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Patients inclusion and exclusion criteria | We studied patients aged between 18 and 75 years, with an American Society of Anesthesiologists (ASA) physical status of I or II and a BMI range from 18 kg m | PMC10184475 | ||
Anesthesia | Patients were routinely monitored by an electrocardiogram (ECG), heart rate (HR), invasive arterial pressure (IBP), pulse oxygen saturation (SpOThe BIS ranges from 100 (awake) to 0 (flat line EEG), and as the number decreases, the anesthetic depth increases. During general anesthesia, a BIS value of 40 to 60 was recommended [ | PMC10184475 | ||
Blood samples | Flow cytometry was used to determine the number of T lymphocyte subsets (including the CD4+/CD8 + ratio, CD3 + T cells, CD4 + T cells, and CD8 + T cells) and natural killer (NK) cells. Venous blood samples were collected immediately before anesthesia induction (T | PMC10184475 | ||
Clinical measurements | Fever, postoperative pain, pain | SITE INFECTION | Before leaving the PACU (postanesthesia care unit), intraoperative awareness was evaluated using the Modified Brice Questionnaire. The level of postoperative pain at rest was assessed 1 day after surgery using a numeric rating scale (NRS) ranging from 0 (no pain) to 10 (most pain imaginable). Postoperative 24 h analgesic pump drug residual volume was obtained from the electronic analgesia pump system. Fever and incision site infections that occur during hospitalization are diagnosed by the surgeon in charge of the patient. Fever is defined as a postoperative temperature over 38 °C [ | PMC10184475 |
Statistical analysis | NRS, fever | SECONDARY, SURGICAL SITE INFECTION | On the principle of the intention-to-treat principle, all analyses were performed. All patients who were randomly assigned were included in the intention-to-treat group. The primary outcome was the CD4+/CD8 + ratio 24 h after surgery, while the secondary outcome measures were the number of lymphocyte subsets, intraoperative awareness, emergence time, NRS score, and analgesic pump drug residual volume at 24 h after surgery, as well as the incidences of surgical site infection and fever during hospitalization. According to the published data [Statistical analysis was performed using the SPSS software (Version 19.0; IBM Corporation, New York). The normality of data distribution was assessed by the Shapiro-Wilk test. Normally distributed continuous data were expressed as the mean ± standard deviation and analyzed using the t-test. The categorical variables were expressed as frequencies (percentages) and analyzed using the chi-square test. The Mann-Whitney U-test was used for continuous variables with a non-normal distribution. The differences in T lymphocyte subsets and NK cells over time were analyzed by Two-way analysis of variance (ANOVA) followed by Bonferroni correction. Statistical significance was set at | PMC10184475 |
Results | A total of 75 Patients were enrolled between February 15 and July 31, 2022. Figure
Flow diagramBaseline patient characteristics are shown in Table
Baseline patient characteristicsASA, American Society of Anesthesiologists; BMI, body mass index; MAP, mean arterial pressure; HR, heart rate. Data are summarised by number (%), median (interquartile range) or mean (standard deviation). Intraoperative characteristics were shown in Table
Intraoperative characteristicsASA, American Society of Anesthesiologists; BMI, body mass index; MAP, mean arterial pressure; HR, heart rate. Data are summarised by number (%), median (interquartile range) or mean (standard deviation).
Changes in the MAP, HR and BIS over time in two groups (Figure
Changes in the CD4+/CD8 + ratio, CD3 + T cell and NK cell were not significantly different in the two groups (Figures
Changes in CD4 + T cell was not significantly different in the two groups (
Changes in CD8 + T cell was not significantly different in the two groups (Data on the serum cytokines are shown in Table
Perioperative Cytokine ConcentrationsData are expressed as median (interquartile range) or mean ± SD with difference (95% CI).TIL = Interleukin; VEGF = Vascular Endothelial Growth Factor; IFN = Interferon.Postoperative characteristics is presented in Table
Postoperative characteristicsData are summarised by number (%), median (interquartile range) or mean (standard deviation). POD1 NRS score, the numerical rating scale score at 1 day postoperatively. Analgesic pump drug residual volume, the analgesic pump drug residual volume at 24 h postoperatively. | PMC10184475 | ||
Acknowledgements | EMERGENCY | Assistance with this study: staff of Emergency Laboratory and Gastrointestinal Surgery of The Affiliated Lianyungang Hospital of Xuzhou Medical University. | PMC10184475 | |
Authors’ contributions | RECRUITMENT | Study design: Zhibin ZHAO, Hengfei LUAN, Xiaobao ZHANG. Patient recruitment: Han LI, Jiachi LI. Randomization and allocation: Han LI, Conghui HAO Data acquisition and analysis: Han LI, Jiachi LI, Conghui HAO. Drafting the manuscript: Han LI, Hengfei LUAN. Revision of the manuscript: all authors. All authors read and approved the final manuscript. | PMC10184475 | |
Funding | This research was supported by Lianyungang 521 project and Clinical Research Fund of The Affiliated Lianyungang Hospital of Xuzhou Medical University (LC13). | PMC10184475 | ||
Availability of data and materials | The datasets used and/or analyzed during the study are available from the corresponding author on reasonable request. | PMC10184475 | ||
Declarations | PMC10184475 | |||
Competing interests | The authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or material discussed in this manuscript. | PMC10184475 | ||
Ethics approval and consent to particiate | Ethical approval for this study (ethics: KY-20211130002-02) was provided by the Ethics Committee of the affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China on 29 January 2022. Written informed consent was obtained from all participants. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR2200056624) on 09/02/ 2022 before enrollment. All methods were performed in accordance with the Declaration of Helsinki. | PMC10184475 | ||
Consent for publication | Not applicable. | PMC10184475 | ||
References | PMC10184475 | |||
Abstract | PMC10108682 | |||
Introduction | septic shock | SEPTIC SHOCK, PYOGENIC LIVER ABSCESS, UTI | This study determined the therapeutic effect of ulinastatin (UTI) on unliquefied pyogenic liver abscesses complicated by septic shock (UPLA‐SS). | PMC10108682 |
Methods | This was a randomized controlled trial involving patients with UPLA‐SS who underwent treatment at our hospital between March 2018 and March 2022. The patients were randomly divided into control ( | PMC10108682 | ||
Results | tumor necrosis | TUMOR NECROSIS | Following treatment, the white blood cell count, and lactate, C‐reactive protein, procalcitonin, tumor necrosis factor‐α, and interleukin‐6 levels were significantly decreased in all patients compared to the admission values ( | PMC10108682 |
Conclusion | infection | SEPTIC SHOCK, INFECTION, PYOGENIC LIVER ABSCESS, UTI | UTI combined with conventional treatment significantly controlled the infection symptoms, improved organ function, and shortened the treatment time in patients with UPLA‐SS.Ulinastatin combined with conventional treatment significantly controlled the infection symptoms, improved organ function, and shortened the treatment time in patients with unliquefied pyogenic liver abscesses complicated by septic shock.
| PMC10108682 |
INTRODUCTION | shock, bacterial endocarditis, liver abscess, intra‐abdominal malignancies, diabetes | INFLAMMATORY RESPONSE, PERIODONTAL INFECTION, SHOCK, LIVER ABSCESS, DIABETES | A liver abscess (LA) is a focal, infectious lesion of the liver caused by microorganisms, such as bacteria, fungi, or amoebas via arterial, venous, biliary tract, and direct dissemination, and is one of the more common acute critical illnesses in the intensive care unit (ICU).The direct hematogenous spread of systemic bacteria, such as bacterial endocarditis or periodontal infections, is known to produce PLAs. Significant risk factors for these processes include immunosuppression, liver transplantation, diabetes, biliary procedures, and intra‐abdominal malignancies.The pathophysiologic mechanism underlying infectious shock due to an unliquefied PLAs is primarilyIt is known that activation of the MyD88‐dependent pathway to induce an inflammatory response is one of the main pathways leading to infectious shock due to a bacterial LA,Urinary trypsin inhibitor, also known as ulinastatin (UTI),It has been shown | PMC10108682 |
MATERIALS AND METHODS | PMC10108682 | |||
General information | This study was a single‐center, randomized, controlled trial (Register number: ChiCTR2200066693). Ninety‐nine patients (58 males and 41 females; average age, 60.18 ± 9.61 years; age range, 33−77 years) with UPLA‐SS who were admitted to the Department of Intensive Care Medicine (Huai'an First Hospital, Nanjing Medical University) from March 2018 to March 2022 were enrolled in the study. The control group was treated with fluid resuscitation, supplemental oxygen, and nutritional support. The circulation was stabilized and vital organ function was maintained. During the initial stage, carbapenems (imipenem/cilastatin [1 g every 8 h] and biapenem [0.3 g every 8 h]) were administered intravenously. Treatment was then adjusted based on the results of pathogenic drug sensitivity tests, as presented in Tables Microbial species detected and antibiotics used in the two groups.Antibiotic susceptibility patterns of bacterial isolates from the two groups.Abbreviations: I, intermediate; R, resistant; S, susceptible. | PMC10108682 | ||
Inclusion and exclusion criteria | followsThe, shock | SHOCK | The inclusion criteria for an unliquefied PLA were as followsThe inclusion criteria for infectious shock were based on the 3rd edition of the definition of infectious shock published by the Society of Critical Care Medicine (SCCM)/European Society of Intensive Care Medicine (ESICM),The exclusion criteria were as follows: (1) LA caused by other microorganisms, such as amoebae, Flowchart of included patients. | PMC10108682 |
Observation indicators | tumor necrosis, fever | LIVER, PCT, TUMOR NECROSIS | Infection‐related objective indices were monitored by comparing changes in Lac, PCT, CRP, tumor necrosis factor‐α (TNF‐α), and interleukin‐6 (IL‐6) levels, and the WBC count before and on the 1st, 2nd, and 3rd days after treatment in the two groups. Infection‐related indices were monitored by comparing the duration of ICU stay, duration of fever, and duration of vasoactive drug use in the 2 groups. Liver function‐related indices were monitored by comparing total bilirubin (TBil), alanine transaminase (ALT), and aspartate transaminase (AST) levels, and other index changes before and on the 1st, 2nd, and 3rd days after treatment in the two groups. The clinical outcomes of patients in both groups were followed. | PMC10108682 |
Statistical analysis | The data were analyzed using SPSS 22.0 statistical software, and the count data were described by rate or composition ratio. Normally‐distributed measurement data are described by the mean ± standard deviation, and data with a skewed distribution are expressed by M (range). Comparisons between groups of count data were made using the test or Fisher's exact probability method. Comparisons between groups of measurement data conforming to a normal distribution were made using a | PMC10108682 | ||
RESULTS | PMC10108682 | |||
Analysis of general clinical data of patients in both groups before treatment | TNF‐α, Tumor necrosis | PCT, TUMOR NECROSIS | The statistical analysis of the baseline and treatment data of both groups did not reveal any significant differences (Analysis of general clinical data before treatment in the two groups.Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; CRP, C‐reactive protein; IL‐6, Interleukin‐6; Lac, Lactic acid; PCT, Procalcitonin; TNF‐α, Tumor necrosis factor‐alpha; TBil, Total bilirubin; WBC, White blood cell. | PMC10108682 |
Indices of infection after treatment in the two groups | infection, TNF‐α, Tumor necrosis | INFECTION, PCT, TUMOR NECROSIS | Post‐treatment, the Lac, CRP, PCT, TNF‐α, and IL‐6 levels, and WBC count in both groups showed a significant reduction compared to pretreatment values (Comparison of objective indicators related to infection after treatment between two groups.Abbreviations: CRP, C‐reactive protein; IL‐6, Interleukin‐6; Lac, Lactic acid; PCT, Procalcitonin; TNF‐α, Tumor necrosis factor‐alpha; TBil, Total bilirubin; WBC, White blood cell. | PMC10108682 |
Indicators of infection after treatment in the two groups | fever | The duration of ICU stay, sustained fever, and vasoactive drug use were significantly shorter in the study group compared to the control group after treatment (Comparison of infection‐related indicators between the two groups after treatment. | PMC10108682 | |
Liver function indices in the two groups after treatment | The TBil, ALT, and AST levels were significantly decreased in both groups after treatment (Recovery of liver function indices after treatment in the two groups.Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; TBil, total bilirubin. | PMC10108682 | ||
Clinical outcomes | The mortality rate in the study group (10.41%) was lower than the control group (17.65%), although the difference was not statistically significant ( | PMC10108682 | ||
DISCUSSION | deaths, ischemia‐reperfusion injury, SIRS, shock, ischemia, hypoperfusion, hypoxia, infections, hyperlactatemia, liver injury, infection, UTI, septic shock, sepsis, septic | INFECTIOUS DISEASES, PCT, INFLAMMATORY RESPONSES, SHOCK, LIVER FAILURE, ISCHEMIA, HYPOPERFUSION, HYPOXIA, INFECTIONS, DISEASE, INFECTION, UTI, SEPTIC SHOCK, SEPSIS, INFECTIOUS DISEASES | Infectious diseases affect the entire course of human development, of which there were nearly 50 million new septic patients worldwide in 2017 and 11 million deaths due to sepsis, accounting for 19.7% of global deaths.UTI is a glycoprotein purified from healthy human urineUTI suppresses neutrophil superoxide generation caused by stimuli, such as formylmethionyl‐leucyl‐phenylalanine in a dose‐dependent manner. The reduction of neutrophil superoxide production generated by stimuli, such as formylmethionyl‐leucyl‐phenylalanine, may reflect the fact that UTI reduces the expression of pro‐synuclein‐activated protein kinase, which successfully scavenges endotoxin and protects cellular mitochondria. Patients with sepsis or septic shock who receive UTI have a reduction in all‐cause mortality and other associated outcomes.This finding indicates that UTI has a dual synergistic effect of anti‐inflammation and protection of organ function because UTI inhibits ischemia and reperfusion and enhances the antioxidant defense, thus leading to restoration of the structure and function of hepatocytes. The WBC count, and CRP, PCT, TNF‐α, and IL‐6 levels are the most common clinical indicators to assess infectious diseases.In this study the trend of improvement in inflammatory monitoring indices, such as the WBC count, and the PCT, CRP, TNF‐α, and IL‐6 levels in the study group were significantly faster than the control group, and the difference between the two groups was statistically significant. After anti‐infection and shock correction, all patients showed a significant reduction in inflammatory markers compared to pretreatment. This finding confirms the effectiveness of UTI in controlling infections and suppressing inflammatory responses with good efficacy, including endotoxin, which is consistent with previous studies on UTI efficacy in treating pulmonary, urinary, and post‐traumatic infections.The liver of patients with an unliquefied bacterial LA, combined with infectious shock, is one of the more heavily involved target organs in these patients, and the production of large amounts of inflammatory mediators in the body during SIRS easily induces apoptosis of hepatocytes, which together with tissue ischemia‐reperfusion injury and microthrombus formation, can easily lead to acute liver injury and even liver failure.When a severe infection occurs, tissue hypoperfusion and cellular hypoxia often already exist before the change in routine hemodynamic monitoring indices, and blood Lac levels are already elevated, thus resulting in hyperlactatemia. The elevated blood Lac levels are an early and sensitive biochemical indicator of inadequate tissue perfusion and oxygen delivery, and therefore blood Lac can be one of the important indicators for assessing disease severity and prognosis.The limitations of the current study were as follows: 1. The specific effect of UTI on antioxidant profiles was not observed. Therefore, further research is expected to address this issue. 2. Studies need to have rigorous study designs, such as double‐blind, randomized, controlled trials to eliminate the effects of other interfering factors on the results. 3. This study was limited to a single center due to resource and time constraints. Further confirmation of our findings with a large multicenter sample is necessary to strengthen the generalizability and external validity. | PMC10108682 |
CONCLUSION | INFLAMMATORY RESPONSE, UTI | Combined application of UTI with conventional treatment significantly reduced the inflammatory response, promoted the recovery of organ function, and shortened the treatment time in patients with UPLA‐SS, thus improving the clinical symptoms of patients, which is worth promoting in clinical practice. | PMC10108682 | |
AUTHOR CONTRIBUTIONS | PMC10108682 | |||
CONFLICT OF INTEREST STATEMENT | The authors declare no conflict of interest. | PMC10108682 | ||
ETHICS STATEMENT | All the procedures in this study were in accordance with the standards of the Ethics Review Committee of our institution (KY‐2017‐134‐01). Written informed consent from the participants and their families were obtained. | PMC10108682 | ||
DATA AVAILABILITY STATEMENT | The data generated or used during the study are available from the corresponding author by request. | PMC10108682 | ||
REFERENCES | PMC10108682 | |||
Background/aim | metabolic impairment, T2D | TYPE 2 DIABETES MELLITUS | Type 2 diabetes mellitus (T2D) is a complex metabolic impairment. Beta cell (BC) failure is the most challenging among its pathogenetic mechanisms. Recognizing reversible contributors to BC failure could guide individualized approach to early T2D treatment. The aim of this study was to compare early short-term insulin treatment vs. glimepiride, both added to metformin, on BC function, glycemic and lipid control, during 12-month follow-up. | PMC10387975 |
Patients and methods | STM, T2D | INS | Eighty newly diagnosed T2D patients, 30–65 years of age, presenting with HbA1c ≥ 9% were enrolled in the study. They were randomly assigned to single-month initial insulin therapy (INS) added to metformin, or to glimepiride and metformin (OAD) as only treatment. Subjects assigned to initial insulin intervention were thereafter switched to OAD. C-peptide (C-Pep) was analyzed at baseline and 2 hours after standardized test meal (STM). All subjects were STM-retested after 3 and 12 months. HbA1c, serum lipids, BMI, HOMA IR, and HOMA B were assessed over follow-up. | PMC10387975 |
Results | ± | INS | HbA1c was lower in INS vs OAD at 3-months: 6.26 ± 0.18% vs 6.78 ± 0.10% (p = 0.016), remaining so by 12 months (p = 0.056). BMI-adjusted ΔC-Pep was greater in INS vs. OAD at 3 months (4.60 ± 0.59 vs. 3.21 ± 0.34 m | PMC10387975 |
Conclusion | T2D improves beta cell function | Early short-term insulin intervention in newly diagnosed T2D improves beta cell function more than glimepiride, both added to metformin, resulting in a superior and longer lasting glycemic and lipid control. | PMC10387975 | |
1. Introduction | glucotoxicity, T2D | TYPE 2 DIABETES MELLITUS | Global impact of type 2 diabetes mellitus (T2D) reaches pandemic proportions [Over the course of T2D progression, increasing doses and number of glucose-lowering medications are typically required, often leading to introduction of insulin treatment, once BC capacity is apparently exhausted. Such insulin treatment represents a form of exogenous replacement of a hormonal deficiency. On the other hand, early insulin treatment aimed at rapid elimination of glucotoxicity and BC recovery could represent a form of disease-modifying treatment [Affordable but reliable testing of BC secretory function is still elusive. Oral-based dynamic tests are attractive due to ease of clinical use and incorporation of incretin activation effects [The aim of our study was to assess beta cell (BC) secretory response to a standardized test meal in newly diagnosed T2D subjects and to compare the effect of early short-term insulin treatment vs. glimepiride, both added to metformin, on BC function, glycemic control and lipid metabolism, during a 12-month follow-up. | PMC10387975 |
2. Patients and methods | STM, T2D, diabetes | DIABETES | This prospective, interventional randomized study, approved by Ethics Board of Zvezdara University Medical Center (Decision dated 29.01.2019), included 80 newly diagnosed T2D patients with initial HbA1c above 9.0%. They were recruited from the outpatient diabetes clinic of the Zvezdara University Medical Center in Belgrade, during the period of February 2019 to March 2020. Upon signing the informed consent form, they had 3 daily visits at the Center. On the first day, an STM was performed. Thereafter, patients were randomly assigned to receive either: metformin 2000 mg daily (or maximal tolerable dose) and glimepiride, or metformin with a 1-month course of daily basal or twice daily biphasic human insulin. Both patients and investigators were blinded for individual baseline C-peptide values. Randomization of patients was done on consecutive basis. The subjects were educated for insulin application by pens, proper diet, and physical activity. They were provided with meters for blood glucose (BG) self-monitoring, before each main meal, at bedtime and upon awakening. On the second and third days, after discussion of monitored BG levels, doses of insulin and glimepiride were adjusted. Subjects on insulin treatment were advised to continue monitoring BG levels and to report values below 4 mmol/L or above 10 mmol/L, for dose adjustment.The exclusion criteria for the investigated patients encompassed: pregnancy or lactation, decreased renal function below eGFR of 60 mL/min/1.73 mAll patients were tested by a standardized test meal (STM) before treatment and at 3- and 12-month visits. STM consisted of a white-flour bread-roll (24 g of carbohydrates) and 200 mL 2.8% milk-fat yoghurt (12 g of carbohydrates). Upon an overnight fast, serum glucose and C-Pep were analyzed before and 2 hours after STM, which was consumed over 5 min [ | PMC10387975 |
2.1. Calculations and statistical analysis | Serum C-Peptide (C-Pep) from all samples was analyzed by ECLIA assay (Cobas Elecsys C-Peptide assay, Roche Diagnostics GmbH, Mannheim, Germany) in Beo-Lab laboratory, Belgrade (baseline normal C-Pep reference range: 1.10–4.40 ng/mL). Absolute increase in serum C-Pep (ΔC-Pep) was calculated as difference between postprandial and baseline C-Pep (ng/mL). ΔC-Pep greater than 2.4 ng/mL was considered significant [Postprandial C-Pep to postprandial glucose ratio (PCPG) was analyzed as a marker of beta cell reserve (mcg/mmol) [HOMA-IR = 1.5 + (FPG × FCP × 331.1) / 2800; HOMA-B = 0.27 × FCP × 331.1 / (FPG - 3.5).Results were presented as count (%), mean ± standard error of mean. Groups were compared for significance of difference using parametric (t-test) and nonparametric (chi-square, Mann–Whitney U, and Friedman) tests. To assess significance of correlation between variables, Pearson and Spearman correlations were used. SPSS Statistics v. 26 software was employed for the statistical analyses. p-values of less than 0.05 were regarded as indicating statistical significance. | PMC10387975 | ||
3. Results | STM, T2D, overweight | OBESE | A total of 80 newly diagnosed T2D patients were included in the analysis, 58.8% male and 41.3% female. All subjects completed the 12-month follow-up period with no dropouts. Their average age at baseline was 54.04 ± 9.41 years, and the average BMI was 29.74 ± 4.91 kg/mBaseline C-Pep did not differ between sexes (females vs males: 2.48 ± 0.26 ng/mL vs 2.16 ± 0.15 ng/mL, p = 0.246). Upon STM, a difference in response was noted between females and males. Absolute ΔC-Pep (1.92 ± 0.33 ng/mL vs 1.04 ± 0.14 ng/mL, p = 0.030) and relative ΔC-Pep% (0.80 ± 0.14% vs 0.50 ± 0.08%; p = 0.048) were both higher in females.Average baseline C-Pep in all 80 newly diagnosed T2D patients positively correlated with BMI (Subjects that were normally nourished (NN), overweight (OW), or obese (OB) did not differ in age. Baseline C-Pep was lower in NN, compared to OW (p = 0.050) and OB (p = 0.020). There was no difference in baseline C-peptide levels between OW and OB subjects ( | PMC10387975 |
3.1. Metabolic changes in newly diagnosed T2D patients on short-term insulin treatment or glimepiride, during the 12 months of follow-up | INS | Forty-two patients were randomly assigned to receive early short-term insulin treatment added on metformin (INS). They did not differ in age, sex, nor BMI from 38 patients assigned to treatment with glimepiride and metformin (OAD). The two groups did not differ in baseline FPG, HbA1c, or serum lipid levels (In both INS and OAD groups, initial HbA1c improved after 3 months, remaining so by 12 months. Early single-month insulin treatment resulted in better glycemic control at 3 months compared to OAD: HbA1c 6.26 ± 0.18% vs. 6.78 ± 0.10% (p = 0.016). The difference in HbA1c was maintained in favor of the INS group during the 12-month follow-up (There was no difference in average BMI between the two groups (28.36 ± 0.69 vs. 32.23 ± 2.07 kg/mAll investigated lipid markers, except HDL-cholesterol (HDL-C), improved after 3 months in both treatment groups, remaining so after 12 months in the INS group ( | PMC10387975 | |
3.2. Beta cell function in newly diagnosed T2D on early short-term insulin treatment or on glimepiride added to metformin, over 12 months of follow-up | T2D | INS | ΔC-Pep in INS group increased after 3 and 12 months, compared to the pretreatment values. The INS group improved STM-derived relative C-Pep (ΔC-Pep%) by 3 months (p = 0.000) and preserved this by 12 months (p = 0.000). The postprandial C-Pep to glucose ratio (PCPG) was also increased in the INS group at 3 months (p = 0.000) and remained so by 12 months (p = 0.000) (In the OAD group, ΔC-Pep increased from its pretreatment value after 3 (p = 0.000) and 12 months (p = 0.001). The OAD group improved STM-derived relative C-Pep increase (ΔC-Pep%) at 3 months (p = 0.000), preserving this by 12 months (p = 0.000). The PCPG at 3 and 12 months in the OAD group was increased compared to pretreatment testing (p = 0.000) Our analysis of the pretreatment STM-derived C-Pep response in the whole group of newly diagnosed T2D patients revealed its strong correlation to BMI. Thus, we have further compared results from the two groups by introducing the BMI-adjusted STM-stimulated relative C-Pep increase (BMDCP). This marker was greater at 3 months in the INS compared to the OAD group (4.60 ± 0.59 vs. 3.21 ± 0.34 mThere was no correlation of average AIP with any of the parameters of C-Pep response to STM: ΔC-Pep, ΔC-Pep%, PCPG—neither for the whole investigated cohort, nor for either sex separately. | PMC10387975 |
4. Discussion | T2D, STM, weight gain, diabetes, hypoglycemic, glucotoxicity, lipotoxicity | OBESE, INSULIN RESISTANCE, DYSFUNCTION, DIABETES | Results of our study support early 1-month insulin and metformin treatment’s superiority over glimepiride and metformin in newly diagnosed T2D, on beta cell (BC) functional recovery, glycemic and lipid control, enduring beyond the short span of treatment itself. The concept of early short-term insulin treatment in newly diagnosed T2D shifts away from the classic role of insulin at a later-stage of T2D. This early intervention may promote BC functional recovery, pointing to a disease-modifying effect of insulin treatment [Our results support previously reported advantages of early short-term insulin compared to oral-only treatment regarding glycemic and lipid control, extending beyond the brief span of treatment itself [Early short-term insulin treatment in newly diagnosed T2D may reverse gluco- and lipotoxicity, as main indirect contributors of BC dysfunction [C-Pep response augmentation parallel to glycemic control improvement, as observed in both of our treatment groups, highlights the universal importance of rapid elimination of glucotoxicity as instrumental in beta cell (BC) function recovery [Unlike comparable previous studies designed with either intensive insulin treatment with multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) [Due to limited duration and lower insulin dose requirements, the concept of early short-term insulin intervention leads to a smaller hypoglycemic risk and less weight gain than the classical late-stage, long-term insulin treatment, as is observed in our study. Furthermore, our preference for basal-insulin-only simplifies the insulin intervention in newly diagnosed T2D with high HbA1c. Our results should encourage practical implementation of early short-term insulin intervention in T2D.To the best of our knowledge, none of the diabetes treatment guidelines incorporate BC function assessment as input for therapeutic algorithms. However, heterogeneity is well-recognized among newly diagnosed T2D patients regarding causal predominance of insulin resistance or BC failure [We report of significantly greater C-Pep response to STM in females. Previous data from the mixed meal tolerance test indicated absence of sex-based difference in C-Pep response [The association of BMI and postprandial hormonal response is complex and most probably multidimensional. Higher baseline and postprandial insulin but with a delayed peak were observed in the obese [In prior studies, atherogenic index of plasma (AIP) was credited as a marker of BC dysfunction, inversely correlating with C-Pep secretion, and possibly predicting the need for insulin treatment [ | PMC10387975 |
5. Conclusion | T2D | Early short-term insulin treatment in newly diagnosed treatment-naïve T2D patients improves beta cell function more than long-term therapy with glimepiride, as reflected in C-peptide response to standardized test meal. Limited insulin intervention added to metformin is superior to glimepiride and metformin treatment regarding glycemic and lipid control. Legacy of its benefits extends to after the intervention duration, without a negative impact on body weight. Convenient insight into beta cell capacity at diagnosis and its response to treatment through a standardized test meal may guide individual approach amidst the known heterogeneity of T2D patients.
None of the authors have any conflicts of interest that may have influenced either the conduct or the presentation of the research.
Study protocol received institutional review board approval and all participants provided informed consent in the format required by the relevant authorities. (Approved by Ethics Board of Zvezdara University Medical Center, Decision dated 29.01.2019.) | PMC10387975 | |
References | STM | INS | Correlation of baseline C-Pep with BMI (Pearson correlation coefficient r = 0.32; p = 0.004).Correlation of Δ C-Pep in STM with BMI (Pearson correlation coefficient r = 0.23; p =0.043).HbA1c changes on early insulin treatment (INS) vs. oral antidiabetics-only (OAD) groups during 12 months of follow-up.Differences in BMI-adjusted STM-stimulated relative C-peptide increase in short-term early insulin treatment vs. oral antidiabetics-only group after 3 and 12 months.Age, HbA1c, Baseline C-Pep, ΔC-Pep, absolute increase in C-peptide; HOMA-IR, homeostatic model assessment of insulin resistance;HOMA-B, homeostasis model assessment of β-cell function.Baseline demographic and metabolic characteristics in INS and OAD groups.FPG, fasting plasma glucose; TC, total cholesterol; TG, triglycerides.BMI and serum lipids during study follow-up in the INS groupTC, total cholesterol; LDL-C, LDL-cholesterol; HDL-C, HDL-cholesterol; TG, triglycerides; AIP, atherogenic index of plasma.BMI and serum lipids during study follow-up in the OAD group.TC, total cholesterol; LDL-C, LDL-cholesterol; HDL-C, HDL-cholesterol; TG, triglycerides; AIP, atherogenic index of plasma.Beta cell function during study follow-up in the INS group.ΔC-Pep, absolute increase in C-peptide; ΔC-Pep%, relative increase in C-peptide;PCPG, postprandial C-Pep to postprandial glucose ratio; BMDCP- BMI-adjusted relative ΔC-Pep.Beta cell function during study follow-up in the OAD group.ΔC-Pep, absolute increase in C-peptide; ΔC-Pep%, relative increase in C-peptide;PCPG, postprandial C-Pep to postprandial glucose ratio; BMDCP- BMI-adjusted relative ΔC-Pep | PMC10387975 |
Background | Atelectasis | ATELECTASIS, PERIOPERATIVE COMPLICATION | Atelectasis during general anesthesia is a risk for perioperative complications. EIT measurements were performed in mechanically ventilated healthy children during elective surgery to demonstrate the changes in ventilation distribution during general anesthesia. The ventilation distribution was quantified by calculating the Global Inhomogeneity index (GI). | PMC10091533 |
Methods | lung disease | LUNG DISEASE | EIT measurements were performed in 23 children (9 weeks—10 years) without lung disease to detect changes in regional ventilation during elective surgery. Three previously defined time points were marked during the measurement: after intubation and start of pressure-controlled ventilation (PCV), change to pressure support ventilation (PSV), and after extubation (spontaneous breathing—SB). Ventilation distribution based on regions of interest (ROI) and changes in end-expiratory volume (∆EELV) were collected at these time points and compared. The Global Inhomogeneity index was calculated at the beginning of pressure-controlled ventilation (PCV). | PMC10091533 |
Results | atelectasis | RECRUITMENT, ATELECTASIS | With increasing spontaneous breathing, dorsal recruitment of atelectasis occurred. The dorsal ventilation fraction increased over the time of general anesthesia with increasing spontaneous breathing, whereas the ventral fraction decreased relatively (Difference ± 5.5 percentage points respectively; 95% CI; 3.5—7.4; | PMC10091533 |
Conclusion | COLLAPSE | Controlled ventilation of healthy children resulted in increased ventilation of the ventral and collapse of the dorsal lung areas. Restart of spontaneous breathing after cessation of surgery resulted in an increase in ventilation in the dorsal with decrease in the ventral lung areas. By calculating the GI, representing the ratio of more to less ventilated lung areas, revealed the presumed homogeneous distribution of ventilation. | PMC10091533 | |
Trial registration | ClinicalTrials.gov Registration ID: NCT04873999. First registration: 05/05/2021. | PMC10091533 | ||
Keywords | PMC10091533 | |||
Background | ventilation-induced lung injury, atelectasis | ATELECTASIS | Ensuring optimal ventilation during invasive ventilation contributes to lung protection. High ventilation pressures, high tidal volumes and regional atelectasis formation contribute significantly to ventilation-induced lung injury [There are already numerous publications for the use of EIT measurements in adults. Data also exist for larger children with a thoracic circumference greater than 70 cm. However, no pediatric EIT belts (thoracic circumference ˂ 70 cm) were commercially available for the PulmoVista EIT device from Dräger until 2021. Therefore, one objective of the current study was to collect data on infants, toddlers, and children with a chest circumference between 36 and 70 cm.Gravity affects the ventilation distribution of ventilated lungs. The purpose of this study was to investigate changes in ventilation distribution during general anesthesia in lung-healthy ventilated children. The question is whether the influence of gravity can be detected by EIT, although the dead weight of the lungs is lower in children than in adults. Furthermore, this study aims to quantify the presumed homogeneity of the ventilation distribution in lung-healthy children by calculating the Global Inhomogeneity index (GI). | PMC10091533 |
Methods | PMC10091533 | |||
Subjects | hernias | DERMOID CYSTS, MINOR, CNS INFECTIONS | The study protocol was approved by the ethics committee of the Ludwig-Maximilians University Munich. This sample size was chosen in order to additionally perform a correlation analysis of the impedance and volume curves. A sample size of 19 participants was calculated. Taking into account 15% possible dropouts, 23 patients were included. Written informed consent was obtained from the parents or legal guardians before participation in the study. Pediatric patients receiving balanced general anesthesia (for induction: intravenous application of propofol 1% and sufentanil or alfentanil, for maintenance: inhalation application of sevoflurane) without using neuromuscular blockers as part of elective surgery, with a chest circumference between 36 and 70 cm and a tidal volume > 20 ml were included. A PEEP of 5 mbar was chosen for all patients. The ventilation pressure was chosen to achieve a tidal volume of 6 ml/kg/body weight. The highest driving pressure required was 11 mbar, the lowest 5 mbar. Patients with a permanent or temporary pacemaker, defibrillator or other implanted medical devices that deliver electrical energy were excluded. Patients in whom the application of the electrode belt could have been affected by wound care or infections in the chest area and female patients in whom pregnancy could not be excluded were not included. Measurements were taken during minor procedures such as closure of inguinal hernias, circumcision, orchidopexy or removal of dermoid cysts. The duration of sedation was shorter than one hour in all patients. | PMC10091533 |
Setting | LUDWIG | Elective pediatric surgical operations at the Traunstein Hospital, Academic Teaching Hospital of the Ludwig Maximilian University of Munich, Germany. | PMC10091533 | |
Cardiopulmonary monitoring | Vital signs, transcutaneous oxygen saturation (SpO | PMC10091533 | ||
Electrical impedance tomography | EIT measurements were performed with the Dräger PulmoVista 500 (Dräger Medical Deutschland GmbH, Lübeck, Germany). The 16-electrode belt was placed between the 3rd and 5th intercostal spaces. Ventilation data were continuously recorded by the EIT device via a serial interface (Medibus, Dräger Medical Deutschland GmbH, Lübeck, Germany).The following EIT parameters were stored during the measurement phases: EIT tidal images, global impedance curves, regional impedance curves and tidal variation of regions of interest (ROI) 1–4, change in end-expiratory lung impedance (ΔEELI) and ventilator flow curve. | PMC10091533 | ||
Experimental protocol | EVENT | Pediatric patients were screened for inclusion and exclusion criteria during the anesthesiology or pediatric surgery informed consent interview. Written informed consent was obtained from the parents/legal guardians after they were informed of the planned study. Demographic data, vital signs and medical history were obtained and documented.For later data evaluation, three time points were defined, which were marked during data recording by means of event markers.PCV = controlled ventilation, PSV = assisted ventilation, and SB = spontaneous breathing.On the day of the intervention, the inclusion and exclusion criteria were reevaluated. General anesthesia was induced and maintained by the responsible anesthesiologist. The appropriate electrode belt was applied and the exact position on the thorax.After a stable EIT signal could be derived, data recording was started before the operation began. To avoid artifacts and ensure usable data, no infant manipulations or ventilatory changes were performed for two minutes. All artifacts (e.g. due to cauterization) were marked during the further course of the measurement. After completion of surgery, extubation and sufficient spontaneous breathing, another two-minute rest measurement was taken.The collected data were processed after measurement using the Dräger EIT Application Version 1.30 (Dräger Medical Deutschland GmbH, Lübeck, Germany). | PMC10091533 | |
Global and regional tidal variation | Global ventilation was divided among the four horizontal regions and the percentage of ventilation was shown for each region. ROI were designated from ventral (ROI 1) to dorsal (ROI 4). The mean values of a one-minute time interval of the regional tidal variations at the previously defined time points (PCV, PSV, SB) were evaluated. | PMC10091533 | ||
End-expiratory lung impedance (EELI) | The difference between two end-expiratory images at two freely selectable cursor positions C1 and C2 quantifies the global and regional changes in end-expiratory lung impedance (∆EELI). This impedance change is shown on the one hand by colors and on the other hand by numerical parameters. The global numerical value represents variations in global end-expiratory status at cursor positions C1 and C2 relative to the global tidal variation at C1. Regional deviations within the defined ROI are represented by the value ∆EELI ROI [The ∆EELI values were collected for the ventilation mode transitions PCV to PSV, PSV to SB and PCV to SB and the ∆EELV values were calculated. For this purpose, the ∆EELI value was multiplied by the measured tidal volume at the reference time (C1) (∆EELV = ∆EELI * TV | PMC10091533 | ||
Global Inhomogeneity index | EVENT | One-minute sequences of each EIT data were selected to calculate the GI. The minute containing the event marker "PCV" was selected. The GI was calculated as described by Zhao [The increasing inhomogeneous distribution of ventilation during controlled ventilation can be visualized with the GI. It quantifies the gas distribution in the lungs and thus enables good comparability. In healthy individuals with normal ventilation distribution, the quotient is 50%. In pathologically altered lungs, where there is unilateral pulmonary ventilation, the GI is 100% [ | PMC10091533 | |
Statistical analysis | atelectasis | RECRUITMENT, ATELECTASIS | The results of this publication are based on an exploratory analysis of the results of the data from ventilated children.The change in regional ventilation fraction during general anesthesia was examined in an exploratory analysis. The changes were analyzed graphically (see Figs. Ventilation distribution based on horizontal layers—ROI 1–4. The middle horizontal marker illustrates the grouping of ROI 1 and 2 as the ventral layer, and ROI 3 and 4 as the dorsal layer. The dorsal layer is 5.5 percentage points more ventilated at the time of spontaneous breathing (SB) than at the time of controlled ventilation (PCV)Plot of ventilation at the three intervention time points PCV, PSV and SB. ROIs 1 and 2 were combined into ROI ventrally, ROIs 3 and 4 into ROI dorsally. In the dorsal regions, there is an increase in ventilation by recruitment of dorsal atelectasis by a mean of 5.5 percentage points with increasing spontaneous breathing. In turn, the ventilation fraction of the ventral lung regions decreasesA Wilcoxon signed-rank test was used to compare the reduction in EELV and the distribution of EELV during ventilation and spontaneous breathing (see Fig. Plot of EELV changes at the three ventilation mode transitions. Ventral lung areas (left) and dorsal lung areas (right) show how the total ∆EELV change is proportionally distributed between the two regions at the corresponding ventilation mode transitions of ventilation. In addition to the boxplots, the change for each individual patient is plotted. To allow assignment over the course of individual study participants, the values are connected by gray lines. The values of the study population do not show a normal distribution. Due to statistical outliers, the median values are used as measure of location. The dorsal regions show an increase, which can be explained by the recruitment of atelectasis due to the onset of spontaneous breathing. Due to the loss of PEEP after termination of mechanical ventilation, the overdistension in the ventral lung regions decreases and thus the proportion of ∆EELVAll statistical analyses of this study were performed using the program "R" (version 4.2) and a | PMC10091533 |
Results | PMC10091533 | |||
Demographic data | Twenty-three patients were included in the study. All underwent EIT measurements during general anesthesia in the course of elective surgery. Demographic data of all study participants are shown in Table Demographic data of healthy children | PMC10091533 | ||
Changes in regional ventilation during general anesthesia | RECRUITMENT | Analysis of the changes in regional ventilation during general anesthesia in healthy children showed that with increasing efforts of spontaneous breathing, from PCV over PSV to SB, the proportion of ventilation in ventral areas decreased by 5.5 percentage points, whereas regional proportion recruitment occurred in dorsal areas. Throughout the measurement period, the majority of ventilation occurred in mid regions 2 and 3. As expected, region 4 showed the smallest proportion of ventilation (Fig. During controlled ventilation, more ventral lung areas were ventilated. The change of the ventilation mode from controlled to pressure-supported had a small and only in ROI 1 significant influence on changes in ventilation distribution (Difference ROI 1: 1.7 percentage points; 95% CI, 0.59—2.8; Dorsal ROI 3 was ventilated 4.4 percentage points (95% CI, -6.2—-2.8; During pressure-supported ventilation, dorsal ROI 3 was ventilated 3.3 percentage points (CI 95%; -5.0—-1.7; The ventilation fraction of dorsal ROI 4 was very low, therefore the ventral two regions (ROI 1 and 2) and the dorsal two regions (ROI 3 and 4) were combined. Figure | PMC10091533 | |
Changes in the ∆EELI/∆EELV | At all ventilation mode transitions a reduction in the end-expiratory volume was measured. With increasing spontaneous breathing the dorsal regions showed an increase, while the ventral regions decrease. Changing the mode of ventilation showed a very small EELV reduction, while the onset of spontaneous breathing showed a more pronounced reduction. Stopping mechanical ventilation with the onset of spontaneous breathing resulted in a significant reduction in EELV compared with the change in mode of ventilation (PCV to PSV: -37 ml [Range: -163—33 ml] vs. PSV to SB: -142 ml [Range: -384—-19 ml]; Difference: 105 ml; 95% CI 75–135; The distribution of ∆EELV in the different lung areas is shown in Fig. Exemplary representation of the EELV reduction at the different ventilation mode transitions. Orange: reduction in EELV; blue: increase in EELV; black: no change. Changing the mode of ventilation from PCV to PSV (left) shows only a small reduction of EELV which is mostly distributed in the ventral lung areas. After termination of mechanical ventilation (PSV to SB, right), the reduction is much more pronounced and distributed more evenly in both lung regions. The ventral portion decreases in favor of the dorsal by 9.9 percentage points | PMC10091533 | ||
Ventilation distribution of healthy children based on Global Inhomogeneity index | SD | The GI was calculated and showed a nearly homogeneous ventilation distribution with a GI of 47% (SD ± 4%, Range: 40, 53, Fig. Global Inhomogeneity index (GI). The GI suggests that healthy children have a very homogeneous distribution of ventilation | PMC10091533 | |
Discussion | pulmonary disease, atelectasis, diaphragmatic contraction | COLLAPSE, PULMONARY DISEASE, ATELECTASIS, POSITIVE | The main findings of this study were: 1.) Dorsal proportion of ventilation occurring during general anesthesia was recruited with increasing spontaneous breathing, whereas the proportion of ventilation decreased in ventral regions. Changing the mode of ventilation from controlled to pressure-supported resulted in a significant reduction of ventilation only in the most ventral region. 2.) Spontaneous breathing after controlled ventilation was associated with a large reduction in end-expiratory volume due to termination of PEEP. 3.) The Global Inhomogeneity index showed homogeneous ventilation distribution of ventilated lung-healthy children.Gunnarsson et al. [In spontaneously breathing patients in the supine position, the dorsal portion of the diaphragm exhibits the greatest movement. Thus a thus a large proportion of ventilation occurs here. Positive pressure ventilation primarily moves the ventral regions of the diaphragm caudally. Therefore, during positive pressure ventilation, the majority of ventilation is distributed in the ventral lung areas [In this study, this effect was investigated in infants and children. The performed exploratory analysis shows significant changes in ventilation distribution during general anesthesia. After induction of anesthesia and under controlled ventilation, the dorsal proportion of ventilation was low. This is probably due to a collapse of dorsal lung areas and increased ventral ventilation. During pressure-supported ventilation, there was already a minimal shift of ventilation towards the dorsal lung areas, although this difference was not significant in the current case series. This dorsal shift was most pronounced at the onset of spontaneous breathing after cessation of ventilation. There was a decrease in ventilation in the ventral areas, because the atelectatic lung areas were recruited. Further studies are needed, but this study provides evidence that controlled ventilation also leads to changes in ventilation distribution in infants, small and older children. Despite the lower weight, dorsal atelectasis with probable ventral lung overdistension may occur, among other reasons, due to the lack of diaphragmatic contraction.During ventilation, positive end-expiratory pressure (PEEP) is applied. This pressure affects the end-expiratory volume of the lungs. As expected, a significant reduction in this volume was detected when comparing the two different modes of mechanical ventilation (with PEEP) and spontaneous breathing (without PEEP). While the change in ventilation mode only had a small effect on the change in end-expiratory lung volume, during spontaneous breathing, end-expiratory lung volume changed significantly and was distributed more evenly in both lung areas. The ventral portion became significantly smaller in favor of the dorsal portion. PEEP both recruited dorsal lung areas and overdistended ventral lung areas. After termination of mechanical ventilation, this PEEP ceased and a reduction in lung volume in these areas was detected. The dorsal tidal ventilation fraction was lower in this study compared with the ventral. Therefore, the dorsal fraction of the decrease in end-expiratory volume after extubation was also smaller than the ventral fraction. Wang et al. [Since all children in this study had no pulmonary disease and were ventilated only for short periods, a roughly homogeneous ventilation distribution can be assumed. This could be confirmed by the GI calculation. The examined children showed an almost homogeneous ventilation distribution with a GI of 47%. Zhao et al. [ | PMC10091533 |
Limitations | The sample size of this study is very small with 23 participants. In addition, there were large differences in age, height and weight of the patients. Therefore, the scatter of the data of the individual patients is sometimes very large and the difference of the mean values is small. The trend of changes of all patients in the same direction is present. | PMC10091533 | ||
Conclusions | atelectasis | ATELECTASIS | This study shows that dorsal atelectasis with decrease in ventilation also occurs in infants, small and older children due to the influence of general anesthesia. At the same time, ventral lung areas are increasingly ventilated. With increasing spontaneous breathing, dorsal lung areas are recruited again. The Global Inhomogeneity index illustrates the homogeneity of the ventilation distribution in lung healthy children. | PMC10091533 |
Acknowledgements | ROTH | We would like to thank all staff members of the pediatric surgery practice, the department of anesthesia, the surgical team and the pediatric clinic of Traunstein Hospital for their help and support during the performance of this study. Special thanks go to the anesthesiologists Dr. Winfried Roth and Ulf van Schwartzenberg and the pediatric surgeons Andreas Schmeller and Christian Blume for their patience and consideration during the measurements. Furthermore, we thank Mr. Eckhard Teschner of Drägerwerk AG & Co. KGaA (Lübeck, Germany) for support with technical and content-related questions, as well as Dr. Plückhahn and Drägerwerk AG & Co. KGaA (Lübeck, Germany), for the possibility of additional data analysis. | PMC10091533 | |
Authors’ contributions | DC performed the clinical trial, interpreted the data, and was a major contributor in writing the manuscript. IW helped to interpreted the data and authored parts of the article. SR performed the statistical analysis. GW interpreted the data and wrote parts of the article. All authors read and approved the final manuscript. | PMC10091533 | ||
Funding | This study was funded by departmental funds and supported by Dräger Medical, Lübeck, Germany. | PMC10091533 | ||
Availability of data and materials | MINOR | The data sets generated and analysed in this study are not publicly available due to protection of minor patients and required consent by Dräger. They can be obtained from the corresponding author upon reasonable request. | PMC10091533 | |
Declarations | PMC10091533 | |||
Ethics approval and consent to participate | W. Eisenmenger | This observational study was approved by the Ethics Committee of Ludwig-Maximilians-University Munich (Chairperson Prof. Dr. W. Eisenmenger, No.: 20–1048 dated 14.04.2021). All methods were performed in accordance with the relevant guidelines and regulations. The written informed consent of the parents or guardians was obtained via written consent. | PMC10091533 | |
Consent for publication | Not applicable. | PMC10091533 | ||
Competing interests | The authors declare no competing interests. | PMC10091533 | ||
References | PMC10091533 | |||
Background | ACUTE RADIATION DERMATITIS | Randomized controlled study was conducted to evaluate the efficacy of Sanyrene® vs. control intervention (DaBao®, a complex of hyaluronic acid and Vitamin E) for acute radiation dermatitis in patients receiving radiotherapy. | PMC10604398 | |
Methods | head and neck cancer, dermatitis, breast cancer | HEAD AND NECK CANCER, DERMATITIS, BREAST CANCER | Patients with breast cancer or head and neck cancer undergoing radiotherapy (≥ 50 Gy) were eligible. Participants were randomly assigned to either Sanyrene arm or control intervention arm in a ratio of 1:1. The primary endpoint was incidence rate of ≥ grade 2 radiation induced dermatitis. (Trial Registration: ChiCTR2100050910, registration date: 9/7/2021) | PMC10604398 |
Results | dermatitis | DERMATITIS | A total of 102 eligible patients were randomly assigned into the study. The rate of ≥ grade 2 radiation dermatitis was 22% in Sanyrene group, as compared with 67.3% in the control intervention group ( | PMC10604398 |
Conclusions | head and neck cancer, dermatitis, breast cancer | HEAD AND NECK CANCER, DERMATITIS, BREAST CANCER | This trial suggests that Sanyrene is effective on preventing serious radiation dermatitis and improving skin related quality of life in patients with breast cancer or head and neck cancer receiving radiotherapy. | PMC10604398 |
Supplementary Information | The online version contains supplementary material available at 10.1186/s13014-023-02363-9. | PMC10604398 | ||
Keywords | PMC10604398 | |||
Introduction | head and neck cancer, HNC, breast cancer | HEAD AND NECK CANCER, SKIN TOXICITY, BREAST CANCER | Radiation therapy (RT) is the standard treatment for most patients with head and neck cancer (HNC) or breast cancer (BC). The routine radiation dose of RT for these patients is often more than 50 Gy either as a primary or postoperative treatment. Many studies have confirmed RT-induced skin toxicity is closely associated with total dose and fractionation schedule [Natural and miscellaneous agents are widely recommended by several guidelines for treatment of RD, such as Vitamin E, hyaluronic acids, aloe vera [ | PMC10604398 |
Materials and methods | PMC10604398 | |||
Patient selection | cellulitis, allergic reaction, HNC | CELLULITIS, AUTOIMMUNE SKIN DISEASE, SKIN TOXICITY, ALLERGIC REACTION | The design of this study was a randomized controlled trial comparing Sanyrene with control intervention in 102 HNC and BC patients receiving radiation therapy. Patients were consecutively enrolled from June 2020 to July 2021 at department of radiation oncology in Xi’an, China. This study (Trial Registration: ChiCTR2100050910) was approved by the medical ethics committee of the first affiliated hospital of the air force medical university. Patients with age ≥ 18 years, ECOG of 0 or 1 and a pathologic diagnosis of HNC and BC receiving radiotherapy (≥ 50 Gy) were eligible. Exclusion criteria were prior RT to the intended field, palliative RT with dose < 50 Gy, receiving breast conserving surgery in BC patients, receiving anti-EGFR monoclonal antibody in HNC patients, pre-existing grade >1 skin toxicity, cellulitis, autoimmune skin disease or incompletely healed wound at intended site. Patients were also excluded if they had known allergic reaction towards any ingredient of Sanyrene, Vitamin E or hyaluronic acid were not able to consent. Receiving concurrent chemotherapy was not an exclusion criterion. | PMC10604398 |
Randomization | cancer | CANCER | After completion of informed consent, participants were randomized to either the intervention arm (Sanyrene) or the control intervention arm in a ratio of 1:1. The randomization procedures were carried out by sealed enveloping from the central office of the Clinical Trials Centre. Blocked randomization was performed using permuted block with a block size of n = 4. Patients were stratified by the presence of cancer site. Only the statistician and the study coordinator knew the block structure, and the statistician and the study coordinator had no clinical involvement during the trial. | PMC10604398 |
Treatment | HNC | LYMPH NODE METASTASIS | RT dose for patients with BC was 50 Gy/25 fractions delivered over 5 weeks. Most patients (88.2%) received 3-dimensional conformal radiation therapy (3D-CRT), and 6 patients (11.8%) received volumetric modulated arc radiation therapy (VMAT). To elevate skin dose, all patients were treated with 5 mm bolus over chest wall before 15 fractions of radiotherapy. For postoperative HNC patients, RT dose at 2 Gy/fraction was administrated once daily with five fraction per week up to total dose of 50-55 Gy. If radical radiotherapy was administrated, patients would receive up to a total dose of ≥ 66 Gy RT with cisplatin-based concurrent chemoradiotherapy (CCRT). Patients with high-risk factors of postoperation, such as positive margin and extracapsular spread in lymph node metastasis, received CCRT. The concurrent chemotherapy regimen was triweekly 80-100 mg/mFor the Sanyrene arm and control arm, patients were asked to start topical application of Sanyrene and control intervention cream respectively on the area of skin being irradiated at the onset of radiotherapy, twice a day up to 14 days post treatment. Sanyrene is a liquid dressing with characteristics of oily, colorless and fragrance of fennel. Control intervention is a white cream with fragrance. If moist desquamation occurred, these interventions would be stopped, then treating nurses applied epidermal growth factor solution and Silver Sulphadiazine impregnated Hydrocolloid Dressing 10 cm×12 cm until the wound healed. | PMC10604398 |
Endpoint evaluation | toxicities, erythema, edema | EDEMA, SECONDARY, ERYTHEMA, SKIN TOXICITY | All patients completed a range of questionnaires by interview every week from the start of radiotherapy treatment until four weeks after the completion of radiotherapy. The acute radiation morbidity scoring criteria of radiation therapy oncology group (RTOG) was used to grade provider-assessed toxicities. The primary endpoint was incidence rate of ≥ grade 2 skin toxicity, including tender or bright erythema, patchy moist desquamation and moderate edema [The secondary endpoint of this study was dermatitis-related Qol which was usually evaluated by the Skindex-16 (SD-16) module. SD-16 comprises an analogue scale (0 = never bothered to 6 = always bothered) to categorize patient response, including emotion, symptoms and functioning [ | PMC10604398 |
Statistical analysis | According to our preliminary research results, the incidence rate of ≥ 2 grade RD in the control group is 65.6%. We estimated that approximately 102 patients would need to be randomized in a 1:1 ratio, with 51 patients in each group. This is to detect a difference in the incidence rate of ≥ grade 2: 65.6% in the control intervention group vs. 36.0% in the Sanyrene group. The estimation assumes a power of 80%, a two-sided significance level of 0.05, and an anticipated dropout rate of about 8%. An interim analysis was performed when reaching approximately half the sample size, the O’Brien–Fleming type boundary (alpha of 0.003) was used for early trial stoppage.Baseline characteristics of patients were displayed in the intention-to-treat trial populations (see the Fig.
CONSORT Diagram | PMC10604398 | ||
Results | PMC10604398 |
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