Delayed Diagnosis of Charcot Foot: A Systematic Review.

This study aims to examine the duration and rate of delayed diagnosis in Charcot foot. We systematically reviewed articles published in Medline, SCOPUS, and Cumulative Index of Nursing and Allied Health Literature to identify articles discussing delayed or misdiagnosis of Charcot foot. Random-effects models were generated to determine the average time from symptom onset to correct diagnosis (diagnostic delay duration) and proportion of patients misdiagnosed prior to being correctly diagnosed (delayed diagnosis rate). Our search identified 142 articles, 7 of which are included in this review. The review found that 53.2% of cases of Charcot osteoarthropathy experienced a delay in diagnosis (95% CI: 28.9%-77.4%). Overall, the duration of diagnostic delay was determined to be 86.9 days (95% CI: 10.5-162.1). We found that patients with Charcot foot experienced prolonged delays from symptom onset to correct diagnosis, and a majority of patients are misdiagnosed. These delays in diagnosis contribute to worse patient outcomes.

Geographical Variation in Traumatic Brain Injury Mortality by Proximity to the Nearest Neurosurgeon.

BACKGROUND: Trauma mortality disproportionately affects populations farther from potentially lifesaving trauma care, and traumatic brain injury (TBI) is no exception. Previous examinations have examined proximity to trauma centers as an explanation for trauma mortality, but little is known about the relationship between proximity to neurosurgeons specifically in TBI mortality. MATERIALS AND METHODS: In this cross-sectional study, county-level TBI mortality rates from 2008 to 2014 were examined in relation to the distance to the nearest neurosurgeon and trauma facility. The locations of practicing neurosurgeons and trauma facilities in the United States were determined by geocoding data from the 2017 Medicare Physician and Other Supplier and Provider of Services files (respectively). The association between TBI mortality and the distance from the population-weighted centroid of the county to a closest neurosurgeon and trauma facility was examined using multivariate negative binomial regression. RESULTS: A total of 761 of the 3108 counties (24.5%) in the continental United States were excluded from the analysis because they had 20 or fewer TBI deaths during this time, producing unstable estimates. Excluded counties accounted for 1.67% of the US population. Multivariate analysis revealed a county's mortality increased 10% for every 25 miles from the nearest neurosurgeon (adjusted incident rate ratio: 1.10 [95% confidence interval: 1.08-1.12]; P < 0.001). The distance to the nearest trauma facility was not found to be significantly associated with mortality (adjusted incident rate ratio: 1.01 [95% confidence interval: 0.99-1.03]; P = 0.36). CONCLUSIONS: These findings suggest that proximity to neurosurgeons may influence county-level TBI mortality. Further research into this topic with more granular data may help to allocate scarce public health resources.

The Safety of Immunosuppressants Used in the Treatment of Immune-Related Adverse Events due to Immune Checkpoint Inhibitors: a Systematic Review.

Purpose: Immune checkpoint inhibitor (ICI) use can lead to immune-related adverse events (irAEs) that require treatment with immunosuppressive medications in moderate to severe cases. Oncology society guidelines recommend systemic steroids and immunosuppressants such as infliximab and vedolizumab for the treatment of refractory cases. Limited information is available about the safety profile and potential adverse effects of these immunosuppressants. We have investigated the safety profile of multiple immunosuppressants which are used in the treatment of ICI-related irAEs. Methods: We performed a systematic review of studies reporting irAEs, from ICI use, and their medical management with immunosuppressants in adult cancer patients. We searched MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov from inception through September 1, 2022, using the following keywords or their equivalents: ICI, immunosuppressant, and irAE. We extracted observational studies and clinical trials that matched our criteria. A random effects model was used to estimate the overall incidence of infections associated with the treatment of irAEs. Results: Among the 11 studies included in this review (1036 total patients), melanoma (548 patients, 52.9%) was the most common primary cancer, followed by lung cancer (139 patients, 13.4%) and genitourinary cancers (131 patients, 12.6%). PD-1/PD-L1 monotherapy (460 patients, 44.4%) was used most, followed by a combination of PD-1/PD-L1 and CTLA-4 therapy (350 patients, 33.8%) and CTLA-4 monotherapy (226 patients, 22%). A total of 1024 (98.8%) patients had their irAEs treated with systemic steroids with majority having colitis and hepatobiliary irAEs; 335 patients (32.3%) were also treated with infliximab (mainly for colitis). Our review found 22.3% of patients treated for irAEs developed infectious adverse events (95% CI: 15.6%-29.1%, p<0.001). Among the 3 studies reporting the types of infections (41 total patients), bacterial (80.5%), followed by fungal (36.6%), infections were most common. Conclusions: Adverse events from irAE treatment occurred in about one-third of patients that received either steroids or a combination of steroids and other immunosuppressants. Clinicians should be aware of these immunosuppressant-related adverse effects, which can negatively impact cancer treatment and patient outcomes, when treating irAEs and consider shortening treatment duration or using alternative strategies when possible to mitigate these complications, future prospective studies should further investigate the safety of immunosuppressants in treating irAEs.

A hybrid multi-particle approach to range assessment-based treatment verification in particle therapy.

Particle therapy (PT) used for cancer treatment can spare healthy tissue and reduce treatment toxicity. However, full exploitation of the dosimetric advantages of PT is not yet possible due to range uncertainties, warranting development of range-monitoring techniques. This study proposes a novel range-monitoring technique introducing the yet unexplored concept of simultaneous detection and imaging of fast neutrons and prompt-gamma rays produced in beam-tissue interactions. A quasi-monolithic organic detector array is proposed, and its feasibility for detecting range shifts in the context of proton therapy is explored through Monte Carlo simulations of realistic patient models and detector resolution effects. The results indicate that range shifts of [Formula: see text] can be detected at relatively low proton intensities ([Formula: see text] protons/spot) when spatial information obtained through imaging of both particle species are used simultaneously. This study lays the foundation for multi-particle detection and imaging systems in the context of range verification in PT.

Minor vs. major leg amputation in adults with diabetes: Six-month readmissions, reamputations, and complications.

AIMS: The objective of this study was comparing medium-term outcomes between comparable minor and major amputations in adults with diabetes. METHODS: We used data from the 2016-2017 National Readmissions Database to construct a representative cohort of 15,581 adults with diabetes with lower extremity amputations. Patients were categorized by level of index amputation (major/minor), and propensity score matched to compare outcomes in candidates for either level of amputation. Readmission and reamputations were assessed at 1, 3, and 6 months following index amputation. RESULTS: In the 6 months following index amputation, large proportions of patients were readmitted (n = 7597, 48.8%) or had reamputations (n = 1990, 12.8%). Patients with minor amputations had greater odds of readmission (OR = 1.25; 95% CI 1.18-1.31), reamputation (OR = 3.71; 95% CI 3.34-4.12), and more proximal reamputation (OR = 2.61; 95% 2.33-2.93) (all P < 0.001). Further, minor amputation patients had higher and lower odds of readmission for postoperative infection (OR = 4.45; 95% CI 3.27-6.05), or sepsis (OR = 0.79; 95% CI 0.68-0.93), respectively. CONCLUSION: Patients desire to save as much limb as possible and should be counseled on higher risk for reamputation, readmission, and infection with minor amputations.

Predicting in-hospital mortality after traumatic brain injury: External validation of CRASH-basic and IMPACT-core in the national trauma data bank.

BACKGROUND: Traumatic brain injury (TBI) prognostic prediction models offer value to individualized treatment planning, systematic outcome assessments and clinical research design but require continuous external validation to ensure generalizability to different settings. The Corticosteroid Randomization After Significant Head Injury (CRASH) and International Mission on Prognosis and Analysis on Clinical Trials in TBI (IMPACT) models are widely available but lack robust assessments of performance in a current national sample of patients. The purpose of this study is to assess the performance of the CRASH-Basic and IMPACT-Core models in predicting in-hospital mortality using a nationwide retrospective cohort from the National Trauma Data Bank (NTDB). METHODS: The 2016 NTDB was used to analyze an adult cohort with moderate-severe TBI (Glasgow Coma Scale [GCS] ≤ 12, head Abbreviated Injury Scale of 2-6). Observed in-hospital mortality or discharge to hospice was compared to the CRASH-Basic and IMPACT-Core models' predicted probability of 14-day or 6-month mortality, respectively. Performance measures included discrimination (area under the receiver operating characteristic curve [AUC]) and calibration (calibration plots and Brier scores). Further sensitivity analysis included patients with GCS ≤ 14 and considered patients discharged to hospice to be alive at 14-days. RESULTS: A total of 26,228 patients were included in this study. Both models demonstrated good ability in differentiating between patients who died and those who survived, with IMPACT demonstrating a marginally greater AUC (0.863; 95% CI: 0.858 - 0.867) than CRASH (0.858; 0.854 - 0.863); p < 0.001. On calibration, IMPACT overpredicted at lower scores and underpredicted at higher scores but had good calibration-in-the-large (indicating no systemic over/underprediction), while CRASH consistently underpredicted mortality. Brier scores were similar (0.152 for IMPACT, 0.162 for CRASH; p < 0.001). Both models showed slight improvement in performance when including patients with GCS ≤ 14. CONCLUSION: Both CRASH-Basic and IMPACT-Core accurately predict in-hospital mortality following moderate-severe TBI, and IMPACT-Core performs well beyond its original GCS cut-off of 12, indicating potential utility for mild TBI (GCS 13-15). By demonstrating validity in the NTDB, these models appear generalizable to new data and offer value to current practice in diverse settings as well as to large-scale research design.

Simulation of the GCR spectrum in the Mars curiosity rover's RAD detector using MCNP6.

The paper presents results from MCNP6 simulations of galactic cosmic ray (GCR) propagation down through the Martian atmosphere to the surface and comparison with RAD measurements made there. This effort is part of a collaborative modeling workshop for space radiation hosted by Southwest Research Institute (SwRI). All modeling teams were tasked with simulating the galactic cosmic ray (GCR) spectrum through the Martian atmosphere and the Radiation Assessment Detector (RAD) on-board the Curiosity rover. The detector had two separate particle acceptance angles, 4π and 30 ° off zenith. All ions with Z = 1 through Z = 28 were tracked in both scenarios while some additional secondary particles were only tracked in the 4π cases. The MCNP6 4π absorbed dose rate was 307.3 ± 1.3 µGy/day while RAD measured 233 µGy/day. Using the ICRP-60 dose equivalent conversion factors built into MCNP6, the simulated 4π dose equivalent rate was found to be 473.1 ± 2.4 µSv/day while RAD reported 710 µSv/day.

The radiation environment on the surface of Mars - Summary of model calculations and comparison to RAD data.

The radiation environment at the Martian surface is, apart from occasional solar energetic particle events, dominated by galactic cosmic radiation, secondary particles produced in their interaction with the Martian atmosphere and albedo particles from the Martian regolith. The highly energetic primary cosmic radiation consists mainly of fully ionized nuclei creating a complex radiation field at the Martian surface. This complex field, its formation and its potential health risk posed to astronauts on future manned missions to Mars can only be fully understood using a combination of measurements and model calculations. In this work the outcome of a workshop held in June 2016 in Boulder, CO, USA is presented: experimental results from the Radiation Assessment Detector of the Mars Science Laboratory are compared to model results from GEANT4, HETC-HEDS, HZETRN, MCNP6, and PHITS. Charged and neutral particle spectra and dose rates measured between 15 November 2015 and 15 January 2016 and model results calculated for this time period are investigated.