17%) preferred to seek malaria treatment from the public sector and was significantly influenced by the worksite stability (adjusted OR = 1.4 and 2.3, respectively for categories 2 and 1); longer duration of stay (adjusted OR = 3.5); and adjusted OR < 2 for received malaria messages, knowledge of malaria symptoms and awareness of means of malaria diagnosis. Qualitative data further elucidated their preference for the informal healthcare sector, due to convenience, trust and good relations, and put migrant workers at risk of substandard care. Moreover, the availability of cheap anti-malarial in unregistered small groceries encouraged self-medication. Infrequent or no contact with rural health centres and voluntary health workers worsened the situation. CONCLUSIONS: Mitigating key drivers that favour poor utilization of public-sector services among highly mobile migrant workers in less stable work-settings should be given priority in a malaria-elimination setting. These issues are challenging for the NMCP in Myanmar and might be generalized to other countries in the GMS to achieve malaria-elimination goals. Further innovative out-reach programmes designed and implemented specific to the nature of mobile/migrant workers is crucial.

Associations of 5HTTLPR polymorphism with major depressive disorder and alcohol dependence: A systematic review and meta-analysis.

OBJECTIVE: The neurotransmitter serotonin is understood to control mood and drug response. Carrying a genetic variant in the serotonin transporter gene (5HTT) may increase the risk of major depressive disorder and alcohol dependence. Previous estimates of the association of the S allele of 5HTTLPR polymorphism with major depressive disorder and alcohol dependence have been inconsistent. METHODS: For the systematic review, we used PubMed MEDLINE and Discovery of The University of Melbourne to search for all relevant case-control studies investigating the associations of 5HTTLPR polymorphism with major depressive disorder and alcohol dependence. Summary odds ratios (OR) and their 95% confidence intervals (CI) were estimated. To investigate whether year of publication, study population or diagnostic criteria used were potential sources of heterogeneity, we performed meta-regression analyses. Publication bias was assessed using Funnel plots and Egger's statistical tests. RESULTS: We included 23 studies of major depressive disorder without alcohol dependence containing 3392 cases and 5093 controls, and 11 studies of alcohol dependence without major depressive disorder containing 2079 cases and 2273 controls. The summary OR for homozygote carriers of the S allele of 5HTTLPR polymorphism compared with heterozygote and non-carriers combined (SS vs SL+LL genotype) was 1.33 (95% CI = [1.19, 1.48]) for major depressive disorder and 1.18 (95% CI = [1.01, 1.38]) for alcohol dependence. The summary OR per S allele of 5HTTLPR polymorphism was 1.16 (95% CI = [1.08, 1.23]) for major depressive disorder and 1.12 (95% CI = [1.01, 1.23]) for alcohol dependence. Meta-regression models showed that the associations did not substantially change after adjusting for year of publication, study population and diagnostic criteria used. There was no evidence for publication bias of the studies included in our meta-analysis. CONCLUSIONS: Our meta-analysis confirms that individuals with the homozygous S allele of 5HTTLPR polymorphism are at increased risks of major depressive disorder as well as alcohol dependence. Further studies are required to investigate the association between 5HTTLPR polymorphism and the comorbidity of major depressive disorder and alcohol dependence as well as gene × environmental interactions.

Mammographic density defined by higher than conventional brightness threshold better predicts breast cancer risk for full-field digital mammograms.

INTRODUCTION: When measured using the computer-assisted method CUMULUS, mammographic density adjusted for age and body mass index predicts breast cancer risk. We asked if new mammographic density measures defined by higher brightness thresholds gave better risk predictions. METHODS: The Korean Breast Cancer Study included 213 women diagnosed with invasive breast cancer and 630 controls matched for age at full-field digital mammogram and menopausal status. Mammographic density was measured using CUMULUS at the conventional threshold (Cumulus), and in effect at two increasingly higher thresholds, which we call Altocumulus and Cirrocumulus, respectively. All measures were Box-Cox transformed and adjusted for age, body mass index, menopausal status and machine. We used conditional logistic regression to estimate the change in Odds PER standard deviation of transformed and Adjusted density measures (OPERA). The area under the receiver operating characteristic curve (AUC) was estimated. RESULTS: Corresponding Altocumulus and Cirrocumulus density measures were correlated with Cumulus measures (r approximately 0.8 and 0.6, respectively). Altocumulus and Cirrocumulus measures were on average 25% and 80% less, respectively, than the Cumulus measure. For dense area, the OPERA was 1.18 (95% confidence interval: 1.01-1.39, P = 0.03) for Cumulus; 1.36 (1.15-1.62, P < 0.001) for Altocumulus; and 1.23 (1.04-1.45, P = 0.01) for Cirrocumulus. After fitting the Altocumulus measure, the Cumulus measure was no longer associated with risk. After fitting the Cumulus measure, the Altocumulus measure was still associated with risk (P = 0.001). The AUCs for dense area was 0.59 for the Altocumulus measure, greater than 0.55 and 0.57 for the Cumulus and Cirrocumulus measures, respectively (P = 0.001). Similar results were found for percentage dense area measures. CONCLUSIONS: Altocumulus measures perform better than Cumulus measures in predicting breast cancer risk, and Cumulus measures are confounded by Altocumulus measures. The mammographically bright regions might be more aetiologically important for breast cancer, with implications for biological, molecular, genetic and epidemiological research and clinical translation.