Although several studies show the prevalence of podiatric conditions in people with end-stage renal disease or renal replacement therapy with hemodialysis, there is little scientific literature on this when subjects are undergoing kidney transplantation. The aim of this study is to determine the prevalence of podiatric skin and nail pathology in renal transplant recipients. A descriptive, observational, prevalence study was conducted at the Nephrology Department of the University Hospital of A Coruña. A total of 371 subjects were studied. The variables studied were sociodemographic , anthropometric (Body Mass Index), comorbidity (Charlson Comorbidity Index), and podological . A high presence of skin (83.1%) and nail pathology (85.4%) was observed, with hyperkeratosis (68.8%), onychogryphosis (39.4%), and onychocryptosis (36.9%) being the most predominant alterations. Although it was not significant, patients with a higher risk of presenting podiatric pathology were of female sex and had a high BMI, and both age and the Charlson comorbidity index were significantly associated with this risk. There was an increased risk of both skin and nail pathology at older age and in the presence of diabetes mellitus. Chronic kidney disease (CKD) is defined as a decrease in kidney function or the presence of persistent kidney damage for at least three months, constituting a major public health problem today ,2,3. In As for the prevalence of podiatric pathology in the group of kidney transplant patients, this has not been studied so far. However, ESRD is increasingly common in older people, especially those with diabetes or hypertension. In this sense, it is known that the prevalence of podiatric pathology in the population over 65 years ranges between 71% and 90.7% . SubjectAlthough several studies show the prevalence of podiatric conditions in people with ESRD or renal replacement therapy with hemodialysis, there is little scientific literature on this when subjects are treated with kidney transplantation ,10,11. IA descriptive study was carried out within a prospective cohort of people who have received a kidney transplant at the University Hospital of A Coruña (HUAC) in the period 1981–2020.The established criteria for the subjects included in this study were: recipients of a kidney transplant with a functioning graft; those who attended consecutive outpatient consultations in Nephrology, and those who gave their informed consent to participate in this study voluntarily. People with lower limb amputations or impaired ambulation were excluded from the research.n = 272 subjects. This sample size allows for estimating the parameters of interest with a certainty of 95% and an accuracy of ±6%. .During the data collection period (from January 2021 to September 2022), a total of 371 subjects were studied through consecutive sampling. Podiatric information was available in The variables studied were: sociodemographic , anthropometric (Body Mass Index (BMI)), medical variables , comorbidity (Charlson Comorbidity Index), podiatric pathology variables , and quality of life .The patient’s associated comorbidity was studied using the Charlson Comorbidity Score . It encoThe study and knowledge of the morphology of the plantar footprint are of great interest for the classification and diagnosis of some foot pathologies. The pedigraph was used for its analysis. Once the pedigraphs have been obtained, the footprints will be categorized as flat or normal.The cutaneous and nail pathology at the foot level will be assessed through an observational clinical examination developed by a specialized podiatrist. In the case of skin conditions, they will be inspected both on the dorsal and plantar aspects of the foot, including interdigital spaces. Pathologies such as keratopathy, hyperhidrosis, fungal and wart affections, and pruritus will be included. Among the nail conditions, onychocryptosis, onychogryphosis, onychomycosis, Muehrcke’s lines, half and half nails, and Terry’s nails, among others, will be assessed. Perimaleolar edema will also be assessed, establishing whether it presents itself or not by Godget’s sign  as positive or negative. Finally, peripheral neuropathy has been studied, which has been quantified through the Neuropathy Disability Score (NDS) ,15, whicFinally, to determine quality of life, different questionnaires were passed, such as the SF-36. This questionnaire was developed in the early 1990s by Ware et al. as a generic instrument for measuring Health-Related Quality of Life (HRQoL), applicable to both patients and healthy populations . It contAs a foot-specific quality of life questionnaire, the Foot Function Index (FFI) is a clinical tool created and validated in 1991 by Budiman-Mak, Conrad, and Roach . It consThe current ethical-legal aspects of the development of this research have been respected, as evidenced by the favorable report of the Clinical Research Ethics Committee of Galicia (2013/155). Each study participant provided signed informed consent once the study information sheet was read, and the appropriate doubts were resolved by the researchers.t or Mann–Whitney test as appropriate after checking normality with the Kolgomorov–Smirnov test. The association of qualitative variables was estimated by means of the Chi-square statistic. Finally, logistic regression models were used to determine the association of different variables with each other.Regarding the statistical analysis, a descriptive analysis of the variables included in this study was performed. The qualitative variables were expressed as an absolute value and as a percentage after the assessment of the 95% confidence interval, formulating it in a frequency table. Quantitative variables were expressed as mean ± standard deviation. The comparison of means was carried out by means of Student’s The present study included 371 people with kidney transplantation, with a mean age of 48.07 ± 12.49 years at the time of transplantation . The samThe most prevalent skin pathology was hyperkeratosis (68.8%), followed by the symptom of pruritus (13.2%). Among nail pathologies, the most predominant were onychogryphosis (36.5%) and onychocryptosis (31.4%). Regarding the biomechanical pathology, we observed that Hallux Abductus Valgus (HAV) was the most prevalent alteration, reaching 58.9% of cases and being bilateral in 78.9%. This prevalence was followed by flat feet (45%), being bilateral in 62.3% of cases, claw toes (41.8%) being found in both feet in 88.5% of cases, and Hallux Extensus (34.2%) with 78.7% in both feet. . Most pap < 0.001). There was a tendency toward a higher risk of presenting podiatric pathology among women (OR = 1.26) and a higher BMI; these differences were not significant. Regarding comorbidity, a higher Charlson index was observed  among patients with both skin and nail alterations, and a higher prevalence of diabetes . Other pathologies not included in the Charlson index were also more prevalent among patients with both podiatric alterations, such as perimalleolar edema, Godget, or peripheral neuropathy, the latter with a 3-fold higher risk in patients with cutaneous and nail alteration compared to patients with a single alteration or none (OR = 3.03). Adjusting for age and sex, it was observed that having diabetes significantly increased the risk of suffering from both podiatric pathologies in at least one of the lower limbs .In the sample studied, it was observed that patients with cutaneous and nail pathology  were oldRegarding the factors associated with the presence of cutaneous and nail pathology , it was A multivariate regression analysis was performed, adjusting for sex, age at transplant, and diabetes, and it was observed that both age and diabetes are variables related to the appearance of skin and nail pathologies. When segmenting the models by patients with and without diabetes, it is observed that in patients with diabetes, being female and age increase the probability of this pathology, although not significantly, while in patients without diabetes, only age has a significant effect .Since the most frequent pathology was HAV, patients with this pathology were older at the time of transplantation than those patients in whom this podiatric alteration was not observed (49.30 ± 12.04 vs. 46.31 ± 12.93 years), had greater comorbidity according to the Charlson index (2.33 ± 1.71 vs. 1.93 ± 1.73), and had a lower BMI . A higheA multivariate logistic regression analysis was performed to identify the joint effect of sociodemographic and anthropometric variables on the presence or absence of HV. A model with the covariates age, sex, Charlson index, flat feet, and claw toes was adjusted to study the impact of these factors on the probability of presenting the alteration of interest. All of them were identified as risk factors. The risk of presenting the pathology under study increases with age (OR = 1.04). The risk of HAV is 2.64 times higher in females than in males. Having flat feet increases the likelihood of HV by five times, but not significantly. Claw toes are an independent risk factor for HV .The results of foot pathology on the individual’s functionality were studied using the Foot Function Index (FFI) questionnaire . The oveThis work constitutes an investigation that tries to cover the knowledge gaps identified in the literature in relation to the skin and nail repercussions in the lower limb from a podiatric perspective in people who have been recipients of a kidney transplant. The scientific evidence is ample in relation to the repercussions on the foot in subjects with ESRD, Diabetes Mellitus, and the elderly; however, there has not been extensive and current literature that identifies the repercussions on the foot when the subjects have been recipients of a kidney transplant. Despite this, there are articles that highlight the importance of identifying skin and nail conditions, as it helps reduce the association of the person’s health status with morbidity and mortality , since i2, the prevalence of diabetes was 24.3%, of which 15.9% occurred after transplantation, and the prevalence of peripheral neuropathy was 16.4%. In the study by Martínez-Mier et al. [2 (range 14–36.9), respectively. This difference in mean BMI may be due to the background of the study population , with the age range of our study being the widest (8.56–74.09). The passage of time between the time of the transplant and the patient’s examination may be another variable to be taken into account, as several studies have shown the existence of an increase in weight after transplantation, which increases over time [Regarding the results of the present study, the mean age was 56.01 ± 11.39, being higher than that found in other studies, which did not reach an average of 50 years ,24. Withr et al. , the meaver time ,28.The prevalence of peripheral neuropathy found in our sample was 16.4%, somewhat lower than that reported by the scientific literature consulted. Mohammadi MH et al. , in a reThe highest prevalence of biomechanical pathology was Hallux Abductus Valgus (HAV) (58.9%), flat feet (45%), and claw toes (41.8%). As there are no specific studies of biomechanical foot pathologies in kidney transplant patients, the comparison of the data found in our study was compared with the data reported in the literature in healthy populations or populations affected by other pathologies. Thus, the prevalence of HAV in the study by Menz et al.  ranged fIn relation to the data identified in the articles on cutaneous and nail lesions, difficulties have been found in locating studies that address these health problems specifically in the lower limb, thus making it difficult to contrast our results with those of other research. In the first place, in relation to cutaneous conditions, a high prevalence of them was observed (83.1%), constituting a high percentage of hyperkeratosis (68.8%) of the total sample studied. Despite this incidence, no similar studies have been found to compare and contrast these results.n = 54). However, a recent study carried out by Ankudowicz et al. [Nail pathology has also been a relevant health problem in the patients studied, since 85.4% have presented it. The Prakash et al.  study foz et al.  in 2018 n = 220) had onychomycosis, a percentage that differs from that of our research (22.0%). In this sense, Lima et al. [Specifically, both onychogryphosis 39.4%) and onychocryptosis (36.9%) stood out among the nail pathologies observed in our work. The study by Dicle et al.  identifia et al. ,39 concl.4% and oAnother nail and skin pathology that appears in transplant patients and that may be influenced by immunosuppressive treatment is mycosis. In this study, the presence of onychomycosis was 22% in at least one foot, and although the patients have not been followed up or immunosuppressive treatment has been taken into account, authors such as Pereiro et al. , in theiIn relation to the sociodemographic characteristics, the disease of the participants studied, and the fact of presenting or not presenting cutaneous and nail pathology, it is noteworthy that there were significant differences in terms of age at examination and transplantation, BMI, the fact of suffering from Diabetes Mellitus before and after transplantation, perimaleolar edema, Godget’s sign, and peripheral neuropathy. Thus, the high prevalence of skin and nail diseases is responsible for the morbidity added to the health status of kidney transplant recipients . In addiWith the results obtained, it can be stated that the presence of skin and nail pathology of exogenous origin will negatively modify both the quality of life considering the foot measured with the FHSQ and the functionality of the foot measured with the FFI, except for nail pathology in the latter case. as its presence does not modify the functionality of the foot measured with the FFI.Authors such as Garrow et al.  not onlyDespite the fact that this study has been carried out as rigorously as possible, the authors acknowledge the existence of weaknesses, among which are the failure to follow up with the patients after the performance of the kidney transplant, the failure to take into account immunosuppressive medication, or the non-inclusion of a control group. Taking this into account would answer questions such as determining the influence that transplantation has on podiatric pathology or the connection that skin and nail pathologies have on graft function. Despite this, the results obtained are considered important since it is the first time that the prevalence of podiatric pathology in these patients has been determined. Based on these preliminary results, future lines of research will be established that include variables that can provide answers to the questions previously exposed.In the sample of kidney transplant patients studied, more than 90% of patients had at least one of the podiatric pathologies under study, and seven out of ten had both.The most prevalent cutaneous and nail pathologies were hyperkeratosis, pruritus, onychogryphosis, and onychocryptosis, while the biomechanical pathologies were Hallux Abductus Valgus, flat feet, and claw toes.Patients with cutaneous and nail pathology were older, had a higher BMI, and had comorbidities such as diabetes, peripheral neuropathy, and perimalleolar edema.The risk of suffering from both cutaneous and nail pathologies increases with age, as does the presence of diabetes after adjusting for sex.The presence of skin and nail pathology of exogenous origin will negatively modify the quality of life.This study shows the high incidence of cutaneous and nail pathology in lower limbs suffered by kidney transplant patients, with older patients, greater comorbidity, and a higher BMI presenting more podiatric alterations. In summary, it is concluded that:


To explore the mediational effect of activities of daily living (ADL) and kinesiophobia on the cardiac function and health status of patients with chronic heart failure (CHF).From October 2021 to January 2022, a total of 244 CHF patients treated in the Department of Cardiology of general hospitals were recruited by the convenience sampling method. They were investigated with the Tampa Scale for Kinesiophobia Heart (TSK‐SV Heart), the Barthel index for assessing ADL, and the EuroQol five‐dimensional questionnaire (EQ‐5D) for assessing the health status.r = −.390 and −0.410, respectively, both p < .01). Besides, the ADL of CHF patients was positively correlated with the health status . The cardiac function of CHF patients was negatively correlated with the ADL , but positively correlated with kinesiophobia . The mediation proportion of ADL plus kinesiophobia between the cardiac function and health status of CHF patients was 43.48%. Both ADL and kinesiophobia partially mediated the effect of cardiac function on health status in CHF patients, but their mediational effects showed no significant difference (p = .777).The cardiac function and kinesiophobia of CHF patients were both negatively correlated with their health status  programs based on the cardiac function, ADL and kinesiophobia of CHF patients may contribute to reduce the medical burden and improve the well‐being of affected people. 1.Only 2.5% of chronic heart failure(CHF) patients were engaged in Cardiac rehabilitation(CR) programs and 77.9% of them participated in daily activities/exercise, the top three of which were walking (73.8%), housework (27.9%) and jogging (21.3%). Kinesiophobia was detected in 170/244 (69.5%) CHF patients who had limited or low‐intensity daily activities/exercises. Both activity of Daily Living (ADL) and kinesiophobia partially mediated the effect of cardiac function on health status in CHF patients, the mediational effects are equal. Kinesiophobia should be relieved and ADL enhanced to improve the health status and prolong the life expectancy of CHF patients. Exclusion criteria: (1) Subjects with unconsciousness or cognitive impairment; (2) Subjects with malignant tumors, severe liver or renal failure. This study was approved by the Ethic Committee of the First Affiliated Hospital with Nanjing Medical University (2019‐SR‐474).A consecutive sample of 244 HF patients were recruited from the Department of Cardiology of the First Affiliated Hospital with Nanjing Medical University from October 2021 to January 2022 by convenience sampling method. Inclusion criteria: (1) CHF diagnosed based on the 2.2Pretrained investigators were responsible for explaining the aim and clinical significance of this study using the unified instructions. The subjects were asked to fill in questionnaires by themselves after obtaining the written informed consent. For those who were unable to write or read by themselves, investigators read the items one by one, and recorded their answers. All completed questionnaires were collected within 48 h before discharge, and checked on the spot. All missed or incorrectly filled items were revised by reinquiring subjects.2.2.1The self‐designed questionnaire for 14 baseline characteristics of subjects included the sex, age, marriage, educational level, occupation, current work situation, current per capita monthly household income (yuan), medical insurance, smoking history, drinking history, comorbidities at admission, course of HF, cardiac function classification, and primary disease.2.2.2The self‐designed questionnaire for exercise status and type included the involvement of CR programs, daily exercises/activities, the frequency, time and type of exercises/activities, and fitness centers near your home.2.2.3The 10‐item Barthel index was calculated for assessing ADL, with a total score of 100 points. A higher Barthel index indicated better ADL.2.2.4α for the TSK‐SV Heart was .859.The Chinese version of TSK‐SV Heart developed by Lei et al.2.2.5α for the EQ‐5D was 0.761. The EQ‐5D score was transformed using the time trade‐off model.The 6‐item EQ‐5D was used to assess health status in five dimensions, including the mobility, self‐care, usual activities, pain/discomfort and anxiety/depression.2.3α = .05. p < .05 was considered as statistically significant.Statistical analysis was performed using SPSS 25.0. Enumeration data were expressed as the frequency and constituent ratio, and measurement data as mean ± standard deviation. The correlation between two variables was identified by the Spearman's rank correlation. Analysis of variance single factor analysis of variance was used. The structural equation modeling and path analysis were performed using IMB SPSS Amos 26.0. The mediation analysis with two mediators was performed by the bootstrap test at 33.1A total of 244 eligible CHF patients with a mean age of 64.45 ± 11.076 (30–93) years and a mean number of 3.05 ± 1.796  comorbidities were recruited, involving 138 (56.6%) men and 106 (43.4%) women. Their baseline characteristics were listed in Table 3.2Only 6 2.5%) of CHF patients used to or were now participating in CR programs. A total of 190 (77.9%) CHF patients could perform ADL. The frequency, time and type of daily activities/exercises are listed in Table .5% of CH3.3Kinesiophobia was detected in 170 (69.5%) of CHF patients who had a minimum TSK‐SV Heart score of 37 points. There were 202 (82.2%) with a minimum Barthel index of 60‐points, suggesting their good ADL (Table 3.4p < .01), but positively correlated with the kinesiophobia (p < .01). In addition, ADL of CHF patients was positively correlated with the health status (p < .01), but negatively correlated with the kinesiophobia (p < .01). A negative correlation was identified between kinesiophobia and health status in CHF patients (p < .01)  Table .3.5χ2/df, goodness‐of‐fit index (GFI), adjusted GFI (AGFI), comparative fit index, Tucker‐Lewis index and the root mean square error or approximation of the model were 1.614, 0.954, 0.924, 0.951, 0.933, and 0.053, suggesting the good fitness of the structural equation model. Furthermore, the significance of mediational effects was tested by bootstrapping in IMB SPSS Amos 26.0 with the sample size of 5000. It is shown that the 95% confidence interval (CI) of bootstrap was 0.036−0.532, in which 0 was not included, suggesting the statistical significance of mediational effects of kinesiophobia and ADL between cardiac function and health status of CHF patients. In the mediation analysis, the total effect c and the direct effect c΄ were 0.023 (p < .01) and 0.013 (p = .001), respectively. The indirect effect (ab) was calculated as ab = a1 × b1 + a2 × b2 = 0.006 + 0.004 = 0.01. Therefore, the mediation proportion of ADL plus kinesiophobia in the correlation between cardiac function and health status, which was calculated as the ratio of the indirect effect to the total effect, was 43.48%. The difference between the mediational effects of two mediators (ADL and kinesiophobia) was 0.001 , suggesting that both ADL and kinesiophobia partially mediated the effect of cardiac function on health status of CHF patients, but their mediational effects had no significant difference , housework (27.9%) and jogging (21.3%). CHF patients were less involved in other low‐risk activities/exercises, like dancing (7.0%) and Tai Chi (1.6%). Despite strong evidence supporting the preventive advantages of CR, previous research has indicated that CR is underutilized by clinicians and patients.Kinesiophobia was detected in 170/244 (69.5%) CHF patients, suggesting that kinesiophobia was highly prevalent in CHF patients, who had limited or low‐intensity daily activities/exercises. Previous studies reported higher Kinesiophobia scores (40.66 ± 5.56‐points) in patients with acute cardiovascular disease and elderly people with CHF than those in our findings, which may be attributed to the acute phase of disease, stronger fear on pain and negative emotions in the elderly.4.3Pairwise correlations were identified among the cardiac function, health status, ADL and kinesiophobia in CHF patients. CHF patients with the severer classification of cardiac function possessed worse ADL, health status and kinesiophobia. Cardiac function could mainly reflect the clinical manifestations, health status and prognosis of HF patients. Decreased exercise capacity is a main symptom of HF, manifested as fatigue, dyspnea, precordial pain, and intolerance to high‐intensity exercise.p < .001).n = 16) and NYHA Ⅳ  class were included in this study. Current studies mainly highlight the correlation between kinesiophobia and activity status in patients with cardiovascular diseases, and influencing factors. However, there is currently a limited number of interventions available to address kinesiophobia. Sahin et al.The presence of kinesiophobia poses a significant risk to the life and health of patients in numerous other diseases, associated with disability, depression, pain and even disuse.4.4Our findings revealed that the cardiac function not only directly influenced the health status of CHF patients, but also indirectly influenced it through kinesiophobia and ADL. The cardiac function of HF patients is closely linked with the pulmonary, renal, endocrine and metabolic functions, often accompanied by pain, depression, gastrointestinal discomfort, fatigue and other complications.Kinesiophobia and ADL mediated the influence of cardiac function on the health status of CHF patients, and their indirect effects accounted for 43.48% of the total effect. Notably, no significant difference in the mediational effect was detected between kinesiophobia and ADL, both being able to predict the health status. Somatic symptoms can be aggravated by negative emotions. As a negative psychological state, kinesiophobia leads to negative cognitive and emotional changes in CHF patients, and decreased ADL is an independent risk factor for acute HF onset and death.5CHF patients exhibit insufficient enthusiasm in CR programs, limited and low‐intensity daily activities/exercises, and prevalent kinesiophobia. Pairwise correlations exist among cardiac function, health status, ADL and kinesiophobia of CHF patients. The cardiac function not only directly impairs health status, but also indirectly through kinesiophobia and ADL, the mediational effects of which are equal. Kinesiophobia should be relieved and ADL enhanced to improve the health status and prolong the life expectancy of HF patients.Tang Yifan: Writing original draft, Investigation, Methodology, Formal analysis. Huang Yanling: Formal analysis, Investigation, Methodology. Wang Weiyun: Investigation, Data curation. Hu Xiaolin: Project administration, Supervision. Gu Zejuan: Project administration. Wang Rong: Project administration. Gao Chunhong: Writing—review and editing, Project administration, Conceptualization, Supervision.The authors declare no conflict of interest.


Maintaining a sufficiently high systolic blood pressure is essential for free flap perfusion after microsurgical breast reconstruction. Yet, many women undergoing these procedures have low postoperative systolic blood pressure. Intravenous volume administration or vasopressors may be needed to maintain systolic blood pressure above a predefined threshold. However, excessive volume administration may lead to volume overload and flap stasis, and the postoperative use of vasopressors may be limited depending on institutional standards. Additional nonpharmacological measures to raise blood pressure might be beneficial. Evidence suggests that the Red Bull energy drink could raise blood pressure. It has been shown to increase systolic and diastolic blood pressure in healthy volunteers and athletes.The primary objective of this study is to determine the difference in systolic blood pressure between an intervention group receiving Red Bull and a control group receiving still water after microsurgical breast reconstruction. Secondary objectives include postoperative heart rate, 24-hour fluid balance, pain level, or necessity for revision surgery due to flap complications.The Red Bull study is a prospective, multicenter randomized controlled trial comparing the effect of postoperative ingestion of Red Bull energy drink against still water in female patients undergoing unilateral microsurgical breast reconstruction. A total of 250 mL of Red Bull (intervention group) or 250 mL of still water (control group) will be administered to the study participants 2 hours postoperatively as well as for breakfast and lunch on postoperative day 1, amounting to a total volume of 750 mL per 24 hours. Female patients between 18 and 70 years of age undergoing unilateral microsurgical breast reconstruction will be included. Exclusion criteria are a history of arterial hypertension, cardiac rhythm disorder, diabetes mellitus, gastric or duodenal ulcer, thyroid disease, and current use of antihypertensive or antiarrhythmic drugs or thyroid hormones, as well as intolerance to Red Bull.Recruitment for the study started in June 2020 and was completed in December 2022. There is evidence that the Red Bull energy drink increases blood pressure in healthy volunteers and athletes. We hypothesize that postoperative ingestion of Red Bull will increase systolic blood pressure in women after microsurgical breast reconstruction. Red Bull could hence be used as a nonpharmacological adjunct to vasopressors or volume administration in women with hypotensive blood pressure after microsurgical breast reconstruction.This paper describes the Red Bull study trial protocol and analysis plan. The information will increase the transparency of the data analysis for the Red Bull study.ClinicalTrials.gov NCT04397419; https://clinicaltrials.gov/ct2/show/NCT04397419DERR1-10.2196/38487 Maintaining a sufficiently high systolic blood pressure is vital for free flap perfusion after microsurgical breast reconstruction. However, many women undergoing microsurgical breast reconstruction have low systolic blood pressure postoperatively. Often, intravenous volume administration or vasopressors are needed to maintain systolic blood pressure above 100 mm Hg. Yet, intravenous volume administration may lead to volume overload and flap stasis, and the use of vasopressors in the postoperative setting may be limited depending on institutional policies. Additional nonpharmacological measures to guarantee adequate postoperative perfusion pressure would be beneficial.Red Bull energy drink has shown varying effects on the hemodynamic profile and pain perception in clinical studies performed on healthy participants and athletes -3. A ranEnergy drinks have shown varying effects on endothelial function ,5. In a Considering the mild diuretic effect of caffeine, Red Bull energy drink may increase urine formation rate and decrease urine specific gravity. Although urinary output increased with caffeine and Red Bull energy drink in 1 study , this trRed Bull energy drink may furthermore increase pain tolerance . Levels Red Bull energy drink was first introduced in Austria in 1987 and launched in Switzerland in 1994. It is among the most popular energy drinks with over 6 billion cans being sold annually worldwide [Despite anecdotal reports that linked Red Bull consumption with ventricular tachycardia and symptoms of cardiovascular disease, limited daily consumption of 500 mL of Red Bull appears safe ,9. When Caffeine is an adenosine receptor antagonist with stimulating properties on the central nervous system It is known to increase blood pressure and peripheral vascular resistance through sympathetic stimulation . TaurineThe authors selected a daily administration of 250-500 mL of Red Bull in the study. Most investigators studied the effect of Red Bull after ingestion of 250, 355, or 500 mL. When ingested in standard amounts, Red Bull energy drink is a safe beverage without notable side effects ,9.Daily oral administration of 500 mL of Red Bull has proven safe, and any side effects after consumption exceeding 500 mL daily have been linked to caffeine . These iThe authors prospectively study the effect of postoperative ingestion of Red Bull energy drink on perfusion-related variables and patient recovery after microsurgical breast reconstruction. To our knowledge, there are no competing trials.This study aims to assess perfusion-related variables, postoperative levels of pain, type of postoperative complications, operative reexploration rate due to complications, and total duration of hospital stay in patients undergoing autologous microsurgical breast reconstruction with postoperative ingestion of Red Bull Energy drink.The primary objective is to assess the difference in systolic blood pressure (mm Hg) between the intervention group and the control group at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after each of 3 Red Bull (intervention group) or water (control group) applications.The secondary objective is to document and assess the following variables in the intervention group and the control group:Diastolic and mean arterial blood pressure (mm Hg) at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after each of 3 Red Bull (intervention group) or water (control group) applications.Postoperative heart rate (1/min) at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after each of 3 Red Bull (intervention group) or water (control group) applications.Postoperative urinary output (mL) during the first postoperative 24 hours.Intraoperative and postoperative fluid administration (mL) until 24 hours after surgery.Intraoperative and postoperative administration of vasoactive drugs (mg) until 24 hours after surgery.Postoperative pain  during the first postoperative 24 hours.Postoperative administration of opioid analgesics .Postoperative administration of nonopioid analgesics .Postoperative administration of benzodiazepines (mg).Rate of operative reexplorations during the first hospitalization (%).Flap loss (%).Duration of hospital stay .Wound healing 4 weeks after surgery (photo documentation).Notable adverse events of Red Bull energy drink in this population are as follows: nervousness, nausea, anxiety, tremor, insomnia, arrhythmia, need for revision surgery, and flap loss.This is an open-label, multicenter, prospective, and randomized controlled trial comprising a cohort of 100 patients. Patient selection and inclusion as well as the anesthetic visit will occur preoperatively in an outpatient clinic. During hospitalization, microsurgical breast reconstruction will be performed under general anesthesia by JF, AML, or DB. Additionally, oral ingestion of Red Bull energy drink (intervention group) or still water (control group) will occur 2 hours after surgery and on a postoperative day 1 for breakfast and for lunch. Finally, wound healing and scarring will be assessed at the 4-week follow-up in our clinic using photo documentation.Participants are expected to participate from the signing of the informed consent form until the 4-week follow-up visit. All patients enrolled prospectively in the trial will receive a Red Bull energy drink or still water. Blinding or masking is not feasible.The study population will be women between 18 and 70 years of age undergoing unilateral microsurgical breast reconstruction by JF, AML, or DB at 2 institutions.As a standard of care, all patients are asked to perform a check-up by their general practitioner (GP) within 2-4 weeks before the microsurgical procedure. Their GP fills in a standardized form provided by the Institute of Anesthesiology, from which all inclusion and exclusion criteria can be drawn. Additionally, the GP performs an electrocardiogram and a blood test  for the patient and sends the result to the institute of anesthesiology at the respective clinic.Inclusion criteriaFemale patients between 18 and 70 years of age.Ability to give written informed consent before participation in the study.Ability to comply with the requirements and restrictions listed in the consent form.Exclusion criteriaHistory of arterial hypertension.History of cardiac rhythm disorder.History of diabetes mellitus.History of gastric or duodenal ulcer.History of hyperthyroidism or hypothyroidism.Current use of antihypertensive drugs, antiarrhythmic drugs, and thyroid hormones.Allergy or intolerance to the component of Red Bull energy drink.Not fulfilling inclusion criteria.All consecutive female patients receiving unilateral autologous microsurgical breast reconstruction will be administered a total of either 750 mL Red Bull energy drink (intervention group) or 750 mL of still water (control group) at predefined intervals. The first dose of 250 mL of Red Bull energy drink or still water will be given 2 hours after surgery in the postanesthesia care unit. The following doses will be given on postoperative day 1 at 8 AM for breakfast (250 mL) and at 12 PM for lunch (250 mL). Full consumption of the study drink will be verified by a nurse. The study will be carried out at the 2 centers where JF, AML, and DB have been accredited: Klinik Pyramide am See, Zurich, Switzerland and Klinik Hirslanden, Zurich, Switzerland. The perioperative protocols have been standardized at both institutions and standard operating procedures have been implemented.The systolic and diastolic blood pressure as well as pulse will be measured noninvasively using a 24-hour ambulatory blood pressure monitor  during the first postoperative 24 hours. The device will be applied to the participant’s arm upon their arrival in the postanesthesia care unit and remain in place for 24 hours. Upon completion of these 24 hours, the readings will be downloaded on the study computer by the study personnel, using the software provided by Anandic Medical Systems AG.Total fluid administered intraoperatively and postoperatively as well as intraoperative and postoperative administration of vasoactive drugs will be recorded. The daily urinary output will be measured 24 hours after surgery. Pain levels will be measured on NRS with values ranging from 0 to 10. The rate of operative reexplorations, flap loss, and total length of primary hospital stay will be recorded. Wound healing and scarring will be assessed 1 month after surgery in our clinic and documented photographically.The variables obtained from the intervention group receiving Red Bull energy drink postoperatively will be compared with the corresponding variables of patients in the control group receiving the same amount of still water.Randomization is undertaken with equal allocation to each study group (Red Bull:still water=1:1) using a computed code. Blinding or masking is not feasible.We will measure the systolic and diastolic blood pressure using ambulatory 24-hour blood pressure monitors  to ensure comparable measurements (same side of arm and same cuff) and reduce intermeasurer variability. All patients will remain in bed during the first 12 hours postoperatively and will have a urinary catheter during this period. This further reduces changes in blood pressure not related to the study intervention. Additionally, all patients entering hospital preoperatively will have fasted for 6 hours (solids) and 2 hours (liquids). Also, oral fluid and food intake during the first 24 hours after a microsurgical procedure is typically low among all patients to ensure that patients could be taken back to theater in a timely manner should flap complications occur. The preoperative regular consumption of caffeinated products and the consumption of additional caffeinated products during the hospital stay will be recorded and incorporated in the final analysis. If a patient requires additional vasopressors postoperatively, this will be documented and incorporated in the final analysis.Difference in systolic blood pressure between the intervention group and control group at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after each of 3 Red Bull (intervention group) or water (control group) ingestions as measured by the ambulatory blood pressure monitoring device.Difference in the following postoperative variables between participants with or without postoperative intake of Red Bull energy drink:Diastolic and mean arterial blood pressure at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after each of 3 Red Bull (intervention group) or water (control group) ingestions as measured by the ambulatory blood pressure monitoring device.Postoperative heart rate (1/min) at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after each of 3 Red Bull (intervention group) or water (control group) applications.Postoperative urinary output (mL) during the first postoperative 24 hours.Intraoperative and postoperative fluid administration (mL) until 24 hours after surgery.Intraoperative and postoperative administration of vasoactive drugs (mL) until 24 hours after surgery.Postoperative pain (NRS) during the first postoperative 24 hours.Rate of operative reexplorations during the first hospitalization (%): flap complications (%) and flap loss (%); total duration of hospital stay ; wound healing 4 weeks after surgery (photo documentation).Patient- and tumor-related data, such as age, BMI (size and weight), tobacco use; diabetes mellitus, indication for surgery (oncologic or prophylactic), neoadjuvant chemotherapy, previous irradiation, side and type of flap, flap weight, and ischemia time will be assessed perioperatively or collected from the medical history.Differences in the incidence of notable adverse events between both groups. Adverse events include nervousness, nausea, anxiety, tremor, insomnia, arrhythmia, need for revision surgery, and flap loss.The schedule of trial enrolment, interventions, and assessments are presented in Participants are recruited for the study in outpatient clinic. All patients undergoing elective microsurgical breast reconstruction will be screened. Patients who consent to participate in the study are randomized at the moment of surgery planning. No compensation or payment is given to the study participants.Data are collected from clinical proformas, clinical notes, and study-specific forms and then entered onto a Excel (Microsoft Corp) file. The data collection form is provided in the The following assumptions estimated from literature and clinical experience:Mean systolic blood pressure (mm Hg): We assume the same SDs  for both groups and the correlation coefficient among repeated measures to be 0.7. If we assume no differences in time in the control group (mean 115 mm Hg) and assume the difference between the intervention group and the control group to be about 10 mm Hg, the required sample size would be 27 per group.Heart rate (1/min): We assume the same SDs (10) for both groups and the correlation among repeated measures to be 0.7. If we assume no differences in time in the control group (mean 80/min) and assume the difference between the intervention group and the control group to be 5/min, the required sample size would be 46 per group.Vasoactive drug Ephedrine (mg): We assume the mean drug dose in the control group to be 63 and the mean drug dose in the intervention group to be 48. Assuming equal SDs  we get 45 per group.The predefined parameters include a significance level (α level) of .05 and power (1-β) of 0.8.We calculated the patients needed to be included using the application STATA  and G*Power . Considering the different calculations and accounting for potential missing data or dropouts, 50 patients per group will be included, leading to a total of 100 patients.t test for independent data . In case data will not follow a normal distribution, an alternative nonparametric test will be used (Mann-Whitney U test).We are planning to measure mean systolic blood pressure at 8 time points. For this, the right statistical model is a mixed ANOVA where the group is an independent (unpaired) factor, and the time is a dependent (paired) factor. The comparison of drug intake between the Red Bull group and the control group will be performed by student As the null hypothesis (H0), we assume that mean systolic blood pressure from baseline to 120 minutes post drinking does not differ between the 2 groups. The analysis will be conducted by a senior statistician (MM) in accordance with the above mentioned statistical methods.The frequency of adverse events and the number of patients experiencing events will be tabulated by relation to the study intervention  and by study group. Nonserious adverse events unrelated to the intervention are recorded in the medical notes only.If vital data relevant for the calculation of the primary and secondary end point are missing  patients will be excluded from the participant list. Dropouts will be replaced by consecutive patients.Ethics approval was granted from the Cantonal Research Committee, Switzerland (KEK-ZH 2020-00493). Patients receive an information sheet and provide informed consent before screening to participate in study-specific procedures. The study will be carried out in accordance with the protocol and with principles enunciated in the current version of the Declaration of Helsinki, the guidelines of Good Clinical Practice issued by ICH, the Swiss Law and Swiss regulatory authority’s requirements.Participants will not be compensated for their participation in this scientific research project.After the statistical analysis of this trial, the principal investigator will make every endeavor to publish the data in a medical journal. Participants will be informed about the outcome of the study once the trial results have been published.Recruitment of the study participants started in June 2020 and was completed in December 2022. As described previously, there is evidence that Red Bull energy drink increases blood pressure in healthy volunteers and athletes ,2. We hyThe Red Bull study is a multicenter randomized controlled trial that will explore the effect of Red Bull energy drink intake on perfusion-related variables and flap outcome after microsurgical breast reconstruction. This paper describes the study protocol and statistical analysis plan. The trial sponsor is Plastic Surgery Group. Recruitment started on June 1, 2020, and completed in December 2022. Database lock and data extraction for analysis were carried out in February 2023 when all randomized patients completed the surgical procedure and follow-up period.There is evidence that the Red Bull energy drink increases blood pressure in healthy volunteers and athletes ,2. We hyThis trial has some strengths. This is the first trial assessing the influence of Red Bull on perfusion-related variables after surgery. To minimize adverse events and limit premature dropout from the study, participants with allergies or intolerance to any component of Red Bull will be excluded from the study. Also, diabetes mellitus is considered an exclusion criterion. Red Bull contains 27.5 g of sugar per 250 mL. Patients with diabetes mellitus might require the intake of sugar-free Red Bull, which could, however, be associated with a different hemodynamic pathway . FurtherAfter the statistical analysis of this trial, the principal investigator will make every endeavor to publish the data in a medical journal. Participants will be informed about the outcome of the study once the trial results have been published. The reporting of results from the outlined statistical analysis will comply with the consolidated standards of reporting trials protocol.


Background: During the SARS-CoV-2 pandemic period, in the treatment approved by the WHO, along with antivirals, antibiotics, nonsteroidal anti-inflammatory drugs and anticoagulants, dexamethasone was always used. This study started from the professional concern related to the vasopressor effect of cortisone on blood pressure (BP). Methods: The study group was achieved by selecting, from a total of 356 patients hospitalized in the clinic, the patients with known hypertensive status at admission for SARS-CoV-2. Dexamethasone was part of the anti-COVID-19 treatment, with an administration of 4–6–8 mg/day, depending on bodyweight, for 10 days. All patients with hypertension received antihypertensive treatment in adjusted doses according to the recorded BP values. Results: Monitoring of BP in hospitalized patients was performed daily, in the morning and evening. If on the 2nd day of treatment, 84% of the patients partially responded to the treatment with a moderate decrease in BP, on the 3rd therapy day, the situation clearly improved: more than 75% of the patients had values of BP that can be classified as high-normal (38.23%) and normal (40.03%). Conclusions: Dexamethasone for treatment of SARS-CoV-2 infection did not have a notable influence on increasing BP, because the doses were low–moderate and prescribed for a short time.  During the SARS-CoV-2 pandemic 2020–2021), in all the treatment schemes approved by the WHO and taken over worldwide by all countries, including the USA and the EU, along with antivirals, antibiotics, nonsteroidal anti-inflammatory drugs and anticoagulants , in all , dexametIn the first months after the pandemic outbreak, especially in the first half of 2020, therapeutic schemes launched by infectionists ,6,7,8,9,In the present study, only drugs that were available and used in the EU and in Romania, respectively, are listed . In the The condition, often serious, of cardiac and COVID-19 patients meant that all our attention was directed towards the most correct application of the SARS-CoV-2 treatment protocol, along with the follow-up of each patient admitted to the cardiology clinic . Only afSodium retention: One of the most commonly accepted theories is that dexamethasone increases sodium retention by the kidneys. This leads to an increase in extracellular fluid volume and subsequently an increase in blood pressure.Vasoconstriction: Dexamethasone has been shown to cause vasoconstriction, or narrowing of the blood vessels, in some animal studies. This can lead to an increase in systemic vascular resistance and subsequently an increase in blood pressure.Sympathetic nervous system activation: While dexamethasone does not directly activate the sympathetic nervous system, it can indirectly affect it by reducing inflammation and suppressing the immune system. This response involves the release of various hormones, including adrenaline, which increase heart rate, blood pressure and breathing rate, among other physiological changes.In the present study, we assess the evolution of arterial hypertension (HBP—high blood pressure) in COVID-19-positive patients admitted to the clinic, due to the fact that dexamethasone was always included in the anti-COVID-19 treatment management. The study started, as mentioned, from the professional “fear” of not encountering medical problems related to the influence  of cortisone preparations on blood pressure level . It is kOur observational study was conducted between 1 July 2020 and 30 June 2021 on a group of 356 patients admitted to the Cardiology Clinic of Philanthropy Clinical Municipal Hospital in Craiova—A COVID-19 support hospital unit (Order no. 555/2020). Thus, hospitalization in all of this hospital’s clinics (and implicitly in the cardiology one) was only allowed for patients infected with SARS-CoV-2 who were also associated with other conditions and whose severity at the time of hospitalization was high and could not receive appropriate care only in infectious diseases units in the neighboring areas [The study group was achieved by selecting, from the total number (356) of patients admitted to the clinic during the observed period, only the patients known to be hypertensive or with acute hypertensive episodes at admission due to SARS-CoV-2 infection. The rest of the patients with other previously known heart conditions and who presented blood pressure (BP) values below 160 mmHg systolic at presentation were not included in the group. It is well known that there is no well-defined “line” between cardiac diseases, but the basic criteria for including or excluding patients in the group was provided by HBP as reason for hospitalization. Anti-COVID-19 treatment included antibiotics, anticoagulants, antivirals and dexamethasone   recommended the use of dexamethasone in patients with severe and critical COVID-19 infection who require oxygen therapy or mechanical ventilation. The drug is not recommended for use in patients with mild or moderate COVID-19 infection . It is iOverall, while dexamethasone has been shown to be an effective treatment for severe COVID-19, its use should be approached with caution in patients with underlying cardiovascular conditions and the elderly population, and it should only be used under the supervision of a healthcare professional.Blood pressure was measured in the morning and evening, as well as for specific symptoms such as headache, dizziness, vertigo and palpitations. In the context of the infectious disease, these symptoms were either difficult to attribute entirely to hypertension or  were partially masked by the dominant symptoms of the COVID-19 infection: dyspnea, fever, cough, asthenia, palpitations, precordialgias and anosmia.Optimal—SBP < 120 mmHg and DBP < 80 mmHg;Normal—SBP 120–129 mmHg and/or DBP 80–84 mmHg;High-normal—SBP 130–139 mmHg and/or DBP 85–89 mmHg;Grade 1—SBP 140–159 mmHg and/or DBP 90–99 mmHg;Grade 2—SBP 160–179 mmHg and/or DBP 100–109 mmHg;Grade 3—SBP ≥ 180 mmHg and/or DBP ≥ 110 mmHg;Isolated systemic hypertension—SBP ≥ 140 mmHg and DBP < 90 mmHg. The phrase should be reformulated as follows:Legend: SBP, systolic blood pressure; DBP, diastolic blood pressure.In patients with high BP, we recorded blood pressure values through morning and evening measurements and also when specific symptoms occurred. As antihypertensive treatment, we only used diuretics, calcium channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACE), angiotensin receptor blockers (ARB) and central agonist of alpha 2 imidazolinic receptors (rilmenidine) in doses adjusted to the recorded BP values (according to the last JNC) ,26,27. TFor the 356 patients with SARS-CoV-2 infections who were admitted between 1 July 2020 and 31 June 2021 to the cardiology clinic, the main cardiologic diagnosis (as the reason for admission) is shown in These hypertensive patients at the time of hospitalization, regardless of their own medication at home or those unmedicated until that moment, received diuretic treatment , CCB (1 cp/day amlodipine 10 mg–5 mg), ACE (1 cp/day perindopril 10 mg–5 mg) and ARB (candesartan 16 mg/day), and in some cases, rilmenidine 1 mg/day. These doses were adjusted according to BP value. We also mention that the antihypertensive medication scheme was initially simple, with the intention of seeing the patient’s response to treatment and to be able to subsequently increase the medication by adding other classes of antihypertensives, or to decrease it depending on the evolution. Among other cardiological conditions, atrial rhythm disorders reached a percentage of 10.67%, followed by ischemic heart disease at 8.70%. Blood pressure (BP) values and evolution were monitored daily in the enrolled patients, in the morning and evening. The graphic representation of their response to treatment was achieved on the 2nd, 3rd and 7th day upon admission, as well as on on the 14th day, before discharge. We mention that antihypertensives doses were adjusted according to individual BP values, and we also note that for 10 days, the patients were medicated with dexamethasone at an average dose of 4–6–8 mg depending on their body weight and the severity of the disease (as recommended by the infectionist). If we study the BP values at admission , systoliHospitalized patients immediately received the medication from the anti-COVID-19 protocols, and therefore also dexamethasone, in doses adjusted according to their bodyweight but not exceeding the value of 8 mg/day, for 10 days. In addition to the treatment recommended by the infectionist, we also instituted antihypertensive treatment as mentioned previously with diuretics, CCB, ACE and ARB. After initiation of classical antihypertensive treatment, at the first blood pressure measurement, in the morning or evening, depending on the time of day when the hospitalization occurred, it can be noticed in For the latter, we decided to increase the diuretic dose and to double the ACE dose.We decided not to intervene with strong antihypertensive therapy because some patients also had other cardiological medication with hypotensive effects, such as beta blockers, and in addition, a significant part of them were still febrile, with intravenous therapy either to correct dehydration or as support for antibiotic, antipyretic and antiviral treatment. Since the results obtained after only one day of treatment are not relevant for the evolution of the studied patients, we present in On the 2nd day of treatment, 84% of the patients partially responded to the treatment with a moderate decrease in BP, and 16% had more important decreases in BP —althoughThe next data representation is from the 7th day of admission , a perioFrom the chart that represents BP values on the 7th day of anti-COVID-19 (with dexamethasone) and antihypertensive treatment, it is noticed that values were closer to normal in almost half of the patients of our group (49.16%), and only in a small part (9.4%), the BP values remained at a slightly higher value (150–140/85–80 mmHg.) We also mention that 10 patients (4.2%) recorded decreases in BP values up to the inferior limit of normal (110–100/70–60 mmHg), although they were under antihypertensive medication at minimal doses of diuretic (indapamide 1.5 mg), CCB (amlodipine 2.5 mg) and ACE (perindropil 2.5 mg); thus, the diuretic from their medication was removed. All patients in the group received dexamethasone for 7 days in doses of 4–6–8 mg/day. Among the hypertensive patients, after 2 weeks of hospitalization , 67.22% We mention that we did not record any paroxysmal increases in BP values in our hypertensive patients throughout their hospitalization during one year of study, although they had cortisone treatment with dexamethasone 4–6–8 mg/day for 10 days, and consequently, we did not experience any hypertensive emergency complications, such as hypertensive encephalopathy, cerebral edema, acute pulmonary edema and ischemic or hemorrhagic strokes. Hypertensive emergency is a serious medical condition that occurs when blood pressure levels rise to dangerously high levels. This can lead to a range of complications, including those mentioned above. The general observation of the study shows that the evolution of hypertensive patients with COVID-19 respiratory infection, at the time of emergency presentation, did not consist of any particular problems regarding the response to classic antihypertensive therapy. The patients had a normal evolution, with a slow decrease in high blood pressure values a few days after admission, and towards the end of the first week of hospitalization, their BP values approached and remained normal. Thus, we cannot say that we faced increased BP values that may be attributed to ongoing dexamethasone treatment. On the contrary, in the first week of hospitalization, in about the 3rd and 4th day of treatment, the drop in BP values was more important than we would have expected, and we had to reduce the doses of antihypertensive medication, and in some patients, the treatment was interrupted. This may suggest that hypertension is not a major barrier to treating COVID-19 respiratory infection with standard antihypertensive therapy. However, it is important to note that hypertension can be a risk factor for severe COVID-19 disease and poor outcomes, as it is associated with increased risk of cardiovascular complications and other comorbidities . In someRegarding dexamethasone administration, as an immune modulator in anti-COVID-19 treatment schemes, we believe that the hypertensive effect did not find expression in the influence of BP values in our patients, since the doses were low–moderate, with only 1 administration per day and for a limited time period of 10 days. BP values of the patients in our study (238 hypertensive patients with SARS-CoV-2) were measured on the even in 14th day of hospitalization which was day of discharge deoarece the European protocol on that date stipulated that patients must be treated in hospital 14 days, considering that from the 14th day they are no longer contagious, regardless of whether they are negative or positive on the RT-PCR test . We consAs for this study’s limitations, we mention that since it was conducted in one hospital only, generalized conclusions are not possible to obtain; moreover, the sample did not allow us to perform a statistical study, the variables being numerous, and the sample itself was not a very large one according to the number of hospitalizations. Additionally, a more thorough comparison between this study’s results and other studies from other hospitals should be done.In the SARS-CoV-2 pandemic, HBP was the main reason for hospitalization in the cardiology clinic for COVID-19-positive patients. The classic antihypertensive treatment scheme  was sufficient for a slow decrease in BP values from the first 2–3 days after admission and treatment, as well as to maintain normal levels until discharge. There were no paroxysmal BP increases and no urgent hypertensive complications that could be attributed to the dexamethasone treatment. The high percentage of elevated BP values at admission can be attributed to the stress caused by the diagnosis of SARS-CoV-2 infection and the prospect of a subsequent unfavorable evolution. The hypercoagulability associated with COVID-19 viral infection could also be incriminated in the mechanism of the increased BP values upon admission. It is possible that the administration of dexamethasone in high doses and over a longer period is responsible for the known hypertensive effect of this drug, but this situation was not recorded in our patients with SARS-CoV-2. Thus, on the contrary, the measurements of blood pressure values were decreased.


Patients with advanced chronic kidney disease (CKD) have the best chance for a longer and healthier life if they receive a kidney transplant. However, many barriers prevent patients from receiving a transplant.To evaluate the effect of a multicomponent intervention designed to target several barriers that prevent eligible patients from completing key steps toward receiving a kidney transplant.This pragmatic, 2-arm, parallel-group, open-label, registry-based, superiority, cluster randomized clinical trial included all 26 CKD programs in Ontario, Canada, from November 1, 2017, to December 31, 2021. These programs provide care for patients with advanced CKD .Using stratified, covariate-constrained randomization, allocation of the CKD programs at a 1:1 ratio was used to compare the multicomponent intervention vs usual care for 4.2 years. The intervention had 4 main components, (1) administrative support to establish local quality improvement teams; (2) transplant educational resources; (3) an initiative for transplant recipients and living donors to share stories and experiences; and (4) program-level performance reports and oversight by administrative leaders.The primary outcome was the rate of steps completed toward receiving a kidney transplant. Each patient could complete up to 4 steps: step 1, referred to a transplant center for evaluation; step 2, had a potential living donor contact a transplant center for evaluation; step 3, added to the deceased donor waitlist; and step 4, received a transplant from a living or deceased donor.The 26 CKD programs  during the trial period included 20 375 potentially transplant-eligible patients with advanced CKD . Despite evidence of intervention uptake, the step completion rate did not significantly differ between the intervention vs usual-care groups: 5334 vs 5638 steps; 24.8 vs 24.1 steps per 100 patient-years; adjusted hazard ratio, 1.00 .This novel multicomponent intervention did not significantly increase the rate of completed steps toward receiving a kidney transplant. Improving access to transplantation remains a global priority that requires substantial effort.NCT03329521ClinicalTrials.gov Identifier:  Does a novel multicomponent intervention help potentially transplant-eligible patients with advanced chronic kidney disease (CKD) complete key steps toward receiving a kidney transplant?In this cluster randomized clinical trial that included 20 375 patients from 26 CKD programs, the intervention compared with usual care did not significantly increase the rate of steps completed toward receiving a kidney transplant.Among transplant-eligible patients with advanced CKD, this multicomponent intervention, which targeted many barriers to receiving a kidney transplant, did not significantly increase overall access to kidney transplant. This randomized clinical trial evaluates the effect of implementing a novel multicomponent intervention designed to target several barriers that prevent eligible patients from completing key steps toward receiving a kidney transplant. Compared with dialysis, a kidney transplant offers patients a better quality of life and many gain 10 or more years of life expectancy.5 Education is required on multiple occasions, for varied audiences, and in several formats.6 Many patients and staff need clarifications about the transplant and living donor process.7 It is not easy to discuss living donations with family and friends.4 Overall, CKD programs need to better coordinate with transplant centers.8 There are too few kidneys from deceased donors, and living donation rates remain stagnant.9 In Ontario, CKD program staff traditionally placed little emphasis on transplant activity in their day-to-day work.5Reasons for this care gap are complex, and barriers exist for patients, families, health care professionals, chronic kidney disease (CKD) programs, transplant centers, and health care systems.10 We conducted the Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD) trial to determine the effect of a novel multicomponent intervention designed to help eligible patients complete key steps toward receiving a kidney transplant.Initiatives have been launched in several countries to address these barriers.NCT03329521.11 The trial was designed, analyzed, and reported following recommended guidelines .We conducted a pragmatic, 2-arm, parallel-group, open-label, registry-based, superiority, cluster-randomized clinical trial. We designed the intervention to affect entire CKD programs (the clusters), so program-level randomization was adopted for logistical reasons and to minimize cross-group contamination. Trial data came mainly from linked administrative health care databases, including dialysis and transplant registries. We published the protocol  and stat15 The trial was embedded in routine care across 26 specialized kidney clinics , 26 home dialysis programs, and 97 hemodialysis units. More than 3400 nurses and 230 nephrologists provided this care.The administrative leaders of all 26 CKD programs in Ontario, Canada (the clusters) agreed to include their program and receive the randomly assigned intervention during the 4.2-year trial period from November 1, 2017, to December 31, 2021. Together these programs treat more than 24 000 patients with advanced CKD  each year.16); note, this process differs in the US, where either a CKD program forwards a patient’s contact information to a transplant center to make the referral or a patient contacts the transplant center directly .17 Interested potential donors contact a transplant center to receive more information and begin their evaluation.The CKD program staff educate patients and families on their treatment options, including transplant. Staff are also responsible for sending referrals to 1 of 6 transplant centers in Ontario. A referral requires the results of many tests . We followed patient outcomes until December 31, 2021, and patient entry into the trial analysis ended on September 30, 2021, to allow for at least 90 days of potential follow-up.We used administrative data to identify and follow up patients with advanced CKD who received care in the 26 CKD programs. Data sets were authorized for use in this trial under section 45 of Ontario’s Personal Health Information Protection Act, linked using unique encoded identifiers, and analyzed at ICES.15 Patients also needed to be potentially transplant-eligible .15 Patients approaching the need for dialysis received care in specialized kidney clinics staffed by multidisciplinary teams. Clinic patients entered the trial when there was the first evidence of (1) an estimated glomerular filtration rate (eGFR) lower than 15 mL/min per 1.73 m2 19 or (2) a 25% or greater 2-year predicted risk of kidney failure .20 To ensure stable kidney function, at least 2 eGFR or 2 KFRE measures were required to enter the trial, with measures separated by at least 90 days but no more than 365 days. The remaining patients entered the trial after evidence of receiving outpatient maintenance dialysis in a center or at home.Entering the trial refers to patients being included in the outcome analyses, and the analyses were performed using linked administrative health care databases after the trial period was over. To enter the trial, patients needed to be aged 18 to 75 years (kidney transplants after age 75 years are rare).5 More details are in the trial protocol  to the intervention or usual-care groups.protocol .5 Briefl22 The multicomponent intervention was codesigned by an 18-member panel to address complex barriers at multiple levels that prevent kidney transplant and living donation.4 The panel had expertise in CKD, transplant, quality improvement, health care data, education, and patient support and included patients, health care staff, administrators, scientists, and representatives from CKD programs, transplant centers, and kidney and transplant government-funded agencies.24 Four main components were developed for the intervention and provided to each CKD program. Instructions were given not to share intervention resources with the usual-care group (to prevent between-group contamination); however, resources were made broadly available after the trial.Details are in the protocol, which features a recommended template to describe a complex intervention.Support from a central operations group  to establish a new local quality improvement team to drive local performance. Each team received $7316 per year to support their activities. In addition, team representatives were invited to new monthly provincial rounds to share experiences and strategies .25 One resource26 was the mass production and online creation of a personalized education and coaching program (Explore Transplant Ontario27).Multiple educational resources were made available to health care staff, patients, and potential donors.A new initiative of more than 85 kidney transplant recipients and living kidney donors who voluntarily spend time in CKD programs, sharing their experiential knowledge and stories and providing emotional support and hope.4628Program-level reports summarizing trends in 13 transplant measures, distributed quarterly to local teams and annually for 1-on-1 performance meetings between leaders of each CKD program and the provincial kidney agency.The primary outcome was the rate of steps completed toward receiving a kidney transplant. Each patient could complete up to 4 steps, and for each patient, we only counted each step once: step 1, referred to a transplant center for evaluation; step 2, had a potential living donor contact a transplant center for evaluation ; step 3, added to the deceased donor waitlist; and step 4, received a transplant from a living or deceased donor.29 and this intervention was not designed to increase the number of kidneys available from deceased donors. Thus, 5 secondary outcomes focused on specific steps, or a combination of steps, for living donor transplant (1) donor evaluation or living donor transplant (step 2 or a subset of step 4), (2) donor evaluation (step 2), (3) referral and donor evaluation (steps 1 and 2), (4) living donor transplant (a subset of step 4), and (5) preemptive living kidney donor transplant (a subset of step 4).The average wait time for a deceased donor kidney in Ontario is 4 years,11 Accounting for the correlation within clusters, the trial was designed to have at least 80% power to detect a between-group difference of 12 steps per 100 patient-years .Details are in the trial protocol and statistical plan .5,11 Acc11 We performed the analyses using SAS statistical software  and R statistical software .30 The analysis was performed between October 2022 and March 2023, after outcome data for the entire trial period became available in the data sources used.Details are in the statistical plan .11 We peAlmost all baseline data were complete .The analyses used an intention-to-treat approach, meaning patients were analyzed according to the random assignment of their CKD program when they entered the trial , regardless of whether they transferred to a CKD program in the alternate group. After trial entry, the only reason for patient loss to follow-up was emigration from the province (which occured in <2.0% of patients with advanced CKD each year). Otherwise, for analysis of the primary outcome, a patient’s observation time was stopped if they reached the trial end date , died, received a kidney transplant, recovered kidney function, or became ineligible to receive a transplant , the multistate model reduced to a classic Cox proportional hazards model. We used cluster-level bootstrapping to obtain standard errors (accounting for the correlated outcomes within CKD programs) and a t-distribution as a small-sample correction for fewer than 40 clusters. eTable 7 in Outcomes were analyzed at the patient level using stratified, constrained, multistate models, accounting for the order of step completion, the clustered design, and the covariates used in the randomization  unadjusted for characteristics, (2) adjusted for additional baseline characteristics, and (3) unconstrained to examine intervention effects on each transition shown visually in eFigures 1A and 1B in In post hoc analyses, we investigated the consistency of the estimated intervention effect in patients who (1) completed no steps toward receiving a transplant before trial entry, (2) entered the trial approaching the need for dialysis, and (3) were receiving maintenance dialysis when they entered the trial.In a post hoc analysis to assess potential contamination bias, we compared kidney transplant rates in the usual-care group during the trial to historical norms. If programs in the usual-care group inadvertently gained access to intervention materials, kidney transplant rates may have increased.During the 4.2-year trial period, the 26 CKD programs cared for 20 375 patients with advanced CKD who were potentially transplant eligible. A total of 9780 patients entered the trial from 13 CKD programs in the intervention group and 10 595 patients from 13 CKD programs in the usual-care group. We included all patients in the intention-to-treat analysis .2, the median (IQR) random urine albumin-to-creatinine ratio was 162 (69-314) mg/mmol, and the 2-year predicted risk of kidney failure was 45% (32%-67%). For patients who entered the trial on November 1, 2017, already receiving maintenance dialysis, the median (IQR) duration of dialysis was 2.6 (1.2-5.1) years. Before entering the trial, 80% of patients had completed no steps toward receiving a kidney transplant. Of the patients who entered the trial approaching the need for dialysis, 48% started maintenance dialysis during the trial.Center and patient characteristics were similar between the 2 groups . For the; eTable 9 in We followed up patients for a median (IQR) of 2.1 (1.0-3.6) years. During follow-up, 290 patients (1.4%) emigrated from the province, 225 recovered their kidney function (1.1%), 2789 became ineligible to receive a kidney transplant (13.7%), and 3432 died (16.8%); these rates were similar between the 2 groups  recorded 5471 meaningful interactions with patients with advanced CKD and 719 meaningful interactions with potential living kidney donors. Each CKD program received regular performance reports and had annual performance meetings with the provincial kidney agency.The onset of the COVID-19 pandemic, 2.4 years into the 4.2-year trial period, substantially affected intervention delivery for at least a year. Transplant activity ceased temporarily, local quality improvement teams met less often, there was a pause on the provincial rounds, health care staff retired or were redeployed, and transplant ambassadors transitioned from in-person to virtual meetings.; eFigures 1A and 1B in The rate of the primary outcome did not differ significantly between the intervention group [n = 9780 patients] vs the usual-care group [10 595 patients]: 5334 vs 5638 steps; 24.8 vs 24.1 steps per 100 patient-years; adjusted hazard ratio 1.00  .The 2019 Advancing American Kidney Health executive order included ambitious goals for increasing the rate of kidney transplant.39 Educational materials were created and used, and patients engaged with a new provincial support group of transplant recipients and living donors. The creation of data-sharing agreements and data collection allowed CKD programs to receive detailed performance reports for the first time. We conducted this pragmatic, randomized clinical trial within a learning health care system to generate robust estimates of how the intervention performed in a routine care setting.40The strengths of this clinical trial include its size, scope, and systematic approach to designing, implementing, and testing a province-wide multicomponent intervention. Diverse stakeholders, including administrators, health care staff, patients, and nephrologists, worked together to develop and implement the intervention, which was designed to address known barriers to receiving a transplant.22 In the interim, we identified 2 staff-related opportunities. First, although many staff in CKD programs appreciated the support and resources, they indicated that growing patient-to-staff ratios meant they lacked time to enact this initiative fully. Acknowledging this concern, the provincial kidney agency began providing annual funding for transplant coordination activities in all CKD programs after the trial was completed. Second, there was substantial turnover among frontline nurses and members of the quality improvement teams. Any future strategy should plan for an ongoing need for intervention reorientation.Nonetheless, it was disappointing that, overall, we could not demonstrate a significant benefit of this intervention compared with usual care. It is unlikely that contamination, which is the use of intervention components by the usual-care group during the trial, is a reason for these findings. We acknowledge that it takes time to improve health care delivery and organize each transplant, and CKD programs faced many challenges during the COVID-19 pandemic. We are now completing a multimodal process evaluation to understand how the intervention can be improved.15 Trial findings may not be generalizable to other health care systems because dialysis practice patterns, patient case-mix, access to multidisciplinary care, and resources available to improve access to kidney transplant may vary across geographical regions.44 Finally, this intervention did not address inequities in access to transplantation, a key priority in health care.47This study has several limitations. The COVID-19 pandemic negatively affected intervention delivery, and the momentum for this initiative may have lessened as health care priorities shifted to focus on the pandemic. We did not determine whether the intervention improved culture, knowledge, or experience. Administrative data to assess transplant eligibility will never replace detailed in-person evaluation.The findings of this randomized clinical trial did not show that a novel multicomponent intervention significantly increased the rate of completed steps toward receiving a kidney transplant. Improving access to transplantation remains a global priority that requires substantial effort.


Adequate mean arterial pressure (MAP), or the average pressure in arteries during one cardiac cycle, plays an important role in ensuring adequate blood flow and perfusion in critically ill patients. MAP values of 65 mmHg or greater have been widely regarded as the ideal value for hospitalized patients in the past, especially those suffering from septic shock. Necrotizing soft tissue infections (NSTIs) present a unique challenge due to their rapid progression and high mortality, which creates the need for specific diagnostic and treatment guidelines that differ from those directed toward the care of sepsis secondary to other causes. Further research is still required to better understand the complex interactions between mean arterial pressure and morbidity and mortality among those with necrotizing soft tissue infections.Data was collected from a retrospective cohort study of 50 adult patients hospitalized with an NSTI from 2015-2021. MAP ranges in the first 48 hours of admission were sorted into four categories: under 60 mmHg, 60-69 mmHg, 70-79 mmHg, and above 79 mmHg. We investigated outcomes relating to increased morbidity, including need for repeat debridement, need for dialysis, or development of acute kidney injury. Statistical logistic regressions were fitted to model the outcome as a function of the available pool of predictors: demographic variables, co-morbidities, and hemodynamic variables, such as MAP and use of vasopressors.In this small study, we found no significant association between time spent in different MAP groups or vasopressor volumes on the need for repeat debridement for NSTI patients or overall patient morbidity and mortality (p=0.1742). Patients who were significantly more likely to need a repeat debridement included those with previously diagnosed diabetes and hypertension .NSTI patients can tolerate mild fluctuations in MAP without these pressures significantly impacting their need for repeat debridement or other sources of morbidity. However, patients who are hypertensive at baseline or diabetic are significantly more likely to require a second surgery, necessitating a more extensive primary debridement.Patients hospitalized for NSTI can fluctuate at pressures below the established MAP goal of 65 mmHg without a significant need for pressors. Those with a history of hypertension or diabetes should be followed closely for possible spread of infection after primary surgery.