Performance of a multigene genomic classifier and clinical parameters in predicting malignancy in a Southeast Asian cohort of patients with cytologically indeterminate thyroid nodules.

BACKGROUND: Most thyroid nodules are benign. It is important to determine the likelihood of malignancy in such nodules to avoid unnecessary surgery. The primary objective of this study was to characterize the genetic landscape and the performance of a multigene genomic classifier in fine-needle aspiration (FNA) biopsies of cytologically indeterminate thyroid nodules in a Southeast Asian cohort. The secondary objective was to assess the predictive contribution of clinical characteristics to thyroid malignancy. METHODS: This prospective, multicenter, blinded study included 132 patients with 134 nodules. Molecular testing (MT) with ThyroSeq v3 was performed on clinical or ex-vivo FNA samples. Centralized pathology review also was performed. RESULTS: Of 134 nodules, consisting of 61% Bethesda category III, 20% category IV, and 19% category V cytology, and 56% were histologically malignant. ThyroSeq yielded negative results in 37.3% of all FNA samples and in 42% of Bethesda category III-IV cytology nodules. Most positive samples had RAS-like (41.7%), followed by BRAF-like (22.6%), and high-risk (17.9%) alterations. Compared with North American patients, the authors observed a higher proportion of RAS-like mutations, specifically NRAS, in Bethesda categories III and IV and more BRAF-like mutations in Bethesda category III. The test had sensitivity, specificity, negative predictive value, and positive predictive value of 89.6%, 73.7%, 84.0%, and 82.1%, respectively. The risk of malignancy was predicted by positive MT and high-suspicion ultrasound characteristics according to American Thyroid Association criteria. CONCLUSIONS: Even in the current Southeast Asian cohort with nodules that had a high pretest cancer probability, MT could lead to potential avoidance of diagnostic surgery in 42% of patients with Bethesda category III-IV nodules. MT positivity was a stronger predictor of malignancy than clinical parameters.

Case 321: Leigh Syndrome.

HISTORY: A 9-month-old preterm male infant born at 33 weeks gestation presented with a 2-month history of developmental decline. The parents reported that over the past several months, they noted regression of milestones, where the infant stopped smiling, crying, expressing himself, or making eye contact. The parents also reported that the infant had multiple seizures during which he would wake up stiff and stare into space for 10-20 seconds while his lips would become blue. The parents were referred to a neurologist, where physical examination was notable for hypotonia. Electroencephalography (EEG) revealed frequent bilateral parietal epileptiform discharges. The patient was subsequently started on lacosamide. The patient's medical history was notable for abnormally low citrulline levels at birth, with negative results of urea cycle disorder testing at the time, along with left inguinal hernia repair performed 3 months ago. More recent laboratory analysis had shown persistently elevated serum lactate and alanine levels. There was no history of travel, recent infection, or vaccine administration. MRI of the brain with spectroscopy was performed for further evaluation.

Case 321.

HISTORY: A 9-month-old preterm male infant born at 33 weeks gestation presented with a 2-month history of developmental decline. The parents reported that over the past several months, they noted regression of milestones, where the infant stopped smiling, crying, expressing himself, or making eye contact. The parents also reported that the infant had multiple seizures during which he would wake up stiff and stare into space for 10-20 seconds while his lips would become blue. The parents were referred to a neurologist, where physical examination was notable for hypotonia. Electroencephalography (EEG) revealed frequent bilateral parietal epileptiform discharges. The patient was subsequently started on lacosamide. The patient's medical history was notable for abnormally low citrulline levels at birth, with negative results of urea cycle disorder testing at the time, along with left inguinal hernia repair performed 3 months ago. More recent laboratory analysis had shown persistently elevated serum lactate and alanine levels. There was no history of travel, recent infection, or vaccine administration. MRI of the brain with spectroscopy was performed for further evaluation (Figs 1-6).

Integrating High-Impact Practices (HIPs) In Medical Curriculum At Northern Border University: Strengths, Challenges, and Examples.

BACKGROUND: High-Impact Practices (HIPs) are educational practices that have been shown to increase rates of student retention, engagement, and persistence to graduation which help them to become high achievers and lifelong learners. Universities strongly encourage faculty members to incorporate one or more of these HIPs in order to improve active learning among students. Students are met with a variety of experiences that are not entirely of their choice, including expectations for academic performance, interactions with faculty, staff, and peers, and extracurricular activities that may or may not match their expectations and skills. Higher retention and high-grade achievement rates are attributed to HIPs. The mechanism by which HIPs improve retention is poorly understood. AIMS AND OBJECTIVES: There are numerous analyses of the objectives particular to undergraduate medical education in recent years. There have been proposed three major target categories. Undergraduate medical education has been positioned within a liberal education framework, where the main objective is to equip students with the critical thinking abilities, broad general education, and subject-specific knowledge they will need to be able to effectively problem-solve, adapt to new roles, and apply public health thinking and practices to a variety of situations. We tried to incorporate HIPs in a medical curriculum at the Faculty of Medicine, Northern Border University, by giving them topics that can be used to create public awareness about the selected objectives which may help the community greatly. METHODOLOGY: Students were asked to make posters or videos on the topics and were asked to write reflections about their experience and give feedback to the coordinators for improvements and to make these HIPs better so that they can be included uniformly in the other courses as well. RESULTS AND CONCLUSIONS: Based on results from a random sample of undergraduate students, we draw the conclusion that HIPs are correlated with engagement, which is the alignment of the student's critical thinking and ability to work in effective teams, group projects, learning communities, and sequence courses. HIPs have an impact on involvement among students across the world. HIPs are effective to the extent that they engage pupils, encouraging a greater commitment, which is one way to understand their success.

Pediatric Respiratory Emergencies-Recognition, Approach, and Management.

This article reviews the current trends and management of respiratory emergencies in children. Respiratory emergencies are a common report in pediatrics and often require prompt recognition and intervention. It is important to differentiate upper from lower respiratory disease processes because the management is often different. With the advent of many vaccinations, the concern for certain diseases has changed with variations in the prevalence of other organisms. This article discusses detection and management of many respiratory emergencies. [Pediatr Ann. 2023;52(4):e146-e152.].

Laparoscopic Appendectomy Translates into Less Analgesics and Faster Return to Work in Asia.

Background: Laparoscopic appendectomy (LA) is claimed to require less analgesic and allow for a faster return to work. This study examines whether these benefits hold true in Asian patient populations. Methods: A retrospective audit of emergency appendectomies over one year was conducted to study outcomes of postoperative pain, length of stay (LOS), duration of analgesia, and hospitalization leave (HL). A telephone questionnaire evaluated post-discharge analgesic intake, residual symptoms at follow-up, adequacy of HL and opinion on teleconsult reviews. Results: Of the 201 patients, 187 (93%) underwent LA. Presurgery symptoms were significantly longer in the open appendectomy (OA) group (mean: OA 3.79, LA 1.81 days; p = 0.026) which also had a higher frequency of perforation (71.4%). LA patients reported less pain compared to OA (LA 3.60 vs. OA 4.14; p = 0.068) but were prescribed the same 2 weeks of analgesics as OA. LOS was significantly less for LA (mean LA 3.09, OA 6.93 days; p = 0.006). Mean HL for LA and OA were 17.9 and 21.8 days respectively (p = 0.05). Nearly 83% patients did not complete the prescribed course of analgesics and 47% patients felt that HL was more than adequate. Seventy-five percent of patients were asymptomatic at hospital follow-up and nearly 41% agreed to teleconsult reviews. Conclusion: Majority of LA patients do not need 2 weeks of analgesics and their HL can be shortened for faster return to work thereby realizing the true benefits of minimally invasive surgery. Selected cases can be offered postoperative teleconsultation.

A rare case of ectopic retrosternal goiter.

It is important for the clinician to be familiar with interpreting a variety of radiological modalities that provide vital information that will aid in the preoperative planning, counseling, and subsequent management of patients with retrosternal goiter.

Minimally invasive video-assisted thyroidectomy in Asian patients: experience from Singapore.

BACKGROUND: Minimally invasive video-assisted thyroidectomy (MIVAT) although well established in Europe has not yet gained widespread acceptance in Asia. We describe our learning experience in the first reported series of 105 cases from Singapore. METHODS: A retrospective analysis of outcomes in 105 patients who underwent MIVAT from April 2011 to 2018 was performed. The inclusion criteria were - symptomatic benign thyroid pathologies and follicular lesions or neoplasms needing a hemi-thyroidectomy. A thyroid lobe volume less than 35 mL was used as cut-off. Patients underwent surgeon-performed thyroid ultrasound with biopsy of solid nodules. All cases were operated by one surgeon using standard Miccoli technique with energy device used in all cases. RESULTS: From a total of 424 patients with nodular goitres undergoing thyroidectomy, 105 (24%) symptomatic eligible patients underwent the MIVAT procedure (M:F - 23:82). The mean incision lengths at start and completion were 1.7 cm (range 1.5-2 cm) and 2.4 cm (range 2-2.7 cm), respectively. Mean operating time was 97 min (range 59-160 min). There were four conversions (3.8%) in the first 25 cases and four patients (3.8%) experienced transient hoarseness with full recovery. Visual analogue pain scores at 6 and 24 h post-operatively were 2.7 and 1.1, respectively. Scar satisfaction was reported as excellent (75%), satisfactory (23%) and poor (2%). CONCLUSION: Although technically more demanding, MIVAT is a safe and useful operation in a thyroid surgeon's armamentarium. The limitation of goitre size, however, allows only a small percentage of symptomatic patients to undergo this procedure.

Evolution of a Dedicated Emergency Surgery and Trauma (ESAT) unit over 3 years: sustained improved outcomes.

INTRODUCTION: The traditional 24-h call model faces pressure from competing needs between emergency and elective services. Recognizing this, a dedicated ESAT service was developed in Khoo Teck Puat Hospital in Singapore, with improved clinical outcomes. It was initially led by a single consultant (SC) in 2014, and subsequently evolved to a weekly consultant rotation (WC) roster in 2017 to achieve sustainability. METHODS: Each consultant led the ESAT WC service for a week and maintained ownership of their patients thereafter. All emergency surgical admissions between two distinct 6-month periods were reviewed, from May to October 2014 (pre-ESAT) and January to June 2017 (ESAT WC). Patient demographics, diagnoses, and operations were compared. Efficiency and clinical outcomes were evaluated. RESULTS: There were 1248 and 1284 patients in the pre-ESAT and ESAT WC group, respectively. Majority were males and in their 50s. Acute appendicitis, gallstone conditions, and soft-tissue infections made up half of the admissions. Trauma workload was comparable (7.8% pre-ESAT vs 9.5% ESAT WC). Cholecystectomies doubled during the ESAT period, 14.2% vs 7.2%, (p = 0.01). More consultants were involved in major cases (95.9% vs 86%), (p = 0.01) and more operations were performed during the day (52.1% vs 47.9%), (p = 0.01). Average time to OT was shorter and there were less major surgical complications (p = 0.02). Mortality (p = 0.08) and length of stay were reduced (4 vs 4.5 days), (p = 0.01). CONCLUSION: The ESAT WC service has sustained improved outcomes in our institution.

Early laparoscopic cholecystectomy by a dedicated emergency surgical unit confers excellent outcomes in acute cholecystitis presenting beyond 72 hours.

BACKGROUND: Early laparoscopic cholecystectomy (ELC) within 72 h of symptom onset is preferred for management of acute cholecystitis (AC). Beyond 72 h, acute-on-chronic fibrosis sets in rendering surgery challenging. This study aims to compare the outcomes of ELC for AC within and beyond 72 h of symptom onset by a dedicated acute surgical unit. METHODS: This is a single-centre retrospective study of 217 patients with AC who underwent ELC by an acute surgical unit from January 2017 to August 2018. Outcomes collected include post-operative morbidity, length of hospitalization and operation duration. A subgroup analysis for the same outcomes was performed for elderly patients. RESULTS: Of the 217 patients, 88 were operated within 72 h of symptom onset while 129 were operated beyond 72 h. Twenty-six patients received ELC after 7 days. There was no occurrence of bile duct injury. There was no statistical difference in conversion rates, wound infections and post-operative collections. Patients receiving ELC beyond 72 h had longer duration of operation (125.4 versus 116 min, P = 0.035) and length of hospitalization (4.59 versus 3.09 days, P = 0.001) without increase in morbidity. Patients older than 75 years had a higher incidence of post-operative collection (P < 0.001). CONCLUSION: Patients with AC undergoing ELC by a dedicated acute surgical unit can have good outcomes even beyond 72 h of symptom onset. Meticulous haemostasis should be performed for the elderly subgroup of patients.

Assessing adequacy of informed consent for elective surgery by student-administered interview.

BACKGROUND: Studies show that patients often sign consent documents without fully comprehending the risks, benefits and potential complications. There is currently no Asian study performed analysing adequacy of informed consent. This study aims to assess adequacy of informed consent by evaluating patient understanding and retention of key information and complications pertaining to surgery via medical student-administered interview. METHODS: A prospective study was performed on 48 patients undergoing groin hernia surgery, laparoscopic cholecystectomy and total thyroidectomy from 2017 to 2018 in a teaching hospital. Standardized assessment forms including major common complications and key details of the surgery were prepared. Structured one-to-one interviews between students and patients were performed and recorded on the morning of surgery. RESULTS: Although 93.8% of the patients claimed to have understood the information regarding their surgery, only 19.4%, 44.4% and 62.5% of the patients could actually recall the serious complications of groin hernia surgery, laparoscopic cholecystectomy and thyroidectomy, respectively. Elderly patients (>65 years) had poorer understanding of surgical procedure compared to the young (80% versus 100%, respectively, P = 0.008) with 26.7% of elderly patients claiming that they did not understand the indication for surgery. High satisfaction rates with this preoperative interview were reported by both patients and students (95.8% and 97.9%, respectively). Time interval from informed consent to surgery did not make any difference. CONCLUSION: Understanding of information and key complications was generally low, especially in the elderly population. The structured preoperative interview achieved the dual goal of reinforcing patient gaps in knowledge and improving student communication skills.

Gadolinium-based contrast agents in pediatric magnetic resonance imaging.

Gadolinium-based contrast agents can increase the accuracy and expediency of an MRI examination. However the benefits of a contrast-enhanced scan must be carefully weighed against the well-documented risks associated with administration of exogenous contrast media. The purpose of this review is to discuss commercially available gadolinium-based contrast agents (GBCAs) in the context of pediatric radiology. We discuss the chemistry, regulatory status, safety and clinical applications, with particular emphasis on imaging of the blood vessels, heart, hepatobiliary tree and central nervous system. We also discuss non-GBCA MRI contrast agents that are less frequently used or not commercially available.

Advanced imaging techniques in pediatric body MRI.

While there are many challenges specific to pediatric abdomino-pelvic MRI, many recent advances are addressing these challenges. It is therefore essential for radiologists to be familiar with the latest advances in MR imaging. Laudable efforts have also recently been implemented in many centers to improve the overall experience of pediatric patients, including the use of dedicated radiology child life specialists, MRI video goggles, and improved MR suite environments. These efforts have allowed a larger number of children to be scanned while awake, with fewer studies being done under sedation or anesthesia; this has resulted in additional challenges from patient motion and difficulties with breath-holding and tolerating longer scan times. In this review, we highlight common challenges faced in imaging the pediatric abdomen and pelvis and discuss the application of the newest techniques to address these challenges. Additionally, we highlight the newest advances in quantified imaging techniques, specifically in MR liver iron quantification. The techniques described in this review are all commercially available and can be readily implemented.

Predictive modelling using neuroimaging data in the presence of confounds.

When training predictive models from neuroimaging data, we typically have available non-imaging variables such as age and gender that affect the imaging data but which we may be uninterested in from a clinical perspective. Such variables are commonly referred to as 'confounds'. In this work, we firstly give a working definition for confound in the context of training predictive models from samples of neuroimaging data. We define a confound as a variable which affects the imaging data and has an association with the target variable in the sample that differs from that in the population-of-interest, i.e., the population over which we intend to apply the estimated predictive model. The focus of this paper is the scenario in which the confound and target variable are independent in the population-of-interest, but the training sample is biased due to a sample association between the target and confound. We then discuss standard approaches for dealing with confounds in predictive modelling such as image adjustment and including the confound as a predictor, before deriving and motivating an Instance Weighting scheme that attempts to account for confounds by focusing model training so that it is optimal for the population-of-interest. We evaluate the standard approaches and Instance Weighting in two regression problems with neuroimaging data in which we train models in the presence of confounding, and predict samples that are representative of the population-of-interest. For comparison, these models are also evaluated when there is no confounding present. In the first experiment we predict the MMSE score using structural MRI from the ADNI database with gender as the confound, while in the second we predict age using structural MRI from the IXI database with acquisition site as the confound. Considered over both datasets we find that none of the methods for dealing with confounding gives more accurate predictions than a baseline model which ignores confounding, although including the confound as a predictor gives models that are less accurate than the baseline model. We do find, however, that different methods appear to focus their predictions on specific subsets of the population-of-interest, and that predictive accuracy is greater when there is no confounding present. We conclude with a discussion comparing the advantages and disadvantages of each approach, and the implications of our evaluation for building predictive models that can be used in clinical practice.

Decoding negative affect personality trait from patterns of brain activation to threat stimuli.

INTRODUCTION: Pattern recognition analysis (PRA) applied to functional magnetic resonance imaging (fMRI) has been used to decode cognitive processes and identify possible biomarkers for mental illness. In the present study, we investigated whether the positive affect (PA) or negative affect (NA) personality traits could be decoded from patterns of brain activation in response to a human threat using a healthy sample. METHODS: fMRI data from 34 volunteers (15 women) were acquired during a simple motor task while the volunteers viewed a set of threat stimuli that were directed either toward them or away from them and matched neutral pictures. For each participant, contrast images from a General Linear Model (GLM) between the threat versus neutral stimuli defined the spatial patterns used as input to the regression model. We applied a multiple kernel learning (MKL) regression combining information from different brain regions hierarchically in a whole brain model to decode the NA and PA from patterns of brain activation in response to threat stimuli. RESULTS: The MKL model was able to decode NA but not PA from the contrast images between threat stimuli directed away versus neutral with a significance above chance. The correlation and the mean squared error (MSE) between predicted and actual NA were 0.52 (p-value=0.01) and 24.43 (p-value=0.01), respectively. The MKL pattern regression model identified a network with 37 regions that contributed to the predictions. Some of the regions were related to perception (e.g., occipital and temporal regions) while others were related to emotional evaluation (e.g., caudate and prefrontal regions). CONCLUSION: These results suggest that there was an interaction between the individuals' NA and the brain response to the threat stimuli directed away, which enabled the MKL model to decode NA from the brain patterns. To our knowledge, this is the first evidence that PRA can be used to decode a personality trait from patterns of brain activation during emotional contexts.

Renal myxoma in a pediatric transplant recipient.

Renal myxoma is a very rare benign neoplasm seen almost exclusively in adults with only 16 reported cases in the literature. All of these cases have been reported in native kidneys with none being reported in a transplant kidney. We report the case of a renal myxoma in a 17-year-old boy's transplant kidney that was found as an incidental mass on ultrasonography and further evaluated with CT and PET scans. PET findings of a renal myxoma are reported here for the first time, and imaging findings from previous cases are briefly reviewed. This case report highlights the fact that adult-predominant tumors and pathology should always be a consideration in pediatric patients who receive organ transplants from adult donors.