Publications by authors named "Mihai Cristian Dumitrascu"

30 Publications

  • Page 1 of 1

Adrenocortical carcinoma: Pediatric aspects (Review).

Exp Ther Med 2022 Apr 16;23(4):287. Epub 2022 Feb 16.

Department of Endocrinology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

Adrenocortical carcinoma (adrenal cortex-derived cancer), an orphan malignancy, is a very aggressive disease that affects both adults and children with an annual incidence of 1-2 adult and 0.2-0.38 pediatric cases/million (in the pediatric population it represents 0.2% of all cancers), with a female predominance. A total of 80-90% of cases have hormonal imbalances such as Cushing syndrome, virilization, and puberty anomalies. Precocious puberty (PP) of iso- or hetero-sexual pattern is independent of gonadotropin-releasing hormone (GnRH) (high testosterone/estrogens and low FSH/LH) but post-operative activation of GnRH may be expected (central PP). PP is accompanied by accelerated growth while Cushing syndrome by reduced growth velocity. Pure androgen-secreting tumors have been exceptionally described. A total of 50-80% of children have different genetic/epigenetic anomalies involving tumor protein p53 (most often, almost half of the cases; with a population cluster in Southern Brazilian children), insulin-like growth factor, multiple endocrine neoplasia type 1 (MEN1), PRKAR1A, dysfunctional alternative lengthening of telomeres. Hereditary syndromes associated to adrenocortical carcinoma include Li-Fraumeni, Beckwith-Wiedemann, MEN1, and Lynch. Recently, mutations in epidermal growth factor receptor have been reported in teenagers, suggesting the future use of tyrosine kinase inhibitors. Adrenalectomy is the first line therapy offering the best prognosis if complete tumor removal is achieved; genetic testing is recommended before surgery. Adjuvant therapies are less standardized in children (mitotane is a key adjuvant drug in addition with different regimes of chemotherapy such as etoposide, Adriamycin and cisplatin). A Ki-67 value of at least 15% is a predictor of poor outcome. Weiss score also serves as a prognostic factor, as well as the tumor size at diagnosis. The prognosis of adrenocortical carcinoma is poor with an overall 5-year survival rate of 55%; a Weiss score of at least 6 is associated with a 2-year survival rate of 35%. At present, pediatric adrenocortical carcinoma still represents a severe condition that requires prompt intervention and a multidisciplinary team. Further development of molecular markers is required for an improved understanding of the disease thus improving the protocols of approach and the prognostic.
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http://dx.doi.org/10.3892/etm.2022.11216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8908472PMC
April 2022

New approaches in predicting and diagnosing preeclampsia: Congo Red Dot Paper Test (Review).

Exp Ther Med 2022 Apr 8;23(4):270. Epub 2022 Feb 8.

Deparment of Obstetrics and Gynecology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

Preeclampsia (PE), a complication of pregnancy that is characterized by hypertension and proteinuria, remains a leading cause of morbidity and mortality during pregnancy, influencing 2.5-7% of singleton and 7-21% of twin pregnancies. At present, diagnosis is based on traditional but unreliable and nonspecific clinical markers, and treatment of PE is suboptimal, with minimal effect on maternal and fetal mortality and morbidity. With the hope of developing an affordable and simple procedure for PE prediction for developing countries, a previous study examined the use of Congo red staining of misfolded and damaged proteins in the urine of women with PE. This feature has diagnostic and prognostic potential since it precedes the onset of clinical manifestations and correlates with disease severity. The test is inexpensive, popular within the medical staff, easy to use, and identifies women with PE in only 3 min. Obstetrical providers benefit from the Congo Red Dot Paper Test analysis, since a negative result promotes lesser waiting times in triage, prevents unneeded admissions, and diminishes the health costs associated per case.
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http://dx.doi.org/10.3892/etm.2022.11196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892616PMC
April 2022

HELLP Syndrome-Holistic Insight into Pathophysiology.

Medicina (Kaunas) 2022 Feb 21;58(2). Epub 2022 Feb 21.

"Iuliu Hatieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.

HELLP syndrome, also known as the syndrome of hemolysis, elevated liver enzymes, and low platelets, represents a severe pregnancy complication typically associated with hypertension. It is associated with increased risks of adverse complications for both mother and fetus. HELLP occurs in 0.2-0.8% of pregnancies, and, in 70-80% of cases, it coexists with preeclampsia (PE). Both of these conditions show a familial tendency. A woman with a history of HELLP pregnancy is at high risk for developing this entity in subsequent pregnancies. We cannot nominate a single worldwide genetic cause for the increased risk of HELLP. Combinations of multiple gene variants, each with a moderate risk, with concurrent maternal and environmental factors are thought to be the etiological mechanisms. This review highlights the significant role of understanding the underlying pathophysiological mechanism of HELLP syndrome. A better knowledge of the disease's course supports early detection, an accurate diagnosis, and proper management of this life-threatening condition.
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http://dx.doi.org/10.3390/medicina58020326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875732PMC
February 2022

Abdominal Compartment Syndrome-When Is Surgical Decompression Needed?

Diagnostics (Basel) 2021 Dec 7;11(12). Epub 2021 Dec 7.

Carol Davila University of Medicine and Pharmacy, General Surgery Department, University Emergency Hospital of Bucharest, 050098 Bucharest, Romania.

Compartment syndrome occurs when increased pressure inside a closed anatomical space compromises tissue perfusion. The sudden increase in pressure inside these spaces requires rapid decompression by means of surgical intervention. In the case of abdominal compartment syndrome (ACS), surgical decompression consists of a laparostomy. The aim of this review is to identify the landmarks and indications for the appropriate moment to perform decompression laparotomy in patients with ACS based on available published data. A targeted literature review was conducted on indications for decompression laparotomy in ACS. The search was focused on three conditions characterized by a high ACS prevalence, namely acute pancreatitis, ruptured abdominal aortic aneurysm and severe burns. There is still a debate around the clinical characteristics which require surgical intervention in ACS. According to the limited data published from observational studies, laparotomy is usually performed when intra-abdominal pressure reaches values ranging from 25 to 36 mmHg on average in the case of acute pancreatitis. In cases of a ruptured abdominal aortic aneurysm, there is a higher urgency to perform decompression laparotomy for ACS due to the possibility of continuous hemorrhage. The most conflicting recommendations on whether surgical treatment should be delayed in favor of other non-surgical interventions come from studies involving patients with severe burns. The results of the review must be interpreted in the context of the limited available robust data from observational studies and clinical trials.
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http://dx.doi.org/10.3390/diagnostics11122294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700353PMC
December 2021

Melanoma in patients with Li-Fraumeni syndrome (Review).

Exp Ther Med 2022 Jan 24;23(1):75. Epub 2021 Nov 24.

Department of Endocrinology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

Li-Fraumeni syndrome (LFS) is a cancer-prone, autosomal dominant syndrome caused by underlying germline gene mutations of , a tumor-suppressor gene encoding the p53 protein with a major role in apoptosis, DNA repair and cell cycle regulation. Cumulative cancer incidence for LFS patients by the age of 70 years is 80-100%, mostly involving adrenocortical carcinoma, brain tumors, bone and soft tissue sarcomas, leukemia and female breast cancer from the age of 20 years. Dominant negative variant is correlated with an increased tumorigenesis risk in LFS. Sporadic mutations are related to almost half of global cancers since p53 in addition to p73 protein represent essential players in anticancer cellular protection. Epidemiological aspects concerning skin cancers, especially malignant melanoma (MM), in LFS are less clear. A low level of statistical evidence demonstrates LFS cases with pediatric MM, multiple MM, spitzoid MM, atypical presentations, mucosal and uveal MM. Retrospective cohorts indicate a higher cumulative risk than the general population by the age of 70 years for MM and basal cell carcinoma. Non-syndromic and syndromic mutations are a major pathway of metastasis, including MM. In LHS, an important level of awareness involves skin cancers despite not being a part of the typical malignancy-containing picture. Additional data are crucially needed. However, at least one dermatologic control is a step in the multidisciplinary panel of surveillance of these patients; but in cases with benign and pre-malign pigmentations, serial dermatoscopy and full body photography are recommended for early melanoma detection in order to improve the prognosis and to reduce the overall malignancy burden.
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http://dx.doi.org/10.3892/etm.2021.10998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8652386PMC
January 2022

Aggressive prolactinoma (Review).

Exp Ther Med 2022 Jan 24;23(1):74. Epub 2021 Nov 24.

Department of Endocrinology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

Aggressive prolactinoma (APRL) is a subgroup of aggressive pituitary tumors (accounting for 10% of all hypophyseal neoplasia) which are defined by: invasion based on radiological and/or histological features, a higher proliferation profile when compared to typical adenomas and rapidly developing resistance to standard medication/protocols in addition to an increased risk of early recurrence. This is a narrative review focusing on APRL in terms of both presentation and management. Upon admission, the suggestive features may include increased serum prolactin with a large tumor diameter (mainly >4 cm), male sex, early age at diagnosis (<20 years), and genetic predisposition [multiple endocrine neoplasia type 1 (, aryl hydrocarbon receptor interacting protein , succinate dehydrogenase ( gene mutations]. Potential prognostic factors are indicated by assessment of E-cadherin, matrix metalloproteinase (MMP)-9, and vascular endothelial growth factor (VEGF) status. Furthermore, during management, APRL may be associated with dopamine agonist (DA) resistance (described in 10-20% of all prolactinomas), post-hypophysectomy relapse, mitotic count >2, Ki-67 proliferation index ≥3%, the need for radiotherapy, lack of response in terms of controlling prolactin levels and tumor growth despite multimodal therapy. However, none of these as an isolated element serves as a surrogate of APRL diagnosis. A fourth-line therapy is necessary with temozolomide, an oral alkylating chemotherapeutic agent, that may induce tumor reduction and serum prolactin reduction in 75% of cases but only 8% have a normalization of prolactin levels. Controversies surrounding the duration of therapy still exist; also regarding the fifth-line therapy, post-temozolomide intervention. Recent data suggest alternatives such as somatostatin analogues (pasireotide), checkpoint inhibitors (ipilimumab, nivolumab), tyrosine kinase inhibitors (TKIs) (lapatinib), and mTOR inhibitors (everolimus). APRL represents a complex condition that is still challenging, and multimodal therapy is essential.
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http://dx.doi.org/10.3892/etm.2021.10997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8652381PMC
January 2022

Peutz-Jeghers syndrome: Skin manifestations and endocrine anomalies (Review).

Exp Ther Med 2021 Dec 29;22(6):1387. Epub 2021 Sep 29.

Department of Endocrinology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

Peutz-Jeghers syndrome (PJS), a rare autosomal dominant serine/threonine kinase 11 ()/ liver kinase B1 () gene-related genodermatosis, is characterized by oral hyperpigmentation (OHP); multiple gastro-intestinal mucosal benign hamartomatous polyps causing local bleeding, occlusion, intussusception, post-resection small bowel syndrome, associated increased risk of small intestinal cancer (incidence during the third decade); and 76% cumulative higher risk than the global population of developing non-gastrointestinal tumors (female predominance) including ovarian/testicular neoplasia, pancreatic and gynecologic (breast, uterus, ovarian) cancers. Suggestive PJS-associated OHP requires STK11 genetic testing. Abdominal pain in an OHP patient may be related to PJS-associated polyps. Other features include focal depigmentation followed by hyperpigmentation, and xeroderma pigmentosum-like lesions. The severity of the dermatological findings is correlated with gastrointestinal polyps. The gene is linked to reserve of primordial follicles, polycystic ovary syndrome, female fertility, and spermatogenesis. PJS is associated with 2 types of ovarian sex-cord stroma tumors (SCSTs): annular tubules (SCTATs) and pure Sertoli cell tumors. SCSTs accounts for 8% of ovarian cancer and SCTATs represents 2% of SCST, which may be associated with the overproduction of progesterone. PJS-SCTAT vs. non-PJS-SCTAT reveals bilateral/multifocal, small tumors with a benign behavior vs. a unique ovarian, large tumor with increased malignant/metastasis risk. Male precocious puberty is due to large cell calcifying Sertoli cell tumors (LCCSCTs). Notably, 30-40% of LCCSCTs are caused by PJS or Carney complex. PJS-LCCSCT is not aggressive, but it may be bilateral/multifocal, with the ultrasound hallmark being micro-calcifications. Testicular, intra-tubular large cell hyalinizing Sertoli cell tumor is the second testicle neoplasia in PJS. The skin and mucosal lesions are useful markers of PJS, assisting with the early identification of hamartomatouspolyps and initiation of serial surveillance of ovarian, or testicular neoplasia.
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http://dx.doi.org/10.3892/etm.2021.10823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506952PMC
December 2021

Adrenal ganglioneuroma: Prognostic factors (Review).

Exp Ther Med 2021 Nov 22;22(5):1338. Epub 2021 Sep 22.

Department of Endocrinology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

Ganglioneuroma, a rare neural crest-derived tumor, exhibits a benign profile in contrast to other neuroblastic tumors (neuroblastoma/ganglioneuroblastoma). Ganglioneuromas can be found anywhere autonomic ganglia are located, mostly abdominal/pelvic sites followed by the adrenal glands (one-third of cases), mediastinum/thorax and cervical area. Affecting especially children more than 10 years of age, Ganglioneuroma is either asymptomatic or may cause local compressive effects; rarely inducing nonspecific abdominal complains or arterial hypertension related to oversecretion of epinephrine/norepinephrine/dopamine. Despite a good prognosis, adrenalectomy is necessary in order to rule out a malignancy. Open procedure represents the standard therapeutic option; alternatively, centers with large laparoscopic pediatric experience and good stratification protocols have reported successful procedures. High uptake of I-MIBG is associated with a more severe outcome in cases with increased mitotic index. In neuroblastic tumors, neuron-specific enolase >33 ng/ml, age at diagnosis <49 months, and blood vessel invasion indicate a poor prognosis. Concurrent extra-adrenal/adrenal ganglioneuroma is associated with a more severe prognosis; post-surgical complications are more frequent in non-adrenal vs. adrenal ganglioneuroma. Exceptionally, immune-mediated paraneoplastic neurologic syndromes have been reported: anti-N-methyl-D-aspartate receptor encephalitis and opsoclonus-myoclonus-ataxia syndrome. ROHHAD syndrome is the underlying cause in 40-56% of cases of neuroendocrine tumors including ganglioneuroma; 70% of tumors are diagnosed within the first 24 months after hypothalamic obesity onset, associated with a severe prognosis due to hypoventilation, sleep apnea, and dysautonomia. Recently, the PKB/AKT/mTOR/S6 pathway was identified as a tumorigenic pathway in pediatric ganglioneuroma, not in neuroblastoma; mTOR inhibitors are a potential option for pre-operatory tumor shrinkage. Pediatric adrenal ganglioneuroma has a good prognosis if adequately treated; its recognition requires adrenalectomy. Further development of specific biomarkers is needed. In the present article, we aimed to introduce a review of the literature involving adrenal ganglioneuroma based on a practical, multidisciplinary perspective of prognostic factors.
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http://dx.doi.org/10.3892/etm.2021.10773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495554PMC
November 2021

Dermatological and endocrine elements in Carney complex (Review).

Exp Ther Med 2021 Nov 17;22(5):1313. Epub 2021 Sep 17.

Department of Endocrinology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

Carney complex (CΝC) is a very rare, autosomal dominant, hereditary syndrome. Seventy percent of individuals with CNC have germline inactivating or deleting mutations of the gene [currently known as protein kinase cAMP-dependent type I regulatory subunit α (), located at the 17q22-24 chromosome level], with 30% of cases presenting with phosphodiesterase gene mutations. A member of the lentiginosis family, dermatological features include: skin pigmentation, cutaneous/mucosal myxomas, usually diagnosed by the age of 20 years (neonatal presentation is exceptional, requiring a meticulous differential diagnosis). Melanocyte-derived tumors such as epithelioid blue nevi (with different levels of pigmentation) and pigmented epithelioid melanocytoma (previously 'animal-type melanoma') are often found. Myxomas, mesenchymal tumors with mostly a benign pattern, may be recurrent. Primary cutaneous melanotic schwannoma are atypical, while non-skin sites are frequent. Corticotropinomas or somatotropinomas are part of the hereditary syndrome-related pituitary adenomas (representing 5% of all). Primary pigmented nodular adrenocortical disease involves bilateral cortical hyperplasia causing Cushing syndrome (CS) at an earlier age than non-CNC cases; osteoporotic fractures seem more prevalent compare to CS of other etiologies. Typically benign, a few cases of adrenocortical carcinoma have been identified. A total of 5% of familial non-medullary thyroid cancer is syndromic, also including CNC. CNC-related thyroid frame includes: hyperthyroidism, follicular hyperplasia/adenomas, follicular carcinoma (usually aggressive, bilateral or multifocal). Large cell calcifying Sertoli cell tumors of the testes have malignant behavior in adults; in children these may induce precocious puberty. Two particular mammary tumors are found: myxoid fibroadenomas and breast myxomatosis. Cutaneous/subcutaneous lesions, pigmented or not, or any focal swelling of non-identified cause needs careful examination, since dermatological elements are among the earliest and most discernable by which to detect lesions in CNC, a systemic condition with multi-level endocrine involvement.
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http://dx.doi.org/10.3892/etm.2021.10748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461626PMC
November 2021

Benefits of α-lipoic acid in high-risk pregnancies (Review).

Exp Ther Med 2021 Nov 31;22(5):1232. Epub 2021 Aug 31.

Department of Obstetrics and Gynecology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

α-Lipoic acid (ALA) is a natural molecule that is inconsistently synthesized by the human body and must be provided from exogenous sources, such as food and dietary supplements. Once absorbed, the oxidized form of ALA is transformed into its reduced form, dihydrolipoic acid (DHLA). ALA/DHLA exert direct and indirect antioxidant, anti-inflammatory and fine immunomodulatory effects. ALA/DHLA reduce the levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and IL-17), while increasing the secretion of anti-inflammatory cytokines (IL-10). They also inhibit cyclooxygenase 2, thereby decreasing the secretion of prostaglandin E2 and nitrogen oxide, and reducing the risk of miscarriage in the first trimester of pregnancy. In patients at risk of abortion, administration of ALA from the first trimester has shown efficacy by accelerating subchorionic hematoma resorption, with a significant decrease in the accompanying abdominal pain. ALA has been proven to be efficient in maintaining the length of the cervix and keeping it closed following one episode of premature labor. Preeclampsia is a dysfunction caused by abnormal placentation and an excessive maternal inflammatory response, leading to extreme hypoxia in the placental bed and exaggerated oxidative stress, with release of oxygen free radicals. Oxidative stress plays a key role in the development of preeclampsia and intrauterine growth restriction. The hypothesis of antioxidant supplementation may play an essential part in disease prevention and fetal neuroprotection.
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http://dx.doi.org/10.3892/etm.2021.10666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438679PMC
November 2021

infection characteristics in a general surgery clinic.

Exp Ther Med 2021 Oct 3;22(4):1112. Epub 2021 Aug 3.

Faculty of Medicine, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

(CD) is an anaerobic, gram-positive bacterium that can produce a spectrum of gastrointestinal diseases ranging from pseudomembranous colitis to diarrhea to toxic megacolon. The infection is even more difficult to manage as CD produces high-end spores, suggesting that this may be the cause of the dangerous recurrent disease as well as dissemination among healthy members in the community. Spores can be hosted in the digestive tract of both symptomatic and asymptomatic patients. The most relevant risk factor in the development of infection (CDI) seems to be the overuse of antimicrobials. Comorbidities are another risk factor that may predispose towards more serious CDI. Treatment options vary from oral antibiotics to extensive surgical interventions. The present study aimed to analyze the prevalence, severity, and management of CDIs in a general surgery department in an effort to determine the correlative elements between the infection and surgical pathology.
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http://dx.doi.org/10.3892/etm.2021.10546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383759PMC
October 2021

Hyperthyroidism management during pregnancy and lactation (Review).

Exp Ther Med 2021 Sep 7;22(3):960. Epub 2021 Jul 7.

Department of Endocrinology 'Titu Maiorescu' University, University of Medicine and Pharmacy, 031593 Bucharest, Romania.

Thyroid dysfunction is a significant public health issue, affecting 5-10 more women compared to men. The estimated incidence is up to 12% and only for women the treatment rises up to 4.3 billion dollars annually. Thyroid pathology can have a major impact on female fertility and it can only be detected when preconception tests are performed. Untreated or poorly treated hyperthyroidism in a mother can affect the fetal development and pregnancy outcome. Between 0.1 and 0.4% of the pregnancies are affected by clinical hyperthyroidism. Thyroid dysfunction is associated with higher rates of pregnancy loss. Hyperthyroidism can complicate fetal health problems intrauterinely and in the neonatal period. The TSH receptor is stimulated by TSH and HCG which has a similar structure. This can lead to gestational thyrotoxicosis. Hyperthyroidism can be treated with propylthiouracil or methimazole and in selected cases, surgical treatment or radioactive iodine can be chosen. In pregnancy, the most used treatment is represented by propylthiouracil which can be used from the first trimester. The aim of this review is to assess the current data regarding the impact of thyroid dysfunction on pregnancy and to synthesize the treatment options during pregnancy and lactation.
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http://dx.doi.org/10.3892/etm.2021.10392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290437PMC
September 2021

Vitiligo and chronic autoimmune thyroiditis.

J Med Life 2021 Mar-Apr;14(2):127-130

Department of Endocrinology, Clinical County Hospital, Cluj-Napoca, Romania.

Vitiligo, the discoloration of the skin, has different autoimmune mechanisms reflected by many biomarkers as shown by skin histology, staining for CD4 and CD8 T lymphocytes, chemokine ligand 9 or circulating cytokines such as interleukin (IL)-1 beta, interferon (IFN)-gamma, transforming growth factor (TGF)-beta, antibodies, markers of oxidative stress, chemokines, and others. In this narrative review, we aim to overview vitiligo in relationship with chronic autoimmune thyroiditis. Regarding vitiligo, more than 50 different genetic loci have been associated with this disease, and the heritability is high. There is a 20% risk of an environmental connection which may also act as a trigger; moreover, the association with human leukocyte antigen (HLA) expression is well recognized. The specific lesions display CD8+ tissue-resident memory T cells as continuous key activators of melanocytes. The association with chronic thyroiditis is based on common autoimmune background and excessive reactive oxygen species that destroy melanocytes and thyrocytes (oxidative stress hypothesis) with thyroxine and melanin as target molecules, thus sharing a common origin: tyrosine. Moreover, common epigenetic anomalies or mutations of the Forkhead transcription factor D3 (FOXD3) have been described. Since vitiligo affects up to 1-2% of the population worldwide and 34% of patients have positive thyroid antibodies, apart from common autoimmunity background and oxidative stress toxicity, the association is clinically relevant for different practitioners.
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http://dx.doi.org/10.25122/jml-2019-0134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169145PMC
June 2021

Anorexia nervosa: COVID-19 pandemic period (Review).

Exp Ther Med 2021 Aug 26;22(2):804. Epub 2021 May 26.

Department of Endocrinology, Clinical County Hospital, 400000 Cluj-Napoca, Romania.

Anorexia nervosa is an eating disorder characterized by restrictive eating and an intense fear of gaining weight. It is a disease with an increasing incidence during the last few decades, and represents a complex psychiatric condition which includes secondary amenorrhea, nutritional and metabolic damage, and impaired endocrine panel up to bone loss as well as cardiac, gastrointestinal and hematological complications. This is a narrative review which includes an update on this eating disorder from the perspective of an endocrine panel of anomalies, especially of the skeleton, considering the pressure of the recent global COVID-19 pandemic changes. Practically affecting every organ, anorexia nervosa needs to be taken into consideration during the pandemic period because of the higher risk of relapse due to new living conditions, social distancing, self-isolation, changes in food access, more intense use of social media platforms, disruption of daily habits, and more difficult access to healthcare practitioners. The lack of physical activity in addition to vitamin D deficiency related to low sun exposure or to the use of facial masks may also be connected to further bone damage related to this disease.
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http://dx.doi.org/10.3892/etm.2021.10236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170656PMC
August 2021

COVID-19-related thyroid conditions (Review).

Exp Ther Med 2021 Jul 13;22(1):756. Epub 2021 May 13.

Departament of Obstetrics and Gynecology, 'Carol Davila' University of Medicine and Pharmacy, 050474, Bucharest, Romania.

In patients who were not previously diagnosed with any thyroid conditions, the scenario of COVID-19-related anomalies of the hypothalamus-pituitary-thyroid axes may include either: A process of central thyroid stimulating hormone (TSH) disturbances via virus-related hypophysitis; an atypical type of subacute thyroiditis which is connected to the virus spread or to excessive cytokine production including a destructive process with irreversible damage of the gland or low T3 (triiodothyronine) syndrome (so called non-thyroid illness syndrome) which is not specifically related to the COVID-19 infection, but which is associated with a very severe illness status. Our objective here was to briefly review thyroid changes due to the COVID-19 infection. Ongoing assessment of the effects of the COVID-19 pandemic will reveal more information on coronavirus-induced thyroid conditions. Routine thyroid assays performed in patients with severe infection/at acute phase of COVID-19 are encouraged in order to detect thyrotoxicosis. After recovery, thyroid function should be assessed to identify potential hypothyroidism. There remain unanswered questions related to the prognostic value of interleukin-6 in infected patients, especially in cases with cytokine storm, and the necessity of thyroid hormone replacement in subjects with hypophysitis-related central hypothyroidism.
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http://dx.doi.org/10.3892/etm.2021.10188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135141PMC
July 2021

Chemical hemorrhagic cystitis: Diagnostic and therapeutic pitfalls (Review).

Exp Ther Med 2021 Jun 14;21(6):624. Epub 2021 Apr 14.

Department of Urology, 'George Emil Palade' University of Medicine, Pharmacy, Science and Technology of Targu-Mures, 540139 Targu-Mures, Romania.

Chemical cystitis (CC) is an inflammation of the bladder caused by various chemical agents ingested intentionally or accidentally. It is linked to chemotherapeutic agents such as cyclophosphamide, therapeutic agents for diverse diseases, and anesthetic agents consumed abusively for recreational effects such as ketamine, or can be linked to environmental and surrounding factors such as soaps, gels, spermicides, and dyes. CC is a pathology with an increasing incidence that is inadequately treated due to its infectious cystitis-like symptoms. The hemorrhagic form can have a rampant evolution. Treatment options of CC and its complications are under continuous research with no accepted standardized sequence. In many situations, the treatments are difficult to obtain, administer, and follow-up. In addition, the lack of experience of the physician may pose other obstacles in delivering treatment to the patient. In conclusion, CC is a disease with an increasing incidence, challenging to diagnose, which is frequently mistreated, and has multiple treatment modalities that still require standardization in administration and sequencing.
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http://dx.doi.org/10.3892/etm.2021.10056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082586PMC
June 2021

Cutaneous Mastocytosis in Childhood-Update from the Literature.

J Clin Med 2021 Apr 2;10(7). Epub 2021 Apr 2.

"Carol Davila" University of Medicine and Pharmacy, 030167 Bucharest, Romania.

Mastocytosis (M) represents a systemic pathology characterized by increased accumulation and clonal proliferation of mast cells in the skin and/or different organs. Broadly, M is classified into two categories: Cutaneous mastocytosis (CM) and systemic mastocytosis (SM). In children, CM is the most frequent form. Unfortunately, pathogenesis is still unclear. It is thought that genetic factors are involved, but further studies are necessary. As for features of CM, the lesions differ in clinical forms. The most important fact is evaluating a pediatric patient with CM. It must comprise laboratory exams (with baseline dosing of total serum tryptase), a skin biopsy (with a pathological exam and, if the diagnosis is unclear, immunohistochemical tests), and a complete clinical evaluation. It is also defining to distinguish between CM and other diseases with cutaneous involvement. As for the management of CM in children, the first intervention implies eliminating trigger factors. The available cures are oral H1 and/or H2 antihistamines, oral cromolyn sodium, oral methoxypsoralen therapy with long-wave psoralen plus ultraviolet A radiation, potent dermatocorticoid, and calcineurin inhibitors. In children, the prognosis of CM is excellent, especially if the disease's onset is in the first or second years of life.
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http://dx.doi.org/10.3390/jcm10071474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038134PMC
April 2021

Teratogenic effect of isotretinoin in both fertile females and males (Review).

Exp Ther Med 2021 May 23;21(5):534. Epub 2021 Mar 23.

Department of Dermatology, 'Elias' Emergency University Hospital, 011461 Bucharest, Romania.

Isotretinoin is an oral derivate of vitamin A that has been used since 1982 for the treatment of multiple dermatologic conditions such as severe acne, rosacea, scarring alopecia, ichthyosis or non-melanoma skin cancer prophylaxis. The recommended dose is 0.5-1 mg/kg/day for a period of 4-6 months in sebaceous gland pathologies. There are many adverse effects caused by isotretinoin but by far the most important is the teratogenicity induced by this drug which is estimated to have a 20-35% risk to infants that are exposed to isotretinoin and includes numerous congenital defects such as craniofacial defects, cardiovascular and neurological malformations or thymic disorders. Isotretinoin induces apoptosis and cell cycle arrest in human sebocytes, emphasizing these as processes associated with its teratogenic effect. The aim of this review is to analyze the latest literature data regarding the teratogenic effect of isotretinoin for both fertile females and males and its biological effects underlying the occurrence of congenital malformations under the influence of isotretinoin.
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http://dx.doi.org/10.3892/etm.2021.9966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014951PMC
May 2021

Delivery and breastfeeding in pregnant patients with COVID-19 (Review).

Exp Ther Med 2021 Mar 25;21(3):278. Epub 2021 Jan 25.

Department of Obstetrics and Gynecology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

COVID-19 infection has rapidly become a global issue that has brought essential changes in the daily life of patients and doctors. The pandemic outbreak represents a significant burden on humankind; yet, life still moves on with approximately 350,000 babies being born every day around the world (UNICEF-2018). Some of these mothers will have other conditions, including COVID-19 infection. As healthcare providers, it is our responsibility to treat all women equal no matter what illness they have and to offer them the best possible conditions to give birth vaginally or via Caesarian section, in a safe environment for them and their babies. The main concern is represented by the limitation of the disease transmission to pregnant patients and newborns while managing maternal or fetal emergencies. We have limited information regarding COVID-19 infection, and the data are constantly changing and evolving. New information is brought to light almost on a weekly basis. This review aims to synthesize the recommendations and current experience regarding the birth method for infected women, labor management, Caesarian section management, and breastfeeding indications in these cases.
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http://dx.doi.org/10.3892/etm.2021.9709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851677PMC
March 2021

Glucocorticoids and Trabecular Bone Score.

J Med Life 2020 Oct-Dec;13(4):449-453

Department of Endocrinology, Clinical County Hospital, Cluj-Napoca, Romania.

TBS (Trabecular Bone Score) is the latest tool for clinicians to evaluate bone micro-architecture based on a pixel greyscale, which is provided by lumbar dual-energy X-ray absorptiometry (DXA). Its use enhances fracture prediction in addition to DXA-BMD (Bone Mineral Density). This is independent of fracture risk assessment (FRAX) and DXA results. We present a narrative review regarding the connection between TBS and Glucocorticoids (GC), either as a drug used for different conditions or as a tumor-produced endogenous excess. TBS is a better discriminator for GC-induced vertebral fractures compared to DXA-BMD. This aspect is similarly available for patients with osteoporosis diagnosed by DXA. TBS is inversely correlated with the cumulative dose of GC (systemic or inhaled), with disease duration, and positively correlated with respiratory function in patients with asthma. Low TBS values are found in females with a T-score at the hip within the osteoporosis range, with diabetes mellitus, or who use GC. Lumbar TBS is a screening tool in menopausal women with type 2 diabetes mellitus. TBS is an independent parameter that provides information regarding skeleton deterioration in diabetic patients receiving GC therapy in a manner complementary to DXA-BMD. TBS might become an essential step regarding the adrenalectomy decision in patients with adrenal incidentaloma in whom autonomous cortisol secretion might damage bone micro-architecture. TBS currently represents a standard tool of fracture risk evaluation in patients receiving GC therapy or with endogenous Cushing's syndrome, a tool easy to be applied by different practitioners since GCs are largely used.
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http://dx.doi.org/10.25122/jml-2019-0131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803323PMC
January 2021

Non-sexual HPV transmission and role of vaccination for a better future (Review).

Exp Ther Med 2020 Dec 13;20(6):186. Epub 2020 Oct 13.

'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

Human papilloma viruses (HPVs) belong to the Papillomaviridae family and are epitheliotropic infecting squamous epithelia (skin and mucosae). HPV is estimated to be the cause of 99% of cervical cancers (there is no evidence of significant genetic predisposition for cervical cancer), 90% of anal cancer, 65% vaginal cancers, 50% vulvar cancers, and 45-90% oropharyngeal cancers. The route of HPV transmission is primarily through skin-to-skin or skin-to-mucosa contact. Sexual transmission is the most documented, but there have been studies suggesting non-sexual courses. The horizontal transfer of HPV includes fomites, fingers, and mouth, skin contact (other than sexual). Self-inoculation is described in studies as a potential HPV transmission route, as it was certified in female virgins, and in children with genital warts (low-risk HPV) without a personal history of sexual abuse. Vertical transmission from mother to child is another HPV transfer course. Several studies have emphasized the possibility of infection through the amniotic fluid, or the placenta, or via contact with maternal genital mucosa during natural birth. Waterborne transmission of HPV has never been demonstrated; however, HPV DNA has been detected in water environments. Routine hygiene measures are proven to be inefficient in preventing HPV transmission, as the studies which have evaluated samples of HPV on contaminated medical equipment (after standard disinfection) have found them to be still positive. Annual costs associated with the morbidity and mortality of HPV-related diseases are estimated at approximately $4 billion. Once the HPV vaccine program in Australia was launched, many studies reported the initial effects: A decrease in the incidence of high-grade cervical abnormalities, no new genital warts cases in females under 21 years. Promoting greater understanding in the general public about the evident benefits of vaccination can create positive vaccine attitudes and scatter the myths of spurious side effects.
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http://dx.doi.org/10.3892/etm.2020.9316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579832PMC
December 2020

Carcinogenic effects of bisphenol A in breast and ovarian cancers.

Oncol Lett 2020 Dec 23;20(6):282. Epub 2020 Sep 23.

Department of Obstetrics and Gynecology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

Endocrine-disrupting chemicals (EDCs) are exogenous chemical compounds ubiquitously found in everyday life of the modern world. EDCs enter the human body where they act similarly to endogenous hormones, altering the functions of the endocrine system and causing adverse effects on human health. Bisphenol A (BPA), the principal representative of this class, is a carbon-based synthetic plastic, and a key element in manufacturing cans, reusable water bottles and medical equipment. BPA mimics the actions of estrogen on multiple levels by activating estrogen receptors α and β. BPA regulates various processes, such as cell proliferation, migration and apoptosis, leading to neoplastic changes. Considering genetic mechanisms, BPA exerts its functions via multiple oncogenic signaling pathways, including the STAT3, PI3K/AKT and MAPK pathways. Furthermore, BPA is associated with various modifications of the reproductive system in both males and females. These alterations include benign lesions, such as endometrial hyperplasia, the development of ovarian cysts, an increase in the ductal density of mammary gland cells and other preneoplastic lesions. These benign lesions may continue to develop to breast or ovarian cancer; the effects of BPA depend on various molecular and epigenetic mechanisms that dictate whether the endocrine or reproductive system is impacted, wherein preexisting benign lesions can become cancerous. The present review supports the need for continuous research on BPA, considering its widespread use and most available data suggesting a carcinogenic effect of BPA on the female reproductive system. Although most studies on BPA have been conducted with human cells or with animal models, it can be argued that more studies should be conducted with humans to further promote understanding of the impact of BPA.
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http://dx.doi.org/10.3892/ol.2020.12145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520752PMC
December 2020

Glucagonoma: From skin lesions to the neuroendocrine component (Review).

Exp Ther Med 2020 Oct 3;20(4):3389-3393. Epub 2020 Jul 3.

Department of Gynecology, Emergency University Hospital, 050098 Bucharest, Romania.

Glucagonoma is a hormonally active rare pancreatic neuroendocrine tumour causing an excess of glucagon. This is a narrative review based on a multidisciplinary approach of the tumour. Typically associated dermatosis is necrolytic migratory erythema (NME) which is most frequently seen at disease onset. Insulin-dependent diabetes mellitus, depression, diarrhoea, deep vein thrombosis are also identified, as parts of so-called 'D' syndrome. Early diagnosis is life saving due to potential aggressive profile and high risk of liver metastasis. NME as paraneoplastic syndrome may be present for months and even years until adequate recognition and therapy; it is remitted after successful pancreatic surgery. Thus the level of practitioners' awareness is essential. If surgery is not curative, debulking techniques may improve the clinical aspects and even the outcome in association with other procedures such as embolization of hepatic metastasis; ablation of radiofrequency type; medical therapy including chemotherapy, targeted therapy with mTOR inhibitors such as everolimus, PRRT (peptide receptor radiotherapy), and somatostatin analogues (including combinations of medical treatments). Increased awareness of the condition involves multidisciplinary practitioners.
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http://dx.doi.org/10.3892/etm.2020.8966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465236PMC
October 2020

Somatostatinoma: Beyond neurofibromatosis type 1 (Review).

Exp Ther Med 2020 Oct 3;20(4):3383-3388. Epub 2020 Jul 3.

Department of Gynecology, Emergency University Hospital, 050098 Bucharest, Romania.

Somatostatinoma is a tumour mainly originating from pancreas or duodenum; overall with an incidence of 1/40 million persons. We introduce a narrative review of literature of somatostatinoma including the relationship with neurofibromatosis type 1. Clinical presentation includes: Diabetes mellitus, cholelithiasis, steatorrhea, abdominal pain, and obstructive jaundice while papillary tumour may cause acute pancreatitis. The neoplasia may develop completely asymptomatic or it is detected as an incidental finding during an imaging or a surgical procedure. It may be sporadic or associated to genetic backgrounds especially for duodenal localisation as neurofibromatosis type 1 ( gene with malfunction of RAS/MAPK pathway) or Pacak-Zhuang syndrome ( gene encoding HIF). Surgery represents the central approach if feasible but the prognostic depends on location, and grading as indicated by WHO 2017 classification of neuroendocrine tumours. Previously known as Von Recklinghausen disease, neurofibromatosis type 1, the most frequent neurocutaneous syndrome, is an autosomal dominant disorder including: Café-au-lait spot, skin fold freckling on flexural zones, and neurofibromas as well as tumours such as gliomas of optic nerve, gastrointestinal stromal tumours (GISTs), iris hamartomas and brain tumours. Duodenal somatostatinoma is associated with the syndrome which actually involves more often a duodenal tumour of GIST type than a somatostatin secreting neoplasia. Other neuroendocrine tumours are reported: Gastrointestinal NENs at the level of rectum or jejunum and pheocromocytoma. Overall, one quarter of subjects have gastrointestinal tumours of different types. Somatostatinoma, when not located on pancreas but in duodenoum, may be registered in subjects with neurofibromatosis type 1 most probably in addition to other tumours. Overall, this type of neuroendocrine tumour with a challenging presentation has a poor prognosis unless adequate radical surgery is promptly offered to the patient.
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http://dx.doi.org/10.3892/etm.2020.8965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465002PMC
October 2020

Paraganglioma presenting as a mesenteric cystic mass: A case report.

Exp Ther Med 2020 Sep 28;20(3):2489-2492. Epub 2020 May 28.

Department 3 - Clinical Sciences, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

The present study aims to raise awareness about the necessity of a thorough differential diagnosis process when diagnosing paraganglioma as it is an extremely rare entity with a high malignant potential. A 64-year-old female patient was admitted to the hospital with symptoms of bowel obstruction and a palpable abdominal mass. Abdominal and pelvic computed tomography revealed a cystic heterogeneously enhanced mass. The tumor was surgically removed and then microscopically analysed. Microscopically, the mass was composed of nests of small polygonal and round cells with central vesicular nuclei, consistent with the diagnosis of mesenteric paraganglioma which was later confirmed by immunohistochemistry. The critical markers for paragangliomas, namely chromogranin A and S100, should be used as the first step in diagnosis, followed by other valuable immunohistochemical markers. A long-term follow-up is extremely important following the diagnosis of paraganglioma as all these tumors have a malignant potential.
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http://dx.doi.org/10.3892/etm.2020.8805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401790PMC
September 2020

Etiologic role of in morphea: A case report.

Exp Ther Med 2020 Sep 29;20(3):2373-2376. Epub 2020 May 29.

'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

Morphea is an inflammatory skin disease with self-limited evolution, presenting as localized sclerosis of the skin and/or underlying tissues. The incidence is not exactly known; the disease occurs more frequently in women, and there is no sex prevalence. Pathogenesis of morphea remains still controversial. Several theories exist and the infection is not yet elucidated. The aim of this report is to present the main mechanisms involved in the etiophatogenesis of morphea and also the thepapeutic options. A case of a 60-year-old woman is presented, who was referred to the clinic for an erythematous-violaceus, asymptomatic eruption, located on the trunk and legs, for appoximately 2 months. The patient's medical history revealed an infection with 1 year previously. After diagnosis of morphea was established, and with systemic therapy (corticosteroids and methotrexate), the evolution was favorable.
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http://dx.doi.org/10.3892/etm.2020.8815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401849PMC
September 2020

Regressive melanoma in a female patient: A case report.

Exp Ther Med 2020 Jul 22;20(1):87-90. Epub 2020 Apr 22.

'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

Regressive melanoma is a phenomenon characterized by partial or complete replacement of cutaneous melanoma by fibrotic structures as a result of local host immune response. The dermoscopic features include 'scar-like' depigmentation that can be described as hypopigmented to pigmented macules, pink macules, linear-irregular vessels, globular vessel pattern, hyperpigmented macular remnants, blue gray 'peppered' papular remnants and white transverse bands. Fully regressive melanoma is very rare, and, in majority of cases, the tumor is associated with metastases, so the prognosis is very poor due to this fact. Regressive melanomas are rare since it represents an advance stage of melanoma evolution. Their treatment requires a collaboration between the dermatologist and the oncologist in order to improve the quality of life of the patient and also the survival rate.
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http://dx.doi.org/10.3892/etm.2020.8675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271722PMC
July 2020

Postoperative Ileus Complicated with Incomplete Evisceration after Hysterectomy for Benign Pathology.

Chirurgia (Bucur) 2020 Jan-Feb;115(1):112-119

Postoperative ileus (POI) is a complex phenomenon with important morbidity and mortality, well known in many surgical fields. POI occurs commonly after abdominal and pelvic surgery, especially in cancer patients. We report the case of a 63-year-old patient without known risk factors for POI, who underwent total hysterectomy with bilateral adnexectomy for ovarian tumor with suspicion of malignancy, invalidated by the extemporaneous pathology examination. The postoperative evolution is marked by reduced bowel movements, lack of intestinal transit for flatus and stool for 6 days. In cooperation with the general surgeon conservative treatment for POI was administered, without effect. The abdomen remained distended, with no nausea or vomiting. On the 6th postoperative day a wound dehiscence with incomplete evisceration occurred, after a CT scan of the abdomen and pelvic region was requested to make a differential diagnosis between an intestinal mass and other pathology involving the bowell. In conjunction with the General Surgery team the surgical reintervention was decided and performed. After the procedure, the patient successfully regained transit, with flatus and stool emission, but another 2 complications occurred, which were successfully treated: sepsis and deep vein thrombosis. Understanding the pathophysiology could help to prevent, diagnose, and implement protocols in order to avoid POI and its complications, to reduce hospital stay and cost burden.
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http://dx.doi.org/10.21614/chirurgia.115.1.112DOI Listing
March 2020

Long-term medical management of uterine fibroids with ulipristal acetate.

Fertil Steril 2016 Jan 23;105(1):165-173.e4. Epub 2015 Oct 23.

ObsEva S.A, Plan-Les-Ouates, Geneva, Switzerland.

Objective: To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily ulipristal acetate for intermittent treatment of symptomatic uterine fibroids.

Design: Double-blind, randomized administration of four 12-week courses of ulipristal acetate.

Setting: Gynecology centers.

Patient(s): Four hundred fifty-one subjects with symptomatic uterine fibroid(s) and heavy menstrual bleeding.

Intervention(s): Four repeated 12-week treatment courses of daily 5 or 10 mg ulipristal acetate.

Main Outcome Measure(s): Endometrial safety and general safety, laboratory parameters, amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), and pain.

Result(s): Efficacy results, such as bleeding control and fibroid volume reduction, were in line with previously published data. Pain and QoL showed marked improvements from screening, even during the off-treatment intervals. The safety profile of ulipristal acetate was confirmed, and repeated treatment courses did not increase the occurrence of adverse reactions. There were no significant changes in laboratory parameters during the study. The percentage of subjects with endometrial thickness ≥ 16 mm was 7.4% (all subjects) after the first treatment course and returned to below screening levels (4.9%) in subsequent treatment courses. As in previous studies, ulipristal acetate did not increase the occurrence of endometrial features of concern. The frequency of nonphysiological changes did not increase with repeated treatment. They were observed in 17.8% and 13.3% of biopsies after treatment courses 2 and 4, respectively, and were reversible after treatment cessation.

Conclusion(s): The results of this study demonstrate the efficacy and further support the safety profile of repeated intermittent treatment of symptomatic fibroids with ulipristal acetate.

Clinical Trial Registration Number: NCT01629563.
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http://dx.doi.org/10.1016/j.fertnstert.2015.09.032DOI Listing
January 2016

Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids.

Fertil Steril 2015 Feb 24;103(2):519-27.e3. Epub 2014 Dec 24.

ObsEva SA, Plan-les-Ouates, Geneva, Switzerland.

Objective: To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily of ulipristal acetate for intermittent treatment of symptomatic uterine fibroids.

Design: Double-blind, randomized administration of two 12-week courses of ulipristal acetate.

Setting: Gynecology centers.

Patient(s): A total of 451 patients with symptomatic uterine fibroid(s) and heavy bleeding.

Intervention(s): Two repeated 12-week treatment courses of daily 5 or 10 mg of ulipristal acetate.

Main Outcome Measure(s): Amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), pain.

Result(s): In the 5- and 10-mg treatment groups (62% and 73% of patients, respectively) achieved amenorrhea during both treatment courses. Proportions of patients achieving controlled bleeding during two treatment courses were >80%. Menstruation resumed after each treatment course and was diminished compared with baseline. After the second treatment course, median reductions from baseline in fibroid volume were 54% and 58% for the patients receiving 5 and 10 mg of ulipristal acetate, respectively. Pain and QoL improved in both groups. Ulipristal acetate was well tolerated with less than 5% of patients discontinuing treatment due to adverse events.

Conclusion(s): Repeated 12-week courses of daily oral ulipristal acetate (5 and 10 mg) effectively control bleeding and pain, reduce fibroid volume, and restore QoL in patients with symptomatic fibroids.

Clinical Trial Registration Number: NCT01629563 (PEARL IV).
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http://dx.doi.org/10.1016/j.fertnstert.2014.10.038DOI Listing
February 2015
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