A prospective study to evaluate the efficacy and safety of vitamin E and levocarnitine prophylaxis against doxorubicin-induced cardiotoxicity in adult breast cancer patients.

BACKGROUND: Doxorubicin induces acute and chronic cardiotoxicity. This study is aimed to evaluate the efficacy and safety of vitamin E and levocarnitine (EL) as cardioprotective agents against acute doxorubicin cardiotoxicity in female adult breast cancer patients. METHODS: A prospective, randomized controlled study was conducted in patients treated with doxorubicin and cyclophosphamide (AC). Patients were randomly assigned to EL plus AC or AC alone for the duration of 4 cycles. Cardiac enzymes (B-type natriuretic peptide, creatine kinase, troponin I (Trop)) and cardiac events were monitored during treatment to evaluate the cardioprotective efficacy of EL. RESULTS: Seventy-four patients were recruited and received four cycles of chemotherapy. The intervention group (n = 35) showed a significant reduction in both the B-type natriuretic peptide and creatine kinase cardiac enzymes compared to the control group (n = 39). The median (IQR) change for BNP was 0.80 (0.00-4.00) for IG versus 1.80 (0.40-3.60) for CG groups (p < 0.001); creatine kinase was -0.08 (-0.25-0.05) for IG versus 0.20 (0.05-0.50) for CG (p < 0.001). The addition of EL decreased the cardiac events by 24.2% (p = 0.02). All adverse events were tolerable and manageable. CONCLUSION: This study supports the addition of EL as prophylaxis against acute doxorubicin cardiotoxicity and it was also very well tolerated by a majority of the patients. The co-administration of EL at higher doxorubicin (240 mg/m2) dose should be further investigated.

Simulating Energy Use, Indoor Temperatures, and Utility Cost Impacts Amidst a Warming Climate in a Multi-family Housing Model.

Rising ambient temperatures due to climate change will impact both indoor temperatures and heating and cooling utility costs. In traditionally colder climates, there are potential tradeoffs in how to meet the reduced heating and increased cooling demands, and issues related to lack of air conditioning (AC) access in older homes and among lower-income populations to prevent extreme heat exposure. We modeled a typical multi-family home in Boston (MA) in the building simulation program EnergyPlus to assess indoor temperature and energy consumption in current (2020) and projected future (2050) weather conditions. Selected households were those without AC (no AC), those who ran AC sometimes (some AC), and those with sufficient resources to run AC always (full AC). We considered stylized cooling subsidy policies that allowed households to move between groups, both independently and in conjunction with energy efficiency retrofits. Results showed that future weather conditions without policy changes yielded an increase in indoor summer temperatures of 2.1 °C (no AC), increased cooling demand (range: 34-50%), but led to a decrease in net yearly total utility costs per apartment (range: - $21 to - $38). Policies that allowed households to move to greater AC utilization yielded average indoor summer temperature decreases (- 3.5 °C to - 6.2 °C) and net yearly total utility increases (range: + $2 to + $94) per apartment unit, with greater savings for retrofitted homes primarily due to large decreases in heating use. Our model results reinforce the importance of coordinated public policies addressing climate change that have an equity lens for both health and climate goals.

Preadipocytes in human granulation tissue: role in wound healing and response to macrophage polarization.

BACKGROUND: Chronic non-healing wounds pose a global health challenge. Under optimized conditions, skin wounds heal by the formation of scar tissue. However, deregulated cell activation leads to persistent inflammation and the formation of granulation tissue, a type of premature scar tissue without epithelialization. Regenerative cells from the wound periphery contribute to the healing process, but little is known about their cellular fate in an inflammatory, macrophage-dominated wound microenvironment. METHODS: We examined CD45-/CD31-/CD34+ preadipocytes and CD68+ macrophages in human granulation tissue from pressure ulcers (n=6) using immunofluorescence, immunohistochemistry, and flow cytometry. In vitro, we studied macrophage-preadipocyte interactions using primary human adipose-derived stem cells (ASCs) exposed to conditioned medium harvested from IFNG/LPS (M1)- or IL4/IL13 (M2)-activated macrophages. Macrophages were derived from THP1 cells or CD14+ monocytes. In addition to confocal microscopy and flow cytometry, ASCs were analyzed for metabolic (OXPHOS, glycolysis), morphological (cytoskeleton), and mitochondrial (ATP production, membrane potential) changes. Angiogenic properties of ASCs were determined by HUVEC-based angiogenesis assay. Protein and mRNA levels were assessed by immunoblotting and quantitative RT-PCR. RESULTS: CD45-/CD31-/CD34+ preadipocytes were observed with a prevalence of up to 1.5% of total viable cells in human granulation tissue. Immunofluorescence staining suggested a spatial proximity of these cells to CD68+ macrophages in vivo. In vitro, ASCs exposed to M1, but not to M2 macrophage secretome showed a pro-fibrotic response characterized by stress fiber formation, elevated alpha smooth muscle actin (SMA), and increased expression of integrins ITGA5 and ITGAV. Macrophage-secreted IL1B and TGFB1 mediated this response via the PI3K/AKT and p38-MAPK pathways. In addition, ASCs exposed to M1-inflammatory stress demonstrated reduced migration, switched to a glycolysis-dominated metabolism with reduced ATP production, and increased levels of inflammatory cytokines such as IL1B, IL8, and MCP1. Notably, M1 but not M2 macrophages enhanced the angiogenic potential of ASCs. CONCLUSION: Preadipocyte fate in wound tissue is influenced by macrophage polarization. Pro-inflammatory M1 macrophages induce a pro-fibrotic response in ASCs through IL1B and TGFB1 signaling, while anti-inflammatory M2 macrophages have limited effects. These findings shed light on cellular interactions in chronic wounds and provide important information for the potential therapeutic use of ASCs in human wound healing.

Determining HER2 Status by Artificial Intelligence: An Investigation of Primary, Metastatic, and HER2 Low Breast Tumors.

The expression of human epidermal growth factor receptor 2 (HER2) protein or gene transcripts is critical for therapeutic decision making in breast cancer. We examined the performance of a digitalized and artificial intelligence (AI)-assisted workflow for HER2 status determination in accordance with the American Society of Clinical Oncology (ASCO)/College of Pathologists (CAP) guidelines. Our preliminary cohort consisted of 495 primary breast carcinomas, and our study cohort included 67 primary breast carcinomas and 30 metastatic deposits, which were evaluated for HER2 status by immunohistochemistry (IHC) and in situ hybridization (ISH). Three practicing breast pathologists independently assessed and scored slides, building the ground truth. Following a washout period, pathologists were provided with the results of the AI digital image analysis (DIA) and asked to reassess the slides. Both rounds of assessment from the pathologists were compared to the AI results and ground truth for each slide. We observed an overall HER2 positivity rate of 15% in our study cohort. Moderate agreement (Cohen's κ 0.59) was observed between the ground truth and AI on IHC, with most discrepancies occurring between 0 and 1+ scores. Inter-observer agreement amongst pathologists was substantial (Fleiss´ κ 0.77) and pathologists' agreement with AI scores was 80.6%. Substantial agreement of the AI with the ground truth (Cohen´s κ 0.80) was detected on ISH-stained slides, and the accuracy of AI was similar for the primary and metastatic tumors. We demonstrated the feasibility of a combined HER2 IHC and ISH AI workflow, with a Cohen's κ of 0.94 when assessed in accordance with the ASCO/CAP recommendations.

In-home environmental exposures predicted from geospatial characteristics of the built environment and electronic health records of children with asthma.

PURPOSE: Children may be exposed to numerous in-home environmental exposures (IHEE) that trigger asthma exacerbations. Spatially linking social and environmental exposures to electronic health records (EHR) can aid exposure assessment, epidemiology, and clinical treatment, but EHR data on exposures are missing for many children with asthma. To address the issue, we predicted presence of indoor asthma trigger allergens, and estimated effects of their key geospatial predictors. METHODS: Our study samples were comprised of children with asthma who provided self-reported IHEE data in EHR at a safety-net hospital in New England during 2004-2015. We used an ensemble machine learning algorithm and 86 multilevel features (e.g., individual, housing, neighborhood) to predict presence of cockroaches, rodents (mice or rats), mold, and bedroom carpeting/rugs in homes. We reduced dimensionality via elastic net regression and estimated effects by the G-computation causal inference method. RESULTS: Our models reasonably predicted presence of cockroaches (area under receiver operating curves [AUC] = 0.65), rodents (AUC = 0.64), and bedroom carpeting/rugs (AUC = 0.64), but not mold (AUC = 0.54). In models adjusted for confounders, higher average household sizes in census tracts were associated with more reports of pests (cockroaches and rodents). Tax-exempt parcels were associated with more reports of cockroaches in homes. Living in a White-segregated neighborhood was linked with lower reported rodent presence, and mixed residential/commercial housing and newer buildings were associated with more reports of bedroom carpeting/rugs in bedrooms. CONCLUSIONS: We innovatively applied a machine learning and causal inference mixture methodology to detail IHEE among children with asthma using EHR and geospatial data, which could have wide applicability and utility.

Impact of meteorology on indoor air quality, energy use, and health in a typical mid-rise multi-family home in the eastern United States.

Heating and cooling requirement differences across climates not only have carbon emissions and energy efficiency implications but also impact indoor air quality (IAQ) and health. Energy and IAQ building simulation models help understand tradeoffs or co-benefits, but these have not been applied to evaluate climate zone or multi-family home differences. We modeled a four-story multi-family home in six U.S. climate zones and quantified energy, IAQ, and health outcomes with EnergyPlus, CONTAM, and a pediatric asthma systems science model. Pollutant sources included cooking and ambient. Outputs were daily PM2.5 and NO2 indoor concentrations, infiltration, energy for heating and cooling, and asthma exacerbations, which were compared across climate zones, apartment units, and resident behaviors. Daily ambient-sourced PM2.5 decreased and cooking-sourced PM2.5 increased with higher ambient temperatures. Infiltration air changes per hour were higher on the first versus the fourth floor and in colder climates. Window opening during cooking led to decreases in total pollutant concentrations (11%-18% for PM2.5 and 9%-15% for NO2 ), 3%-4% decreases in asthma exacerbations within climate zones, and minimal impacts on cooling, but led to increased heating demand (4%-8%). Our results demonstrate the influence of meteorology, multi-family building characteristics, and resident behavior on IAQ, energy, and health, focused on multi-zone methodology.

Early postoperative arterial lactate concentrations to stratify risk of post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) represents the major determinant for death after liver resection. Early recognition is essential. Perioperative lactate dynamics for risk assessment of PHLF and associated morbidity were evaluated. METHODS: This was a multicentre observational study of patients undergoing hepatectomy with validation in international high-volume units. Receiver operating characteristics analysis and cut-off calculation for the predictive value of lactate for clinically relevant International Study Group of Liver Surgery grade B/C PHLF (clinically relevant PHLF (CR-PHLF)) were performed. Lactate and other perioperative factors were assessed in a multivariable CR-PHLF regression model. RESULTS: The exploratory cohort comprised 509 patients. CR-PHLF, death, overall morbidity and severe morbidity occurred in 7.7, 3.3, 40.9 and 29.3 per cent of patients respectively. The areas under the curve (AUCs) regarding CR-PHLF were 0.829 (95 per cent c.i. 0.770 to 0.888) for maximum lactate within 24 h (Lactate_Max) and 0.870 (95 per cent c.i. 0.818 to 0.922) for postoperative day 1 levels (Lactate_POD1). The respective AUCs in the validation cohort (482 patients) were 0.812 and 0.751 and optimal Lactate_Max cut-offs were identical in both cohorts. Exploration cohort patients with Lactate_Max 50 mg/dl or greater more often developed CR-PHLF (50.0 per cent) than those with Lactate_Max between 20 and 49.9 mg/dl (7.4 per cent) or less than 20 mg/dl (0.5 per cent; P < 0.001). This also applied to death (18.4, 2.7 and 1.4 per cent), severe morbidity (71.1, 35.7 and 14.1 per cent) and associated complications such as acute kidney injury (26.3, 3.1 and 2.3 per cent) and haemorrhage (15.8, 3.1 and 1.4 per cent). These results were confirmed in the validation group. Combining Lactate_Max with Lactate_POD1 further increased AUC (ΔAUC = 0.053) utilizing lactate dynamics for risk assessment. Lactate_Max, major resections, age, cirrhosis and chronic kidney disease were independent risk factors for CR-PHLF. A freely available calculator facilitates clinical risk stratification (www.liver-calculator.com). CONCLUSION: Early postoperative lactate values are powerful, readily available markers for CR-PHLF and associated complications after hepatectomy with potential for guiding postoperative care.Presented in part as an oral video abstract at the 2020 online Congress of the European Society for Surgical Research and the 2021 Congress of the Austrian Surgical Society.

Liver failure represents a major complication after liver resection and determines the risk of postoperative death, therefore early anticipation and risk stratification are highly relevant. This study, of 991 patients in three international centres, shows that the maximum lactate blood level within 24 h after surgery is a very strong factor predicting the further course after liver operations. Lactate could potentially aid in clinical decision making such as prophylactic treatment, intensified observation or early discharge of patients.

Organizational contextual factors that predict success of a quality improvement collaborative approach to enhance integrated HIV-tuberculosis services: a sub-study of the Scaling up TB/HIV Integration trial.

BACKGROUND: A quality improvement (QI) collaborative approach to enhancing integrated HIV-Tuberculosis (TB) services may be effective in scaling up and improving the quality of service delivery. Little is known of the role of organizational contextual factors (OCFs) in influencing the success of QI collaboratives. This study aims to determine which OCFs were associated with improvement in a QI collaborative intervention to enhance integrated HIV-TB services delivery. METHODS: This is a nested sub-study embedded in a cluster-randomized controlled trial. Sixteen nurse supervisors (clusters) overseeing 40 clinics were randomized (1:1) to receive QI training and mentorship, or standard of care support (SOC). In the QI arm, eight nurse supervisors and 20 clinics formed a "collaborative" which aimed to improve HIV-TB process indicators, namely HIV testing, TB screening, isoniazid preventive therapy (IPT) initiations, viral load testing, and antiretroviral therapy for TB patients. OCFs measured at baseline were physical infrastructure, key staff, flexibility of clinic hours, monitoring data for improvement (MDI), and leadership support. Surveys were administered to clinic staff at baseline and month 12 to assess perceptions of supportiveness of contexts for change, and clinic organization for delivering integrated HIV-TB services. Linear mixed modelling was used to test for associations between OCFs and HIV-TB process indicators. RESULTS: A total of 209 clinic staff participated in the study; 97 (46.4%) and 112 (53.6%) from QI and SOC arms, respectively. There were no differences between the QI and SOC arms scores achieved for physical infrastructure (78.9% vs 64.7%; p = 0.058), key staff (95.8 vs 92; p = 0.270), clinic hours (66.9 vs 65.5; p = 0.900), MDI (63.3 vs 65; p = 0.875, leadership support (46.0 vs 57.4; p = 0.265), and perceptions of supportiveness of contexts for change (76.2 vs 79.7; p = 0.128 and clinic organization for delivering integrated HIV-TB services (74.1 vs 80.1; p = 0.916). IPT initiation was the only indicator that was significantly improved in the parent study. MDI was a significantly associated with increasing IPT initiation rates [beta coefficient (ß) = 0.004; p = 0.004]. DISCUSSION: MDI is a practice that should be fostered in public health facilities to increase the likelihood of success of future QI collaboratives to improve HIV-TB service delivery. TRIAL REGISTRATION: Clinicaltrials.gov , NCT02654613 . Registered 01 June 2015.

Oxidant therapy improves adipogenic differentiation of adipose-derived stem cells in human wound healing.

BACKGROUND: Adipose-derived stem cells (ASC) and adipocytes are involved in numerous physiological and pathophysiological conditions, which have been extensively described in subcutaneous and visceral fat depots over the past two decades. However, much less is known about ASC and adipocytes outside classical fat tissue depots and their necessity in tissue remodeling after injury. Therefore, we investigated the etiology of adipocytes in human granulation tissue and define their possible role wound healing. METHODS: Identification of human wound tissue adipocytes was determined by immunohistochemical staining of granulation tissue sections from patients undergoing surgical debridement. Stromal cell fractions from granulation tissue and subcutaneous fat tissue were generated by collagenase type II-based protocols. Pro- and anti-inflammatory wound bed conditions were mimicked by THP1- and CD14+ monocyte-derived macrophage models in vitro. Effects of macrophage secretome on ASC differentiation and metabolism were determined by immunoblotting, flow cytometry, and microscopy assessing early and late adipocyte differentiation states. Functional rescuing experiments were conducted by lentiviral transduction of wildtype PPARG, IL1RA, and N-chlorotaurine (NCT) treatment. RESULTS: Single and clustered adipocyte populations were detected in 11 out of 13 granulation tissue specimens and single-cell suspensions from granulation tissue showed adipogenic differentiation potential. Pro-inflammatory signaling by IFNG/LPS-stimulated macrophages (M (IFNG/LPS)) inhibited the maturation of lipid droplets in differentiated ASC. In contrast, anti-inflammatory IL4/IL13-activated macrophages (M (IL4/IL13)) revealed minor effects on adipocyte development. The M (IFNG/LPS)-induced phenotype was associated with a switch from endogenous fatty acid synthesis to glycolysis-dominated cell metabolism and increased pro-inflammatory cytokine production. Impaired adipogenesis was associated with increased, but seemingly non-functional, CEBPB levels, which failed to induce downstream PPARG and CEBPA. Neither transgenic PPARG overexpression, nor inhibition of IL1B was sufficient to rescue the anti-adipogenic effects induced by IFNG/LPS-activated macrophages. Instead, macrophage co-treatment during stimulation with NCT, a mild oxidant produced by activated granulocytes present in human wounds in vivo, significantly attenuated the anti-adipogenic effects. CONCLUSIONS: In conclusion, the appearance of adipocytes in wound tissue indicates a prevailing anti-inflammatory environment that could be promoted by NCT treatment and may be associated with improved healing outcomes.

Addressing the interaction between food insecurity, depression risk and informal work: findings of a cross-sectional survey among informal women workers with young children in South Africa.

BACKGROUND: There is a high burden of depression globally, including in South Africa. Maternal depression is associated with poverty, unstable income, food insecurity, and lack of partner support, and may lead to poor outcomes for mothers and children. In South Africa one-third of working women are in informal work, which is associated with socioeconomic vulnerability. METHODS: A cross sectional survey explored work setting and conditions, food security and risk of depression among informal working women with young children (0-3 years). Depression risk was assessed using the Edinburgh Postnatal Depression Score (EPDS) and Whooley score. Food insecurity was evaluated using Household Food Insecurity Access Scale. Data was analysed using SPSS and Stata. RESULTS: Interviews were conducted with 265 informal women workers. Types of work included domestic work, home-based work, informal employees and own account workers, most of whom were informal traders. Most participants (149/265; 56.2%) earned between US$70-200 per month, but some participants (79/265; 29.8%) earned < US$70 per month, and few earned > US$200 per month (37/265; 14.0%). Many participants experienced mild (38/267; 14.3%), moderate (72/265; 27.2%) or severe (43/265; 16%) food insecurity. Severe food insecurity was significantly higher among participants with the lowest income compared to those with the highest income (p = 0.027). Women who received financial support from the baby's father were less likely to be food insecure (p = 0.03). Using EPDS scores, 22/265 (8.3%) women were designated as being at risk of depression. This was similar among postnatal women and women with older children. Household food insecurity was significantly associated with depression risk (p < 0.001). CONCLUSIONS: Informal women workers were shown to be vulnerable with low incomes and high rates of food insecurity, thus increasing the risk for poor maternal health. However, levels of depression risk were low compared to previous estimates in South Africa, suggesting that informal workers may have high levels of resilience. Interventions to improve social protection, access to health services, and support for safe childcare in the workplace could improve the health and wellbeing of these mothers and support them to care for their children.

A tree-planting decision support tool for urban heat mitigation.

Heat poses an urgent threat to public health in cities, as the urban heat island (UHI) effect can amplify exposures, contributing to high heat-related mortality and morbidity. Urban trees have the potential to mitigate heat by providing substantial cooling, as well as co-benefits such as reductions in energy consumption. The City of Boston has attempted to expand its urban canopy, yet maintenance costs and high tree mortality have hindered successful canopy expansion. Here, we present an interactive web application called Right Place, Right Tree-Boston that aims to support informed decision-making for planting new trees. To highlight priority regions for canopy expansion, we developed a Boston-specific Heat Vulnerability Index (HVI) and present this alongside maps of summer daytime land surface temperatures. We also provide information about tree pests and diseases, suitability of species for various conditions, land ownership, maintenance tips, and alternatives to tree planting. This web application is designed to support decision-making at multiple spatial scales, to assist city officials as well as residents who are interested in expanding or maintaining Boston's urban forest.

Umbilical cord interleukin-6 predicts outcome in very low birthweight infants in a high HIV-burden setting: a prospective cohort study.

OBJECTIVES: South Africa has a double burden of high neonatal mortality and maternal HIV prevalence. Common to both is a proinflammatory in utero and perinatal milieu. The aim of this study was to determine cytokine profiles in HIV exposed (HE) and HIV unexposed (HU) very low birthweight (VLBW) infants and to determine whether these were associated with predischarge outcomes. DESIGN: Single-centre, prospective cohort study conducted from 1 June 2017 to 31 January 2019. PATIENTS: Inborn infants with birth weight of <1500 g were enrolled and cord blood was collected for interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) assays. Participants provided informed consent and ethics approval was obtained. OUTCOME MEASURES: The primary outcome was umbilical cord cytokine levels according to maternal HIV status. Secondary outcomes included death and/or serious neonatal infection, necrotising enterocolitis, intraventricular haemorrhage, periventricular leucomalacia, chronic lung disease and haemodynamically significant patent ductus arteriosus before discharge. RESULTS: A total of 279 cases were included with 269 cytokine assays performed on 122 HEs and 147 HUs. Median IL-6 levels were 53.0 pg/mL in HEs and 21.0 pg/mL in HUs (p=0.07). Median TNF-α levels were 7.2 pg/mL in HEs and 6.5 pg/mL in HUs (p=0.6). There was significantly more late-onset sepsis in the HE group compared with the HU group (41.2% vs 27.9%) (p=0.03). IL-6 levels were significantly higher for those with any adverse outcome (p=0.006) and death and/or any adverse outcome (p=0.0001). TNF-α levels did not differ according to predischarge outcomes. CONCLUSION: There is no significant difference in IL-6 and TNF-α levels in cord blood of HE compared with HU VLBWs. However, IL-6 levels are significantly higher in VLBWs with adverse predischarge outcomes, and VLBW HEs are at increased risk of adverse predischarge outcomes compared with HUs, particularly late-onset sepsis.

Changing youth behaviour in South Africa.

BACKGROUND: Youth behaviour in South Africa continues to be a public health concern. Primary prevention interventions remain a pre-requisite for promotion of improved social and health outcomes. AIM: The aim of the study was to assess the impact of a behavioural youth risk reduction intervention among grade 10 learners. SETTING: The Study was conducted in KwaZulu-Natal high schools, at UMgungundlovu District Municipality. METHODS: We conducted a cluster randomised controlled trial at 16 KwaZulu-Natal high schools where learners completed a self- administered questionnaire assessing youth risk behaviours. Schools were divided into two arms, intervention and a control arms. RESULTS: The intervention reduced learners' reports of carrying of a weapon to school in the past 30 days, but did not significantly reduce other assessed risk behaviours. Although the intervention appeared more likely to reduce learners' risk behaviours when compared to the control group, such as carrying weapons, risky sexual behaviour and alcohol and drug abuse. CONCLUSION: This study was unable to show statistical significance for these outcomes.

Evaluation of the effectiveness of a quality improvement intervention to support integration of maternal, child and HIV care in primary health care facilities in South Africa.

BACKGROUND: Despite policies and guidelines recommending integration of health services in South Africa, provision of maternal and child health services remains fragmented. This study evaluated a rapid, scaleable, quality improvement (QI) intervention to improve integration of maternal and child health and HIV services at a primary health level, in KwaZulu-Natal, South Africa. METHODS: A three-month intervention comprised of six QI mentoring visits, learning sessions with clinic staff to share learnings, and a self-administered checklist aimed to assist health workers monitor and implement an integrated package of health services for mothers and children. The study evaluated 27 clinics in four sub-districts using a stepped-wedge design. Each sub-district received the intervention sequentially in a randomly selected order. Five waves of data collection were conducted in all participating clinics between December 2016-February 2017. A multi-level, mixed effects logistic regression was used to account for random cluster fixed time and group effects using Stata V13.1. RESULTS: Improvements in some growth monitoring indicators were achieved in intervention clinics compared to control clinics, including measuring the length of the baby (77% vs 63%; p = 0.001) and health workers asking mothers about the child's feeding (74% vs 67%; p = 0.003), but the proportion of mothers who received feeding advice remained unchanged (38% vs 35%; p = 0.48). Significantly more mothers in the intervention group were asked about their baby's health (44% vs 36%; p = 0.001), and completeness of record keeping improved (40% vs 26%; I = < 0.0001). Discussions with the mother about some maternal health services improved: significantly more mothers in the intervention group were asked about HIV (26.5% vs 19.5%; p = 0.009) and family planning (33.5% vs 19.5%; p <  0.001), but this did not result in additional services being provided to mothers at the clinic visit. CONCLUSION: This robust evaluation shows significant improvements in coverage of some services, but the QI intervention was unable to achieve the substantial changes required to provide a comprehensive package of services to all mothers and children. We suggest the QI process be adapted to complex under-resourced health systems, building on the strengths of this approach, to provide workable health systems strengthening solutions for scalable implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04278612. Date of Registration: February 19, 2020. Retrospectively registered.

Systematic review on peri-operative lactate measurements to predict outcomes in patients undergoing liver resection.

Lactate measurements have proven utility as a triage tool, therapeutic guide, and prognostic indicator, with broad use in Acute Care and transplantation. Its value in guiding therapy and predicting outcomes following liver resection is less well-defined. This systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines assessed the relationship between peri-operative lactate levels and morbidity and mortality after liver resection. Seven relevant studies comprising 2573 patients in total were identified. Six studies assessed intra-operative or early postoperative lactate levels, one publication examined pre-operative levels. All studies demonstrated a significant association between peri-operative lactate levels and adverse outcomes. The influence of pre-operative diabetes and cirrhosis on postoperative lactate levels was shown in one study each, no study assessed the association of lactate with post-hepatectomy liver failure according to defined criteria. The heterogeneity of study measurements and end-points precluded a meta-analysis from being performed. Early postoperative lactate >3-3.7 mmol/L is associated with mortality but validation of clear cut-off levels for outcome prediction is pending. Literature suggests lactate is a useful predictive marker for outcomes post liver surgery, especially when measured in the early postoperative phase. Further research is required to standardize the use of lactate measurements in a meaningful therapeutic manner.

Surgeon's Focussed Ultrasound Examination of the Long Saphenous Vein Reduces Surgical Time and Wound Complications.

BACKGROUND: Despite increased use of arterial grafts, the long saphenous vein (LSV) is often utilised as conduit for coronary artery bypass graft (CABG). Preoperative ultrasound (U/S) vein assessment is limited to patients with varicosities, clinical signs suggestive of poor vein conduits and a history of cardiac or vascular surgery. The aim of this study was to evaluate the usefulness and logistics of the surgeon incorporating intraoperative U/S assessment of the LSV into their regular practice. METHODS: All patients undergoing coronary artery revascularisation and open vein harvest in our institution were recruited from July 2016 to February 2017. Demographics, including known risk factors for wound complications were documented, in addition to surgical details such as harvest time, vein length and surgical repairs of the conduit. Focussed U/S assessment was performed intraoperatively by the surgical registrar before beginning the procedure. The diameter of the leg pre and postoperatively, as well as the incidence, type and severity of wound complications were documented for further statistical analysis. RESULTS: A total of 103 patients were included in this study. Two patients died perioperatively and were excluded from the study. The remaining 101 patients were separated in two cohorts-U/S group (n=32) and blind technique group (n=69). Demographics were similar between the groups, whilst other risk factors for harvest complications, such as presence of superficial varicosities on clinical examination and renal failure were significantly more frequent in the U/S group. The median harvest time was significantly lower within the U/S group (25 mins versus 40 mins; p=0.001), as was the rate of overall wound complications (6.2% vs 23.2%; p=0.04). CONCLUSIONS: Ultrasound assessment of the LSV by the surgical team intraoperatively is feasible, easy to learn and does not demand extra costs or delays. It significantly reduces surgical harvest time and it is associated with a reduced incidence of wound complications, swelling and postoperative mobility impairment.

Bio-inspired Domino oxa-Michael/Diels-Alder/oxa-Michael Dimerization of para-Quinols.

A bio-inspired, pyrrolidine-mediated, dimerization of para-quinols has been developed. It represents one of the most complex, yet general, dimerization reactions ever disclosed, selectively forming four new bonds, four new rings, and eight new contiguous stereogenic centres. The para-quinol starting materials are easily handled, bench-stable compounds, accessed in just one step from aromatic feedstocks. The reaction can be scaled up to give grams of polycyclic material, primed for further elaboration.

Renal cell metastasis to the thyroid gland: An emerging phenomenon.

INTRODUCTION: Suspected thyroid malignancies are usually assumed to be primary in origin. Rarely, in 1-3% of cases, the tumour arises from a secondary source such as a melanoma or breast carcinoma. There is a growing body of research concerning metastatic spread of renal cell carcinoma to the thyroid gland. PRESENTATION OF CASE: This case report describes the presentation and diagnostic work-up of an 84yr male presenting with a goitre and hoarse voice. Histopathological examination of the excised 95 × 65 × 55 mm tissue mass revealed metastatic clear cell renal cell carcinoma. DISCUSSION: This disease pattern has become increasingly apparent in recent literature. A literature review of 150 documented cases worldwide showed that the mean interval for this spread to occur is 9 years. CONCLUSION: There is a need for further investigation into the underlying pathophysiology of this phenomenon and increased awareness from clinicians of its existence.