Personalized Management of Malignant and Non-Malignant Ectopic Mediastinal Thyroid: A Proposed 10-Item Algorithm Approach.

We aimed to analyze the management of the ectopic mediastinal thyroid (EMT) with respect to EMT-related cancer and non-malignant findings related to the pathological report, clinical presentation, imaging traits, endocrine profile, connective tissue to the cervical (eutopic) thyroid gland, biopsy or fine needle aspiration (FNA) results, surgical techniques and post-operatory outcome. This was a comprehensive review based on revising any type of freely PubMed-accessible English, full-length original papers including the keywords "ectopic thyroid" and "mediastinum" from inception until March 2024. We included 89 original articles that specified EMTs data. We classified them into four main groups: (I) studies/case series (n = 10; N = 36 EMT patients); (II) malignant EMTs (N = 22 subjects; except for one newborn with immature teratoma in the EMT, only adults were reported; mean age of 62.94 years; ranges: 34 to 90 years; female to male ratio of 0.9). Histological analysis in adults showed the following: papillary (N = 11/21); follicular variant of the papillary type (N = 2/21); Hürthle cell thyroid follicular malignancy (N = 1/21); poorly differentiated (N = 1/21); anaplastic (N = 2/21); medullary (N = 1/21); lymphoma (N = 2/21); and MALT (mucosa-associated lymphoid tissue) (N = 1/21); (III) benign EMTs with no thyroid anomalies (N = 37 subjects; mean age of 56.32 years; ranges: 30 to 80 years; female to male ratio of 1.8); (IV) benign EMTs with thyroid anomalies (N = 23; female to male ratio of 5.6; average age of 52.1 years). This panel involved clinical/subclinical hypothyroidism (iatrogenic, congenital, thyroiditis-induced, and transitory type upon EMT removal); thyrotoxicosis (including autonomous activity in EMTs that suppressed eutopic gland); autoimmune thyroiditis/Graves's disease; nodules/multinodular goiter and cancer in eutopic thyroid or prior thyroidectomy (before EMT detection). We propose a 10-item algorithm that might help navigate through the EMT domain. To conclude, across this focused-sample analysis (to our knowledge, the largest of its kind) of EMTs, the EMT clinical index of suspicion remains low; a higher rate of cancer is reported than prior data (18.8%), incident imagery-based detection was found in 10-14% of the EMTs; surgery offered an overall good outcome. A wide range of imagery, biopsy/FNA and surgical procedures is part of an otherwise complex personalized management.

Analysis of Aetiological Agents in Infectious Endocarditis in the Central Military Emergency University Hospital "Dr. Carol Davila" Bucharest.

BACKGROUND: Infective endocarditis (IE) is a pathological condition caused by various microbial agents that can lead to severe complications affecting the heart. Accurate diagnosis is crucial for the effective management of patients with IE. Blood culture is the gold standard for identifying the primary infectious agents, which is a key factor in diagnosing IE using the modified Duke criteria. OBJECTIVE: The main objective of this study was to investigate the distribution of the etiological agents of IE and the most common secondary diagnoses associated with it. METHOD: A total of 152 patients aged 23-95 years with a diagnosis of IE and proven etiology (through blood cultures or serological tests) were included in this study. RESULTS: The most common etiological agent identified through blood tests was Enterococcus faecalis, which was detected in 39 patients (23.5%). Staphylococcus aureus was the second most common agent and was identified in 33 patients (19.9%), followed by Staphylococcus epidermidis, which was identified in 12 patients (13.1%). Nine patients (5.8%) had high levels of anti-Coxiella burnetti IgG phase I and II antibodies. CONCLUSIONS: IE is a leading cause of death in the Department of Infectious Diseases. Early and accurate diagnosis, along with interdisciplinary treatment, can significantly increase the chances of patient survival. Currently, Enterococcus faecalis and Staphylococcus aureus are the dominant etiological agents of IE, highlighting the need to revise protocols for prophylaxis, diagnosis, and initial treatment of this condition.

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.

Neuroendocrine Neoplasia: From Pathophysiology to Novel Therapeutic Approaches.

Neuroendocrine neoplasia (NEN) represents a sensational field of modern medicine; immense progress in emerging biochemical, molecular, endocrine, immunohistochemical, and serum tumour markers of disease, respectively, which are part of early diagnosis, genetic testing, and multidisciplinary approaches [...].

Insights into Hyperparathyroidism-Jaw Tumour Syndrome: From Endocrine Acumen to the Spectrum of CDC73 Gene and Parafibromin-Deficient Tumours.

A total of 1 out of 10 patients with primary hyperparathyroidism (PHP) presents an underlying genetic form, such as multiple endocrine neoplasia types 1, 2A, etc., as well as hyperparathyroidism-jaw tumour syndrome (HJT). We aimed to summarise the recent data, thus raising more awareness regarding HJT, from the clinical perspective of PHP in association with the challenges and pitfalls of CDC73 genetic testing and parafibromin staining. This narrative review included a sample-focused analysis from the past decade according to a PubMed search. We identified 17 original human studies (≥4 patients per article). The mean age at disease onset was between 20.8 and 39.5 years, while the largest study found that 71% of patients had HJT recognised before the age of 30. Males and females seemed to be equally affected, in contrast with sporadic PHP. PHP represented the central manifestation of HJT, occurring as the first manifestation in up to 85% of HJT cases. A biochemistry panel found a mean serum calcium level above the level of 12 mg/dL in PHP. PTH was elevated in HJT as well, with average values of at least 236.6 pg/mL. The most frequent pathological type in PHP was a parathyroid adenoma, but the incidence of a parathyroid carcinoma was much higher than in non-HJT cases (15% of all parathyroid tumours), with the diagnosis being established between the age of 15 and 37.5. In some families up to 85% of carriers suffered from a parathyroid carcinoma thus indicating that certain CDC73 pathogenic variants may harbour a higher risk. An important issue in HJT was represented by the parafibromin profile in the parathyroid tumours since in HJT both parathyroid adenomas and carcinomas might display a deficient immunoreactivity. Another frequent manifestation in HJT was ossifying fibromas of the jaw (affecting 5.4% to 50% of patients; the largest study found a prevalence of 15.4%). HJT was associated with a wide variety of kidney lesion (mostly: kidney cysts, with a prevalence of up to 75%, and renal tumours involved in 19% of patients). The risk of uterine lesions seemed increased in HJT, especially with concern to leiomyomas, adenofibromas, and adenomyosis. The underlying pathogenic mechanisms and the involvement of CDC73 pathogenic variants and parafibromin expression are yet to be explored. Currently, the heterogeneous expression of parafibromin status and, the wide spectrum of CDC73 mutations including the variety of clinical presentations in HJT, make it difficult to predict the phenotype based on the genotype. The central role of HJT-PHP is, however, the main clinical element, while the elevated risk of parathyroid carcinoma requires a special awareness.

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.

Cross-Disciplinary Approach of Adrenal Tumors: Insights into Primary Aldosteronism-Related Mineral Metabolism Status and Osteoporotic Fracture Risk.

Our objective was to overview the novel aspects in the field of adrenal gland neoplasms, namely, the management of bone status with respect to primary aldosteronism (PA). In the current narrative review, a PubMed study was conducted from inception until June 2023. The inclusion criteria were: human (clinically relevant) studies of any study design (at least 10 patients per study); English papers; and the following combination of key words within the title and/or abstract: "aldosterone" AND "bone", "skeleton", "osteoporosis", "fracture", "calcium", "parathyroid", "DXA", "osteocalcin", "P1NP", "alkaline phosphatase", "bone marker", "trabecular bone score", or "FRAX". The exclusion criteria were in vitro or animal studies, reviews, and case reports/series. We screened 1027 articles and finally included 23 studies (13 of case-control type, 3 cross-sectional, 5 prospective, 1 observational cohort, and 1 retrospective study). The assessments provided in these studies were as follows: nine studies addressed Dual-Energy X-ray Absorptiometry (DXA), another study pointed out a bone microarchitecture evaluation underlying trabecular bone score (TBS), and seven studies investigated the bone turnover markers (BTMs) profile. Moreover, 14 studies followed the subjects after adrenalectomy versus medical treatment, and 21 studies addressed secondary hyperparathyroidism in PA patients. According to our study on published data during a period of almost 40 years (n = 23, N = 3965 subjects aged between 38 and 64, with a mean age 56.75, and a female-to-male ratio of 1.05), a higher PTH in PA versus controls (healthy persons or subjects with essential hypertension) is expected, secondary hyperparathyroidism being associated in almost half of the adults diagnosed with PA. Additionally, mineral metabolism anomalies in PA may include lower serum calcium and higher urinary calcium output, all these three parameters being reversible under specific therapy for PA, regardless medical or surgical. The PA subgroup with high PTH seems at higher cardiovascular risk, while unilateral rather than bilateral disease was prone to this PTH anomaly. Moreover, bone mineral density (BMD) according to central DXA might show a higher fracture risk only in certain adults, TBS being a promising alternative (with a still unknown perspective of diabetes' influence on DXA-TBS results in PA). However, an overall increased fracture prevalence in PA is described in most studies, especially with respect to the vertebral site, the fracture risk that seems correctable upon aldosterone excess remission. These data recommend PA as a cause of secondary osteoporosis, a treatable one via PA intervention. There is still an area of debate the way to address BMTs profile in PA, the case's selection toward specific bone evaluation in every day practice, and further on, the understanding of the potential genetic influence at the level of bone and mineral complications in PA patients.

From acute hypercalcaemia to post-parathyroidectomy hungry bone syndrome in a patient with primary hyperparathyroidism-associated brown tumours.

Not required for Clinical Vignette.

Hyponatremia as a Prognostic Factor in Advanced Stage Ovarian Cancer Patients.

Background: hyponatremia represents one of the most commonly encountered conditions in hospitalized patients, multiple mechanisms being cited so far, neoplastic syndromes being an important cause. The aim of the current paper is to analyse the presence and influence of the short- and long-term outcomes of hyponatremia on ovarian cancer patients submitted to surgery for advanced stage ovarian cancer. Method: 57 patients diagnosed with advanced stage ovarian cancer were submitted to surgery between 2014-2020. The patients were further classified according to the preoperative value of sodium into two groups. Results: there were 21 cases with preoperative normal values of sodium and respectively 36 cases with hyponatremia. Patients with preoperative hyponatremia associated a significantly higher rate of early postoperative complications and a significantly poorer long-term outcome. Therefore, cases with hyponatremia reported a mean disease-free survival of 10.8 months and respectively a mean overall survival of 18.5 months while cases with normal natrium levels reported a mean disease-free survival of 31.4 months and respectively a mean overall survival of 49.7 months (p=0.0001 and p 0.001). Conclusions: patients with lower preoperative values of sodium have a higher risk of developing postoperative complications and a significantly poorer outcome when compared to cases presenting normal levels of sodium preoperatively.

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.

Differential Outcomes of VATS and Open Surgery in Lung Cancer Patients with Antecedent Oncological Diagnoses.

Primary lung cancer is a devastating disease with high morbidity and mortality rates. Patients with a previous oncological history may present with multiple comorbidities, unique clinical features, and unique outcomes after surgical intervention for primary lung cancer. This study aimed to compare the clinical features and outcomes of patients with a previous oncological history who underwent video-assisted thoracoscopic surgery (VATS) or open surgery (OS) for primary lung cancer. A retrospective analysis was conducted on 84 patients with a previous oncological history who underwent surgical intervention for primary lung cancer between January 2018 and January 2023. Among them, 55 patients underwent VATS, while 29 patients underwent OS. Demographic and clinical characteristics, perioperative variables, and postoperative outcomes of the two surgical groups were collected and compared. Most of the 84 patients were women (58.4%) with a high smoking prevalence (44.1%) and a median of 32.3 packs-year. The patients' histories were most predominant for gynecologic cancers (44.4%) and colorectal cancers (18.6%). The results showed that the VATS group had a significantly shorter median hospital stay than the OS group (6.0 days vs. 12.0 days, p-value < 0.001). Additionally, the VATS group had lower incidences of air leaks 24 h post-surgery (12.7% vs. 48.3%, p-value < 0.001) and intractable pain (3.6% vs. 17.2%, p-value = 0.031), as well as significantly lower operative times (270 min vs. 350 min, p-value = 0.046). However, there were no significant differences between the VATS and OS groups in overall survival (log-rank p-value = 0.447). Furthermore, although the 3-month survival was significantly higher in the VATS group (98.2% vs. 79.3%, p-value = 0.003), only one patient from the VATS group (1.8%) and two patients from the OS group (6.9%) were still alive five years after the intervention. In conclusion, VATS is a safe and effective surgical option for patients with a previous oncological history who require surgical intervention for primary lung cancer, with shorter operative times, shorter hospital stays, and lower rates of complications compared to those of OS patients, without compromising oncological outcomes. Nevertheless, both surgical options failed to improve the 5-year survival rate, probably due to the high prevalence of comorbidities and the burden of previous cancer in this population.

TAVI in a Heart Transplant Recipient-Rare Case Report and Review of the Literature.

The global demand for cardiac transplants continues to rise, even with advancements in assistive devices. Currently, the estimated annual mortality rate stands at 3-5%, and patients often face a waiting time of approximately four years on transplant waiting lists. Consequently, many transplant centers have started to consider heart transplants from donors who may be deemed "less than ideal" or marginal. However, the decision to accept such donors must be highly individualized, taking into consideration the risks associated with remaining on the waiting list versus those posed by the transplantation procedure itself. A potential solution lies in the creation of two distinct recipient lists, matched with donor criteria, allowing marginal donors to provide the lifeline that selected patients require. This paper follows a two-step approach. Firstly, it offers an overview of the current state of affairs regarding the topic of transcatheter aortic valve implantation (TAVI) in orthotopic heart transplant (OHT) patients. Secondly, it presents firsthand experience from our clinical center with a comprehensive case presentation of a patient in this unique medical context. The clinical case refers to a 62-year-old male patient, a smoker with a history of hypertension, dyslipidemia, and a prior OHT a decade earlier, who presented with fatigue during minimal physical exertion. The Heart Team carefully reviewed the case, considering the patient's immunosuppressed status and the heightened risk associated with a repeat intervention. In this instance, transcatheter aortic valve implantation (TAVI) was deemed the appropriate treatment. The TAVI procedure yielded successful results, leading to improved clinical status and enhanced cardiac function. The inclusion of marginal donors has introduced novel challenges related to the utilization of previously diseased marginal organs. TAVI has already demonstrated its efficacy and versatility in treating high-risk patients, including heart transplant recipients. Consequently, it emerges as a vital tool in addressing the unique challenges posed by the inclusion of marginal donors.

Pediatric Neuroendocrine Neoplasia of the Parathyroid Glands: Delving into Primary Hyperparathyroidism.

Our objective was to overview the most recent data on primary hyperparathyroidism (PHP) in children and teenagers from a multidisciplinary perspective. Methods: narrative review based on full-length, English-language papers (from PubMed, between January 2020 and July 2023). Results: 48 papers (14 studies of ≥10 subjects/study, and 34 case reports/series of <10 patients/study). Study-sample-based analysis: except for one case-control study, all of the studies were retrospective, representing both multicenter (n = 5) and single-center (n = 7) studies, and cohort sizes varied from small (N = 10 to 19), to medium-sized (N = 23 to 36) and large (N = 63 to 83); in total, the reviewed studies covered 493 individuals with PHP. Case reports/series (n = 34, N = 41): the mean ages studied varied from 10.2 to 14 years in case reports, and the mean age was 17 years in case series. No clear female predominance was identified, unlike that observed in the adult population. Concerning the assessments, there were four major types of endpoints: imaging data collection, such as ultrasound, 99mTc Sestamibi, or dual-phase computed tomography (CT); gene testing/familial syndrome identification; preoperative findings; and exposure to surgical outcome/preoperative drugs, like cinacalcet, over a 2.2-year median (plus two case reports of denosumab used as an off-label calcium-lowering agent). Single-gland cases (representing 85% of sporadic cases and 19% of genetic PHP cases) showed 100% sensitivity for neck ultrasounds, with 98% concordance with 99mTc Sestamibi, as well as a 91% sensitivity for dual-phase CT, with 25% of the lesions being ectopic parathyroids (mostly mediastinal intra-thymic). Case reports included another 9/41 patients with ectopic parathyroid adenomas, 3/41 with parathyroid carcinomas, and 8/41 subjects with brown tumors. Genetic PHP (which has a prevalence of 5-26.9%) mostly involved MEN1, followed by CDC73, CASR, RET, and CDKN1B, as well as one case of VHL. Symptomatic PHP: 70-100% of all cases. Asymptomatic PHP: 60% of genetic PHP cases. Renal involvement: 10.5% of a cohort with genetic PHP, 71% of sporadic PHP cases; 50% (in a cohort with a mean age of 16.7), 29% (in a cohort with a mean age of 15.2); 0% (in infancy) to 50-62% (in teenagers). Bone anomalies: 83% of the children in one study and 62% of those in two other studies. Gastrointestinal issues: 40% of one cohort, but the data are heterogeneous. Cure rate through parathyroidectomy: 97-98%. Recurrent PHP: 2% of sporadic PHP cases and 38% of familial PHP cases. Hungry bone syndrome: maximum rate of 34-40%. Case reports identified another 7/41 subjects with the same post-parathyroidectomy condition; a potential connection with ectopic presentation or brown tumors is suggested, but there are limited data. Minimally invasive thoracoscopic approaches for ectopic tumors seemed safe. The current level of statistical evidence on pediatric PHP qualifies our study- and case-sample-based analysis (n = 48, N = 534) as one of the largest of its kind. Awareness of PHP is the key factor to benefit our young patients.

Platelet to Lymphocyte Ratio as a Predictive Tool for the Perioperative and Postoperative Outcomes in Advanced Stage Ovarian Cancer.

Background: platelet to lymphocyte ratio remains a significant prognostic factor in different malignancies. The aim of the current paper is to study the correlation between the preoperative values of platelet to lymphocyte ratio (PLR) and the postoperative outcomes in ovarian cancer patients. Method: we conducted a retrospective study on 57 patients submitted to cytoreductive surgery between 2014-2020. We determined the optimal cut off value of PLR for predicting survival outcomes by using the Receiver Operating Characteristic curve a value of 350 being obtained. The patients were further classified in two groups according to the PLR value. Results: there were 37 patients with PLR 350 and respectively 20 patients with PLR 350. Patients in the second group were significantly older and presented significantly higher rates of perioperative complications, a significantly higher level of circulating platelets, of CA125 and respectively a significantly lower level of circulating lymphocytes and of preoperative hemoglobin level. Meanwhile, patients in the second group reported a significantly poorer disease free and overall survival. Conclusions: ovarian cancer patients with higher preoperative levels of PLR trend to have a poorer early and long-term postoperative outcome. Therefore, in such cases more aggressive systemic therapies might be needed.

A Surprising Case of Triple Acute Hepatitis Infection.

Viral hepatitis continues to be the leading cause of morbidity and mortality worldwide, but the burden has significantly diminished thanks to the large-scale use of vaccines and antivirals. However, there are still challenges regarding viral hepatitis management, especially when more than one pathogenic agent is involved. We present the case of a 45-year-old woman who had a simultaneous infection involving three hepatitis viruses: HAV, HBV, and HEV.

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.

Neuroendocrine Parathyroid Tumors: Quality of Life in Patients with Primary Hyperparathyroidism.

Tumors of the parathyroid glands, when associated with PTH (parathyroid hormone) excess, display a large area of complications; in addition to the classical clinical picture of primary hyperparathyroidism (PHP), a complex panel of other symptoms/signs can be identified, including memory and cognitive impairment, chronic asthenia/fatigue, reduced muscle functionality, depressive mood, non-specific bone pain, and loss of sleep quality. The perception of quality of life (QoL) can be supplementarily enhanced by their progressive onset, which makes many patients not be fully aware of them. Their improvement was reported very early after parathyroidectomy (PTx), yet the level of statistical evidence does not qualify these non-classical elements as standalone indications for PTx. Our objective is introducing an up-to-date on QoL scores with regards to the patients diagnosed with PHP, particularly taking into consideration PHP management from baseline to post-operatory outcome, including in cases with multiple endocrine neoplasia. This is a narrative review of literature. We revised full-length papers published in English through PubMed research conducted between January 2018 and May 2023 by using the key words "quality of life" and "primary hyperparathyroidism". We particularly looked at data on self-reported QoL (through questionnaires). We excluded from the search the studies focused on non-PTH related hypercalcemia, secondary, and/or renal/tertiary hyperparathyroidism, and vitamin D supplementation. Overall, we identified 76 papers and selected for the final analysis 16 original studies on QoL and PHP (a total of 1327 subjects diagnosed with syndromic and non-syndromic PHP). The studies with the largest number of individuals were of 92, 104, 110, 134, 159, as well as 191. A few cohorts (n = 5) were of small size (between 20 and 40 patients in each of them). Concerning the study design, except for 2 papers, all the mentioned studies provided longitudinal information, particularly the timeframe from baseline (before PTx) and after surgery. The post-operatory follow-up was of 3-6 months, but mostly between 1 and 3 years (maximum a decade of surveillance). The age of the patients varies between medians of 56, 62, 64, and 68 years. Most frequent questionnaires were SF-36, PHPQoL, and PAS. Despite not being unanimously similar, an overall reduced score of QoL in patients with PHP versus controls was registered, as well as general improvement following PTx. Variations of QoL results might have a multifactorial background from different comorbidities, studied populations, technical aspects of collecting the data, etc. QoL scores in PHP represents a complex heterogeneous picture, from their correlation with clinical features and lab assays (e.g., the level of serum calcium), the associated comorbidities (such as multiple endocrine neoplasia syndromes), up to the assessment of the QoL improvement after parathyroidectomy (PTx). While current studies do not unanimously agree on each QoL domain, the assessment of QoL might represent a supplementary argument to consider when deciding for PTx, especially in asymptomatic cases and in patients who do not fit into well-known categories of surgery candidates, according to current guidelines, thus assessing QoL in PHP is part of a current research gap. QoL evaluation in PHP remains an open issue, towards which awareness should be cultivated by both endocrinologists and surgeons. The introduction of a routine evaluation of the QoL scores in patients, as well as the selection of the most appropriate questionnaire(s), represents an open chapter thus awareness in mandatory.

Management of Adrenal Cortical Adenomas: Assessment of Bone Status in Patients with (Non-Functioning) Adrenal Incidentalomas.

Our aim is to analyse the bone profile in adults with (non-functioning) adrenal incidentalomas (AIs), specifically addressing the impact of autonomous cortisol secretion (ACS). This narrative review, based on a PubMed search from inception to February 2023 (case reports, non-ACS, and other secondary causes of osteoporosis were excluded), included 40 original studies, a total of 3046 patients with female prevalence (female:male ratio of 1921:1125), aged between 20.5 and 95.5 years old. This three decade-based analysis showed that 37 studies provided dual-energy X-ray absorptiometry (DXA) information; another five studies reports results on bone micro-architecture, including trabecular bone score (TBS), spinal deformity index, and high-resolution peripheral quantitative computed tomography; 20 cohorts included data on bone turnover markers (BTMs), while four longitudinal studies followed subjects between 1 and 10.5 years old (surgical versus non-adrenalectomy arms). Post-dexamethasone suppression test (DST) cortisol was inversely associated with bone mineral density (BMD). TBS predicted incidental vertebral fractures (VFx) regardless of BMD, being associated with post-DST cortisol independently of age and BMD. Low BTMs were identified in ACS, but not all studies agreed. An increased prevalence of ACS-related osteoporosis was confirmed in most studies (highest prevalence of 87.5%), as well as of VFx, including in pre-menopause (42.5%), post-menopause (78.6%), and male patients (72.7%) depending on the study, with a 10-fold increased incidental VFx risk up to a 12-fold increased risk after a 2-year follow-up. No specific medication against osteoporosis is indicated in ACS, but adrenalectomy (according to four studies) should be part of the long-term strategy. This bone profile case sample-based study (to our knowledge, one of the largest of its kind) showed that AIs, including the subgroup designated as having ACS, embraces a large panel of osseous complications. The level of evidence remains far from generous; there are still no homogenous results defining ACS and identifying skeletal involvement, which might be a consequence of different investigation clusters underling adrenal and bone assessments over time. However, bone status evaluations and associated therapy decisions remain an essential element of the management of adults with AIs-ACS.

Addison's Disease: Diagnosis and Management Strategies.

We aim to overview Addison's disease (AD) with regard to current diagnosis and management. This is a narrative review of full-length articles published in English between January 2022 and December 2022 (including online ahead of print versions) in PubMed-indexed journals. We included original studies in living humans regardless of the level of statistical significance starting from the key search terms "Addison's disease" or "primary adrenal insufficiency" in title or abstract. We excluded articles with secondary adrenal insufficiency. Briefly, 199 and 355 papers, respectively were identified; we manually checked each of them, excluded the duplicates, and then selected 129 based on their clinical relevance in order to address our 1-year analysis. We organized the data in different subsections covering all published aspects on the subject of AD. To our knowledge, this is the largest AD retrospective from 2022 on published data. A massive role of genetic diagnosis especially in pediatric cases is highlighted; the importance of both pediatric and adult awareness remains since unusual presentations continue to be described. COVID-19 infection is a strong player amid this third year of pandemic although we still not do have large cohorts in this particular matter as seen, for instance, in thyroid anomalies. In our opinion, the most important topic for research is immune checkpoint inhibitors, which cause a large panel of endocrine side effects, AD being one of them.