COVID-19 mortality prediction in Hungarian ICU settings implementing random forest algorithm.

The emergence of newer SARS-CoV-2 variants of concern (VOCs) profoundly changed the ICU demography; this shift in the virus's genotype and its correlation to lethality in the ICUs is still not fully investigated. We aimed to survey ICU patients' clinical and laboratory parameters in correlation with SARS-CoV-2 variant genotypes to lethality. 503 COVID-19 ICU patients were included in our study beginning in January 2021 through November 2022 in Hungary. Furthermore, we implemented random forest (RF) as a potential predictor regarding SARS-CoV-2 lethality among 649 ICU patients in two ICU centers. Survival analysis and comparison of hypertension (HT), diabetes mellitus (DM), and vaccination effects were conducted. Logistic regression identified DM as a significant mortality risk factor (OR: 1.55, 95% CI 1.06-2.29, p = 0.025), while HT showed marginal significance. Additionally, vaccination demonstrated protection against mortality (p = 0.028). RF detected lethality with 81.42% accuracy (95% CI 73.01-88.11%, [AUC]: 91.6%), key predictors being PaO2/FiO2 ratio, lymphocyte count, and chest Computed Tomography Severity Score (CTSS). Although a smaller number of patients require ICU treatment among Omicron cases, the likelihood of survival has not proportionately increased for those who are admitted to the ICU. In conclusion, our RF model supports more effective clinical decision-making among ICU COVID-19 patients.

[Macronodular adrenal hyperplasia causing Cushing's syndrome due to ARMC5 gene mutation.] / Cushing-szindrómát okozó macronodularis mellékvese-hyperplasia ARMC5-génmutáció következtében.

Our 69-year-old female patient was investigated for a 20 kg weight gain over 2 years. The patient's medical history included hypertension, hyperuricemia, bilateral cataract surgery and musculosceletal complaints. Diabetes mellitus was not found. Physical examination revealed abdominal obesity, proximal myopathy and atrophic, vulnerable skin. The "overnight", low-dose and long, low-dose dexamethasone suppression tests indicated autonomous cortisol overproduction (plasma cortisol level: 172.6 and 153.2 nmol/L, cut-off: 50 nmol/L). The suppressed ACTH (<1.11 pmol/L, normal value: 1.12-10.75 pmol/L) suggested ACTH-independent hypercortisolism. Abdominal CT described macronodular enlargement of both adrenals. The size of the largest nodule was 23 × 20 mm in the right, and 24 × 30 mm on the left side (with -33 ± 37 HU density values on native scans). The 131I-cholesterol adrenal scintigraphy and SPECT/CT showed almost equally intensive radiopharmacon uptake on both sides. Based on the clinical results, bilateral macronodular adrenal hyperplasia associated with ACTH-independent hypercortisolism was diagnosed. Genomic DNA was obtained from the peripheral blood leukocytes. Targeted sequencing of 25 genes potentially involved in adrenal tumorigenesis revealed a new disease-causing armadillo repeat-containing 5 (ARMC5) gene mutation (c.1724del28 bp, g.31,476,067-31,476,094). Because of the autosomal dominant inheritance of this genetic alteration, the patient's two children underwent genetic screening for the ARMC5 mutation. The same mutation was found in the younger child of our patient. To the best of our knowledge, this is the first published Hungarian case of ARMC5 mutation with bilateral macronodular adrenal hyperplasia and ACTH-independent Cushing's syndrome. The genetic alteration is present in two generations of the family of the index patient. Orv Hetil. 2023; 164(32): 1271-1277.

Retrospective analysis of low-risk differentiated thyroid tumours: is lobectomy the adequate approach? / Kis rizikójú differenciált pajzsmirigydaganatok retrospektív analízise: lobectomia a megfelelo választás?

Introduction: According to the recommendation of the American Thyroid Association 2015 guideline, the treatment of 1-4 cm (T1b-2) low-risk differentiated thyroid cancer (DTC) is lobectomy without radioiodine therapy. Objective: Retrospective analysis of multifocality in surgical and histological data of T1-2 patients living on moderate iodine intake. Methods: Analysis of the pathological characterisation of 81 low-risk (T1-2) DTC patients who underwent total thy-roidectomy. Patients were treated at Flor Ferenc Hospital, Kistarcsa, Hungary, between 2013 and 2019. Results: 64 patients had T1, while 17 patients had T2 status. 65/81 (80.2%) patients had papillary, and 16/81 (19.8%) had follicular subtype. Lymph node metastasis was detected up to 18.4% in papillary and 18% in follicular patients. Multifocal tumours were detected in 25% (16/64) of T1 patients, of these 10.9% (7/64) was unilateral and 14.1% (9/64) was bilateral. Multifocal tumours were detected in 11.7% (2/17) of T2 patients; both were bilateral. Distribution of T1-2 bilateral multifocal patients (11/81; 13.5%) was n = 3 T1a-, n = 6 T1b and n = 2 T2 stadium, from these 10 patients received radioiodine treatment. The sizes of contralateral tumours were <5 mm in 9 patients, and >5 mm in 2 patients. Conclusions: Due to the frequent (13.5%) bilateral multifocality in T1-2 DTC patients, we suggest total thyroidec-tomy instead of lobectomy. After lobectomy, the follow-up of the contralateral tumours is almost impossible by ul-trasonography due to the small tumour size (on average 2.8 mm) and frequently detected benign nodules; therefore the multifocality might remain undetected, which can distort the plan for adjuvant treatment.

Ultrasound-Based Indications for Thyroid Fine-Needle Aspiration: Outcome of a TIRADS-Based Approach versus Operators' Expertise.

BACKGROUND: Thyroid nodule image reporting and data systems (TIRADS) provide the indications for fine-needle aspiration (FNA) based on a combination of nodule sonographic features and size. We compared the TIRADS-based recommendations for FNA with those based on the personal expertise of qualified US investigators in the diagnosis of thyroid malignancy. METHODS: Seven highly experienced ultrasound (US) investigators from 4 countries evaluated, online, the US video recordings of 123 histologically verified thyroid nodules. Technical resources provided the operators with a diagnostic approach close to the real-world practice. Altogether, 4,305 TIRADS scores were computed. The combined diagnostic potential of TIRADS (TIRSYS) and the personal recommendations of the investigators (PERS) were compared against 3 possible goals: to recognize all malignant lesions (allCA), nonpapillary plus non-pT1 papillary cancers (nPnT1PCA), or stage II-IV cancers (st2-4CA). RESULTS: For allCA and nPnT1PCA, TIRSYS had lower sensitivity than PERS (69.8 vs. 87.2 and 83.5 vs. 92.6%, respectively, p <0.01), while in st2-4CA the sensitivities were the same (99.1 vs. 98.6% and TIRSYS vs. PERS, respectively). TIRSYS had a higher specificity than PERS in all 3 types of cancers (p < 0.001). PERS recommended FNA in a similar proportion of lesions smaller or larger than 1 cm (76.9 vs. 82.7%; ns). CONCLUSIONS: Recommendations for FNA based on the investigators' US expertise demonstrated a better sensitivity for thyroid cancer in the 2 best prognostic groups, while TIRADS methodology showed superior specificity over the full prognostic range of cancers. Thus, personal experience provided more accurate diagnoses of malignancy, missing a lower number of small thyroid cancers, but the TIRADS approach resulted in a similar accuracy for the diagnosis of potentially aggressive lesions while sparing a relevant number of FNAs. Until it is not clearly stated what the goal of the US evaluation is, that is to diagnose all or only clinically relevant thyroid cancers, it cannot be determined whether one diagnostic approach is superior to the other for recommending FNA.

Thyroid-stimulating hormone receptor (TSHR) fusion proteins in Graves' disease.

Graves' disease is an autoimmune disorder, which is characterized by stimulatory antibodies targeting the human thyrotropin receptor (TSHR), resulting in hyperthyroidism and multiple organ damage. We systematically investigated monomeric and dimeric fusion proteins of the A subunit of TSHR for efficacy to bind to the monoclonal patient antibody M22, to interact with Graves' patient serum samples, and to impact on anti-TSHR antibody titers, hyperthyroidism, tachycardia and other in vivo read-outs in a long-term mouse model of Graves' disease induced by immunization with a recombinant adenovirus encoding TSHR A. Binding assays and functional measurements of TSHR-dependent cAMP formation showed binding of monomeric TSHR-His and dimeric TSHR-Fc to the anti-TSHR antibody M22 at low-effective concentrations (EC50 of 5.7 nmol/L and 8.6 nmol/L) and inhibition of the effects of this antibody at high efficiencies (IC50 values of 16-20 nmol/L). Both proteins also block the effects of polyclonal anti-TSHR antibodies occurring in Graves' patient sera with somewhat lower average efficiencies (mean IC50 values of 29 nmol/L and 68 nmol/L). However, in vivo characterization of epicutaneous patch administrations of TSHR-Fc at doses of 0.3 and 0.6 mg/kg body weight in a murine Graves' disease model did not result in any improvement of disease parameters. In conclusion, high affinity binding of TSHR-Fc to pathological anti-TSHR antibodies was not matched by efficacy to improve Graves' disease parameter in a long-term mouse model.

[Etanercept-induced subacute thyroiditis. Case report and literature review]. / Etanercept okozta szubakut pajzsmirigygyulladás.

65 years old male patient received 4 mg/day methylprednisolone baseline therapy and 50 mg/week etanercept treatment for 5 years due to rheumatoid arthritis. The patient experienced pain in neck, and developed weakness, fever and dysphagia. He had normal blood count but accelerated erythrocyte sedimentation rate (88 mm/hour), elevated CRP (49.3 mg/l) and hyperthyroidism (TSH 0.006 mIU/l, fT4 27.22 pmol/l, fT3 5.61 pmol/l). The autoimmune origin could be excluded because of normal values of antibodies against thyreoidea peroxidase and TSH receptor. The ultrasound investigation showed focal hypoechogenic structure and low vascularisation. Based on the laboratory and ultrasound results as well as clinical signs etanercept related subacute thyroiditis was supposed. As part of the treatment we interrupted the etanercept treatment and gave 16 mg methylprednisolone for 5 days, then 8 mg for 7 days, after that the patient received the daily 4 mg of methylprednisolone as baseline therapy. After rapid improvement the symptoms got worse again so we repeated the administration of methylprednisolone treatment with a higher dose (16 mg/day for 5 days then 8 mg/day for two months). Thyroid functions and the inflammatory markers got normalized. We conclude the necessity of monitoring the thyroid function during etanercept treatment thus avoiding this rare but serious side effect. Orv Hetil. 2017; 158(39): 1550-1554.

[Consensus on the change of criteria for cure of acromegaly during the last decade]. / Konszenzus a kritériumok változásáról az acromegalia gyógyulásának megítélésében - nemzetközi ajánlás, 2010.

The Acromegaly Consensus Group redefined the consensus criteria for cure of acromegaly. 74 neurosurgeons and experienced endocrinologists summarized the latest results on diagnosis and treatment of acromegaly. In this consensus statement the reliable growth hormone and insulin-like growth factor-1 assays were established. Definition of disease control was discussed based on the available publications and evidence. This short communication summarizes the clinical aspects of consensus criteria for diagnosis and cure of acromegaly based on the original article.

[Growth hormone receptor antagonist in the treatment of acromegaly]. / Növekedésihormonreceptor-antagonista alkalmazásának lehetoségei acromegaliában.

Exploration of construction, function and interaction of human growth hormone and growth hormone receptor in details resulted in the innovation of the new growth hormone receptor antagonist, pegvisomant. Pegvisomant with different mechanism of action extended the tools of medical management of acromegaly. Importance of the novel treatment modality is high. In one hand the necessity of the strict control of growth hormone/insulin-like growth factor-I axis has been proven regarding the mortality of the disease. On the other hand, despite the use of all current modes of treatment (surgery, radiotherapy, dopamine agonists, somatostatin analogs), a significant cohort of patients with acromegaly remains inadequately controlled. Pegvisomant has been registered in 2004. Since 2006, it has been used in Hungary for the treatment of acromegaly in patients who have had an inadequate response to surgery and/or radiation therapy and/or other medical therapies, or for whom these therapies are not appropriate. Clinical use of pegvisomant in the treatment of acromegaly is effective, well tolerated, and safe, based on international Acrostudy database. In order to improve the efficacy of therapy clinical trials started with pegvisomant and somatostatin analog combination treatment. Evidence of several further effects of the growth hormone/insulin-like growth factor-I axis suggests other potential uses of growth hormone receptor antagonists.

[Familial isolated pituitary adenoma syndrome]. / Familiáris izolált hypophysisadenoma.

Familial pituitary adenomas occur in multiple endocrine neoplasia type 1, Carney complex, as well as in familial isolated pituitary adenoma syndrome. Familial isolated pituitary adenoma syndrome is an autosomal dominant disease with incomplete penetrance. Pituitary adenomas occur in familial setting but without any other specific tumors. In 20-40% of families with this syndrome, mutations have been identified in the aryl hydrocarbon receptor interacting protein gene while in the rest of the families the causative gene or genes have not been identified. Families carrying aryl hydrocarbon receptor interacting protein gene mutations have a distinct phenotype with younger age at diagnosis and a predominance of somatotroph and lactotroph adenomas. Germline mutations of the aryl hydrocarbon receptor interacting protein gene can be occasionally identified in usually young-onset seemingly sporadic cases. Genetic and clinical testing of relatives of patients with aryl hydrocarbon receptor interacting protein gene mutations can lead to earlier diagnosis and treatment at an earlier stage of the pituitary tumor.

[Successfully operated cases of mediastinal and retroperitoneal bronchial cysts]. / Mediastinalis és retroperitonealis bronchogen cysták sikeresen operált esetei és tanulságaik.

CASE REPORT: Two young men were operated in our department for bronchiogen cysts with unusual locations. In the first case a mediastinal cyst caused severe swallowing problems, while in the second a retroperitoneal cyst resembled to an adrenal adenoma. It was only the postoperative histology, which clarified the exact diagnosis of the removed cysts. DISCUSSION: Only a few percent of mediastinal tumours are bronchial cysts that develop due to developmental disorders. Symptomatic ones are more easily detectable. Bronchial cysts localized in the abdominal cavity or retroperitoneum are especially rare. In most of the cases the final diagnosis is made only after excision with histological examination of the cyst.

Low level of cyclin D1 protein expression in thyroid microcarcinomas from an autopsy series.

In a recent epidemiological screening study in an autopsy series, we found a high prevalence of microcarcinomas (MCs) (21/443 = 4.74%). We found no iodine intake-, gender-, or age-dependent differences in the prevalence of MCs. The results suggest a different and benign behavior of MCs compared to clinical cancer. The role of cyclin D1 overexpression in the pathogenesis of thyroid tumors is not known clearly; however, overexpression of this protein was reported in well-differentiated papillary cancers and in incidentally found metastasizing MCs. To date, cyclin D1 expression has not been investigated in autopsy-derived thyroid MCs. Eight MCs were available for immunostaining and comparison with 15 clinically detected papillary thyroid cancers. Fourteen out of 15 clinical carcinomas expressed cyclin D1 (93.3%), while in the MCs this ratio was 1 out of 8 (12.5%) (p = 0.0001). The only cyclin D1-positive MC was multifocal (both lobes of the gland were affected). We concluded that the benign behavior of most autopsy-derived MCs may be associated with the lack of cyclin D1 overexpression.