Anaplastic sarcoma of the kidney (DICER1-sarcoma of the kidney): A report from the International Pleuropulmonary Blastoma/DICER1 Registry.

BACKGROUND: Anaplastic sarcoma of the kidney (ASK) is a DICER1-related neoplasm first identified as a distinctive tumor type through the evaluation of unusual cases of putative anaplastic Wilms tumors. Subsequent case reports identified the presence of biallelic DICER1 variants as well as progression from cystic nephroma, a benign DICER1-related neoplasm. Despite increasing recognition of ASK as a distinct entity, the optimal treatment remains unclear. METHODS: Individuals with known or suspected DICER1-related tumors including ASK were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry. Additionally, a comprehensive review of reported cases of ASK was undertaken, and data were aggregated for analysis with the aim to identify prognostic factors and clinical characteristics to guide decisions regarding genetic testing, treatment, and surveillance. RESULTS: Ten cases of ASK were identified in the Registry along with 37 previously published cases. Staging data, per Children's Oncology Group guidelines, was available for 40 patients: 13 were stage I, 12 were stage II, 10 were stage III, and five were stage IV. Outcome data were available for 37 patients. Most (38 of 46) patients received upfront chemotherapy and 14 patients received upfront radiation. Two-year event-free survival (EFS) for stage I-II ASK was 81.8% (95% confidence interval [CI]: 67.2%-99.6%), compared with 46.6% EFS (95% CI: 24.7%-87.8%) for stage III-IV (p = .07). Two-year overall survival (OS) for stage I-II ASK was 88.9% (95% CI: 75.5%-100.0%), compared with 70.0% (95% CI: 46.7%-100.0%) for stage III-IV (p = .20). Chemotherapy was associated with improved EFS and OS with hazard ratios of 0.09 (95% CI: 0.02-0.31) and 0.08 (95% CI: 0.02-0.42), respectively. CONCLUSION: ASK is a rare DICER1-related renal neoplasm. In the current report, we identify clinical and treatment-related factors associated with outcome including the importance of chemotherapy in treating ASK. Ongoing data collection and genomic analysis are indicated to optimize outcomes for children and adults with these rare tumors.

Outcomes in ovarian Sertoli-Leydig cell tumor: A report from the International Pleuropulmonary Blastoma/DICER1 and Ovarian and Testicular Stromal Tumor Registries.

OBJECTIVE: Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We sought to describe prognostic factors, treatment and outcomes for individuals with ovarian SLCT. METHODS: Individuals with SLCT were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Medical records were systematically abstracted, and pathology was centrally reviewed when available. RESULTS: In total, 191 participants with ovarian SLCT enrolled, with most (92%, 175/191) presenting with FIGO stage I disease. Germline DICER1 results were available for 156 patients; of these 58% had a pathogenic or likely pathogenic germline variant. Somatic (tumor) DICER1 testing showed RNase IIIb hotspot variants in 97% (88/91) of intermediately and poorly differentiated tumors. Adjuvant chemotherapy was administered in 40% (77/191) of cases, and among these, nearly all patients received platinum-based regimens (95%, 73/77), and 30% (23/77) received regimens that included an alkylating agent. Three-year recurrence-free survival for patients with stage IA tumors was 93.6% (95% CI: 88.2-99.3%) compared to 67.1% (95% CI: 55.2-81.6%) for all stage IC and 60.6% (95% CI: 40.3-91.0%) for stage II-IV (p < .001) tumors. Among patients with FIGO stage I tumors, those with mesenchymal heterologous elements treated with surgery alone were at higher risk for recurrence (HR: 74.18, 95% CI: 17.99-305.85). CONCLUSION: Most individuals with SLCT fare well, though specific risk factors such as mesenchymal heterologous elements are associated with poor prognosis. We also highlight the role of DICER1 surveillance in early detection of SLCT, facilitating stage IA resection.

Case Series of People With HIV on the Long-Acting Combination of Lenacapavir and Cabotegravir: Call for a Trial.

Background: Injectable cabotegravir (CAB)/rilpivirine (RPV) is the only combination long-acting (LA) antiretroviral regimen approved for HIV. RPV may not be effective among individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, which has >10% prevalence in many countries. Lenacapavir (LEN) is an LA capsid inhibitor given every 6 months, but has not been studied in combination with other LA agents. Methods: We assembled a case series from 4 US academic medical centers where patients with adherence challenges were prescribed LEN subcutaneously every 26 weeks/CAB (+/- RPV) intramuscularly every 4 or 8 weeks. Descriptive statistics, including viral load (VL) outcomes, were summarized. Results: All patients (n = 34: 76% male; 24% cis/trans female; 41% Black; 38% Latino/a; median age [range], 47 [28-75] years; 29% and 71% on CAB every 4 or 8 weeks) reported challenges adhering to oral ART. The reasons for using LEN/CAB with or without RPV were documented or suspected NNRTI mutations (n = 21, 59%), integrase mutations (n = 5, 15%), high VL (n = 6, 18%), or continued viremia on CAB/RPV alone (n = 4, 12%). Injection site reactions on LA LEN were reported in 44% (32% grade I, 12% grade 2). All patients but 2 (32/34; 94%) were suppressed (VL <75 copies/mL) after starting LEN at a median (range) of 8 (4-16) weeks, with 16/34 (47%) suppressed at baseline. Conclusions: In this case series of 34 patients on LEN/CAB, high rates of virologic suppression (94%) were observed. Reasons for using LEN/CAB included adherence challenges and underlying resistance, mostly to NNRTIs. These data support a clinical trial of LEN/CAB among persons with NNRTI resistance.

Prevalence of lung cysts in adolescents and adults with a germline DICER1 pathogenic/likely pathogenic variant: a report from the National Institutes of Health and International Pleuropulmonary Blastoma/DICER1 Registry.

BACKGROUND: Pleuropulmonary blastoma (PPB), the hallmark tumour associated with DICER1-related tumour predisposition, is characterised by an age-related progression from a cystic lesion (type I) to a high-grade sarcoma with mixed cystic and solid features (type II) or purely solid lesion (type III). Not all cystic PPBs progress; type Ir (regressed), hypothesised to represent regressed or non-progressed type I PPB, is an air-filled, cystic lesion lacking a primitive sarcomatous component. This study aims to evaluate the prevalence of non-progressed lung cysts detected by CT scan in adolescents and adults with germline DICER1 pathogenic/likely pathogenic (P/LP) variants. METHODS: Individuals were enrolled in the National Cancer Institute Natural History of DICER1 Syndrome study, the International PPB/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Individuals with a germline DICER1 P/LP variant with first chest CT at 12 years of age or older were selected for this analysis. RESULTS: In the combined databases, 110 individuals with a germline DICER1 P/LP variant who underwent first chest CT at or after the age of 12 were identified. Cystic lung lesions were identified in 38% (42/110) with a total of 72 cystic lesions detected. No demographic differences were noted between those with lung cysts and those without lung cysts. Five cysts were resected with four centrally reviewed as type Ir PPB. CONCLUSION: Lung cysts are common in adolescents and adults with germline DICER1 variation. Further study is needed to understand the mechanism of non-progression or regression of lung cysts in childhood to guide judicious intervention.

Relationships between physical behaviour phenotypes of mothers in pregnancy and their offspring with child body composition.

AIM: The aim of this study was to identify physical behaviour phenotypes in mothers in the first trimester and in their offspring at 24 months of age. The secondary aim was to examine relationships between mother and child behaviours with child body composition at age 24 months. METHODS: Longitudinal secondary analysis of the Glowing cohort collected between 1 February 2011 and 22 August 2017 in Little Rock, Arkansas. Behaviours were measured using ankle-worn accelerometers in mothers during the first trimester and offspring at 24 months of age, including total activity, sleep, sedentary time and a novel variable of daily variation, patternicity. Child body fat was measured using quantitative nuclear magnetic resonance. RESULTS: Three phenotypes were identified for mothers and children (n = 159 complete dyads). There were no relationships between mother and child phenotypes, but higher maternal patternicity was associated with higher child patternicity (0.2, 95% CI 0.1, 0.3, p = 0.001). There were no associations between mother or child phenotypes with child body composition, however higher child activity was associated with lower body fat (-0.01, 95% CI: -0.02, -0.001, p = 0.031). CONCLUSION: Limited associations were found between mothers' pregnancy physical behaviours with child behaviours or child body composition at 24 months of age. Factors such as child diet or current parental physical activity may be better predictors of early childhood outcomes.

Prehospital Naloxone Administration Patterns during the Era of Synthetic Opioids.

Background: The opioid epidemic is an ongoing public health emergency, exacerbated in recent years by the introduction and rising prevalence of synthetic opioids. The National EMS Scope of Practice Model was changed in 2017 to recommend allowing basic life support (BLS) clinicians to administer intranasal (IN) naloxone. This study examines local IN naloxone administration rates for 4 years after the new recommendation, and Glasgow Coma Scale (GCS) scores and respiratory rates before and after naloxone administration.Methods: This retrospective cohort study evaluated naloxone administrations between April 1st 2017 and March 31st 2021 in a mixed urban-suburban EMS system. Naloxone dosages, routes of administration, and frequency of administrations were captured along with demographic information. Analysis of change in the ratio of IN to intravenous (IV) naloxone administrations per patient was performed, with the intention of capturing administration patterns in the area. Analyses were performed for change over time of IN naloxone rates of administration, change in respiratory rates, and change in GCS scores after antidote administration. ALS and BLS clinician certification levels were also identified. Bootstrapping procedures were used to estimate 95% confidence intervals for correlation coefficients.Results: Two thousand and ninety patients were analyzed. There was no statistically significant change in the IN/parenteral ratio over time (p = 0.79). Repeat dosing increased over time from 1.2 ± 0.4 administrations per patient to 1.3 ± 0.5 administrations per patient (r = 0.078, 95% CI: 0.036 - 0.120; p = 0.036). Mean respiratory rates before (mean = 12.6 - 12.6, r = -0.04, 95% CI: -0.09 - 0.01; p = 0.1) and after (mean = 15.2 - 14.9, r = -0.03, 95% CI: -0.08 - 0.01; p = 0.172) naloxone administration have not changed. While initial GCS scores have become significantly lower, GCS scores after administration of naloxone have not changed (initial median GCS 10 - 6, p < 0.001; final median GCS 15 - 15, p = 0.23).Conclusions: Current dosing protocols of naloxone appear effective in the era of synthetic opioids in our region, although patients may be marginally more likely to require repeat naloxone doses.

Feasibility of laparoscopic microwave ablation of caudate tumors: a case series.

Microwave ablation of liver tumors allows preservation of liver parenchyma with good oncologic outcomes. However, ablation of tumors in the caudate lobe is particularly challenging. Adjacent critical anatomy, particularly the biliary hilum, has led to caudate location being considered a relative contraindication to ablation. To date, no series have described laparoscopic microwave ablation of caudate tumors of the liver. We describe our early experience with laparoscopic microwave ablation of caudate tumors. In this retrospective review of a prospectively maintained single-institution database, six patients with six primary or secondary caudate tumors underwent laparoscopic microwave ablation with no complications. At a median follow-up of 10.5 months, five out of six patients are free of caudate recurrence. Laparoscopic microwave ablation of caudate tumors is feasible. Long-term follow-up is needed to determine if local recurrence risk is higher than in other anatomical segments.

Assessing the role of positron emission tomography and bone scintigraphy in imaging of pleuropulmonary blastoma (PPB): A report from the International PPB/DICER1 Registry.

BACKGROUND: Pleuropulmonary blastoma (PPB) is the most common primary lung neoplasm of infancy and early childhood. Given the rarity of PPB, the role of positron emission tomography (PET) and bone scintigraphy (bone scans) in diagnostic evaluation and surveillance has not been documented to date. Available PET and bone scan data are presented in this study. PROCEDURES: Patients with PPB enrolled in the International PPB/DICER1 Registry and available PET imaging and/or bone scan reports were retrospectively abstracted. RESULTS: On retrospective analysis, 133 patients with type II and III (advanced) PPB were identified with available report(s) (PET scan only = 34, bone scan only = 83, and both bone scan and PET = 16). All advanced primary PPB (n = 11) and recurrent (n = 8) tumors prior to treatment presented with 18 F-fluorodeoxyglucose (FDG)-avid lesions, with median maximum standardized uptake values of 7.4 and 6.7, respectively. False positive FDG uptake in the thorax was noted during surveillance (specificity: 59%). Bone metastases were FDG-avid prior to treatment. Central nervous system metastases were not discernable on PET imaging. Sensitivity and specificity of bone scans for metastatic bone disease were 89% and 92%, respectively. Bone scans had a negative predictive value of 99%, although positive predictive value was 53%. Four patients with distant bone metastases had concordant true positive bone scan and PET. CONCLUSION: Primary, recurrent, and/or extracranial metastatic PPB presents with an FDG-avid lesion on PET imaging. Additional prospective studies are needed to fully assess the utility of nuclear medicine imaging in surveillance for patients with advanced PPB.

Physical Activity, Sedentary and Sleep Phenotypes in Women During the First Trimester of Pregnancy.

OBJECTIVES: Patterns of physical behaviors including physical activity, sedentary time, and sleep are unknown during pregnancy, but are likely to influence health outcomes. The purpose was to first identify "physical behavior phenotypes" from accelerometer-measured physical behaviors in pregnant women during the first trimester and secondly, to explore the associations between the identified phenotypes with demographic variables and body-mass-index (BMI). METHODS: Data were from the Glowing Study (gov ID: NCT01131117), collected between 2011 and 2017 with accelerometer-measured physical behaviors of women in their 12th week of pregnancy. Latent class analysis was used to identify patterns of total physical activity, sleep time, sedentary time, and variation in physical activity. Maternal Body-Mass-Index (BMI). BMI and sociodemographic characteristics were compared between physical behavior phenotypes. RESULTS: A total of 212 pregnant women were included in the study (mean age 30.2 years (range 22.1 to 42.4), mean days wear 4.3 (SD 0.7)). Three physical behavior phenotypes were identified from the four physical behavior constructs: low sedentary and stable activity (n = 136, 64%), variable activity (n = 39, 18%), high sedentary and low sleep (n = 37, 17%). BMI, race, and education were significantly different between the three phenotypes, with the low sedentary and stable activity phenotype having the lowest BMI and a higher percentage of white and college educated women. CONCLUSIONS FOR PRACTICE: Total physical activity and physical behavior phenotypes during the first trimester were associated with early-pregnancy BMI, race, and education. Future research should examine whether these physical behavior phenotypes are associated with maternal and child health outcomes.

EMS Non-Transport of Low-Risk COVID-19 Patients.

Objectives: COVID-19 infections in the community have the potential to overwhelm both prehospital and in-hospital resources. Transport of well-appearing patients, in the absence of available emergency department treatment capacity, increases strain on the hospital and EMS system. In May of 2020, the Connecticut Office of EMS issued a voluntary, EMS-initiated, non-transport protocol for selected low-risk patients with symptoms consistent with COVID-19. We evaluated the implementation of this non-transport protocol in a mixed urban/suburban EMS system.Methods: We conducted a retrospective review of contemporaneously recorded quality improvement documentation for uses of the Connecticut COVID-19 non-transport protocol by EMS clinicians within our EMS system during two implementations: from 12/14/2020 to 5/1/21, and again from 1/3/22 to 2/18/22, which coincided with large COVID-19 case surges in our region.Results: The vast majority of patients treated under the non-transport protocol were not reevaluated by EMS or in our emergency departments in the subsequent 24 hours. There was reasonable adherence to the protocol, with 83% of cases appropriate for the non-transport protocol. The most common reasons for protocol violations were age outside of protocol scope (pediatric patients), failure of documentation, or vital signs outside of the established protocol parameters. We did not find an increased 24-hour ED visit rate in patients who were inappropriately triaged to the protocol. Of patients who had ED visits within 24 hours, only two were admitted, none to higher levels of care.Conclusion: Within this small study, EMS clinicians in our system were able to safely and accurately apply a non-transport protocol for patients presenting with symptoms consistent with COVID-19. This is consistent with previous literature suggesting that EMS-initiated non-transport is a viable strategy to reduce the burden on health systems.

An Evaluation of Prehospital Adenosine Use.

BACKGROUND: Adenosine has been safely used by paramedics for the treatment of stable supraventricular tachycardia since the mid-1990s. However, there continues to be variability in paramedics' ability to identify appropriate indications for adenosine administration. As the first of a planned series of studies aimed at improving the accuracy of SVT diagnosis and successful administration of adenosine by paramedics, this study details the current usage patterns of adenosine by paramedics. METHODS: This cross-sectional retrospective study investigated adenosine use within a large northeast EMS region from January 1, 2019, through September 30, 2021. Excluding pediatric and duplicate case reports, we created a dataset containing patient age, sex, and vital signs before, during, and after adenosine administration; intravenous line location; and coded medical history from paramedic narrative documentation, including a history of atrial fibrillation, suspected arrhythmia diagnosis, and effect of adenosine. In cases with available prehospital electrocardiograms (EKGs) for review, two physicians independently coded the arrhythmia diagnosis and outcome of adenosine administration. Statistical analysis included interrater reliability with Cohen's kappa statistic. RESULTS: One hundred eighty-three cases were included for final analysis, 84 did not have a documented EKG for review. Categorization of presenting rhythms in these cases occurred by a physician reviewing EMS narrative and documentation. Forty of these 84 cases (48%) were adjudicated as SVT likely, 32 (38%) as SVT unlikely and 12 (14%) as uncategorized due to lack of supporting documentation. Of the 99 cases with EKGs available to review, there was substantial agreement of arrhythmia diagnosis interpretation between physician reviewers (Cohen's kappa 0.77-1.0); 54 cases were adjudicated as SVT by two physician reviewers. Other identified cardiac rhythms included atrial fibrillation (16), sinus tachycardia (11), and ventricular tachycardia (2). Adenosine cardioversion occurred in 47 of the 99 cases with EKGs available for physician review (47.5%). Adenosine cardioversion was also deemed to occur in 87% (47/54) of cases when the EKG rhythm was physician adjudicated SVT. CONCLUSIONS: This study supports the use of adenosine as a prehospital treatment for SVT while highlighting the need for continued efforts to improve paramedics' identification and management of tachyarrhythmias.

Health-related quality of life in children and adolescents with pleuropulmonary blastoma: A report from the International PPB/DICER1 Registry.

PURPOSE: Pleuropulmonary blastoma (PPB) is the most common lung cancer of infancy and early childhood and is associated with germline DICER1 variants. Type I and Ir PPB are cystic lesions treated surgically, with a subset of children with type I receiving chemotherapy. Type II and III are more aggressive lesions, treated with surgery, intensive chemotherapy and potentially radiation. We sought to assess health-related quality of life (HRQoL) in children with PPB and known germline DICER1 variants. METHODS: Children with a diagnosis of PPB or germline DICER1 pathogenic variant without history of PPB or other DICER1-related neoplasm (DICER1+ only) were enrolled in the International PPB/DICER1 Registry. Parent reports for participants aged 2-17 years for the PedsQL v.4 and PedsQL Multidimensional Fatigue Scale v.3 were collected. Fatigue, physical, and psychosocial function scores were compared. RESULTS: Analysis included 84 participants (PPB type Ir = 20, type I = 15, type II/III = 27, DICER1+ only = 22). Total fatigue scores of participants with type I and II/III PPB were lower compared to DICER1+ only, with effect size larger in type II/III (-0.82 vs. -0.40). Total psychosocial and physical functioning scores were lower in participants with type I and type II/III PPB compared to DICER1+ only, with larger effects noted in type II/III. Female sex was suggestive of worse HRQoL for both type I/Ir and type II/III cohorts. CONCLUSIONS: These data demonstrate the importance of regular HRQoL assessment in patients with a history of PPB as well as the importance and feasibility of studying HRQoL in children with rare tumors.

Type I and Ir pleuropulmonary blastoma (PPB): A report from the International PPB/DICER1 Registry.

BACKGROUND: Pleuropulmonary blastoma (PPB) is the most common lung cancer of infancy and early childhood. Type I PPB is a purely cystic lesion that has a microscopic population of primitive small cells with or without rhabdomyoblastic features and may progress to type II or III PPB, whereas type Ir lacks primitive small cells. METHODS: Children with suspected PPB were enrolled in the International PPB/DICER1 Registry. Pathology was centrally reviewed, and follow-up was ascertained annually. RESULTS: Between 2006 and 2022, 205 children had centrally reviewed type I or Ir PPB; 39% of children with type I and 5% of children with type Ir PPB received chemotherapy. Outcomes were favorable, although 11 children (nine with type I and two with type Ir PPB) experienced progression to type II/III (n = 8) or regrowth of type I PPB at the surgical site (n = 3), none of whom received chemotherapy before progression. Age and cyst size in combination were more suitable than either factor alone in predicting whether a particular lesion was type I or Ir PPB. CONCLUSIONS: For young children with type I PPB, outcomes are favorable, but complete resection is indicated because of the risk for progression. Chemotherapy may be useful in a subset of children at increased risk for recurrence/progression. Efforts to risk stratify children with type I PPB to optimize outcomes while reducing treatment-related side effects are underway.

Outcomes for Children With Type II and Type III Pleuropulmonary Blastoma Following Chemotherapy: A Report From the International PPB/DICER1 Registry.

PURPOSE: Pleuropulmonary blastoma (PPB) is the most common primary lung neoplasm of infancy and early childhood. Type II and type III PPB have historically been associated with a poor prognosis. METHODS: Patients with known or suspected PPB were enrolled in the International PPB/DICER1 Registry. Medical records were abstracted with follow-up ascertained annually. All PPB diagnoses were confirmed by central pathology review. Beginning in 2007, the IVADo regimen (ifosfamide, vincristine, actinomycin-D, and doxorubicin) was recommended as a potential treatment regimen for children with type II and type III PPB. This regimen was compared with a historical control cohort. RESULTS: From 1987 to 2021, 314 children with centrally confirmed type II and type III PPB who received upfront chemotherapy were enrolled; 132 children (75 with type II and 57 with type III) received IVADo chemotherapy. Adjusted analyses suggest improved overall survival for children treated with IVADo in comparison with historical controls with an estimated hazard ratio of 0.65 (95% CI, 0.39 to 1.08). Compared with localized disease, distant metastasis at diagnosis was associated with worse PPB event-free survival and overall survival with hazard ratio of 4.23 (95% CI, 2.42 to 7.38) and 4.69 (95% CI, 2.50 to 8.80), respectively. CONCLUSION: The use of IVADo in children with type II and type III PPB resulted in similar-to-improved outcomes compared with historical controls. Inferior outcomes with metastatic disease suggest the need for novel therapies. This large cohort of uniformly treated children with advanced PPB serves as a benchmark for future multicenter therapeutic studies for this rare pediatric tumor.

Deep Learning Classification of Breast Cancer Tissue from Terahertz Imaging Through Wavelet Synchro-Squeezed Transformation and Transfer Learning.

Terahertz imaging and spectroscopy is an exciting technology that has the potential to provide insights in medical imaging. Prior research has leveraged statistical inference to classify tissue regions from terahertz images. To date, these approaches have shown that the segmentation problem is challenging for images of fresh tissue and for tumors that have invaded muscular regions. Artificial intelligence, particularly machine learning and deep learning, has been shown to improve performance in some medical imaging challenges. This paper builds on that literature by modifying a set of deep learning approaches to the challenge of classifying tissue regions of images captured by terahertz imaging and spectroscopy of freshly excised murine xenograft tissue. Our approach is to preprocess the images through a wavelet synchronous-squeezed transformation (WSST) to convert time-sequential terahertz data of each THz pixel to a spectrogram. Spectrograms are used as input tensors to a deep convolution neural network for pixel-wise classification. Based on the classification result of each pixel, a cancer tissue segmentation map is achieved. In experimentation, we adopt leave-one-sample-out cross-validation strategy, and evaluate our chosen networks and results using multiple metrics such as accuracy, precision, intersection, and size. The results from this experimentation demonstrate improvement in classification accuracy compared to statistical methods, an improvement to segmentation between muscle and cancerous regions in xenograft tumors, and identify areas to improve the imaging and classification methodology.

Response to Comment on "Pushing the frontiers of density functionals by solving the fractional electron problem".

Gerasimov et al. claim that the ability of DM21 to respect fractional charge (FC) and fractional spin (FS) conditions outside of the training set has not been demonstrated in our paper. This is based on (i) asserting that the training set has a ~50% overlap with our bond-breaking benchmark (BBB) and (ii) questioning the validity and accuracy of our other generalization examples. We disagree with their analysis and believe that the points raised are either incorrect or not relevant to the main conclusions of the paper and to the assessment of general quality of DM21.

Hyperspectral terahertz imaging and optical clearance for cancer classification in breast tumor surgical specimen.

Purpose: We investigate the enhancement in terahertz (THz) images of freshly excised breast tumors upon treatment with an optical clearance agent. The hyperspectral imaging and spectral classifications are used to quantitatively demonstrate the image enhancement. Glycerol solution with 60% concentration is applied to excised breast tumor specimens for various time durations to investigate the effectiveness on image enhancement. Approach: THz reflection spectroscopy is utilized to obtain the absorption coefficient and the index of refraction of untreated and glycerol-treated tissues at each frequency up to 3 THz. Two classifiers, spectral angular mapping (SAM) based on several kernels and Euclidean minimum distance (EMD) are implemented to evaluate the effectiveness of the treatment. The testing raw data is obtained from five breast cancer specimens: two untreated specimens and three specimens treated with glycerol solution for 20, 40, or 60 min. All tumors used in the testing data have healthy tissues adjacent to cancerous ones consistent with the challenge faced in lumpectomy surgeries. Results: The glycerol-treated tissues showed a decrease in the absorption coefficients compared with untreated tissues, especially as the period of treatment increased. Although the sensitivity metric of the classifier presented higher values in the untreated tissues compared with the treated ones, the specificity and accuracy metrics demonstrated higher values for the treated tissues compared with the untreated ones. Conclusions: The biocompatible glycerol solution is a potential optical clearance agent in THz imaging while keeping the histopathology imaging intact. The SAM technique provided a good classification of cancerous tissues despite the small amount of cancer in the training data (only 7%). The SAM exponential kernel and EMD presented classification accuracy of ∼ 80 % to 85% compared with linear and polynomial kernels that provided accuracy ranging from 70% to 80%. Overall, glycerol treatment provides a potential improvement in cancer classification in freshly excised breast tumors.

Early Changes in Patient Access Interval during the COVID-19 Pandemic.

Background: COVID-19 was first reported in the United States in January 2020. Its spread throughout the country required EMS systems to rapidly adapt to patient needs while protecting EMS personnel. EMS agencies developed protocols requiring personnel to don enhanced personal protective equipment prior to patient contact. We hypothesized that the Patient Access Interval (PAI), defined as the time from wheels stopped on scene to initial patient contact, had increased during the COVID pandemic. This had the potential to affect patient outcomes, particularly in time-sensitive emergencies such as cardiac arrest or respiratory distress. Methods: This retrospective cohort study used commercial ambulance data from the four largest cities in Connecticut at two different time points: (Pre-COVID) March-May 2019, and (COVID) March-May 2020. PAI was calculated from contemporaneously reported scene times. Total cases were analyzed, and sub-analyses performed for calls located at extended care facilities (ECFs), for all emergent (Echo/Delta) calls, and for medical cardiac arrest calls. Results: 92,846 total cases were evaluated: 50,083 from 2019, and 42,763 from 2020. Cases that did not include necessary time data for PAI were removed, yielding 75,796 total cases (41,852 from 2019, 33,944 from 2020). The average PAI increased from 1 minute 55 seconds (1 m:55s) Pre-COVID to 2 m:18s COVID. ECF PAI increased from 2 m:39s to 3 m:42s. Echo/Delta PAI increased from 1 m:42s to 2 m:07s. Medical cardiac arrest PAI increased from 1 m:27s to 2 m:04s, and ECF cardiac arrest PAI increased from 2 m:18s to 4 m:35s (all comparisons p < 0.01). Conclusions: There were statistically significant increases in all studied PAIs during COVID. The 23 second increase in PAI for all calls may not have been clinically significant in most cases; however, for life-threatening patient presentations, the increase may have been particularly relevant. The increased PAI was compounded in the ECF environment, possibly due to state-mandated screening and temperature checks of EMS personnel before entering facilities. This was highlighted in the ECF cardiac arrest data, which demonstrated a clinically significant increase in PAI of 2m:17s. While this study was limited by the accuracy of contemporaneous time reports by EMS, the results support our hypothesis that PAI had increased during the COVID pandemic.