bluuebunny/crossref_metadata_2025 huggingface dataset:
#2404 Predictors of mortality in patients with chronic kidney disease stages 3-4 without heart disease
Authors: Ostlund Ylva , Guron Gregor , Saeed Aso
Published: May 2024

Background and Aims

Cardiovascular disease is common in patients with chronic kidney disease (CKD). This may, at least in part, explain the high risk of mortality in this patient group. The aim of the present study was to identify factors associated with mortality in patients with CKD stages 3 and 4 without a diagnosis of heart disease.

Method

Study subjects were derived from a cohort of patients with CKD stages 3 and 4 who were recruited from our Nephrology Outpatient Clinic between February 2009 and December 2011. Ninety-one patients without a diagnosis of heart disease were included in this cross-sectional study. Mortality data were collected in April 2023.

Results

All-cause mortality was 28.6% (26 patients) during a mean follow-up of 11.2 ± 2.7 years.

Comparison of baseline data between non-survivors and survivors showed that non-survivors were significantly older, had lower glomerular filtration rate (GFR), higher ambulatory systolic blood pressure (ASBP), less nocturnal dipping of ASBP, higher carotid–femoral pulse wave velocity (cfPWV) and higher serum levels of troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) [Tables 1 and 2]. In addition, the proportion of patients with diabetes and on treatment with beta-blockers was elevated in non-survivors [Tables 1 and 2]. There were no statistically significant differences between groups in smoking history, treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, diuretics, calcium channel blockers, alpha-blockers, statins, active vitamin D analogs, calcium-based or non-calcium-based phosphate binders.

In a binary logistic regression analysis, to identify independent predictors of mortality, we included age, gender, baseline GFR, serum NT-proBNP, TnT, cfPWV, percent of nocturnal dipping of ASBP, diagnosis of diabetes, and treatment with beta-blockers. Only less nocturnal dipping of ASBP (Exp [β] value of 0.86, 95% CI 0.77–0.97, p = 0.016) and advancing age (Exp [β] value of 0.91, 95% CI 0.84–0.99, p = 0.024) significantly predicted all-cause mortality.

Conclusion

In patients with CKD stage 3 and 4 without a diagnosis of heart disease only older age and less nocturnal dipping of ASBP were independently associated with mortality. Although baseline levels of serum NT-proBNP and TnT were elevated in non-survivors, neither serum NT-proBNP nor TnT showed independent associations with mortality in this cohort.
#1137 Association between cognitive function, depressive symptoms and quality of life in older patients with severely reduced GFR and kidney failure
Authors: Demirhan Imre , Van Oevelen Mathijs , Voorend Carlijn , Mooijaart Simon , van Buren Marjolijn , Bos Willem Jan W , Abrahams Alferso
Published: May 2024

Background and Aims

Impaired cognitive function and reduced health-related quality of life (HRQoL) are common in older patients with chronic kidney disease (CKD) with severely reduced GFR and kidney failure. Older patients with CKD often regard HRQoL as a health priority, but it is unknown whether cognitive function associates with HRQoL and whether depressive symptoms mediate this association. We therefore aim to examine the association between cognitive function and HRQoL, and explore the mediating role of depressive symptoms.

Method

Patients aged 65 years and older with an eGFR between 20 and 10 mL/min/1.73 m2 participating in the ongoing DIALysis or not: Outcomes in older kidney patients with GerIatriC Assessment (DIALOGICA) study were included. Cognitive function, depressive symptoms and HRQoL were assessed using the Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS-15) and Twelve-Item Short Form Health Survey (SF-12) questionnaire, respectively. The SF-12 yields a Mental Component Summary (MCS) score and Physical Component Summary score (PCS). We created a diagram of the hypothesized direct and indirect pathways between cognition and HRQoL, with depressive symptoms as the purported mediator (Fig. 1). We used cross-sectional multivariable linear regression analyses to examine the association between cognitive function and both mental and physical HRQoL, and multivariable mediation analyses to explore the role of depressive symptoms.

Results

In total, 403 patients were included with a mean age of 76.5 years, with a standard deviation (SD) of 5.8 and a mean eGFR of 14.5 mL/min/1.73 m2 (SD 3.0). A majority of patients were male (71.5%). Cognitive function associated significantly with mental HRQoL (adjusted β 0.30, 95% confidence interval (CI) 0.05; 0.55, p 0.021), but not with physical HRQoL (adjusted β 0.18, 95% CI −0.09; 0.44, p 0.20). The mediation effect of depressive symptoms between cognitive function and MCS remained significant after adjustment (indirect effect 0.15, 95% CI 0.04; 0.26). Thus, lower cognitive function was associated with lower mental HRQoL, which was partly mediated by corresponding increases in depressive symptoms.

Conclusion

Cognitive function is associated with mental HRQoL, but not with physical HRQoL in older patients with severely reduced GFR and kidney failure. This association is partially mediated by depressive symptoms. These findings underline the importance of screening for cognitive impairment and depressive symptoms in this population and may increase the understanding of what potentially affects HRQoL. As HRQoL is seen as a health priority, further research should explore whether cognitive interventions or treatment of depressive symptoms result in improvement of HRQoL in this population.
#2283 Vitamin D metabolism in end stage kidney failure: people receiving haemodialysis can still synthesise 1,25-dihydroxyvitamin D
Authors: Huish Sharon , Hewison Martin
Published: May 2024

Background and Aims

A large proportion of haemodialysed patients remain vitamin D deficient, contributing to the development, and severity, of chronic kidney disease-mineral bone disorder (CKD-MBD). This study aimed to investigate the effect of vitamin D (cholecalciferol) supplementation on serum levels of 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 in a group of people receiving haemodialysis.

Method

Eighty-one haemodialysis patients (dialysis vintage ≥1 month) with low serum total 25(OH)D consented to participate. 40,000IU cholecalciferol was given weekly for 12-weeks followed by a maintenance dose of 20,000IU fortnightly (administered by dialysis nursing staff as part of routine care). Patients remained on active vitamin D (1,25(OH)2D3 and analogues) as part of routine care (clinician prescribed for management of calcium and PTH). Baseline and 12-month data were compared using related-samples Wilcoxon signed rank test (Table 1). NHS research ethics committee approval was received.

Results

Complete data were available and analysed for 55 patients. 1,25(OH)2D3 levels were low at baseline (48.3pmol/L, IQR 35.9-57.9pmol/L) despite 44 of 55 patients (80%) being prescribed an active vitamin D analogue (normal range 60-120pmol/L). Cholecalciferol supplementation normalised both serum 25(OH)D3 and 1,25(OH)2D3 and significantly increased 24,25(OH)2D3 (Table 1).

Conclusion

Synthesis of 1,25(OH)2D3 is maintained (in kidney failure) but is substrate dependent, and low serum 25(OH)D was evident at baseline. 1,25(OH)2D3 deficiency is therefore partly a consequence of 25(OH)D deficiency, rather than solely due to elevated FGF23 and reduced renal 1α-hydroxylase activity (which is shown to be present in kidney failure). Cholecalciferol supplementation increases the inactive substrate 25(OH)D3 rather than directly increasing 1,25(OH)2D3. Increases in 25(OH)D3 and 24,25(OH)2D3 are disproportionate to 1,25(OH)2D3 increases, demonstrating the known tight regulation of 1,25(OH)2D3 synthesis and secretion (in response to calcium and parathyroid hormone). Conventional oral vitamin D supplementation may provide a cheap and safe strategy for the management of vitamin D homeostasis in chronic kidney disease.
#1086 Blood-brain barrier permeability in patients with end-stage kidney disease: results from the BREIN study
Authors: Bobot Mickaël , Guedj Eric , Resseguier Noémie , Faraut Julien , Garrigue Philippe , Jourde-Chiche Noemie , Hache Guillaume , Vial Romain , Bouchouareb Dammar , Gonzalez Sandra , Guillet Benjamin , Burtey Stephane
Published: May 2024

Background and Aims

Chronic kidney disease (CKD) is associated with an increased risk of cognitive impairment. In several models of CKD in rodents, we highlighted that CKD was associated with cognitive impairment and increased blood-brain barrier (BBB) permeability, quantified using 99mTc-DTPA scintigraphy imaging (SPECT/CT). BBB permeability was both correlated with cognitive impairment and with indoxyl sulfate (IS) levels. Inactivation of Aryl Hydrocarbon Receptor (AhR), receptor of the IS, protected the CKD mouse from the IS-induced BBB permeability. The objective of the BREIN study is to confirm the existence of an increased BBB permeability in humans with CKD.

Method

The prospective cohort study BREIN (NCT04328415) prospectively included patients with end-stage kidney disease (ESKD), and healthy volunteers (Ctrl) matched in age (±5 years), gender, and educational level to a patient. In patients and volunteers, BBB permeability was quantified by brain 99mTc-DTPA SPECT/CT performed by a senior nuclear physician and as percentage of injected activity (%IA). A battery of neuro-cognitive tests was performed, serum uremic toxins accumulation and AhR activation were assessed in all participants.

Results

15 ESKD patients and 14 healthy volunteers were included. In ESKD patients had higher BBB permeability compared to controls: 0.29 0.07 vs. 0.14 0.06%IA, p < 0.0001. ESKD patients displayed lower MoCA score: 22.0 ± 5.0 vs. 27.3 ± 2.8, p = 0.008, impaired short-term memory (doors test): 12.5 ± 3.4 vs. 16.5 ± 3.4, p = 0.009, higher Beck depression score 8.1 ± 9.1 vs. 2.7 ± 3.4, p = 0.046, and slightly more daily cognitive complaints: 42.5 ± 29.3 vs. 29.8 ± 14.0 p = 0.153. ESKD patients displayed higher IS levels (2.8 ± 2.3 mmol/L vs. 0.9 ± 0.7 mmol/L, p = 0.006) and AhR activation (37.5 ± 17.8% vs. 24.7 ± 10.4%, p = 0.027). In ESKD patients, no significant correlation was found between BBB permeability and scores in cognitive tests, or serum uremic toxins levels.

Conclusion

This study confirms that ESKD patients display an increased BBB permeability compared to matched healthy volunteers, as well as cognitive and impairment. Association with uremic toxins and cognitive impairment needs to be assessed in larger cohorts.
#1923 Anticoagulation and risk of stroke in patients with incident atrial fibrillation and CKD stages 4-5—results from the nationwide FinACAF study
Authors: Jyrkilä Heini , Kaartinen Kati , Martola Leena , Halminen Olli , Haukka Jari , Linna Miika , Mustonen Pirjo , Putaala Jukka , Teppo Konsta , Hartikainen Juha , Airaksinen Juhani , Lehto Mika
Published: May 2024

Background and Aims

Atrial fibrillation (AF) is common in patients with chronic kidney disease (CKD). It is well known that CKD in AF patients increases the risk of thromboembolic complications, and also bleeding. However, there is lack of safety and efficacy data of oral anticoagulation (OAC) in patients with advanced CKD.

Method

The FinACAF study includes data from 411 000 patients covering all Finnish AF patients from 2004 to 2018. Using national unique personal identification numbers, individual patients’ data from several registries and laboratory databases were linked together. The inclusion criteria of this study were all patients 20 years or older with a new-onset, non-valvular AF between 2010 and 2018 and a measured estimated glomerular filtration rate (eGFR) within the proximity of the AF diagnosis. Risk of stroke in patients with CKD stages 4-5 (eGFR < 30 ml/min/1.73 m2) was evaluated. Patients on dialysis and those with functioning graft were excluded. Participants were followed for the occurrence of ischemic stroke (IS) until December 31st 2018 or until death or until the OAC exposure reached a maximum duration of 730 days, whichever came first. The follow-up period was capped at 730 days due to the limited number of patients with direct oral anticoagulation (DOAC) exposure exceeding 730 days. Hazard ratios [95% confidence intervals (CI)] comparing different OACs or no OAC were derived from the Cox regression model.

Results

The study cohort included 4148 patients. The mean (SD) eGFR was 21.5 (6.7) ml/min/1.73 m2. 1940 patients had no OAC, 1658 patients had warfarin and 550 patients had any DOAC (396 apixaban, 121 rivaroxaban, 17 dabigatran and 16 edoxaban). During the follow-up 146 patients (3.5%) had ischemic stroke. Compared to patients with no OAC (reference) HRs were 0.42 [95% CI 0.30-0.59)] for the patients with warfarin and 0.28 [95% CI 0.01-0.52)] for the patients with DOACs. Cumulative hazards for ischemic stroke are shown in the Figure.

Conclusion

Among patients with incident AF and advanced CKD, the risk of stroke was lowest in patients with DOACs and the worst in patients with no OAC. Warfarin users were positioned in between these two groups. Further analysis is needed to evaluate also the safety of different OACs in our cohort.
#2114 TIE2 activation promotes vascular protection of tubules to reduce PDGFB driven tubulointerstitial fibrosis in experimental chronic kidney disease
Authors: Pietilä Riikka , Marks Amanda , Betsholtz Christer , Jeansson Marie
Published: May 2024

Background and Aims

The relevance of endothelial dysfunction for tubulointerstitial fibrosis in chronic kidney disease (CKD) is poorly understood. Here, we utilize gain- and loss-of-function experiments to investigate the role of endothelial tyrosine kinase TIE2 for vascular-mediated protection in experimental CKD.

Method

TIE2 activation was achieved using a human TIE2-activating antibody (ABX), or conditional endothelial knockout of vascular endothelial protein tyrosine phosphatase (Veptp). Conditional endothelial knockout of Tie2 served as a TIE2-incompetent signalling model. CKD was induced by unilateral ureter obstruction (UUO).

Results

ABX treated and Veptp knockout mice were significantly protected from UUO-induced endothelial dysfunction, tubular injury, and tubulointerstitial fibrosis. Capillary density was preserved as well as fenestrations of peritubular capillaries. In contrast, Tie2 knockout mice had aggravated disease. Mechanistically, the link between endothelial dysfunction and tubulointerstitial fibrosis was tubular expression of PDGFB, which was reduced by ABX treatment and Veptp knockout. A role for endothelial-to-mesenchymal transition was ruled out by careful lineage tracing of endothelial cells and reporter for mesenchymal cells. UUO-induced tubulointerstitial fibrosis was reduced in Pdgfb knockout mice, supporting causality of PDGFB in mesenchymal activation and fibrosis. ABX treated and Veptp knockout mice had significantly lower UUO-induced PDGFB levels.

Conclusion

Our data supports a key role of the endothelium and TIE2 signalling in CKD. We introduce ABX as a new therapeutic approach in CKD and demonstrate the sequence of events from endothelial dysfunction to tubulointerstitial fibrosis.
#313 Enhanced urinary phosphorous reduction: comparative study of oxylanthanum carbonate and tenapanor in rat
Authors: Medicherla Satya , Reddy Guru , Gupta Pramod , Gupta Shalabh
Published: May 2024

Background and Aims

End-stage renal disease (ESRD) affects >7 M people worldwide and ∼70% of patients with ESRD have hyperphosphatemia. Oxylanthanum carbonate (OLC) is a novel nanotechnology product that combines lanthanum, which has the highest binding capacity vs other phosphate (P) binders, with a smaller pill size that is swallowed with water vs chewed. Tenapanor is a sodium hydrogen exchanger inhibitor used to reduce serum P in adults with chronic kidney disease (CKD) on dialysis. A previous study conducted by King et al found that when administered together, tenapanor and sevelamer decreased urinary p excretion significantly more than either tenapanor or sevelamer alone across all sevelamer dose levels. Employing an identical study design and dosing regimen, the objective of our study was to evaluate the effects of tenapanor and OLC on P excretion.

Method

In our study, we utilized the study design and dosage regimen from King et al involving sevelamer and tenapanor. 64 male Sprague Dawley rats were fed standard chow 1 week prior to study start. On study day −1, animals were randomized into 3 study groups (n = 8): 1) vehicle, 2) tenapanor 0.15 mg/kg, 3) Vehicle + OLC 0.75%, 4) Vehicle + OLC 1.5%, 5) Vehicle + OLC 3%, 6) tenapanor 0.15 mg/kg + OLC 0.75%, 7) tenapanor 0.15 mg/kg + OLC 1.5%, and 8) tenapanor 0.15 mg/kg + OLC 3%. Vehicle and tenapanor were dosed PO twice/day whereas OLC was incorporated into the diets. 24-hour urine samples were collected using metabolic cages on day 9, 10, and 11 for urinary P measurements.

Results

Compared to vehicle alone (group 1), P reduction of tenapanor (group 2) was 8.5 mg/day (not significant), while P reduction of OLC (group 5) was 25.3 mg/day (significant). OLC had 16.8 mg/day more P reduction than tenapanor (Fig. 1).

Conclusion

OLC demonstrated 3x more effective urine P reduction vs tenapanor. Subsequent analyses will focus on examining the combination of tenapanor and OLC. Combining OLC and tenapanor utilizes 2 different mechanisms of action to manage P levels while having a low pill burden, which may lead to synergistic effects to be investigated in future studies.
#1387 Comprehensive evaluation of clinical consequences in diverse forms of fistula elevation procedure
Authors: Nanami Masayoshi , Mimura Yasuyuki , Kuma Akihiro , Hasuike Yukiko , Nakanishi Takeshi , Kuragano Takahiro
Published: May 2024

Background and Aims

Arteriovenous fistula (AVF) superficialization is a recommended alternative autologous vascular access (VA) in patients for whom conventional AVF creation is not possible because of insufficient forearm vessels. This procedure utilizes a deeply located vein as an outflow conduit in AVF creation and makes the vein accessible for cannulation. Tunnel transposition (TT) is employed in a standard manner as a venous superficialization technique. This is accomplished by tunneling the transected vein through a subcutaneous tunnel. However, TT is frequently associated with stenosis at the area of transposition because the transposed vein is torsed, kinked, or compressed by external tissue. Thus, TT tends to be exclusively applied to the basilic vein in the upper arm considering both the anatomic positional relation and the inherent limitations of this procedure. We recently reported that elevation transposition (ET) can serve as a practical substitute for TT (Contrib Nephrol. 2019:198:1-11). ET is a simplified minimally invasive superficialization approach in which the vein is elevated and positioned in a subcutaneous pocket immediately beneath the incision. In AVF superficialization employing ET (i.e., fistula elevation procedure [FEP]), three potential outflow veins are available in the upper arm: the cephalic, basilic, and brachial veins. This study was performed to comprehensively evaluate the clinical consequences of three valid FEP techniques to ascertain whether they are reasonable alternatives to autologous VA and which, if any, have superior performance.

Method

The demographic and outcome data of 111 patients who underwent the FEP from April 2016 to June 2023 were retrospectively collected and analyzed. The outcomes of the three fistula techniques were assessed and compared in terms of patency rates, requirements for VA intervention therapy (VAIVT), and complication rates.

Results

The mean follow-up period was 36.2 ± 20.1 (range, 1.3-80.8) months. The basilic, cephalic, and brachial vein-based FEP was performed in 63.1%, 23.4%, and 13.5% of cases, respectively. The overall cumulative primary and secondary patency rates were 76.2% and 98.2% at 1 year and 70.7% and 97.0% at 2 years, respectively. VAIVT was required in 32.4% of cases, and the patency rates at 1 and 2 years after VAIVT were 65.3% and 62.0%, respectively. There were no significant differences in these patency rates among the three FEP types. Minor complications such as lymphorrhea or epidermolysis occurred in only 4.5% of cases.

Conclusion

Our results suggest that the FEP provides three equivalently reliable options to accommodate the deeply located venous anatomy of the upper arm on individual-patient basis. The diversity of the FEP may contribute to avoiding prosthetic VA and central venous catheter-based dialysis, at least in part, by expanding the applicability of the autologous VA.
#3142 Evaluation of antipruritic effect of tacrolimus on hemodialysis patients with uremic pruritus, a double-blind, randomized, clinical trial
Authors: Roozbeh Jamshid , Masjedi Fatemeh
Published: May 2024

Background and Aims

Pruritus in patients undergoing hemodialysis is a highly prevalent complication that affects quality of life. Several medications are currently used for the treatment of uremic pruritus, but these are not satisfactory.

There are few studies about the beneficial effect of oral Tacrolimus on dermatologic problems such as pruritus. Considering the condition of hemodialysis in ESKD patients and the probable presence of oral Tacrolimus in their future treatment plan, this trial is designed to assess the antipruritic effect of Tacrolimus compared with placebo.

Method

This multicenter, randomized, double-blind, placebo-controlled clinical trial included 75 patients undergoing hemodialysis. The patients were randomized to a treatment group (Tacrolimus 1 mg/day) or a control group (placebo). The treatment lasted eight weeks, followed by a 2-week observational period. Visual Analogue Scale (VAS), % affected Body Surface Area (%BSA), and 12-Pruritus Severity Scale questionnaire (12-PSS) were measured before and after treatment periods. Moreover, sleep quality and the effect of sex were also evaluated.

Results

Seventy-five patients under hemodialysis (mean age of 58.18 ± 09.39 years) completed the study. Mean changes in VAS, %BSA, and 12-PSS after the interventions (Tacrolimus vs. placebo, mean ± SD) were as follows, respectively: −3.77 ± 2.13 vs. −1.07 ± 1.17, −18.97 ± 12.20 vs. 2.44 ± 3.23, and −4.67 ± 3.21 vs. −1.32 ± 2.45 (P < 0.0001). An improvement in sleep quality was found in 52.6% (20/38) of patients after Tacrolimus intake (P < 0.01). Overall, Tacrolimus was more effective in women than men (P < 0.016).

Conclusion

Based on the preliminary results of this study, Tacrolimus can be introduced as an effective drug for the management of pruritus and can be an add-on therapy in uremic patients.
#1419 A single, easy-to-use question to assess pruritus intensity in daily dialysis practice
Authors: Mccafferty Kieran , Morin Isabelle , Menzaghi Frederique , Schaufler Thilo
Published: May 2024

Background and Aims

Chronic kidney disease-associated pruritus (CKD-aP) has been shown to negatively impact certain clinical outcomes and quality of life (QoL) in patients with kidney failure. However, regular screening for CKD-aP is not yet routine dialysis practice and no consensus on the preferred instrument exists. To facilitate implementation of regular screening for CKD-aP we assessed the performance of two different instruments validated in patients with CKD-aP.

Method

The Worst Itching Intensity Numerical Rating Scale (WI-NRS) asks patients to indicate the worst itch intensity in the past 24 hours (range 0 [no itch] to 10 [worst itch imaginable]). The 5-D Itch scale assesses itch-related QoL (range 5-25 where higher values indicate worse QoL) and includes one question on itch intensity over the past 2 weeks (5-D ‘degree’ domain, range 1 [not present] to 5 [unbearable]).

Both instruments were included in two phase-3 clinical trials, KALM-1 and KALM-2, that established the favourable benefit-risk profile of difelikefalin over placebo in patients on haemodialysis with moderate to severe CKD-aP. WI-NRS was collected daily during the trial and 5-D Itch at the first dialysis visit in weeks 5, 9, 11 and 13.

We assessed the correlations between both the 5-D total score and degree domain and a) the single WI-NRS measurement collected on the same day and b) the average of daily WI-NRS scores collected over the previous 2 weeks in all patients independent of treatment exposure.

Results

The two instruments demonstrated moderate to strong correlations (range 0.5635-0.7039, p < 0.0001) independent of whether the total 5-D Itch score or the 5-D itch degree question were compared with a single, same-day WI-NRS measurement or with the mean WI-NRS scores over the 2-week recall period of the 5-D Itch (Table).

In addition, correlations remained consistent over time, supporting the reliability of the findings.

Conclusion

Using the WI-NRS to ask patients about their worst itch in the past 24 hours is a simple and swift approach for reliably identifying those with bothersome pruritus that also affects their itch-related QoL.
A Qualitative Study of Barriers and Motivators to Prevent Secondhand Smoke Exposure Among Pregnant Women and Children in Egypt: Identifying Appropriate Approaches for Change
Authors: Hassanein Zeinab M , Nalbant Gamze , Bogdanovica Ilze , Langley Tessa , Murray Rachael L
Published: May 2024

Introduction

The prevalence of daily secondhand smoke (SHS) exposure among pregnant nonsmoking women and children in Egypt is estimated to be about 50% and 55%, respectively. This study aimed to explore barriers to preventing SHS exposure among pregnant women/children and smoking in the home in Egypt.

Aims and Methods

Six focus group discussions with pregnant women or mothers of children residing in urban–rural areas (n = 61) were conducted. Data were managed and analyzed using the Framework Method.

Results

Sixty-one participants aged 18–49 were recruited. They reported being never smokers and SHS exposure for themselves and their children was mainly at home. Pregnant women or mothers had some general knowledge of the dangers of SHS, but their knowledge appeared incomplete. The most commonly reported barriers to preventing SHS exposure/adopting a smoke-free home or workplace were social acceptance of smoking and SHS exposure, masculinity and gender norms of accepting smoking among men as a normative behavior, fear among women of damaging a relationship with family or even divorce, women resigning themselves to SHS exposure, and doctors not being supportive of smoking cessation. The majority of interviewees’ families were reported to allow smoking anywhere in the home. Others implemented some measures to prevent SHS; however, these tended to be inconsistently implemented.

Conclusions

Changing the norm of accepting smoking among men as a normative behavior within Egyptian society and better enforcement of smoke-free policies, will help to protect pregnant women and children from SHS.

Implications

This study suggests promising approaches to support the promotion of smoke-free homes and the prevention of SHS exposure among pregnant women and children in public places in Egypt. Better enforcement of smoke-free policies is needed. Healthcare professionals should support smoking cessation services in primary health centers. SHS policy, practice, and research should focus on husbands/fathers as they are the main source of SHS. There is a need for denormalization of SHS exposure in Egyptian society.
Nutrigenetic and Epigenetic Mechanisms of Maternal Nutrition–Induced Glucolipid Metabolism Changes in the Offspring
Authors: Jiao Peng , Lu Huizhen , Hao Lizhuang , Degen A Allan , Cheng Jianbo , Yin Zongjun , Mao Shengyong , Xue Yanfeng
Published: May 2024

Maternal nutrition during pregnancy regulates the offspring’s metabolic homeostasis, including insulin sensitivity and the metabolism of glucose and lipids. The fetus undergoes a crucial period of plasticity in the uterus; metabolic changes in the fetus during pregnancy caused by maternal nutrition not only influence fetal growth and development but also have a long-term or even life-long impact for the offspring. Epigenetic modifications, such as DNA methylation, histone modification, and non-coding RNAs, play important roles in intergenerational and transgenerational effects. In this context, this narrative review comprehensively summarizes and analyzes the molecular mechanisms underlying how maternal nutrition, including a high-fat diet, polyunsaturated fatty acid diet, methyl donor nutrient supplementation, feed restriction, and protein restriction during pregnancy, impacts the genes involved in glucolipid metabolism in the liver, adipose tissue, hypothalamus, muscle, and oocytes of the offspring in terms of the epigenetic modifications. This will provide a foundation for the further exploration of nutrigenetic and epigenetic mechanisms for integrative mother–child nutrition and promotion of the offspring’s health through the regulation of maternal nutrition during pregnancy. Note: This paper is part of the Nutrition Reviews Special Collection on Precision Nutrition.
The effects of omega-3 polyunsaturated fatty acids on muscle and whole-body protein synthesis: a systematic review and meta-analysis
Authors: Therdyothin Atiporn , Prokopidis Konstantinos , Galli Francesco , Witard Oliver C , Isanejad Masoud
Published: May 2024

Context

Sarcopenia describes the age-related decline in skeletal muscle mass and strength that is driven, at least in part, by an imbalance between rates of muscle protein synthesis (MPS) and muscle protein breakdown. An expanding body of literature has examined the effect of omega-3 polyunsaturated fatty acid (n-3 PUFA) ingestion on MPS rates in older adults, with mixed findings.

Objective

The aim of this systematic review and meta-analysis was to investigate the effectiveness of n-3 PUFA ingestion in stimulating rates of MPS and whole-body protein synthesis in healthy adults and clinical populations.

Data Sources

Searches were conducted of the PubMed, Web of Science, Cochrane Library, and Scopus databases from inception until December 2022 for articles on randomized controlled trials comparing the effect of n-3 PUFA ingestion vs a control or placebo on rates of MPS and whole-body protein synthesis. The search yielded 302 studies, of which 8 were eligible for inclusion.

Data Extraction

The random effects inverse-variance model was used and standardized mean differences (SMDs) with 95%CIs were calculated to assess the pooled effect. Risk of bias was assessed by the Cochrane Risk-of-Bias 2 tool.

Data Analysis

The main analysis indicated no effect of n-3 PUFA supplementation on MPS rates (k = 6; SMD: 0.03; 95%CI, −0.35 to 0.40; I2 = 30%; P = .89). Subgroup analysis based on age, n-3 PUFA dose, duration of supplementation, and method used to measure fractional synthetic rate also revealed no effect of n-3 PUFA ingestion on MPS. In contrast, the main analysis demonstrated an effect of n-3 PUFA ingestion on increasing whole-body protein synthesis rates (k = 3; SMD: 0.51; 95%CI, 0.12–0.90; I2 = 0%; P = .01).

Conclusions

n-3 PUFA ingestion augments the stimulation of whole-body protein synthesis rates in healthy adults and clinical populations.

Systematic Review Registration

PROSPERO registration no. 42022366986.
Opioid metabolism and drug-drug interaction in cancer
Authors: Aapro Matti , Fogli Stefano , Morlion Bart , Danesi Romano
Published: May 2024

Concomitant use of multiple drugs in most patients with cancer may result in drug-drug interactions (DDIs), potentially causing serious adverse effects. These patients often experience unrelieved cancer-related pain (CRP) during and after cancer treatment, which can lead to a reduced quality of life. Opioids can be used as part of a multimodal pain management strategy when non-opioid analgesics are not providing adequate pain relief, not tolerated, or are contraindicated. However, due to their narrow therapeutic window, opioids are more susceptible to adverse events when a DDI occurs. Clinically relevant DDIs with opioids are usually pharmacokinetic, mainly occurring via metabolism by cytochrome P450 (CYP). This article aims to provide an overview of potential DDIs with opioids often used in the treatment of moderate-to-severe CRP and commonly used anticancer drugs such as chemotherapeutics, tyrosine kinase inhibitors (TKIs), or biologics. A DDI-checker tool was used to contextualize the tool-informed DDI assessment outcomes with clinical implications and practice. The findings were compared to observations from a literature search conducted in Embase and PubMed to identify clinical evidence for these potential DDIs. The limited results mainly included case studies and retrospective reviews. Some potential DDIs on the DDI-checker were aligned with literature findings, while others were contradictory. In conclusion, while DDI-checkers are useful tools in identifying potential DDIs, it is necessary to incorporate literature verification and comprehensive clinical assessment of the patient before implementing tool-informed decisions in clinical practice.
Adjuvant treatment strategy evolution and risk stratification for hormone receptor-positive, human epidermal growth factor receptor-2 negative early breast cancer in China
Authors: Fan Ying , Ji Danyang , Jiang Mingxia , Tan Yujing , Yang Yang , Li Tianyi , Ma Xiao , Xu Binghe
Published: May 2024

Background

Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2−) early breast cancer (EBC) with high-risk clinicopathological features face an increased risk of recurrence. This study explored the evolving treatment landscape and clinical outcomes in patients with EBC using a nationwide database.

Patients and Methods

The study cohort comprised HR+/HER2−, stages 1-3, patients with EBC who underwent surgery and received adjuvant endocrine therapy (AET) from January 2013 to March 2021. High-risk patients were defined by ≥4 positive axillary lymph nodes, or 1-3 positive lymph node(s) with at least one high-risk feature (histologic grade 3, tumor size ≥5 cm, or Ki-67 ≥20%). A low-risk cohort included patients not meeting the criteria. Survival analysis was conducted with a cutoff of September 2021.

Results

The study included 4088 eligible patients (1310 high-risk patients and 2778 low-risk patients). High-risk patients were more likely to receive adjuvant chemotherapy and radiotherapy compared to low-risk patients. From 2013 to 2021, an increasing proportion of patients received aromatase inhibitors and ovarian function suppression as part of their AET. The 2-, 5-, and 7-year invasive disease-free survival for high-risk cohort were 90.67%, 75.26%, and 57.10%, respectively, these rates were notably higher for low-risk cohort at 97.14%, 89.85%, and 84.83%. High-risk patients demonstrated a higher risk of recurrence or death compared with low-risk patients (hazard ratio, 2.38; 95% CI, 1.82-3.12).

Conclusion

In the setting of standard or even intensive AET, patients with EBC with high-risk features still present high recurrence risk, highlighting the urgent need for innovative adjuvant treatment strategies.
Cybersecurity
Authors: Miller Seumas , Bossomaier Terry
Published: May 2024

Cybersecurity is often defined in terms of data security. This definition is too narrow. A broader definition includes security issues, such as disinformation and incitement on social media platforms. Cyberthreats include viruses, ransomware, and so on, and cybersecurity responses are often technical in character (e.g., firewalls, encryption). However, cybersecurity is not simply a technical issue. Consider the threat of disinformation and countermeasures to it. The internet and other cybertechnologies are embedded in institutions. This is obvious in the case of internet governance bodies such as ICANN. However, this institutional landscape also includes global technology companies (e.g., Facebook), criminal organizations, and state actors and their security agencies (e.g., NSA in the US). Moreover, some state actors are engaged in cyberwar (e.g., Russia). Therefore, a key notion is that of an institution. Institutions ought to have as their raison d’être to provide collective good such as, which, in the case of institutions operating in cyberspace, means cybersecurity.
Entanglement
Authors: Schofield John
Published: May 2024

This chapter discusses a recurring issue and a characteristic of wicked problems: the fact they are all entangled with one another; any attempt to fix one problem can create problems elsewhere, mirroring archaeology whereby material entanglement characterizes the archaeological record. Entanglement is a central theme across many disciplines, not least quantum theory. This theoretical chapter discusses how archaeologists have engaged with entanglement and how this sits alongside other frameworks such as actor network theory. The concept of messiness, used as an alternative to wicked problems to describe entangled and intractable social and environmental issues, is discussed. Other alternative frameworks discussed include ecosystems and assemblage theory, systems thinking and complexity theory which offer different ways to conceptualize and address wicked problems thus providing an essential terminology and conceptual framework for archaeologists and heritage practitioners.
Music and prenatal stress, anxiety, and depression
Authors: Sanfilippo Katie Rose M. , Stewart Lauren , Glover Vivette
Published: May 2024

Chapter 2 explores the potential role of music in addressing prenatal stress, anxiety, and depression. High stress levels and affective symptoms not only affect wellbeing during and after pregnancy but also may alter foetal and infant development. This chapter summarises some of the work being conducted in this area, primarily research on music-listening interventions, music therapy, and music groups, which have been found to be helpful in reducing stress, anxiety, and depression during pregnancy. There are still few studies in this area and even fewer that examine the potential benefits of musical care for people with specific needs such as those with high levels of anxiety or depression symptoms. This chapter ends with some suggestions for practice, but more importantly, highlights gaps in our knowledge and understanding and potential ways forward.
Online personalised music-making with patients in hospital during pregnancy
Authors: Shaughnessy Caitlin , Hall Andrew , Perkins Rosie
Published: May 2024

Chapter 6 reports on the development and implementation of an online programme of personalised, live music for patients in hospital maternity wards during the COVID-19 pandemic. The chapter introduces the music-making practice, which was based on Meaningful Music in Health Care (MiMiC), an innovative, artistic practice developed by Hanze University Groningen and the University Medical Center Groningen, the Netherlands. Evaluation of patients’ experiences of the programme are presented, revealing that live, person-centred music can build personalised connections, support emotional regulation, and offer opportunities for respite. Alongside this, perspectives from the musicians on the skills required for delivery are shared. Implications are considered for the future delivery of live, personalised, online music interventions in hospital maternity settings to support parental wellbeing.
Music for parent and child interaction
Authors: Pitt Jessica , Fox Sophie
Published: May 2024

Chapter 10 explores parent-child musical interaction, outlining the origins of musicality inherent in emotionally important relationships from infancy. It discusses communication in early childhood and presents musical interaction as an important component to the earliest communicative expressions of young children. By removing words and focusing on musical playfulness, the work of an early childhood music-arts organisation—Magic Acorns—has discovered through extensive research-informed, reflective practice that parental wellbeing is enhanced when children are recognised as communicators. Findings for practice are outlined, calling for attuned, improvisatory practice built on reduced adult talk, as a decolonising and liberating approach. The chapter questions neoliberal, measurement-driven societal pressures and proposes an ethics of care as the starting point for practice focusing on interaction, music-play, parents, and young children.
Religion, Philosophy, and Allegory in Early Greek Thought
Authors: Hladký Vojtěch
Published: May 2024

The chapter situates the Derveni papyrus in the contemporary religious and philosophical context. Based on the research of other scholars, it points out that in the given period, the division between the rational philosophical thought is not as sharp as in modern thought. We have rather to do with a continuous scale. Thus, most notably, unlike in modern religious thought, Greek gods that appear in the Derveni poem are closer to physical principles the Presocratic philosophers posit. But, in turn, these physical principles are far from the inert matter of modern physics. A specific form of relation of traditional religion and philosophy is allegorical interpretation which plays the key role also in the Derveni papyrus. The chapter gives an overview of the development and the forms of early allegorical interpretation. Its most prominent proponents were the followers of Anaxagoras whose influence is can be detected also in the Derveni treatise.
Initial Efforts
Authors: Stauffer George B.
Published: May 2024

Very few of Bach’s earliest compositions survive, leading to the idea that he may have destroyed the manuscripts of the pieces at a later point, viewing them as “youthful sins.” But the Neumeister Chorales, discovered only in 1985, provide a look at the type of works Bach was writing between 1695 and 1705 or so—that is, when he was still a teenager. Within the Neumeister anthology, Bach’s settings display an inventiveness and eclecticism that distinguishes them from the works of other composers in the album. Written mostly for manuals alone, the pieces are small but remarkably adventurous, brimming with new ideas. The handful of free works from the period show similar qualities, plus a penchant for virtuoso pedal writing. By 1703 Bach was able to win the audition—if not the appointment—for an organist position in Sangerhausen. Chapter 3 explores his compositional accomplishments at this early but critical moment.
Bach in Arnstadt and Mühlhausen
Authors: Stauffer George B.
Published: May 2024

Chapter 4 examines the nature of Bach’s organist appointments in Arnstadt and Mühlhausen. Shortly after the failed attempt to win the organist post in Sangerhausen in 1703, Bach was summoned to Arnstadt to inspect the recently completed Wender pipe organ in the New Church. His recital demonstrating the instrument so impressed the Church Council that they quickly appointed him organist of the church. Although quarrels with the Council eventually led to Bach’s move to Mühlhausen four years later, his time in Arnstadt was remarkably productive and led to his “first fruits” in the realm of organ composition, as the Obituary of 1750 put it. Bach’s tenure as organist of St. Blasius’s Church in Mühlhausen was short-lived, lasting only one year. But it provided him with the opportunity to write his first cantatas. These vocal works, like his organ compositions of the time, show the strong influence of North German style.
Chorale-Based Works
Authors: Stauffer George B.
Published: May 2024

Chapter 5 focuses on the “first fruits” of Bach’s chorale-prelude-writing in Arnstadt and Mühlhausen. Unlike the Neumeister Chorales from Ohrdruf and Lüneburg, the Arnstadt/Mühlhausen works incorporate obbligato pedal lines and display more expansive forms, often combining North German virtuoso figuration and echo techniques with Central German designs and cantabile part-writing. Works such as “Christ Lag in Todesbanden,” BWV718, and “Valet will ich dir geben,” BWV 735a, show Bach’s determination to use dense, intense contrapuntal textures. During this early period the young Bach also composed his initial chorale partitas—sets of variations on meditative hymn tunes that were highly popular in Thuringia. A work such as the Partita on “O Gott, du frommer Gott,” BWV 767, composed at this time, shows Bach’s indebtedness to both Johann Pachelbel and Georg Böhm. But it also exhibits a highly individual stamp that foreshadows Bach’s Weimar style.
Bach in Weimar
Authors: Stauffer George B.
Published: May 2024

Within a year of arriving in Mühlhausen, Bach accepted a position elsewhere, as organist to the ducal court in Weimar. Although Weimar was a sleepy, provincial town, it offered Bach special opportunities to expand his horizons through the extensive music collections of the court and of Johann Gottfried Walther, organist of the City Church. Bach was admired and well supported by the reigning dukes, Wilhelm Ernst and his nephew Ernst August, and the young Prince Johann Ernst, a prodigy and composer of progressive instrumental pieces. It was in Weimar that Bach wrote “the bulk of his organ works,” according to the Obituary, and it was there that he first encountered the concertos of Vivaldi, an event that radically changed his approach to composition. Chapter 6 surveys these events and discusses the French and Italian music Bach performed, studied, and transcribed during this productive period.
The Orgel-Büchlein
Authors: Stauffer George B.
Published: May 2024

One of Bach’s most important undertakings during the initial Weimar years was the Orgel-Büchlein, a project calling for the composition of 164 chorale settings. Bach completed only 45 of the intended pieces, but that was sufficient to allow him to work out a new method of writing organ music with strict three-, four-, and five-part texture and obbligato pedal. In the settings Bach also made great use of rhetorical figures to portray the various affects of the chorale texts. It was a turning point in the development of his keyboard idiom. Chapter 8 looks at the genesis of the Orgel-Büchlein (Bach seems to have compiled it over a period of several years, adding pieces little by little), its function as a compositional workbook and teaching collection, and the style of the pieces it contains. Bach appears to have lost interest in the project once he had worked out his compositional method.
Free Works
Authors: Stauffer George B.
Published: May 2024

Bach’s greatest contribution in the realm of free organ works, examined in chapter 12, was his rejection of the North German multisectional praeludium in favor of the Central German prelude and fugue. He had written prelude-fugue pairs earlier, but the result was often unbalanced, with large, ambitious fugues accompanied by cursory preludes. In Weimar, Bach developed new methods not only of expanding and organizing fugues but also of creating large, self-sufficient preludes as equal partners. He accomplished this initially by modifying aspects of North German and French styles, in works such as the Fantasia and Fugue in G Minor, BWV 542, and the Fantasia and Fugue in C Minor, BWV 562/1a and 546/2a. He then transformed the prelude-fugue pair by adopting the Venetian concerto principles of Antonio Vivaldi, in works such as the Toccata and Fugue in F Major, BWV 540, and the “Dorian” Toccata and Fugue in D Minor, BWV 538—compositions that broke new ground altogether.
Free Works
Authors: Stauffer George B.
Published: May 2024

Bach also wrote a number of independent fugues and singular pieces in Weimar—the subject of chapter 13. The “Little” Fugue in G Minor, BWV 568, and the “Gigue” Fugue in G Major, BWV 577, show his use of unified episodes and carefully controlled four-part texture, respectively. By contrast, the Fantasia in G Major, BWV 572, illustrates his Germanic interpretation of the French plein jeu setting, and the Toccata in C Major, BWV 564, demonstrates his adoption of the three-movement Italian concerto form. Both works were one-time experiments. Finally, in the Passacaglia in C Minor, BWV 582, Bach summarized the Central German and North German ostinato forms, not only writing a set of 20 brilliantly organized variations on a theme borrowed from André Raison but capping them with an immense permutation fugue on the same subject. It is as if Bach wanted to outdo the idols of his youth, Pachelbel and Buxtehude.