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Background: Bacterial vaginosis significantly affects gynecological health of women, and recurrence is common with a high prevalence in patients who received sucrose gel treatment. Evidence has found that nursing intervention has benefits in improving the rate of recurrence of gynecological diseases. The purpose of this study was to investigate the influence of nursing intervention on patients with recurrent bacterial vaginosis treated with sucrose gel., Methods: A total of 1096 patients with bacterial vaginosis were recruited and randomly divided into the intervention nursing group (n = 548) and the control group (n = 548) between May 2022 and October 2022. Patients with bacterial vaginosis in the nursing intervention group received the individualized nursing intervention program, while patients in the control group received routine nursing for vaginitis and follow-up. The clinical efficacy and the short form health survey MOS 36 items (SF-36) scale were used to evaluate the efficacy of nursing intervention efficacy in patients with vaginosis treated with sucrose gel., Results: Our results indicate that the nursing intervention was associated with significant improvements in physical functioning, depression, mental health, bodily vitality pain, and symptoms related to bacterial vaginosis compared to the control group patients. The social functioning-36 score in the nursing intervention group was higher than that in the control group during the 6-month period. Nursing intervention significantly decreased the recurrence of bacterial vaginosis via improvement quality of life and psychological states., Conclusions: In conclusion, the data in this study indicate that the nursing intervention improves recurrent bacterial vaginosis and the quality of life of patients treated with sucrose gel., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

To compare recurrence rates after a 1-year follow-up period of healed neuroischemic diabetic foot ulcers after treatment with or without sucrose octasulfate impregnated dressing. A 1-year prospective study with two arms was conducted between April 2021 and April 2023 on 92 patients with healed neuroischemic diabetic foot ulcers. Patients were divided into two groups; the treatment group, that includes patients healed with a sucrose octasulfate-impregnated dressing, and the control group, which includes patients treated with other local treatments different from sucrose octasulfate-impregnated dressings. After healing, patients were prospectively followed up during 1-year and assessed monthly in the specialised outpatient clinics. The main outcome of the study was ulcer recurrence after wound healing within 1 year follow-up. Secondary outcomes were minor or major amputation and all causes of death. Fifty patients in the treatment group and 42 patients in the control group were included. Fourteen (28%) patients suffered from a reulceration event in the treatment group compared to 28 (66.7%) in the control group, p < 0.001. Time to recurrence in the treatment group was 10 (16.26-2.75) and 11.50 (30.75-5.25) weeks in the control group, p = 0.464. There were no observed differences in the minor amputation rates between the two groups: 15.2% (n = 7) in the treatment group and 7.1% (n = 3) in the control group (p = 0.362). Major amputations and death outcomes were exclusively observed in the treatment group. Specifically, four major amputations (8.7%) in the treatment group were complications arising from recurring events complicated by infection during the SARS-CoV-2 period. Seven patients died due to complications not related with local therapy. The relative risk of recurrence was 20.18 times higher in the control group compared with those treated with octasulfate dressing (p < 0.001). Treatment with sucrose octasulfate-impregnated dressings can decrease recurrence rates of neuroischaemic diabetic foot ulcers more effectively than neutral dressings. Besides, it may enhance the foot's clinical properties in patients with poor microcirculation, which could aid in preventing future recurrences., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Small infants experience a myriad of stimuli while in the Neonatal Intensive Care Unit (NICU), with many being painful or stressful experiences, although medically necessary., Purpose: To determine what is known about nonpharmacological developmental care interventions used in the NICU to mitigate procedural pain of infants born under 32 weeks gestation., Search/strategy: Five electronic databases were searched: Medline, CINAHL, Scopus, Embase and the Cochrane Library. The inclusion criteria were as follows: experimental and nonexperimental studies from all publication years with infants born at less than 32 weeks gestational age; peer-reviewed research articles studying nonpharmacological interventions such as skin-to-skin care, facilitated tucking, nonnutritive sucking, hand hugs, and swaddling; and English language articles. Our search yielded 1435 articles. After the elimination of 736 duplicates, a further 570 were deemed irrelevant based on their abstract/titles. Then, 124 full-text articles were analyzed with our inclusion and exclusion criteria., Findings: Twenty-seven studies were reviewed. Sucrose, facilitated tucking, pacifier, skin-to-skin care, and human milk appeared to lessen pain experienced during heel sticks, suctioning, nasogastric tube insertions, and echocardiograms. All nonpharmacological interventions failed to prove efficacious to adequately manage pain during retinopathy of prematurity (ROP) examinations., Implications for Practice: Evidence review demonstrates that healthcare practitioners should use nonpharmacological measures to help prevent pain from day-to-day procedures in the NICU including heel sticks, nasogastric tube insertions, suctioning, echocardiograms, and subcutaneous injections., Implications for Research: Future research is necessary to better understand and measure how pain is manifested by very small premature infants. Specific research on mitigating the pain of examinations for retinopathy of prematurity is also needed., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by The National Association of Neonatal Nurses.)

Background: Hyperphosphatemia is associated with increased morbidity and mortality in patients with end-stage kidney disease (ESKD). Whereas clinical and observational studies have demonstrated the effectiveness of sucroferric oxyhydroxide (SO) in controlling serum phosphorus (sP) in ESKD, data on the real-world impact of switching to SO in patients on peritoneal dialysis (PD) are limited. In this retrospective database analysis, we examine the impact of SO on sP management over a 1-year period among PD patients prescribed SO as part of routine clinical care., Methods: We analyzed de-identified data from adults on PD in Fresenius Kidney Care clinics who were prescribed SO monotherapy between May 2018 and December 2019 as part of routine clinical management. Changes from baseline in sP levels, phosphate binder (PB) pill burden, and laboratory parameters were evaluated during the four consecutive 91-day intervals of SO treatment., Results: The mean age of the 402 patients who completed 1 year of SO was 55.2 years at baseline, and they had been on PD for an average of 19.9 months. SO was initiated with no baseline PB recorded in 36.1% of patients, whereas the remaining 257 patients were switched to SO from sevelamer (39.7%), calcium acetate (30.4%), lanthanum (1.2%), ferric citrate (14.0%), or more than one PB (14.8%). Mean sP at baseline was 6.26 mg/dL. After being prescribed SO, the percentage of patients achieving sP ≤ 5.5 mg/dL increased from 32.1% (baseline) to 46.5-54.0% during the 1-year follow-up, whereas the mean number of PB pills taken per day decreased from 7.7 at baseline (among patients on a baseline PB) to 4.6 to 5.4. Serum phosphorus and PB pill burden decreased regardless of changes in residual kidney function over the 12-month period. Similar results were observed for the full cohort (976 patients who either completed or discontinued SO during the 1-year follow-up)., Conclusions: Patients on PD who were prescribed SO as part of routine care for phosphorus management experienced significant reductions in SP and PB pills per day and improvements in sP target achievement, suggesting the effectiveness of SO on SP management with a concurrent reduction in pill burden., (© 2024. The Author(s).)

The impact of diet composition and energy content on schistosomiasis evolution and treatment efficacy is still controversial. This study compared the impact of sucrose-rich diet and intermittent fasting on Schistosoma mansoni infection and praziquantel (PZQ)-based chemotherapy response in mice. BALB/c mice were infected with S. mansoni and followed for 15 weeks. The animals were randomized into nine groups receiving high glycemic load (high-sucrose diet - HSD), low caloric load (standard chow alternate-day fasting - ADF), and standard chow ad libitum (AL). Eight weeks after S. mansoni infection, these groups remained untreated or were treated with PZQ (300 mg/kg/day) for 3 days. Our results indicated that parasite load (S. mansoni eggs and parasite DNA levels), granulomatous inflammation (granulomas number and size), and liver microstructural damage (reduction in hepatocytes number, increase in nucleus-cytoplasm ratio, connective stroma expansion and fibrosis) were increased in ADF-treated animals. These animals also showed decreased eggs retention, granulomatous inflammation and collagen accumulation in the small intestine. Conversely, HSD diet and PZQ treatment attenuated all these parameters and stimulated hepatic regenerative response. PZQ also stimulated fibrosis resolution in HSD-treated mice, effect that was limited ADF-exposed mice. Our findings indicate that dietary glycemic and energy load can modulate schistosomiasis progression and the severity of hepatic and intestinal granulomatous inflammation in untreated and PZQ-treated mice. Thus, lower intestinal eggs retention may potentially be linked to worsening liver disease in ADF, while attenuation of hepatic and intestinal granulomatous inflammation is consistent with reduced parasite load in HSD- and PZQ-treated animals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Despite women representing most of those affected by major depression, preclinical studies have focused almost exclusively on male subjects, partially due to a lack of ideal animal paradigms. As the persistent need regarding the sex balance of neuroscience research and female-specific pathology of mental disorders surges, the establishment of natural etiology-based and systematically validated animal paradigms for depression with female subjects becomes an urgent scientific problem. This study aims to establish, characterize, and validate a "Multiple Integrated Social Stress (MISS)" model of depression in female C57BL/6J mice by manipulating and integrating daily social stressors that females are experiencing. Female C57BL/6J mice randomly experienced social competition failure in tube test, modified vicarious social defeat stress, unescapable overcrowding stress followed by social isolation on each day, for ten consecutive days. Compared with their controls, female MISS mice exhibited a relatively decreased preference for social interaction and sucrose, along with increased immobility in the tail suspension test, which could last for at least one month. These MISS mice also exhibited increased levels of blood serum corticosterone, interleukin-6 L and 1β. In the pharmacological experiment, MISS-induced dysfunctions in social interaction, sucrose preference, and tail suspension tests were amended by systematically administrating a single dose of sub-anesthetic ketamine, a rapid-onset antidepressant. Compared with controls, MISS females exhibited decreased c-Fos activation in their anterior cingulate cortex, prefrontal cortex, nucleus accumbens and some other depression-related brain regions. Furthermore, 24 h after the last exposure to the paradigm, MISS mice demonstrated a decreased center zone time in the open field test and decreased open arm time in the elevated plus-maze test, indicating anxiety-like behavioral phenotypes. Interestingly, MISS mice developed an excessive nesting ability, suggesting a likely behavioral phenotype of obsessive-compulsive disorder. These data showed that the MISS paradigm was sufficient to generate pathological profiles in female mice to mimic core symptoms, serum biochemistry and neural adaptations of depression in clinical patients. The present study offers a multiple integrated natural etiology-based animal model tool for studying female stress susceptibility., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Acute myeloid leukemia (AML) with an internal tandem duplication in the fms-like tyrosine kinase receptor 3 gene (FLT3-ITD) is associated with poor survival, and few studies have examined the impact of modifiable behaviors, such as nutrient quality and timing, in this subset of acute leukemia., Methods: The influence of diet composition (low-sucrose and/or low-fat diets) and timing of diet were tested in tandem with anthracycline treatment in orthotopic xenograft mouse models. A pilot clinical study to test receptivity of pediatric leukemia patients to macronutrient matched foods was conducted. A role for the circadian protein, BMAL1 (brain and muscle ARNT-like 1), in effects of diet timing was studied by overexpression in FLT3-ITD-bearing AML cells., Results: Reduced tumor burden in FLT3-ITD AML-bearing mice was observed with interventions utilizing low-sucrose and/or low-fat diets, or time-restricted feeding (TRF) compared to mice fed normal chow ad libitum. In a tasting study, macronutrient matched low-sucrose and low-fat meals were offered to pediatric acute leukemia patients who largely reported liking the meals. Expression of the circadian protein, BMAL1, was heightened with TRF and the low-sucrose diet. BMAL1 overexpression and treatment with a pharmacological inducer of BMAL1 was cytotoxic to FLT3-ITD AML cells., Conclusions: Mouse models for FLT3-ITD AML show that diet composition and timing slows progression of FLT3-ITD AML growth in vivo, potentially mediated by BMAL1. These interventions to enhance therapy efficacy show preliminary feasibility, as pediatric leukemia patients responded favorable to preparation of macronutrient matched meals., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Alzheimer's disease (AD) is a neurodegenerative disorder with insidious onset and progressive development. There is an urgent need to find drugs that prevent and slow AD progression. We focus our attention on 3,6'-disinapoyl sucrose (DISS), an oligosaccharide with antidepressant and antioxidant activities. In this work, APP/PS1 transgenic mice were used to explore the neuroprotective impact of DISS to provide new applications for prevention and therapy of AD. This study aims to assess DISS's neuroprotective impact on learning and memory deficits in APP/PS1 transgenic mice using behavioral tests (Morris water maze, novel object recognition test, and passive avoidance test). Morphological alterations of hippocampus neurons were observed by Nissl staining and neuronal apoptosis was assessed by TUNEL assay. By using ELISA, the expressions of inflammatory factors were evaluated, and Western blotting was used to measure the protein expressions of neuron-related regulators in the hippocampus. DISS significantly ameliorated the cognitive disorder in APP/PS1 transgenic mice, reduced apoptosis by decreasing the ratio of Bax/B-cell lymphoma/leukemia-2 (Bcl-2) in hippocampal neurons, and restored the abnormal secretion of inflammatory factors (IL-2, TNF-α, IL-1β, and IL-6). Moreover, the gavage of high-dose DISS can boost the expressions of CREB/brain-derived neurotrophic factor (BDNF). Overall, our results indicate that DISS improves cognitive function in APP/PS1 transgenic mice by inhibiting neural apoptosis and activating the CREB/BDNF signal pathway. NEW & NOTEWORTHY In this study, for the first time, DISS was used in APP/PS1 transgenic mice to explore its neuroprotective effect. After gavage DISS for 1 mo, the impairment of learning and spatial memory ability and the loss of neurons in APP/PS1 mice were alleviated. DISS reduced a neuroprotective effect in AD mice via decreasing neuronal apoptosis, enhancing the expressions of CREB phosphorylation and BDNF, pointing to DISS as a new therapeutic target for AD.

We report a patient with an extremely rare, combined diagnosis of PMM2-CDG and hereditary fructose intolerance (HFI). By comparing with other patients, under-galactosylation was identified as a feature of HFI. Fructose/sorbitol/sucrose restriction was initiated right afterwards. The patient is at the mild end of the PMM2-CDG spectrum, raising the question of sorbitol's role in the pathogenesis of PMM2-CDG and whether fructose/sorbitol/sucrose restriction could benefit other PMM2-CDG patients. Additionally, epalrestat, an emerging potential PMM2-CDG therapy, may benefit HFI patients., Competing Interests: Declaration of Competing Interest This work was supported by U54 NS115198 (GB, ACE and MH)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

It is well-established that oral sucrose ingested shortly before exercise improves early exercise tolerance in individuals with McArdle disease. This is by supplying blood-borne glucose for muscle metabolism to compensate for the blocked glycogenolysis. The present study investigated if individuals with McArdle disease could benefit further from repeated sucrose ingestion during prolonged exercise. In this double-blind, placebo-controlled, cross-over study, the participants were randomized to ingest either sucrose or placebo first and subsequently the opposite on two separate days. The participants ingested the drink 10 min before and thrice (after 10, 25, and 40 min) during a 60-min submaximal exercise test on a cycle ergometer. The primary outcome was exercise capacity as indicated by heart rate (HR) and perceived exertion (PE) responses to exercise. Secondary outcomes included changes in blood metabolites, insulin and carbohydrate, and fatty acid oxidation rates during exercise. Nine participants with McArdle disease were included in the study. We confirmed improvement of exercise capacity with oral sucrose vs. placebo during early exercise (pre-second wind) indicated by lower peak HR and PE (p < 0.02). We found no further beneficial effect with repeated sucrose versus placebo ingestion during prolonged exercise, as indicated by no difference in HR or PE post-second wind (p > 0.05). Glucose, lactate, insulin, and carbohydrate oxidation rates increased, and fatty acid oxidation decreased with sucrose versus placebo (p ≤ 0.0002). We can conclude that repeated sucrose ingestion is not recommended during prolonged exercise. This finding can prevent excessive caloric intake and reduce the risk of obesity and insulin resistance., (© 2023 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Background: This study aimed to compare the efficacy of intravenous, intranasal fentanyl and oral sucrose in reducing the pain response during retinopathy of prematurity examinations using premature infant pain profile (PIPP) scores., Method: The study included 42 infants who underwent retinopathy screening examinations. The infants were divided into three groups: oral sucrose, intranasal fentanyl, and intravenous fentanyl. Vital signs (heart rate, arterial oxygen saturation, and mean arterial pressure) were recorded. The PIPP was used to determine pain severity. Cerebral oxygenation and middle cerebral artery blood flow were evaluated using near-infrared spectroscopy and Doppler ultrasonography, respectively. The data obtained were compared between groups., Results: There was no significant difference between the three groups regarding postconceptional and postnatal ages or birth weights and weight at the time of examination. All babies had moderate pain during the examination. No correlation was observed between analgesia method and pain scores (P = 0.159). In all three groups, heart rate and mean arterial pressure increased, whereas oxygen saturation decreased during the exam compared with pre-examination values. However, heart rate (HR), mean arterial pressure (MAP) and arterial oxygen saturation (sPO 2 ) values did not differ between groups (HR, P = 0.150; MAP, P = 0.245; sPO 2 , P = 0.140). The cerebral oxygenation (rSO 2 ) values between the three groups were found to be similar [rSO 2 : P = 0.545, P = 0.247, P = 0.803; fractional tissue oxygen extraction (FTOE): P = 0.553, P = 0.278]. Regarding cerebral blood flow values, we also did not find any difference between the three groups [mean blood flow velocity (Vmean): P = 0.569, P = 0.975; maximum flow velocity (Vmax): P = 0.820, P = 0.997]., Conclusions: Intravenous and intranasal fentanyl and oral sucrose were not superior to each other in preventing pain during the examination for retinopathy of prematurity (ROP). Sucrose may be a good alternative for pain control during ROP examination. Our findings suggest that ROP exam may not affect cerebral oxygenation or cerebral blood flow. Larger scale studies are needed to determine the best pharmacological option to reduce pain during ROP exams and evaluate the effects of this procedure on cerebral oxygenation and blood flow., (© 2023. Children's Hospital, Zhejiang University School of Medicine.)

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P <0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P <0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t =4.760, P <0.001] and the proportion of patients with SF levels of ≥100 μg/L ( P =0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P =0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.

This article describes a chronic mild stress (CMS) model for predicting antidepressant response and investigating mechanisms of antidepressant action in rats. Following exposure to a variety of mild stressors for several weeks, the rats' behavior is modified in several ways that parallel symptoms of depression. Among these is a substantial reduction in consumption of a 1% sucrose solution, which models the cardinal symptom of major depression, anhedonia. Our standard procedure employs a battery of behavioral tests, comprising weekly assessment of sucrose intake and, at the end of treatment, the elevated plus-maze and novel object recognition tests to assess the anxiogenic and dyscognitive effects of CMS. Chronic administration of antidepressant drugs reverses the decreased sucrose intake and other behavioral changes in these subjects. Also effective are second-generation antipsychotics. The CMS model can be employed in discovery programs to identify anti-anhedonic drugs (e.g., antidepressants and antipsychotics) that act more quickly than existing agents. While most antidepressants require 3 to 5 weeks to normalize behavior, some treatments provide a faster onset of action. For example, the CMS-induced deficits can be reversed by acute or sub-chronic application of treatments that act rapidly in depressed patients, such as deep brain stimulation (DBS), ketamine, and scopolamine, as well as several compounds that have yet to be tested in humans but have fast-onset antidepressant-like effects in animals, such as the 5-HT-1A biased agonists NLX-101 and GLYX-13. Application of the CMS model in Wistar-Kyoto (WKY) rats causes similar behavioral changes to those seen in Wistars, but these are not reversed by antidepressant treatment. However, WKY rats respond to DBS and ketamine, which are effective in patients who are antidepressant non-responders, establishing CMS in WKY rats as a model of treatment-resistant depression. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Induction of chronic mild stress in rats as a model of depression and treatment-resistant depression., (© 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.)

Ethnopharmacology Relevance: Gastrodia elata Blume (GE) is a traditional Chinese dietary therapy used to treat neurological disorders. Gastrodia elata Blume water extract (WGE) has been shown to ameliorate inflammation and improve social frustration in mice in a chronic social defeat model. However, studies on the anti-depressive-like effects and cognitive impairment alleviation related to the impact of WGE on the gut microbiome of ApoE -/- mice remain elusive., Aim of the Study: The present study aimed to investigate the anti-depressive-like effect and cognitive impairment alleviation and mechanisms of WGE in ApoE -/- mice subjected to unpredictable chronic mild stress (UCMS), as well as its impact on the gut microbiome of the mice., Materials and Methods: Sixty ApoE -/- mice (6 months old) were randomly grouped into six groups: control, UCMS, WGE groups [5, 10, 20 mL WGE/kg body weight (bw) + UCMS], and a positive group (fluoxetine 20 mg/kg bw + UCMS). After four weeks of the UCMS paradigm, the sucrose preference, novel object recognition, and open field tests were conducted. The neurotransmitters serotonin (5-HT), dopamine (DA) and their metabolites were measured in the prefrontal cortex. Serum was collected to measure corticosterone and amyloid-42 (Aβ-42) levels. Feces were collected, and the gut microbiome was analyzed., Results: WGE restored sucrose preference, exploratory behavior, recognition ability, and decreased the levels of serum corticosterone and Aβ-42 in ApoE -/- mice to alleviate depressive-like behavior and cognitive impairment. Furthermore, WGE regulated the monoamine neurotransmitter via reduced the 5-HT and DA turnover rates in the prefrontal cortex. Moreover, WGE elevated the levels of potentially beneficial bacteria such as Bifidobacterium, Akkermansia, Alloprevotella, Defluviitaleaceae&#95;UCG-011, and Bifidobacterium pseudolongum as well as balanced fecal short-chain fatty acids (SCFAs)., Conclusion: WGE demonstrates anti-depressive-like effects, cognitive impairment alleviation, and gut microbiome and metabolite regulation in ApoE -/- mice. Our results support the possibility of developing a functional and complementary medicine to prevent or alleviate depression and cognitive decline using WGE in CVDs patients., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Background: Evidence for analgesic effects of parent-led pain management strategies during painful procedures in newborn infants exists; however, such strategies are inconsistently used in practice. A publicly available parent-targeted video demonstrates breastfeeding, skin-to-skin care, and sucrose during painful procedures. Australian parents' use and knowledge of this video and these strategies was unknown., Purpose: To determine parents' use of pain management strategies, and perceived acceptability and usefulness of the parent-targeted video., Methods: A cross-sectional, online, anonymous survey with embedded video. Participants were recruited via social media channels of the Miracle Babies Foundation, an Australian parent support network. Target participants were parents or family members of infants currently or previously hospitalized in neonatal special and/or intensive care nurseries, or high dependency units., Results: A total of 162 of 189 respondents provided sufficient data for analysis; all identified as mothers. Only 6 (4%) had previously seen the video; however, nearly all rated it as potentially useful and helpful (n = 124, 82%). Although most reported that sucrose had been used (n = 112, 84%), fewer reported having used skin-to-skin care (n = 50, 37%), or breastfeeding (n = 33, 25%). Most intended to advocate for skin-to-skin care (n = 108, 88%) or breastfeeding (n = 100, 81%) in future procedures. Perceived barriers to utilizing strategies included lack of information-sharing and organizational practices that excluded parent involvement., Implications for Practice and Research: The video may be valuable in supporting mothers to advocate for their involvement during painful procedures in preterm and sick hospitalized infants. Further research is recommended to explore coordinated strategies targeting parents and healthcare professionals to overcome barriers to implementing parent-led infant pain management strategies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 by The National Association of Neonatal Nurses.)

Background: Inconsistent pain management practices can have negative physiologic and neurodevelopmental consequences in the neonate. Low rates of oral sucrose use with comfort measures for pain management during minor painful procedures were identified at a level III neonatal intensive care unit. Underutilization of pain management resources occurs despite the availability of evidence-based pain management interventions., Purpose: To improve consistency in the use of oral sucrose solution with comfort measures during peripheral intravenous catheter insertion attempts in the neonatal intensive care unit in patients greater than or equal to 32 0/7th weeks postmenstrual age., Methods: Quality improvement methods were used to implement an evidence-based procedural pain algorithm for minor painful procedures and optimize pain management processes over a 15-week period in a 26-bed, level III neonatal intensive care unit., Results: There was an increase in the average percentage of documented use of sucrose with comfort measures during peripheral intravenous catheter insertion attempts from 20% to 27%. There was a 41% increase in the average presence of a sucrose order indicated for procedural pain. There were improvements in staff knowledge of sucrose dosing and perceived behavior of staff after completing the education., Implications for Practice and Research: Procedural pain management should be used as a quality indicator and guidelines should be established with the support of key stakeholders in neonatal intensive care settings. Future projects should address barriers related to workflow and accessibility of sucrose, include other common needlestick procedures, and expand the role of parent participation in pain management practices.Video Abstract available at:https://journals.lww.com/advancesinneonatalcare/pages/video.aspx?v=60 ., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 by The National Association of Neonatal Nurses.)

Objective: To compare the analgesic effect of oral sucrose water (Su) vs local application of lidocaine liposome (LC) in blood collection and intramuscular injection in neonates., Methods: A total of 300 neonates admitted to Sichuan Provincial People's Hospital in China between June 2019 and December 2021 who were to receive intramuscular injection and heel blood collection were enrolled in the study. The neonates were assigned to one of the following groups (n = 30 in each): control, 30% Su, 25% Su, 24% Su, 12% Su, 8% Su, LC 15-min, LC 30-min, LC 45-min or the combination group. The groups received different concentrations of Su or the application of LC liposome at different timepoints and the control group was given no analgesia. Before and after puncture, the Neonatal Facial Coding System-Revised (NFCS-R) was used for pain evaluation in the neonates. The heart rate (HR), respiratory rate, blood oxygen saturation (SpO2) and blood pressure (BP) in each group were compared, and the starting and ending time of crying and latent crying time were recorded and analyzed. After the optimal concentration of Su and optimal application time of LC were understood, the combination group was used to evaluate the analgesic effect of Su combined with LC., Results: Using various concentrations of Su, neonate pain was alleviated to varying degrees; 24%, 25%, and 30% Su did not reveal any difference in various investigation items, although their effect was superior to 8% and 12% Su. The LC 30-min and LC 45-min groups performed better than the LC 15-min group with regard to NFCS-R score, vital signs and BP. However, no notable difference was observed between the LC 15-min and LC 45-min groups in latent time. Moreover, the combination of 24% Su and application of LC 30 minutes before puncture provided a better analgesic effect than a single anesthesia intervention., Conclusion: The combination of 24% Su and the application of LC 30 minutes before puncture delivered better analgesic effect than a single anesthesia intervention alone.

Background: Management of oral iron overdoses is well-established, but there is limited literature regarding intravenous iron sucrose overdoses. Indications for administering deferoxamine after oral iron overdoses include clinical signs and symptoms of toxicity, along with a serum iron concentration ≥ 500 μg/dL. Reported signs and symptoms of iron sucrose overdose do not appear to correlate with those of oral iron overdoses., Case Report: We present a case of intravenous iron sucrose overdose in a clinically well-appearing patient with a presenting serum iron concentration that was several times higher than the usual threshold concentration for initiating deferoxamine treatment. A 21-year-old woman presented to the emergency department after an accidental intravenous iron sucrose overdose. The patient received a home infusion of 1000 mg iron sucrose, which was five times the prescribed dose. Her presenting serum iron concentration was 1799 μg/dL, with bicarbonate and anion gap both within normal limits and an unremarkable physical examination. Because she did not have evidence of severe iron toxicity, she was treated supportively and deferoxamine was not administered. Her serum iron concentration decreased below the toxic range over the next 14 h, and she was discharged home the next day. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This patient was managed successfully with expectant care alone, suggesting that iron sucrose overdose has much lower toxicity than oral iron salt overdose. This discrepancy between measured iron concentrations and clinical presentation may be explained by the elimination kinetics of iron sucrose having separate redistribution and elimination phases., (Published by Elsevier Inc.)

Background: Pain management in dentistry is inevitable without the use of local anesthesia. However, the agonizing experience of dental injections incorporates a fear of dentist in children. Therefore, the painless administration of local anesthetic agents is crucial in providing optimum dental care., Aim: To compare the effectiveness of four different techniques in minimizing the pain during administration of local anesthesia in 7-11 years old children., Study Design: In this split mouth study design, 132 healthy and cooperative children of age 7-11 years, who needed bilateral extraction of primary molars were children were randomly allocated to four different groups: Group I (cryotherapy), Group II (30% sucrose solution), Group III (combination of cryotherapy + sucrose) and Group IV (topical anesthetic agent). The pain perception during administration of local anesthesia (IANB) was recorded before, during and after anesthesia using VAS (visual analogue scale), oxygen saturation (SpO 2 ) and pulse rate (PR), SEM (sound, eye, body movement) and FLACC (face, legs, activity, cry, consolability) scale., Results: The mean difference of scores of VAS scale showed a statistically significant difference ( p < 0.05) in all the groups. The FLACC and SEM scores, pulse rate (PR) and SpO 2 of Group I (popsicle) showed a statistically significant difference ( p < 0.05) when compared to Group III (ice-cubes) and Group IV (topical anesthetic)., Conclusion: Pain management using a combination of cryotherapy & sweet substance in pediatric patients can be a safe and effective alternative to the conventional topical anesthetic agents in minimizing pain as the sweet taste acts a reward and offers the advantage of providing a positive dental experience for the patient., Competing Interests: No conflict of interest., (©2022 The Author(s). Published by MRE Press.)

Background: The switch/sucrose nonfermentable complex mutations (SWI/SNF-mut) are common in non-small cell lung cancer (NSCLC). However, the association of SWI/SNF-mut with the clinical outcomes of immune checkpoint inhibitors (ICIs), particularly of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), has not been established., Methods: We retrospectively collected data of patients at Cancer Hospital Chinese Academy of Medical Sciences. Patients with advanced NSCLC who received programmed cell death protein-1 or programmed cell death ligand 1 (PD-[L]1) inhibitors were included in cohort 1 and those with EGFR mutations (EGFR-mutant) received EGFR-TKIs monotherapy were included in cohort 2. Two reported Memorial Sloan-Kettering Cancer Center (MSKCC) cohorts received immunotherapy alone used as the validation for cohort 1. We analyzed the relationship between SWI/SNF alterations and clinical outcomes in each cohort., Results: In total, 1162 patients were included, of which 230 patients (19.8%) were identified as SWI/SNF-mut with the most common genetic alterations being ARID1A (33.4%) and SMARCA4 (28.3%). In cohort 1 (n = 146), patients with co-mutations of SWI/SNF and Kirsten rat sarcoma oncogene (KRAS) (SWI/SNFmutKRASmut, n = 18) had significantly prolonged progression-free survival (PFS) (8.6 m vs. 1.9 m; hazard ratio [HR],  0.31; 95% confidence intervals [CI], 0.11-0.83; p = 0.032) to PD-(L)1 inhibitors monotherapy, which was consistent with the MSKCC cohorts (not reach [NR] vs. 6.3 m; HR, 0.36, 95% CI, 0.15-0.82; p = 0.016). In cohort 2 (n = 205), ARID1A-mut (n = 16) was associated with improved PFS after EGFR-TKIs (20.6 m vs. 11.2 m; HR, 0.47, 95% CI, 0.27-0.94; p = 0.023)., Conclusions: In advanced NSCLC, patients with SWI/SNFmutKRASmut seem to benefit more from ICIs. Furthermore, ARID1A-mut may provide a protective effect to EGFR-TKIs in EGFR-mutant patients. However, this is a retrospective single-institution analysis that requires further validation by large prospective studies., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

One of the therapeutic approaches for decreasing postprandial hyperglycemia is to retard absorption of glucose by the inhibition of carbohydrate hydrolyzing enzymes, α-amylase, and α-glucosidases, in the digestive organs. Coffee consumption has been reported to beneficial effects for controlling calorie and cardiovascular diseases, however, the clear efficacy and mode of action are yet to be proved well. Therefore, in this study we evaluated in- vitro rat intestinal α-glucosidases and porcine α-amylase inhibitory activities as well as in vivo (Sprague-Dawley rat model) blood glucose lowering effects of selected coffee extracts. The water extracted Sumatra coffee (SWE) showed strong α-glucosidase inhibitory activity (IC 50 , 4.39 mg/mL) in a dose-dependent manner followed by Ethiopian water extract (EWE) (IC 50 , 4.97) and Guatemala water extract (GWE) (IC 50 , 5.19). Excepted for GWE all the coffee types significantly reduced the plasma glucose level at 0.5 h after oral intake (0.5 g/kg-body weight) in sucrose and starch-loaded SD rats. In sucrose loading test SWE (p < 0.001) and EWE (p < 0.05) had significantly postprandial blood glucose reduction effect, when compared to control. The maximum blood glucose levels (Cmax) of EWE administration group were decreased by about 18% (from 222.3 ± 16.0 to 182.5 ± 15.4, p < 0.01) and 19% (from 236.2 ± 25.1 to 191.3 ± 13.2 h·mg/dL, p < 0.01) in sucrose and starch loading tests, respectively. These results indicate that selected coffee extract may improve exaggerated postprandial spikes in blood glucose via inhibition of intestinal sucrase and thus delays carbohydrate absorption. These in vitro and in vivo studies therefore could provide the biochemical rationale for the benefit of coffee-based dietary supplement and the basis for further clinical study., (© 2022. The Author(s).)

Background: Accumulative data links inflammation and immune dysregulation to the pathophysiology of mental disorders; little is known regarding leukotrienes' (LTs) involvement in this process. Circumstantial evidence suggests that treatment with leukotriene modifying agents (LTMAs) such as montelukast (MTK) may induce adverse neuropsychiatric events. Further methodic evaluation is warranted., Objective: This study aims to examine behavioral effects, as well as inflammatory mediator levels of chronic MTK treatment in male and female rats., Methods: Depression-like phenotypes were induced by exposing male and female rats to a chronic unpredictable mild stress (CUMS) protocol for four weeks. Thereafter, rats were treated (intraperitoneally) once daily, for two weeks, with either vehicle (dimethyl sulfoxide 0.2 ml/rat) or 20 mg/kg MTK. Following treatment protocols, behavioral tests were conducted and brain regions were evaluated for inflammatory mediators including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and prostaglandin (PG) E2., Results: Overall, MTK did not invoke negative behavioral phenotypes (except for an aggression-inducing effect in males). Numerous positive behavioral outcomes were observed, including reduction in aggressive behavior in females and reduced manic/hyperactive-like behavior and increased sucrose consumption (suggestive of antidepressant-like effect) in males. Furthermore, in control males, MTK increased IL-6 levels in the hypothalamus and TNF-α in the frontal cortex, while in control females it generated a robust anti-inflammatory effect. In females that were subjected to CUMS, MTK caused a prominent reduction in TNF-α and IL-6 in brain regions, whereas in CUMS-subjected males its effects were inconsistent., Conclusion: Contrary to prior postulations, MTK may be associated with select beneficial behavioral outcomes. Additionally, MTK differentially affects male vs. female rats in respect to brain inflammatory mediators, plausibly explaining the dissimilar behavioral phenotypes of sexes under MTK treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rostevanov, Betesh-Abay, Nassar, Rubin, Uzzan, Kaplanski, Biton and Azab.)

Schistosoma mansoni-induced granulomas result in severe damage to the host's liver, as well as neurological and metabolic disorders. We evaluated the biochemical and behavioral changes during schistosomiasis under three diet protocols: ad libitum (AL), alternate-day fasting (ADF) and a high-sucrose/caloric diet (HSD). Healthy male BALB/c mice were divided into noninfected, matched infected and infected/treated [praziquantel (PZQ)] groups. Caloric intake and energy efficiency coefficients associated with diets were measured. Behavioral (exploratory and locomotor) and biochemical (glucose, triglycerides, total cholesterol, AST, ALT, ALP, and γ-GT) tests and histological analysis were performed. Fifteen weeks postinfection, HSD and PZQ promoted weight gain, with higher caloric consumption than ADF (p < 0.05), reflecting serum glucose levels and lipid profiles. HSD and PZQ prevented liver dysfunction (AST and ALT) and significantly prevented increases in granuloma area (p < 0.05). HSD and PZQ also significantly improved mouse physical performance in exploratory and locomotor behavior (p < 0.05), reversing the impaired motivation caused by infection. These findings showed that ADF worsened the course of S. mansoni infection, while HSD and PZQ, even with synergistic effects, prevented and/or attenuated biochemical and behavioral impairment from infection., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Bombax costatum Pellegr. & Vuillet is used traditionally in Northern Cameroon to treat memory impairment, anxiety, insomnia and depression., Aim of the Study: Investigating the effect of Bombax costatum stem bark aqueous extract (BC) on depression associated with amnesia and vascular disorder, using a chronic mild unpredictable stress (CMUS) model in rats for 30 days., Materials and Methods: Sucrose Preference Test (SPT), Forced Swimming Test (FST), corticosteronemia, brain serotonin and dopamine level were evaluated as indices of antidepressant-like effect. The Novel Object Recognition Task (NOR), the Morris Water Maze (MWM) and acetylcholinesterase activity in the hippocampus were also used to verify memory integrity. Oxidative and nitrosative stress markers, the lipid profile and atherogenic index were estimated in blood serum to assess vasoprotective effect. Chlorophenylalanine and haloperidol, were used to delineate the extract's mechanism of action., Results: CMUS induced a decrease in sucrose preference and swimming time in the SPT and FST respectively while BC (27.5 and 55 mg/kg) increased sucrose preference and swimming time. Increments in these parameters were however reversed by the treatment of rats with chlorophenylalanine a serotonin synthesis inhibitor and haloperidol a D2 receptor antagonist. An increase in blood corticosterone level, prefrontal cortex malondialdehyde and nitric oxide concentrations were reversed by the extract. Moreover, BC increased the time spent in the target quadrant of the MWM test and the discrimination index in the NOR test. This was associated with an increase in hippocampus superoxide dismutase and catalase levels, a decrease in acetylcholine esterase level, total blood cholesterol and atherogenicity index compared to CMUS group., Conclusion: Thirty days CMUS induces a depressive state in rats. BC reverses this condition when administered alongside stress exposure. This antidepressive effect is associated with antiamnesic, antioxidant and vasoprotective actions, suggesting its use as a potential candidate in the management of major depressive disorder., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Hyperphosphatemia is common in patients on peritoneal dialysis (PD). Restricting dietary phosphorus often leads to a decrease in protein intake, which may result in hypoalbuminemia. The high pill burden of phosphate binders may also contribute to compromised appetite and dietary intake. Hypoalbuminemia is associated with an increased risk of morbidity and mortality in PD patients. The goal of this study was to determine if sucroferric oxyhydroxide improves albumin and self-reported measures of appetite in PD patients., Methods: We performed a prospective, open-label, 6-month, pilot study of 17 adult PD patients from the Denver Metro Area. Patients had to use automated peritoneal dialysis for ≥ 3 months, have a serum albumin ≤ 3.8 g/dL, and have serum phosphate ≥ 5.5 mg/dL or ≤ 5.5 mg/dL on a binder other than SO. SO was titrated to a goal serum phosphate of < 5.5 mg/dL. The primary outcome was change in serum phosphate, albumin, and phosphorus-attuned albumin (defined as albumin divided by phosphorus) over 6 months., Results: The mean (SD) age and dialysis vintage was 55 ± 13 years and 3.8 ± 2.7 years, respectively. Participants' serum phosphate significantly decreased with fewer phosphate binder pills/day after switching to SO. There was no change in serum albumin, appetite, or dietary intake. However, participants had significant improvements in phosphorus-attuned albumin., Conclusion: The transition to SO improved phosphorus control, phosphorus-attuned albumin, and pill burden. There were no significant changes in self-reported appetite or dietary intake during the study. These findings suggest that PD patients maintained nutritional status with SO therapy., Trial Registration: First registered at ClinicalTrials.gov ( NCT04046263 ) on 06/08/2019., (© 2022. The Author(s).)

Examination for retinopathy of prematurity (ROP) is a very painful procedure. Therefore, pain management is essential given the possibility of sensory and behavioral problems in newborns, who are constantly exposed to painful stimuli. In this light, the use of nonpharmacological methods alone or in combination with pharmacological methods is recommended for pain control. This systematic review and meta-analysis was to evaluate the effects of nonpharmacological treatments on pain during ROP examination. Randomized controlled trials published in English between 2011 and 2021 and available in the electronic databases of Medline, Web of Science, Nursing & Allied Health, and PubMed were reviewed. The meta-analysis was performed using Review Manager 5.4. Six randomized controlled studies were included. Glucose (mean difference [MD]: -1.64, 95% confidence interval [CI]: -2.34 to 0.94, P < .0001) and sucrose (MD: -2.50, 95% CI: -3.20 to -1.79, P < .0001) solutions were effective in reducing pain. However, breast milk did not reduce the Premature Infant Pain Profile score (MD: -2.50, 95% CI: -6.10 to 1.10, P > .05). The application of sucrose and glucose solutions for pain management during ROP examination can be effective and safe., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To compare the pain scores between the two groups, breast milk (BM) and 24% sucrose, in preterm neonates undergoing automated heel lance for the blood draw., Methods: The study is designed as a randomized, single-blinded, non-inferiority trial. Infants born between 30 1/7weeks and 36 6/7 weeks of gestation were randomly assigned to receive either 24% sucrose or expressed BM. The Premature Infant Pain Profile-Revised (PIPP-R) was utilized to provide pain scores., Results: No differences were noted in the baseline characteristics between the two groups. The quantile regression estimates for PIPP-R scores during the procedure were statistically non-significant at all percentile levels of distribution (50%ile coefficient 0, 95% CI -0.49 to 0.49)., Conclusion: We conclude that BM is not inferior to 24% sucrose in providing analgesia during heel lance in moderate and late preterm infants., Trial Registration: This trial was registered at www., Clinicaltrials: gov (identifier NCT04898881)., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Neonatal pain not only has negative impact on the acute physiological parameters of the neonate but also has got the potential to cause long-term neurodevelopmental disabilities. However, neonatal pain especially related to procedures is not well recognised and often poorly managed in neonatal intensive care unit (NICU)., Local Problem: Oral sucrose solution became available commercially in late 2017 and this provided us the opportunity to alleviate some of the procedural pain in neonates admitted in our NICU., Methods: Point of care quality improvement method (POCQI) was leveraged to identify root causes, change ideas and solutions were tested using PDSA cycles. Four procedures were selected by team for sucrose analgesia namely intravenous cannula insertion, tracheal suctioning, removal of tapes and phlebotomy. Change ideas tested included training of staff and doctors, providing dosage chart in NICU, method of administration of sucrose, affixing sucrose vial to baby bed, using prefilled sucrose syringe and bedside availability of sucrose and checklist for documentation. The study was conducted over a period of 8 weeks from 15 June 2017 on all eligible babies getting admitted., Aim Statement: We aim to increase compliance to administration of sucrose analgesia to all eligible newborns (undergoing 4 selected procedures intravenous cannula insertion, tracheal suctioning, removal of tapes and phlebotomy) in NICU prior to painful procedure from current 0% to >80% by 8 weeks., Results: This quality improvement study implementing the use of evidence-based sucrose analgesia using PDSA cycles found that percentage of babies getting sucrose analgesia has increased from baseline 0% to 96.27% in the study period and is sustained at >80% for 4 years., Conclusions: POCQI methodology can be used effectively to implement a new simple strategy of administering oral sucrose solution to address procedural pain in care pathway of neonates admitted in NICU. Sustaining the gains achieved by POCQI needs active leadership involvement and addressing adaptive or behavioural challenges with solutions like team huddles., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To compare the efficacy of 25% dextrose with 24% sucrose for heel-lance analgesia in preterm infants admitted to the NICU., Methods: In this noninferiority, double-blind, randomized controlled trial, preterm infants born at 28 weeks and 0 days to 35 weeks and 6 days of gestation who were due for a scheduled heel-lance procedure were enrolled. Infants randomly assigned to the intervention arm received 0.5 mL 25% dextrose, whereas infants in the active control group received 0.5 mL 24% sucrose orally just 2 minutes before the heel-lance procedure. The primary outcome was Premature Infant Pain Profile (PIPP) score 30 seconds after the procedure. Secondary outcomes included PIPP scores at 60 and 120 seconds, PIPP-Revised scores at 30, 60, and 120 seconds, and any adverse events., Results: Sixty-four infants were enrolled (32 in each group). The mean (SD) PIPP score at 30 seconds was 6.41 (2.56) in the dextrose group and 7.03 (2.23) in the sucrose group (mean difference, -0.63 (95% confidence interval, -1.85 to 0.60; P = .31). The upper margin of the confidence interval did not cross the predefined noninferiority margin of 2. The mean PIPP scores at 60 (5.03 [2.18] vs 5.39 [1.48]) and 120 (4.75 [1.97] vs 4.94 [1.46]) seconds were also similar. The PIPP-Revised scores between the 2 groups at all time intervals were comparable. One infant in the intervention group had a transient coughing episode., Conclusions: In preterm infants under intensive care, 25% dextrose is noninferior to 24% sucrose for heel-lance analgesia as assessed by PIPP score., (Copyright © 2022 by the American Academy of Pediatrics.)

Hyperphosphatemia is a common complication in dialysis-dependent patients with chronic kidney disease. Most dialysis-dependent patients need oral phosphate binder therapy to control serum phosphorus concentrations. Most phosphate binders have a high daily pill burden, which may reduce treatment adherence and impair phosphorus control. Sucroferric oxyhydroxide is a potent iron-based phosphate binder approved for use in dialysis-dependent patients in 2013. A randomized controlled trial of sucroferric oxyhydroxide demonstrated its efficacy for reduction of serum phosphorus with a lower pill burden than sevelamer carbonate. Clinical trials carefully select patients, monitor adherence, and routinely titrate medications to a protocol-defined goal. Consequently, trials may not reflect real-world use of medications. Since its approval, we and others have performed retrospective and prospective analyses of sucroferric oxyhydroxide in real-world clinical practice in > 6400 hemodialysis and approximately 500 peritoneal dialysis patients in the USA and Europe. Consistent with the clinical trial data, real-world observational studies have demonstrated that sucroferric oxyhydroxide can effectively reduce serum phosphorus with a lower daily pill burden than most other phosphate binders. These studies have also shown sucroferric oxyhydroxide provides effective serum phosphorus control in different treatment settings, including as monotherapy in phosphate binder-naïve patients, in patients switching from other phosphate binders, or when used in combination with other phosphate binders. These observational studies indicate a favorable safety and tolerability profile, and minimal, if any, systemic iron absorption. This article reviews the key results from these observational studies of sucroferric oxyhydroxide and evaluates its role in the management of hyperphosphatemia in clinical practice., (© 2022. The Author(s).)

Introduction: Feruloyl Sucrose Esters (FSEs) are a class of Phenylpropanoid Sucrose Esters (PSEs) widely distributed in plants. They were investigated as potential selective Alpha Glucosidase Inhibitors (AGIs) to eliminate the side effects associated with the current commercial AGIs. The latter effectively lowers blood glucose levels in diabetic patients but causes severe gastrointestinal side effects., Methods: Systematic structure-activity relationship (SAR) studies using in silico, in vitro and in vivo experiments were used to accomplish this aim. FSEs were evaluated for their in vitro inhibition of starch and oligosaccharide digesting enzymes α-glucosidase and α- amylase followed by in silico docking studies to identify the binding modes. A lead candidate, FSE 12 was investigated in an STZ mouse model., Results: All active FSEs showed desired higher % inhibition of α-glucosidase and desired lower inhibition of α -amylase in comparison to AGI gold standard acarbose. This suggests a greater selectivity of the FSEs towards α -glucosidase than α -amylase, which is proposed to eliminate the gastrointestinal side effects. From the in vitro studies, the position and number of the feruloyl substituents on the sucrose core, the aromatic 'OH' group, and the diisopropylidene bridges were key determinants of the % inhibition of α - glucosidase and α -amylase. In particular, the diisopropylidene bridges are critical for achieving inhibition selectivity. Molecular docking studies of the FSEs corroborates the in vitro results. The molecular docking studies further reveal that the presence of free aromatic 'OH' groups and the substitution at position 3 on the sucrose core are critical for the inhibition of both the enzymes. From the in vitro and molecular docking studies, FSE 12 was selected as a lead candidate for validation in vivo. The oral co-administration of FSE 12 with starch abrogated the increase in post-prandial glucose and significantly reduced blood glucose excursion in STZ-treated mice compared to control (starch only) mice., Conclusion: Our studies reveal the potential of FSEs as selective AGIs for the treatment of diabetes, with a hypothetical reduction of side effects associated with commercial AGIs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: A study was conducted to determine whether iron-based phosphate binders (IBPBs) need to be preferred for hyperphosphatemia and anemia management in patients on dialysis., Methods: For this meta-analysis, we searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for randomized controlled trials that evaluated the efficacy and safety of IBPBs in decreasing phosphate and correcting anemia in dialysis patients., Results: Nineteen trials comprising 4719 participants were included. Compared with placebo, serum phosphate decreased significantly after treatment with ferric citrate (FC), fermagate (one study), and SBR759 (one study). Hemoglobin increased significantly after treatment with FC and sucroferric oxyhydroxide (PA21). In addition, FC and PA21 reduced serum intact parathyroid hormone (iPTH) and increased ferritin and transferrin saturation, but SBR759 did not. Compared with active treatment, the non-inferiority of IBPBs in reducing serum phosphate and iPTH was demonstrated. FC significantly improved serum hemoglobin and iron-related parameters and decreased the use of intravenous iron and erythropoiesis-stimulating agent, whereas PA21 did not increase serum hemoglobin level. The incidences of infection and hospitalization were similar between the two groups, with FC having a higher risk of diarrhea than the placebo and active treatments., Conclusion: FC was associated with the control of hyperphosphatemia and the improvement of anemia. However, PA21 did not show superiority for alleviating anemia compared with the active treatment. Other IBPBs, such as fermagate and SBR759, remained poorly understood due to the limited number of studies. Further trials are required to assess the effect of IBPBs on the risk of cardiovascular events and all-cause mortality., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.)

Objective: The efficacy of oral sweet solutions to decrease pain in infants during painful procedures remains uncertain. This study aimed to compare the efficacy of an oral sucrose solution versus placebo in reducing pain during bladder catheterization in infants in the Emergency Department (ED)., Methods: A randomized, double-blind clinical trial was conducted in a pediatric university-affiliated hospital ED. Infants 1-3 months old were recruited and randomly allocated to receive 2 ml of sucrose or placebo, 2 min before bladder catheterization. The primary outcome measure was the difference in pain scores as assessed by the Face, Legs, Activity, Cry and Consolability (FLACC) Pain Scale during procedure. Secondary outcome measures were the difference in pain scores using the Neonatal Infant Pain Scale (NIPS), crying time, variations in heart rate and adverse events., Results: Eighty-three participants were recruited and completed the study, 41 and 42 in the sucrose and placebo groups, respectively. The mean difference in FLACC scores compared to baseline was 5.3 in the sucrose group vs. 6.4 in the placebo group during catheterization. There were no differences in FLACC scores or NIPS scores measured at 1, 3 and 5 min post procedure. Mean crying times were similar: 97 vs. 110 s. No significant difference was found in participants' heart rate variations. No adverse events were reported., Conclusions: In infants undergoing bladder catheterization in the ED, administration of an oral sweet solution was not associated with lower pain as measured by the FLACC and NIPS scales. Participants' heart rate variations and crying times did not change when sucrose was provided., (© 2021. The Author(s), under exclusive licence to Canadian Association of Emergency Physicians (CAEP)/ Association Canadienne de Médecine d'Urgence (ACMU).)

Background: Oral sweet solutions have been proposed as effective pain-reducing agents for procedures., Objectives: To compare the efficacy of an oral sucrose solution vs. placebo in alleviating pain in children (1-3 months) during nasopharyngeal aspiration (NPA)., Methods: A randomized, double-blind, controlled clinical trial was conducted in a pediatric hospital emergency department. Participants (aged 1-3 months) requiring NPA were randomly allocated to receive 2 mL of 88% sucrose (SUC) or 2 mL of a placebo (PLA) 2 min prior to the procedure. The primary outcome was the mean difference in pain scores at 1 min post NPA as assessed by the Face, Legs, Activity, Cry and Consolability (FLACC) Pain Scale., Results: Seventy-two participants completed the study, 37 receiving SUC and 35 PLA. The mean difference in FLACC scores compared with baseline was 3.3 (2.5-4.1) for SUC vs. 3.2 (2.3-4.1) for PLA (p = .094) at 1 min and -1.2 (-1.7-0.7) for SUC vs. -0.8 (-1.5 to -0.1) for PLA (p = 0.66) at 3 min after NPA. For the Neonatal Infant Pain Scale scores, it was 2.3 (1.6-3.0) (SUC) vs. 2.5 (1.8-3.2) (PLA) (p = .086) at 1 min and -1.2 (-1.6 to -0.8) (SUC) vs. -0.8 (-1.3 to 0.2) (PLA) (p = 0.59) 3 min after NPA. There was no difference in the mean crying time, 114 (98-130) s, SUC vs. 109 (92-126) s, PLA (p = 0.81). No significant difference was found in participants' heart rate at 1 min 174 (154-194) beats/min in SUC vs. 179 (160-198) beats/min in PLA (p = 0.32)., Conclusions: In infants (1-3 months) undergoing NPA, administration of an oral sweet solution did not statistically decrease pain scores., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Patients with haemophilia A who have similar FVIII levels show clinical heterogeneity, and 10-15% of patients with severe haemophilia do not have a severe bleeding phenotype. The aim of this study was to assess whether global haemostasis tests, such as thrombin generation assay (TGA) and thromboelastography (TEG), can predict the bleeding pattern of severe haemophilia better than trough levels and pharmacokinetic profiles, particularly in the prophylactic setting. The study group consisted of 39 patients with haemophilia A and 75 healthy controls. The annual bleeding rate (ABR) and Hemophilia Joint Health Score 2.1 (HJHS) of the patients were determined. Basal factor FVIII, inhibitor levels, TEG and TGA of participants with prophylaxis were performed after a washout period. Then, a recombinant FVIII product was administered to patients. After factor replacement, the above tests were repeated at 30 min, 6 and 48 h. There was a significant difference in the ABR and HJHS between the groups according to the basal factor VIII activity of patients after wash-out. TEG and TGA parameters of patients with factor activity above 1% were significantly better than those of patients with factor activity below 1%. After factor concentrate administration, factor activities, TEG and TGA parameters at 30 min, 6 and 48 h were similar in the two groups. We showed that the 1% trough level but not for the 3% trough level is critical for both clinical phenotypes and thrombin generation for haemophilia patients in the prophylactic setting., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Management of chronic wounds remains one of the major challenges for health professionals and patients. An evidence-based decision is important to ensure that patients are receiving the best treatment proven to reduce healing time and improve outcomes, including economic benefits and patients' health-related quality of life (HRQoL). Due to recent restrictions because of the COVID-19 pandemic, including closure of wound care centres within hospitals and a drop in patient volume, chronic wound management needs simple-to-use dressings which are still effective and evidence-based solutions. This systematic review was conducted to identify the clinical evidence available on a sucrose octasulfate dressing (TLC-NOSF, UrgoStart dressing range, Laboratoires Urgo, France) to explore its efficacy in the management of chronic wounds, particularly lower limb ulcers, diabetic foot ulcers and pressure ulcers., Method: A literature search of PubMed, Cochrane Library and Google Scholar was conducted based on the PICO model (patient/population, intervention, comparison and outcomes) to retrieve publications of different levels of evidence in order to evaluate outcomes of the use of TLC-NOSF dressings., Results: A total of 21 publications of different levels, ranging from double-blind randomised control trials to case reports, involving over 12,000 patients, were identified through PubMed, with a further eight publications through Google Scholar and two publications through Cochrane Library. A total of seven results were omitted due to the lack of relevance or repetition., Conclusion: All the evidence provided suggest that these dressings provide clinicians with an evidence-based option for the management of chronic wounds; that the TLC-NOSF dressings are beneficial in promoting the healing process, reducing healing times, enhancing patients' HRQoL, and in allowing a more cost-effective procedure.

Background: In patients on maintenance dialysis, cardiovascular mortality risk is remarkably high, which can be partly explained by severe coronary artery calcification (CAC). Hyperphosphatemia has been reported to be associated with the severity of CAC. However, the optimal phosphate range in patients on dialysis remains unknown. This study was planned to compare the effects on CAC progression of two types of noncalcium-based phosphate binders and of two different phosphate target ranges., Methods: We conducted a randomized, open-label, multicenter, interventional trial with a two by two factorial design. A total of 160 adults on dialysis were enrolled and randomized to the sucroferric oxyhydroxide or lanthanum carbonate group, with the aim of reducing serum phosphate to two target levels (3.5-4.5 mg/dl in the strict group and 5.0-6.0 mg/dl in the standard group). The primary end point was percentage change in CAC scores during the 12-month treatment., Results: The full analysis set included 115 patients. We observed no significant difference in percentage change in CAC scores between the lanthanum carbonate group and the sucroferric oxyhydroxide group. On the other hand, percentage change in CAC scores in the strict group (median of 8.52; interquartile range, -1.0-23.9) was significantly lower than that in the standard group (median of 21.8; interquartile range, 10.0-36.1; P =0.006). This effect was pronounced in older (aged 65-74 years) versus younger (aged 20-64 years) participants ( P value for interaction =0.003). We observed a similar finding for the absolute change in CAC scores., Conclusions: Further study with a larger sample size is needed, but strict phosphate control shows promise for delaying progression of CAC in patients undergoing maintenance hemodialysis., Clinical Trial Registry Name and Registration Number: Evaluate the New Phosphate Iron-Based Binder Sucroferric Oxyhydroxide in Dialysis Patients with the Goal of Advancing the Practice of EBM (EPISODE), jRCTs051180048., (Copyright © 2021 by the American Society of Nephrology.)

Background: The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), demonstrated its effectiveness for lowering serum phosphate levels, with low daily pill burden, in clinical trials of dialysis patients with hyperphosphatemia. This retrospective database analysis evaluated the real-world effectiveness of SFOH for controlling serum phosphate in European hemodialysis patients., Methods: De-identified patient data were extracted from a clinical database (EuCliD®) for adult hemodialysis patients from France, Italy, Portugal, Russia and Spain who were newly prescribed SFOH for up to 1 year as part of routine clinical care. Serum phosphate and pill burden were compared between baseline (3-month period before starting SFOH) and four consecutive quarterly periods of SFOH therapy (Q1-Q4; 12 months) in the overall cohort and three subgroups: PB-naïve patients treated with SFOH monotherapy (mSFOH), and PB-pretreated patients who were either switched to SFOH monotherapy (PB → mSFOH), or received SFOH in addition to another PB (PB + SFOH)., Results: 1096 hemodialysis patients (mean age: 60.6 years; 65.8% male) were analyzed, including 796, 188 and 53 patients in, respectively, the PB + SFOH, mSFOH, and PB → mSFOH groups. In the overall cohort, serum phosphate decreased significantly from 1.88 mmol/L at baseline to 1.77-1.69 mmol/L during Q1-Q4, and the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased from 41.3% at baseline to 56.2-62.7% during SFOH treatment. Mean PB pill burden decreased from 6.3 pills/day at baseline to 5.0-5.3 pills/day during Q1-Q4. The subgroup analysis found the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased significantly from baseline during SFOH treatment in the PB + SFOH group (from 38.1% up to 60.9% [Q2]) and the mSFOH group (from 49.5% up to 75.2% [Q2]), but there were no significant changes in the PB → mSFOH group. For the PB + SFOH group, serum phosphate reductions were achieved with a similar number of PB pills prescribed at baseline prior to SFOH treatment (6.5 vs 6.2 pills/day at Q4). SFOH daily pill burden was low across all 3 subgroups (2.1-2.8 pills/day)., Conclusion: In this real-world study of European hemodialysis patients, prescription of SFOH as monotherapy to PB-naïve patients, or in addition to existing PB therapy, was associated with significant improvements in serum phosphate control and a low daily pill burden.

Background: Premature infants hospitalized in the neonatal intensive care unit are routinely exposed to many painful procedures. Pain experienced during the neonatal period may lead to negative outcomes, especially in preterm neonates, hence pain in infants should be reduced. Kangaroo care and oral sucrose are some of the methods that can help reduce pain., Aim: This study aimed to compare the effects of kangaroo care and oral sucrose on pain relief in preterm infants during heel lancing., Methods: Our study involved 64 infants. The infants were randomly divided into two groups using a randomized block design of drawing out slips from a thick, non-transparent envelope. There were 64 slips in this envelope (32 for kangaroo care and 32 for oral sucrose). Kangaroo care was given to the preterm infants in the first group and oral sucrose to those in the second group. In both groups, heart rate and oxygen saturation were measured and pain score was evaluated by two observers using the Premature Infant Pain Profile (PIPP) before, during, and 2 minutes after blood sampling by heel lancing., Results: There was a statistically significant difference between the groups in favor of the kangaroo group in terms of change in the PIPP values after heel lancing. Kangaroo care is more effective than oral sucrose in pain relief during heel lancing in preterm infants., Conclusions: In addition to many benefits it offers to infants, kangaroo care can be used to reduce pain during painful procedures in premature infants., (Copyright © 2020 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Introduction: The lack of adherence to phosphate -binders (PB) is the most important factor in not achieving the objectives of serum phosphorus (sP). Studies in the real-world population are needed to understand the influence of PBs on adherence and how to modify it., Methods: Prospective study conducted during 3 months in usual clinical practice. Out of 105 hemodialysis patients, 57 were switched to SFOH and 48 maintained their baseline treatment (control group). sP levels and the percentage of patients with sP levels <5mg/dl were compared. Adherence before and after introduction of SFOH, number of pills of PB, preferences in the administration mode and side effects were analyzed., Results: The percentage of patients with controlled sP (<5mg/dl) increased significantly in the SFOH users' group (62.1-92.9%, p<0.001), but not in the control group (83-83.3%, p=NS). The average of daily tablets decreased significantly in the SFOH group (7.2-2.3 comp, p<0.001), but not in the control group (5.6-5.6, p=NS) and 100% of the patients used only one PB in SFOH group. The use of SFOH increased the adherence according to the SMAQ questionnaire (57.8-84.3%; OR 13.1, p<0.001). The possibility to choose the preferred mode of administration (split-swallowing 89% compared to chewing 11%), improved the acceptance (44.7-78%). 14% of the patients experienced side effects and in 5.2% SFOH was discontinued for this reason., Conclusions: SFOH controlled serum sP in 93% of patients, 100% in monotherapy, and with fewer tablets. The exploration and adaptation of preferences in the mode of administration influenced the acceptance of the drug by the patient and, probably, the future adherence., (Copyright © 2020 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Because end-stage renal disease patients undergoing hemodialysis frequently take acid suppressants for the treatment or prevention of gastrointestinal diseases, it is important to clarify the drug-interactions between acid suppressants and phosphate binders on the control of serum phosphate levels. In the present study, we examined whether the phosphate-lowering effects of three phosphate binders, lanthanum carbonate (LC), ferric citrate hydrate (FCH), and sucroferric oxyhydroxide (SFOH), were affected by proton pump inhibitors (PPIs) in maintenance hemodialysis patients. Laboratory data for 71 patients who had been newly prescribed one of the three phosphate binders were examined. LC at a dosage of 500 ± 217 mg/day significantly decreased serum phosphate levels by -18% in the absence of a PPI ( n  = 9), while a dosage of 700 ± 230 mg/day only decreased it by -3% in the presence of a PPI ( n  = 10). Thus, the efficacy of LC in reducing serum phosphate levels was significantly hindered by the presence of PPIs. FCH significantly decreased serum phosphate levels by -18% in the absence of a PPI ( n  = 7, FCH: 571 ± 189 mg/day) and by -17% in the presence of a PPI ( n  = 20, FCH: 638 ± 151 mg/day). The decrease in serum phosphate levels by SFOH (393 ± 197 mg/day) was -7% in the absence of a PPI ( n  = 7), and SFOH at a dosage of 556 ± 316 mg/day significantly decreased serum phosphate levels by -13% in the presence of a PPI ( n  = 18). These results suggest that the phosphate-lowering effect of LC, but not of FCH or SFOH, is diminished in the presence of PPIs in hemodialysis patients.

Management of diabetic foot ulcers with a TLC-NOSF dressing, based on evidence and clinical practice The incidence of diabetic foot ulcers (DFU) has increased in the past decade, both in Chile and worldwide, as a result of the progressive growth in diabetes prevalence. Because DFU are associated with a high risk of infection and amputation, it is crucial to choose effective and evidence-based treatments. A dressing combining technology lipidocolloid with nano-oligo saccharide factor (TLC-NOSF) has demonstrated its effectiveness in managing DFU. This article reviews the evidence around TLC-NOSF and its implementation in clinical practice.

Objective: A common and frequent complication of diabetes is diabetic foot ulcers (DFU), which can have high treatment costs and severe adverse events. This study aims to evaluate the effects of wound duration on wound healing and the impact on costs, including treatment with a new sucrose octasulfate dressing compared with a control dressing., Method: Based on the Explorer study (a two-armed randomised double-blind clinical trial), a cost-effectiveness analysis compared four different patient groups distinguished by their wound duration and additionally two DFU treatment options: a sucrose octasulfate dressing and a neutral dressing (as control). Clinical outcomes and total direct costs of wound dressings were evaluated over 20 weeks from the perspective of the Social Health Insurance in Germany. Simulation of long-term outcomes and costs were demonstrated by a five cycle Markov model., Results: The results show total wound healing rates between 71% and 14.8%, and direct treatment costs for DFU in the range of €2482-3278 (sucrose octasulfate dressing) and €2768-3194 (control dressing). Patients with a wound duration of ≤2 months revealed the highest wound healing rates for both the sucrose octasulfate dressing and control dressing (71% and 41%, respectively) and had the lowest direct treatment costs of €2482 and €2768, respectively. The 100-week Markov model amplified the results. Patients with ≤2 months' wound duration achieved wound healing rates of 98% and 88%, respectively and costs of €3450 and €6054, respectively (CE=€3520, €6864). Sensitivity analysis revealed that the dressing changes per week were the most significant uncertainty factor., Conclusion: Based on the findings of this study, early treatment of DFU with a sucrose octasulfate dressing is recommended from a health economic view due to lower treatment costs, greater cost-effectiveness and higher wound healing rates.

Introduction: Sucroferric oxyhydroxide (PA21) is an efficacious, well-tolerated iron-based phosphate binder and a promising alternative to existing compounds. We compared the effects of PA21 with those of a conventional phosphate binder on renal function, mineral homeostasis and vascular calcification in a chronic kidney disease-mineral and bone disorder (CKD-MBD) rat model., Methods: To induce stable renal failure, rats were administered a 0.25% adenine diet for 8 weeks. Concomitantly, rats were treated with vehicle, 2.5 g/kg/day PA21, 5.0 g/kg/day PA21 or 3.0 g/kg/day calcium carbonate (CaCO3). Renal function and calcium/phosphorus/iron metabolism were evaluated during the study course. Renal fibrosis, inflammation, vascular calcifications and bone histomorphometry were quantified., Results: Rats treated with 2.5 or 5.0 g/kg/day PA21 showed significantly lower serum creatinine and phosphorus and higher ionized calcium levels after 8 weeks of treatment compared with vehicle-treated rats. The better preserved renal function with PA21 went along with less severe anaemia, which was not observed with CaCO3. Both PA21 doses, in contrast to CaCO3, prevented a dramatic increase in fibroblast growth factor (FGF)-23 and significantly reduced the vascular calcium content while both compounds ameliorated CKD-related hyperparathyroid bone., Conclusions: PA21 treatment prevented an increase in serum FGF-23 and had, aside from its phosphate-lowering capacity, a beneficial impact on renal function decline (as assessed by the renal creatinine clearance) and related disorders. The protective effect of this iron-based phosphate binder on the kidney in rats, together with its low pill burden in humans, led us to investigate its use in patients with impaired renal function not yet on dialysis., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Patients with chronic wounds should receive wound treatment in addition to causative therapy. In this context, the lack of adequate evidence for wound healing products has been repeatedly discussed. Using the example of TLC-sucrose octasulfate (TLC: technology lipido-colloid), the present review shows that there is significant data with good evidence and comparability in this area. One therapeutic approach to promote wound healing is the inhibition of matrix-metalloproteinases, for example by sucrose octasulfate. For wound products containing TLC-sucrose octasulfate, several sequential clinical studies have been conducted in recent years. The WHAT study was an open randomized controlled trial (RCT) with 117 patients with venous leg ulcers (VLU). The CHALLENGE study was a double-blind RCT with 187 patients with VLU. The SPID study was a pilot study with 33 patients with diabetic foot ulcers (DFU). The two prospective, multicenter clinical pilot studies NEREIDES and CASSIOPEE examined a total of 88 patients with VLU in different phases of healing. In the REALITY study, a pooled data analysis was performed on eight observational studies with 10,220 patients with chronic wounds of different genesis. In the double-blind, two-armed EXPLORER RCT, 240 patients with neuro-ischemic DFU were followed from first presentation until complete healing. In all studies, a significant promotion of wound healing could be shown by the use of wound healing products with TLC-sucrose octasulfate.

Background: In patients with chronic kidney disease (CKD), dysbiosis in the gastrointestinal microbiome is thought to be associated with increased production of uremic toxins, such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS). Sucroferric oxyhydroxide (SFO), an iron-based phosphate binder, may affect the gastrointestinal microbiome and the production of uremic toxins. We aimed to examine whether SFO administration affected distribution of gastrointestinal microbiome and serum uremic toxin levels in CKD patients undergoing hemodialysis., Methods: In this single-center, open-label, interventional study, 18 maintenance hemodialysis patients with hyperphosphatemia were prescribed with SFO. We collected serum samples before and after 3 months of administration, and serum levels of IS and PCS were measured. A control group of 20 hemodialysis patients without SFO was evaluated. We evaluated gastrointestinal microbiome of patients pre- and post-SFO administration by 16S rDNA sequencing and bioinformatics analysis., Results: Serum IS and PCS levels were significantly elevated after administration of SFO (IS before 2.52 ± 1.60 mg/dl vs. after 3.13 ± 1.51 mg/dl, P = 0.008; PCS before 2.32 ± 2.44 mg/dl vs. after 3.45 ± 2.11 mg/dl, P = 0.002), while serum IS and PCS levels did not change in the control group. Microbiome analysis in the SFO group showed no significant change in diversity and major components in phylum, class, order, family, gene, and species., Conclusion: Administration of SFO increased the serum levels of IS and PCS with no change of major components of gastrointestinal microbiome.

Due to the complexity and fragility of biological drug products, several challenges exist in their formulation development. Excipients are added to increase product stability, maintain tonicity, and facilitate drug delivery. The potential implications of these additive substances merit clinical consideration. We assessed the safety risk of excipients on the basis of their type and variability through an assessment framework, which quantifies excipient complexity in 230 biological formulations, and identifies excipient-related adverse events through published case reports. A biologic on average contained 4.45 excipients, half of that found in oral medications. The frequency distribution was heavily skewed towards the most commonly occurring excipients: water (40.4%), sodium chloride (38.3%), polysorbate 80 (28.7%), sucrose (24.4%), and mannitol (20.9%), with 44.4% of formulations not listing the concentration of the most commonly occurring inactive ingredients. A literature search revealed only 17 case reports of excipient-related adverse events, suggesting the need for more clarity for clinicians on the safety of chemical additives. These cases included injection site reactions, anaphylaxis, hyperglycemia, and acute renal failure. With the expansion of the biopharmaceutical market, it is important to consider the safety data of biologic excipients, so that therapy can be tailored appropriately for a specific patient., Competing Interests: The authors have declared that no competing interests exist.