Defining tumor growth in vestibular schwannomas: a volumetric inter-observer variability study in contrast-enhanced T1-weighted MRI.

PURPOSE: For patients with vestibular schwannomas (VS), a conservative observational approach is increasingly used. Therefore, the need for accurate and reliable volumetric tumor monitoring is important. Currently, a volumetric cutoff of 20% increase in tumor volume is widely used to define tumor growth in VS. The study investigates the tumor volume dependency on the limits of agreement (LoA) for volumetric measurements of VS by means of an inter-observer study. METHODS: This retrospective study included 100 VS patients who underwent contrast-enhanced T1-weighted MRI. Five observers volumetrically annotated the images. Observer agreement and reliability was measured using the LoA, estimated using the limits of agreement with the mean (LOAM) method, and the intraclass correlation coefficient (ICC). RESULTS: The 100 patients had a median average tumor volume of 903 mm3 (IQR: 193-3101). Patients were divided into four volumetric size categories based on tumor volume quartile. The smallest tumor volume quartile showed a LOAM relative to the mean of 26.8% (95% CI: 23.7-33.6), whereas for the largest tumor volume quartile this figure was found to be 7.3% (95% CI: 6.5-9.7) and when excluding peritumoral cysts: 4.8% (95% CI: 4.2-6.2). CONCLUSION: Agreement limits within volumetric annotation of VS are affected by tumor volume, since the LoA improves with increasing tumor volume. As a result, for tumors larger than 200 mm3, growth can reliably be detected at an earlier stage, compared to the currently widely used cutoff of 20%. However, for very small tumors, growth should be assessed with higher agreement limits than previously thought.

Can Periprosthetic Joint Infection of Tumor Prostheses Be Controlled With Debridement, Antibiotics, and Implant Retention?

BACKGROUND: Two-stage revision for periprosthetic joint infection (PJI) in patients who have undergone segmental replacement of the distal femur or proximal tibia after tumor resection can be associated with considerable morbidity, pain, and risk of complications because the procedure often results in removal of long, well-fixed stems from the diaphysis. A less-aggressive surgical approach, such as debridement, antibiotics, and implant retention (DAIR), may be attractive to patients and surgeons because of less morbidity, but the likelihood of eradicating infection in comparison to the traditional two-stage revision is not well established for oncology patients. Furthermore, the relative risk of subsequent amputation for DAIR versus two-stage revision has not been defined for this population. QUESTIONS/PURPOSES: (1) How does DAIR compare with two-stage revision in terms of infection control for patients with distal femoral or proximal tibial segmental modular endoprostheses? (2) Is DAIR as an initial procedure associated with an increased risk of amputation compared with two-stage revision for infection? METHODS: From the longitudinally maintained orthopaedic oncology surgical database at our institution, we identified 69 patients who had been treated for a clinical diagnosis of PJI at the knee between 1993 and 2015. We excluded 32% (22) of patients who did not meet at least one of the major criteria of the Musculoskeletal Infection Society (MSIS) for PJI, 3% (2) of patients who underwent immediate amputation, 3% (2) of patients who had a follow-up time of < 24 months, and 7% (5) of patients who did not have a primary tumor of the distal femur or proximal tibia. The study consisted of 38 patients, of whom eight underwent two-stage revision, 26 underwent DAIR, and four underwent extended DAIR (removal of all segmental components but with retention of stems and components fixed in bone) for their initial surgical procedure. To be considered free of infection, patients had to meet MSIS standards, including no positive cultures, drainage, or surgical debridement for a minimum of 2 years from the last operation. Factors associated with time-dependent risk of infection relapse, clearance, amputation, and patient survival were analyzed using Kaplan-Meier survivorship curves and the log-rank test to compare factors. Association of demographic and treatment factors was assessed using chi-square and Fisher exact tests. RESULTS: Continuous infection-free survival at 5 years was 16% (95% CI 2% to 29%) for patients undergoing DAIR compared with 75% (95% CI 45% to 100%) for patients undergoing two-stage revision (p = 0.006). The median (range) number of total surgical procedures was 3 per patient (1 to 10) for DAIR and 2 (2 to 5) for two-stage revision. Twenty-nine percent (11 of 38) of patients eventually underwent amputation. Survival without amputation was 69% (95% CI 51% to 86%) for DAIR compared with 88% (95% CI 65% to 100%) for two-stage revision at 5 years (p = 0.34). The cumulative proportion of patients achieving infection-free status (> 2 years continuously after last treatment) and limb preservation was 58% (95% CI 36% to 80%) for patients initially treated with DAIR versus 87% (95% CI 65% to 100%) for patients first treated with two-stage revision (p = 0.001). CONCLUSION: Infection control was better with two-stage revision than DAIR. The chance of eventual clearance of infection with limb preservation was better when two-stage revision was chosen as the initial treatment. However, the loss to follow-up in the two-stage revision group would likely make the true proportion of infection control lower than our estimate. Our experience would suggest that the process of infection eradication is a complex and difficult one. Most patients undergo multiple operations. Nearly one-third of patients eventually underwent amputation, and this was a serious risk for both groups. While we cannot strongly recommend one approach over the other based on our data, we would still consider the use of DAIR in patients who present with acute short duration of symptoms (< 3 weeks), no radiographic signs of erosion around fixed implants, and organisms other than Staphylococcus aureus. We would advocate the extended DAIR procedure with removal of all segmental or modular components, and we would caution patients that there is a high likelihood of needing further surgery. A prospective trial with strict adherence to indications may be needed to evaluate the relative merits of an extended DAIR procedure versus a two-stage revision. LEVEL OF EVIDENCE: Level III, therapeutic study.

Potentially Inappropriate End of Life Care and Healthcare Costs in the Last 30 Days of Life in Regions Providing Integrated Palliative Care in the Netherlands: A Registration-based Study.

Introduction: This study aimed to assess the effect of integrated palliative care (IPC) on potentially inappropriate end- of-life care and healthcare-costs in the last 30 days of life in the Netherlands. Methods: Nationwide health-insurance claims data were used to assess potentially inappropriate end-of-life care (≥2 emergency room visits; ≥2 hospital admissions; >14 days hospitalization; chemotherapy; ICU admission; hospital death) and healthcare-costs in all deceased adults in IPC regions pre- and post- implementation and in those receiving IPC compared to a 1:2 matched control group. Results: In regions providing IPC deceased adults (n = 37,468) received significantly less potentially inappropriate end-of-life care post-implementation compared to pre-implementation (26.5% vs 27.9%; p < 0.05). Deceased adults who received IPC (n = 210) also received significantly less potentially inappropriate end-of-life care compared to a matched control group (14.8% vs 28.3%; p < 0.05). Mean hospital costs significantly decreased for deceased adults who received IPC (€2,817), while mean costs increased for general practitioner services (€311) and home care (€1,632). Discussion: These results highlight the importance of implementation of integrated palliative care and suitable payment. Further research in a larger sample is needed. Conclusion: This study shows less potentially inappropriate end-of-life care and a shift in healthcare costs from hospital to general practitioner and home care with IPC.

High-angular-sensitivity X-ray phase-contrast microtomography of soft tissue through a two-directional beam-tracking synchrotron set-up.

Two-directional beam-tracking (2DBT) is a method for phase-contrast imaging and tomography that uses an intensity modulator to structure the X-ray beam into an array of independent circular beamlets that are resolved by a high-resolution detector. It features isotropic spatial resolution, provides two-dimensional phase sensitivity, and enables the three-dimensional reconstructions of the refractive index decrement, δ, and the attenuation coefficient, µ. In this work, the angular sensitivity and the spatial resolution of 2DBT images in a synchrotron-based implementation is reported. In its best configuration, angular sensitivities of ∼20 nrad and spatial resolution of at least 6.25 µm in phase-contrast images were obtained. Exemplar application to the three-dimensional imaging of soft tissue samples, including a mouse liver and a decellularized porcine dermis, is also demonstrated.

Circulating Tumor DNA Predicts Early Recurrence Following Locoregional Therapy for Oligometastatic Colorectal Cancer.

(1) Background: Local therapies offer a potentially curative approach for patients with oligometastatic colorectal cancer (CRC). An evidence-based consensus recommendation for systemic therapy following definitive locoregional therapy is lacking. Tumor-informed circulating tumor DNA (ctDNA) might provide information to help guide management in this setting. (2) Methods: A multi-institutional retrospective study was conducted, including patients with CRC that underwent curative-intent locoregional therapy to an isolated site of metastatic disease, followed by tumor-informed ctDNA assessment. The Kaplan-Meier method and log-rank tests were used to compare disease-free survival based on ctDNA results. ctDNA test performance was compared to carcinoembryonic antigen (CEA) test results using McNemar's test. (3) Results: Our study cohort consisted of 87 patients treated with locoregional interventions who underwent ctDNA testing. The initial ctDNA test post-intervention was positive in 28 patients and negative in 59 patients. The median follow-up time was 14.0 months. Detectable ctDNA post-intervention was significantly associated with early disease recurrence, with a median disease-free survival (DFS) of 6.63 months compared to 21.30 months in ctDNA-negative patients (p < 0.001). ctDNA detected a numerically higher proportion of recurrences than CEA (p < 0.097). Post-intervention systemic therapy was not associated with improved DFS (p = 0.745). (4) Conclusions: ctDNA results are prognostically important in oligometastatic CRC, and further prospective studies are urgently needed to define its role in guiding clinical decisions.

Improved tumour delivery of iron oxide nanoparticles for magnetic hyperthermia therapy of melanoma via ultrasound guidance and 111In SPECT quantification.

Magnetic field hyperthermia relies on the intra-tumoural delivery of magnetic nanoparticles by interstitial injection, followed by their heating on exposure to a remotely-applied alternating magnetic field (AMF). This offers a potential sole or adjuvant route to treating drug-resistant tumours for which no alternatives are currently available. However, two challenges in nanoparticle delivery currently hinder the effective clinical translation of this technology: obtaining enough magnetic material within the tumour to enable sufficient heating; and doing this accurately to limit or avoid damage to surrounding healthy tissue. A further complication is the lack of established methods to non-invasively quantify nanoparticle biodistribution, which is necessary to evaluate the performance of improved delivery strategies. Here we employ 111In radiolabelling and single-photon emission computed tomography (SPECT) to non-invasively quantify distribution of a clinical grade iron-oxide-based nanoparticle in a mouse model of melanoma. We show that compared to manual injection, ultrasound guided delivery together with syringe-pump-controlled infusion improves both the nanoparticle concentration within the tumour, and the accuracy of delivery - reducing off-target peri-tumoural delivery. Following AMF heating, injected melanomas shrank significantly compared to non-injected controls, validating therapeutic efficacy. Systemic off-target delivery was quantified and extrapolated to predict off-target energy absorbance within safe limits for the main sites of background accumulation. With many nanoparticle-based therapies currently in development for cancer, this image-guided delivery strategy has wide potential impact beyond the field of magnetic hyperthermia. Future use in representative patient cohorts would also be enabled by the high clinical availability of both SPECT and ultrasound imaging.

Regulation of a single inositol 1-phosphate synthase homeologue by HSFA6B contributes to fibre yield maintenance under drought conditions in upland cotton.

Drought stress substantially impacts crop physiology resulting in alteration of growth and productivity. Understanding the genetic and molecular crosstalk between stress responses and agronomically important traits such as fibre yield is particularly complicated in the allopolyploid species, upland cotton (Gossypium hirsutum), due to reduced sequence variability between A and D subgenomes. To better understand how drought stress impacts yield, the transcriptomes of 22 genetically and phenotypically diverse upland cotton accessions grown under well-watered and water-limited conditions in the Arizona low desert were sequenced. Gene co-expression analyses were performed, uncovering a group of stress response genes, in particular transcription factors GhDREB2A-A and GhHSFA6B-D, associated with improved yield under water-limited conditions in an ABA-independent manner. DNA affinity purification sequencing (DAP-seq), as well as public cistrome data from Arabidopsis, were used to identify targets of these two TFs. Among these targets were two lint yield-associated genes previously identified through genome-wide association studies (GWAS)-based approaches, GhABP-D and GhIPS1-A. Biochemical and phylogenetic approaches were used to determine that GhIPS1-A is positively regulated by GhHSFA6B-D, and that this regulatory mechanism is specific to Gossypium spp. containing the A (old world) genome. Finally, an SNP was identified within the GhHSFA6B-D binding site in GhIPS1-A that is positively associated with yield under water-limiting conditions. These data lay out a regulatory connection between abiotic stress and fibre yield in cotton that appears conserved in other systems such as Arabidopsis.

Experiences and preliminary effects of the Comprehensive chrOnic caRe outpatiEnt (CORE) clinic for patients with multimorbidity in the hospital setting.

RATIONALE: Healthcare systems remain disease oriented despite growing sustainability concerns caused by inadequate management of patients with multimorbidity. Comprehensive care programmes (CCPs) can play an important role in streamlining care delivery, but large differences in setup and results hinder firm conclusions on their effectiveness. Many elements for successful implementation of CCPs are identified, but strategies to overcome barriers and embed programmes within health systems remain unknown. AIMS AND OBJECTIVES: To address this knowledge gap through a detailed study of implementing a CCP in a Dutch hospital setting, including patient experiences, facilitators, barriers and ways to overcome those barriers. Additionally, this study aims to explore effects on patient satisfaction and healthcare use. METHODS: A qualitative study design with 39 semistructured interviews and focus groups between July 2020 and February 2023 with 16 patients and 17 involved professionals. Additionally, effects on quantitative outcomes for patient satisfaction (PACIC-20) and healthcare use were explored. RESULTS: Professionals expressed a wide range of topics related to implementation and ways to overcome barriers at hospital and system level. Alterations in the design to accommodate varying care demands, focus on inclusions through referrals, and lack of long-term support and appropriate financing were key topics. Patients expressed varying experiences, stated a strong desire for comprehensive information, and emphasised the importance of trust in caregivers. Patient satisfaction showed no effects, while healthcare use showed slight decreases in trends, but patient numbers were limited. CONCLUSION: The introduction of a CCP is feasible, and exploratory analysis on effectiveness shows lower hospital care use without decreasing patient satisfaction. However, this is accompanied by several challenges that show current fragmented systems still do not support implementation of integrated care initiatives. Overcoming those comes with substantial costs and may require a strong bottom-up implementation within a motivated team and actions on all levels of healthcare systems.

Pharmacologic inhibition of dipeptidyl peptidase 1 (cathepsin C) does not block in vitro granzyme-mediated target cell killing by CD8 T or NK cells.

Recently developed small-molecule inhibitors of the lysosomal protease dipeptidyl peptidase 1 (DPP1), also known as cathepsin C (CatC), can suppress suppurative inflammation in vivo by blocking the processing of zymogenic (pro-) forms of neutrophil serine proteases (NSPs), including neutrophil elastase, proteinase 3, and cathepsin G. DPP1 also plays an important role in activating granzyme serine proteases that are expressed by cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. Therefore, it is critical to determine whether DPP1 inhibition can also cause off-target suppression of CTL/NK-cell-mediated killing of virus-infected or malignant cells. Herein, we demonstrate that the processing of human granzymes A and B, transitioning from zymogen to active proteases, is not solely dependent on DPP1. Thus, the killing of target cells by primary human CD8+ T cells, NK cells, and gene-engineered anti-CD19 CAR T cells was not blocked in vitro even after prior exposure to high concentrations of the reversible DPP1 inhibitor brensocatib. Consistent with this observation, the turnover of model granzyme A/B peptide substrates in the human CTL/NK cell lysates was not significantly reduced by brensocatib. In contrast, preincubation with brensocatib almost entirely abolished (>90%) both the cytotoxic activity of mouse CD8+ T cells and granzyme substrate turnover. Overall, our finding that the effects of DPP1 inhibition on human cytotoxic lymphocytes are attenuated in comparison to those of mice indicates that granzyme processing/activation pathways differ between mice and humans. Moreover, the in vitro data suggest that human subjects treated with reversible DPP1 inhibitors, such as brensocatib, are unlikely to experience any appreciable deficits in CTL/NK-cell-mediated immunities.

The Omega Mastopexy Technique for the Correction of Breast Ptosis after Breast Implant Explantation.

Background: The past few years have seen a 50% increase in breast implant explantations. Patients with ptotic breasts may desire mastopexy, although conventional techniques are often invasive. We describe our experience with the omega mastopexy technique after breast implant explantation and capsulectomy. Methods: In the past 2 years, 10 patients with breast Regnault classification ptosis grade I-III underwent the omega mastopexy technique following breast implant explantation and capsulectomy. A detailed description of our operating technique is provided. Results: This series includes a total of 10 patients. The median age was 48.5 (IQR 42.8-52.5), median body mass index 26 (23.8-28.3) and median implant volume 355 (IQR 325-375). Excellent and stable aesthetic results were achieved without recurring ptosis. One patient, an active smoker, underwent reexcision after 1 year due to hypertrophic scars. No complications have been reported until this date at 2 years follow-up. Conclusions: The omega mastopexy technique offers an excellent alternative to classic lifting techniques for ptotic breasts after breast implant explantation. Patients with increased risk of wound healing impairment are especially likely to benefit.

BIGH3 mediates apoptosis and gap junction failure in osteocytes during renal cell carcinoma bone metastasis progression.

Renal cell carcinoma (RCC) bone metastatis progression is driven by crosstalk between tumor cells and the bone microenvironment, which includes osteoblasts, osteoclasts, and osteocytes. RCC bone metastases (RCCBM) are predominantly osteolytic and resistant to antiresorptive therapy. The molecular mechanisms underlying pathologic osteolysis and disruption of bone homeostasis remain incompletely understood. We previously reported that BIGH3/TGFBI (transforming growth factor-beta-induced protein ig-h3, shortened to BIGH3 henceforth) secreted by colonizing RCC cells drives osteolysis by inhibiting osteoblast differentiation, impairing healing of osteolytic lesions, which is reversible with osteoanabolic agents. Here, we report that BIGH3 induces osteocyte apoptosis in both human RCCBM tissue specimens and in a preclinical mouse model. We also demonstrate that BIGH3 reduces Cx43 expression, blocking gap junction (GJ) function and osteocyte network communication. BIGH3-mediated GJ inhibition is blocked by the lysosomal inhibitor hydroxychloroquine (HCQ), but not osteoanabolic agents. Our results broaden the understanding of pathologic osteolysis in RCCBM and indicate that targeting the BIGH3 mechanism could be a combinational strategy for the treatment of RCCBM-induced bone disease that overcomes the limited efficacy of antiresorptives that target osteoclasts.

Recent advances and challenges in the analysis of natural toxins.

Natural toxins (NTs) are poisonous secondary metabolites produced by living organisms developed to ward off predators. Especially low molecular weight NTs (MW<∼1 kDa), such as mycotoxins, phycotoxins, and plant toxins, are considered an important and growing food safety concern. Therefore, accurate risk assessment of food and feed for the presence of NTs is crucial. Currently, the analysis of NTs is predominantly performed with targeted high pressure liquid chromatography tandem mass spectrometry (HPLC-MS/MS) methods. Although these methods are highly sensitive and accurate, they are relatively expensive and time-consuming, while unknown or unexpected NTs will be missed. To overcome this, novel on-site screening methods and non-targeted HPLC high resolution mass spectrometry (HRMS) methods have been developed. On-site screening methods can give non-specialists the possibility for broad "scanning" of potential geographical regions of interest, while also providing sensitive and specific analysis at the point-of-need. Non-targeted chromatography-HRMS methods can detect unexpected as well as unknown NTs and their metabolites in a lab-based approach. The aim of this chapter is to provide an insight in the recent advances, challenges, and perspectives in the field of NTs analysis both from the on-site and the laboratory perspective.

Validation of a Handheld 6-Lead Device for QT Interval Monitoring in Resource-Limited Settings.

Importance: Rifampin-resistant tuberculosis treatment regimens require electrocardiographic (ECG) monitoring due to the use of multiple QTc-prolonging agents. Formal 12-lead ECG devices represent a significant burden in resource-constrained clinics worldwide and a potential barrier to treatment scale-up in some settings. Objective: To evaluate the diagnostic accuracy of a handheld 6-lead ECG device within resource-constrained clinics. Design, Setting, and Participants: This diagnostic study was performed within a multicenter, pragmatic (broad eligibility criteria with no exclusions for randomized participants), phase 3 rifampin-resistant tuberculosis treatment trial (BEAT Tuberculosis [Building Evidence for Advancing New Treatment for Tuberculosis]) in South Africa. A total of 192 consecutive trial participants were assessed, and 191 were recruited for this substudy between January 21, 2021, and March 27, 2023. A low proportion (3 of 432 [0.7%]) of all screened trial participants were excluded due to a QTc interval greater than 450 milliseconds. Triplicate reference standard 12-lead ECG results were human calibrated with readers blinded to 6-lead ECG results. Main Outcomes and Measures: Diagnostic accuracy, repeatability, and feasibility of a 6-lead ECG device. Results: A total of 191 participants (median age, 36 years [IQR, 28-45 years]; 81 female participants [42.4%]; 91 participants [47.6%] living with HIV) with a median of 4 clinic visits (IQR, 3-4 visits) contributed 2070 and 2015 12-lead and 6-lead ECG assessments, respectively. Across 170 participants attending 489 total clinic visits where valid triplicate QTc measurements were available for both devices, the mean 12-lead QTc measurement was 418 milliseconds (range, 321-519 milliseconds), and the mean 6-lead QTc measurement was 422 milliseconds (range, 288-574 milliseconds; proportion of variation explained, R2 = 0.4; P < .001). At a QTc interval threshold of 500 milliseconds, the 6-lead ECG device had a negative predictive value of 99.8% (95% CI, 98.8%-99.9%) and a positive predictive value of 16.7% (95% CI, 0.4%-64.1%). The normal expected range of within-individual variability of the 6-lead ECG device was high (±50.2 milliseconds [coefficient of variation, 6.0%]) relative to the 12-lead ECG device (±22.0 milliseconds [coefficient of variation, 2.7%]). The mean (SD) increase in the 12-lead QTc measurement during treatment was 10.1 (25.8) milliseconds, with 0.8% of clinic visits (4 of 489) having a QTc interval of 500 milliseconds or more. Conclusions and Relevance: This study suggests that simplified, handheld 6-lead ECG devices are effective triage tests that could reduce the need to perform 12-lead ECG monitoring in resource-constrained settings.

Single-fraction radiation retreatment for bone metastases: role of a rapid access clinic.

OBJECTIVES: This study investigates retreatment rates in single-fraction radiation therapy (SFRT) for painful bone metastasis in patients with limited life expectancy. We compared retreatment-free survival (RFS) in patients from a rapid access bone metastases clinic (RABC) and non-RABC patients, identifying factors associated with retreatment. METHODS: In this observational study, we analysed RABC patients who received SFRT between April 2018 and November 2019, using non-RABC SFRT patients as a comparison group. Patients with prior or perioperative radiation therapy (RT) were excluded. The primary endpoint was same-site and any-site retreatment with RT or surgery. Patient characteristics were compared using χ2 and Student's t-tests, with RFS estimates based on a multistate model considering death as a competing risk using Aalen-Johansen estimates. RESULTS: We identified 151 patients (79 RABC, 72 non-RABC) with 225 treatments (102 RABC, 123 non-RABC) meeting eligibility criteria. Of the 22 (10.8%) same-site retreatments, 5 (22.7%) received surgery, 14 (63.6%) received RT and 3 (13.6%) received both RT and surgery. We found no significant differences in any-site RFS (p=0.97) or same-site RFS (p=0.11). CONCLUSIONS: RFS is high and similar comparable in the RABC and non-RABC cohorts. Retreatment rates are low, even in patients with low Eastern Cooperative Oncology Group scores.

Neuroendocrine Tumors of Unknown Primary in the Setting of Cytoreductive Hepatectomy.

BACKGROUND: Surgical cytoreduction for neuroendocrine tumor liver metastasis (NETLM) consistently shows positive long-term outcomes. Despite reservations in guidelines for surgery when the primary tumor is unidentified (UP-NET), this study compared the surgical and oncologic long-term outcomes between patients with these rare cases undergoing cytoreductive surgery and patients who had liver resection for known primaries. METHODS: The study identified 32 unknown primary liver metastases (UP-NETLM) in 522 retrospectively evaluated patients who underwent resection of well-differentiated NETLM between January 2000 and December 2020. Tumor and patient characteristics were compared with those in 490 cases of liver metastasis from small intestinal (SI-NETLM) or pancreatic (pNETLM) primaries. Survival analysis was performed to highlight long-term outcome differences. Surgical outcomes were compared between liver resections alone and simultaneous primary resections to assess surgical risk distinctions. RESULTS: The UP-NET patients had fewer NETLMs (p = 0.004), which on the average were larger than SI-NETLMs or pNETLMs (p = 0.002). Expression of Ki-67 was balanced among the groups. Major hepatectomy was performed more often in the UP-NETLM group (p = 0.017). The 10-year survival rate of 53% for UP-NETLM was comparable with that for SI-NETML (58%; p = 0.463) and pNETLMs (47%; p = 0.497). The median hepatic progression-free survival was 26 months for the UP-NETLM patients and 25 months for the SI-NETLM patients compared to 12 months for the pNETLM patients (p < 0.001). Perioperative mortality was lower than 2%, and severe postoperative morbidity occurred in 21%, similarly distributed among all the groups. CONCLUSION: The surgical risk and long-term outcomes for the UP-NETLM patients were comparable with those for other NETLM cases, affirming the validity of equally aggressive surgical cytoreduction as a therapeutic option in carefully selected cases.

Percutaneous Cementation for Improvement of Pain and Function for Osteolytic Pelvic Metastasis: A Systematic Review.

INTRODUCTION: Pelvic metastasis is a common presentation among patients presenting with skeletal metastasis. Image-guided percutaneous cementation of these lesions is becoming increasingly popular for the treatment of these lesions. The objective of this study was to conduct a systematic review that investigates clinical outcomes after percutaneous cementation for pelvic metastasis. METHODS: A systematic review was registered with International Prospective Register of Systematic Reviews and performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed, SCOPUS, and Ovid MEDLINE databases. All level I to IV clinical studies published in the English language investigating the clinical outcomes after percutaneous cementation for pelvic metastasis were included. RESULTS: Fourteen studies with 579 patients (278 men, 301 women) and 631 metastatic pelvic lesions were included in the study. The mean follow-up range was 0.7 to 26.4 months. Percutaneous cementation alone was performed in 441 patients (76.2%). Supplemental ablative procedures were performed in 77 patients (13.3%), and supplemental internal fixation using cannulated screws was performed in 107 patients (18.5%). Twelve studies with 430 patients (74.2%) reported pain-related and/or functional outcome scores, of which all studies reported overall clinically notable improvement at short-term follow-up. All studies reported periprocedural complications. Local cement leakage was the most common complication (162/631 lesions, 25.7%) followed by transient local pain (25/579 patients, 4.3%). There were no reported cases of major complications. Seven patients (1.2%) underwent re-intervention for persistent symptoms. CONCLUSIONS: Percutaneous cementation may be an effective method for treating pain and function related to pelvic metastasis. The most common complication was cement leakage surrounding the lesion. The rates of major complications were low, and most complications appeared minor and transient. Additional prospective studies are needed to further assess the efficacy of this procedure. LEVEL OF EVIDENCE: IV, systematic review of level I to IV therapeutic studies.

Fewer emergency department alarms is associated with reduced use of medications for acute agitation.

BACKGROUND AND OBJECTIVES: Patient monitoring systems provide critical information but often produce loud, frequent alarms that worsen patient agitation and stress. This may increase the use of physical and chemical restraints with implications for patient morbidity and autonomy. This study analyzes how augmenting alarm thresholds affects the proportion of alarm-free time and the frequency of medications administered to treat acute agitation. METHODS: Our emergency department's patient monitoring system was modified on June 28, 2022 to increase the tachycardia alarm threshold from 130 to 150 and to remove alarm sounds for several arrhythmias, including bigeminy and premature ventricular beats. A pre-post study was performed lasting 55 days before and 55 days after this intervention. The primary outcome was change in number of daily patient alarms. The secondary outcomes were alarm-free time per day and median number of antipsychotic and benzodiazepine medications administered per day. The safety outcome was the median number of patients transferred daily to the resuscitation area. We used quantile regression to compare outcomes between the pre- and post-intervention period and linear regression to correlate alarm-free time with the number of sedating medications administered. RESULTS: Between the pre- and post-intervention period, the median number of alarms per day decreased from 1332 to 845 (-37%). This was primarily driven by reduced low-priority arrhythmia alarms from 262 to 21 (-92%), while the median daily census was unchanged (33 vs 32). Median hours per day free from alarms increased from 1.0 to 2.4 (difference 1.4, 95% CI 0.8-2.1). The median number of sedating medications administered per day decreased from 14 to 10 (difference - 4, 95% CI -1 to -7) while the number of escalations in level of care to our resuscitation care area did not change significantly. Multivariable linear regression showed a 60-min increase of alarm-free time per day was associated with 0.8 (95% CI 0.1-1.4) fewer administrations of sedating medication while an additional patient on the behavioral health census was associated with 0.5 (95% CI 0.0-1.1) more administrations of sedating medication. CONCLUSION: A reasonable change in alarm parameter settings may increase the time patients and healthcare workers spend in the emergency department without alarm noise, which in this study was associated with fewer doses of sedating medications administered.

An Efficient Brain-Switch for Asynchronous Brain-Computer Interfaces.

Intracortical brain computer interfaces (iBCIs) utilizing extracellular recordings mainly employ in vivo signal processing application-specific integrated circuits (ASICs) to detect action potentials (spikes). Conventionally, "brain-switches" based on spiking activity have been employed to realize asynchronous (self-paced) iBCIs, estimating when the user involves in the underlying BCI task. Several studies have demonstrated that local field potentials (LFPs) can effectively replace action potentials, drastically reducing the power consumption and processing requirements of in vivo ASICs. This article presents the first LFP-based brain-switch design and implementation using gated recurrent neural networks (RNNs). Compared to the previously reported brain-switches, our design requires no exhaustive learning phase for the estimation of optimal recording channels or frequency band selection, making it more applicable to practical asynchronous iBCIs. The synthesized ASIC of the designed in vivo LFP-based feature extraction unit, in a standard 180-nm CMOS process, occupies only 0.09 mm2 of silicon area, and the post place-and-route synthesis results indicate that it consumes 91.87 nW of power while operating at 2 kHz. Compared to the previously published ASICs, the proposed LFP-based brain-switch consumes the least power for in vivo digital signal processing and achieves comparable state estimation performance to that of spike-based brain-switches.

Traumatic Abdominal Wall Hernia: Management Using a Standardized Approach.

Traumatic abdominal wall hernias are a rare complication of high energy blunt trauma. There exist several studies evaluating and outlining potential management options but still no generalized consensus on management. This series was meant to evaluate the diagnosis and management of traumatic abdominal wall hernias. A prospectively maintained database was used to identify patients with TAWH from 2021 to 2022. The primary outcome was operative management. Secondary outcomes included: time to diagnosis and post-operative outcomes. Of the 19 patients in this case series, 100% (n = 19/19) were secondary to blunt trauma with a mean ISS of 21. Exploratory laparotomy was performed in 17 cases. 14 cases had concomitant traumatic injuries to visceral structures. Complications were found in nearly half of the patients with 3 experiencing wound dehiscence. Future studies should be aimed at standardizing management approach taking into account nature of the mechanism and concomitant injuries.