Shear Wave Elastography and Thyroid Imaging Reporting and Data System (TIRADS) for the Risk Stratification of Thyroid Nodules—Results of a Prospective Study

Purpose: To compare the diagnostic performance of thyroid imaging reporting and data system (TIRADS) in combination with shear wave elastography (SWE) for the assessment of thyroid nodules. Methods: A prospective study was conducted with the following inclusion criteria: preoperative B-mode ultrasound (US) including TIRADS classification (Kwak-TIRADS, EU-TIRADS), quantitative SWE and available histological results. Results: Out of 43 patients, 61 thyroid nodules were detected; 10 nodules were found to be thyroid cancer (7 PTC, 1 FTC, 2 HüCC) and 51 were benign. According to Kwak-TIRADS the majority of benign nodules (47 out of 51, 92.2%) were classified in the low-risk- and intermediate-risk class, four nodules were classified as high-risk (7.8%). When using EU-TIRADS, the benign nodules were distributed almost equally across all risk classes, 21 (41.2%) nodules were classified in the low-risk class, 16 (31.4%) in the intermediate-risk class and 14 (27.4%) in the high-risk class. In contrast, most of the malignant nodules (eight out of ten) were classified as high-risk on EU-TIRADS. One carcinoma was classified as low-risk and one as intermediate-risk nodule. For SWE, ROC analysis showed an optimal cutoff of 18.5 kPa to distinguish malignant and benign nodules (sensitivity 80.0%, specificity 49.0%, PPV 23.5% and NPV 92.6%). The addition of elastography resulted in an increase of accuracy from 65.6% to 82.0% when using Kwak-TIRADS and from 49.2% to 72.1% when using EU-TIRADS. Conclusion: Our data demonstrate that the combination of TIRADS and SWE seems to be superior for the risk stratification of thyroid nodules than each method by itself. However, verification of these results in a larger patient population is mandatory.

Surgical risk assessment in Hiv-infected patients treated within the penitentiary system of Kemerovo region

Aim. To assess the surgical risk in HIV-infected patients who received the surgical treatment within the penitentiary system of Kemerovo Region.Materials and Methods. We retrospectively analysed the physical status and the extent of surgical risk in 296 HIV-infected patients who underwent elective (n = 201) or emergency (n = 95) surgery in Hospital №1 (Kemerovo) from 2015 to 2018. Physical status was assessed according to American Society of Anesthesiologists (ASA) Physical Status Classification System. Surgical risk was scored according to Moscow Scientific Society of Anesthesiologists and Critical Care.Results. The majority of patients had 3 (48.4 and 36.3% in emergency and elective patients, respectively) or 4a (30.5 and 45.8% in emergency and elective patients, respectively) stages of HIV infection. Opportunistic infections were diagnosed in 49.3% of patients and were always accompanied by superficial mycoses. Physical status of most patients (47.4% and 63.7% in emergency and elective patients, respectively) corresponded to ASA physical status class 3. Emergency patients mainly had surgical risk class 3 (n = 50, 52.6%) while elective patients often had surgical risk class 2 (n = 106, 52.7%). The prevalence of postoperative complications, most often impaired wound healing, was 9.8%.Conclusion. More than 80% of HIV-infected patients who underwent surgical interventions within the penitentiary system of Kuzbass were at III or IV stages of HIV infection, entailing a high frequency of opportunistic diseases such as superficial mycoses and dictating the need to include antifungal treatment into the surgical treatment. Impaired wound healing was the most frequent postoperative complication.

COSMONET: An R Package for Survival Analysis Using Screening-Network Methods

Identifying relevant genomic features that can act as prognostic markers for building predictive survival models is one of the central themes in medical research, affecting the future of personalized medicine and omics technologies. However, the high dimension of genome-wide omic data, the strong correlation among the features, and the low sample size significantly increase the complexity of cancer survival analysis, demanding the development of specific statistical methods and software. Here, we present a novel R package, COSMONET (COx Survival Methods based On NETworks), that provides a complete workflow from the pre-processing of omics data to the selection of gene signatures and prediction of survival outcomes. In particular, COSMONET implements (i) three different screening approaches to reduce the initial dimension of the data from a high-dimensional space p to a moderate scale d, (ii) a network-penalized Cox regression algorithm to identify the gene signature, (iii) several approaches to determine an optimal cut-off on the prognostic index (PI) to separate high- and low-risk patients, and (iv) a prediction step for patients’ risk class based on the evaluation of PIs. Moreover, COSMONET provides functions for data pre-processing, visualization, survival prediction, and gene enrichment analysis. We illustrate COSMONET through a step-by-step R vignette using two cancer datasets.

Lefamulin in Patients with Community-Acquired Bacterial Pneumonia Caused by Atypical Respiratory Pathogens: Pooled Results from Two Phase 3 Trials

Lefamulin was the first systemic pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia based on two phase 3 trials (Lefamulin Evaluation Against Pneumonia [LEAP]-1 and LEAP-2). This pooled analysis evaluated lefamulin efficacy and safety in adults with community-acquired bacterial pneumonia caused by atypical pathogens (Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae). In LEAP-1, participants received intravenous lefamulin 150 mg every 12 h for 5–7 days or moxifloxacin 400 mg every 24 h for 7 days, with optional intravenous-to-oral switch. In LEAP-2, participants received oral lefamulin 600 mg every 12 h for 5 days or moxifloxacin 400 mg every 24 h for 7 days. Primary outcomes were early clinical response at 96 ± 24 h after first dose and investigator assessment of clinical response at test of cure (5–10 days after last dose). Atypical pathogens were identified in 25.0% (91/364) of lefamulin-treated patients and 25.2% (87/345) of moxifloxacin-treated patients; most were identified by ≥1 standard diagnostic modality (M. pneumoniae 71.2% [52/73]; L. pneumophila 96.9% [63/65]; C. pneumoniae 79.3% [46/58]); the most common standard diagnostic modality was serology. In terms of disease severity, more than 90% of patients had CURB-65 (confusion of new onset, blood urea nitrogen > 19 mg/dL, respiratory rate ≥ 30 breaths/min, blood pressure <90 mm Hg systolic or ≤60 mm Hg diastolic, and age ≥ 65 years) scores of 0–2; approximately 50% of patients had PORT (Pneumonia Outcomes Research Team) risk class of III, and the remaining patients were more likely to have PORT risk class of II or IV versus V. In patients with atypical pathogens, early clinical response (lefamulin 84.4–96.6%; moxifloxacin 90.3–96.8%) and investigator assessment of clinical response at test of cure (lefamulin 74.1–89.7%; moxifloxacin 74.2–97.1%) were high and similar between arms. Treatment-emergent adverse event rates were similar in the lefamulin (34.1% [31/91]) and moxifloxacin (32.2% [28/87]) groups. Limitations to this analysis include its post hoc nature, the small numbers of patients infected with atypical pathogens, the possibility of PCR-based diagnostic methods to identify non-etiologically relevant pathogens, and the possibility that these findings may not be generalizable to all patients. Lefamulin as short-course empiric monotherapy, including 5-day oral therapy, was well tolerated in adults with community-acquired bacterial pneumonia and demonstrated high clinical response rates against atypical pathogens.

Bridging juvenile justice and behavioral health systems: development of a clinical pathways approach to connect youth at risk for suicidal behavior to care

Background Justice-involved youth have high rates of suicidal behavior and co-morbid psychiatric disorders, yet low rates of service use. Implementation efforts aimed at supporting cross-agency linkage protocols may be useful components of interventions promoting behavioral healthcare service access for youths on probation. The purpose of this study was to develop clear referral Pathways for three suicide risk classifications of youth, across 10 counties in a single state through a community-academic partnership in New York state, a strategic planning process between county Probation departments and community Behavioral Health. Results We sought to clarify service destinations for youth in three classes of risk for suicidal behavior: Class I (Crisis, Imminent Risk); Class II (Crisis, Non-Imminent Risk); and Class III (Non-Crisis but in Need of Service). Prior to Pathway Meetings, there was a low degree of agreement between Probation and Behavioral Health leadership for the appropriate service destination for youths in crisis, whether at imminent risk (Class I: 57.8% overlap) or at lower than imminent risk (Class II: 45.6% overlap). Options for referral destinations for Classes I and II decreased significantly (indicating greater overlap) as a result of Pathway Meetings [(Class I: from 2.5 to 1.1 (t(9) = 3.28, p < 0.01); Class II: from 2.8 to 1.3 (t(9) = 4.025, p < 0.003)]. Pathway Meetings allowed Behavioral Health and Juvenile Justice systems to make joint decisions regarding referral pathways, resulting in innovative solutions, such as the use of mobile crisis. Conclusions The community-academic partnership served to bring internal (Juvenile Justice) and external (Behavioral Health) contexts together to successfully generate agreed upon Pathways to care for youths demonstrating risk for suicidal behavior. Bridging Behavioral Health and Juvenile Justice systems together to agree to referral Pathways for each risk class can increase appropriate service use. Trial registration ClinicalTrials.gov, NCT03586895. Registered 21 June 2018, https://register.clinicaltrials.gov/prs/app/template/EditRecord.vm?epmode=Edit&listmode=Edit&uid=U0003B7I&ts=4&sid=S00080NN&cx=-n4kinh

Development of an Index to Measure West Nile Virus Transmission Risk in New Jersey Counties

ABSTRACT We developed an index for use by New Jersey counties to measure West Nile virus (WNV) transmission risk to the human population. We used a latent profile analysis to develop the index, identifying categories of environmental conditions associated with WNV transmission risk to humans. The final model included 4 indicators of transmission risk: mosquito abundance and minimum field infection rate, temperature, and human case count. We used data from 2004 to 2018 from all 21 New Jersey counties aggregated into 11 2-wk units per county per year (N = 3,465). Three WNV risk classes were identified. The Low Risk class had low levels of all variables. The Moderate Risk class had high abundance, average temperature levels, and low levels of the other variables. The High Risk class had substantially above average human case likelihood, average temperature, and high mosquito infection rates. These results suggest the presence of 3 distinct WNV risk profiles, which can be used to guide the development of public health actions intended to mitigate WNV transmission risk to the human population.

Pattern of Medical Device Adverse Events in a Tertiary Level Hospital in Northern India: An Ambispective Study

Background: This is the first study to evaluate the pattern of adverse events related to medical devices in India. We aimed to evaluate medical device adverse events (MDAEs) reported at a tertiary level teaching hospital in northern India.Methods: This descriptive study was conducted ambispectively at PGIMER, Chandigarh. We used the medical device risk classification given by the Indian regulatory authority which was framed in line with the recommendation of the Global Harmonization Task Force. The prospective study (PS) was done from January 2020 to December 2020 with a concurrent retrospective study (RS) proceeding to three years so as to learn more about the reporting culture, demographics, risk class of devices and the type of adverse events.Result. We obtained 224 MDAE in the prospective study and identified 413 MDAE in retrospective study. Reporting culture of retrospective adverse events to the national materiovigilance programme of India (MvPI) was negligible. Marginally increased incidence of MDAE reported among male patients (PS; 52%, RS; 57%) and age group between 21-30 years (PS; 19.1%, RS; 23.2%) in both studies. Fewer number of MDAEs were also reported from infants (7.5%) and the elderly (6.9%) population. Regarding risk class, MDAEs were frequent in low to moderate risk devices (Class B: 66%) in the prospective study, while it was documented only for high-risk devices (Class C: 51% & Class D: 49%) in the retrospective study. However, serious adverse events (SAEs) were equally prevalent among moderate to high-risk devices (Class B: 33%, C: 34% &D: 33%). An increased frequency of SAE was observed among non-notified medical devices (60.4%). Concerning reporting culture, nurses reported the majority of MDAEs (65%). Overall 14% of the incidents were documented as near-miss events.Conclusion: Medical devices elicit adverse events irrespective of their risk class, notification status and patient demographic factors. Escalated reporting of MDAEs by surgeons and biomedical engineers is recommended at India.

Changes in CMR Parameters and Prediction of Cardiac Complications in Thalassemia Major: Fibrosis Tells Us More Than Iron

Introduction. Cardiovascular magnetic Resonance (CMR) has dramatically changed the clinical practice and improved the prognosis in thalassemia major (TM). This is the first study evaluating the predictive value of changes in CMR parameters (myocardial iron, function, and fibrosis) for cardiac complications in TM. Methods. We followed prospectively 709 TM patients (374 females; 29.77±8.53 years) consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network who performed a baseline and a 1 st follow up CMR scan after 18 months. Myocardial iron overload (MIO) was measured by multislice multiecho T2* technique and atrial dimensions and biventricular function by cine images. Macroscopic myocardial fibrosis was detected by late gadolinium enhancement technique. Risk classes were defined based on the 4 patterns of MIO from worst to normal. For patients with baseline MIO (at least one segmental T2*&lt;20 ms), improvement was defined as a transition to a better risk class, stabilization as no change in risk class, and worsening as a transition to a worse risk class. For patients without baseline MIO, the worsening was the transition to a worse risk class. The percentage change was used for continuous variables. For biventricular ejection fractions, improvement was a %change&gt;10%, stabilization a %change between -10% and 10%, and worsening a %change&lt;-10%. For biventricular volumes, LV mass index, and atrial areas, improvement was a % change&lt;-10%, stabilization a % change between -10% and 10%, and worsening a % change&gt;10%. Myocardial fibrosis was considered absent if not detected in any of the two CMRs and present if detected in at least one examination . Results. During a mean follow-up of 89.4±33.3 months, cardiac events were recorded in 50 (7.1%) patients: 24 (48%) episodes of heart failure, 24 (48%) arrhythmias (23 supraventricular and 1 hypokinetic), and 2 (4.0%) pulmonary hypertension. Mean time from the 1 st follow up CMR to the development of a cardiac complication was 75.31±35.35 months. In the univariate Cox regression analysis, cardiac iron cleareance and myocardial fibrosis were identified as univariate prognosticators (Table 1). In the multivariate analysis only myocardial fibrosis remained an independent predictor factor. Conclusion. The presence of myocardial fibrosis at the baseline CMR or developed within 18 months emerges as the strongest long-term predictor for cardiac complications in TM. Our data demonstrate the importance in using the contrast medium for CMR scans in thalassemia patients. Figure 1 Figure 1. Disclosures Pepe: Bayer S.p.A.: Other: no profit support; Chiesi Farmaceutici S.p.A: Other: no profit support. Maggio: Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corp: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees.

Analytical validity of DecisionDx-SCC, a gene expression profile test to identify risk of metastasis in cutaneous squamous cell carcinoma (SCC) patients

Background To improve identification of patients with cutaneous squamous cell carcinoma (SCC) at high risk for metastatic disease, the DecisionDx-SCC assay, a prognostic 40-gene expression profile (40-GEP) test, was developed and validated. The 40-GEP assay utilizes RT-PCR gene expression analysis on primary tumor biopsy tissue to evaluate the expression of 34 signature gene targets and 6 normalization genes. The test provides classifications of low risk (Class 1), moderate risk (Class 2A), and high risk (Class 2B) of metastasis within 3 years of diagnosis. The primary objective of this study was to validate the analytical performance of the 40 gene expression signature. Methods The repeatability and reproducibility of the 40-GEP test was evaluated by performance of inter-assay, intra-assay, and inter-operator precision experiments along with monitoring the reliability of sample and reagent stability for class call concordance. The technical performance of clinical orders from September 2020 through July 2021 for the 40-GEP test was assessed. Results Patient hematoxylin and eosin (H&E) stained slides were reviewed by a board-certified pathologist to assess minimum acceptable tumor content. Class specific controls (Class 1 and Class 2B) were evaluated with Levey Jennings analysis and demonstrated consistent and reproducible results. Inter-assay, inter-operator and intra-assay concordance were all ≥90%, with short-term and long-term RNA stability also meeting minimum concordance requirements. Of the 2,446 orders received, 93.4% remained eligible for testing, with 96.8% of all tested samples that completed the assay demonstrating actionable class call results. Conclusion DecisionDx-SCC demonstrates a high degree of analytical precision, yielding high concordance rates across multiple performance experiments, along with exhibiting robust technical reliability on clinical samples.

Management and Outcome of Parathyroid Carcinoma-Induced Primary Hyperparathyroidism: A Single-Centre Experience

Background. Parathyroid carcinoma (PC) is the rarest endocrine cancer and an infrequent cause of primary hyperparathyroidism (PHPT), responsible for less than 1% of cases. Due to its rarity, treatment is challenging. Methods. A retrospective cohort study on 462 patients referred for parathyroidectomy to Thyroid and Parathyroid Unit at Santi Paolo e Carlo Hospital, Milan, Italy, from 2011 to 2021. We identified and individually described the patients affected with PC. Then, we split all patients treated for PHPT into four groups based on the cause: PC, adenoma, atypical adenoma, and hyperplasia. Patients’ demographics, preoperative evaluation results, intraoperative findings, and outcomes for the PC group were compared with groups of PHPT due to benign causes. Results. Eight cases of PC were identified, five males and three females. Seven cases presented with symptoms of hypercalcemia and one with a neck mass. Five underwent en bloc resections and three local excisions. Histopathological features showed capsular invasion in four patients, capsular and soft tissue invasion in three patients, and vascular invasion in one case. No patients had distant metastasis. One patient was classed as high risk based on the Schulte classification system. All patients treated for PC were alive and disease-free at a mean follow-up of 38.4 months. When compared with other PHPT patients, PC patients were more frequently male and had higher preoperative blood calcium and PTH and lower phosphate levels, larger and heavier parathyroids excised, lower postoperative calcium, and a higher rate of postoperative hypoparathyroidism. Conclusion. Our study highlights some aspects valuable to suspect PC and differentiate PHPT-PC from benign causes of PHPT preoperatively. Preoperative suspicion of malignancy is essential to guarantee the best course of treatment for patients. Although limited for size and follow-up, the excellent outcome of our series seems to support the value of both surgery extension and risk class according to the Schulte classification as possible prognostic factors for recurrence.