Visibility of esophageal squamous cell carcinoma under iodine staining on texture and color enhancement imaging.

Objective: Iodine staining on white light imaging (WLI) is the gold standard for detecting and demarcating esophageal squamous cell carcinoma (ESCC). We examined the effects of texture and color enhancement imaging (TXI) on improving the endoscopic visibility of ESCC under iodine staining. Methods: Twenty ESCC lesions that underwent endoscopic submucosal dissection were retrospectively included. The color difference between ESCC and the surrounding mucosa (ΔEe) on WLI, TXI, and narrow-band imaging was assessed, and ΔEe under 1% iodine staining on WLI and TXI. Furthermore, the visibility grade determined by endoscopists was evaluated on each imaging. Result: The median ΔEe was greater on TXI than on WLI (14.53 vs. 10.71, respectively; p < 0.005). Moreover, the median ΔEe on TXI under iodine staining was greater than the median ΔEe on TXI and narrow-band imaging (39.20 vs. 14.53 vs. 16.42, respectively; p < 0.005 for both). A positive correlation in ΔEe under iodine staining was found between TXI and WLI (correlation coefficient = 0.61, p < 0.01). Moreover, ΔEe under iodine staining on TXI in each lesion was greater than the corresponding ΔEe on WLI. The visibility grade assessed by endoscopists on TXI was also significantly greater than that on WLI under iodine staining (p < 0.01). Conclusions: The visibility of ESCC after iodine staining was greater on TXI than on WLI.

Co-producing a board game to learn and engage about dementia inequalities: First impacts on knowledge in the general population.

BACKGROUND: Receiving and accessing care after a diagnosis of dementia, both for the person and their carer, are fraught with inequalities. The aim of this public engagement activity was to co-produce a board game about dementia inequalities to facilitate learning, dialogue and educate about different barriers, and facilitators, to diagnosis and care and to test the game's impact on dementia knowledge with the general public. METHODS: Two virtual and two face-to-face workshops with people with dementia, unpaid carers, health and social care professionals and Third Sector representatives were held between October 2022 and June 2023. Virtual workshops involved discussions of inequalities and how a board game may feature inequalities. The first face-to-face workshop was split into the same activities, aided by outcomes from workshops 1 and 2. Workshop 4 attendees tested the prototype. The impact of the game on knowledge about dementia and inequalities was tested at a game play workshop in October 2023. RESULTS: Forty stakeholders attended four workshops. Workshops provided step-by-step thoughts on how the game could be designed or modified. The final game, prototype tested in workshop 4, consists of a one-sided, two-half board depicting the prediagnosis process (left half) and postdiagnosis process (right half). Fifty-two members of the general public participated in the game play workshop, which led to significant improvements in knowledge about dementia (p < .001) and inequalities (p < .001). DISCUSSION: The game can be used to improve knowledge about dementia inequalities for health and social care professionals, carers, people living with dementia, decision makers and the general public. PATIENT OR PUBLIC CONTRIBUTION: This engagement activity fully involved people with dementia, unpaid carers, health and social care professionals and Third Sector representatives throughout, with two unpaid carers as public advisers on the team.

Serum Beta-Secretase 1 Activity Is a Potential Marker for the Differential Diagnosis between Alzheimer's Disease and Frontotemporal Dementia: A Pilot Study.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the two major neurodegenerative diseases causing dementia. Due to similar clinical phenotypes, differential diagnosis is challenging without specific biomarkers. Beta-site Amyloid Precursor Protein cleaving enzyme 1 (BACE1) is a ß-secretase pivotal in AD pathogenesis. In AD and mild cognitive impairment subjects, BACE1 activity is increased in brain/cerebrospinal fluid, and plasma levels appear to reflect those in the brain. In this study, we aim to evaluate serum BACE1 activity in FTD, since, to date, there is no evidence about its role. The serum of 30 FTD patients and 30 controls was analyzed to evaluate (i) BACE1 activity, using a fluorescent assay, and (ii) Glial Fibrillary Acid Protein (GFAP) and Neurofilament Light chain (NfL) levels, using a Simoa kit. As expected, a significant increase in GFAP and NfL levels was observed in FTD patients compared to controls. Serum BACE1 activity was not altered in FTD patients. A significant increase in serum BACE1 activity was shown in AD vs. FTD and controls. Our results support the hypothesis that serum BACE1 activity is a potential biomarker for the differential diagnosis between AD and FTD.

Revisiting X-linked congenital ichthyosis.

X-linked recessive ichthyosis (XLI) is a hereditary skin disease characterized by generalized dryness and scaling of the skin, with frequent extracutaneous manifestations. It is the second most common type of ichthyosis, with a prevalence of 1/6,000 to 1/2,000 in males and without any racial or geographical differences. The causative gene for XLI is the steroid sulfatase gene (STS), located on Xp22.3. STS deficiency causes an abnormal cholesterol sulfate (CS) accumulation in the stratum corneum (SC). Excess CS induces epidermal permeability barrier dysfunction and scaling abnormalities. This review summarizes XLI's genetic, clinical, and pathological features, pathogenesis, diagnosis and differential diagnoses, and therapeutic perspectives. Further understanding the role of the STS gene pathogenic variants in XLI may contribute to a more accurate and efficient clinical diagnosis of XLI and provide novel strategies for its treatment and prenatal diagnosis.

Ultrafast Metaphotonic PCR Chip with Near-Perfect Absorber.

Polymerase chain reaction (PCR) is the gold standard for nucleic acid amplification and quantification in diverse fields such as life sciences, global health, medicine, agricultural science, forensic science, and environmental science for global sustainability. However, implementing a cost-effective PCR remains challenging for rapid preventive medical action to the widespread pandemic diseases due to the absence of highly efficient and low-cost PCR chip-based POC molecular diagnostics. Here, this work reports an ultrafast metaphotonic PCR chip as a solution of a cost-effective and low-power-consumption POC device for the emerging global challenge of sustainable healthcare. This work designs a near-perfect photonic meta-absorber using ring-shaped titanium nitride to maximize the photothermal effect and realize rapid heating and cooling cycles during the PCR process. This work fabricates a large-area photonic meta-absorber on a 6-inch wafer cost-effectively using simple colloidal lithography. In addition, this work demonstrates 30 thermocycles from 65 (annealing temperature) to 95 °C (denaturation temperature) within 3 min 15 s, achieving an average 16.66 °C s-1 heating rate and 7.77 °C s-1 cooling rate during thermocycling, succeeding rapid metaphotonic PCR. This work believes a metaphotonic PCR chip can be used to create a low-cost, ultrafast molecular diagnostic chip with a meta-absorber.

Radiographic and diagnostic approaches for mandibular asymmetries in orthodontic practice: a narrative review.

Mandibular asymmetry refers to dimensional differences between the left and right sides of the mandible in terms of size, form and volume. This condition may result in problems with functionality as well as appearance. Early intervention is often deemed optimal for addressing mandibular asymmetry; however, there is a lack of consensus regarding the diagnostic approach and strategy for identifying asymmetries in developing individuals. The purpose of this narrative review (NR) is to provide a clinician-focused update on the radiographic techniques for identifying mandibular asymmetries in orthodontic patients. Selective database searches were conducted until November 2023 to assess the available literature on mandibular asymmetry diagnosis. A health-sciences librarian developed a search strategy utilizing appropriate terms associated with mandibular asymmetry diagnosis. The databases used were Web of Science, Embase, Scopus, Liliacs and PubMed. Fifty-two studies were included in this review and data regarding the evaluation of mandibular asymmetries were presented with a narrative approach delineating clinical indications based on retrieved findings. There is no unanimous consensus on the method for diagnosing mandibular asymmetries. Cone beam computed tomography emerges as the preferred examination method for diagnosing mandibular asymmetry, thanks to the assessment of a 3D structure with a 3D image. However, the use of only orthopantomography could be advisable as a first-line diagnostic tool in children due to less radiation exposure.

Scout images acquired prior to cone beam CT acquisitions: reproducibility of findings and added diagnostic information.

OBJECTIVES: The aim of the present study was to assess the reproducibility of findings in cone beam computed tomography (CBCT) scout images. Furthermore, the study aimed to assess whether a scout image shows pathology not seen within the CBCT volume (ie, added diagnostic information) and therefore must be assessed on the same terms as the full volume. METHODS: Using a retrospective design, 233 CBCT reports and scout images were assessed. Kappa statistics and percentage of accordance were used to evaluate intra- and interobserver reproducibility as well as agreement between scout and CBCT report. RESULTS: Intra- and interobserver reproducibility were overall low (kappa ranging from -0.008 to 1.000). Agreement between findings reported in the CBCT and scout was also low. One-hundred-fourteen impacted teeth, one apical periodontitis, and two sinus conditions seen in the scout image were not registered in the full volume report due to the extended size of the scout image. CONCLUSIONS: Reproducibility of findings in scout images compared to CBCT volumes was low, and the scout showed very little additional diagnostic information. ADVANCES IN KNOWLEDGE: This study shows that although the reproducibility of viewing scout images is low, rare findings can go undetected if the scout is not assessed. Legislation regarding interpretation of scout images needs to be discussed.

Analysis of individual alpha frequency in a large cohort from a tertiary memory center.

BACKGROUND AND PURPOSE: Precise and timely diagnosis is crucial for the optimal use of emerging disease-modifying treatments for Alzheimer disease (AD). Electroencephalography (EEG), which is noninvasive and cost-effective, can capture neural abnormalities linked to various dementias. This study explores the use of individual alpha frequency (IAF) derived from EEG as a diagnostic and prognostic tool in cognitively impaired patients. METHODS: This retrospective study included 375 patients from the tertiary Memory Clinic of IRCCS San Raffaele Hospital, Milan, Italy. Participants underwent clinical and neuropsychological assessments, brain imaging, cerebrospinal fluid biomarker analysis, and resting-state EEG. Patients were categorized by amyloid status, the AT(N) classification system, clinical diagnosis, and mild cognitive impairment (MCI) progression to AD dementia. IAF was calculated and compared among study groups. Receiver operating characteristic (ROC) analysis was used to calculate its discriminative performance. RESULTS: IAF was higher in amyloid-negative subjects and varied significantly across AT(N) groups. ROC analysis confirmed IAF's ability to distinguish A-T-N- from the A+T+N+ and A+T-N+ groups. IAF was lower in AD and Lewy body dementia patients compared to MCI and other dementia types, with moderate discriminatory capability. Among A+ MCI patients, IAF was significantly lower in those who converted to AD within 2 years compared to stable MCI patients and predicted time to conversion (p < 0.001, R = 0.38). CONCLUSIONS: IAF is a valuable tool for dementia diagnosis and prognosis, correlating with amyloid status and neurodegeneration. It effectively predicts MCI progression to AD, supporting its use in early, targeted interventions in the context of disease-modifying treatments.

Comparison of the Application Value of Transthoracic Echocardiography in Diagnosing Patent Foramen Ovale Under Different States of Stimulation: A Retrospective Study.

OBJECTIVE: This study aims to evaluate the application value of contrast-enhanced transthoracic echocardiography (cTEE) in the diagnosis of patent foramen ovale (PFO) under different states of stimulation, with the goal of enhancing the accuracy and efficiency of PFO diagnosis. METHODS: This research consecutively enrolled patients suspected of having PFO from October 2022 to February 2024, presenting primary clinical symptoms such as unexplained syncope, headache, dizziness, and stroke. Patients underwent standard transthoracic echocardiography (TTE) and cTEE under three different states of stimulation (resting state, coughing, and Valsalva maneuver). Based on the presence of microbubbles in the left heart and their initial appearance time, patients were classified into PFO and control groups, with further diagnostic confirmation via transesophageal echocardiography (TEE) or foramen ovale closure procedures. RESULTS: The study results revealed significant differences between the PFO and control groups regarding age (p = 0.034) and headache symptoms (p = 0.001). In the PFO group, TTE showed a higher positivity rate both at rest and during coughing, highlighting the association between PFO and specific clinical symptoms. The number of microbubbles observed during TTE increased significantly under various stimulation states, particularly during the Valsalva maneuver (p < 0.05). This increase became more pronounced as the duration of the maneuver was extended, underscoring the differential response of PFO patients under varied physiological testing conditions, especially during prolonged Valsalva maneuvers. CONCLUSION: The study confirms the significant value of cTEE in diagnosing PFO under different stimulation states, particularly emphasizing the application of the Valsalva maneuver to significantly improve the sensitivity and specificity of PFO detection. Thus, incorporating cTEE examinations under various stimulation states holds significant clinical importance for enhancing the accuracy and efficiency of PFO diagnosis.

Immune checkpoint inhibitor therapy­related pneumonitis: How, when and why to diagnose and manage (Review).

Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment by enhancing the immune response against tumor cells. However, their influence on immune pathways can lead to immune-related adverse events such as pneumonitis, necessitating rapid diagnosis and management to prevent severe complications. These adverse events arise from the activation of the immune system by immunotherapeutic drugs, leading to immune-mediated inflammation and tissue damage in various organs and tissues throughout the body. The present review article discusses the pathophysiology, clinical presentation, diagnostic modalities and management strategies for ICI-related pneumonitis, emphasizing early recognition and tailored interventions. Future research endeavors should focus on elucidating the underlying mechanisms of pneumonitis and identifying predictive biomarkers to guide personalized treatment strategies in this evolving field of oncology.

Sarcopenia Diagnostic Technique Based on Artificial Intelligence Using Bio-signal of Neuromuscular System: A Proof-of-Concept Study.

In this paper, we propose an artificial intelligence (AI)-based sarcopenia diagnostic technique for stroke patients utilizing bio-signals from the neuromuscular system. Handgrip, skeletal muscle mass index, and gait speed are prerequisite components for sarcopenia diagnoses. However, measurement of these parameters is often challenging for most hemiplegic stroke patients. For these reasons, there is an imperative need to develop a sarcopenia diagnostic technique that requires minimal volitional participation but nevertheless still assesses the muscle changes related to sarcopenia. The proposed AI diagnostic technique collects motor unit responses from stroke patients in a resting state via stimulated muscle contraction signals (SMCSs) recorded from surface electromyography while applying electrical stimulation to the muscle. For this study, we extracted features from SMCS collected from stroke patients and trained our AI model for sarcopenia diagnosis. We validated the performance of the trained AI models for each gender against other diagnostic parameters. The accuracy of the AI sarcopenia model was 96%, and 95% for male and females, respectively. Through these results, we were able to provide preliminary proof that SMCS could be a potential surrogate biomarker to reflect sarcopenia in stroke patients.

A Rare Presentation of Multiple Myeloma With Spontaneous Haematoma.

Multiple myeloma (MM) typically presents with characteristic symptoms such as bone pain, hypercalcaemia, renal dysfunction, and anaemia. However, atypical presentations of MM, though rare, have been reported. These atypical presentations pose a diagnostic challenge due to their varied clinical manifestations, leading to potential delays in diagnosis and treatment initiation. We present the case of a 75-year-old woman who presented to the emergency department with a spontaneous haematoma on the dorsal aspect of her left hand and wrist. Despite lacking classical symptoms of MM, such as bone pain or renal dysfunction, laboratory investigations revealed abnormal findings, including high serum protein levels, low albumin, and abnormal immunoglobulin levels. Serum protein electrophoresis and immunotyping confirmed a diagnosis of MM, specifically the immunoglobulin-G lambda type. Additionally, urine protein electrophoresis further supported the diagnosis. Imaging studies did not show radiological evidence of myeloma. The absence of classical symptoms in our patient underscores the importance of considering MM in the differential diagnosis of atypical cutaneous presentations. Laboratory investigations, particularly serum protein electrophoresis and immunotyping, played a crucial role in establishing the diagnosis. The patient was treated with pulsed dexamethasone and plasmapheresis, followed by initiation of VCD chemotherapy protocol. Atypical presentations of MM present diagnostic challenges for clinicians. Our case highlights the importance of maintaining a high index of suspicion for MM, even in the absence of classical symptoms. Early recognition and diagnosis are essential for prompt management and improved patient outcomes. Clinicians should remain vigilant for atypical presentations of MM to ensure timely intervention and treatment initiation.

The Role of Circulating MicroRNAs in Cardiovascular Diseases: A Novel Biomarker for Diagnosis and Potential Therapeutic Targets?

MicroRNAs, involved in a large variety of pathological conditions, tend to be potential specific biomarkers in cardiovascular diseases. Moreover, these short, non-coding RNAs, regulate post-transcriptional gene expression and protein synthesis, making them ideal for therapeutic targets. Down-regulation and up-regulation of specific microRNAs are currently studied as a novel approach to the diagnosis and treatment of cardiovascular diseases, such as chronic and acute coronary syndromes, atherosclerosis, heart failure, and arrhythmia. MicroRNAs are interesting and attractive targets for cardiovascular-associated therapeutics because of their stability, tissue-specific expression pattern, and secretion of body fluids. Extended research on their isolation, detection, and function will provide the standardization needed for using microRNAs as biomarkers and potential therapeutic targets. This review will summarize recent data on the implication of microRNAs in cardiovascular diseases, their potential role as biomarkers for diagnosis, and also the challenges of using microRNAs as future therapeutic targets.

Evolving concepts in the treatment of posterior shoulder instability with glenohumeral bone loss.

Posterior shoulder instability is an increasingly recognized phenomenon and comprises approximately 5% of all shoulder instability cases. Posterior shoulder instability presents a complex clinical challenge, particularly when associated with bone loss. Bone loss may be present in up to 25% of patients with posterior shoulder instability. Understanding its etiology, diagnosis, and treatment options is crucial for optimal patient outcomes. Young athletic individuals, especially football linemen and throwing athletes, are commonly affected, with symptoms ranging from insidious onset pain to noticeable changes in athletic performance. History, physical examination, and imaging, including radiographs and advanced three-dimensional imaging, play pivotal roles in diagnosis, with specific tests like the Jerk, Kim, and load and shift tests aiding in provocation. Posterior glenoid bone loss (pGBL), whether dysplastic, attritional, or acute, significantly impacts management decisions. When pGBL exceeds critical thresholds, soft tissue repair alone may be insufficient, necessitating glenoid reconstruction with bone block procedures. Both iliac crest autograft and distal tibial allograft (DTA) offer viable options, with considerations including donor site morbidity and graft integration. Surgical techniques for reverse Hill-Sachs lesions vary from subscapularis transfers to arthroscopic balloon osteoplasty, each aiming to restore native anatomy and prevent engagement. Bipolar bone loss, involving both glenoid and humeral head defects, presents additional challenges and may require combined soft tissue and bony procedures. Quantifying bone loss and understanding its implications are essential for surgical planning. While various techniques show promise, further research is needed to elucidate their long-term outcomes and refine treatment algorithms for posterior shoulder instability with bone loss.

Case report and functional verification of a novel mutation in the interferon regulatory transcription factor 6 gene in a family with orofacial clefts.

BACKGROUND: This study aimed to identify the causative genetic variant in a Chinese family with orofacial clefts. METHODS: We retrospectively analyzed the clinical information of a family with orofacial clefts. Then, we performed an etiological genetic analysis of the family using whole exome sequencing analysis and Sanger sequencing. We created a hybrid code-shifting mutation cell line (293T-462het) and evaluated its impact on cell proliferation, migration, and apoptosis, as well as E-cadherin and vimentin expression. RESULTS: Whole exome sequencing revealed a novel heterozygous variant c.1386del (p.A462Pfs*28) in the interferon regulatory transcription factor 6 (IRF6) gene in a family with orofacial clefts. Sanger sequencing further confirmed that this heterozygous variant was the genetic cause of orofacial clefts in this family. The c.1386del variant of IRF6 was classified as likely pathogenic. The heterozygous mutation IRF6 (c.1386del) enhanced cell proliferation and migration while inhibiting cell apoptosis and regulating the expression of E-cadherin and vimentin. CONCLUSION: This study identified a novel c.1386del mutation in the IRF6 gene and explored how this mutation leads to lip and palate defects. Our results provide a solid theoretical foundation for future genetic detection of these orofacial defects.

Comparison of diagnostic methods for laboratory diagnosis of the zoonotic tapeworm Dipylidium caninum in cats.

The tapeworm Dipylidium caninum is the most widely distributed cestode infecting dogs, cats, and sometimes humans, worldwide. The diagnosis of the infection caused by D. caninum is achieved via the visualization of proglottids in feces or with traditional microscopic tests, but both lack sensitivity. The present study has evaluated and compared the diagnostic performance of a PCR protocol on different feline biological samples to detect D. caninum. A sample of feces, a Scotch tape test from the perianal area, and a rectal swab were collected from a total of 100 privately owned cats from Italy and Greece. All fecal samples were subjected to macroscopic examination and to floatation. Based on the results of the above tests the cats were divided in three groups, i.e. (i) cats positive for D. caninum (regardless of positivity for other endoparasites (Group A; n = 50 cats), (ii) cats negative for D. caninum but infected by other helminths (Group B; n = 25 cats), and (iii) cats negative for intestinal endoparasites (Group C; n = 25 cats). For each sample, the DNA was extracted from feces, floatation supernatant, Scotch tape test and rectal swabs and subjected to PCR. For 33 cats from Group A, at least one sample type scored positive at PCR. Of these, all were PCR-positive in the floatation aliquot, while nine and one cats were positive by PCR on feces and Scotch tape test, respectively. Swabs were negative by PCR for all the cats. None of the samples from cats of Groups B and C was positive by any PCR. Sequences obtained from amplicons generated from samples of cats enrolled in Italy had 99-100 % identity with the recently described D. caninum feline genotype. The data presented here suggest that PCR could be a useful tool for diagnosing D. caninum infections, under certain circumstances, e.g. when proglottids are unidentified, unseen or overlooked, even though it has limitations, e.g. false negative results due to fecal PCR inhibitors, uneven distribution of parasitic elements, or to intermittent proglottid and/or egg shedding. Thus, it may not be, currently, the best diagnostic choice for dipylidiosis.

SATCAS: A CRISPR/Cas13a-based simultaneous amplification and testing platform for one-pot RNA detection and SNPs distinguish in clinical diagnosis.

The clinical diagnosis of pathogen infectious diseases increasingly requires sensitive and rapid RNA detection technologies. The RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a system has shown immense potential in molecular diagnostics due to its trans-cleavage activity. However, most Cas13a-based detection methods require an amplicon transcription step, and the multi-step open-tube operations are prone to contamination, limiting their widespread application. Here, we propose an ultrasensitive (single-copy range, ∼aM) and rapid (within 40 min) isothermal one-pot RNA detection platform, termed SATCAS (Simultaneous Amplification and Testing platform based on Cas13a). This method effectively distinguishes viable bacteria (0%-100%) under constant total bacterial conditions, demonstrating its robustness and universality. SATCAS excels in identifying single nucleotide polymorphisms (SNPs), particularly detecting 0.5% drug-resistant mutations. We validated SATCAS by detecting infections in biological samples from 68 HBV, 23 EBV, and 48 SARS-CoV-2 patients, achieving 100% sensitivity, 92.86% specificity, and 97.06% accuracy in HBV infection testing. We anticipate that SATCAS has broad application potential in the early diagnosis, subtyping, drug resistance detection, and point-of-care monitoring of pathogen infectious diseases.

Comparison of microbiological and molecular diagnosis for identification of respiratory secondary infections in COVID-19 patients and their antimicrobial resistance patterns.

We report the use of a new multiplex Real-Time PCR platform to simultaneously identify 24 pathogens and 3 antimicrobial-resistance genes directly from respiratory samples of COVID-19 patients. Results were compared to culture-based diagnosis. Secondary infections were detected in 60% of COVID-19 patients by molecular analysis and 73% by microbiological assays, with no significant differences in accuracy, indicating Gram-negative bacteria as the predominant species. Among fungal superinfections, Aspergillus spp. were detected by both methods in more than 7% of COVID-19 patients. Oxacillin-resistant S. aureus and carbapenem-resistant K. pneumoniae were highlighted by both methods. Secondary microbial infections in SARS-CoV-2 patients are associated with poor outcomes and an increased risk of death. Since PCR-based tests significantly reduce the turnaround time to 4 hours and 30 minutes (compared to 48 hours for microbial culture), we strongly support the routine use of molecular techniques, in conjunction with microbiological analysis, to identify co/secondary infections.

The prevalence of cervical contribution in patients reporting shoulder pain. An observational study.

BACKGROUND: Shoulder pain is the third most common musculoskeletal disorder yet diagnosis remains challenging. In some cases, shoulder symptoms can be partially attributed to a cervical origin. OBJECTIVES: To estimate the prevalence of cervical contribution in patients presenting with shoulder pain. To determine symptom reproduction and symptom modification (i.e., pain intensity and pain location) after cervical spine screening (CSS) and compare these changes between patients with and without cervical contribution. DESIGN: Observational study. METHOD: Sixty patients were included. Cervical contribution was present if a ≥30.0% change in shoulder pain intensity on active movement was recorded after CSS. The CSS consisted of several tests and shoulder symptom modification or reproduction was noted. The presence of a centralization phenomenon was also noted and was considered to be present if the location of pain diminished from more distal areas after the CSS. RESULTS: A 50.0% prevalence of cervical contribution (CI95% 37,35-62,65) was found. Cervical contribution was more likely in those that demonstrated centralization of their pain after the CSS (p = 0.002) and those that had a history of previous neck pain (p = 0.007). Symptom reproduction occurred for 23 out of the 60 participants (38.3%), being present in 18 of those with cervical contribution (60.0%). After the CSS, a statistically significant decrease of shoulder pain intensity was found for those classified as having cervical contribution (p < 0.001). CONCLUSIONS: Cervical contribution is prevalent in 50% of patients presenting with shoulder pain; this was evidenced as shoulder symptom modification and, to a lesser extent, symptom reproduction following a CSS.

Prenatal Diagnosis of Myhre Syndrome in Two Cases: Further Delineation of the Cardiac and External Phenotype.

Myhre syndrome is a rare genetic disease caused by recurrent gain-of-function variants in SMAD4 (Ile500Thr, Ile500Val, Arg496Cys, and Ile500Met) characterized by postnatal short stature with pseudo-muscular build, joint stiffness, variable intellectual disability, hearing loss, and a distinctive pattern of dysmorphic facial features. The course can be severe in some cases, with life-threatening cardiac and pulmonary complications caused by connective tissue involvement. These progressive features over time make early clinical diagnosis difficult but possible by astute clinicians who evaluate young children with autism or short stature and unusual appearance. Only two cases of Myhre syndrome diagnosed during the prenatal period have been reported. Here, we present a detailed description of two unrelated fetuses with Myhre syndrome, each molecularly confirmed by genome or exome sequencing, who underwent fetal examination after termination of pregnancy. One had severe intrauterine growth retardation associated with crossed fused renal ectopia, and the other one had pulmonary atresia with ventricular septal defect (a form of tetralogy of Fallot). Both had mild dysmorphic features with a wide nasofrontal angle. Our results and a systematic prenatal literature review add insight into the early natural history of Myhre syndrome and highlight the contribution of prenatal next-generation sequencing in prenatal diagnosis and the importance of fetal autopsy in Myhre syndrome.