Acute hospitalizations after proton therapy versus intensity-modulated radiotherapy for locally advanced non-small cell lung cancer in the durvalumab era.

INTRODUCTION: It was hypothesized that use of proton beam therapy (PBT) in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiation and consolidative immune checkpoint inhibition is associated with fewer unplanned hospitalizations compared with intensity-modulated radiotherapy (IMRT). METHODS: Patients with locally advanced non-small cell lung cancer treated between October 2017 and December 2021 with concurrent chemoradiation with either IMRT or PBT ± consolidative immune checkpoint inhibition were retrospectively identified. Logistic regression was used to assess the association of radiation therapy technique with 90-day hospitalization and grade 3 (G3+) lymphopenia. Competing risk regression was used to compare G3+ pneumonitis, G3+ esophagitis, and G3+ cardiac events. Kaplan-Meier method was used for progression-free survival and overall survival. Inverse probability treatment weighting was applied to adjust for differences in PBT and IMRT groups. RESULTS: Of 316 patients, 117 (37%) received PBT and 199 (63%) received IMRT. The PBT group was older (p < .001) and had higher Charlson Comorbidity Index scores (p = .02). The PBT group received a lower mean heart dose (p < .0001), left anterior descending artery V15 Gy (p = .001), mean lung dose (p = .008), and effective dose to immune circulating cells (p < .001). On inverse probability treatment weighting analysis, PBT was associated with fewer unplanned hospitalizations (adjusted odds ratio, 0.55; 95% CI, 0.38-0.81; p = .002) and less G3+ lymphopenia (adjusted odds ratio, 0.55; 95% CI, 0.37-0.81; p = .003). There was no difference in other G3+ toxicities, progression-free survival, or overall survival. CONCLUSIONS: PBT is associated with fewer unplanned hospitalizations, lower effective dose to immune circulating cells and less G3+ lymphopenia compared with IMRT. Minimizing dose to lymphocytes may be warranted, but prospective data are needed.

The effects of delayed appropriate antimicrobial therapy on children with Staphylococcus aureus blood infection.

Early appropriate antimicrobial therapy plays a critical role for patients with Staphylococcus aureus bloodstream infection (SAB). We aim to determine the optimal time-window for appropriate antimicrobial therapy and evaluate the effects of delayed therapy on adverse clinical outcomes (in-hospital mortality, sepsis, and septic shock) in children with SAB by propensity score matching (PSM) analysis. Receiver-operating characteristic was used to determine the cut-off point of the time to appropriate therapy (TTAT), the patients were divided into timely and delayed appropriate antimicrobial therapy (delayed therapy) groups accordingly. The PSM was used to balance the characteristics between the two groups, controlling the effects of potential confounders. Kaplan-Meier methods and Cox proportional hazards regression were applied to the matched groups to analyze the association between delayed therapy and clinical outcomes. Inverse probability of treatment weighting and propensity score covariate adjustment were also performed to investigate the sensitivity of the results under different propensity score-based approaches. In total, 247 patients were included in this study. The optimal cut-off point of TTAT was identified as 6.4 h, with 85.0% sensitivity and 69.2% specificity (AUC 0.803, 95% confidence interval 0.702-0.904). Eighty-seven (35.22%) of the 247 patients who received delayed therapy (TTAT ≥ 6.4 h) had higher in-hospital mortality (19.54% vs 1.88%, p < 0.001), higher incidences of sepsis (44.83% vs 15.00%, p < 0.001) and septic shock (32.18% vs 6.25%, p < 0.001) when compared to timely therapy (TTAT < 6.4 h) patients. After PSM analysis, a total of 134 episodes (67 in each of the two matched groups) were further analyzed. No statistically significant difference was observed in in-hospital mortality between delayed and timely -therapy groups (log-rank test, P = 0.157). Patients with delayed therapy had a higher incidence of sepsis or septic shock than those with timely therapy (log-rank test, P = 0.009; P = 0.018, respectively). Compared to the timely-therapy group, the hazard ratio and 95% confidence interval in delayed-therapy group were 2.512 (1.227-5.144, P = 0.012) for sepsis, 3.109 (1.166-8.290, P = 0.023) for septic shock.    Conclusion: Appropriate therapy delayed 6.4 h may increase the incidence of sepsis and septic shock, with similar in-hospital mortality in patients with SAB. What is Known: • Staphylococcus aureus (S. aureus) is a major cause of bloodstream infections in children. Undoubtedly, early antimicrobial application plays a critical role in the treatment of children with Staphylococcus aureus bloodstream infections (SAB). • However, rapid, and aggressive administration of antimicrobials may lead to the overuse of these drugs and the emergence of multidrug-resistant microorganisms. Therefore, it is crucial to determine the optimal time-window for appropriate antimicrobial administration in children with SAB. Unfortunately, the optimal time-window for appropriate antimicrobial administration in children with SAB remains unclear. What is New: • Determining the optimal time-window for appropriate antimicrobial administration in patients with matched data variables is particularly important. The Propensity score matching (PSM) analysis effectively controls for confounding factors to a considerable extent when assessing the impact of treatment, thereby approximating the effects observed in randomized controlled trials. • To our knowledge, this is the first study using PSM method to assess the effects of delayed appropriate antimicrobial therapy on adverse outcomes in children with SAB. In low-risk populations with SAB, a delay of 6.4 h in appropriate therapy might increase the occurrence rate for sepsis and septic shock; however, no correlation has been found between this delay and an increased risk for hospital mortality.

Inappropriate empirical antibiotic therapy was an independent risk factor of pediatric persistent S. aureus bloodstream infection.

Persistent S. aureus bloodstream infection (PSBSI) increased the incidence of metastatic infection and mortality. We aimed to clarify its risk factors and correlation with metastatic infection and septic shock in children. This retrospective and observational study enrolled children with S. aureus bloodstream infection who admitted to Children's Hospital of Chongqing Medical University between January 2016 and December 2021. The logistic regression model was used for multivariable analyses to determine independent factors associated with PSBSI and clarify the effect of persistent S. aureus bloodstream infection and other factors on metastatic infection and septic shock. One hundred and twenty-seven children were included in this study retrospectively. There were thirty-two cases in the persistent S. aureus bloodstream infection group and ninety-five children in the non-persistent infection group. Multivariate logistic regression analysis indicated that inappropriate empirical antibiotic therapy (OR, 7.26; 95%CI, 2.48-21.30; P<0.01) was an independent risk factor of persistent S. aureus bloodstream infection. Persistent S. aureus bloodstream infection (OR, 6.40; 95%CI, 2.08-19.70; P<0.01) and community-acquired S. aureus bloodstream infection (OR, 4.75; 95%CI, 1.34-16.89; P=0.02) were independent predictors of metastatic infection. Pittsburgh bacteremia scores ≥ 2 (OR, 28.81; 95%CI, 5.26-157.99; P<0.01), hypoalbuminemia (OR, 13.34; 95%CI, 2.43-73.28; P<0.01) and persistent S. aureus bloodstream infection (OR, 5.48; 95%CI, 1.13-26.54; P=0.04) were independent risk factors of septic shock. CONCLUSION: Inappropriate empirical antibiotic therapy was an independent risk factor of pediatric persistent S. aureus bloodstream infection. Pediatric persistent S. aureus bloodstream infection was associated with metastatic infection and septic shock. WHAT IS KNOWN: • Pathogenic features such as Methicillin-resistant S. aureus and sources of infection such as central venous catheter related infection were risk factors of PSBSI in adults. • PSBSI increased the incidence of metastatic infection and mortality in adults. WHAT IS NEW: • Inappropriate empirical antibiotic therapy was an independent risk factor of pediatric persistent S. aureus bloodstream infection. • Pediatric persistent S. aureus bloodstream infection was associated with metastatic infection and septic shock.

Lack of volume-outcome association in ECMO bridge to heart transplantation.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a bridge to cardiac transplantation. As the 2018 United Network for Organ Sharing (UNOS) heart allocation policy change elevated waitlist status for patients receiving mechanical circulatory support (MCS), we aimed to determine if a center's annual heart transplant volume was associated with ECMO-support duration and posttransplant outcomes. METHODS: Adults heart transplant candidates between January 1, 2011, and December 31, 2021, were isolated in the UNOS database. VA-ECMO use was identified at the time of listing for transplant. Average annual transplant volume was calculated by the center, with stratification as high (≥20 cardiac transplants, high volume center [HVC]) or low (<20 cardiac transplants, low volume center [LVC]) volume centers. Results are reported as mean (interquartile range) or n (%). RESULTS: In total, 543 patients at HVCs and 275 at LVCs were listed for transplant supported with VA-ECMO. Those listed at HVCs were more likely to be supported by intra-aortic balloon pump (103 [19%] vs. 32 [11.6%], p = .008) and inotropes (267 [49.2%] vs. 106 [38.5%], p = .004) at time of listing. Patients at HVCs received ECMO support for 6 [4-9] days, compared to 8 [4-15] days at low-volume centers (p = .030), and but were cannulated a similar time before listing (2 [1-5] vs. 3 [1-7] days, p = .517). There were no differences in rates of transplant (p = .2126), waitlist mortality (p = .8645), delisting due to clinical deterioration (p = .8419), or recovery (p = .1773) between groups. Among transplanted patients, there were no differences in support duration (6 [4-8] vs. 6 [4-10], p = .187), or time from registration to transplant (5 [2-20] vs. 7 [3-22] days, p = .560). Posttransplant survival did not vary (p = .293). CONCLUSIONS: LVCs can successfully bridge patients to transplant with VA-ECMO and achieve comparable outcomes to HVCs.

Self-supervised acoustic representation learning via acoustic-embedding memory unit modified space autoencoder for underwater target recognition.

Since the expensive annotation of high-quality signals obtained from passive sonars and the weak generalization ability of the single feature in the ocean, this paper proposes the self-supervised acoustic representation learning under acoustic-embedding memory unit modified space autoencoder (ASAE) and performs the underwater target recognition task. In the manner of the animal-like acoustic auditory system, the first step is to design a self-supervised representation learning method called space autoencoder (SAE) to merge Mel filter-bank (FBank) with the acoustic discrimination and gammatone filter-bank (GBank) with the anti-noise robustness into SAE spectrogram (SAE Spec). Meanwhile, due to poor high-level semantic information in SAE Spec, an acoustic-embedding memory unit (AEMU) is introduced as the strategy of adversarial enhancement. During the auxiliary task, more negative samples are joined in the improved contrastive loss function to obtain adversarial enhanced features called ASAE spectrogram (ASAE Spec). Ultimately, the comprehensive contrast experiments and ablation experiments on two underwater datasets show that ASAE Spec increases by more than 0.96% in accuracy, convergence rate, and anti-noise robustness of other mainstream acoustic features. The results prove the potential value of ASAE in practical applications.

The learning curve of robotic coronary arterial bypass surgery: A report from the STS database.

BACKGROUND: There is limited data to inform minimum case requirements for training in robotically assisted coronary artery bypass grafting (RA-CABG). Current recommendations rely on nonclinical endpoints and expert opinion. OBJECTIVES: To determine the minimum number of RA-CABG procedures required to achieve stable clinical outcomes. METHODS: We included isolated RA-CABG in the Society of Thoracic Surgeons (STS) registry performed between 2014 and 2019 by surgeons without prior RA-CABG experience. Outcomes were approach conversion, reoperation, major morbidity or mortality, and procedural success. Case sequence number was used as a continuous variable in logistic regression with restricted cubic splines with fixed effects. Outcomes were compared between operations performed earlier versus later in case sequences using unadjusted and adjusted metrics. RESULTS: There were 1195 cases performed by 114 surgeons. A visual inflection point occurs by a surgeon's 10th procedure for approach conversion, major morbidity or mortality, and overall procedural success after which outcomes stabilize. There was a significant decrease in the rate of approach conversion (7.7% and 2.5%), reoperation (18.9% and 10.8%), and major morbidity or mortality (21.7% and 12.9%), as well as an increase in the rate of procedural success (72.9% and 85.3%) with increasing experience between groups. In a multivariable logistic regression model, case sequences of >10 were an independent predictor of decreased approach conversion (odds ratio [OR]: 0.27; 95% confidence interval [CI]: 0.09-0.84) and increased rate procedural success (OR: 1.96; 95% CI: 1.00-3.84). CONCLUSIONS: The learning curve for RA-CABG is initially steep, but stable clinical outcomes are achieved after the 10th procedure.

Comparative toxicity outcomes of proton-beam therapy versus intensity-modulated radiotherapy for prostate cancer in the postoperative setting.

BACKGROUND: Despite increasing utilization of proton-beam therapy (PBT) in the postprostatectomy setting, no data exist regarding toxicity outcomes relative to intensity-modulated radiotherapy (IMRT). The authors compared acute and late genitourinary (GU) and gastrointestinal (GI) toxicity outcomes in patients with prostate cancer (PC) who received treatment with postprostatectomy IMRT versus PBT. METHODS: With institutional review board approval, patients with PC who received adjuvant or salvage IMRT or PBT (70.2 gray with an endorectal balloon) after prostatectomy from 2009 through 2017 were reviewed. Factors including combined IMRT and PBT and/or concurrent malignancies prompted exclusion. A case-matched cohort analysis was performed using nearest-neighbor 3-to-1 matching by age and GU/GI disorder history. Logistic and Cox regressions were used to identify univariate and multivariate associations between toxicities and cohort/dosimetric characteristics. Toxicity-free survival (TFS) was assessed using the Kaplan-Meier method. RESULTS: Three hundred seven men (mean ± SD age, 59.7 ± 6.3 years; IMRT, n = 237; PBT, n = 70) were identified, generating 70 matched pairs. The median follow-up was 48.6 and 46.1 months for the IMRT and PBT groups, respectively. Although PBT was superior at reducing low-range (volumes receiving 10% to 40% of the dose, respectively) bladder and rectal doses (all P ≤ .01), treatment modality was not associated with differences in clinician-reported acute or late GU/GI toxicities (all P ≥ .05). Five-year grade ≥2 GU and grade ≥1 GI TFS was 61.1% and 73.7% for IMRT, respectively, and 70.7% and 75.3% for PBT, respectively; and 5-year grade ≥3 GU and GI TFS was >95% for both groups (all P ≥ .05). CONCLUSIONS: Postprostatectomy PBT minimized low-range bladder and rectal doses relative to IMRT; however, treatment modality was not associated with clinician-reported GU/GI toxicities. Future prospective investigation and ongoing follow-up will determine whether dosimetric differences between IMRT and PBT confer clinically meaningful differences in long-term outcomes.

Analysis of semen parameters in a young cohort of cancer patients.

BACKGROUND: Infertility can be the result of some common cancer treatments and can significantly impact quality of life. Semen cryopreservation allows for fertility preservation. We analyzed the semen parameters of specimens collected from pubertal males from the Children's Hospital of Philadelphia (CHOP) in order to expand current knowledge on the quality of these specimens and inform a standard clinical practice. PROCEDURE: Males who were at least Tanner stage III and newly diagnosed with cancer at CHOP were approached regarding sperm banking. The success and quality of the samples collected were analyzed and compared in relation to prior treatment, age, and diagnosis. RESULTS: From 399 patients approached for semen collection, 339 (85%) attempted to bank sperm, of which 265 (78%) were successful and 60 (15%) refused to participate. Therapy prior to sperm banking significantly impacted a successful collection (P < 0.01). Only 16.9% of the untreated patients were azoospermic, whereas 84.0% of the treated subjects were azoospermic. Older patients were less likely to be azoospermic and have a greater quality collection when compared with younger patients (P < 0.01). However, 65% of our youngest patients still were able to cryopreserve semen. There was no difference in azoospermia across diagnostic groups (P = 0.35), though there were differences in quality of semen parameters across diagnoses. CONCLUSION: Our data support that sperm banking pubertal males prior to the initiation of therapy is feasible. While there were differences in quality of semen parameters across age and diagnostic groups, most males, regardless of age or diagnosis, had adequate specimens for cryopreservation.

Framing Financial Incentives to Increase Physical Activity Among Overweight and Obese Adults: A Randomized, Controlled Trial.

BACKGROUND: Financial incentive designs to increase physical activity have not been well-examined. OBJECTIVE: To test the effectiveness of 3 methods to frame financial incentives to increase physical activity among overweight and obese adults. DESIGN: Randomized, controlled trial. (ClinicalTrials.gov: NCT 02030119). SETTING: University of Pennsylvania. PARTICIPANTS: 281 adult employees (body mass index ≥27 kg/m2). INTERVENTION: 13-week intervention. Participants had a goal of 7000 steps per day and were randomly assigned to a control group with daily feedback or 1 of 3 financial incentive programs with daily feedback: a gain incentive ($1.40 given each day the goal was achieved), lottery incentive (daily eligibility [expected value approximately $1.40] if goal was achieved), or loss incentive ($42 allocated monthly upfront and $1.40 removed each day the goal was not achieved). Participants were followed for another 13 weeks with daily performance feedback but no incentives. MEASUREMENTS: Primary outcome was the mean proportion of participant-days that the 7000-step goal was achieved during the intervention. Secondary outcomes included the mean proportion of participant-days achieving the goal during follow-up and the mean daily steps during intervention and follow-up. RESULTS: The mean proportion of participant-days achieving the goal was 0.30 (95% CI, 0.22 to 0.37) in the control group, 0.35 (CI, 0.28 to 0.42) in the gain-incentive group, 0.36 (CI, 0.29 to 0.43) in the lottery-incentive group, and 0.45 (CI, 0.38 to 0.52) in the loss-incentive group. In adjusted analyses, only the loss-incentive group had a significantly greater mean proportion of participant-days achieving the goal than control (adjusted difference, 0.16 [CI, 0.06 to 0.26]; P = 0.001), but the adjusted difference in mean daily steps was not significant (861 [CI, 24 to 1746]; P = 0.056). During follow-up, daily steps decreased for all incentive groups and were not different from control. LIMITATION: Single employer. CONCLUSION: Financial incentives framed as a loss were most effective for achieving physical activity goals. PRIMARY FUNDING SOURCE: National Institute on Aging.