Historical Control Research Articles

Balanced Crystalloid (Sterofundin) vs. Normal Saline for Diabetic Ketoacidosis: A Prospective Intervention Trial with Historical Controls.

Fluid therapy with normal saline (NS) in diabetic ketoacidosis (DKA) can cause hyperchloremic acidosis and delay DKA resolution. Balanced crystalloids may address this concern, though results with Ringer lactate and Plasma-Lyte have been mixed. This study aimed to compare the effectiveness of Sterofundin (SF) vs. NS in the management of DKA. A prospective, intervention trial with historical controls was conducted at the Postgraduate Institute of Medical Education and Research, Chandigarh, India. Patients aged 13 years or older with DKA were enrolled. The primary outcome was the time taken to DKA resolution, with a predefined superiority margin of a one-fourth reduction in resolution time. Secondary outcomes included total intravenous fluid and short-acting regular insulin requirements, the need for 0.45% saline, hospital stay duration, and in-hospital mortality. A total of 150 patients (mean age 36.8 years, 56.7% males) were included, with 75 receiving SF (intervention group) and 75 receiving NS (historical control group). The SF group showed a significantly shorter mean time to DKA resolution (13.8 ± 6.0 hours) compared to the NS group (18.1 ± 5.5 hours; P < 0.001). SF patients required less total intravenous fluid (4500 mL vs. 6000 mL; P = 0.004), less insulin (98 units vs. 112 units; P = 0.017), and had a lower need for 0.45% saline (8% vs. 74.3%; P < 0.001). Patients receiving SF had shorter hospital stays (4 [IQR 3-5] days vs. 4 [IQR 4-6] days; P = 0.020). Mortality rates were similar between the groups (SF: 9.3%, NS: 8.1%; P = 0.791). SF may be a superior alternative to NS for fluid therapy in DKA.

Five-year Follow-up of a Prospective Food and Drug Administration Investigational Device Exemption Trial Evaluating a PEEK-on-Ceramic Cervical Disc Replacement.

Prospective trial comparing the investigation group to propensity matched historic control group. To evaluate 5-year results of single-level PEEK-on-ceramic cervical total disc replacement (TDR) compared to a propensity matched anterior cervical discectomy and fusion (ACDF) control group. Cervical TDR has gained acceptance as treatment for symptomatic disc degeneration. The design and materials used in these devices continue to evolve. Data were collected in the Food and Drug Administration Investigational Device Exemption trial for the PEEK-on-ceramic Simplify(®) Cervical Artificial Disc (n=150) with comparison to a propensity matched ACDF control group (n=117). All patients were treated for single-level cervical disc degeneration with radiculopathy and/or myelopathy. Clinical outcome was based on composite clinical success (CCS), Neck Disability Index (NDI), visual analog scales (VAS) assessing pain, re-operations, and satisfaction. Radiographic measures included segmental range of motion (ROM), disc space height, and heterotopic ossification (HO). Evaluations were performed pre-operatively and post-operatively within 2 and 6 weeks, and 3, 6, 12 months, and annually thereafter. At 5-year follow-up, CCS was significantly greater with TDR than ACDF (91.1% vs. 74.6%; P<0.01). In the TDR group, the mean NDI score was 63.3 pre-operatively, reduced significantly to 23.1 at 6 weeks and remained below 20 throughout 5-year follow-up. In the ACDF group, the mean pre-operative NDI score was 62.4, decreasing to 33.7 at 6 weeks, and ranged from 25.9 to 21.5 throughout follow-up. Mean NDI scores were significantly lower in TDR group at all post-operative points (P<0.05). Mean TDR ROM was 7.3o pre-operatively and 10.1o at 5 years. Bridging HO occurred in 9%. With TDR, there were 6 re-operations (4.0%) vs. 11 (9.4%) with ACDF (P>0.40). PEEK-on-ceramic TDR produced significantly improved outcomes maintained throughout 5-year follow-up, were similar or superior to ACDF, supporting TDR in appropriately selected patients.

Decreasing chronic graft-versus-host disease rates in all populations

AbstractSince 2005, there has been a steady decline in chronic graft-versus-host disease (cGVHD) at the Fred Hutchinson Cancer Center. To better understand this phenomenon, we studied the risk of cGVHD requiring systemic immunosuppression (cGVHD-IS) as a function of hematopoietic cell transplantation (HCT) date in 3066 survivors from 2005 through 2019. Cox regression models were fit to assess associations of HCT date (as a continuous linear variable) with cause-specific hazards of cGVHD using unadjusted and adjusted models. Median follow-up for study subjects was 7.0 years (range, 1.0-17.2). Two-year probabilities of cGVHD-IS declined among all survivors from 45% to 52% (2005-2007) to ∼40% (2008-2012) and then further to ∼26% by 2017. A decline was also observed when the analysis was restricted to 502 pediatric survivors, with cGVHD-IS probabilities <10% since 2013. Among 305 adult and pediatric survivors who underwent transplantation for nonmalignant diseases, cGVHD rates showed greater fluctuation but remained <20% after 2016. Each 5-year increase in HCT date was associated with a 27% decrease in the cause-specific hazard of cGVHD (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.68-0.78; P < .0001); the HR was 0.81 (95% CI, 0.75-0.87; P < .0001) even after adjusting for various factors (age, donor/stem-cell source, race, sex, conditioning intensity, GVHD prophylaxis, among others) that could lead to cGVHD reduction. The decline in cGVHD was not fully explained by demographic shifts and greater use of HCT approaches that are generally associated with lower cGVHD rates. This observation underscores that single-cohort cGVHD prevention studies should use contemporaneous and not historical controls for comparison.

Role of prazosin in patients with Guillain-Barré syndrome with sympathetic overactivity: A cohort study.

In Guillain-Barré syndrome (GBS), patients with dysautonomia demonstrate sympathetic overactivity (SO). This study assessed the role of prazosin (α1-blocker) in the management of SO. This cohort study was conducted from January 2022 to September 2023. Thirty-two GBS patients with SO received prazosin (2.5-10 mg three times a day) (prazosin group). For comparison, we included historical controls that included 33 GBS patients having SO with similar baseline characteristics, including median age and disability, who did not receive prazosin, from a GBS registry of patients admitted during February 2018-December 2021. The primary endpoint was days to resolution of SO. Secondary endpoints were daily fluctuations in the systolic (SBP) and diastolic blood pressure (DBP), duration of hospital stay, in-hospital mortality, and disability at 3 months. The median ages of both the treatment and the control groups were 36 (IQR 25-49) years and 43 (66.2%) were males. The demographic and clinical parameters were comparable. Prazosin resulted in significantly earlier normalization of SO compared to the control group (median 15 vs. 20 days; p = .01). The mean fluctuations in the SBP and DBP at 15 days were significantly lower in the prazosin group. However, the duration of hospital stay and good recovery at 3 months were comparable. Three patients developed hypotension, while two patients died (ventilator-associated pneumonia) in the prazosin group. This study provides new evidence supporting the role of prazosin in SO, and needs randomized trials to confirm our findings.

Impact of SPY Fluorescence Angiography on Incidence of Ureteroenteric Stricture After Urinary Diversion.

Ureteroenteric strictures (UESs) are a common and morbid complication of radical cystectomy and urinary diversions. UES occurs in 4% to 25% of all patients undergoing urinary diversion, and anastomotic ischemia is implicated in stricture formation. SPY fluorescence angiography is a technology that can be employed during open surgery that allows for evaluation of ureteral perfusion. We performed a prospective single-institution study of intraoperative use of SPY for ureteral assessment with a primary outcome of UES incidence compared with a cohort of historic controls prior to the use of SPY during urinary diversion at our institution. Chart abstraction was conducted to determine the presence of confirmed stricture in these patients, defined as endoscopic diagnosis or definitive imaging findings. Statistical analysis was performed using χ2 test for UES incidence. Demographics characteristics were analyzed with Wilcoxon rank sum test and χ2 test. A total of 332 patients underwent urinary diversion during the study period. UES occurred in 31 of 277 patients (11.1%) in the control group compared with 1 of 55 patients (1.8%) enrolled in the SPY arm (P = .03). The per-ureter UES rate was 6.7% (33/582) in the control group compared with 0.9% (1/107) in the SPY group. Median follow-up in the SPY group was 17.5 months and 58.6 months in the control group. Median Charlson Comorbidity Index was 5 in the SPY group and 4 in the control group. There were no other significant demographic differences between the study groups. SPY fluorescent angiography can be used during open urinary diversion to ensure perfusion to ureteroenteric anastomosis. Our single-institution study demonstrates a decreased incidence of UES when ureteral perfusion assessment is performed. NCT05022199.

Optimizing oocyte yield utilizing a machine learning model for dose and trigger decisions, a multi-center, prospective study

The objective of this study was to evaluate clinical outcomes for patients undergoing IVF treatment where an artificial intelligence (AI) platform was utilized by clinicians to help determine the optimal starting dose of FSH and timing of trigger injection. This was a prospective clinical trial with historical control arm. Four physicians from two assisted reproductive technology treatment centers in the United States participated in the study. The treatment arm included patients undergoing autologous IVF cycles between December 2022–April 2023 where the physician use AI to help select starting dose of follicle stimulating hormone (FSH) and trigger injection timing (N = 291). The control arm included historical patients treated where the same doctor did not use AI between September 2021 and September 2022. The main outcome measures were total FSH used and average number of mature metaphase II (MII) oocytes. There was a non-significant trend towards improved patient outcomes and a reduction in FSH with physician use of AI. Overall, the average number of MIIs in the treatment vs. control arm was 12.20 vs 11.24 (improvement = 0.96, p = 0.16). The average number of oocytes retrieved in the treatment vs. control arm was 16.01 vs 14.54 (improvement = 1.47, p = 0.08). The average total FSH in the treatment arm was 3671.95 IUs and the average in the control arm was 3846.29 IUs (difference = −174.35 IUs, p = 0.13). These results suggests that AI can safely assist in refining the starting dose of FSH while narrowing down the timing of the trigger injection during ovarian stimulation, benefiting the patient in optimizing the count of MII oocytes retrieved.

A novel intrasaccular aneurysm device with high complete occlusion rate: initial results in a rabbit model

BackgroundIntrasaccular flow-disrupting devices are a safe and effective treatment strategy for intracranial aneurysms. We utilized high-frequency optical coherence tomography (HF-OCT) and digital subtraction angiography (DSA) to evaluate SEAL Arc, a...

Addiction Consult Service and Inpatient Outcomes Among Patients with OUD.

Despite rising hospitalizations for opioid use disorder (OUD), rates of inpatient medications for OUD (MOUD) initiation are low. Addiction consult services (ACSs) facilitate inpatient MOUD initiation and linkage to post-discharge MOUD, but few studies have rigorously examined ACS OUD outcomes. To determine the association between ACS consultation and inpatient MOUD initiation, discharge MOUD provision, and post-discharge MOUD linkage. Retrospective study comparing admissions that received an ACS consult and propensity score-matched historical control admissions. One hundred admissions with an OUD-related diagnosis, of patients not currently receiving MOUD who received an ACS consult, and 100 matched historical controls. Consultation from an interprofessional ACS offering expertise in MOUD initiation and linkage to post-discharge MOUD. The primary outcome was inpatient MOUD initiation (methadone or buprenorphine). Secondary outcomes were inpatient buprenorphine initiation, inpatient methadone initiation, discharge prescription for buprenorphine, linkage to post-discharge MOUD (buprenorphine prescription within 60days and new methadone administration at a methadone program within 30days after discharge), patient-directed discharge, 30-day readmission, and 30-day emergency department (ED) visit. Among 200 admissions with an OUD-related diagnosis, those that received an ACS consultation were significantly more likely to have inpatient MOUD initiation (OR 2.57 [CI 1.44-4.61]), inpatient buprenorphine initiation (OR 5.50 [2.14-14.15]), a discharge prescription for buprenorphine (OR 17.22 [3.94-75.13]), a buprenorphine prescription within 60days (22.0% vs. 0.0%, p < 0.001; of those with inpatient buprenorphine initiation: 84.6% vs. 0.0%), and new methadone administration at a methadone program within 30days after discharge (7.0% vs. 0.0%, p = 0.007; of those with inpatient methadone initiation: 19.4% vs. 0.0%). There were no significant differences in other secondary outcomes. There was a strong association between ACS consultation and inpatient MOUD initiation and linkage to post-discharge MOUD. ACSs promote the delivery of evidence-based care for patients with OUD.

A lower initial dose of bosutinib for patients with chronic myeloid leukemia patients resistant and/or intolerant to prior therapy: a single-arm, multicenter, phase 2 trial (BOGI trial)

Although bosutinib is generally safe and effective, drug-related toxicities (DRTs) such as diarrhea or increased transaminase levels often lead to treatment discontinuation. To clarify whether a lower initial dose of bosutinib (i.e., starting at 200 mg) would reduce rates of discontinuation due to DRTs, we conducted a phase 2 study of BOsutinib Gradual Increase (BOGI trial, UMIN 000032282) as a second/third-line treatment for chronic myeloid leukemia (CML). Between February 4, 2019 and May 24, 2022, 35 patients were enrolled. The rate of bosutinib discontinuation at 12 months was 25.7% vs. 35.9% in a historical control study (Japanese phase 1/2 study) (p = 0.102). The rate of bosutinib discontinuation due to DRTs was significantly lower, at 11.4% vs. 28.2% (p = 0.015). The incidence of grade 3/4 transaminase elevation was 20% vs. 29% (p = 0.427), while the incidence of diarrhea was 3% vs. 25% (p = 0.009). The median dose intensity of bosutinib was higher (391.7 mg/day vs. 353.9 mg/day). Pharmacokinetic analysis of bosutinib showed that patients who achieved a major molecular response tended to have high trough concentrations. Thus, a low initial dose of bosutinib followed by dose escalation reduced discontinuation due to severe DRTs while maintaining high dose intensity and efficacy.

Navigating non-medical androgen use: Towards a harm reduction paradigm

Non-medical androgen use is on the rise, with short-term side effects being well-documented whereas long-term consequences remain less understood but are likely to entail cardiovascular illness and permanent endocrine disruptions. Current educational initiatives are falling short in curbing this significant increase, signaling the need for a different approach. In this context, harm reduction emerges as a promising secondary prevention strategy. The key principles of the harm reduction approach outlined in this article emphasize educating individuals about side effects, limiting androgen use, and monitoring health closely. Successful implementation of this strategy hinges upon healthcare providers possessing expertise in the field, fostering non-judgmental interpersonal relationships, and securing cooperation of the athlete. The efficacy of this strategy will be rigorously evaluated in the HARNAS trial, comparing its outcomes with those of a historical control group. The findings from this trial are anticipated to be published in the coming years, shedding light on the effectiveness of this pioneering approach.

Optimizing outcomes in paraesophageal hernia repair: a novel critical view

BackgroundThe recurrence rate of paraesophageal hernia repair (PEHR) is high with reported rates of recurrence varying between 25 and 42%. We present a novel approach to PEHR that involves the visualization of a critical view to decrease recurrence rate. Our study aims to investigate the outcomes of PEHR following the implementation of a critical view.MethodsThis is a single-center retrospective study that examines operative outcomes in patients who underwent PEHR with a critical view in comparison to patients who underwent standard repair. The critical view is defined as full dissection of the posterior mediastinum with complete mobilization of the esophagus to the level of the inferior pulmonary vein, visualization of the left crus of the diaphragm as well as the left gastric artery while the distal esophagus is retracted to expose the spleen in the background. Bivariate chi-squared analysis and multivariable logistic and linear regressions were used for statistical analysis.ResultsA total of 297 patients underwent PEHR between 2015 and 2023, including 207 with critical view and 90 with standard repair which represents the historic control. Type III hernias were most common (48%) followed by type I (36%), type IV (13%), and type II (2.0%). Robotic-assisted repair was most common (65%), followed by laparoscopic (22%) and open repair (14%). Fundoplications performed included Dor (59%), Nissen (14%), Belsey (5%), and Toupet (2%). Patients who underwent PEHR with critical view had lower hernia recurrence rates compared to standard (9.7% vs 20%, P < .01) and lower reoperation rates (0.5% vs 10%, P < .001). There were no differences in postoperative complications on unadjusted bivariate analysis; however, adjusted outcomes revealed a lower odds of postoperative complications in patients with critical view (AOR .13, 95% CI .05–.31, P < .001).ConclusionWe present dissection of a novel critical view during repair of all types of paraesophageal hernia that results in reproducible, consistent, and durable postoperative outcomes, including a significant reduction in recurrence and reoperation.

Comparison of Tenecteplase Versus Alteplase for the Treatment of Pulmonary Embolism and Cardiac Arrest with Suspected Pulmonary Embolism.

High-risk pulmonary embolism (PE) is a life-threatening disease state with current guidelines recommending reperfusion therapy with systemic thrombolytics in addition to anticoagulation. This was a prospective observational cohort study with a historical control group comparing tenecteplase to alteplase for the treatment of PE or cardiac arrest with suspected PE. The primary outcome was the incidence of institutional protocol deviations defined as incorrect thrombolytic dose administered or the incorrect product compounded. Secondary outcomes included any bleeding event, major bleeding event, all-cause mortality, and for patients with a cardiac arrest, successful return of spontaneous circulation (ROSC). Fifty-four patients were included in the study. Protocol deviations occurred in one patient receiving tenecteplase and one patient receiving alteplase (4.0% vs 3.4%; P = 1.0). There was no difference in all-cause mortality (80% vs 86.2%; P = .72), any bleed (12% vs 13.8%; P = 1.0), major bleed (8.0% vs 6.9%; P = 1.0), or ROSC achievement (22.2% vs 28.6%; P = .73) when comparing tenecteplase to alteplase. Our study demonstrates that tenecteplase may be an alternative thrombolytic to alteplase for treatment of PE or cardiac arrest with suspected PE. Further studies comparing the different systemic thrombolytic agents for PE or cardiac arrest with suspected PE are needed.

Efficacy of robot-assisted partial nephrectomy compared to conventional laparoscopic partial nephrectomy for completely endophytic renal tumor: a multicenter, prospective study

BackgroundThis study aimed to compare the efficacy of robot-assisted partial nephrectomy for completely endophytic renal tumors with the reported outcomes of conventional laparoscopic partial nephrectomy and investigate the transition of renal function after robot-assisted partial nephrectomy.MethodsWe conducted a prospective, multicenter, single-arm, open-label trial across 17 academic centers in Japan. Patients with endophytic renal tumors classified as cT1, cN0, cM0 were included and underwent robot-assisted partial nephrectomy. We defined two primary outcomes to assess functional and oncological aspects of the procedure, which were represented by the warm ischemic time and positive surgical margin, respectively. Comparisons were made using control values previously reported in laparoscopic partial nephrectomy studies. In the historical control group, the warm ischemia time was 25.2, and the positive surgical margin was 13%.ResultsOur per-protocol analysis included 98 participants. The mean warm ischemic time was 20.3 min (99% confidence interval 18.3–22.3; p < 0.0001 vs. 25.2). None of the 98 participants had a positive surgical margin (99% confidence interval 0–5.3%; p < 0.0001 vs. 13.0%). The renal function ratio of eGFR before and after protocol treatment multiplied by splits was 0.70 (95% confidence interval: 0.66–0.75). Factors such as preoperative eGFR, resected weight, and warm ischemic time influenced the functional loss of the partially nephrectomized kidney after robot-assisted partial nephrectomy.ConclusionsRobot-assisted partial nephrectomy for completely endophytic renal tumors offers a shorter warm ischemia time and comparable positive surgical margin rate compared with conventional laparoscopic partial nephrectomy.

Patients Beyond the Optimal Range of rATG-AUC Still Benefit from the Targeted Dosing Strategy in Unmanipulated Haplo-PBSCT

Rabbit antithymocyte globulin (rATG) is widely used in allogeneic hematopoietic stem cell transplantation to prevent graft failure and severe graft-versus-host disease (GVHD). We developed a rATG-targeted dosing strategy based on the optimal areas under the concentration-time curve (AUC) of active rATG. This study compared the outcomes of the optimal AUC arm with nonoptimal AUC arm to assess the effect of the rATG-targeted dosing strategy. Eighty patients (median age: 32 years) with hematological malignancies who received their first haplo-PBSCT were enrolled successively. With rATG-targeted dosing, the AUC values of 60 patients (75%, optimal AUC arm) fell within the optimal range (100-148.5 UE/mL/day) and 20 fell beyond this range (nonoptimal AUC arm). In the historical control group of 102 haplo-PBSCT patients who received a fixed dose of rATG (10 mg/kg), less patients fell within the optimal range (57.8%, P = .016). Looking at the nonoptimal AUC arms in both groups, lower cumulative incidence of CMV was noted in the targeted dosing group compared with the historical control group(50.0%, 95% CI, 30.8%-72.9% versus 81.4%, 95% CI, 68.6%-91.3%; P = .004). The cumulative incidences of EBV, relapse, overall survival and disease-free survival tended to be superior in the nonoptimal AUC arm in the targeted dosing group compared with the historical control. In the targeted dosing group, the cumulative incidence of cytomegalovirus (CMV) reactivation on day +180 tended to be lower in the optimal AUC arm (30.0%, 95% CI, 20.1%-43.3%) compared with the nonoptimal AUC arm (50.0%, 95% CI, 30.8%-72.9%, P = .199) without statistical difference. There were no significant differences of acute or chronic GVHD, relapse, nonrelapse mortality, overall survival, disease-free survival or lymphocyte reconstitution between the two arms. In conclusion, the rATG-targeted dosing strategy made the exposure of active rATG in more patients with the optimal AUC range. Even patients who fell beyond this range would still benefit from the strategy.

Prediction of segmental motor outcomes in traumatic spinal cord injury: Advances beyond sum scores

Background and objectivesNeurological and functional recovery after traumatic spinal cord injury (SCI) is highly challenged by the level of the lesion and the high heterogeneity in severity (different degrees of in/complete SCI) and spinal cord syndromes (hemi-, ant-, central-, and posterior cord). So far outcome predictions in clinical trials are limited in targeting sum motor scores of the upper (UEMS) and lower limb (LEMS) while neglecting that the distribution of motor function is essential for functional outcomes. The development of data-driven prediction models of detailed segmental motor recovery for all spinal segments from the level of lesion towards the lowest motor segments will improve the design of rehabilitation programs and the sensitivity of clinical trials. MethodsThis study used acute-phase International Standards for Neurological Classification of SCI exams to forecast 6-month recovery of segmental motor scores as the primary evaluation endpoint. Secondary endpoints included severity grade improvement, independent walking, and self-care ability. Different similarity metrics were explored for k-nearest neighbor (kNN) matching within 1267 patients from the European Multicenter Study about Spinal Cord Injury before validation in 411 patients from the Sygen trial. The kNN performance was compared to linear and logistic regression models. ResultsWe obtained a population-wide root-mean-squared error (RMSE) in motor score sequence of 0.76(0.14, 2.77) and competitive functional score predictions (AUCwalker = 0.92, AUCself-carer = 0.83) for the kNN algorithm, improving beyond the linear regression task (RMSElinear = 0.98(0.22, 2.57)). The validation cohort showed comparable results (RMSE = 0.75(0.13, 2.57), AUCwalker = 0.92). We deploy the final historic control model as a web tool for easy user interaction (https://hicsci.ethz.ch/). DiscussionOur approach is the first to provide predictions across all motor segments independent of the level and severity of SCI. We provide a machine learning concept that is highly interpretable, i.e. the prediction formation process is transparent, that has been validated across European and American data sets, and provides reliable and validated algorithms to incorporate external control data to increase sensitivity and feasibility of multinational clinical trials.

Induction chemotherapy backbone in frail patients with advanced NSCLC treated with chemotherapy plus pembrolizumab: a single institution retrospective audit of dose intensities from modified regimens.

Guidelines historically recommended mono-chemotherapy for the 1st line treatment of elderly patients with non-small cell lung cancer (NSCLC) and poor performance status (PS). Nowadays, there is no clear indication whether chemo-immunotherapy (chemo-IO) combinations can be effectively delivered in this population. We collected induction chemotherapy data in consecutive patients with advanced NSCLC treated with carboplatin-based chemotherapy regimens plus pembrolizumab, to compute the received dose intensity (RDI) from standard regimens or patient-tailored regimens modified due to age, comorbidities and PS. Comorbidities were stratified according to the comorbidity-polypharmacy score (CPS). The established cut-off of ≥85% for RDI was used to define adequate delivery. 116 pts were treated from Feb-20 to July-23, of whom 96 and 20 with non-squamous and squamous NSCLC, treated with carboplatin-pemetrexed or carboplatin-paclitaxel doublets plus pembrolizumab, respectively. The majority of patients were aged ≥ 70 years (52.6%), the median CPS was 5, with 58.6% having a CPS ≥5, whilst 47.4%, 44.8% and 7.8% had an Eastern Cooperative Oncology Group (ECOG) - PS of 0, 1 and 2, respectively. PD-L1 TPS were <1% in 31.9% and 1-49% in 65.4%. Overall, 47.4% received a priori modified regimens due to poor PS, age, or comorbidities. Among patients with non-squamous NSCLC, median received doses of carboplatin and pemetrexed were 1.37 AUC/week and 138.8 mg/m2/week, with RDIs of 86% and 75% (p < 0.01) for patients treated with standard or modified regimens, respectively. Of note, the RDI was 57.9% among patients with ECOG-PS 2. However, patients treated with modified regimens experienced similar toxicities as those treated with standard regimens, despite being older (p < 0.01), with higher PS (p < 0.01) and more comorbid (p = 0.03). Patients treated with modified regimens achieved a shorter survival (7.1 vs 13.9 months), which is comparable to IO-free historical controls. Among patients with squamous NSCLC, 90% received modified regimens upfront, with median received doses of carboplatin and paclitaxel of 1.19 AUC/week and 40 mg/m2/week, and an overall RDI of 73.5%. Although regimen modifications ensure a safe administration of chemotherapy plus pembrolizumab in frail patients, the RDI seems to be subtherapeutic, especially in those with squamous histology. Dedicated trials are needed to implement combination strategies in this population.

Overcoming challenges to reduce time to antibiotic therapy in febrile neutropenic children: insights from a Mexican center

BackgroundProviding quality supportive therapy for children with cancer is essential to reduce the high mortality rates in low- and middle-income countries. Febrile neutropenia is the most common life-threatening complication of cancer in children. The objective of this study was to evaluate the long-term effectiveness of the ‘Golden Hour’ intervention in reducing the time to administer antibiotics and its impact on clinical outcomes in a Mexican hospital. MethodsA comparative study of children with febrile neutropenia who attended the emergency department at the Hospital Universitario “Dr. José Eleuterio González” was performed between January 2017 and December 2022. In May 2019, this center joined the collaborative ‘Mexico in Alliance with St. Jude’ project. An adapted improvement program was developed based on the implementation of an algorithm comprising institutional guidance, supplies kit, standardization of sample processing, training of healthcare providers, and patient education. The time to antibiotic administration was compared with clinical outcomes between the historical control and post-intervention groups. ResultsA total of 291 patients were included, 122 in the pre-intervention period and 169 in the intervention period. Only 5.7% of the pre-intervention group received the first dose of antibiotics within 60 minutes of presenting to the emergency department compared to 84.6% in the intervention group (p-value <0.000). The median times to antibiotic administration in the pre-intervention and post-intervention periods were 269.4 and 50.54 minutes, respectively (p-value <0.000). Clinical deterioration and admission to the pediatric intensive care unit decreased significantly from 6.6% to 2.3% (p-value = 0.03). ConclusionsSustainability of the quality improvement project ‘Golden Hour’ in low- to mid-income countries demonstrated high effectiveness in reducing time to antibiotic administration among children with febrile neutropenia and improved clinical outcomes over three years of implementation.

AB011. A propensity-score matched prospective study on the impact of tumour treating fields (TTF) on overall survival and quality of life in newly diagnosed WHO grade 4 astrocytoma patients.

World Health Organization (WHO) grade 4 astrocytoma is a high-grade brain tumour in adults. Tumour treating fields (TTF) has been shown to improve overall survival (OS). Few studies have explored quality-of-life (QoL) in these patients. This study aims to assess the QoL of TTF patients and OS. This was a prospective multicenter study of adult patients diagnosed with WHO grade 4 astrocytoma from 2018 to 2023 receiving TTF for >1 month after completing standard therapy. A propensity-score matched comparison with a 1:2 ratio with historical control was performed for OS analysis. The patients completed European Organisation for Research and Treatment of Cancer (EORTC) QLQ-30/BN20 questionnaires before TTF and at 3-month interval. Primary outcomes included OS, and secondary outcomes included QoL and TTF-associated adverse effects at 3 months. A total of 141 patients were reviewed, with TTF patients (n=47, 33%) and propensity-score matched controls (n=94). The mean duration of TTF use was 10±8 months. The mean age of the TTF group was 54±13 years, and for the control group 52±13 years. Sixty percent (n=28) were male, similar to the control group with 71% (n=67) (P=0.16). Seventy-two percent of TTF patients had preoperative Karnofsky Performance Scale (KPS) score ≥80, while controls had 70% (P=0.79). Five (11%) TTF patients and 8 (9%) controls were IDH1 mutant (P=0.70). Twenty (43%) TTF patients and 42 (45%) controls were O6-methylguanine-DNA methyltransferase promoter (pMGMT) methylated (P=0.81). Twenty-one (45%) of TTF patients and 55 (59%) of controls had gross total resection (P=0.72). After adjusting for independent predictors for OS, the median OS of the TTF group was 22.4 months [interquartile range (IQR): 18.6-26.5 months], significantly longer than the control group (17.2 months; IQR: 12.1-22.3 months) (log-rank test: P=0.01). Forty-seven TTF patients and 40 control patients completed EORTC questionnaires. There was no difference for EORTC functional and symptom scores between the TTF and control group [P=0.45, analysis of variance (ANOVA)] at 3 months. Thirty-two (67%) of TTF patients reported associated RTOG grade I scalp dermatitis. TTF for WHO grade 4 astrocytoma patients is an independent predictor for OS. QoL between the groups was similar, and overall QoL over time for TTF patients was not affected. TTF is a novel and effective outpatient treatment with minimal adverse effects.

Clinical Impact of Standardized Interpretation and Reporting of Multimodality Neuromonitoring Data.

Evaluate the consistency and clinical impact of standardized multimodality neuromonitoring (MNM) interpretation and reporting within a system of care for patients with severe traumatic brain injury (sTBI). Retrospective, observational historical case-control study. Single-center academic level I trauma center. Standardized interpretation of MNM data summarized within daily reports. Consecutive patients with sTBI undergoing MNM were included. Historical controls were patients monitored before implementation of standardized MNM interpretation; cases were defined as patients with available MNM interpretative reports. Patient characteristics, physiologic data, and clinical outcomes were recorded, and clinical MNM reporting elements were abstracted. The primary outcome was the Glasgow Outcome Scale score 3-6 months postinjury. One hundred twenty-nine patients were included (age 42 ± 18 yr, 82% men); 45 (35%) patients were monitored before standardized MNM interpretation and reporting, and 84 (65%) patients were monitored after that. Patients undergoing standardized interpretative reporting received fewer hyperosmotic agents (3 [1-6] vs. 6 [1-8]; p = 0.04) and spent less time above an intracranial threshold of 22 mm Hg (22% ± 26% vs. 28% ± 24%; p = 0.05). The MNM interpretation cohort had a lower proportion of anesthetic days (48% [24-70%] vs. 67% [33-91%]; p = 0.02) and higher average end-tidal carbon dioxide during monitoring (34 ± 6 mm Hg vs. 32 ± 6 mm Hg; p < 0.01; d = 0.36). After controlling for injury severity, patients undergoing standardized MNM interpretation and reporting had an odds of 1.5 (95% CI, 1.37-1.59) for better outcomes. Standardized interpretation and reporting of MNM data are a novel approach to provide clinical insight and to guide individualized critical care. In patients with sTBI, independent MNM interpretation and communication to bedside clinical care teams may result in improved intracranial pressure control, fewer medical interventions, and changes in ventilatory management. In this study, the implementation of a system for management, including standardized MNM interpretation, was associated with a significant improvement in outcome.

Virtual surgical planning and use of a 3D-printed, patient-specific reduction system for minimally invasive plate osteosynthesis of diaphyseal tibial fractures in dogs: A historic case control study.

To compare the efficacy and clinical outcomes of computed tomography (CT)-based virtual surgical planning (VSP) and a three-dimensional (3D)-printed, patient-specific reduction system to conventional indirect reduction techniques for diaphyseal tibial fractures stabilized using minimally invasive plate osteosynthesis (MIPO) in dogs. A prospective clinical study with a historic control cohort. Dogs undergoing MIPO stabilization of diaphyseal tibial fractures using a custom 3D-printed reduction system (3D-MIPO; n = 15) or conventional indirect reduction techniques (c-MIPO; n = 14). Dogs were prospectively enrolled to the 3D-MIPO group and CT scans were used to design and fabricate a custom 3D-printed reduction system to facilitate MIPO. Medical records were searched to identify dogs for the c-MIPO group. Pre-, intra- and postoperative parameters were compared between groups. The duration from presentation until surgery was 23 h longer in the 3D-MIPO group (p = .002). Fewer intraoperative fluoroscopic images were acquired (p < .001) and mean surgical duration was 34 min shorter in the 3D-MIPO group (p = .014). Median postoperative tibial length, frontal alignment, and sagittal alignment were within 4 mm, 3° and 3°, respectively, of the contralateral tibia in both groups and did not differ between reduction groups (p > .1). Postoperative complications occurred in 27% and 14% of fractures in the 3D-MIPO and c-MIPO groups, respectively. Both reduction methods yielded comparable results. Although the preoperative planning and guide preparation was time consuming, surgery times were shorter and fluoroscopy use was lessin the 3D-MIPO group. VSP and the custom 3D-printed reduction system facilitated efficient MIPO.