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Methods | PMC10512773 | |||
Study participants | AKI, sepsis | SEPSIS | This was a single-center double-blind randomized clinical trial that screened all consecutive patients admitted for AKI who met the diagnostic criteria for sepsis and had been evaluated by the Nephrology Department at the Hospital Civil de Guadalajara Fray Antonio Alcalde, a large referral center that cares for patients without health care insurance and with low socioeconomic status in Jalisco, México.Patients were enrolled from February 2019 to March 2022. Due to the COVID-19 pandemic, we enrolled patients at a slower rate and over a relatively long period (2019 through 2021). The trial was conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization Guidelines for Good Clinical Practice. All patients gave their written informed consent before any study-related procedure. The study, which was approved by the local ethics committee (HCG/CEI-1342/18), was prospectively registered in clinicaltrials.gov (NCT03877081) on 03/15/2019. No funding was received to conduct this study. | PMC10512773 |
Definitions | nausea, diarrhea, vomiting, rash, AKI | ADVERSE EVENT, KIDNEY DISEASE | AKI was defined as an increase in serum creatinine (sCr) levels according to Kidney Disease Improving Global Outcomes (KDIGO) [All comorbidities and clinical data were prospectively collected during the first evaluation.Adverse events were prespecified according to those most frequently reported with the use of probiotics, such as abdominal distension, nausea, rash, vomiting and diarrhea [ | PMC10512773 |
Study outcomes | ADVERSE EVENTS | The primary outcome was KFR on day 7 (sCr return to <0.30 mg/dL from the baseline value). Secondary outcomes included variables related to KFR during the treatment and the follow-up period, namely, the change in urinary volume, percentage of decrease in sCr levels, in-hospital mortality, mortality during follow-up, KRT requirement, electrolyte levels and acid–base abnormalities. The prespecified adverse events mentioned above were prospectively reported. | PMC10512773 | |
Randomization and treatment assignments | AKI | Randomization was carried out by a computer-generated stratified sequence with a 1:1 allocation ratio in blocks of 5, with the groups stratified by sex. The researchers, who used a concealed opaque envelope system, performed group assignment after informed consent was obtained. A double-blind, double-dummy design was used. The nephrology staff administered the treatment in white bottles that were only marked with the patient’s assignment number.Given the lack of previous clinical trials on this topic, a formal sample size calculation was not performed, and we chose a convenient sample size of 92 patients. All patients received the personalized management suggested by the KDIGO AKI bundle of care guidelines [Patients who met the inclusion criteria and signed informed consent were randomized to the intervention group (probiotics) or the control group (placebo), and 2 capsules The results are reported following the CONSORT guidelines for clinical trials. | PMC10512773 | |
Interventions | Patients in the intervention group received 2 capsules of Simbin-RNL® or 2 capsules of placebo (maltodextrin) every 24 h for 7 consecutive days. The gastro-resistant Simbin-RNL® capsule contained 540 mg of a mixture of | PMC10512773 | ||
Statistical analysis | death, SD | REGRESSION | Categorical variables are presented as numbers and percentages, and comparisons between groups were performed with the chi-square or Fisher exact test as appropriate. The Shapiro–Wilk test was performed to assess data distribution; continuous variables are summarized as the means ± standard deviations (SD) if the data were normally distributed or medians and interquartile ranges (25–75th) if the data were nonnormally distributed and were compared using Student’s t test or the Mann–Whitney U test, respectively. For variables measured at multiple time points, repeated measures analysis of variance tests were used for comparisons between groups. Time to renal recovery and time to death were both plotted on Kaplan–Meier curves, and the groups were compared with the log-rank test. A multiple regression analysis was performed with the enter method, and all the baseline variables with a p value ≤0.20 were entered into the model in bivariate analysis. All tests were two-tailed, and results with a p value less than 0.05 were considered significant. Statistical analysis was performed, and graphics were generated with MedCalc Statistical Software (Ostend, Belgium. Ver 19.1.3) and GraphPad Prism (California, USA. Ver 9.2.0), respectively. | PMC10512773 |
Results | AKI, sepsis | SEPSIS | From February 2019 to March 2022, 621 patients with AKI underwent nephrology consultation, and 123 did not have sepsis or they lacked variables of interest for the analysis; thus, 498 were assessed for eligibility, among whom 372 did not meet inclusion criteria, and 34 did not sign the consent form; therefore, 92 patients were randomized, with 48 in the intervention group (probiotics) and 44 in the placebo group (CONSORT Flow diagram.The baseline demographic characteristics of the randomized study participants are described in Study baseline characteristics according to the probiotics or placebo groups.Regarding adherence, 81% in the probiotic group and 77% in the control group consumed at least 80% of the doses ( | PMC10512773 |
Primary outcome | The KFR by day 7 is presented in Primary objective, kidney function recovery during the 7 days of the study trial.Primary and Secondary objectives. | PMC10512773 | ||
Secondary outcomes | uremia | REGRESSION, SECONDARY, VOLUME OVERLOAD, UREMIA | The results of the secondary outcomes are shown in Secondary outcomes, A) Survival, B) serum urea, and C) urinary output, during the 7 days of the study trial.A total of 17 (19%) patients required KRT during the study follow-up period, which was mostly due to uremia, volume overload, and electrolyte abnormalities; this included 12 (26%) in the probiotic group and 5 (12) in the placebo group, with an RR of 2.19 (95% CI 0.84–5.72, Additionally, urea levels (mg/dL) decreased significantly in the probiotic group from 154 (70–173) to 80 (31–148), which was not observed in the placebo group, in which they only decreased from 130 (70–173) to 109 (53–160), (Urinary volume (ml/day) increased from 1,000 (500–1,500) to 1,100 (750–1,400) in the intervention group (The patients were followed for a median of 382 days (193–967), and it was observed that their renal function deteriorated, which was based on an overall eGFR of 39 (23–94 mL/min/1.73 mIn an exploratory multiple regression analysis, including baseline sodium and potassium levels, heart rate, diastolic blood pressure and stages KDIGO 3 in the model and weighting by group, the results for renal recovery and mortality remained nonsignificant, with | PMC10512773 |
Additional outcomes of interest | Potassium levels decreased, and chloride levels increased during the study in both groups, but they did not differ significantly between intervention groups. Only sodium levels decreased in the probiotic group (134 ± 5.9), and they increased in the placebo group (137 ± 5.8) ( | PMC10512773 | ||
Adverse events | ADVERSE EVENTS, ADVERSE EVENT | The prespecified adverse events during the study period are presented in Adverse events during the 7 days of study period. | PMC10512773 | |
Discussion | CKD, fibrosis, intestinal dysbiosis, kidney dysfunction, sepsis-induced AKI, AKI, sepsis | ADVERSE EVENTS, FIBROSIS, KIDNEY DYSFUNCTION, SECONDARY, SEPSIS | In this double-blind randomized clinical trial carried out in patients with AKI secondary to sepsis, we found for the first time that the administration of probiotics for 7 days did not improve KFR compared with placebo treatment, but it had a trend to decrease the mortality rate, in addition to having an acceptable safety profile.KFR was observed in half of the patients in this study during the 7-day period, which was similar to what was previously reported for patients with sepsis-induced AKI [It is plausible to think that uremic toxins derived from intestinal dysbiosis promote kidney dysfunction and fibrosis, a clear example is Trimethylamine-N-oxide (TMAO), a gut microbial-dependent metabolite, plays a direct contributory role in the development and progression of CKD and was even associated with an increased risk of dying [We showed that the administration of probiotics tended to decrease mortality in rats. AKI related to sepsis has a poor prognosis. A meta-analysis reported that 45% of affected patients die during their stay in intensive care units and up to 49% die during hospitalization [Regarding other parameters that have been used to evaluate renal function in patients with AKI, such as the need for KRT and sCr concentrations, we did not observe a positive effect of the administration of probiotics. However, serum urea concentrations only improved significantly in the probiotic group, not in the placebo group, although no significant differences were found between them. This effect could be explained by the modulation of intestinal dysbiosis with probiotics and thus the attenuation of urea generation by intestinal bacteria [The finding of higher urinary volume and serum sodium levels in the placebo group than in the probiotics group could be explained by the excretion of free water and thus vascular decongestion. We believe this difference does not profoundly impact the clinical course of these patients since urinary volume and sodium remained within ranges considered safe [It is important to comment on the values of eGFR observed during the long-term follow-up of these patients (∼1 year), which was 39 mL/min/1.73 mConsidering the reported adverse events, we believe that the administration of probiotics to patients with sepsis-induced AKI was well tolerated and had an acceptable safety level. No adverse events were considered serious, and none of the patients stopped treatment due to any adverse events reported.For decades, different therapeutic agents have been investigated for the management of AKI associated with sepsis with disappointing results; the use of agents such as statins [ | PMC10512773 |
Limitations and strengths | inflammation, AKI septic | INFLAMMATION | Our results must be interpreted with caution, as this was a single-center study without an The strengths of the study lie in its design and the adequate adherence of the patient groups to treatment; to our knowledge, this is the first randomized control trial of AKI septic patients treated with probiotics [In the next study regarding this topic, we suggest measuring the microbiome between groups to quantify an actual difference between those administered the probiotics vs placebo, measure inflammatory markers given the speculation around inflammation and immune regulation. Lastly, a larger and multicenter trial. | PMC10512773 |
Conclusion | AKI, sepsis | SEPSIS | In AKI associated with sepsis, the administration of probiotics for 7 days was safe, and compared with placebo, it did not improve renal function, but there was a trend toward decreased mortality. | PMC10512773 |
Ethics approval and consent to participate | DEL | The study was approved by the Institutional Review Board HCG/CEI-1342/18, was registered with the Clinical Trials identifier NCT03877081, 03/15/2019 Informed consent was obtained from all subjects. All methods were carried out in accordance with relevant guidelines and regulations. All experimental protocols were approved by the Institutional Review Board ‘Comité de ética en Investigación del OPD Hospital Civil de Guadalajara Fray Antonio Alcalde’. | PMC10512773 | |
Authors’ contributions | RCD | CPH, MAY, GCA | JSCI, MIE, AMG-G, ACH, RCD, GCA, were responsible for the design, analysis and interpretation of the data. EMHB, ACRM, FRA, MLPM, MPC, JATG, CPH, GNB, RMG, LAV, KRL and GGG were responsible for data collection. All authors have read and approved the manuscript.The preprint version of the manuscript was posted in May 30th, 2023 DOI: | PMC10512773 |
Disclosure statement | No potential conflict of interest was reported by the author(s). | PMC10512773 | ||
Availability of data and materials | Are available in the historical archive of the Hospital Civil Fray Antonio Alcalde. If any information is requested, please contact Principal Investigator Dr. Jonathan Chávez-Iñiguez ( | PMC10512773 | ||
References | PMC10512773 | |||
Background | PONV, postoperative nausea and vomiting | The use of multimodal pharmacological prophylactic regimes has decreased postoperative nausea and vomiting (PONV) in general but it still occurs in over 60% of female patients after bariatric surgery. This study aimed to evaluate the efficacy of ST36 acupoint injection with anisodamine in prevention of PONV among female patients after bariatric surgery. | PMC10338617 | |
Methods | PONV, depression, anxiety | COMPLICATIONS | Ninety patients undergoing laparoscopic sleeve gastrectomy were randomly allocated to anisodamine or control group at the ratio of 2:1. Anisodamine or normal saline was injected into Zusanli (ST36) bilaterally after induction of general anesthesia. The incidence and severity of PONV were assessed during the first 3 postoperative days and at 3 months. The quality of early recovery of anesthesia, gastrointestinal function, sleep quality, anxiety, depression, and complications were also evaluated. | PMC10338617 |
Results | vomiting | Baseline and perioperative characteristics were comparable between two groups. In the anisodamine group, 25 patients (42.4%) experienced vomiting within postoperative 24 h compared with 21 (72.4%) in the control group (relative risk 0.59; 95% confidence interval 0.40–0.85). Time to first rescue antiemetic was 6.5 h in anisodamine group, and 1.7 h in the control group ( | PMC10338617 | |
Conclusions | obesity, nausea | OBESITY | The addition of ST36 acupoint injection with anisodamine significantly reduced postoperative vomiting without affecting nausea in female patients with obesity undergoing laparoscopic sleeve gastrectomy. | PMC10338617 |
Supplementary Information | The online version contains supplementary material available at 10.1007/s00464-023-10037-6. | PMC10338617 | ||
Keywords | PONV, postoperative nausea and vomiting, arthritis, shock | CARDIAC ARRHYTHMIAS, CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING, ARTHRITIS, SHOCK | More than 30% of postoperative patients in general still suffer from postoperative nausea and vomiting (PONV) within 24 h after surgery, and can be as high as 60–80% of high-risk patients based on Apfel score [Previous in vivo and in vitro studies have found that anisodamine can have therapeutic benefits in cardiac arrhythmias, bacteremic shock, arthritis and other conditions [There are substantial evidence supporting acupuncture as an adjunctive treatment for postoperative or chemotherapy-induced nausea and vomiting [We hypothesized that adding anisodamine to ST36 acupoint injection would obviate the need for repeated needling and improve its efficacy in preventing PONV. To compare this form of acupuncture to combination prophylaxis, we designed this double-blinded, randomized controlled trial among female patients undergoing laparoscopic sleeve gastrectomy (LSG). | PMC10338617 |
Materials and methods | PMC10338617 | |||
Trial design and ethics | This single-center prospective, randomised, double-blinded study was approved by the Ethics Committee of the Second Affiliated Hospital of Anhui Medical University, Anhui province, China (Chairperson Prof. Yanghua Tian) on December 2, 2021 (Ref YX2021-114) in accordance to the principles of the Declaration of Helsinki. The trial was registered in clinicaltrials.gov (NCT05240482) and carried out at the Second Affiliated Hospital of Anhui Medical University from 20 February to 6 July 2022. Written informed consent was obtained from all participants. The time period of this trial consisted of a 72-h follow-up after bariatric surgery in the hospital and a follow-up period of an additional 3 months after discharge.The LSG was performed by the same bariatric surgical team, basically referring to the International Sleeve Gastrectomy Expert Panel Consensus Statement [ | PMC10338617 | ||
Participants | OSAHS, obesity, psychological disorder, endocrine disorder, obstructive sleep apnea hypopnea syndrome, rash, liver, coagulation derangements, allergic diathesis | OBESITY, OBSTRUCTIVE SLEEP APNEA HYPOPNEA SYNDROME, GASTROESOPHAGEAL REFLUX, ENDOCRINE DISORDER, DISEASES OF THE HEART, SYSTEMIC INFECTION | All adult female patients with an American Society of Anesthesia (ASA) physical status I–III, scheduled for elective LSG surgery were screened. The exclusion criteria: contraindications to acupoint injection, such as a local rash at the site of skin injection or systemic infection, any history of allergic diathesis for drugs used in the study, gastroesophageal reflux, severe obstructive sleep apnea hypopnea syndrome (OSAHS), uncontrolled systemic diseases of the heart, lung, kidney, or liver, coagulation derangements, psychological disorder, current use of medications before surgery that would interference with relevant assessments (including the use of opioids, antiemetics or glucocorticoids), obesity due to a diagnosed endocrine disorder and without consent. | PMC10338617 |
Randomization and blinding | All participants were randomly assigned to anisodamine group (bilateral ST36 acupoint injection with anisodamine) or control group (bilateral ST36 injection with normal saline) in a 2:1 ratio. The randomization was computer-generated by using The allocation sequence was concealed until the end of data collection, and the drug or placebo was prepared by the independent researcher thus maintaining blinding of the patients, acupuncturist, outcome assessors. | PMC10338617 | ||
Standardized anesthesia management | Dexmedetomidine (0.5 μg kg | PMC10338617 | ||
ST36 acupoint injection and PONV management | PONV, Acupuncture | Acupuncture treatment was performed by a licensed acupuncturist who had at least 5 years of acupuncture experience. All participants received bilateral ST36 acupuncture injection with anisodamine (5 mg/1 ml per site) or normal saline (1 ml per site) [All patients received prophylaxis for PONV with dexamethasone (10 mg i.v.) during GA induction, and dorasetron (12.5 mg) at 20 min before the end of surgery [ | PMC10338617 | |
Outcomes | PONV, depression, vomiting, anxiety | SECONDARY, POSTOPERATIVE COMPLICATIONS | The primary outcome is the incidence of vomiting within the first 24 h postoperatively.The secondary outcomes include: the time to the first rescue antiemetic; the incidence of PONV assessed at 2, 6, 48, and 72 h after surgery; the severity of PONV measured by the Verbal Rating Scale (VRS) (none, mild, moderate, or severe) at the same time points; the incidence of postoperative complications; the early recovery outcomes indicators (the time of first drink, ambulate and flatus) and the postoperative LOS. Time to first rescue antiemetic was defined as the time from extubation to the first rescue antiemetic. The changes in gastrointestinal function, sleep-related quality of life, anxiety and depression status from baseline to postoperative 3 months were assessed by the Gastrointestinal Symptom Rating Scale (GSRS) [ | PMC10338617 |
Statistical analysis | postoperative vomiting, vomiting | Based on the incidence of postoperative vomiting in our pilot study, the proportions of patients who experienced vomiting within 24 h after surgery in the control group and anisodamine group were 80% and 40% respectively (Table S1). The sample size was calculated to be 84 patients (28 in control and 56 in anisodamine), with a significance level of 5% in the two-sided test and a detection power of 95% which allowing for 15% loss to follow-up.Continuous variables were presented as mean ± standard deviation (SD) if normally distributed or median (interquartile ranges, IQR) if not. The assumption of data normality was confirmed using a Shapiro-Wilk test. The comparisons between groups were conducted with | PMC10338617 | |
Discussion | PONV, vomiting, patients-specific | In this trial, anisodamine was creatively used on ST36 acupoint injection in female patients during LSG. During the first postoperative 24 h, we successfully observed a significant reduction of the incidence of vomiting, an increase of the time to first rescue antiemetic, as well as less rescue antiemetic in patients with anisodamine injection. It’s noted that ST36 acupoint injection without or with anisodamine had no effect on the early recovery in the hospital and quality of life after discharge.Since female gender is one of the strongest patients-specific predictors among recognized independent risk factors for PONV [Anisodamine, scopolamine and atropine are common tropine alkaloids with similar pharmacological effects [Acupuncture, as a nonpharmacologic prophylaxis therapy, has been proposed as an alternative option for multiple multimodal antiemetic therapy because of its safety and affordability [In addition to prophylactic antiemetics, minimizing opioid use through multimodal analgesic regimens can also be effective in reducing the risk of PONV. We established a multimodal analgesic regimen, including perioperative administration of dexmedetomidine and transverse abdominal plane block, in the standardized GA protocol to partially reduce the risk of PONV. A meta-analysis including 697 participants underwent bariatric surgery also indicated that dexmedetomidine significantly reduced PONV in post anesthesia care unit and POD1 with OR from 0.24 to 0.28 [ | PMC10338617 | |
Strengths and limitations | postoperative vomiting, postoperative nausea., PONV, Vomiting | This trial, based on previous studies, simplifies the procedure and duration of acupuncture and provides a comparable preventive effect on postoperative vomiting, which contributes to the popularization of acupuncture in preventing PONV. The results also provide strong evidence using anisodamine for PONV prevention.This trial has several limitations. First, this study was conducted in a population with a high risk of PONV and achieved a 30% reduction. It was considered unlikely that this intervention could achieve a comparable effect among female patients undergoing other surgical groups. Vomiting in postoperative 24 h still occurred in 42% of patients who received ST36 acupoint injection with anisodamine. Thirdly, compared to standard prophylaxis, ST36 acupoint injection with anisodamine did not reduce the incidence of postoperative nausea. In addition, the leak rate in this study was higher than the previous reported. Further exploration of effective preventions for this population is still needed. | PMC10338617 | |
Conclusions | PONV | ST36 acupoint injection with anisodamine had incremental benefit when used as part of combination prophylaxis for reducing PONV. It could be a new option contained in multimodal prophylactic antiemetic regime in female patients undergoing laparoscopic sleeve gastrectomy. | PMC10338617 | |
Funding | This study was supported by Basic and clinical cooperative research promotion plan of Anhui Medical University (Grant 2019xkjT026), the National Natural Science Foundation of China (Grant 81801050), Scientific Research Platform Base Construction and Promotion Project of Anhui Medical University (Grant 2020xkjT060), Key research and development program of Anhui Province (Grant 2022e07020048), and Scientific Research Fund of Anhui Medical University (Grant 2022xkj040). | PMC10338617 | ||
Declarations | PMC10338617 | |||
Disclosures | Dr. Qi Xue, Qijing Xing, Ling Dong, Min Guo, Xiaoyan Zhang, Xinchun Wei, Dr. Benli Jia, Prof. Yong Wang, Hong Chen, Prof. Xianwen Hu, Prof. Hong Liu, Prof. Ye Zhang, Prof. Gordon Tin Chun Wong, Dr. Chunxia Huang have no conflicts of interest or financial ties to disclose. | PMC10338617 | ||
References | PMC10338617 | |||
Keywords | Open access funding provided by SCELC, Statewide California Electronic Library Consortium | PMC10412661 | ||
Introduction | TNBC, mTNBC, breast cancers, tumor | TRIPLE-NEGATIVE BREAST CANCER, TUMOR, BREAST CANCER, CHEMOTHERAPY EFFECTS, SOLID TUMORS | Triple-negative breast cancer (TNBC) accounts for 10–15% of all breast cancers and is characterized by lack of estrogen receptor (ER), progression receptor (PR), and human epidermal growth factor receptor 2 (HER2) overexpression. TNBC is molecularly heterogeneous, and metastatic TNBC (mTNBC) carries poor prognosis due to the overall lack of effective targeted therapy [Pembrolizumab, a monoclonal anti-PD-1 antibody, is approved for the treatment of multiple solid tumors [Multiple preclinical studies have demonstrated an immune potentiating effect of anthracycline [We hypothesized that the combination of pembrolizumab and doxorubicin is synergistic in facilitating both cellular immune response and chemotherapy effects in treatment of mTNBC. The current trial, although small, was designed to test the safety and efficacy of the combination of pembrolizumab and doxorubicin in anthracycline-naïve patients with mTNBC. In addition to the safety and efficacy data, we also report tumor immune biomarkers and peripheral blood immune subset composition including dynamic changes over time that should be validated in larger studies. | PMC10412661 |
Methods | PMC10412661 | |||
Study design and patient population | TNBC, mTNBC | ONCOLOGY, DISEASE, IMMUNODEFICIENCY | This open-label single institutional phase I trial for patients with metastatic TNBC was conducted between March 2016 and November 2019 with institutional review board (IRB) approval in accordance with the World Medical Association Declaration of Helsinki, International Conference on Harmonization Good Clinical Practice guidelines, and the US code of federal regulations. Informed voluntary consent forms were signed by all patients prior to study entry. This study is registered at the ClinicalTrials.gov under number NCT02648477. Main eligibility criteria included patients who were 18 years or older with mTNBC defined by ASCO/CAP guideline, no prior anthracycline exposure, measurable disease based on RECIST 1.1, and ≤ 2 prior systemic anticancer therapies in the metastatic setting. Additional inclusion criteria were an Eastern Cooperative Oncology Group (ECOG) performance status 0–1; life expectancy ≥ 3 months; and adequate bone marrow, renal, and hepatic function. Main exclusion criteria included prior anthracycline therapy; prior pembrolizumab therapy; or prior diagnosis of immunodeficiency, use of systemic steroid, or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. | PMC10412661 |
Study procedure | Eligible patients received pembrolizumab 200 mg IV with doxorubicin 50–60 mg/m | PMC10412661 | ||
Clinical response statistics | toxicities | SECONDARY | The primary objective of the study was to evaluate ORR of pembrolizumab plus doxorubicin. The secondary objective was to assess clinical benefit rate (CBR) (no progression for > 24 weeks), progression-free survival (PFS), and overall survival (OS). Additional secondary endpoints were to assess the safety and tolerability of anthracycline plus pembrolizumab regimen. Responses were assessed by RECIST 1.1, and safety analysis was carried out based on toxicities assessed by CTCAE 4.0.A safety lead-in employing a 3-at-risk rolling design was used [ | PMC10412661 |
Tumor immune biomarkers | tumor, Tumor, Breast Cancer | TUMOR, TUMOR, BREAST CANCER | Tumor biopsies were formalin-fixed paraffin-embedded (FFPE). Percentage of stromal TILs (sTILs) in tumor was evaluated using hematoxylin and eosin (H&E) diagnostic sections per International Immuno-Oncology Biomarker Working Group on Breast Cancer Guidelines [ | PMC10412661 |
Peripheral blood immune correlatives | SEPARATION | Peripheral blood was collected at baseline (pre-treatment), C2D1, and post-cycle 3 (C4D1 or C6D1) for flow cytometry analysis. Peripheral blood was obtained using heparin collection tubes, and peripheral blood mononuclear cells (PBMCs) were isolated within 6 h using Ficoll-Paque Separation according to manufacturer’s instructions (GE Healthcare). PBMCs were cryopreserved in 10% DMSO, 90% FBS and thawed rapidly for flow cytometry analysis. Single-cell suspensions were prepared on ice in 2% FBS in PBS. Antibody cocktails were diluted in Brilliant Violet Buffer (BD Biosciences). Samples were acquired using a Cytek Aurora spectral cytometer with user settings established by Spectroflo QC beads. Unmixing and compensation were performed in Spectroflo software using a mix of reference controls from either single stained PBMCs or single stained OneComp compensation beads (eBioscience). Samples were stained with fluorescently tagged antibodies (Supplemental Table 4). Antibodies were titrated for optimal signal-to-noise ratio prior to use. Flow cytometry analysis was performed using Flowjo vX, and the CATALYST R package was used for FlowSOM analysis and UMAP projections [ | PMC10412661 | |
Correlative studies statistics | Graphs and statistics were performed using GraphPad Prism 8.4.3. Statistics were generated using unpaired two-tailed Student T tests or multiple comparisons T tests with Dunnet’s or Holm-Sidak corrections as described. Calculated p values are displayed as * | PMC10412661 | ||
Results | PMC10412661 | |||
Patients | anthracycline-naive, death, respiratory failure, chronic respiratory disease | RESPIRATORY FAILURE, CHRONIC RESPIRATORY DISEASE | Between March 2016 and November 2019, a total of 10 patients were enrolled and treated with doxorubicin and pembrolizumab. The trial was stopped early due to poor accrual because of difficulty in identifying patients who were anthracycline-naive. All 10 patients were included in the safety evaluation. One patient with chronic respiratory disease developed respiratory failure which led to death and was not evaluable for efficacy. Baseline patient characteristics are listed in Table Baseline patient characteristics ( | PMC10412661 |
Treatment | The first 3 patients received doxorubicin at 50 mg/m | PMC10412661 | ||
Response and survival | sepsis, death, neutropenia, Tumor | SEPSIS, NEUTROPENIA, TUMOR | Of 10 patients treated, one patient (age 87) developed neutropenia, sepsis, and death after 1Relative Change in Tumor Size ( | PMC10412661 |
Exceptional responder | ER/PR-positive, adenopathy, high-grade TNBC | DISEASE, MAY, ADENOPATHY, RESIDUAL DISEASE, PATHOLOGY, HER2-NEGATIVE BREAST CANCER | Patient was initially diagnosed with ER/PR-positive, HER2-negative breast cancer in 2002. She was treated with surgery, adjuvant cyclophosphamide methotrexate fluorouracil (CMF), and radiation therapy, followed by 5 years of adjuvant tamoxifen. In 2011, patient who recurred with high-grade TNBC received neoadjuvant docetaxel and cyclophosphamide, followed by bilateral mastectomy. Surgical pathology demonstrated yPT2N1 residual disease. Patient further received adjuvant gemcitabine and cisplatin and then had progressive disease with adenopathy in the axilla and mediastinum. Patient received the following lines of therapy: first-line carboplatin and paclitaxel from September 2015 to December 2016; second-line Xeloda from January 2017 to April 2017; third-line doxorubicin; and 22 cycles pembrolizumab from May 2017 to July 2018. Patient had an exceptional response but progressed on study. | PMC10412661 |
Treatment associated toxicities | neutropenia | ADVERSE EVENTS, ADVERSE EVENT, NEUTROPENIA | Grade 3–4 adverse events (AEs) per CTCAE 4.0 were neutropenia Grade 2–4 adverse event with attributions in “definite”, “possible”, “probable” per CTCAE 4.0 | PMC10412661 |
Tumor immune biomarkers | PD, tumor | DISEASE, TUMOR | PD-L1 (22C3) testing showed 4 patients who were PD-L1 positive, 4 patients who were PD-L1 negative, and 2 patients who did not have PD-L1 results. Stromal TILs analysis of available tumor tissue was performed for 4 patients and showed 1 CR patient with 90% TILs (lymph node), 1 UPR patient with 5% TILs (axillary mass), 1 UPR patient with 10% TILs (liver), and 1 PD patient with 3% TILs (axillary mass). Five patients did not have TILs analysis due to exhausted tissue block. Overall, no association between baseline levels of TILs or PD-L1 status with response was observed (Supplemental Table 2). We do note that the patient with CR had 90% TILs in the biopsied lymph node, although we were unable to assess TILs in the patient’s other disease sites such as lung and dermal tissues. It is therefore unclear if the high TIL density is associated with the biopsy site of lymph node or with patient response. Genomic alterations for patients with sequencing results did not show association with response (Supplemental Table 3). | PMC10412661 |
PMBC immune cell composition | PD, CR/PR/SD | Baseline and on-treatment characteristics of peripheral blood immune cell composition were analyzed in response to therapy. Two high parameter (> 28) spectral cytometry panels were designed to identify both broad immune subsets and detailed T cell subsets. At baseline, we found no association of response and frequencies of CD3 + T cells, natural killer (NK) cells, natural killer T cells (NKT), γδ T cells, or B cells within total CD45 + leukocytes (Supplemental Fig. 1A). Intriguingly, the patient with PD had the highest fraction (11.0% PD vs. 6.3% mean CR/PR/SD) of terminally differentiated NK cells (CD56dim CD16 +) among all NK cells at baseline (Supplemental Fig. 1B). Moreover, the patient with PD also demonstrated fewer naïve B cells (48.4% in PD vs. 75.8% mean in CR/PR/SD and higher levels of plasmablasts (15.2% in PD vs. 1.5% mean in CR/PR/SD) among all B cells compared to other patients (Supplemental Fig. 1C). No differences in the subset composition of monocytes (classical, ClMono; intermediate, IntMono; non-classical, NcMono) or dendritic cells (conventional type 1, cDC1; conventional type 2, cDC2; plasmacytoid, pDC) were observed (Supplemental Fig. 1D and E). We then examined how these major immune populations changed during treatment. From pre-treatment to C2D1, the fraction of CD3 + T cells among total CD45 + cells increased significantly ( | PMC10412661 | |
T cell compositional changes over the course of treatment | heterogenous, PD, tumor, CM | TUMOR | Given the increased frequency of T cells from pre-treatment to C2D1, we next set to dissect features of T cell subsets in greater detail over the course of therapy and in context of tumor response. Within CD8 + and CD4 + T cell populations, we found no significant differences in frequencies of canonical naïve, central memory (CM), effector memory (EM), or effector memory CD45RA + (EMRA) populations at baseline (Supplemental Fig. 2). However, the patient with PD had the lowest frequency of naïve CD8 + T cells (5.7% vs. 22.6% mean in CR/PR/SD) and second lowest frequency of naïve CD4 + T cells (20.1% vs. 39.7% mean in CR/PR/SD) among all patients.Unbiased clustering was performed and identified 20 unique clusters of T cell subsets that were then manually annotated based on marker expression (Fig. T cell subset in association with response to doxorubicin and pembrolizumab. Circulating T cells were assessed by flow cytometry for complex phenotyping. Dimensionality reduction by the FlowSOM algorithm was performed to identify T cell metaclusters in an unbiased manner. Baseline frequencies of T cell subsets were heterogeneous across different response groups (Fig. We next asked how T cell composition was altered over the course of therapy. Interpatient variability in frequency changes was high across all T cell subsets, with no significant differences between pre-treatment frequencies and frequencies at C2D1 or Post Cycle 3 (Supplemental Fig. 3A and B). Similarly, fold changes in T cell populations were heterogenous across patient response status (Supplemental Fig. 3C and 3D). Surprisingly, the cell populations that showed the greatest change over the course of therapy were an increase in naïve CD8 + and naïve CD4 + T cells from pre-treatment to C2D1 (Dynamics of a proliferating CD8 + T cell population in patients treated with doxorubicin and pembrolizumab. Ki-67 + proliferating T cells were identified as shown in representative dot plots from pre-treatment and C2D1 ( | PMC10412661 |
Expansion of a proliferative, exhausted CD8 + T cell population over the course of treatment | PD | Among all patients, the increase in CD8 + proliferating T cells was greatest in the patient with CR (1.7-fold change vs. mean 0.8 in PD/SD/PR), which led us to further investigate this T cell subset. From pre-treatment to C2D1, CD8 + proliferating T cells increased from 5.2 to 9.2% in the patient with CR but reduced from 3.3 to 1.1% in the patient with PD (Fig. We next assessed dynamics of PD-1Phenotype changes of PD-1 high proliferating T cells over the course of treatment with doxorubicin and pembrolizumab for one patient with CR. CD127 expression and CD38 expression was compared between Ki-67- (gray), PD-1Since the generation of a PD-1 | PMC10412661 | |
Discussion | PD, mTNBC, pembrolizumab-treated melanoma | PROLIFERATIVE, BREAST CANCER | Although limited by small sample size, the results of the current trial provide evidence that doxorubicin can be safely combined with pembrolizumab with Several studies have demonstrated utility of chemo-immunotherapy combination in treatment of mTNBC. FDA accelerated approval was granted to atezolizumab in March 2019 based on data from IMpassion130 trial (NCT02425891) which demonstrated a statistically significant benefit to PFS with the atezolizumab and nab-paclitaxel vs. nab-paclitaxel alone (HR, 0.60; 95% CI 0.48–0.77; Anthracyclines are among the most active agents for treatment of breast cancer. Anthracycline elicited immunogenic apoptosis in the preclinical setting [Our profiling of T cell dynamics in mTNBC patients treated with doxorubicin and pembrolizumab provides insight into immunotherapy response mechanisms. In this study, baseline immune biomarkers were not associated with response to treatment. In the patient with PD, significantly low levels of naïve CD8 + and CD4 + T cells at baseline indicating the presence of naïve CD8 + and CD4 + T cell is necessary for response to immune checkpoint blockade. Indeed, recent evidence has suggested that PD-1 blockade instills anti-tumor T cell immunity via the generation of non-preexisting T cell clonotypes [Importantly, we find that the expansion and not baseline percentages of proliferative exhausted CD8 + T cells that correlates with response to PD-1 blockade, which is in agreement with studies of pembrolizumab-treated melanoma patients [Increasing attention is now being turned toward understanding how existing cytotoxic chemotherapies generate or shape an immune response, and how these may best partner with immunotherapies [In conclusion, anthracycline-naïve patients with mTNBC treated with the combination of pembrolizumab and doxorubicin showed an encouraging response rate and robust T cell responses. The combination was generally well tolerated, and the utility of this combination needs to be further studied. | PMC10412661 |
Supplementary Information | PD, SD, CM | DISEASE PROGRESSION, DISEASE | Below is the link to the electronic supplementary material.Supplemental Fig. 1. Broad immune characterization of peripheral blood of patients treated with doxorubicin and pembrolizumab at baseline. A) Pre-treatment peripheral blood samples were examined by flow cytometry for lymphocyte composition frequencies, including CD3 + T cells, CD3 − CD56 + natural killer (NK) cells, CD3 + CD56 + natural killer T (NKT) cells, TCRγδ T cells, and CD19 + B cells. B) The composition of NK cells was further assessed for CD56bright (early), CD16bright (mature), and CD56dim CD16dim (terminal) NK cell subsets. C) B cell subsets were assessed as IgD + CD27- (Naïve), IgD- CD27 + (memory), or CD38 + plasmablasts. D) Monocyte subsets were assessed as a fraction of a myeloid cell gate for frequencies of CD14 + CD16- classical monocytes (clMono), CD14 + CD16 + intermediate monocytes (intMono), and CD14- CD16 + non-classical monocytes (ncMono). E) Dendritic cell subsets were similarly assessed as a fraction of a myeloid cell gate for frequencies of CD141 + dendritic cells (cDC1), CD1c + dendritic cells (cDC2), and CD123 + plasmacytoid dendritic cells (pDC). F) Percent change from pre-treatment to C2D1 (purple) and from pre-treatment to post Cycle 3 (green) is shown. Patient with disease progression (PD, n = 1) is depicted in dark blue, stable disease (SD, n = 2) in light blue, confirmed and unconfirmed partial response (PR = 5) in dark red, and complete response (CR, n = 1) in light red. *p < 0.05. Supplemental Fig. 2. Canonical T cell subsets at baseline. CD8 + T cells (A) and CD4 + T cells (B) were further assessed by flow cytometry for frequencies of naïve (CCR7 + , CD45RA +), central memory (CM; CCR7 + , CD45RA-), effector memory (EM; CCR7-, CD45RA-), and effector memory CD45RA + (EMRA, CCR7-, CD45RA +) cell subsets. Frequencies of regulatory T cells (Tregs) were also assessed within CD4 + T cells. Data are shown separately for patients with PD (dark blue), SD (light blue), PR (dark red), and CR (light red). Supplemental Fig. 3. Detailed T cell composition changes over the course of therapy in patients treated with doxorubicin and pembrolizumab. Percentage change of all identified CD8 + T cell subsets (A) and CD4 + T cell subsets (B) from pre-treatment to C2D1 (purple) and pre-treatment to post Cycle 3 (red). Fold change in CD8 + (C) and CD4 + (D) T cell subsets are shown separately for patients with PD (dark blue), SD (light blue), PR (dark red), and CR (light red). Supplemental Fig. 4. Detailed dynamics of proliferating CD8 + T cells in patients treated with doxorubicin plus pembrolizumab. Pre-treatment frequencies (A), fold change from pre-treatment to C2D1 (B), and fold change from pre-treatment to C3D1 (C) are shown for PD-1low Ki-67 + and PD-1high Ki-67 + CD8 + T cells. PD (dark red), SD (light red), PR (light blue), and CR (dark blue). Fold change of all T cell subsets, with the inclusion of identified PD-1low Ki-67 + and PD-1high Ki-67 + populations, from pre-treatment to C2D1 (D) and from pre-treatment to C3D1 (E). (PDF 243 kb) | PMC10412661 |
Acknowledgements | Cancer | CANCER | Merck provided research funding this study. The COH Biostatistics Core and Analytical Cytometry Core was supported by the National Cancer Institute of the National Institutes of Health (P30CA033572). This work was also supported by the National Institutes of Health (NIH)/National Cancer Institute (NCI) grant RO1CA206911 (Emily Wang) and the Circle 1500 philanthropic group at City of Hope. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NCI. | PMC10412661 |
Author contributions | GS designed and supervised the study; JW and YY supervised data collection and analysis, manuscript preparation; XG, JL and SEY provided clinical data, study operations support, and manuscript preparation; PHF, CR, and YC provided statistical design and data analysis; CE, WG, and PPL performed and interpreted correlative studies; CE contributed to manuscript preparation; MM, AT, NM provided data collection; MK, GS, JM, and JW consented patients to the study; and all authors approved the manuscript. | PMC10412661 | ||
Funding | Cancer | CANCER | Open access funding provided by SCELC, Statewide California Electronic Library Consortium. This study was funded by Merck and supported by City of Hope Comprehensive Cancer Center. | PMC10412661 |
Data availability | All data and materials are presented in the article and additional files. Raw data are available upon request. | PMC10412661 | ||
Declarations | PMC10412661 | |||
Conflict of interest | Dr. Yuan has contracted research sponsored by Imugene, Minerva, Merck, Novartis, Genentech, and Pfizer, is a consultant for Pfizer, Immunomedics, and is on the Speakers Bureau for Genentech, AstraZeneca, Daiichi Sankyo, and Gilead. The other authors declare that they have no competing interests. | PMC10412661 | ||
Ethics approval and consent to participate | The study was approved by City of Hope IRB registered under NCT02648477. Procedures were performed in accordance with the ethical standards of the City of Hope, the national research committee, and the 1964 Declaration of Helsinki and International Conference on Harmonization Guidelines for Good Clinical Practice and later amendments. | PMC10412661 | ||
Consent for publication | Not applicable. | PMC10412661 | ||
References | PMC10412661 | |||
Abstract | MPD, ESRD | END-STAGE RENAL DISEASE, ESRD, COMPLICATIONS | These authors contributed equally to this work.During urgent-start peritoneal dialysis (USPD) in end-stage renal disease (ESRD) patients, both adequate dialysis and skill training for fluid exchange are essential. However, automated peritoneal dialysis (APD) alone or manual fluid exchange peritoneal dialysis (MPD) alone could meet the above demands. Therefore, our study combined APD with MPD (A-MPD), and compared A-MPD with MPD, aiming to find the most appropriate treatment mode. This was a single-center, prospective, randomized controlled study. All eligible patients were randomized into the MPD and A-MPD groups. All patients underwent a five-day USPD treatment 48 h after catheter implantation, and they were followed up for six months after discharge. Overall, 74 patients were enrolled in this study. Among these, 14 and 60 patients quit due to complications during USPD and completed the study (A-MPD = 31, MPD = 29), respectively. Compared with MPD, the A-MPD treatment mode had a better effect on removing serum creatinine, blood urea nitrogen, and potassium and improving serum carbon dioxide combining power levels; it had less time expenditure on the fluid exchange by nurses ( | PMC10269400 |
Keywords | PMC10269400 | |||
Introduction | bacteremia, PD, MPD, ESRD | END-STAGE RENAL DISEASE, ESRD | Peritoneal dialysis (PD) is an effective treatment for patients with end-stage renal disease (ESRD). PD initiation is usually recommended at least two weeks after peritoneal dialysis catheter (PDC) implantation [Urgent-start peritoneal dialysis (USPD) is defined as the initiation of PD within two weeks of PDC implantation. Interestingly, our previous meta-analysis showed that all-cause mortality was comparable between patients undergoing USPD and urgent-start HD; however, the incidence of bacteremia was higher in patients receiving urgent-start HD [PD is usually performed using a manual fluid exchange peritoneal dialysis (MPD) or automated peritoneal dialysis (APD). APD has been proven to be a safe and effective alternative to urgent-start HD [Both adequate dialysis and skill training for fluid exchange are essential in USPD. However, APD alone or MPD alone could not meet the above demands. We hypothesize that a combination of APD with MPD (A-MPD) in USPD could have a better effect in removing small-molecule toxins and skill training. It may also allow the patients to receive multiple PD modes and choose the most suitable one for them. In this randomized controlled study, we compared A-MPD with MPD, aiming to investigate the efficacy and practicability of A-MPD and seek the most appropriate mode in ESRD patients undergoing USPD. | PMC10269400 |
Materials and methods | PMC10269400 | |||
Design | WEST | This single-center, prospective, randomized, open-label, controlled study was approved by the Ethics Committee of West China Hospital of Sichuan University (approval number: 2020-891) and registered in the Chinese Clinical Trials Registry ( | PMC10269400 | |
Participants | ESRD, PD, electrolyte disorders, sepsis, acute heart failure | SEPSIS, RECRUITMENT, ELECTROLYTE DISORDER, COMPLICATIONS, UREMIC ENCEPHALOPATHY, WEST, SYSTEMIC INFECTION, HEART, ESRD, DISEASES, ACUTE HEART FAILURE | Nephrologists provided patients with ESRD requiring urgent dialysis with detailed information on possible treatment modalities. Individuals who preferred PD and were suitable for PD were eligible if they were aged 18–75 years. The study recruitment period was from March to December 2021 at the Department of Nephrology, West China Hospital of Sichuan University.Exclusion criteria were as follows: (1) conditions requiring emergent hemodialysis, including uncontrolled severe acute heart failure (New York Heart Association, Grade IV), uremic encephalopathy, severe electrolyte disorders (serum potassium [s-K+] > 6.5 mmol/L), and unstable vital signs; (2) complications associated with other serious diseases, such as severe systemic infections or sepsis; and (3) refusal to participate in the study; and (4) participation in other clinical studies.All eligible patients were randomized into two groups according to a computer-generated randomization chart; the MPD and A-MPD groups. In addition, general information was recorded, including age, sex, causes of ESRD, body mass index (BMI), body surface area (BSA), surgical PDC implantation method, and laboratory measurements. | PMC10269400 |
PDC implantation and PD schemes | PD | All patients received Tenckhoff catheters and prophylactic antibiotics were administered preoperatively. Two experienced nephrologists performed catheter implantations using open dissection, and those through laparoscopy were performed by a surgeon. All the PDC were implanted at the day surgery center. USPD was initiated 48 h after PDC implantation and continued for five days during hospitalization.The PD schemes were based on the patients’ BSA [Standard prescription for the patients of USPD.A-MPD: automated peritoneal dialysis combined with manual fluid exchange peritoneal dialysis; MPD: manual fluid exchange peritoneal dialysis.Nurses treating PD taught and assisted patients in completing manual fluid exchanges and performing the cyclers. All patients were trained in manual fluid exchange by nurses treating PD during hospitalization and were administered the test before discharge. However, patients who failed the test were retrained and reevaluated until they qualified. The time spent by the nurses treating PD and the test scores of the patients were recorded. Finally, all patients were followed up six months after discharge. | PMC10269400 | |
Termination of the study | PD, hernia, peritonitis | PERITONITIS, COMPLICATIONS, LEAKAGE | When patients experienced complications, such as leakage and mechanical complications of PDC, which disturbed normal PD therapy, medication and conservative treatment were administered, and PD was suspended for 3 days. In addition, the patients continued the study and completed the five-day USPD after such complications were resolved. Otherwise, the patients would terminate the study, and further treatment would involve replacing the PDC under laparoscopy, suspension of PD for a longer time, or initiating urgent hemodialysis if needed. The patients also terminated the study once peritonitis or inguinal hernia occurred. | PMC10269400 |
Outcome measurements | catheter-related infection, exit-site infection, inguinal hernia, PD, tunnel infection, peritonitis, Catheter-related infections | PERITONITIS, COMPLICATIONS, LEAKAGE | The primary outcomes included clearance of small-molecule uremic toxins and PD technical survival rate. All patients underwent laboratory measurements before and after USPD, including serum levels of creatinine, blood urea nitrogen, albumin, sodium, potassium, magnesium, phosphorus, carbon dioxide combining power (COSecondary outcomes included the incidence of short-term PD-related complications (including peritoneal fluid leakage, PDC malfunction, peritonitis, catheter-related infection, and inguinal hernia), time expenditure of nurses treating PD, and patient test scores. Catheter-related infections included exit-site infection and tunnel infection [ | PMC10269400 |
Statistical analysis | All statistical analyses were performed using the Statistical Package for Social Sciences (SPSS) software (version 26.0). Continuous variables, which conformed to the normal distribution, were expressed as mean ± standard deviation, and comparisons between groups were performed using the Student’s | PMC10269400 | ||
Results | PMC10269400 | |||
Demographic and baseline characteristics | MPD | Overall, 74 patients were enrolled in this study. Among these, 60 completed the study, including 29 and 31 patients in the MPD and A-MPD groups, respectively (Flow diagram of enrollment, randomization, and follow-up of patients. MPD: manual fluid exchange peritoneal dialysis; A-MPD: combination of automated peritoneal dialysis (APD) with MPD; PDC: peritoneal dialysis catheter.Demographic and baseline characteristics.eGFR: estimated glomerular filtration rate; COCorrected serum calcium = serum calcium(mmol/L)+(40 albumin(g/L))*0.02. | PMC10269400 | |
Comparison of the laboratory parameters | After the five-day USPD treatment, the serum levels of creatinine, blood urea nitrogen, albumin, potassium, magnesium, and iPTH decreased dramatically (Self-comparison of laboratory parameters before and after USPD within groups.COComparison of the difference of laboratory parameters before and after USPD between the two groups.COCorrected serum calcium = serum calcium(mmol/L)+(40 albumin(g/L))*0.02.Δ1 and Δ2, the value for the difference before and after USPD (before USPD – 5 days after USPD) in A-MPD group and MPD group, respectively. | PMC10269400 | ||
Short-term PD-related complications | COMPLICATIONS | In total, 21 patients experienced short-term complications during USPD treatment (PD-related complications during 5-day USPD treatment.PDC: peritoneal dialysis catheter.Reasons of quitting the study.PDC: peritoneal dialysis catheter. | PMC10269400 | |
Time expenditure of nurses treating PD and patients’ test scores | PD | The mean time expenditure for dialysate exchange by nurses for the A-MPD group was 248.45 ± 6.20 min during the five days (including two manual fluid exchanges and connection and disconnection of cycler per day). The mean time expenditure in the MPD group was 256.86 ± 11.70 min/day (including four manual fluid exchanges per day). The time expenditure of nurses treating PD in the A-MPD group was significantly shorter than that in the MPD group (The time expenditure of PD nurses and test score of patients.The mean test scores of patients in the A-MPD and MPD groups were 183.63 ± 15.83 and 167.59 ± 20.32, respectively. Notably, patients’ test scores in the A-MPD group were significantly higher than those in the MPD group ( | PMC10269400 | |
PD technique survival and patient survival | PD, peritonitis | PERITONITIS | Here, 60 patients were followed up for 6 months. Two patients in the A-MPD group developed peritonitis during follow-up; one underwent removal of the PDC and was switched to hemodialysis, while the other resumed peritoneal dialysis after antibiotic treatment. In contrast, one patient in the MPD group received renal transplantation, and two patients were lost to follow-up. No statistically significant difference in PD technical survival was found between the two groups (Technique and patient survival during 6 months. | PMC10269400 |
Discussion | PD, ’ mistakes, MPD | COMPLICATION, COMPLICATIONS, LEAKAGE | This study is the first to combine APD with MPD in the treatment of USPD. Compared with MPD, the A-MPD mode had a better effect on removing small-molecule toxins. Simultaneously, the A-MPD mode could effectively save time for nurses treating PD and improve the skill training of patients. The incidence of short-term complications, PD technique survival, and mortality were not significantly different between the two modes. Therefore, the A-MPD mode may be recommended as an adaptable and suitable PD mode for USPD treatment.Recent studies have shown that the APD mode has a better effect on removing small-molecule toxins than MPD in USPD [The design of the A-MPD model should consider the adequacy of dialysis, the practicability, the time expenditure of nurses treating PD, and the tolerance of patients. For the MPD mode, previous studies have adopted four to six exchanges per day [An interesting finding of our study is that patients in the A-MPD group received higher test scores with shorter time expenditures for nurses treating PD. Once the cycler was connected to the PDC, the nurses treating PD did not need to wait by the patient’s bed or weigh the dialysate, which obviously reduces time expenditure. This probably gave the nurses treating PD more time and patience to conduct patient training and promptly correct patients’ mistakes during dialysate exchange. Meanwhile, if the patients only had APD, they learned MPD using only the artificial model. The patients then had no opportunity to do MPD on themselves and had no real practical experience. This finding further demonstrates that A-MPD could reduce the burden of the nurse and improve the skill of patients, which is more suitable than APD or MPD alone.Previous studies have found that the APD mode could increase the loss of serum albumin more than MPD in patients during USPD [Dialysate leakage is a common complication after PDC implantation, and its incidence in USPD reported in the literature ranges from 2.2% to 37% [No significant difference in the PD technique survival or mortality was found between the two groups during the six-month follow-up period. Therefore, we consider that the five-day USPD treatment would not affect the PD technical survival rate and mortality during follow-up because of our study’s limited sample size and many other factors that affect PD after discharge.In this study, the PD catheters were implanted by open surgical dissection or laparoscopy. Recently, percutaneous catheterization was more and more widely used in USPD. A real-world, multicenter, retrospective cohort study found percutaneous catheterization was more commonly used for a break interval <24 h and laparoscopic or open surgery method was more commonly used for a break interval >7 days [Our study had some limitations. First, it was a single-center study with a limited number of patients. Therefore, more multicenter studies with larger sample sizes are required. Second, the optimal prescriptions for USPD still need to be determined. Here, we considered the dialysis dose, dwell time, exchange cycles, the patient’s tolerance, safety, the patient’s training, and time expenditure. Future studies should consider the symptoms, urine volume, and ultrafiltration, among others, and individualize the prescription according to each patient. | PMC10269400 |
Conclusion | PD, acidosis, hyperkalemia | ACIDOSIS | The combination of APD with MPD during USPD treatment had more advantages in removing small-molecule toxins, correcting hyperkalemia and acidosis, reducing the burden of nurses by saving time and improving patients’ skills in fluid exchange. Therefore, this mode could be recommended as an adoptable and suitable PD modality for USPD in the future. | PMC10269400 |
Acknowledgments | The authors express their sincere appreciation to all colleagues involved in the study for their participation in this trial. The authors would also like to acknowledge all the patients who participated in this trial. | PMC10269400 | ||
Authors’ contributions | XXX | XXX and HXQ enrolled patients in the study, evaluated the effect and safety, and collected the data. HXQ, PL, LX, and ZXL performed manual fluid exchange, APD, patient education, and training. XXX, WXF, and ZZY contributed to data analysis and manuscript preparation. LZ contributed to the concept, design, data analysis, interpretation, and manuscript preparation and supervised the study. All authors have read and approved the final manuscript. | PMC10269400 | |
Ethics approval and consent to participate | WEST | The study was approved by the Medical Ethics Committee of the West China Hospital of Sichuan University, Sichuan, China. This study followed the Declaration of Helsinki and written informed consent was obtained from the participants. | PMC10269400 | |
Disclosure statement | No potential conflict of interest was reported by the author(s). | PMC10269400 | ||
Data availability statement | The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request. | PMC10269400 | ||
References | PMC10269400 | |||
Evaluation and scale of operating procedures | The total score is 200 points. The patient is considered to be qualified if he or she got more than 120 points. | PMC10269400 | ||
Introduction | The COVID-19 pandemic exposed people to significant and prolonged stress. The psychosocial impacts of the pandemic have been well recognised and reported in high-income countries (HICs) but it is important to understand the unique challenges posed by COVID-19 in low- and middle-income countries (LMICs) where limited international comparisons have been undertaken. This protocol was therefore devised to study the psychosocial impacts of the COVID-19 pandemic in seven LMICs using scales that had been designed for or translated for this purpose. | PMC10105919 | ||
Methods and analysis | post-traumatic, post-traumatic stress | This cross-sectional study uses an online survey to administer a novel COVID Psychosocial Impacts Scale (CPIS) alongside established measures of psychological distress, post-traumatic stress, well-being and post-traumatic growth in the appropriate language. Participants will include adults aged 18 years and above, recruited from Indonesia, Iraq, Iran, Malaysia, Pakistan, Somalia and Turkey, with a pragmatic target sample size of 500 in each country.Data will be analysed descriptively on sociodemographic and study variables. In addition, CPIS will be analysed psychometrically (for reliability and validity) to assess the suitability of use in a given context. Finally, within-subjects and between-subjects analyses will be carried out using multi-level mixed-effect models to examine associations between key sociodemographic and study variables. | PMC10105919 | |
Ethics and dissemination | Ethical approval was granted by the Human Ethics Committee, University of Otago, New Zealand (Ref. No. 21/102). In addition, international collaborators obtained local authorisation or ethical approval in their respective host universities before data collection commenced.Participants will give informed consent before taking part. Data will be collected and stored securely on the University of Otago, New Zealand Qualtrics platform using an auto-generated non-identifiable letter-number string. Data will be available on reasonable request. Findings will be disseminated by publications in scientific journals and/or conference presentations. | PMC10105919 | ||
Strengths and limitations of this study | post-traumatic | RECRUITMENT | This cross-sectional observational study will make a significant contribution to understanding the psychosocial impacts of the COVID-19 pandemic in seven low- and middle-income countries with different pandemic impacts.This study will quantify psychometric measures in countries where there is currently limited access to newly developed scales relating to COVID-19 and associated measures of psychological distress, well-being and post-traumatic growth in appropriate languages.The findings will provide psychometric information on the novel COVID Psychosocial Impacts Scale (CPIS) in differing pandemic contexts.There are limitations associated with selective recruitment and response rate in this study; which may limit the generalisability of the findings and comparability between groups. | PMC10105919 |
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