Correction: Nistor et al. Primary Cardiac Intimal Sarcoma: Multi-Layered Strategy and Core Role of MDM2 Amplification/Co-Amplification and MDM2 Immunostaining. Diagnostics 2024, 14, 919.

Camelia Stanciu Gavan, Adelina Birceanu, and Cezar Betianu were not included as authors in the original publication [...].

Primary Cardiac Intimal Sarcoma: Multi-Layered Strategy and Core Role of MDM2 Amplification/Co-Amplification and MDM2 Immunostaining.

Primary cardiac tumours are relatively uncommon (75% are benign). Across the other 25%, representing malignant neoplasia, sarcomas account for 75-95%, and primary cardiac intimal sarcoma (PCIS) is one of the rarest findings. We aimed to present a comprehensive review and practical considerations from a multidisciplinary perspective with regard to the most recent published data in the specific domain of PCIS. We covered the issues of awareness amid daily practice clinical presentation to ultra-qualified management in order to achieve an adequate diagnosis and prompt intervention, also emphasizing the core role of MDM2 immunostaining and MDM2 genetic analysis. An additional base for practical points was provided by a novel on-point clinical vignette with MDM2-positive status. According to our methods (PubMed database search of full-length, English publications from January 2021 to March 2023), we identified three studies and 23 single case reports represented by 22 adults (male-to-female ratio of 1.2; male population with an average age of 53.75 years, range: 35-81; woman mean age of 55.5 years, range: 34-70) and a 4-year-old child. The tumour-related clinical picture was recognized in a matter of one day to ten months on first admission. These non-specific data (with a very low index of suspicion) included heart failure at least NYHA class II, mitral regurgitation and pulmonary hypertension, acute myocardial infarction, ischemic stroke, obstructive shock, and paroxysmal atrial fibrillation. Awareness might come from other complaints such as (most common) dyspnoea, palpitation, chest pressure, cough, asthenia, sudden fatigue, weakness, malaise, anorexia, weight loss, headache, hyperhidrosis, night sweats, and epigastric pain. Two individuals were initially misdiagnosed as having endocarditis. A history of prior treated non-cardiac malignancy was registered in 3/23 subjects. Distant metastasis as the first step of detection (n = 2/23; specifically, brain and intestinal) or during follow-up (n = 6/23; namely, intestinal, brain and bone, in two cases for each, and adrenal) required additional imagery tools (26% of the patients had distant metastasis). Transoesophageal echocardiography, computed tomography (CT), magnetic resonance imagery, and even 18F-FDG positronic emission tomography-CT (which shows hypermetabolic lesions in PCIS) represent the basis of multimodal tools of investigation. Tumour size varied from 3 cm to ≥9 cm (average largest diameter of 5.5 cm). The most frequent sites were the left atrium followed by the right ventricle and the right atrium. Post-operatory histological confirmation was provided in 20/23 cases and, upon tumour biopsy, in 3/23 of them. The post-surgery maximum free-disease interval was 8 years, the fatal outcome was at the earliest two weeks since initial admission. MDM2 analysis was provided in 7/23 subjects in terms of MDM2-positive status (two out of three subjects) at immunohistochemistry and MDM2 amplification (four out of five subjects) at genetic analysis. Additionally, another three studies addressed PCISs, and two of them offered specific MDM2/MDM2 assays (n = 35 patients with PCISs); among the provided data, we mention that one cohort (n = 20) identified a rate of 55% with regard to MDM2 amplification in intimal sarcomas, and this correlated with a myxoid pattern; another cohort (n = 15) showed that MDM2-positive had a better prognostic than MDM2-negative immunostaining. To summarize, MDM2 amplification and co-amplification, for example, with MDM4, CDK4, HMGA3, CCND3, PDGFRA, TERT, KIT, CCND3, and HDAC9, might improve the diagnosis of PCIS in addition to MDM2 immunostaining since 10-20% of these tumours are MDM2-negative. Further studies are necessary to highlight MDM2 applicability as a prognostic factor and as an element to be taken into account amid multi-layered management in an otherwise very aggressive malignancy.

Trabecular Bone Score (TBS) in Individuals with Type 2 Diabetes Mellitus: An Updated Review.

Bone fragility is a complication of type 2 diabetes mellitus (T2DM) that has been identified in recent decades. Trabecular bone score (TBS) appears to be more accurate than bone mineral density (BMD) in diabetic bone disease, particularly in menopausal women with T2DM, to independently capture the fracture risk. Our purpose was to provide the most recent overview on TBS-associated clinical data in T2DM. The core of this narrative review is based on original studies (PubMed-indexed journals, full-length, English articles). The sample-based analysis (n = 11, N = 4653) confirmed the use of TBS in T2DM particularly in females (females/males ratio of 1.9), with ages varying between 35 and 91 (mean 65.34) years. With concern to the study design, apart from the transversal studies, two others were prospective, while another two were case-control. These early-post-pandemic data included studies of various sample sizes, such as: males and females (N of 245, 361, 511, and 2294), only women (N of 80, 96, 104, 243, 493, and 887), and only men (N = 169). Overall, this 21-month study on published data confirmed the prior profile of BMD-TBS in T2DM, while the issue of whether checking the fracture risk is mandatory in adults with uncontrolled T2DM remains to be proven or whether, on the other hand, a reduced TBS might function as a surrogate marker of complicated/uncontrolled T2DM. The interventional approach with bisphosphonates for treating T2DM-associated osteoporosis remains a standard one (n = 2). One control study on 4 mg zoledronic acid showed after 1 year a statistically significant increase of lumbar BMD in both diabetic and non-diabetic groups (+3.6%, p = 0.01 and +6.2%, p = 0.01, respectively). Further studies will pinpoint additive benefits on glucose status of anti-osteoporotic drugs or will confirm if certain glucose-lowering regimes are supplementarily beneficial for fracture risk reduction. The novelty of this literature research: these insights showed once again that the patients with T2DM often have a lower TBS than those without diabetes or with normal glucose levels. Therefore, the decline in TBS may reflect an early stage of bone health impairment in T2DM. The novelty of the TBS as a handy, non-invasive method that proved to be an index of bone microarchitecture confirms its practicality as an easily applicable tool for assessing bone fragility in T2DM.

Metabolic and Other Endocrine Elements with Regard to Lifestyle Choices: Focus on E-Cigarettes.

Our objective was to overview recent data on metabolic/endocrine disorders with respect to e-cigarette (e-cig) use. This is a narrative review; we researched English, full-length, original articles on PubMed (between January 2020 and August 2023) by using different keywords in the area of metabolic/endocrine issues. We only included original clinical studies (n = 22) and excluded case reports and experimental studies. 3 studies (N1 = 22,385; N2 = 600,046; N3 = 5101) addressed prediabetes risk; N1 showed a 1.57-fold increased risk of dual vs. never smokers, a higher risk that was not confirmed in N2 (based on self-reported assessments). Current non-smokers (N1) who were dual smokers still have an increased odd of prediabetes (a 1.27-fold risk increase). N3 and another 2 studies addressed type 2 diabetes mellitus (DM): a lower prevalence of DM among dual users (3.3%) vs. cigarette smoking (5.9%) was identified. 6 studies investigated obesity profile (4 of them found positive correlations with e-cig use). One study (N4 = 373,781) showed that e-cig use was associated with obesity in the general population (OR = 1.6, 95%CI: 1.3-2.1, p < 0.05); another (N5 = 7505, 0.82% were e-cig-only) showed that obesity had a higher prevalence in dual smokers (51%) vs. cig-only (41.2%, p < 0.05), while another (N6 = 3055) found that female (not male) e-cig smokers had higher body mass index vs. non-smokers. Data on metabolic syndrome (MS) are provided for dual smokers (n = 2): one case-control study found that female dual smokers had higher odds of MS than non-smokers. The need for awareness with respect to potential e-cig--associated medical issues should be part of modern medicine, including daily anamnesis. Whether the metabolic/endocrine frame is part of the general picture is yet to be determined. Surveillance protocols should help clinicians to easily access the medical background of one subject, including this specific matter of e-cig with/without conventional cigarettes smoking and other habits/lifestyle elements, especially when taking into consideration metabolism anomalies.

Landscape of Adrenal Tumours in Patients with Congenital Adrenal Hyperplasia.

Our aim is to update the topic of adrenal tumours (ATs) in congenital adrenal hyperplasia (CAH) based on a multidisciplinary, clinical perspective via an endocrine approach. This narrative review is based on a PubMed search of full-length, English articles between January 2014 and July 2023. We included 52 original papers: 9 studies, 8 case series, and 35 single case reports. Firstly, we introduce a case-based analysis of 59 CAH-ATs cases with four types of enzymatic defects (CYP21A2, CYP17A1, CYP17B1, and HSD3B2). Secondarily, we analysed prevalence studies; their sample size varied from 53 to 26,000 individuals. AT prevalence among CAH was of 13.3-20%. CAH prevalence among individuals with previous imaging diagnosis of AT was of 0.3-3.6%. Overall, this 10-year, sample-based analysis represents one of the most complex studies in the area of CAH-ATs so far. These masses should be taken into consideration. They may reach impressive sizes of up to 30-40 cm, with compressive effects. Adrenalectomy was chosen based on an individual multidisciplinary decision. Many tumours are detected in subjects with a poor disease control, or they represent the first step toward CAH identification. We noted a left lateralization with a less clear pathogenic explanation. The most frequent tumour remains myelolipoma. The risk of adrenocortical carcinoma should not be overlooked. Noting the increasing prevalence of adrenal incidentalomas, CAH testing might be indicated to identify non-classical forms of CAH.

Sternum Metastases: From Case-Identifying Strategy to Multidisciplinary Management.

We aimed to overview the most recent data on sternal metastases from a multidisciplinary approach (diagnosis strategies, outcome, and histological reports). This narrative review based on a PubMed search (between January 2020 and 22 July 2023) using key words such as "sternal", "manubrium", and "metastasis" within the title and/or abstract only included original papers that specifically addressed secondary sternal spreading of cancer in adults, for a total of 48 original articles (14 studies and 34 single case reports). A prior unpublished case in point is also introduced (percutaneous incisional biopsy was used to address a 10 cm sternal tumour upon first admission on an apparently healthy male). The studies (n = 14) may be classified into one of three groups: studies addressing the incidence of bone metastases (including sternum) amid different primary cancers, such as prostate cancer (N = 122 with bone metastases, 83% of them with chest wall metastases), head and neck cancers (N = 3620, 0.8% with bone metastases, and 10.34% of this subgroup with sternum involvement); and glioblastoma (N = 92 with bone metastases, 37% of them with non-vertebral metastases, including the sternum); assessment cohorts, including breast cancer (N = 410; accuracy and sensitivity of PET/CT vs. bone scintigraphy is superior with concern to sternum spreading) and bone metastases of unknown origin (N = 83, including a subgroup with sternum metastases; some features of PET/CT help the differentiation with multiple myeloma); and cohorts with various therapeutic approaches, such as palliative arterial embolization (N = 10), thymic neuroendocrine neoplasia (1/5 detected with sternum metastases), survival rates for sternum metastases vs. non-sternum chest wall involvement (N = 87), oligo-metastatic (sternal) breast cancer (3 studies, N = 16 for all of them), oligo-metastatic head and neck cancer (N = 81), conformal radiotherapy (N = 24,215, including an analysis on sternum spreading), and EBRT followed by MR-HIFU (N = 6). Core data coming from the isolated case reports (N = 34) showed a female to male ratio of 1.6; the females' ages were between 34 and 80 (mean of 57.28) and the males' ages varied between 33 and 79 (average of 58.78) years. The originating tumour profile revealed that the most frequent types were mammary (N = 8, all females) and thyroid (N = 9, both women and men), followed by bladder (N = 3), lung (N = 2), and kidney (N = 2). There was also one case for each of the following: adenoid cystic carcinoma of the jaw, malignant melanoma, caecum MiNEN, a brain and an extracranial meningioma, tongue carcinoma, cholangiocarcinoma, osteosarcoma, and hepatocellular carcinoma. To our knowledge, this is the most complex and the largest analysis of prior published data within the time frame of our methods. These data open up new perspectives of this intricate, dynamic, and challenging domain of sternum metastases. Awareness is a mandatory factor since the patients may have a complex multidisciplinary medical and/or surgical background or they are admitted for the first time with this condition; thus, the convolute puzzle will start from this newly detected sternal lump. Abbreviations: N = number of patients; n = number of studies; PET/CT = positron emission tomography/computed tomography; EVRT = external beam radiotherapy; MR-HIFU = magnetic resonance-guided high-intensity focused ultrasound; MiNEN = mixed neuroendocrine-non-neuroendocrine tumour.

Subxiphoid Mediastinoscopic Autonomous Double Fenestration.

The coexistence of pleural and pericardial effusions in frail patients with or without confirmed neoplasia necessitates the use of a minimally invasive technique that has a minor impact on the patient's general status and allows for fast fluid evacuation and biopsy sampling if necessary. We present a subxiphoid mediastinoscopic autonomous (simultaneous noncommunicating) double fenestration approach for these patients with both diagnostic and therapeutic advantages in selected cases. Using the mediastinoscope alone through the subxiphoid incision can considerably reduce the duration of operation, allow for fluid evacuation, and significantly alleviate the patient's symptoms. This method enables the sampling of pleural and pericardial fluids and targeted tissue, if necessary.

Pitfalls of DualTracer 99m-Technetium (Tc) Pertechnetate and Sestamibi Scintigraphy before Parathyroidectomy: Between Primary-Hyperparathyroidism-Associated Parathyroid Tumour and Ectopic Thyroid Tissue.

Diagnosis of primary hyperparathyroidism (PHP) is based on blood assessments in terms of synchronous high calcium and PTH (parathormone), but further management, particularly parathyroid surgery that provides the disease cure in 95-99% of cases, requires an adequate localisation of the parathyroid tumour/tumours as the originating source, with ultrasound and 99m-Technetium (99m-Tc) sestamibi scintigraphy being the most widely used. We aimed to introduce an adult female case diagnosed with PHP displaying unexpected intra-operatory findings (ectopic thyroid tissue) in relation to concordant pre-operatory imaging modalities (ultrasound + dual-phase 99m-Tc pertechnetate and sestamibi scintigraphy + computed tomography) that indicated bilateral inferior parathyroid tumours. A sudden drop in PTH following the removal of the first tumour was the clue for performing an extemporaneous exam for the second mass that turned out to be non-malignant ectopic thyroid tissue. We overviewed some major aspects starting from this case in point: the potential pitfalls of pre-operatory imaging in PHP; the concordance/discordance of pre-parathyroidectomy localisation modalities; the need of using an additional intra-operatory procedure; and the clues of providing a distinction between pathological parathyroids and thyroid tissue. This was a case of adult PHP, whereas triple localisation methods were used before parathyroidectomy, showing concordant results; however, the second parathyroid adenoma was a false positive image and an ectopic thyroid tissue was confirmed. The pre-operatory index of suspicion was non-existent in this patient. Hybrid imaging modalities are most probably required if both thyroid and parathyroid anomalies are suspected, but, essentially, awareness of the potential pitfalls is mandatory from the endocrine and surgical perspectives. Current gaps in imaging knowledge to guide us in this area are expected to be solved by the significant progress in functional imaging modalities. However, the act of surgery, including the decision of a PTH assay or extemporaneous exam (as seen in our case), represents the key to a successful removal procedure. Moreover, many parathyroid surgeons may currently perform 4-gland exploration routinely, precisely to avoid the shortcomings of preoperative localisation.

Triple Sleeve Bronchial Resection with Total Lung Preservation.

Triple sleeve bronchial resection with bronchial anastomosis is a complex surgical procedure, more difficult than the standard techniques of bronchial resection and anastomosis, commonly used to treat benign or low-grade malignant neoplasms (such as carcinoid tumours) that are located on the central bronchial axis (primary and lobar bronchi). When performed carefully by a highly trained surgeon, bronchial sleeve resection and reconstruction is a safe and effective surgical procedure. The complete preservation of the lung parenchyma is the main advantage of this surgical technique, along with a radical bronchial tumour resection. Sparing pulmonary function is crucial for both young (to maintain an optimal effort capacity) and elderly patients as well as those with impaired cardiopulmonary function (they may not tolerate lobectomy or pneumonectomy).

Management of Lung Cancer Presenting with Solitary Bone Metastasis.

Lung neoplasm is the main cause of cancer-related mortality, and bone metastasis is among the most common secondary tumors. The vast majority of patients also present with multiple bone metastases, which makes systemic and adjuvant pain therapy preferable to surgery. The optimal approach for a resectable non-small-cell lung tumor that also presents a unique, resectable bone metastasis is not fully established. The number of papers addressing this subject is small, and most are case reports; nevertheless, survival rates seem to increase with radical surgery. The sequencing of local versus systemic treatment should always be discussed within the multidisciplinary team that will choose the best approach for each patient. As targeted systemic therapies become more accessible, radical surgery, together with existing reconstructive methods, will lead to an increase in life expectancy and a better quality of life.

Clavicular Malignancies: A Borderline Surgical Management.

Nearly 1% of all bone cancers are primary clavicular tumors and because of their rarity, treating clinicians are unfamiliar with their diagnosis, classification, treatment options, and prognosis. In terms of preserving function and avoiding complications, clavicle reconstruction seems logical; however, further studies are needed to support this measure. Reconstruction techniques are difficult taking into account the anatomical structures surrounding the clavicle. When chest wall defects are present, a multidisciplinary team, including an orthopedist and thoracic and plastic surgeons, is of paramount importance for optimal surgical management. Malignant clavicle tumors may include primary and secondary malignancies and neighboring tumors with clavicular invasion. Surgical resection of complex thoracic tumors invading the clavicles can result in larger defects, requiring chest wall reconstruction, which is a substantial challenge for surgeons. Correct diagnosis with proper preoperative planning is essential for limiting complications. Post-resection reconstruction of the partial or total claviculectomy is important for several reasons, including maintaining the biomechanics of the scapular girdle, protecting the vessels and nerves, reducing pain, and maintaining the anatomical appearance of the shoulder. The chest wall resection and reconstruction techniques can involve either partial or full chest wall thickness, influencing the choice of reconstructive technique and materials. In the present paper, we aimed to synthesize the anatomical and physiopathological aspects and the small number of therapeutic surgical options that are currently available for these patients.