BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

INTRODUCTION: The use of periarticular (PA) tranexamic acid (TXA) and its efficacy in comparison with intra-articular (IA) TXA have not been well explored in the literature. This retrospective cohort study aimed to compare the effects of IA and PA TXA with analgesic components in reducing blood loss and improving immediate postoperative pain relief and functional outcomes in patients after unilateral primary total knee arthroplasty (TKA). METHODS: A total of 63 patients underwent TKA, and they were divided into the IA TXA delivery group ( n = 42) and PA TXA delivery group ( n = 21). All patients were administered 1 g of TXA. They also received pericapsular infiltration consisting of 0.5 mL of adrenaline, 0.4 mL of morphine, 1 g of vancomycin, 1 mL of ketorolac and 15 mL of ropivacaine. Outcomes for blood loss and surrogate markers for immediate functional recovery were measured. RESULTS: Of the 63 patients, 54% were female and 46% male. The mean drop in postoperative haemoglobin levels in the PA and IA groups was 2.0 g/dL and 1.6 g/dL, respectively, and this was not statistically significant ( P = 0.10). The mean haematocrit drop in the PA and IA groups was 6.1% and 5.3%, respectively, and this was also not statistically significant ( P = 0.58). The postoperative day (POD) 1 and discharge day flexion angles, POD 1 and POD 2 visual analogue scale (VAS) scores, gait distance on discharge and length of hospitalisation stay were largely similar in the two groups. CONCLUSION Our study showed that both IA and PA TXA with analgesic components were equally efficient in reducing blood loss and improving immediate postoperative pain relief and functional outcomes.
Humans ; Male ; Female ; Tranexamic Acid/adverse effects* ; Arthroplasty, Replacement, Knee/adverse effects* ; Antifibrinolytic Agents/adverse effects* ; Retrospective Studies ; Postoperative Hemorrhage ; Blood Loss, Surgical/prevention & control* ; Administration, Intravenous ; Analgesia ; Analgesics/therapeutic use* ; Pain, Postoperative/drug therapy* ; Injections, Intra-Articular

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m² of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.
Humans ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Immunosuppressive Agents/adverse effects* ; Cyclophosphamide/therapeutic use* ; Lupus Erythematosus, Systemic/drug therapy* ; Administration, Intravenous ; Alopecia/drug therapy*

BACKGROUND: Intravenous thrombolysis (IVT) is an effective way for treating acute ischemic stroke (AIS). However, its effects have not been established among AIS patients with unclear stroke symptoms or with stroke onset for >4.5 h. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and Google Scholar databases for randomized controlled trials that compared IVT (IVT group) and placebo or usual care (control group [CG]) in AIS patients with disease onset for >4.5 h. The outcomes of interest included the favorable functional outcome (defined as modified Rankin Scale [mRS] scores 0-1) at 90 days, the functional independence (defined as mRS scores 0-2) at 90 days, proportion of patients with symptomatic intracerebral hemorrhage (sICH) and death at 90 days. We assessed the risk of bias using the Cochrane tool. Pre-specified subgroup analyses were performed by age (≤70 years or >70 years), National Institute of Health Stroke Scale (NIHSS, ≤10 or >10) and time window (4.5-9.0 h or >9.0 h). RESULTS: Four trials involving 848 patients were eligible. The risk of bias of included trials was low. Patients in the IVT group were more likely to achieve favorable functional outcomes (45.8% vs. 36.7%; OR 1.48, 95% CI 1.12-1.96) and functional independence (63.8% vs. 55.7%; OR 1.43, 95% CI 1.08-1.90) at 90 days, but had higher risk of sICH (3.0% vs. 0.5%; OR 5.28, 95% CI 1.35-20.68) at 90 days than those in the CG. No significant difference in death at 90 days was found between the two groups (7.0% vs. 4.1%; OR 1.80; 95% CI 0.97-3.34). CONCLUSIONS Use of IVT in patients with extended time window may improve their functional outcomes at 90 days, although IVT may induce increased risk of sICH. Care of these patients should well balance the potential benefits and harms of IVT.
Administration, Intravenous ; Aged ; Brain Ischemia/drug therapy* ; Fibrinolytic Agents/therapeutic use* ; Humans ; Ischemic Stroke ; Stroke/drug therapy* ; Thrombolytic Therapy ; Treatment Outcome

Administration, Intravenous ; Ascorbic Acid/therapeutic use* ; COVID-19 ; Humans ; Pneumonia ; SARS-CoV-2

BACKGROUND: The worldwide incidence of osteomyelitis is approximately 21.8 cases per 100,000 person-years. The cornerstone of treatment is prolonged (4-6 weeks) intravenous antibiotic administration. This entails additional cost, inconvenience, and added manpower from the healthcare system. Thus, studies have explored the possible use of oral antibiotics as alternatives to improve patient compliance and reduce costs. Our meta-analysis aimed to compare the efficacy of oral versus intravenous antibiotics in treating adult patients with osteomyelitis. MATERIALS AND METHODS: Electronic databases (PubMed, Medline, EMBASE, Cochrane Central Register of Controlled Trials, Google Scholar, and Research Gate) from 1966 to April 2020 were searched using the terms “oral antibiotics”, “osteomyelitis”, “randomized controlled trial”. Only studies that directly compared oral versus intravenous antibiotics and confirmed osteomyelitis through biopsy and/or imaging were included. Primary outcome is remission (resolution of symptoms with no relapse and bacteriologic eradication); secondary outcomes, (a) relapse (persistence of the pathogen after treatment) and (b) adverse events. The validity of included studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. We performed a random-effects model in Review Manager Version 5.3 with 95% confidence interval. The I 2 test was used to assess heterogeneity. RESULTS: Seven of 89 trials comprised of 1,282 patients were included in the final analysis. All studies included patients with osteomyelitis of the lower extremities. Oral antibiotics used were Ciprofloxacin, Ofloxacin, and Co-trimoxazole; intravenous antibiotics used were deemed appropriate by the infectious disease specialist. Patients were only given either oral or intravenous antibiotics. Results showed an 8% increase in remission rates [RR 1.08 (0.81 to 1.44, 95% CI, Z = 0.52, p=0.60)] with no heterogeneity (I2 = 0%) in the intravenous antibiotics group. However, this was not statistically significant. Furthermore, there was a 62% decrease in relapse rates in the intravenous antibiotics group [RR 1.62 (0.85 to 3.07, 95% CI, Z = 1.47, p = 0.14)] with no heterogeneity (I2 = 0%) but was not statistically significant. CONCLUSION: Oral are comparable to intravenous antibiotics in treating osteomyelitis in terms of remission and relapse rates. However, larger and double-blinded trials should be done to generate more robust data to validate these claims.
Osteomyelitis ; Administration, Intravenous ' ; Parenteral Nutrition

intravenous administration (RR=1.81) and previous AAD episodes (RR=1.87). Abdominal pain occurred in 27/289 (9.3%), particularly in children >6 years (RR=4.15), with previous abdominal pain (RR=7.2) or constipation (RR=4.06). Constipation was recorded in 23/289 (8.0%), with increased risk in children having surgery (RR=2.56) or previous constipation (RR=7.38). Probiotic supplementation significantly reduced AAD (RR=0.30) and abdominal pain (RR=0.36). Lactobacillus rhamnosus GG (LGG) and L. reuteri significantly reduced AAD (RR=0.37 and 0.35) and abdominal pain (RR=0.37 and 0.24).CONCLUSION: AAD occurred in 20.4% of children, with increased risk at younger age, lower respiratory and urinary tract infections, intravenous treatment and previous AAD. LGG and L. reuteri reduced both AAD and associated abdominal pain.]]>
Abdominal Pain ; Administration, Intravenous ; Anti-Bacterial Agents ; Child ; Constipation ; Diarrhea ; Humans ; Incidence ; Inpatients ; Lactobacillus reuteri ; Lactobacillus rhamnosus ; Probiotics ; Prospective Studies ; Protective Factors ; Urinary Tract Infections

Administration, Intravenous ; Asian People ; Consensus ; Humans ; Iron ; Medicine, Chinese Traditional

OBJECTIVE: To evaluate the efficacy of volume therapy with sodium acetate Ringer solution during the perioperative period in children with cyanotic congenital heart disease (CHD). METHODS: The children who underwent elective surgery for cyanotic CHD admitted to Shanghai Children's Medical Center Affiliated to the Medical School of Shanghai Jiaotong University from September to December 2018 were divided into three groups according to random number table with the informed consent of their legal representatives. All of the children received volume therapy with infusion of sodium acetate Ringer solution intravenously upon anesthesia induction. The volume of infusion was calculated according to the "4-2-1" formula (group A, the rehydration volume was 4 mL×kg^-1×h^-1 for the first 10 kg body weight, 2 mL×kg^-1×h^-1 for the second 10 kg, and 1 mL×kg^-1×h^-1 for the third 10 kg and above), and the volume was increased by 50% or 100% in groups B and C, respectively. The intravenous infusion lasted for 30 minutes in all the three groups. Arterial blood gas analysis was performed before and 30 minutes after infusion to observe the acid-base status and electrolyte level. Pulse oxygen saturation (SpO₂), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) before and 10, 20, 30 minutes after infusion, central venous pressure (CVP) at 30 minutes after infusion were recorded, as well as adverse events occurred after infusion. RESULTS: Twenty-six children with cyanotic CHD, 17 male and 9 female, aged from 1 to 36 months, body weight 3.6 to 16.0 kg, and America Society of Anesthesiologists (ASA) level of III or IV, were enrolled in the study. The pH value in group B at 30 minutes after infusion was significantly higher than that before infusion (7.35±0.05 vs. 7.32±0.06, P < 0.05), while no significant changes were found before and after infusion in the other two groups. The hematocrits (Hct) after infusion in three groups were significantly lower than those before infusion (0.433±0.141 vs. 0.473±0.146 in group A, 0.324±0.054 vs. 0.372±0.063 in group B, 0.363±0.097 vs. 0.418±0.111 in group C, all P < 0.01), indicating that all the children in the three groups achieved effective hemodilution. However, there was no significant difference in blood gas analysis before and after infusion among the three groups. The level of blood lactic acid (Lac) in all CHD children was decreased from (1.33±0.63) mmol/L to (0.98±0.36) mmol/L after infusion of sodium acetate Ringer solution, the serum Ca²⁺ concentration was decreased from (1.22±0.06) mmol/L to (1.19±0.06) mmol/L, and the serum Cl^- concentration was increased from (108.74±2.70) mmol/L to (109.77±2.54) mmol/L with the statistically significant differences (all P < 0.01). However, no significant difference was found in Lac or electrolyte levels before and after infusion among the three groups. There was no significant difference in vital signs before and after infusion among the three groups, but the period of infusion had an effect on SpO₂ (F = 5.998, P < 0.01), HR (F = 34.279, P < 0.01) and SBP (F = 4.345, P < 0.05). HR in groups A and C were significantly lower than those before infusion, and SBP in group A was decreased gradually with the prolongation of infusion time. The CVP value at 30 minutes after infusion in group B was higher than that in group A. No adverse reactions such as rash or anaphylactic shock occurred after infusion of sodium acetate Ringer solution in all children. CONCLUSIONS The perioperative volume therapy with sodium acetate Ringer solution in children with cyanotic CHD can effectively prevent the increase in Lac level and does not aggravate metabolic acidosis. The volume of infusion was well tolerated by all the children without disturbing the hemodynamic parameters.
Child, Preschool ; China ; Cyanosis/therapy* ; Female ; Fluid Therapy ; Heart Defects, Congenital/therapy* ; Humans ; Infant ; Infant, Newborn ; Infusions, Intravenous ; Male ; Perioperative Care ; Sodium Acetate/administration & dosage* ; Treatment Outcome

BACKGROUND: Sevoflurane is widely used to anesthetize children because of its rapid action with minimal irritation of the airways. However, there is a high risk of agitation after emergence from anesthesia. Strabismus surgery, in particular, can trigger agitation because patients have their eyes covered in the postoperative period. The aim of this study was to determine whether or not esmolol and lidocaine could decrease emergence agitation in children. METHODS: Eighty-four patients aged 3 to 9 years undergoing strabismus surgery were randomly assigned to a control group (saline only), a group that received intravenous lidocaine 1.5 mg/kg, and a group that received intravenous esmolol 0.5 mg/kg and lidocaine 1.5 mg/kg. Agitation was measured using the objective pain score, Cole 5-point score, and Richmond Agitation Sedation Scale score at the end of surgery, on arrival in the recovery room, and 10 and 30 min after arrival. RESULTS: The group that received the combination of esmolol and lidocaine showed lower OPS and RASS scores than the other two groups when patients awoke from anesthesia (OPS = 0 (0-4), RASS = -4 [(-5)-1]) and were transferred to the recovery room (OPS = 0 (0-8), RASS = -1 [(-5)-3]) (P < 0.05). There was no significant difference in the severity of agitation among the three groups at other time points (P > 0.05). CONCLUSIONS: When pediatric strabismus surgery is accompanied by sevoflurane anesthesia, an intravenous injection of esmolol and lidocaine could alleviate agitation until arrival in the recovery room. TRIAL REGISTRATION Clinical Research Information Service, No. KCT0002925; https://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=11532.
Anesthesia ; methods ; Child ; Child, Preschool ; Double-Blind Method ; Humans ; Injections, Intravenous ; Lidocaine ; administration & dosage ; pharmacology ; Propanolamines ; administration & dosage ; pharmacology ; Sevoflurane ; therapeutic use ; Strabismus ; surgery ; Wakefulness ; drug effects