Diagnostic Utility of Genetic and Immunohistochemical H3-3A Mutation Analysis in Giant Cell Tumour of Bone

To validate the reliability and implementation of an objective diagnostic method for giant cell tumour of bone (GCTB). H3-3A gene mutation testing was performed using two different methods, Sanger sequencing and immunohistochemical (IHC) assays. A total of 214 patients, including 120 with GCTB and 94 with other giant cell-rich bone lesions, participated in the study. Sanger sequencing and IHC with anti-histone H3.3 G34W and G34V antibodies were performed on formalin-fixed, paraffin-embedded tissues, which were previously decalcified in EDTA if needed. The sensitivity and specificity of the molecular method was 100% (95% CI: 96.97–100%) and 100% (95% CI: 96.15–100%), respectively. The sensitivity and specificity of IHC was 94.32% (95% CI: 87.24–98.13%) and 100% (95% CI: 93.94–100.0%), respectively. P.G35 mutations were discovered in 2/9 (22.2%) secondary malignant GCTBs and 9/13 (69.2%) GCTB after denosumab treatment. We confirmed in a large series of patients that evaluation of H3-3A mutational status using direct sequencing is a reliable tool for diagnosing GCTB, and it should be incorporated into the diagnostic algorithm. Additionally, we discovered IHC can be used as a screening tool. Proper tissue processing and decalcification are necessary. The presence of the H3-3A mutation did not exclude malignant GCTB. Denosumab did not eradicate the neoplastic cell population of GCTB.

Diagnostic value of 18F-FDG PET-CT in detecting malignant peripheral nerve sheath tumors among adult and pediatric neurofibromatosis type 1 patients

Purpose Detecting malignant peripheral nerve sheath tumors (MPNSTs) remains difficult. 18F-FDG PET-CT has been shown helpful, but ideal threshold values of semi-quantitative markers remain unclear, partially because of variation among scanners. Using EU-certified scanners diagnostic accuracy of ideal and commonly used 18F-FDG PET-CT thresholds were investigated and differences between adult and pediatric lesions were evaluated. Methods A retrospective cohort study was performed including patients from two hospitals with a clinical or radiological suspicion of MPNST between 2013 and 2019. Several markers were studied for ideal threshold values and differences among adults and children. A diagnostic algorithm was subsequently developed. Results Sixty patients were included (10 MPNSTs). Ideal threshold values were 5.8 for SUVmax (sensitivity 0.70, specificity 0.92), 5.0 for SUVpeak (sensitivity 0.70, specificity 0.97), 1.7 for TLmax (sensitivity 0.90, specificity 0.86), and 2.3 for TLmean (sensitivity 0.90, specificity 0.79). The standard TLmean threshold value of 2.0 yielded a sensitivity of 0.90 and specificity of 0.74, while the standard SUVmax threshold value of 3.5 yielded a sensitivity of 0.80 and specificity of 0.63. SUVmax and adjusted SUV for lean body mass (SUL) were lower in children, but tumor-to-liver ratios were similar in adult and pediatric lesions. Using TLmean > 2.0 or TLmean < 2.0 and SUVmax > 3.5, a sensitivity and specificity of 1.00 and 0.63 can be achieved. Conclusion 18F-FDG PET-CT offers adequate accuracy to detect MPNSTs. SUV values in pediatric MPNSTs may be lower, but tumor-to-liver ratios are not. By combining TLmean and SUVmax values, a 100% sensitivity can be achieved with acceptable specificity.

Celiac Disease in Autism Spectrum Disorder: Data from an Italian Child Cohort

Background: In recent decades some studies described the frequent co-occurrence of celiac disease autoimmunity and/or overt celiac disease in patients with autism. Therefore, it was suggested that celiac disease could play a possible role in the etiopathogenesis of autism spectrum disorder. However, several other studies have not confirmed this association. The aim of the present study was to elucidate the potential association between autism spectrum disorder and celiac disease.Methods: We prospectively collected data from an Italian cohort of 223 children at the time of their clinical diagnosis of autism spectrum disorder in the 2019-2020 period. A serological celiac disease screening was performed and data were available for 196 patients; male (M):female (F) ratio = 4.4:1; median age = 3.6 years; age range = 1.6–12.8 years. Full-blown celiac disease was established according to the diagnostic algorithm of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) 2012 or 2019 guidelines. Fisher’s exact test was used to compare the celiac disease seroprevalence and prevalence in our autism spectrum disorder cohort and in the Italian healthy pediatric population studied by Gatti et al. to highlight the possible differences between the two groups.Results: A not statistically significant difference between the celiac disease seroprevalence in our autism spectrum disorder cohort (4.08%) and Gatti’s Italian healthy group (2.22%) was found, p = 0.0810; OR = 1.871. A similar result emerged for overt celiac disease prevalences (2.24% versus 1.58%, respectively), p = 0.2862; OR = 1.431.Conclusions: Our data validates a weakness of association between autism spectrum disorder and celiac disease. Regular screening for celiac disease in young patients with autism spectrum disorder is not strongly recommended to a greater extent than in the general population.

Sarcopenia assessed by 4-step EWGSOP2 in elderly hemodialysis patients: Feasibility and limitations

Background In 2019, EWGSOP2 proposed 4 steps to diagnose and assess sarcopenia. We aimed to quantify the prevalence of sarcopenia according to the EWGSOP2 diagnostic algorithm and to assess its applicability in elderly patients on hemodialysis. Methods Prospective study of 60 outpatients on chronic hemodialysis aged 75- to 95-years, sarcopenia was assessed according to the 4-step EWGSOP2: Find: Strength, Assistance walking, Rise from a chair, Climb stairs, and Falls (SARC-F); Assess: grip strength by dynamometry (GSD) and sit to stand to sit 5 (STS5); Confirm: appendicular skeletal muscle mass (ASM) by bioimpedance; Severity: gait speed (GS), Timed-Up and Go (TUG), and Short Physical Performance Battery (SPPB). Results The sequential four steps resulted in a prevalence of confirmed or severe sarcopenia of 20%. Most (97%) patients fulfilled at least one criterion for probable sarcopenia. The sensitivity of SARC-F for confirmed sarcopenia was low (46%). Skipping the SARC-F step increased the prevalence of confirmed and severe sarcopenia to 40% and 37%, respectively. However, 78% of all patients had evidence of dynapenia consistent with severe sarcopenia. Muscle mass (ASM) was normal in 60% of patients, while only 25% had normal muscle strength values (GSD). Conclusions According to the 4-step EWGSOP2, the prevalence of confirmed or severe sarcopenia was low in elderly hemodialysis patients. The diagnosis of confirmed sarcopenia underestimated the prevalence of dynapenia consistent with severe sarcopenia. Future studies should address whether a 2-step EWGSOP2 assessment (Assess-Severity) is simpler to apply and may provide better prognostic information than 4-step EWGSOP2 in elderly persons on hemodialysis.

Complicated Appendicitis: A Surgical Controversy Concerning Risk Factors, Diagnostic Algorithm and Therapeutic Management

By surgeon’s perspective, complicated appendicitis is defined as perforated appendicitis, periappendicular abscess, gangrenous appendicitis or peritonitis, noted on radiological studies upon hospital admission, operative reports or pathology results of the surgical specimen. Despite that this clinical condition is truly common in everyday surgical routine, its causes and risk factors are still unclear. Some parameters have been associated with complicated appendicitis, like older age, type 2 diabetes, symptoms for longer duration, appendicoliths/fecaliths, delays in surgery after onset of symptoms and after admission. Furthermore, currently, there is no standard diagnostic algorithm for complicated appendicitis. To be specific, radiological findings lack sensitivity, intraoperative assessment may overestimate it while, histopathological examination is regarded as more specific diagnostic method. In addition, the optimal treatment for complicated appendicitis remains controversial between an immediate surgical operation (laparotomy/laparoscopy) or a trial of nonoperative management. Hereby, by reviewing the current literature, we would aim to clarify the risk factors and the diagnostic procedure of complicated appendicitis as well as to compare the operative management with the conservative one according to the type of complicated appendicitis, the success rate and the postoperative complications.

Neck pain: diagnostic and therapeutic features

Neck pain is a fairly common complaint when visiting a doctor, its occurrence frequency is 10–21% per year, and neck pain takes the 4th place among the causes of disability; almost 50% of patients continue to experience unpleasant sensations or repeated pain episodes. The elderly people are the most prone to the neck pain, this is associated with the progressive degenerative changes in the facet joints and intervertebral discs. However, reasons of this symptom can be of different kinds. Cervicalgia diagnosis is directed primarily to eliminate symptomatic pains associated with severe somatic pathology, immune diseases, infections and oncology. Comorbid diseases and risk factors can combine with each other causing the polyetiologic pain syndrome. Main steps of the cervicalgia diagnostic algorithm are the following: collection of complaints and anamnesis in detail, physical and neurological examination, and also use of visualization methods. Visualization and electrodiagnostic methods are not always informative for patients with chronic cervicalgia and in the degenerative etiology of the syndrome. MRI and the surgeon consultation must be recommended to patients with deteriorating neurological symptoms or with long-term constant pain. Conservative therapy of cervicalgia implies a combination of non-drug methods (compliance with regime, orthopedic treatment, leaf, physiotherapy, etc.) and pharmacotherapy. The last depends on the presence of a neuropathic component of pain and the duration of pain syndrome. The pain therapy with a nociceptive nature is usually implies a combination of non-steroidal anti-inflammatory remedies, non-opioid analgesics and muscle relaxants. Whereas neuropathic pains first-line preparations are tricyclic antidepressants, duloxetine, venlafaxine, pregabalin, gabapentine. The therapy success depends on the proper individual estimation of the pain factors, pain chronization and possible treatment complications. The therapeutic forecast of the acute nonspecific cervicalgia is usually good, but it becomes less predictable if the pain acquires chronic character.

Diagnostic algorithm of centrally mediated abdominal pain syndrome — does it need changes? According to the materials of Rome IV Criteria

The article discusses the algorithm for diagnosing of centrally mediated abdominal pain syndrome (CAPS), formerly called functional abdominal pain syndrome, contained in the Rome Criteria of the IV revision (2016). Recommendations for the diagnosis of CAPS, mainly based on the compliance of the signs available in patients with the developed diagnostic criteria with a minimum of additional laboratory tests, are criticized, since such an approach is fraught with possible errors. The author considers the diagnosis of CAPS as a “diagnosis of exclusion”, which can be made only after a thorough examination of patients using laboratory and instrumental research methods (including ultrasound and endoscopic), confi rming the absence of organic diseases in patients.

Care Gaps and Recommendations in Vestibular Migraine: An Expert Panel Summit

Vestibular migraine (VM) is an increasingly recognized pathology yet remains as an underdiagnosed cause of vestibular disorders. While current diagnostic criteria are codified in the 2012 Barany Society document and included in the third edition of the international classification of headache disorders, the pathophysiology of this disorder is still elusive. The Association for Migraine Disorders hosted a multidisciplinary, international expert workshop in October 2020 and identified seven current care gaps that the scientific community needs to resolve, including a better understanding of the range of symptoms and phenotypes of VM, the lack of a diagnostic marker, a better understanding of pathophysiologic mechanisms, as well as the lack of clear recommendations for interventions (nonpharmacologic and pharmacologic) and finally, the need for specific outcome measures that will guide clinicians as well as research into the efficacy of interventions. The expert group issued several recommendations to address those areas including establishing a global VM registry, creating an improved diagnostic algorithm using available vestibular tests as well as others that are in development, conducting appropriate trials of high quality to validate current clinically available treatment and fostering collaborative efforts to elucidate the pathophysiologic mechanisms underlying VM, specifically the role of the trigemino-vascular pathways.