Promoting application of enhanced recovery after surgery protocols during perioperative localized abdominal and thoracic neuroblastomas.

To investigate the safety and efficacy of the application of enhanced recovery after surgery (ERAS) protocols in the perioperative period of abdominal and thoracic localized neuroblastomas (NBs). In this retrospective study, 68 children with NBs who underwent surgical resection of the tumor were enrolled. The ERAS protocols for NB excision were implemented in the ERAS group (n = 39) and the consequences were compared with children treated with traditional care (n = 29, TRAD group). The main outcomes of our interest included the incidence of surgery-related complications, the postoperative length of stay (LOS), and the Face/Legs/Activity/Cry/Consolability (FLACC) quantitative table from postoperative days (POD) 1-5. We also evaluated the median intraoperative fluid volume and anesthesia recovery time; blood glucose levels at the beginning of anesthesia, POD1, and 3; WBC counts, CRP values, and the concentration of plasma nutritional indicators on POD1 and 3; time of early ambulation, first anal exhaust, total enteral nutrition (TEN), and discontinue intravenous infusion postoperatively; usage proportion and duration of abdominal and thoracic drainages, nasogastric decompression tubes and urinary catheters; cost of hospitalization, parental satisfaction rate, and readmission rate of surgery ward within 30 days. Compared to the TRAD group, the ERAS group had lower surgery-related complications, albeit not significantly (P > 0.05); the median postoperative LOS decreased from 11.0 to 8.0 days (P < 0.001), the LOS of abdominal NB was significantly shortened (P < 0.001) compared to thoracic NB (P = 0.07) between the two groups; the FLACC scores decreased significantly from POD1-5 (all P < 0.01). The ERAS group had an improved median intraoperative infusion speed (5.0 mL/kg/h vs 8.0 mL/kg/h), time of early ambulation (1.0 days vs 3.0 days), first anal exhaust (2.0 days vs 2.0 days), TEN (5.0 vs 7.0 days), discontinuation of intravenous infusion (5.0 days vs 8.0 days), and total cost of hospitalization (33,897.2 Yuan vs 38,876.3 Yuan); (all P < 0.01). The usage proportion and duration of surgical drainages and tubes were apparently reduced. The mean blood glucose level was higher at the beginning of anesthesia but lower on POD1 and 3 in the ERAS group (P < 0.01). No statistically significant difference was detected in WBC counts and concentrations of hemoglobin and albumin between the two groups of patients (P > 0.05), while the concentrations of prealbumin on POD3 were higher and the CRP level on POD1 was lower in the ERAS group than the TRAD group (P < 0.01). The satisfaction rate of parents was only slightly higher, but the difference was not statistically significant (P = 0.730). No obvious differences were observed in the aspects of NB resection (P = 0.462) and 30-day readmissions of surgery ward (P = 1.000). The application of ERAS protocols has a significant potential to accelerate perioperative rehabilitation in children undergoing abdominal and thoracic NBs' surgical resection.

He J ，Wang Z ，Yu X ，Su Y ，Hong M ，Zhu K ... -  《-》

Is Next-day Discharge Safe After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis?

While the implementation of enhanced recovery after surgery protocols and improvements in pain control have decreased the length of stay (LOS) after scoliosis surgery, adolescents are typically hospitalized for several days after posterior spinal instrumented fusion (PSF). The purpose of this study was to determine whether next-day discharge after PSF for adolescent idiopathic scoliosis (AIS) had an equivalent safety profile compared with longer LOS. The secondary purpose was to examine perioperative factors associated with next-day discharge. We performed a retrospective study of all patients who underwent PSF for AIS at a single institution from 2017 to 2022. We compared patients based on postoperative LOS with an early discharge group consisting of those who were discharged on the first postoperative day 1 (POD1; n = 40) and a standard discharge group consisting of those who were discharged after POD1 (n = 71). We documented preoperative variables, including patient demographics and curve characteristics, intraoperative variables, including levels fused, implant density, operative time, and blood loss, and postoperative variables, including emergency department (ED) visits within 30 days and hospital readmissions within 90 days. One hundred eleven patients were included with a mean curve magnitude of 67 degrees. Forty patients (36%) were discharged on POD1. There were one (3%) ED visit and 2 (5%) readmissions in the early discharge group and 3 (4%) ED visits and 2 (3%) readmissions in the standard discharge group ( P = 0.64 and 0.55, respectively). Patients in whom intravenous methadone was used intraoperatively were more likely to discharge POD1 ( P = 0.02). There were no other significant differences in perioperative variables between the two groups including: BMI, distance from home to hospital, magnitude of main curve, curve flexibility, number of levels fused, estimated blood loss, implant density, operative time, or postoperative pain scores. Next-day discharge after PSF for AIS has an equivalent safety profile compared with longer LOS. Over one-third of patients were discharged on POD1, and there was no statistically significant difference in ED visits or hospital readmissions between the groups. Patients in whom intravenous methadone was used intraoperatively were more likely to discharge POD1. In a retrospective study of posterior spinal fusions for AIS, we found no increase in ED visits or hospital readmissions for those discharged the next day. Level III.

Kirk AM ，Barré AM ，Prusick VW ，Conley C ，Muchow RD ... -  《-》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》

Effect of peritoneal drainage on the prognosis following appendectomy in pediatric patients with appendicitis: a retrospective study based on appendicitis grade.

Liao J ，Zhou J ，Chen F ，Xie G ，Wei H ，Wang J ... -  《-》

Safety, pharmacokinetics, and pharmacodynamics of LBP-EC01, a CRISPR-Cas3-enhanced bacteriophage cocktail, in uncomplicated urinary tract infections due to Escherichia coli (ELIMINATE): the randomised, open-label, first part of a two-part phase 2 trial.

The rate of antibiotic resistance continues to grow, outpacing small-molecule-drug development efforts. Novel therapies are needed to combat this growing threat, particularly for the treatment of urinary tract infections (UTIs), which are one of the largest contributors to antibiotic use and associated antibiotic resistance. LBP-EC01 is a novel, genetically enhanced, six-bacteriophage cocktail developed by Locus Biosciences (Morrisville, NC, USA) to address UTIs caused by Escherichia coli, regardless of antibiotic resistance status. In this first part of the two-part phase 2 ELIMINATE trial, we aimed to define a dosing regimen of LBP-EC01 for the treatment of uncomplicated UTIs that could advance to the second, randomised, controlled, double-blinded portion of the study. This first part of ELIMINATE is a randomised, uncontrolled, open-label, phase 2 trial that took place in six private clinical sites in the USA. Eligible participants were female by self-identification, aged between 18 years and 70 years, and had an uncomplicated UTI at the time of enrolment, as well as a history of at least one drug-resistant UTI caused by E coli within the 12 months before enrolment. Participants were initially randomised in a 1:1:1 ratio into three treatment groups, but this part of the trial was terminated on the recommendation of the safety review committee after a non-serious tolerability signal was observed based on systemic drug exposure. A protocol update was then implemented, comprised of three new treatment groups. Groups A to C were dosed with intraurethral 2 × 1012 plaque-forming units (PFU) of LBP-EC01 on days 1 and 2 by catheter, plus one of three intravenous doses daily on days 1-3 of LBP-EC01 (1 mL of 1 × 1010 PFU intravenous bolus in group A, 1 mL of 1 × 109 PFU intravenous bolus in group B, and a 2 h 1 × 1011 PFU intravenous infusion in 100 mL of sodium lactate solution in group C). In all groups, oral trimethoprim-sulfamethoxazole (TMP-SMX; 160 mg and 800 mg) was given twice daily on days 1-3. The primary outcome was the level of LBP-EC01 in urine and blood across the treatment period and over 48 h after the last dose and was assessed in patients in the intention-to-treat (ITT) population who received at least one dose of LBP-EC01 and had concentration-time data available throughout the days 1-3 dosing period (pharmacokinetic population). Safety, a secondary endpoint, was assessed in enrolled patients who received at least one dose of study drug (safety population). As exploratory pharmacodynamic endpoints, we assessed E coli levels in urine and clinical symptoms of UTI in patients with at least 1·0 × 105 colony-forming units per mL E coli in urine at baseline who took at least one dose of study drug and completed their day 10 test-of-cure assessment (pharmacodynamic-evaluable population). This trial is registered with ClinicalTrials.gov, NCT05488340, and is ongoing. Between Aug 22, 2022, and Aug 28, 2023, 44 patients were screened for eligibility, and 39 were randomly assigned (ITT population). Initially, eight participants were assigned to the first three groups. After the protocol was updated, 31 participants were allocated into groups A (11 patients), B (ten patients), and C (ten patients). One patient in group C withdrew consent on day 2 for personal reasons, but as she had received the first dose of the study drug was included in the modified ITT population. Maximum urine drug concentrations were consistent across intraurethral dosing, with a maximum mean concentration of 6·3 × 108 PFU per mL (geometric mean 8·8 log10 PFU per mL and geometric SD [gSD] 0·3). Blood plasma level of bacteriophages was intravenous dose-dependent, with maximum mean concentrations of 4·0 × 103 (geometric mean 3·6 log10 PFU per mL [gSD 1·5]) in group A, 2·5 × 103 (3·4 log10 PFU per mL [1·7]) in group B, and 8·0 × 105 (5·9 log10 PFU per mL [1·4]) in group C. No serious adverse events were observed. 44 adverse events were reported across 18 (46%) of the 39 participants in the safety population, with more adverse events seen with higher intravenous doses. Three patients in groups 1 to 3 and one patient in group C, all of whom received 1 × 1011 LBP-EC01 intravenously, had non-serious tachycardia and afebrile chills after the second intravenous dose. A rapid reduction of E coli in urine was observed by 4 h after the first treatment and maintained at day 10 in all 16 evaluable patients; these individuals had complete resolution of UTI symptoms by day 10. A regimen consisting of 2 days of intraurethral LBP-EC01 and 3 days of concurrent intravenous LBP-EC01 (1 × 1010 PFU) and oral TMP-SMX twice a day was well tolerated, with consistent pharmacokinetic profiles in urine and blood. LBP-EC01 and TMP-SMX dosing resulted in a rapid and durable reduction of E coli, with corresponding elimination of clinical symptoms in evaluable patients. LBP-EC01 holds promise in providing an alternative therapy for uncomplicated UTIs, with further testing of the group A dosing regimen planned in the controlled, double-blind, second part of ELIMINATE. Federal funds from the US Department of Health and Human Services, Administration for Strategic Preparedness and Response, and Biomedical Advanced Research and Development Authority (BARDA).

Kim P ，Sanchez AM ，Penke TJR ，Tuson HH ，Kime JC ，McKee RW ，Slone WL ，Conley NR ，McMillan LJ ，Prybol CJ ，Garofolo PM ... -  《-》