Intra-arterial Pressure Enabled Drug Delivery Significantly Increases Penetration of Glass Microspheres in a Porcine Liver Tumor Model.

PURPOSE: To test the hypothesis that Pressure Enabled Drug Delivery (PEDD) with a TriNav device (TNV-21120-35, TriSalus Life Sciences, Westminster, CO) would improve the delivery of surrogate therapeutic glass microspheres (GM) via hepatic artery infusion (HAI) to liver tumors when compared to a conventional endhole microcatheter. MATERIALS AND METHODS: The study was conducted in transgenic pigs (Oncopigs) with induced liver tumors. Tumors were infused intra-arterially with fluorescently labeled GM. PEDD with a TriNav device was compared to conventional endhole delivery in both lobar and selective infusions. Near-Infrared (nearIR) imaging was used to detect GM fluorescent signal in tumors. Image analysis with a custom Deep Learning algorithm (Visiopharm A/S) was used to quantitate signal intensity in relation to the tumor border. RESULTS: With lobar infusions, significant increases in GM signal intensity were observed in and around tumors after PEDD (n=10) when compared to conventional delivery (n=7), with PEDD increasing penetration into the tumor by 117% (p = 0.004). In selective infusions, PEDD (n=9) increased penetration into the tumor by 39% relative to conventional delivery (n=8, p =0.032). Lobar PEDD delivery of GM to the tumor was statistically equivalent to conventional selective delivery (p=0.497). CONCLUSIONS: PEDD with a TriNav device significantly improved GM uptake in liver tumors relative to conventional infusion in both lobar and selective procedures. Lobar GM delivery with PEDD was equivalent to conventional selective delivery with an endhole device, suggesting that proximal PEDD infusions may enable effective delivery without selection of distal target vessels.

Preoperative Expectations of Women Undergoing Breast Reconstruction Surgery.

Background: The study investigated the expectations of patients undergoing immediate breast reconstruction after mastectomy, considering factors such as the cause for mastectomy (cancer versus prophylactic due BRCA1 or BRCA2 gene mutations), age, marital status, and education. Methods: The study had a cross-sectional design. Eligible patients at Oslo University Hospital received a link to the BREAST-Q Expectations questionnaire, which they filled out before surgery from 2019 to 2022. Results: One hundred forty-six patients completed the questionnaire (79.8% response rate). The mean age was 46.6 years, and the majority (95.1%) were undergoing reconstruction with implants. Most patients (86.9%) wanted to be involved in the decision-making. The highest expectation was for breast appearance and the lowest for sensation after surgery. Patients not diagnosed with cancer (n = 27) before surgery expected significantly more pain after surgery compared with patients diagnosed with cancer (P = 0.016). Patients 40 years or younger had higher expectation of pain after surgery than patients 41 years or older, 73.2 versus 54.2, P < 0.001, respectively. After 10 years, 26.7% of the patients expected that further reconstruction procedures might be necessary. Conclusions: Our study's results regarding patient's expectations with breast reconstruction, as assessed using the BREAST-Q Expectations module, align with previous research in terms of overall trends. However, our study provides a more nuanced understanding by exploring variations within different patient subgroups. These differences emphasize the need for personalized preoperative counseling and support to align patient's expectations with realistic outcomes.

Chimeric antigen receptor macrophages target and resorb amyloid plaques.

Substantial evidence suggests a role for immunotherapy in treating Alzheimer's disease (AD). While the precise pathophysiology of AD is incompletely understood, clinical trials of antibodies targeting aggregated forms of ß amyloid (Aß) have shown that reducing amyloid plaques can mitigate cognitive decline in patients with early-stage AD. Here, we describe what we believe to be a novel approach to target and degrade amyloid plaques by genetically engineering macrophages to express an Aß-targeting chimeric antigen receptor (CAR-Ms). When injected intrahippocampally, first-generation CAR-Ms have limited persistence and fail to significantly reduce plaque load, which led us to engineer next-generation CAR-Ms that secrete M-CSF and self-maintain without exogenous cytokines. Cytokine secreting "reinforced CAR-Ms" have greater survival in the brain niche and significantly reduce plaque load locally in vivo. These findings support CAR-Ms as a platform to rationally target, resorb, and degrade pathogenic material that accumulates with age, as exemplified by targeting Aß in AD.

Association between underweight status and chylothorax after esophagectomy for esophageal cancer: A propensity score-matched analysis.

Objective: To use a nationwide database of hospitalizations to investigate underweight status as a risk factor for postesophagectomy complications. Methods: We identified all patients who underwent esophagectomy with a diagnosis of esophageal cancer and known body mass index in the 2018-2020 Nationwide Readmissions Database. All hospital visits for esophagectomy and within 30 days of initial discharge were analyzed for postoperative complications, including chylothorax. Patients who were underweight were propensity score matched with patients who were not. Multivariable logistic regression was performed to identify complications that were significantly associated with underweight status. Results: There were 1877 patients with esophageal cancer meeting inclusion criteria. Following propensity score matching, 433 patients who were underweight were matched to 433 patients who were not. In the multivariable model of the matched sample, which adjusted for age, sex, Charlson Comorbidity Index, history of chemotherapy or radiation therapy, and preoperative surgical feeding access, patients who were underweight were estimated to have 2.06 times the odds for chylothorax (95% confidence interval [CI], 1.07-4.25, P = .035). Underweight status was also significantly associated with acute bleed (odds ratio [OR], 1.52; 95% CI, 1.12-2.05, P = .007), pneumothorax (OR, 2.33; 95% CI, 1.19-4.85; P = .017), pneumonia (OR, 2.30; 95% CI, 1.53-3.50, P < .001), and in-hospital mortality (OR, 2.42; 95% CI, 1.31-4.69, P = .006). Conclusions: Underweight status was found to be a risk factor for chylothorax after esophagectomy, which may have implications for perioperative care of esophageal cancer patients. Future studies should assess whether using feeding tubes or total parenteral nutrition preoperatively or thoracic duct ligation intraoperatively decreases risk of chylothorax among patients who were underweight.

Management of recurrent lumbar disc herniation: a comparative analysis of posterior lumbar interbody fusion and repeat discectomy.

Background: For recurrent lumbar disc herniation, many experts suggest a repeat discectomy without stabilization due to its minimal tissue manipulation, lower blood loss, shorter hospital stay, and lower cost, recent research on the role of instability in disc herniation has made fusion techniques popular among spinal surgeons. The authors compare the postoperative outcomes of posterior lumbar interbody fusion (PLIF) and repeat discectomy for same-level recurrent disc herniation. Methods: The patients included had previously undergone discectomy and presented with a same-level recurrent lumbar disc herniation. The patients were placed into two groups: 1) discectomy only, 2) PLIF based on the absence or presence of segmental instability. Preoperative and postoperative Oswestry disability index scores, duration of surgery, blood loss, duration of hospitalization, and complications were analyzed. Results: The repeat discectomy and fusion groups had 40 and 34 patients, respectively. The patients were followed up for 2.68 (1-4) years. There was no difference in the duration of hospitalization (3.73 vs. 3.29 days P=0.581) and operative time (101.25 vs. 108.82 mins, P=0.48). Repeat discectomy had lower intraoperative blood loss, 88.75 ml (50-150) versus 111.47 ml (30-250) in PLIF (P=0.289). PLIF had better ODI pain score 4.21 (0-10) versus 9.27 (0-20) (P-value of 0.018). Recurrence was 22.5% in repeat discectomy versus 0 in PLIF. Conclusion: PLIF and repeat discectomy for recurrent lumbar disc herniation have comparable intraoperative blood loss, duration of surgery, and hospital stay. PLIF is associated with lower durotomy rates and better long-term pain control than discectomy. This is due to recurrence and progression of degenerative process in discectomy patients, which are eliminated and slowed, respectively, by PLIF.

Real-world evidence of Pressure-Enabled Drug Delivery for trans-arterial chemoembolization and radioembolization among patients with hepatocellular carcinoma and liver metastases.

OBJECTIVES: Pressure-Enabled Drug Delivery (PEDD), a method using pressure to advance catheter-delivered drug distribution, can improve treatment for hepatocellular carcinoma (HCC) and liver metastases, but real-world evidence is limited. We compared baseline patient characteristics, clinical complexity, and post-procedure healthcare resource utilization (HRUs) and clinical complications for PEDD and non-PEDD procedures. METHODS: This study used a retrospective, longitudinal, cohort design of claims data from Clarivate's Real World Data Repository, which includes 98% of US payers with over 300 million unique patients from all US states. We identified patients with a trans-arterial chemoembolization (TACE) or trans-arterial radioembolization (TARE) from 1 January 2019 to 31 December 2022. Subsamples grouped patients with HCC receiving a TARE procedure at their first embolization and patients with metastatic colorectal cancer (CRC) that received a TARE procedure. We reported descriptive comparisons of our full sample of patients with HCC and liver metastases receiving PEDD versus non-PEDD procedures. We then conducted a matching-adjusted comparison of HRUs and clinical complications for PEDD and non-PEDD patients among our subsamples (HCC receiving a TARE procedure at their first embolization and patients with metastatic CRC that received a TARE procedure). Matching was based on baseline demographic and clinical characteristics using coarsened exact matching and propensity-score matching. HRUs included inpatient, outpatient, and emergency department visits. Clinical complications included ascites, cholecystitis, fatigue, gastric ulcer, gastritis, jaundice, LFT increase, lymphopenia, portal hypertension, and post-embolization syndrome. RESULTS: PEDD procedures were used on patients with worse baseline disease burdens: baseline Charlson comorbidity index (mean of 6.5 vs. 5.8), any prior clinical complication related to underlying disease (33.7 vs. 31.0%), and prior systemic therapy (22.1% vs. 16.2%). PEDD patients had a greater number of procedural codes indicative of technical complexity for TACE (PEDD mean = 226.3; non-PEDD mean = 134.5; p value <.01) and TARE (PEDD mean = 205.56; non-PEDD mean = 94.8; p value <0.01). Matching-adjusted analyses of patients with HCC and CRC demonstrated comparable HRU and clinical complications for PEDD and non-PEDD procedures post-index. CONCLUSION: Despite higher baseline disease burden and complexity, post-procedure HRU and clinical complications for PEDD patients were similar to non-PEDD patients. The complex baseline clinical profile may reflect selection of challenging cases for PEDD use. Future studies should validate the benefits observed with PEDD embolization in larger samples with greater statistical power.

Prevalence and Predictors of Concomitant Meniscal and Ligamentous Injuries Associated With ACL Surgery: An Analysis of 20 Years of ACL Reconstruction at a Tertiary Care Children's Hospital.

BACKGROUND: There is an increasing rate of procedures being performed for concomitant injuries during anterior cruciate ligament (ACL) surgery. Few studies have examined risk factors for these associated injuries in young patients. HYPOTHESIS: There are patient-related factors predictive of concomitant knee pathology that differ between age-based cohorts. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Natural language processing was used to extract clinical variables from available notes of patients undergoing ACL surgery between 2000 and 2020 at a single institution (5174 ACL surgeries; mean age, 17 ± 4 years; 53.1% female; accuracy, >98%). Patients were stratified to pediatric (5-13 years), adolescent (14-19 years), and young adult (20-35 years) cohorts. Logistic regression was used to determine predictors of concomitant injury to the menisci, medial collateral ligament (MCL), posterolateral corner (PLC), and posterior cruciate ligament (PCL). RESULTS: Between 2000 and 2020, 54% of pediatric, 71% of adolescent, and 70% of adult patients had ≥1 concomitant soft tissue injury. In children and adolescents, increased age was consistently predictive of sustaining a concomitant injury (P < .02). Female children had increased odds of concomitant medial meniscal injury, while female adults had decreased odds (P≤ .046). Adolescent and adult female patients had decreased odds of concomitant lateral meniscal injury (P≤ .027). Female children had increased odds of injury to the MCL (P = .015), whereas female children and adolescents had decreased odds of PCL injury (P≤ .044). Adolescents undergoing revision ACL surgery had increased odds of meniscal injury (P≤ .001) and decreased odds of concomitant MCL injury (P = .028). Increased body mass index (BMI) was associated with increased odds of concomitant medial meniscal injury in all cohorts (P≤ .041), lateral meniscal injury in adults (P = .045), and PLC injury in children (P = .016). Contact injuries were associated with increased odds of MCL injury in adolescents (P = .017) and PLC injury in adolescents and adults (P < .014). CONCLUSION: These findings support the hypothesis, as there were multiple factors that significantly affected the risk of concomitant injuries that differed between cohorts. Increased age, BMI, and contact injury history were generally associated with increased odds of sustaining a concomitant injury, whereas female sex and revision ACL surgery had mixed effects. Further studies are essential to investigate the sex-based differences in risk for concomitant injuries and to develop tailored treatment plans that minimize the risk of secondary ACL injury.

Longer hospitalizations, more complications, and greater readmissions for patients with comorbid psychiatric disorders undergoing pulmonary lobectomy.

OBJECTIVE: To examine the influence of comorbid psychiatric disorders (PSYD) on postoperative outcomes in patients undergoing pulmonary lobectomy. METHODS: A retrospective analysis of the Healthcare Cost and Utilization Project Nationwide Readmissions Database from 2016 to 2018 was performed. Patients with lung cancer with and without psychiatric comorbidities who underwent pulmonary lobectomy were collated and analyzed (International Classification of Diseases, 10th Revision, Clinical Modification Mental, Behavioral and Neurodevelopmental disorders [F01-99]). The association of PSYD with complications, length of stay, and readmissions was assessed using a multivariable regression analysis. Additional subgroup analyses were performed. RESULTS: A total of 41,691 patients met inclusion criteria. Of these, 27.84% (11,605) of the patients had at least 1 PSYD. PSYD was associated with a significantly increased risk of postoperative complications (relative risk, 1.041; 95% CI, 1.015-1.068; P = .0018), pulmonary complications (relative risk, 1.125; 95% CI, 1.08-1.171; P < .0001), longer length of stay (PSYD mean, 6.79 days and non-PSYD mean, 5.68 days; P < .0001), higher 30-day readmission rate (9.2% vs 7.9%; P < .0001), and 90-day readmission rate (15.4% vs 12.9%; P < .007). Among patients with PSYD, those with cognitive disorders and psychotic disorders (eg, schizophrenia) appear to have the highest rates and risks of postoperative morbidity and in-hospital mortality. CONCLUSIONS: Patients with lung cancer with comorbid psychiatric disorders undergoing lobectomy experience worse postoperative outcomes with longer hospitalization, increased rates of overall and pulmonary complications, and greater readmissions suggesting potential opportunities for improved psychiatric care during the perioperative period.

Vaccine response after pneumococcal vaccination in allogeneic hematopoietic stem cell transplant recipients.

Current guidelines for vaccination in allogeneic hematopoietic stem cell transplant (HCT) recipients recommend initiation of pneumococcal vaccination series three to six months post-HCT, with most data supporting initiation at six months due to a more robust immune response. This single-center, retrospective, observational chart review aimed to evaluate the impact of initiating the pneumococcal vaccine series at three months post-HCT compared to six months post-HCT. The primary endpoints were defined as a percentage of patients with a serologic response of >1 and >1.3 µg/mL for over 50% of the defined serotypes. Outcomes showed no difference in immunologic response between the two groups.

Association of perioperative plasma concentration of neurofilament light with delirium after cardiac surgery: a nested observational study.

BACKGROUND: Neurofilament light is a blood-based biomarker of neuroaxonal injury that can provide insight into perioperative brain vulnerability and injury. Prior studies have suggested that increased baseline and postoperative concentrations of neurofilament light are associated with delirium after noncardiac surgery, but results are inconsistent. Results have not been reported in cardiac surgery patients, who are among those at highest risk for delirium. We hypothesised that perioperative blood concentrations of neurofilament light (both baseline and change from baseline to postoperative day 1) are associated with delirium after cardiac surgery. METHODS: This study was nested in a trial of arterial blood pressure targeting during cardiopulmonary bypass using cerebral autoregulation metrics. Blood concentrations of neurofilament light were measured at baseline and on postoperative day 1. The primary outcome was postoperative delirium. Regression models were used to examine the associations between neurofilament light concentration and delirium and delirium severity, adjusting for age, sex, race, logistic European System for Cardiac Operative Risk Evaluation, bypass duration, and cognition. RESULTS: Delirium occurred in 44.6% of 175 patients. Baseline neurofilament light concentration was higher in delirious than in non-delirious patients (median 20.7 pg ml-1 [IQR 16.1-33.2] vs median 15.5 pg ml-1 [IQR 12.1-24.2], P<0.001). In adjusted models, greater baseline neurofilament light concentration was associated with delirium (odds ratio, 1.027; 95% confidence interval, 1.003-1.053; P=0.029) and delirium severity. From baseline to postoperative day 1, neurofilament light concentration increased by 42%, but there was no association with delirium. CONCLUSIONS: Baseline neurofilament light concentration, but not change from baseline to postoperative day 1, was associated with delirium after cardiac surgery.

Characterisation of former manufactured gas plant soils using parent and alkylated polycyclic aromatic hydrocarbons and Rock-Eval(6) pyrolysis.

Soils sampled from 10 former manufactured gas plants (MGP) in the UK were investigated using gas chromatography mass spectrometry (GC-MS/MS) and Rock-Eval (6) Pyrolysis (RE). RE is a screening tool used to characterise bulk organic matter in soils via the release of carbon compounds during pyrolysis and oxidation. Both the distributions and concentrations of 30 parent and 21 alkylated polycyclic aromatic hydrocarbons (PAHs) and the parameters of RE were analysed to establish relationships between soils and the MGP processes history. Principal component analysis (PCA) using the PAHs distributions and RE parameters can assist with differentiating between MGP processes. MGP processes utilizing oil provided the clearest results, attributed to petrogenic signatures with high proportions of low molecular weight PAHs. Processes using lower temperature processes were distinguished by higher proportions of high molecular weight PAHs. RE parameters alone were unable to distinguish MGP processes but showed potential in estimating the lability and thus the amount of PAH that could be released from soils. This research provides new insights that may be useful in understanding and characterising the risks posed to human health from PAHs in soils.

Adjuvant chemotherapy, not radiotherapy, prolongs survival for node-negative non-small cell lung cancer with positive surgical margins.

Objective: The study objective was to determine differences in survival depending on adjuvant therapy type, timing, and sequence in node-negative disease with positive margins after non-small cell lung cancer resection. Methods: The National Cancer Database was queried for patients with positive margins after surgical resection of treatment-naïve cT1-4N0M0 pN0 non-small cell lung cancer who underwent adjuvant radiotherapy or chemotherapy from 2010 to 2016. Adjuvant treatment groups were defined as surgery alone, chemotherapy alone, radiotherapy alone, concurrent chemoradiotherapy, sequential chemotherapy then radiotherapy, and sequential radiotherapy then chemotherapy. The impact of adjuvant radiotherapy initiation timing on survival was evaluated using multivariable Cox regression. Kaplan-Meier curves were generated to compare 5-year survival. Results: A total of 1713 patients met inclusion criteria. Five-year survival estimates differed significantly between cohorts: surgery alone, 40.7%; chemotherapy alone, 47.0%; radiotherapy alone, 35.1%; concurrent chemoradiotherapy, 45.7%; sequential chemotherapy then radiotherapy, 36.6%; and sequential radiotherapy then chemotherapy, 32.2% (P = .033). Compared with surgery alone, adjuvant radiotherapy alone had a lower estimated survival at 5 years, although overall survival did not differ significantly (P = .8). Chemotherapy alone improved 5-year survival compared with surgery alone (P = .0016) and provided a statistically significant survival advantage over adjuvant radiotherapy (P = .002). Compared with radiotherapy-inclusive multimodal therapies, chemotherapy alone yielded similar 5-year survival (P = .066). Multivariable Cox regression showed an inverse linear association between time to adjuvant radiotherapy initiation and survival, but with an insignificant trend (10-day hazard ratio, 1.004; P = .90). Conclusions: In treatment-naïve cT1-4N0M0 pN0 non-small cell lung cancer with positive surgical margins, only adjuvant chemotherapy was associated with a survival improvement compared with surgery alone, with no radiotherapy-inclusive treatment providing additional survival benefit. Delayed timing of radiotherapy initiation was not associated with a survival reduction.

Chest Wall Contouring in Transgender Men: A 20-Year Experience from a National Center.

Several western countries have experienced a drastic increase of referrals to specialist gender services of transgender and gender-diverse people. Chest wall contouring is an important element in treatment of gender dysphoria. National data concerning this group have yet to be investigated. The aim of this study was to examine and evaluate the techniques and surgical outcome of chest wall contouring from the last 20 years from a single center in Norway. Methods: This study is a retrospective review of all female-to-male patients who underwent chest wall contouring surgery at Oslo University Hospital between 2000 and 2020. Statistical analysis with comparison of techniques and evaluation of development over time was examined. Results: In total, 333 patients underwent bilateral chest wall contouring, 209 (62.8%) with inframammary incision with free nipple graft (IM), and 124 (37.2%) with periareolar technique (PA). In 20 years, the average age decreased from 31 (19-68) to 24.9 years (17-61). Average body mass index was significantly lower in the PA-group than in the IM-group. Complication rate was 20.7%, with postoperative bleeding being the most frequent (9.6%). Revision surgery was required in 24.9% of the cases; periareolar technique required significantly more procedures. Conclusions: The number of patients referred and operated on has increased drastically over a 20-year period. When comparing the techniques, the outcome concerning complications and revisions is at an acceptable level. Postoperative bleeding and revision surgery occur more often with the periareolar technique. There remains a knowledge gap concerning quality of life and satisfaction after surgery within this patient group.

Hydrogen Bonding Compensation on the Convex Solvent-Exposed Helical Face of IA3, an Intrinsically Disordered Protein.

Saccharomyces cerevisiae IA3 is a 68 amino acid peptide inhibitor of yeast proteinase A (YPRA) characterized as a random coil when in solution, folding into an N-terminal amphipathic alpha helix for residues 2-32 when bound to YPRA, with residues 33-68 unresolved in the crystal complex. Circular dichroism (CD) spectroscopy results show that amino acid substitutions that remove hydrogen-bonding interactions observed within the hydrophilic face of the N-terminal domain (NTD) of IA3-YPRA crystal complex reduce the 2,2,2-trifluoroethanol (TFE)-induced helical transition in solution. Although nearly all substitutions decreased TFE-induced helicity compared to wild-type (WT), each construct did retain helical character in the presence of 30% (v/v) TFE and retained disorder in the absence of TFE. The NTDs of 8 different Saccharomyces species have nearly identical amino acid sequences, indicating that the NTD of IA3 may be highly evolved to adopt a helical fold when bound to YPRA and in the presence of TFE but remain unstructured in solution. Only one natural amino acid substitution explored within the solvent-exposed face of the NTD of IA3 induced TFE-helicity greater than the WT sequence. However, chemical modification of a cysteine by a nitroxide spin label that contains an acetamide side chain did enhance TFE-induced helicity. This finding suggests that non-natural amino acids that can increase hydrogen bonding or alter hydration through side-chain interactions may be important to consider when rationally designing intrinsically disordered proteins (IDPs) with varied biotechnological applications.

Chimeric Antigen Receptor Macrophages Target and Resorb Amyloid Plaques in a Mouse Model of Alzheimer's Disease.

Substantial evidence suggests a role for immunotherapy in treating Alzheimer's disease (AD). Several monoclonal antibodies targeting aggregated forms of beta amyloid (Aß), have been shown to reduce amyloid plaques and in some cases, mitigate cognitive decline in early-stage AD patients. We sought to determine if genetically engineered macrophages could improve the targeting and degradation of amyloid plaques. Chimeric antigen receptor macrophages (CAR-Ms), which show promise as a cancer treatment, are an appealing strategy to enhance target recognition and phagocytosis of amyloid plaques in AD. We genetically engineered macrophages to express a CAR containing the anti-amyloid antibody aducanumab as the external domain and the Fc receptor signaling domain internally. CAR-Ms recognize and degrade Aß in vitro and on APP/PS1 brain slices ex vivo; however, when injected intrahippocampally, these first-generation CAR-Ms have limited persistence and fail to reduce plaque load. We overcame this limitation by creating CAR-Ms that secrete M-CSF and self-maintain without exogenous cytokines. These CAR-Ms have greater survival in the brain niche, and significantly reduce plaque load locally in vivo. These proof-of-principle studies demonstrate that CAR-Ms, previously only applied to cancer, may be utilized to target and degrade unwanted materials, such as amyloid plaques in the brains of AD mice.

Epidemiology of cranial infections in battlefield-related penetrating and open cranial injuries.

BACKGROUND: Penetrating brain injuries are a potentially lethal injury associated with substantial morbidity and mortality. We examined characteristics and outcomes among military personnel who sustained battlefield-related open and penetrating cranial injuries during military conflicts in Iraq and Afghanistan. METHODS: Military personnel wounded during deployment (2009-2014) were included if they sustained an open or penetrating cranial injury and were admitted to participating hospitals in the United States. Injury characteristics, treatment course, neurosurgical interventions, antibiotic use, and infection profiles were examined. RESULTS: The study population included 106 wounded personnel, of whom 12 (11.3%) had an intracranial infection. Posttrauma prophylactic antibiotics were prescribed in more than 98% of patients. Patients who developed central nervous system (CNS) infections were more likely to have undergone a ventriculostomy ( p = 0.003), had a ventriculostomy in place for a longer period (17 vs. 11 days; p = 0.007), had more neurosurgical procedures ( p < 0.001), and have lower presenting Glasgow Coma Scale ( p = 0.01) and higher Sequential Organ Failure Assessment scores ( p = 0.018). Time to diagnosis of CNS infection was a median of 12 days postinjury (interquartile range, 7-22 days) with differences in timing by injury severity (critical head injury had median of 6 days, while maximal [currently untreatable] head injury had a median of 13.5 days), presence of other injury profiles in addition to head/face/neck (median, 22 days), and the presence of other infections in addition to CNS infections (median, 13.5 days). The overall length of hospitalization was a median of 50 days, and two patients died. CONCLUSION: Approximately 11% of wounded military personnel with open and penetrating cranial injuries developed CNS infections. These patients were more critically injured (e.g., lower Glasgow Coma Scale and higher Sequential Organ Failure Assessment scores) and required more invasive neurosurgical procedures. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Repeat discectomy for recurrent same level disc herniation: A literature review of the past 5 years.

Background: Recurrent disc herniations remain a challenge in spinal surgery. Although some authors recommend a repeat discectomy, others offer more invasive secondary fusions. Here, we reviewed the literature (2017-2022) regarding the safety/efficacy of treating recurrent disc herniations with repeated discectomy alone. Methods: Our literature search of recurrent lumbar disc herniations included; Medline, PubMed, Google scholar, and the Cochrane database. We focused on the types of discectomy performed, perioperative morbidity, costs, length of surgery, pain scores, and incidence of secondary dural tears. Results: We identified 769 cases that included 126 microdiscectomies, and 643 endoscopic discectomies. Rates of disc recurrence ranged from 1% to 25% with accompanying secondary durotomy varying from 2% to 15%. In addition, operative times were relatively short, ranging from 29.2 min to 125 min, with a relatively small average estimated blood loss (i.e., minimal to maximally 150 mls). Conclusion: Repeated discectomy was the most commonly performed treatment for same-level recurrent disc herniations. Despite minimal intraoperative blood loss and short operating times, there was a significant risk of durotomy. Notably, patients must be informed that more extensive bone removal for treating recurrent disc increases the risk for instability warranting subsequent fusion.

Intrinsic tumor resistance to CAR T cells is a dynamic transcriptional state that is exploitable with low-dose radiation.

Chimeric antigen receptor (CAR) T-cell therapy represents a major advancement for hematologic malignancies, with some patients achieving long-term remission. However, the majority of treated patients still die of their disease. A consistent predictor of response is tumor quantity, wherein a higher disease burden before CAR T-cell therapy portends a worse prognosis. Focal radiation to bulky sites of the disease can decrease tumor quantity before CAR T-cell therapy, but whether this strategy improves survival is unknown. We find that substantially reducing systemic tumor quantity using high-dose radiation to areas of bulky disease, which is commonly done clinically, is less impactful on overall survival in mice achieved by CAR T cells than targeting all sites of disease with low-dose total tumor irradiation (TTI) before CAR T-cell therapy. This finding highlights another predictor of response, tumor quality, the intrinsic resistance of an individual patient's tumor cells to CAR T-cell killing. Little is known about whether or how an individual tumor's intrinsic resistance may change under different circumstances. We find a transcriptional "death receptor score" that reflects a tumor's intrinsic sensitivity to CAR T cells can be temporarily increased by low-dose TTI, and the timing of this transcriptional change correlates with improved in vivo leukemia control by an otherwise limited number of CAR T cells. This suggests an actionable method for potentially improving outcomes in patients predicted to respond poorly to this promising therapy and highlights that intrinsic tumor attributes may be equally or more important predictors of CAR T-cell response as tumor burden.

Bridging and downstaging with TACE in early and intermediate stage hepatocellular carcinoma: Predictors of receiving a liver transplant.

Background and Aims: In patients with surgically unresectable early and intermediate stage hepatocellular carcinoma (HCC), only liver transplant (LT) offers a cure. Locoregional therapies, such as transarterial chemoembolization (TACE), are widely used to bridge patients waiting for an LT or downstage tumors beyond Milan Criteria (MC). However, there are no formal guidelines on the number of TACE procedures patients should receive. Our study explores the extent to which repeated TACE might offer diminishing gains toward LT. Approach: We retrospectively analyzed 324 patients with BCLC stage A and B HCC who had received TACE with the intention of disease downstaging or bridging to LT. In addition to baseline demographics, we collected data on LT status, survival, and the number of TACE procedures. Overall survival (OS) rates were estimated using the Kaplan-Meier method, and correlative studies were calculated using chi-square or Fisher's exact test. Results: Out of 324 patients, 126 (39%) received an LT, 32 (25%) of whom had responded favorably to TACE. LT significantly improved OS: HR 0.174 (0.094-0.322, P < .001). However, the LT rate significantly decreased if patients received ≥3 vs < 3 TACE procedures (21.6% vs 48.6%, P < .001). If their cancer was beyond MC after the third TACE, the LT rate was 3.7%. Conclusions: An increased number of TACE procedures may have diminishing returns in preparing patients for LT. Our study suggests that alternatives to LT, such as novel systemic therapies, should be considered for patients whose cancers are beyond MC after three TACE procedures.