Surgical outcomes and follow-up results of 53 pediatric craniopharyngioma cases: a single-center study.

OBJECTIVE: Craniopharyngiomas are locally invasive neoplasms, and they cause potential lifelong morbidity because of their tendency for local recurrence. Despite advancements in endoscopic techniques, gross-total resection (GTR) of tumors with invasion or adhesion to important surrounding anatomical structures is extremely difficult. The authors present a single-center study that evaluated the impact of the endoscopic endonasal approach (EEA) on the surgical outcomes of pediatric craniopharyngiomas, the factors affecting the resection rate, and recurrence. METHODS: A total of 44 pediatric patients (age ≤ 18 years) who were treated via the EEA for craniopharyngioma from August 1997 to June 2022, as well as their 53 operations, were included in this study. The preoperative radiological configuration and surgical data of these cases were assessed. Also, preoperative and postoperative clinical (endocrinologic, neurological, and ophthalmological), hypothalamic, physical and social development, and neurocognitive assessment data were described. RESULTS: In total, 37 cases (69.8%) had no history of operation beforehand. The most common symptoms at presentation were endocrine disturbances (98.1%), headache without vomiting (84.3%), and visual disturbance (51%). Cases were classified as infrasellar (1.9%), sellar (32.1%), sellar-suprasellar (52.8%), and suprasellar (13.2%) localization. GTR was achieved in 34/53 cases (64.1%). The rate of GTR was higher in infrasellar and sellar tumors compared with sellar-suprasellar and suprasellar tumors (p = 0.003), and preoperative hypothalamic involvement was associated with lower likelihood of GTR (p = 0.024). Moreover, with experience, the rate of GTR increased (p = 0.037). Postoperative complications, other than endocrine impairment, occurred in 10/53 cases (18.9%). The mean duration of follow-up was 53.57 months. At follow-up, 21/53 (39.6%) cases presented with tumor recurrence. The 5-year progression-free survival (PFS) rate was 48.5%. There was a statistically significant difference between the GTR and other-than-GTR groups in terms of PFS (p < 0.001). According to univariate analysis, smaller tumor (p = 0.017), infrasellar and sellar localization (p = 0.031), and GTR (p < 0.001) were significantly associated with decreased rate of recurrence. Also, there was a statistically significant association between the recurrence rate and adhesion strength of the tumor (p < 0.001). CONCLUSIONS: This retrospective cohort study revealed surgical indications for EEA, as well as factors affecting the resection rate, recurrence, and quality of life during the follow-up period of the included cases. The authors believe that GTR should be the goal for craniopharyngioma treatment, but the authors' treatment approach was to provide a balance between radical surgery with maximum safety and adjuvant treatment for long-term disease control.

ARID3A and ARID3B exert direct regulatory control over the long non-coding RNAs (lncRNAs) MALAT1 and NORAD within the context of non-small cell lung cancer (NSCLC).

Lung cancer, known for its high mortality rates and poor prognosis, remains one of the most prevalent cancer types. Early detection and effective treatment methods are crucial for improving survival rates. Non-small cell lung cancer (NSCLC) accounts for approximately 85 % of all lung cancer cases. Long non-coding RNAs (lncRNAs), which play vital roles in various biological processes, have been implicated in the development of cancer and can impact key therapeutic targets in different cancer types. In NSCLC, the dysregulation of specific lncRNAs, such as MALAT1 and NORAD, has been associated with neoplastic initiation, progression, metastasis, tumor angiogenesis, chemoresistance, and genomic instability. Both MALAT1 and NORAD directly regulate the expression of the transcription factor E2F1, thereby influencing cell cycle progression. Additionally, MALAT1 has been reported to affect the expression of p53 target genes, leading to cell cycle progression through the repression of p53 promoter activity. NORAD, on the other hand, is indirectly regulated by p53. The AT-rich interaction domain (ARID) family of DNA-binding proteins, particularly ARID3A and ARID3B, are involved in various biological processes such as cell proliferation, differentiation, and development. They also play significant roles in E2F-dependent transcription and are transcriptional targets of p53. The intricate balance between promoting cellular proliferation through the pRB-E2F pathway and inducing growth arrest through the p53 pathway underscores the crucial regulatory role of ARID3A, ARID3B, and their interaction with lncRNAs MALAT1 and NORAD. In this study, we aimed to investigate the potential interactive and functional connections among ARID3A, ARID3B, MALAT1, and NORAD in NSCLC, considering their involvement in the pRB-E2F and p53 pathways. Our findings strongly suggest that ARID3A and ARID3B play a regulatory role in controlling MALAT1 and NORAD in NSCLC. Specifically, our study demonstrates that the activities of MALAT1 and NORAD were markedly increased upon the overexpression of ARID3A and ARID3B. Therefore, we can conclude that ARID3A and ARID3B likely contribute significantly to the oncogenic functions of MALAT1 and NORAD in NSCLC. Consequently, targeting ARID3A and ARID3B could hold promise as a therapeutic approach in NSCLC, given their direct control over the expression of MALAT1 and NORAD.

A reference center study in thyrotropin-secreting pituitary adenomas: clinicopathological, therapeutic and long-term follow-up outcomes.

PURPOSE: This study aims to analyze the clinicopathological features, diagnostic steps, and therapeutic results of TSHomas and to reveal the effective factors on remission. METHODS: The clinical, radiological, and pathological features and surgical and endocrinological results of 41 TSHoma cases followed between 2005 and 2022 were retrospectively analyzed. The factors affecting the surgical cure were investigated by comparing the groups with and without remission. RESULTS: A total of 41 patients (23 male,18 female) were included in the study and the mean age was 42 (31.5-49). Palpitation and headache were the most common complaints. The time from the onset of symptoms to diagnosis was 8 (3-20) months. There were 8 patients with a preoperative clinical and biochemical diagnosis of TSH + GH co-secretion. In the TRH stimulation test, a blunted TSH response was obtained in 18 patients (90.0%). Complete suppression could not be obtained in any of the patients who underwent the T3 suppression test. The median maximum tumor diameter was 19.0 mm (6.8-41). There was microadenoma in 4 (9.8%) patients and macroadenoma in 37 patients (92.8%). Remission was achieved in 31 (75.6%) of 40 patients who underwent endoscopic transsphenoidal surgery (eTSS). The Ki-67 labeling index was 2% (1.00-4.00) in the entire patient group. Preoperative use of antithyroid drugs appears to be significantly associated with surgical cure. CONCLUSION: Diagnosis of TSHoma is still full of challenges and dynamic tests remain important. Recognition and good management of inappropriate TSH secretion states affect subsequent surgical outcomes.

Investigation of CD56, ADAM17 and FGF21 Expressions in the Placentas of Preeclampsia Cases.

Objective: In the present study, we investigated the expression of CD56, ADAM17 and FGF21 antibodies (Ab), which we think have an effect on the pathophysiology of preeclampsia (PE), in pregnant patients with healthy placentas and placentas with PE. The expression of these antibodies has been investigated in a limited amount of former research, but their role in PE has not yet been clarified. With this study, we aimed to contribute to the elucidation of the pathophysiology of PE and the detection of new target molecules for treatment. Materials and Methods: Parturients with singleton pregnancy at 32 weeks or above without any maternal or fetal pathology who were admitted to the Department of Obstetrics and Gynecology, Zonguldak Bülent Ecevit University Practice and Research Hospital between 11 January 2020 and 7 January 2022 were included in the present study. Pregnant women with coexisting disease or a pathology related to the placenta (ablation placenta, vasa previa, hemangioma, etc.) were excluded. CD56, ADAM17 and FGF21 antibodies were histopathologically and immunohistochemically detected in 60 placentas with PE (study group) and 43 healthy placentas (control group). Results: CD56, ADAM17 and FGF21 proteins were all more intensely expressed in preeclamptic placentas and a statistically significant difference was found between the two groups for all three antibodies (p < 0.001). Deciduitis, perivillous fibrin deposition, intervillous fibrin, intervillous hemorrhage, infarct, calcification, laminar necrosis and syncytial node were found to be significantly more common in the study group (p < 0.001). Conclusions: We observed that CD56, ADAM17 and FGF21 expressions increased in preeclamptic placentas. These Ab may be responsible for the pathogenesis of PE, which can be illuminated with further studies.

Thirst intensity survey in ADPKD patients.

INTRODUCTION: With increased fluid intake and tolvaptan treatment, the growth rate of cysts can be theoretically decelerated in autosomal polycystic kidney disease. In this prospective study, it was planned to evaluate thirst sensation in these patients and the parameters affecting its intensity. METHODS: Forty-one ADPKD patients on tolvaptan and 40 ADPKD patients not on tolvaptan as the control group were evaluated for thirst distress sensation and intensity. The feeling of thirst and the discomfort caused by excessive fluid intake was assessed with Thirst Distress Scale-HF 12 questions (60/12). Thirst intensity was evaluated with a 100 mm visual scale. RESULTS: Of the whole group, 35.8% (29) were males, and 64.2% (52) were females. The mean age of the tolvaptan group was 39.17 ± 9.35 years and for the control group, it was 41.95 ± 12.29 years. There was a negative correlation between the thirst distress score of the patients and an increase in creatinine level after a year of tolvaptan treatment (r = - 0.335, p = 0.035). The patients not taking thiazide had higher thirst intensity scores (p = 0.004). There was no impact of tolvaptan dosage, total kidney volume, serum sodium, urinary osmolarity or eGFR on thirst distress and thirst intensity scores. DISCUSSION/CONCLUSION: Only thiazide co-treatment had a positive impact on thirst distress and intensity when given tolvaptan. Thirst Distress Scale for ADPKD patients can be used to classify patients before and during tolvaptan treatment.

Correction to: Efects of AGEs, sRAGE and HMGB1 on Clinical Outcomes in Multiple Myeloma.

[This corrects the article DOI: 10.1007/s12288-022-01574-6.].

An unusual manifestation in a pediatric patient with MAFB mutation: Sacroiliitis in multicentric carpotarsal osteolysis syndrome.

Multicentric carpotarsal osteolysis (MCTO) syndrome, is typically characterized by progressive bone resorption in especially carpal and tarsal bones, in addition to abnormal facial appearance and proteinuria. This disorder is caused by monoallelic pathogenic MAFB mutations, which result in excessive osteoclastogenesis via aberrant receptor activator of nuclear factor kappa-B ligand activation. Most cases are sporadic with de-novo mutations, and it is still unclear why carpal and tarsal bones are predominantly affected. The early phases of MCTO resemble juvenile idiopathic arthritis (JIA) with ankle and wrist swelling and pain, even with inflammatory changes in magnetic resonance imaging. Herein we report a pediatric patient, previously treated with antirheumatic drugs, and eventually diagnosed with MCTO. This case was a descriptive case with exophthalmos, significant proteinuria, and total loss of carpal and tarsal bones at the time of genetic diagnosis. Similar to the literature, our case had typical radiological findings despite methotrexate and anti-tumor necrosis factor-alpha treatment. However, while arthritis affecting joints other than wrists and ankles has not been reported so far in the literature, our case had bilateral sacroiliitis which completely resolved after adalimumab treatment. We cannot be sure if sacroiliitis was incidental or occurred as a component of the disease, nonetheless, we think that sharing our experience may lead to easy and early recognition of MCTO, with more knowledge on rare manifestations of MCTO, and thus we may be able to clarify the benefits of denosumab, which is the most promising agent in early phases of the disease.

Effects of AGEs, sRAGE and HMGB1 on Clinical Outcomes in Multiple Myeloma.

Purpose: The receptor for advanced glycation end products (RAGE) upregulated during the onset and progression of cancer and bone-related pathologies. In this study, we aimed to investigate the role of serum advanced glycation end products (AGEs), soluble RAGE (sRAGE) and high mobility group box 1 (HMGB1), in multiple myeloma (MM). Methods: AGEs, sRAGE and HMGB1 concentrations of 54 newly diagnosed MM patients and 30 healthy volunteers were measured by ELISA. The estimations were done only once at diagnosis. The medical records of the patients were evaluated. Results: There was no significant difference between the AGEs and sRAGE levels between the patient and control groups (p = 0.273, p = 0.313). In ROC analysis, a HMGB1 cutoff value of > 9170 pg/ml accurately discriminated MM patients (AUC = 0.672, 95% CI 0.561-0.77, p = 0.0034). AGEs level was found to be significantly higher in early-stage disease and HMGB1 in advanced disease (p = 0.022, p = 0.026). High HMGB1 levels were detected in patients whose with better first-line treatment response (p = 0.019). At 36 months, 54% of patients with low AGE were alive, compared to 79% of patients with high AGE (p = 0.055). Patients with high HMGB1 levels tended to have a longer PFS (median 43 mo [95% CI; 20.68-65.31] ) compared to patients with low HMGB1 levels (median 25 mo [95% CI; 12.39-37.6], p = 0.054). Conclusion: In this study, a significant elevation of serum HMGB1 level was found in MM patients. In addition, the positive effects of RAGE ligands on treatment response and prognosis were determined.

Okadaic Acid-Induced Alzheimer's in Rat Brain: Phytochemical Cucurbitacin E Contributes to Memory Gain by Reducing TAU Protein Accumulation.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive decline, with hallmark pathologies related to amyloid beta (Aß) and TAU. Natural phytochemicals show promise for drug discovery to fill the current therapeutic innovation gap in AD. This study investigated the effect of cucurbitacin E (CuE), one of the bioactive components of Ecballium elaterium, on TAU fibril formation in okadaic acid-induced AD in rats. In a randomized design, we assigned 30 female Sprague Dawley rats to one of five experimental groups: (1) control, (2) stereotaxic surgery, (3) stereotaxic surgery + artificial cerebrospinal fluid, (4) stereotaxic surgery + okadaic acid (AD model), and (5) stereotaxic surgery + okadaic acid + CuE treatment. For experimental groups 4 and 5, rats were administered OKA-ICV (200 ng/kg) followed by CuE (4 mg/[kg·day], intraperitoneally) for 20 days. Expression of the MAPK1/3 and MAPK14 genes associated with TAU metabolism, hippocampal protein levels of these genes, cognitive functions of the rats, and histological accumulation of TAU in the brain were evaluated. Our findings in this preclinical model collectively suggest that phytochemical CuE contributes to memory gain by reducing TAU protein accumulation, which warrants further evaluation in future in vitro and in vivo studies.

Programmed Cell Death Ligand 1 Expression Level and Prognostic Significance in Acute Myeloid Leukemia.

Purpose: We aimed to evaluate the expression level of programmed death ligand-1 (PD-L1) and its effects on prognosis in acute myeloid leukemia. Methods: The flow cytometry was used to detect PD-L1 expression on leukemic cells of 86 de novo acute myeloid leukemia patients with longitudinal follow-up. Results: Median follow-up was 13 (0-73) months. The mean of expression level was 3.22 ± 0.47 at diagnosis and ranged from 0 to 28%. PD-L1 expression tended to be lower in patients with acute promyelocytic leukemia (2.47 ± 1.08, p = 0.09) but there was no significant difference between neither diagnostic nor cytogenetic subgroups. There was no difference in PD-L1 levels between the patients who achieved complete remission (3.4 ± 0.61) and those who did not (2.91 ± 0.72, p = 0.94). The patients with low PD-L1 at diagnosis (median 25 mo [95% CI; 0-56.7]) had a longer overall survival compared with high PD-L1 (median 13 mo [95% CI; 5.52-25.17], p = 0.079). PD-L1 expression was lower at relapse (2.04 ± 0.79) compared to initial diagnosis (4.52 ± 0.93, p = 0.049). The patients who had overall survival longer than 1 year showed lower PD-L1 expression at relapse (0.66 ± 0.93) compared with who had not (5.06 ± 4.28, p = 0.052). A negative correlation between CD33 and PD-L1 (r = - 0.303, p = 0.005) was detected. Conclusion: Despite its low expression levels, PD-L1 appears to be a clinically important prognostic factor. The negative correlation determined between PD-L1 and CD33 supports the combination approach of PD-L1 inhibitors and CD33 targeted immunotherapies. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-021-01473-2.

Endoscopic approach for giant pituitary adenoma: clinical outcomes of 205 patients and comparison of two proposed classification systems for preoperative prediction of extent of resection.

OBJECTIVE: Giant pituitary adenoma is considered a challenging pathology for surgery owing to its complications and low resection rate. In this study, the authors present their experience of using the endoscopic endonasal approach to treat patients with giant pituitary adenoma, and they aimed to develop a classification system for prediction of extent of resection. METHODS: The institutional medical records of patients diagnosed with giant pituitary adenoma who underwent endoscopic endonasal transsphenoidal surgery between August 1997 and December 2019 were retrospectively reviewed. Surgical and clinical outcomes were evaluated in detail. The effects of tumor characteristics on extent of resection were analyzed. The findings were used to develop two classification systems that could preoperatively predict extent of resection. Morphological score was based on tumor characteristics, and landmark-based classification was defined according to surgical zones based on neurovascular landmarks. The effects of change in surgical strategy, which aimed to maximize tumor resection and capsule dissection, on rates of resection and complications were evaluated before and after 2017. RESULTS: This study included 205 patients, with a mean patient age of 46.95 years and mean preoperative tumor diameter of 46.56 mm. Gross-total resection (GTR) was achieved in 35.12% of patients, near-total resection (NTR) in 39.51%, and subtotal resection (STR) in 25.36%. Extent of resection differed significantly between the grades and zones of the classification systems (p < 0.001 for both). Among patients with grade 3 tumor, 75.75% of patients achieved STR, 21.21% achieved NTR, and 3.03% achieved GTR. Among patients with zone 3 tumor, 65.75% achieved STR, 32.87% achieved NTR, and 1.36% achieved GTR. Both grade 3 and zone 3 indicated limited extent of resection. The mean (range) follow-up duration was 50.16 (9-247) months. Postoperative recovery of at least one hormone axis was seen in 15.24% of patients with pituitary deficiency, and development of new hormonal deficiency was observed in 22.43% of patients. Complications included permanent diabetes insipidus (7.80%), cerebrospinal fluid leakage (3.90%), postoperative apoplexy (3.90%), meningitis (3.41%), and epistaxis (3.41%). The surgical mortality rate was 1.46%. Among 85 patients treated before 2017, 27.05% of patients achieved GTR, 37.64% achieved NTR, and 35.29% achieved STR; among 120 patients treated after 2017, 40.83% achieved GTR, 40.83% achieved NTR, and 18.33% achieved STR. Seven patients in the pre-2017 cohort had postoperative apoplexy versus only 1 patient in the post-2017 cohort. There were no statistically significant differences between the two periods in terms of the incidence rates of other complications. CONCLUSIONS: Capsule dissection and GTR are valuable for preventing serious complications and reducing recurrence of giant adenoma. Treatment of giant pituitary adenoma may be better managed with the help of a classification system that provides information about extent of resection that can be achieved with an endoscopic approach.

Evaluation of HPV, smear and colposcopy results in patients with diabetes.

BACKGROUND AND AIMS: This study aimed to evaluate whether there is a difference in human papillomavirus (HPV), smear, and cervical biopsy results between patients with and without diabetes mellitus (DM). METHODS: Retrospectively, 136 patients with positive high risk (HR) HPV screening results with and without DM who underwent colposcopy between 2015 and 2019 were identified. The clinicopathological characteristics and HR HPV screening results were reported and analyzed. The results of the patients with and without DM were compared. RESULTS: HPV 16 positivity, Atypical Squamous Cells of Undetermined Significance (ASCUS), and Cervical Intraepithelial Neoplasia 1 (CIN 1) in smear and biopsy results were higher in patients with DM than patients without DM. CONCLUSIONS: The higher HPV positivity in patients with diabetes may require reforming the frequency and method of cervical cancer screening to be applied to this patient group.

Monogenic lupus due to DNASE1L3 deficiency in a pediatric patient with urticarial rash, hypocomplementemia, pulmonary hemorrhage, and immune-complex glomerulonephritis.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease and usually involves the skin, musculoskeletal system, and kidneys. More than 30 genes have been to monogenic lupus, so far. Monogenic lupus is often characterized by an early-onset, similar family history, and syndromic appearance. Herein we present a pediatric patient with DNASE1L3 deficiency, suffering from both urticarial skin lesions, recurrent hemoptysis, and renal involvement, eventually diagnosed as this rare monogenic lupus. The patient suffered from recurrent urticarial rash and hemoptysis since the age of 15 months of age. He had microscopic hematuria, mild proteinuria, hypocomplementemia, and positive antinuclear antibody, anti-dsDNA, and antineutrophil cytoplasmic antibodies. Renal biopsy yielded immunocomplex glomerulonephritis. Due to early-onset, similar sibling history and consanguineous parents, we suspected monogenic lupus and performed whole-exome sequencing, which further revealed a homozygous T97Ifs*2 mutation (NM_004944.4: c.290_291delCA/p.Thr97Ilefs*2) in DNASE1L3 gene. In conclusion, DNASE1L3 deficiency should be thought when juvenile SLE occurs with early disease-onset, pulmonary hemorrhage, glomerulonephritis, and recurrent urticarial rash along with ANCA positivity.

Camptodactyly-Arthropathy-Coxa Vara-Pericarditis Syndrome Resembling Juvenile Idiopathic Arthritis: A Single-Center Experience from Southern Turkey.

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome, caused by biallelic pathogenic mutations in the PRG4 gene, is characterized by early-onset camptodactyly, noninflammatory arthropathy, coxa vara deformity, and rarely, pericardial effusion. Herein, we report 3 patients with CACP syndrome from 2 unrelated families. All patients are female, born to consanguineous parents, and had camptodactyly since the first years of their lives. Two patients had a prior diagnosis of juvenile idiopathic arthritis. Hip changes were present in 2 patients, and 2 of 3 patients had undergone surgery for camptodactyly. Routine echocardiographic evaluations were normal during the 2-year follow-up. This paper represents the third study including CACP patients from Turkey. Clinically, all 3 patients resembled juvenile idiopathic arthritis cases and received unnecessary medication. There is also an ongoing need for improving awareness of CACP and an effective treatment focusing on the lubrication of the joint space in CACP patients.

Clinical features of childhood uveitis at a tertiary referral center in Southern Turkey.

PURPOSE: To report the epidemiology, etiology, ocular characteristics, management, and visual outcomes of pediatric uveitis patients in Southern Turkey. METHODS: The clinical records of pediatric patients with a diagnosis of uveitis under the age of 16 years and followed up longer than 6 months were analyzed retrospectively. RESULTS: The study included 102 patients and 173 affected eyes. The mean age at presentation was 11.4 ± 3.7 years. Uveitis was predominantly bilateral (69.6%), anterior (45.1%), and chronic (58.8%). The leading diagnoses were idiopathic uveitis (38.2%), pars planitis (19.6%), and juvenile idiopathic arthritis-associated uveitis (14.7%). Infectious uveitis accounted for 12.7%, and toxoplasmosis was the most common cause (10.8%). At least one complication was observed in 76.3% of the eyes, and optic disk edema (37%) was the most frequent. Corticosteroids were used in 97.1% and systemic immunomodulatory agents in 49% of the patients. Ocular surgery was performed in 17.3% of the eyes, and cataract extraction was the most common (8.7%). The mean BCVA was 0.39 ± 0.66 LogMAR at baseline and 0.25 ± 0.53 LogMAR at the last recorded visit. CONCLUSION: Pediatric uveitis is a challenging disease that requires meticulous management. Anterior uveitis is the most frequent form. Despite a changing trend for an increase in diagnostic variety, idiopathic cases still constitute the majority. A significant number of patients receive systemic therapy, develop complications, and require surgical intervention. Early diagnosis and appropriate treatment might improve visual outcomes and reduce the risk of visual loss.

The concordance between colposcopic biopsy and loop electrosurgical excision procedures in patients with known smear cytology and human papillomavirus results.

Objective: The objective of the study was to evaluate the concordance between colposcopic biopsy and loop electrosurgical excision procedure (LEEP) methods to diagnose cervical pre-invasive lesions and cervical cancer, and to calculate the low and high prediction rates of lesions for both methods. Methods: A total of 241 patients who underwent LEEP after colposcopic biopsy for different indications and also known cervical cytology and human papillomavirus test results were included in the study. Clinical variables such as age, gravida, parity, menopausal status, smoking, endocervical curettage results, and surgical margins were recorded. Results: The total concordance between colposcopic biopsy and LEEP was 41.9%. The rates of finding a more serious lesion than in colposcopic biopsy with LEEP (underestimation) for negative, Cervical Intraepithelial Neoplasia (CIN) 1, CIN 2, and CIN 3 were calculated as 100%, 12.8%, 14.8%, and 3.9%, respectively. Rates of finding a less serious lesion than detected in colposcopic biopsy with LEEP (overestimation) for CIN 1, CIN 2, and CIN 3, cervical carcinoma were calculated as 56.4%, 33.3%, 3.9%, and 0%, respectively. Underestimation was seen in a total of 28 patients, and overestimation was present in 113 patients. Parity was found to be the only associated factor that affected the final diagnosis for high-grade lesions in univariate logistic regression analysis (odds ratio=1.234, 95% confidence interval: 1.005-1.514). Conclusion: Discrepancies between colposcopically directed punch biopsy and subsequent histopathologic LEEP findings are common. New methods to reduce the inconsistency between colposcopic biopsy and LEEP are necessary to prevent patients from being under or over treated.

Differentiating children with familial Mediterranean fever from other recurrent fever syndromes: The utility of new Eurofever/PRINTO classification criteria.

Objectives: In this study, we aimed to investigate the performance of Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria in pediatric patients with familial Mediterranean fever (FMF). Patients and methods: This retrospective, cross-sectional study included a total of 130 pediatric FMF patients (67 males, 63 females; mean age: 12.4±3.6 years; range, 2.5 to 17.7 years) with at least one M694V mutation in MEFV gene between July 2010 and July 2019. Demographic features and disease characteristics were recorded. The control group was consisted of 41 patients (19 males, 22 females; mean age: 7.8±4.0 years; range, 2.1 to 17.8 years) with other hereditary autoinflammatory diseases (AIDs), including periodic fevers with aphthous stomatitis, pharyngitis, and adenitis syndrome (n=30), mevalonate kinase deficiency (n=9), and tumor necrosis factor receptor-associated periodic syndrome (n=2). Sensitivity and specificity of the Eurofever/PRINTO classification criteria were calculated. Results: The sensitivity and specificity were 97.7% and 56.1% for Yalcinkaya-Ozen criteria, respectively and 93.1% and 90.2% for Tel Hashomer criteria, respectively. The Eurofever/PRINTO classification criteria reached a sensitivity and specificity of 94.6% and 82.9% and 93.1% and 80.5%, respectively, when genetic plus clinical criteria and clinical-only criteria were applied. Conclusion: The Eurofever/PRINTO classification criteria have a comparable sensitivity for avoidance of FMF underdiagnosis in childhood. The Yalcinkaya-Ozen criteria have the highest sensitivity without a significant specificity. The Tel Hashomer criteria and Eurofever/PRINTO classification criteria were superior to Yalcinkaya-Ozen criteria to differentiate FMF from other AIDs, thus leading to less complications relevant to underdiagnosis of other AIDs.

Growth Parameters of Turkish Children With an Autoinflammatory Disease Before and After Canakinumab Treatment.

OBJECTIVE: To evaluate the effect of canakinumab on growth parameters of patients with autoinflammatory diseases. METHODS: This retrospective study included Colchicine resistant familial Mediterranean fever (FMF), Mevalonate kinase deficiency (MKD), Tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), Deficiency of adenosine deaminase 2 (DADA2) patients treated with canakinumab for at least six consecutive months. RESULTS: Eleven patients with FMF, 9 with MKD, 3 with TRAPS, and 1 with DADA2 were included. The median age (range) at diagnosis and drug initiation was 6.06 (1.45-16.06) years and 9.72 (1.82-19.11) years, respectively. The mean weight, height, and BMI SD scores significantly increased after canakinumab. There were significant improvements in laboratory parameters and disease activities. However, growth parameters after the drug did not differ according to gender, the duration of diagnostic delay, and age at the diagnosis. CONCLUSIONS: Canakinumab seems to have a positive effect on growth in patients with autoinflammatory diseases by controlling disease activity and inflammation.

The role of endothelial nitric oxide synthase gene polymorphisms in patients with lung cancer.

OBJECTIVES: Lung cancer is a disease characterized by uncontrolled cell growth in the lung tissues. The most common causes of lung cancer include smoking, exposure to radon gas, asbestos, environmental pollutants as well as genetic factors. Nitric oxide (NO) has potential mutagenic and carcinogenic activity and may play an important role in lung cancer. Endothelial NO, synthesized from L-arginine by endothelial NO synthase (eNOS), inhibits apoptosis and promotes angiogenesis and tumor cell proliferation. The aim of the present study was to examine the possible relationship between eNOS gene intron 4 variable number of tandem repeat (VNTR) and exon 7-G894T (Glu298Asp) polymorphisms and lung cancer risk. METHODS: DNA was extracted from peripheral blood leukocytes of 107 lung cancer patients and 100 control subjects. Designated polymorphisms were identified by polymerase chain reaction (PCR) and/or restriction fragment length polymorphism (RFLP). RESULTS: Our study showed that the frequencies of the b/b genotype and b allele of eNOS gene intron 4 VNTR polymorphism were significantly higher in lung cancer patients than in controls (P < 0.05). However, there was no significant association between eNOS gene G894T polymorphism and lung cancer risk (P > 0.05). CONCLUSION: These results suggest that the presence of the intron 4 VNTR* b allele and b/b genotype may be a genetic risk factor for development of lung cancer. Further larger-scale studies are needed to confirm these findings.