Differential Diagnosis Research Articles

Pictorial Review of Rare Pancreatic Tumors and Tumor-like Lesions: Radiologic–Pathologic Correlation

Rare pancreatic tumors and non-neoplastic tumor-like lesions present a diagnostic challenge due to their uncommon occurrence and overlapping imaging characteristics with more prevalent pancreatic neoplasms. Advances in imaging technologies and diagnostic criteria have contributed to increased detection of these rare entities in clinical practice. This pictorial review focuses on the radiologic–pathologic correlation of rare pancreatic tumors, including colloid carcinoma, acinar cell carcinoma, pancreatoblastoma, primary pancreatic lymphoma, and non-neoplastic tumor-like lesions such as hamartomas and inflammatory pseudotumors. Detailed imaging features, such as signal intensities on MRI and enhancement patterns on CT, are correlated with pathological findings to assist in the differential diagnosis. Familiarity with these characteristics is crucial for radiologists to ensure accurate diagnosis and guide appropriate treatment strategies, as management and prognosis significantly differ from common pancreatic neoplasms.

Artificial intelligence in cardiology: a machine learning model for supraventricular tachycardia discrimination

Abstract Background Distinguishing atrioventricular nodal reentrant tachycardia (AVNRT) from orthodromic atrioventricular reentrant tachycardia (AVRT) presents a diagnostic challenge, with clinical and electrocardiogram (ECG) features playing a crucial role in differential diagnosis. Purpose The aim of this study was to devise and validate a predictive algorithm that utilises basic clinical and ECG parameters to accurately classify AVNRT versus AVRT. Furthermore, this algorithm was integrated into a user-friendly, web-based tool to support clinical decision-making. Methods We conducted a prospective analysis of 704 patients (median age: 53.6 years; 59.7% female) with electrophysiologically confirmed AVNRT (n=535) or AVRT (n=169). A comprehensive evaluation was performed using a structured questionnaire tailored to arrhythmia-specific symptoms. The study utilised advanced machine learning techniques for classification, employing feature selection methods to enhance predictive accuracy. The analysis included 19 demographic, clinical, and ECG variables, adopting an 80-20% split for training and internal validation. The algorithm's performance was evaluated against a model comprising all variables (Full Model), expert ECG interpretations (ExpertECG), objective ECG criteria (ECG model), and a baseline dummy classifier, with efficacy assessed by the Area Under the Receiver Operating Characteristic curve (AUC) and the Area Under the Precision-Recall Curve (AUPRC). Results The optimised model, utilising the XGBoost algorithm with six critical variables (initial age at first episode, biological sex, presence of neck palpitations, pseudoR wave in lead V1/pseudoS wave in inferior leads, visibility of retrograde P-waves, and tachycardia cycle length), exhibited superior performance, achieving an AUC of 0.916 and an AUPRC of 0.823. This model significantly outperformed other comparative models in terms of predictive accuracy (Figure 1). Implementation of the model into a web-based interface was accomplished using Shiny, enhancing its accessibility for clinical application (Figure 2). Conclusions This study illustrates the efficacy of employing machine learning algorithms to utilise bedside clinical and ECG variables for accurately differentiating between AVNRT and AVRT. The creation of a web-based calculator marks a significant advancement, empowering clinicians, especially non-specialists, with a potent tool for providing personalised diagnostic insights. Future research should focus on external validation to ascertain the model's generalisability and its applicability in broader clinical settings.Figure 1Figure 2

False-positive cardiac troponin I values in healthy athletes post COVID-19 Infection: concerning insights from a prospective cohort study

Abstract Background Cardiac troponin I and T (cTnI, cTnT) are cardiac-specific biomarkers that detect and quantify cardiomyocyte injury. In patients with symptoms possibly indicating acute myocardial infarction (AMI), detection of elevated cTnT or cTnI concentrations usually mandates invasive coronary angiography. Accordingly, false-positive cTnT or cTnI concentrations could have detrimental consequences. Unfortunately, little is known about the prevalence and triggers of false-positive cTnI concentrations. Based on two index cases seen by one of us, we hypothesized that false-positive cTnI values may be common after COVID-19 infection and that macrotroponin, a complex formed between endogenous cTn autoantibodies and circulating cTn, may be the underlying cause. Purpose We aimed to test these hypotheses in a prospective cohort study. Methods We prospectively investigated professional athletes coming to the mandatory return to sports investigation at least 10 days after COVID-19 infection between 2022 and 2023 in an observational study. The presence of false-positive cTnI was centrally adjudicated in individuals that had elevated cTnI concentrations with one (or two) high-sensitivity cTnI assays, but normal high-sensitivity cardiac troponin T concentrations and normal electrocardiography (ECG), normal echocardiography, and normal cardiac magnetic resonance imaging (CMR). Divergences in hs-cTn concentrations were investigated using sex-specific upper limits of normal (ULN) of 4 different assays (hs-cTnI: Alinity/Abbott Diagnostic, hs-cTnI: Atellica/Siemens Healthineers, hs-cTnI: Access Beckman Coulter; hs-cTnT: Cobas/Roche Diagnostics). Athletes were instructed to cease training 48 hours before blood testing. Athletes with divergent hs-cTn assay results underwent further analysis for macrotroponin using sucrose gradient ultracentrifugation. Results Among 35 enrolled athletes (median age 24 years, 19 women and 16 men), 18 athletes had normal hs-cTn concentrations with all four hs-cTnT/I assays. In 17 athletes (48.6%), hs-cTn concentration was increased in at least one assay above the ULN, mostly one hs-cTnI method (hs-cTnI, Alinity) with normal concentrations of the other assays and normal cardiac imaging results. In contrast, two athletes had elevations in all hs-cTnI/T assays. Sucrose gradient ultracentrifugation provided evidence of macrotroponin in 15 of the 17 athletes (88%). Conclusions False-positive cTnI values are common after COVID-19 infection and should be considered in the differential diagnosis. Assay interference by macrotroponin seems to be the underlying mechanisms in most individuals. Documentation of normal hs-cTnT concentrations helps in the early detection of false-positive cTnI values.

The added value of cardiopulmonary exercise testing in the diagnosis of heart failure with preserved ejection fraction

Abstract Background Diagnosing heart failure with preserved ejection fraction (HFpEF) is challenging. Two validated algorithms, the HFA-PEFF and H2FPEF scores, have been proposed to guide our clinical practice. Many patients are categorized into an intermediate probability for HFpEF, representing a diagnostic "gray zone." This necessitates further evaluation, including right heart catheterization (RHC) at rest and possibly during exercise, to confirm or exclude the diagnosis. RHC, while informative, is resource-consuming and requires execution in specialized centers. Cardiopulmonary exercise testing (CPET) may offer a non-invasive and cost-effective alternative for differential dyspnea diagnosis. Purpose To evaluate the role of CPET in the diagnostic algorithm of unexplained dyspnea/suspected HFpEF. Methods This single-center retrospective study analyzed patients with a left ventricular ejection fraction (LVEF) ≥ 50% who underwent CPET for unexplained dyspnea from 2016 to 2020. We assessed HFpEF probability using the H2FPEF score and the HFA-PEFF algorithm. We hypothesized that specific CPET parameters (VO2 peak< 80% of predicted and/or VE/VCO2 slope > 35) might provide complementary information to the HFpEF probability scores. Additionally, we hypothesized that CPET could help identifying HFpEF in patients with intermediate probability in a subcohort of patients who underwent exercise RHC. Results Out of 103 patients, 61 (59%) were categorized as intermediate probability of HFpEF according to the HFA-PEFF score, and 59 (57%) according to the H2FPEF score. CPET results (VO2 peak and VE/VCO2 slope) were not associated with the pre-test probability of HFpEF as defined by either of the two scores. Exercise RHC was performed in 26 (43%) and in 27 (46%) patients with intermediate HFA-PEFF score and intermediate H2FPEF score, respectively. Among these patients with intermediate HFpEF probability, VO2 peak < 80% and/or VE/VCO2 slope > 35 had a good specificity and positive predictive value for HFpEF, as compared with exercise RHC (Table). Conclusions CPET provides complementary information to HFA-PEFF and H2FPEF scores. In particular, our results suggest that CPET may reclassify as HFpEF over 25% of patients with an intermediate HFpEF probability according to either the HFA-PEFF score or the H2FPEF score, potentially obviating the need for RHC. Thus, CPET might be incorporated into the HFpEF diagnostic algorithms.Table

Atypical Presentation of Multiple Myeloma: From Heart Failure to Multiple Myeloma

Multiple myeloma (MM) is a hematological malignancy commonly associated with bone pain, hypercalcemia, and renal failure. However, its presentation can occasionally mimic other medical conditions, which may delay diagnosis. This case report describes a patient who was initially diagnosed and treated for heart failure but was later found to have MM, highlighting the importance of considering MM in the differential diagnosis of heart failure. A 56-year-old lady presented with recurrent episodes of shortness of breath, orthopnea, paroxysmal nocturnal dypsnea and bilateral lower limb swelling which she had been treated for decompensated heart failure with optimal therapy. She denied any family history of cardiovascular disease personal history of underlying medical condition and was a nonsmoker. This patient was diagnosed with multiple myeloma and probability of concomitant cardiac amyloidosis and commenced on bortezomib, thalidomide and dexamethasone (VTD) regime and standard optimal therapy of heart failure but her condition deteriorated. After a few days of starting chemotherapy, patient demised despite all the resuscitative effort. Multiple myeloma is common hematological malignancy with its distinct clinical features of “CRAB”, however, more attention and alertness should also be exercised by clinicians as to be able to diagnose it early.

The resurgence of pertussis in Central Serbia in the period from June to December 2023

Abstract Background There was a registered increase in the number of confirmed pertussis cases in Central Serbia between June and December 2023. Among the possible causes of pertussis resurgence are increased awareness of pertussis among healthcare workers, availability of the sensitive RT PCR method in diagnostic, the limited duration of vaccine-induced immunity as well as decline of immunization coverage influenced by the COVID-19 pandemic. Methods The nasopharyngeal samples from clinics and primary care departments were transferred to Institute of Public Health of Serbia. DNA was extracted from each sample using the MagMAX Viral/Pathogen kit. The presence of B. pertussis was determined using two PCR assays, VIASURE Bordetella Real Time PCR Detection Kit and Bosphore B. pertussis/parapertussis Genotyping Kit, Anatolia Geneworks. Results RT-PCR confirmed a total of 338 pertussis cases in Institute of Public Health of Serbia during the observed period. Most of confirmed cases were among children 9-14 years old (49,7%) followed by infants younger than 12 months (21,9%). The more severe cases were among the unvaccinated and uncomplete vaccinated infants, 78,4% of which required hospitalization with two deaths in this age group. Conclusions Based on the analysis of the obtained results, we can highlight the importance of using sensitive methods in pathogen detection. Rapid diagnosis, laboratory confirmation and notification ensure early public health intervention to minimize the spread of disease. Despite long tradition of mandatory immunization against pertussis in the Republic of Serbia, wanning of vaccine induced immunity poses potential risk for the resurgence of pertussis. For pertussis control, in the future, it will be essential to achieve high immunization coverage as well as to introduce a booster dose of pertussis containing vaccine for children aged 14 and to implement vaccination of pregnant women. Key messages • For the better pertussis control vaccination of adolescents and adults, as well as vaccination of pregnant women should be considered in the future vaccination policies. • Clinicians should consider pertussis in the differential diagnosis of persistent cough illness in people of all ages, even those previously immunized.

Large Language Model Influence on Diagnostic Reasoning

Large language models (LLMs) have shown promise in their performance on both multiple-choice and open-ended medical reasoning examinations, but it remains unknown whether the use of such tools improves physician diagnostic reasoning. To assess the effect of an LLM on physicians' diagnostic reasoning compared with conventional resources. A single-blind randomized clinical trial was conducted from November 29 to December 29, 2023. Using remote video conferencing and in-person participation across multiple academic medical institutions, physicians with training in family medicine, internal medicine, or emergency medicine were recruited. Participants were randomized to either access the LLM in addition to conventional diagnostic resources or conventional resources only, stratified by career stage. Participants were allocated 60 minutes to review up to 6 clinical vignettes. The primary outcome was performance on a standardized rubric of diagnostic performance based on differential diagnosis accuracy, appropriateness of supporting and opposing factors, and next diagnostic evaluation steps, validated and graded via blinded expert consensus. Secondary outcomes included time spent per case (in seconds) and final diagnosis accuracy. All analyses followed the intention-to-treat principle. A secondary exploratory analysis evaluated the standalone performance of the LLM by comparing the primary outcomes between the LLM alone group and the conventional resource group. Fifty physicians (26 attendings, 24 residents; median years in practice, 3 [IQR, 2-8]) participated virtually as well as at 1 in-person site. The median diagnostic reasoning score per case was 76% (IQR, 66%-87%) for the LLM group and 74% (IQR, 63%-84%) for the conventional resources-only group, with an adjusted difference of 2 percentage points (95% CI, -4 to 8 percentage points; P = .60). The median time spent per case for the LLM group was 519 (IQR, 371-668) seconds, compared with 565 (IQR, 456-788) seconds for the conventional resources group, with a time difference of -82 (95% CI, -195 to 31; P = .20) seconds. The LLM alone scored 16 percentage points (95% CI, 2-30 percentage points; P = .03) higher than the conventional resources group. In this trial, the availability of an LLM to physicians as a diagnostic aid did not significantly improve clinical reasoning compared with conventional resources. The LLM alone demonstrated higher performance than both physician groups, indicating the need for technology and workforce development to realize the potential of physician-artificial intelligence collaboration in clinical practice. ClinicalTrials.gov Identifier: NCT06157944.

Application of Artificial Intelligence Models to Predict the Onset or Recurrence of Neovascular Age-Related Macular Degeneration

Neovascular age-related macular degeneration (nAMD) is one of the major causes of vision impairment that affect millions of people worldwide. Early detection of nAMD is crucial because, if untreated, it can lead to blindness. Software and algorithms that utilize artificial intelligence (AI) have become valuable tools for early detection, assisting doctors in diagnosing and facilitating differential diagnosis. AI is particularly important for remote or isolated communities, as it allows patients to endure tests and receive rapid initial diagnoses without the necessity of extensive travel and long wait times for medical consultations. Similarly, AI is notable also in big hubs because cutting-edge technologies and networking help and speed processes such as detection, diagnosis, and follow-up times. The automatic detection of retinal changes might be optimized by AI, allowing one to choose the most effective treatment for nAMD. The complex retinal tissue is well-suited for scanning and easily accessible by modern AI-assisted multi-imaging techniques. AI enables us to enhance patient management by effectively evaluating extensive data, facilitating timely diagnosis and long-term prognosis. Novel applications of AI to nAMD have focused on image analysis, specifically for the automated segmentation, extraction, and quantification of imaging-based features included within optical coherence tomography (OCT) pictures. To date, we cannot state that AI could accurately forecast the therapy that would be necessary for a single patient to achieve the best visual outcome. A small number of large datasets with high-quality OCT, lack of data about alternative treatment strategies, and absence of OCT standards are the challenges for the development of AI models for nAMD.

Takotsubo Cardiomyopathy After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for a Recurrent Colon Cancer: A Life-Threatening Complication

(1) Background: Takotsubo cardiomyopathy, or stress cardiomyopathy, is an acute heart failure condition with transient left ventricular (LV) motion abnormalities but no significant coronary artery obstruction. It mimics acute coronary syndrome (ACS), with symptoms like chest pain, dyspnea, and ECG changes. (2) Case Report: We present the case of a 44-year-old female with relapsed colon cancer and peritoneal carcinomatosis. After undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), she experienced cardiac arrest from ventricular fibrillation 18 h postoperatively. Echocardiography revealed a reduced LV ejection fraction (20%) and apical akinesia, suggesting a Takotsubo Cardiomyopathy. Intensive resuscitation and inotropic support led to gradual recovery. Coronary angiography confirmed no coronary artery obstruction. (3) Discussion: This case highlights TTS as a rare but severe complication following major oncological surgeries, possibly triggered by both physical and emotional stressors. TTS should be considered in the differential diagnosis of perioperative cardiac events in cancer patients. (4) Conclusions: Prompt recognition and management of TTS in the perioperative period are crucial to improving outcomes, especially in high-risk oncological patients undergoing extensive surgeries.

Contemporary characteristics, outcomes and novel risk score for Takotsubo cardiomyopathy: a national inpatient sample analysis

Abstract Background Takotsubo cardiomyopathy (TC) is an established differential diagnosis in the category of myocardial infarction with non-obstructive coronaries with significant recent interest but limited data on prognostication. We reviewed the characteristics and in-hospital outcomes and developed a novel risk score for TC. Methods Adult patients (≥18 years of age) with a diagnosis of acute coronary syndrome (ACS) and TC were identified from the National Inpatient Sample 2016-2020 in the United States. The cohort was divided into ACS with and without TC, and the related baseline data was retrieved. Multivariable regression analysis was performed to identify clinical factors associated with TC and its adverse outcomes and to create a risk-scoring system estimating mortality risk in the TC cohort. Results Amongst 7,219,004 adult patients admitted for ACS, 78,214 (1.0%) were diagnosed with TC, with a mean age of 68.2 years, 64,526 (82.5%) being female, and 5,475 (7.0%, compared with 8.4% for other ACS) in-hospital mortality events. Key factors significantly associated with TC diagnosis were female sex (OR 6.78 (95%CI 6.47-7.09), p<0.001) and chronic heart failure (OR 1.60 (95%CI 1.54-1.66), p<0.001). Based on multivariable analyses for in-hospital mortality in TC patients, a novel risk score was developed, with parameters and score assignment listed in the Figure. The score can be divided into three categories: low risk (-3 to +3), moderate risk (4 to 7), and high risk (8 to 19), and its area under curves for in-hospital mortality were 0.716 in the derivation and 0.726 in the validation cohorts. Conclusion TC remains a high-risk diagnosis in a minority of ACS hospitalizations, with comparable in-hospital mortality rates to other causes of ACS. A novel score was developed to risk stratify TC inpatients with moderate discrimination and internal validation, warranting external validation.Takotsubo Cardiomyopathy Risk Score

Severe Neonatal Episodic Laryngospasm (SNEL) due to Mutation in the SCN4A Gene as a Rare Differential Diagnosis in Paroxysmal Inspiratory Stridor with Cyanosis in Infancy.

Severe Neonatal Episodic Laryngospasm (SNEL) due to Mutation in the SCN4A Gene as a Rare Differential Diagnosis in Paroxysmal Inspiratory Stridor with Cyanosis in Infancy.

Thiamine-Responsive Megaloblastic Anemia (TRMA) Syndrome mimicking myelodysplastic neoplasm (MDS)

Thiamine-responsive megaloblastic anemia syndrome (TRMA) is a rare autosomal recessive disease with a homozygous or compound-heterozygous mutation in the SLC19A2 gene characterized by megaloblastic anemia, diabetes mellitus (DM), and sensorineural hearing-loss with onset in childhood. Folic acid and vitamin B12 in serum are normal with dysplastic erythropoiesis in the bone marrow often mimicking myelodysplastic neoplasms (MDN) as a potential differential diagnosis. Thiamine substitution leads to normalization of anemia, without effects on hearing-loss or DM. We report about a 38-year-old male patient, presented with a 12-year history of anemia, insulin dependent DM, optic neuropathy and a cataract since early childhood. The laboratory showed megaloblastic anemia. Other values were normal. The bone marrow smear showed dysplastic erythropoiesis with megaloblastic changes, and normal findings in cytogenetic and molecular genetic examinations. Next-generation sequencing based diagnostics revealed a heterozygous missense variant in the SLC19A2 gene on the maternal allele and a 3.4 Mb inversion in the chromosomal region 1q24.2 with breaking points in FAM78B and SLC19A2 on the paternal allele. Treatment with oral thiamine 100 mg daily was initiated, and 12 weeks later Hb levels and bone marrow morphology had normalized. Late-onset TRMA should be considered in adult patients with indicative comorbidities and a typical phenotype, which may mimic features of MDS.

High-grade astrocytoma with piloid features in the conus medullaris: a rare presentation of a new World Health Organization diagnosis. Illustrative case.

Neuroepithelial tumors with histological features of pilocytic astrocytoma (PA), increased mitotic activity with high-grade features of microvascular proliferation, and palisading necrosis have often been designated as anaplastic PAs. High-grade astrocytoma with piloid features (HGAP) was recently classified as its own entity by the World Health Organization (WHO) in 2021, after being grouped under anaplastic PA. This rare tumor typically arises in the cerebellum. The authors present the case of a patient with HGAP in the conus medullaris, a rare occurrence, with only 17 reported HGAP cases in other parts of the spinal cord. An 83-year-old female patient presented with progressive lower-extremity weakness over 2 weeks. Subsequent imaging revealed an intramedullary spinal cord mass near the conus. Histopathological analysis confirmed a neuroepithelial tumor. Chromosomal microarray revealed the diagnosis of HGAP, an exceedingly unusual tumor to be found near the conus. The tumor characteristics showed uniformly low cellularity and low proliferation of medium-sized ovoid cells with elongated nuclei, embedded in a loose pilocytic matrix. This report presents the case of a patient with HGAP in the conus medullaris, a new WHO diagnosis that needs to be included in the differential diagnosis for conus masses. https://thejns.org/doi/10.3171/CASE24390.

Development and validation of a smartphone based app to guide the differential diagnosis in patients with primary left ventricular hypertrophy: the Thick Heart App

Abstract Introduction Patients presenting with primary Left Ventricular Hypertrophy (LVH) suffers from a diagnostic delay quantified in years. They are often misdiagnosed because of both physician-related and disease-related reasons including fragmented knowledge among different specialties and rarity of the conditions. Purpose We developed and validate a free digital support tool in the form of an App to provide support and to guide the physician in the differential diagnostic process of patients presenting with primary LVH. Methods We studied 712 patients with definitive diagnosis of sarcomeric HCM or one of its genocopies (414 (58%) males, 48±24 years) referred to four tertiary centers in Europe. Pre-specified RF were categorized into five domains: family history; signs/symptoms; electrocardiography, echocardiographic and laboratory. Each patient’s characteristics were inserted by two independent and blind investigators on the App of the digital support tool. The possible diagnostic outcome was categorized as follows: (a) most likely diagnosis (age range for the condition, at least 1 extremely specific RFs or >1 specific RF; (b) possible diagnosis (age range, 1 specific RF); (c) less likely diagnosis (outside age range, no RF selected). Results Ris were common in patients presenting with a genotyped HCM (2568 RFs, 3.5 per patient). RF on physical examination was associated with non sarcomeric aetiology (318/319 physical examination RF identified in non-sarcomeric HCM), whereas 68% of RF associated with sarcomeric HCM were derived from accurate ECG and echocardiography analysis. Sarcomeric HCM, TTR-amyloidosis, Danon and PRKAG2 cardiomyopathy relied extensively on ECG and echocardiographic systematic analyisis (68%, 69%, 67% and 69% respectively). In contrast, AFD, Friederich’s ataxia, Noonan syndrome with multiple lentiges (NSML), mitochondrial, Pompe and Noonan cardiomyopathy presented red flags potentially identifiable in the general practioner setting by anamnesis, physical examination and routine laboratory (57%, 59%, 52%, 57%, 57% and 58% respectively) in the vast majority of case. A total of 697/712 (97.8%) were correctly categorized in the most likely and possible diagnosis section. The App proved to be sensible for sarcomeric HCM, FD (0.99 and 0.91, NPV 0.98 and 0.83) and extremely capable in the identification of rare causes of LVH (Danon, Friederich’s ataxia, LEOPARD, Pompe, Noonan and PRKAG2 diseases). By design, specificity was not high, in particular for sarcomeric HCM and FD. Conclusions The present validation of an App based free digital support tool in the form of an App proved to be extremely sensible in providing the support to the screening of different causes of primary LVH in patients presenting with a HCM phenotype. Further external and multicenter validation is warranted.

Synthetic assessment of cardiac autonomic modulation and Baevsky stress index in patients with synucleinopathies

Abstract Background The Baevsky Stress Index (BSTRi), calculated from Heart Rate Variability (HRV) data, has been proposed for quantitative assessment of physiological stress, with higher scores indicating higher levels of physical and/or psychological stress [1]. Cardiac autonomic modulation can be synthetically quantified by calculating the parasympathetic (PNSi) and the sympathetic (SNSi) indexes. The values of the BSTRi, SNSi, and PNSi in patients with synucleinopathies of different prognoses have not been reported yet. Purpose To quantify, in patients with Parkinson's disease (PD) and Multisystem Atrophy (MSA), the BSTRi, its correlation with the PNSi and the SNSi indexes, and their potential value for a synthetic assessment of cardiac autonomic modulation and early differential diagnosis between PD and MSA. Methods Holter ECG data of 66 patients with Parkinsonian syndromes were retrospectively analyzed after 10 years of follow-up. Out of them, 34 patients with a certain diagnosis of PD (17) and MSA (17) were selected for this study. HRV was analyzed with the Kubios software (version 4.0), providing automatic calculation of the BSTRi, PNSi, and SNSi [2], as well as of time domain (TD), frequency domain (FD), nonlinear (NL), and time-varying (TV) HRV parameters. HRV was calculated from selected short-term intervals (of 5 minutes), during daily activity (ACT5’), and non-REM sleep (NREM5’), and from 24-hours Holter recordings. Patients’ HRV findings were compared with those of 51 age-matched healthy subjects (HS). Results An example of individual automatic graphic summary is shown in Figure 1. Both short-term and 24-hour BSTRi and SNSi values were significantly (p < 0.05) higher in PD and MSA compared to those of HS, in all investigated conditions. Short-term PNSi was significantly higher in HS than in PD in all conditions, but only during NREM5’ in MSA patients (Table 1). No significant difference was found between the indexes of PD and MSA patients. As in HS (R=92), BSTRi was positively correlated with the SNSi in MSA (average R= 0.83 and 0.89 during ACT5’ and NREM5’, respectively), but less evident in PD (R=0.67). The inverse correlation between PNSi and SNSi (R=0.75 in HS) was lost in both MSA and PD. Conclusions Higher values of BSTRi in PD and MSA compared to HS suggest that patients with synucleinopathies do experience higher levels of psychophysiological stress, which may affect their quality of life negatively. However, since no significant difference was found in this study between BSTRi values of PD and MSA patients, BSTRi seems at present unreliable for early differentiation between the two diseases. Telematic assessment of BSTRi, SNSi, and PNSi could be useful for remote monitoring of PD and MSA patients’ psychophysiological stress, to provide timely intervention and adaptive treatment.Fig.1 Example of graphic summary (ACT5')

Obstructive hydrocephalus due to developmental venous anomalies: a pediatric imaging case series.

Developmental venous anomalies are a rare cause of obstructive hydrocephalus in the pediatric population. In this study, we present the most extensive case series of DVA-induced obstructive hydrocephalus in the pediatric population. We thoroughly describe the imaging findings related to this uncommon entity and comprehensively discuss its clinical presentation and management strategies. The goal is to alert pediatric neuroradiologists to consider this rare condition in the differential diagnosis of hydrocephalus, particularly during prenatal screening or in pediatric cases. The electronic patient record systems of 2 tertiary care children's hospitals were reviewed to identify pediatric patients with confirmed DVAs leading to obstructive hydrocephalus. Age at diagnosis, gender, MRI findings (including location of the obstruction), clinical presentation, and symptoms were recorded. Data on treatment and follow-up imaging were also collected. The search yielded 5 cases of pediatric patients with DVA-induced obstructive hydrocephalus. The mean age at diagnosis of the DVA was 2.9 years (range: 0-7 years), and in two cases, ventriculomegaly was diagnosed in utero during prenatal cranial ultrasound screenings. In all patients, the DVA caused stenosis of the aqueduct of Sylvius, and one case presented with multiple DVAs. Although aqueductal stenosis caused by a DVA is rare, it is crucial to consider it in the differential diagnosis of hydrocephalus during prenatal screening or in the pediatric population. Brain MRI, especially post-contrast T1WI, and SWI sequences are particularly valuable for visualizing the typical "caput medusae" appearance of DVAs and detecting associated complications such as hemorrhages.

Left ventricular longitudinal strain analysis using cardiac computed tomography for the diagnosis of cardiac amyloidosis

Abstract Introduction Cardiac amyloidosis (CA) results in a restrictive cardiomyopathy caused by extracellular deposition of proteins in the myocardium, demanding early identification for effective management. Left ventricular (LV) strain, mainly evaluated by echocardiography or cardiac magnetic resonance, provides sensitive and specific indicators for detecting CA, particularly apical sparing. It represents a pattern where the longitudinal strain (LS) in the basal and middle segments of LV is more impaired compared to the apical segments.¹ Cardiac computed tomography (CT) is useful not only for coronary artery evaluation but also for myocardial assessment, including LV ejection fraction (LVEF). Advanced software made it possible to analyse LS on cardiac CT (Figures A,B). Hypothesis: LS analysis using four-dimensional cardiac CT is helpful for the differential diagnosis of LV hypertrophied myocardial diseases and for detecting CA. Methods We analyzed 60 patients with LV hypertrophied myocardial diseases who underwent cardiac CT using 256-detector row or 320-detector row CT since 2009. Twenty patients of them were diagnosed with CA ( 70 ± 10 years, 14 males), the other 20 patients were diagnosed with hypertrophic cardiomyopathy (HCM) ( 60 ± 14 years, 12 males), and the rest of the 20 patients were diagnosed with severe aortic valve stenosis (AS) ( 86 ± 6 years, nine males). We analyzed LV global LS (GLS) and segmental LS using specific software and four-dimensional CT data. We evaluated relative apical LS as the value dividing the average LS of apical segments by the sum of the average LS of basal segments and mid-ventricular segments (Figure C). If the value was ≥ 1, apical sparing was defined as present. We compared the LS data and the percentage of apical sparing among those three myocardial diseases. Results There was no significant difference in LVEF among the three groups (52 ± 14%, 55 ± 27%, and 50 ± 18%, respectively; P = 0.15). There was no significant difference in GLS among the three groups (-10.6 ± 3.6%, -10.2 ± 5.2%, and -11.6 ± 3.8%, respectively; P = 0.87). Apical sparing was observed in 13 cases (65%) of CA, which was significantly higher than 3 cases (15%) of HCM or 4 cases(20%) of AS (P = 0.0002). Conclusions LV strain analysis using cardiac CT is helpful for detecting apical sparing. Advanced image analysis software has enabled LV strain analysis by cardiac CT, which is useful for the differential diagnosis of CA among LV hypertrophied diseases.Figure A,B,C

Ectopic thyroid tissue in adrenal gland – A case report and review of literature

Ectopic thyroid tissue along the line of descent of thyroid from foramen caecum along thyroglossal duct to the normal anatomic location in neck has been reported. Ectopic thyroid tissue in adrenal gland (ETTAG) is rarely encountered and very few cases have been reported in literature. The most common differential diagnosis to be considered when thyroid follicles are noted in adrenal gland are metastasis from a thyroid malignancy or a teratoma or an ectopic thyroid tissue in adrenal gland. We present a case of an adrenal incidentaloma in a young pregnant female which was diagnosed to be ectopic thyroid tissue in adrenal gland. The review of literature of similar cases of this rare embryological aberrance is discussed. To our knowledge, only 16 such cases have been documented in literature and our case is the first one from Indian subcontinent and the largest documented with respect to size.

A Real-Life Study in Patients Newly Diagnosed with Autoimmune Hashimoto’s Thyroiditis: Analysis of Asthenia as Admission Complaint

Background: Amid the large panel of autoimmune thyroid diseases, Hashimoto’s thyroiditis (HT) represents a major point across multidisciplinary daily practice. When it comes to the clinical picture, particularly in regard to asthenia (also described as “fatigue” or “decreased energy”), the differential diagnosis is challenging, and a meticulous anamnesis should be backed up by focused lab investigations. Our objective was to analyze the thyroid panel in newly diagnosed patients with HT in relationship with the presence of asthenia as an admission complaint. Methods: This was a retrospective, multi-centric, real-life study conducted in secondary endocrine units (university hospitals) from July 2022 to July 2023. The exclusion criteria were COVID-19 infection; an active malignancy, etc. Results: The cohort (N = 120) included an asthenia group (AS, 49.2%) and a non-AS group of a similar age (49.3 ± 14.7 vs. 47.1 ± 14.8 y, p = 0.426). Headache was more frequent in the AS group (35.6% vs. 18%, p = 0.03). Thyroid function and HT-related antibodies assays were similar between the groups and show no correlation with serum total cholesterol and triglycerides, respectively. TSH levels did not vary among the age sub-groups (p = 0.701). One third of the studied population was affected by hypothyroidism (TSH > 4.5 μIU/mL), being seen at a higher rate in the AS (39%) vs. non-AS group (23%). Total cholesterol positively correlated with the patients’ age (r = 0.180, p = 0.049) and triglycerides (N = 120; r = 0.324, p < 0.001), as found only in the non-AS group (r = 0.246, p = 0.006, respectively, r = 0.319, p < 0.001). Conclusions: The analysis of the AS vs. non-AS group pinpointed the fact that, in regard to daily practice, asthenia as an admission complaint seems less of an indicator of an underlying thyroid dysfunction or a higher level of serum antibodies against thyroid in patients without a full clinical picture of thyrotoxicosis or myxoedema.

TB or Not TB, That is the Question?

A 26-year-old female presented with a 3-month history of dry cough, unintentional weight loss, night sweats and fatigue. Her background history was significant for ulcerative colitis, managed with Adalimumab for almost 2 years. Clinical examination was unremarkable, apart from some mild pallor. Abnormal chest x-ray findings prompted a computerised tomography (CT) thorax which demonstrated multifocal peri-bronchial consolidation. The differential diagnosis was multifocal organising pneumonia and tuberculosis (TB). Extensive investigations, including invasive bronchial imaging and biopsy, ultimately ruled out TB. This paper reports a case of Adalimumab-induced organising pneumonia and discusses its clinical implications.