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.

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.

Inquiry of the Metabolic Traits in Relationship with Daily Magnesium Intake: Focus on Type 2 Diabetic Population.

Magnesium (Mg), an essential nutrient with a wide area of physiological roles, stands as a cofactor in over 600 enzymatic reactions involved in the synthesis of proteins and nucleic acids, DNA repair, neuromuscular functions, neuronal transmission, cardiac rhythm regulation, and the modulation of metabolic pathways, as well as acting as a natural blocker for the calcium channels. Our objective was to highlight the most recent clinical data with respect to daily Mg intake (DMI) and metabolic traits, particularly type 2 diabetes mellitus (DM). This was a PubMed-based review of the English-language medical papers across different key terms of search; the time frame was from January 2019 until April 2024. We included (clinically relevant) original studies and excluded cases reports, series, reviews, editorials, opinion, experimental studies, and non-human data as well as studies that did not specifically assessed DMI and only provided assays of serum Mg, studies on patients diagnosed with type 1 or secondary DM. A total of 30 studies were included and we organized the key findings into several sections as follows. Studies investigating DMI in relationship with the adherence to local recommendations in diabetic subjects (n = 2, one transversal and another retrospective cohort; N = 2823) found that most of them had lower DMI. Deficient DMI was correlated with the risk of developing/having DM across five studies (n = 5, one prospective and four of cross-sectional design; N = 47,166). An inverse correlation between DMI and DM prevalence was identified, but these data are presented amid a rather heterogeneous spectrum. Four novel studies (N = 7279) analysed the relationship between DMI and DM control according to various methods (HbA1c, fasting and postprandial glycaemia, and insulin); the association may be linear in diabetic subjects only at certain levels of DMI; additionally, the multifactorial influence on HBA1c should take into consideration this dietary determinant, as well, but there are no homogenous results. Three studies concerning DMI and diabetic complications (one cross-sectional, one prospective, and another case-control study) in terms of retinopathy (n = 1, N = 3794) and nephropathy (n = 2, N = 4805) suggested a lower DMI was associated with a higher risk of such complications. Additionally, two other studies (one prospective and one retrospective cohort) focused on mortality (N = 6744), which, taking only certain mortality indicators into consideration, might be decreased in the subgroups with a higher DMI. Seven studies (N = 30,610) analysed the perspective of DMI in the general population with the endpoint of different features amid glucose profile, particularly, insulin resistance. Concerning HOMA-IR, there were three confirmatory studies and one non-confirmatory, while fasting plasma glucose was highlighted as inversely correlated with a DMI (n = 1). The highest level of evidence regarding Mg supplementation effects on glucose metabolism stands on seven randomised controlled trials (N = 350). However, the sample size was reduced (from 14 to 86 individuals per study, either diabetic or pre-diabetic) and outcomes were rather discordant. These clinical aspects are essential from a multidisciplinary perspective and further trials are mandatory to address the current areas of discordant results.

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 [...].

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.

Horner's Syndrome and Lymphocele Following Thyroid Surgery.

Horner's syndrome (HS), caused by lesions of the 3-neuron oculosympathetic nerve pathway (ONP), includes the triad: blepharoptosis, miosis and anhidrosis (ipsilateral with ONP damage). Thyroid−related HS represents an unusual entity underling thyroid nodules/goiter/cancer−HS (T-HS), and post-thyroidectomy HS (Tx-HS). We aim to overview Tx-HS. This is a narrative review. We revised PubMed published, full-length, English papers from inception to November 2022. Additionally, we introduced data on post-thyroidectomy lymphocele/chylous leakage (Tx-L), and introduced a new pediatric case with both Tx-HS and Tx-L. Tx-HS: the level of statistical evidence varies from isolated case reports, studies analyzing the large panel of post-thyroidectomy complications reporting HS among the rarest side effects (as opposite to hypocalcemia), or different series of patients with HS due to various disorders, including T-HS/Tx-HS. Tx-HS is related to benign or malignant thyroid conditions, regardless the type of surgery. A pre-operatory rate of T-HS of 0.14%; a post-operatory rate of Tx-HS between 0.03% and 5% (mostly, 0.2%) are identified; a possible higher risk on endoscopic rather than open procedure is described. Incomplete HS forms, and pediatric onset are identified, too; the earliest identification is after 2 h since intervention. A progressive remission is expected in most cases within the first 2−6 months to one year. The management is mostly conservative; some used glucocorticoids and neurotrophic agents. One major pitfall is an additional contributor factor like a local compression due to post-operatory collections (hematoma, cysts, fistula, Tx-L) and their correction improves the outcome. The prognostic probably depends on the severity of cervical sympathetic chain (CSC) lesions: indirect, mild injury due to local compressive masses, intra-operatory damage of CSC like ischemia and stretching of CSC by the retractor associate HS recovery, while CSC section is irreversible. Other iatrogenic contributors to HS are: intra-operatory manipulation of parathyroid glands, thyroid microwave/radiofrequency ablation, and high-intensity focused ultrasound, and percutaneous ethanol injection into thyroid nodules. Tx-L, rarely reported (mostly <0.5%, except for a ratio of 8.3% in one study), correlates with extended surgery, especially lateral/central neck dissection, and the presence of congenitally­aberrant lymphatic duct; it is, also, described after endoscopic procedures and chest-breast approach; it starts within days after surgery. Typically low-fat diet (even fasting and parental nutrition) and tube drainage are useful (as part of conservative management); some used octreotide, local sealing solutions like hypertonic glucose, Viscum album extract, n-Butyl-2-cyanoacrylate. Re-intervention is required in severe cases due to the risk of lymphorrhoea and chylothorax. Early identification of Tx-HS and Tx-L improves the outcome. Some iatrogenic complications are inevitable and a multifactorial model of prediction is still required, also taking into consideration standardized operatory procedures, skillful intra-operatory manipulation, and close post-operatory follow-up of the patients, especially during modern era when thyroid surgery registered a massive progress allowing an early discharge of the patients.

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.

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.

Challenges of Pituitary Apoplexy in Pregnancy.

Our purpose is to provide new insights concerning the challenges of pituitary apoplexy in pregnancy (PAP) and the postpartum period (PAPP). This is a narrative review of the English literature using a PubMed search. The inclusion criteria were clinically relevant original studies (January 2012-December 2022). Overall, we included 35 original studies: 7 observational studies (selected cases on PA) and 28 case reports, including 4 case series (N = 49; PAP/PAPP = 43/6). The characteristics of PAP patients (N = 43) are as follows: maternal age between 21 and 41 (mean of 27.76) years; 21/43 subjects with a presentation during the third trimester (only one case during first trimester); average weak of gestation of 26.38; most females were prim gravidae; 19 (out of 30 patients with available data on delivery) underwent a cesarean section. Headache remains the main clinical feature and is potentially associated with a heterogeneous panel (including visual anomalies, nausea, vomiting, cranial nerve palsies, diabetes insipidus, photophobia, and neck stiffness). Pre-pregnancy medication included dopamine agonists (15/43) and terguride (1/43) in addition to subsequent insulin therapy for gestational diabetes (N = 2) and type 1 diabetes mellitus (N = 1). Overall, 29/43 females received the conservative approach, and 22/43 women had trans-sphenoidal surgery (TSS) (and 10/22 had the initial approach). Furthermore, 18/43 patients had a pituitary adenoma undiagnosed before pregnancy. Most PA-associated tumors were prolactinomas (N = 26/43), with the majority of them (N = 16/26) being larger than 1 cm. A maternal-fetal deadly outcome is reported in a single case. The characteristics of PAPP patients (N = 6) are as follows: mean age at diagnosis of 33 years; 3/6 subjects had PA during their second pregnancy; the timing of PA varied between 5 min and 12 days after delivery; headache was the main clinical element; 5/6 had no underlying pituitary adenoma; 5/6 patients were managed conservatively and 1/6 underwent TSS; pituitary function recovered (N = 3) or led to persistent hypopituitarism (N = 3). In conclusion, PAP represents a rare, life-threatening condition. Headache is the most frequent presentation, and its prompt distinction from other conditions associated with headache, such as preeclampsia and meningitis, is essential. The index of suspicion should be high, especially in patients with additional risk factors such as pre-gestation treatment with dopamine agonists, diabetes mellitus, anticoagulation therapy, or large pituitary tumors. The management is conservative in most cases, and it mainly includes corticosteroid substitution and dopamine agonists. The most frequent surgical indication is neuro-ophthalmological deterioration, although the actual risk of pituitary surgery during pregnancy remains unknown. PAPP is exceptionally reported. To our knowledge, this sample-case series study is the largest of its kind that is meant to increase the awareness to the benefit of the maternal-fetal outcomes from multidisciplinary insights.

Pituitary Apoplexy in Patients with Pituitary Neuroendocrine Tumors (PitNET).

Various complications of pituitary neuroendocrine tumors (PitNET) are reported, and an intratumor hemorrhage or infarct underlying pituitary apoplexy (PA) represents an uncommon, yet potentially life-threatening, feature, and thus early recognition and prompt intervention are important. Our purpose is to overview PA from clinical presentation to management and outcome. This is a narrative review of the English-language, PubMed-based original articles from 2012 to 2022 concerning PA, with the exception of pregnancy- and COVID-19-associated PA, and non-spontaneous PA (prior specific therapy for PitNET). We identified 194 original papers including 1452 patients with PA (926 males, 525 females, and one transgender male; a male-to-female ratio of 1.76; mean age at PA diagnostic of 50.52 years, the youngest being 9, the oldest being 85). Clinical presentation included severe headache in the majority of cases (but some exceptions are registered, as well); neuro-ophthalmic panel with nausea and vomiting, meningism, and cerebral ischemia; respectively, decreased visual acuity to complete blindness in two cases; visual field defects: hemianopia, cranial nerve palsies manifesting as diplopia in the majority, followed by ptosis and ophthalmoplegia (most frequent cranial nerve affected was the oculomotor nerve, and, rarely, abducens and trochlear); proptosis (N = 2 cases). Risk factors are high blood pressure followed by diabetes mellitus as the main elements. Qualitative analysis also pointed out infections, trauma, hematologic conditions (thrombocytopenia, polycythemia), Takotsubo cardiomyopathy, and T3 thyrotoxicosis. Iatrogenic elements may be classified into three main categories: medication, diagnostic tests and techniques, and surgical procedures. The first group is dominated by anticoagulant and antiplatelet drugs; additionally, at a low level of statistical evidence, we mention androgen deprivation therapy for prostate cancer, chemotherapy, thyroxine therapy, oral contraceptives, and phosphodiesterase 5 inhibitors. The second category includes a dexamethasone suppression test, clomiphene use, combined endocrine stimulation tests, and a regadenoson myocardial perfusion scan. The third category involves major surgery, laparoscopic surgery, coronary artery bypass surgery, mitral valvuloplasty, endonasal surgery, and lumbar fusion surgery in a prone position. PA in PitNETs still represents a challenging condition requiring a multidisciplinary team from first presentation to short- and long-term management. Controversies involve the specific panel of risk factors and adequate protocols with concern to neurosurgical decisions and their timing versus conservative approach. The present decade-based analysis, to our knowledge the largest so far on published cases, confirms a lack of unanimous approach and criteria of intervention, a large panel of circumstantial events, and potential triggers with different levels of statistical significance, in addition to a heterogeneous clinical picture (if any, as seen in subacute PA) and a spectrum of evolution that varies from spontaneous remission and control of PitNET-associated hormonal excess to exitus. Awareness is mandatory. A total of 25 cohorts have been published so far with more than 10 PA cases/studies, whereas the largest cohorts enrolled around 100 patients. Further studies are necessary.

Clinical Evidence Regarding the Dynamic of Baker Cyst Dimensions after Intermittent Vacuum Therapy as Rehabilitation Treatment in Patients with Knee Osteoarthritis.

The Baker cyst (BC), also known as the popliteal cyst or parameniscal cyst, is a fluid-filled sac that normally develops in the back of the knee, between the semimembranosus and medial head of the gastrocnemius. We aimed to evaluate the effectiveness of physiotherapy (10 days of treatment) that associates intermittent vacuum therapy (IVT) on the lower limbs in the treatment of the BC, respectively, in its size reduction. Sixty-five patients with knee osteoarthritis using Kellgren-Lawrence criteria and the presence of BC (ultrasonography evaluation), were divided into the Control and Vacuum groups. We collected the following features: sex, age, level of education, occupation, environment, body mass index, Knee Injury and Osteoarthritis Outcome Score, Western Ontario, and McMaster Universities Osteoarthritis Index, the Functional Independence Measurement, the Fall Risk Score, and the Visual Analog Scale were recorded at baseline and after 10 days. Both groups are similar in terms of demographic features. Regarding the clinical functional parameters, the results elicit a statistically significant change in all parameters between admission and discharge, including the echo volume at BC. Physical medicine and rehabilitation increase the autonomy of patients with BC. Clinical-functional improvement begins in the first 10 days of complex rehabilitation treatment; it is statistically significant and is not different between the two groups, which brings an additional argument for the effectiveness of conservative therapy in the treatment of BC. Although IVT has not demonstrated its superiority over classical balneo-physical therapy, additional research, and long-term monitoring are needed to provide additional arguments regarding this aspect.

Effectiveness of Intermittent Hypoxia-Hyperoxia Therapy in Different Pathologies with Possible Metabolic Implications.

Intermittent oxygen therapy (IHT), initially used in the hypoxic administration variant, has been shown to be effective in various pathologies studied, from cardiopulmonary to vascular and metabolic pathologies and more. IHT used to prevent and treat various diseases has thus gained more and more attention as the years have passed. The mechanisms underlying the beneficial effects have been investigated at multiple biological levels, from systemic physiological reactions to genomic regulation. In the last decade, a new method of intermittent oxygen therapy has been developed that combines hypoxic and hyperoxic periods. They can be applied both at rest and during physical exercise, hence the specific indications in sports medicine. It has been hypothesized that replacing normoxia with moderate hyperoxia may increase the adaptive response to the intermittent hypoxic stimulus by upregulating reactive oxygen species and hypoxia-inducible genes. This systematic literature review is based on the "Preferred Reporting Items for Systematic Reviews and Meta-Analysis"-"PRISMA"-methodology, the widely internationally accepted method.

Antibacterial and Phytochemical Screening of Artemisia Species.

Taking into account the increasing number of antibiotic-resistant bacteria, actual research focused on plant extracts is vital. The aim of our study was to investigate leaf and stem ethanolic extracts of Artemisia absinthium L. and Artemisia annua L. in order to explore their antioxidant and antibacterial activities. Total phenolic content (TPC) was evaluated spectrophotometrically. Antioxidant activity was evaluated by DPPH and ABTS. The antibacterial activity of wormwood extracts was assessed by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) in Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, and Salmonella enteritidis cultures, and by zone of inhibition in Klebsiella carbapenem-resistant enterobacteriaceae (CRE) and Escherichia coli extended-spectrum ß-lactamases cultures (ESBL). The Artemisia annua L. leaf extract (AnL) exhibited the highest TPC (518.09 mg/mL) and the highest expression of sinapic acid (285.69 ± 0.002 µg/mL). Nevertheless, the highest antioxidant capacity (1360.51 ± 0.04 µM Trolox/g DW by ABTS and 735.77 ± 0.02 µM Trolox/g DW by DPPH) was found in Artemisia absinthium L. leaf from the second year of vegetation (AbL2). AnL extract exhibited the lowest MIC and MBC for all tested bacteria and the maximal zone of inhibition for Klebsiella CRE and Escherichia coli ESBL. Our study revealed that AbL2 exhibited the best antioxidant potential, while AnL extract had the strongest antibacterial effect.

Thyroid Carcinoma Showing Thymus-like Differentiation (CASTLE): A Case Report.

BACKGROUND AND OBJECTIVES: Carcinoma showing thymus-like differentiation (CASTLE) is a low-grade thyroid carcinoma, with an indolent clinical course and usually a favorable prognosis. The clinical and imagistic features are not specific for CASTLE but similar to other malignant lesions of the thyroid. Definite diagnosis is based on an immunohistochemical examination, as this carcinoma shows positive CD5 immunoreactivity when compared to other aggressive thyroid carcinomas. CASE PRESENTATION: The main focus of this study is to outline a rare case of CASTLE compressing the trachea in a 50-year-old female patient who was initially diagnosed with undifferentiated thyroid carcinoma, for which she underwent unsuccessful surgery, as well as postoperative radiotherapy and chemotherapy. After receiving a second medical opinion, the patient underwent a challenging radical resection consisting in total thyroidectomy and central neck dissection, with no local recurrence after 6 months and 2 years of follow-up and negative metastatic follow-up. The correct diagnosis has been established based on pathological and immunohistochemical examinations. CONCLUSIONS: In summary, the diagnosis of CASTLE is difficult and requires an experienced histological analysis and CD5 immunoreactivity. Lack of metastasis, complete removal of the tumor, and a low degree of tumor infiltration into nearby structures are all associated with better long-term survival.

Safety of Electrotherapy Treatment in Patients with Knee Osteoarthritis and Cardiac Diseases.

OBJECTIVE: To assess the safety of electrotherapy applied in the knee area in patients with known atrial arrhythmias or ischemic heart disease, as it is not known whether this treatment induces or aggravates arrhythmias during or immediately after therapy. MATERIAL AND METHODS: The analytical and transversal study involved 46 patients with degenerative knee osteoarthritis (OA), with or without cardiac diseases, from the Clinical Rehabilitation Hospital inpatient center, Cluj-Napoca, Romania. All patients underwent a 10-day physical therapy program for knee OA (electrotherapy, massage and kinesiotherapy). Heart rate and the total number of ventricular and supraventricular extrasystoles were evaluated before and after treatment, by 24 h Holter ECG monitoring. RESULTS: There was no significant increase in heart rate or in the number of ventricular or supraventricular extrasystoles before or after electrotherapy treatment, regardless of the positive or negative history of arrhythmia or ischemic heart disease (all p > 0.05). Mean values during day 1 were: 35.15 (95% CI [9.60−60.75]) for ventricular ones extrasystoles and 91.7 (95% CI [51.69−131.7]) for supraventricular ones, which during day 2 were 38.09 (95% CI [3.68−72.50]), 110.48 (95% CI [48.59−172.36]), respectively. CONCLUSION: One of the most important things to consider when dealing with an OA patient is that they are most likely older than 65 years, which increases the chance of having a cardiac disease. This raises the need for viable interventions regarding the management of this disease in patients that probably have multiple comorbidities, and where pharmacological and surgical management are not possible, limited or have multiple side effects. Electrotherapy used for treating knee OA did not cause a significant increase in heart rate or number of ventricular and supraventricular extrasystoles in this category of patients.

The Influence of Diet and Physical Activity on Oxidative Stress in Romanian Females with Osteoarthritis.

Osteoarthritis (OA) is the most prevalent chronic joint disease, increases in prevalence with age, and affects most individuals over 65. The present study aimed to assess the oxidative status in relation to diet and physical activity in patients with OA. We used a cross-sectional study applied to 98 females with OA. Blood samples were collected to determine oxidative stress markers: malonyl dialdehyde (MDA), reduced glutathione (GSH), oxidized glutathione (GSSG), and GSH/GSSG. Diet was estimated with a standardized food frequency questionnaire. We used the International Physical Activity Questionnaire (IPAQ) to assess the females' physical activity. Multiple regression analyses were executed to determine the association between the oxidative markers and the intake of vegetables and fruit. The study showed that most patients were overweight or obese (88.8%). The level of physical activity was above the recommended level for adults, mainly based on household activities. The intake of vegetables and fruit was low. The MDA marker was inversely, statistically significantly associated with the consumption of vegetables (p < 0.05). Public health policies must address modifiable risk factors to reduce energy intake and obesity and increase the intake of vegetables and fruit. Higher consumption of vegetables and fruit may provide natural antioxidants that can balance oxidative compounds.

The role of combined techniques of scintigraphy and SPECT/CT in the diagnosis of primary hyperparathyroidism: A case report.

RATIONALE: Primary hyperparathyroidism, usually as a result of a hyperfunctioning parathyroid gland, represents more than 90% cases of patients evaluated for hypercalcemia. Combined techniques of preoperative scintigraphy and SPECT/CT serve as a successful minimally-invasive parathyroidectomy. This recent imaging method provides four-dimensional functional images with advanced contrast resolution which greatly facilitates preoperative localization of parathyroid adenomas. PATIENT CONCERNS: We presented the case of a male Caucasian patient, aged 67 years, who was investigated for hypercalcemia. Increased levels of parathormone, cervical ultrasonography without pathological changes, and negative planar parathyroid scintigraphy have led to the performance of a parathyroid scintigraphy combined with SPECT/CT. DIAGNOSES: The diagnosis of right inferior parathyroid adenoma was confirmed by the 99mTc-MIBI-SPECT/CT that revealed on early phase increased radiotracer uptake in the area of projection of the lower third of the right thyroid lobe. The SPECT/CT scan localized this area behind the lower pole of the right thyroid lobe, in the right side of the trachea, with CT correspondent of hypodense lesion, with a maximum diameter of 20 mm. INTERVENTIONS: During hospitalization, the decision to undergo surgical intervention was taken. The patient underwent surgical intervention, and minimally-invasive right inferior parathyroidectomy was performed. OUTCOMES: The histopathological examination confirmed the diagnosis and the patient's recovery was complete, with the normalization of parathormone, calcium levels, and metabolic parameters. LESSONS: Modern combined techniques of scintigraphy and SPECT/CT proved to be of excellent clinical utility in the preoperative diagnosis of primary hyperparathyroidism, localizing a parathyroid tumor undetected by planar scintigraphy alone.

Hashimoto's thyroiditis associated with thyroid adenoma with Hürthle cells - case report.

Chronic thyroiditis may present a focal lesion, often-palpable abnormality, simulating nodular disease. The number and morphology of the Hürthle cells (HC) vary in the thyroid aspirate. Distinguishing between neoplastic and non-neoplastic HC lesions is difficult when using the fine-needle aspiration cytology (FNAC). We present the case of a 46-year-old female with a large right nodular goiter and hypothyroidism and high titer of anti-thyroid peroxidase antibody (TPO). The thyroid ultrasound showed a large well-defined nodule (more than 6.8 cm) with hypoechogenicity and microcalcification. FNAC (Mayo Clinic technique) smears revealed HC arranged in flat sheets in 75% in the sample with moderate nuclear pleomorphism, abundant granular cytoplasm showing eosinophilia and well-defined cytoplasmic borders, a lightly eccentric enlarged nuclei; the colloid was reduced and lymphocytes were also described. The final histological examination revealed that oncocyte cell proliferation is limited to the thyroid parenchyma and does not exceed the capsule and has no vascular invasion. The presence of lymphocytic infiltration and a performing FNAC (like Mayo Clinic technique) is absolutely necessary in a focal autoimmune thyroiditis in order to exclude HC carcinoma.

An immunocompetent young patient with tuberculosis of the penis: a challenging case.

Tuberculous chancre is an extremely rare form of cutaneous tuberculosis. The genital area is a possible site of presentation. We present a case of a young male with a persistent balanopreputial ulceration resembling a luetic chancre with negative serology for syphilis. The diagnosis was based on the specific pathologic features and the positive intradermal reaction to tuberculin. A successful treatment was achieved by combining antituberculosis treatment and surgical approach with circumcision. After six months of antituberculosis treatment, the patient developed paradoxical inguinal lymph node enlargement, which, after surgical excision and biopsy, was not followed by a relapse of the disease and needed no further therapy. Tuberculosis should be considered a potential diagnosis in the case of a persistent genital ulcer.