Single-Center Study of 72 Patients with Severe Combined Immunodeficiency: Clinical and Laboratory Features and Outcomes.

Severe combined immunodeficiency is an inborn error of immunity characterized by impairments in the numbers and functions of T and B lymphocytes due to various genetic causes, and if it remains untreated, patients succumb to infections during the first 2 years of life. PURPOSE AND METHODS: This study reported retrospective data from 72 infants diagnosed with SCID including their major clinical features, HSCT characteristics, and outcomes over a 20-year period (1997-2017). RESULTS: Sixty-one of 72 SCID patients in the study underwent HSCT from 1997 to 2017. Median ages at the time of diagnosis and transplantation were 3.5 months and 5 months, respectively. Consanguinity was present in 68% of the patients, and T - B - NK + phenotype was predominantly identified. The overall survival was 80.3% over a 20-year period. However, the patients transplanted during an active infection had a lower survival rate of 73.9% compared to 100% for patients transplanted infection-free or with a previous infection that had resolved. The survival rate was significantly higher among recipients of HLA-identical transplants (92.9%), compared to recipients of mismatched related transplants (70%). The overall survival increased from 50 (1997-2006) to 85% (2007-2017) during the last 10 years. CONCLUSIONS: This is one of the largest single-center studies in Turkey with extensive experience about SCID patients. Early diagnosis of SCID patients before the onset of an infection and early transplantation are shown to be extremely important factors affecting the outcome and increasing the survival regardless of the donor type based on the results of this study.

Family-centeredness of services for young children with Down syndrome: an observational study from Turkey

Background/aim: Physicians require information on the family centeredness of services for children with Down syndrome, one of the most frequently encountered disabilities in childhood. We aimed to determine the family-centeredness of services for young children with Down syndrome and using a bioecological theory framework we hypothesized that child, family and service-related factors would be associated with such services. Materials and methods: In a crosssectional design, children with Down syndrome seen at Ankara University Developmental Pediatrics Division (AUDPD) between February 2020 and June 2020 were included if they had received services in the community for at least 12 months. Mothers responded to the measure of process of care-20 (MPOC-20) used to measure family centeredness. Results: All 65 eligible children were included; 57% were boys and median age was 25.0 (IQR: 18.5­38.0) months. The MPOC-20 subscale scores were highest for the "respectful and supportive care (RSC)" (median 6.0; IQR: 4.8­6.8) and lowest for the "providing specific information" (median 3.0; IQR: 4.4­6.5) subscales. On univariate analyses, maternal education

Does thrombocyte size give us an idea about thrombocytosis etiology?

In the presence of a pathogenetic mutation in JAK2 or MPL, a differential diagnosis of essential thrombocythemia (ET) from reactive causes is relatively simple. However, in patients with suspected ET who lack JAK2 and MPL mutations, the exclusion of secondary causes is especially important. The study was aimed to explore the clinical application of particularly mean platelet volume (MPV), hemoglobin, red blood cell indices, white blood cell, serum iron profile, and C-reactive protein level in the differential diagnosis of thrombocytosis. Medical records of 49 patients, consisting of reactive thrombocytosis (RT) and ET were retrospectively reviewed. The mean MPV level in RT group was 7.49 fL, and in ET group was 8.80 fL (P < 0.01). A cutoff point of <8.33 fL was found to have significant predictive value according to ROC curve analysis. This cutoff was associated with 83% positive predictive value (PPV) and 74% negative predictive value (NPV) in the diagnosis of ET and had a sensitivity of 65% and specificity of 89% for ET. Investigation of MPV is cheap, quick, and noninvasive, and may serve as a predictor of primary thrombocytosis. High sensitivity, specificity, PPV, and NPV enable this test an important tool and a possible surrogate marker in clinical practice.

Does reactive thrombocytosis observed in iron deficiency anemia affect plasma viscosity?

OBJECTIVE: The accompanying thrombocytosis is referred to as the major factor associated with thromboembolism in iron deficiency anemia (IDA). Increased viscosity may increase the risk of thrombosis. We hypothesized that increased platelet count -with reactive thrombocytosis- might also affect plasma viscosity. We planned to evaluate the influence of normal and high platelet count on plasma viscosity in IDA patients. MATERIAL AND METHODS: The patient population consisted of fifty-three newly diagnosed and untreated women aged between 18 and 62 years with IDA. Group 1 consisted of 33 patients, platelet levels below 400 x 10(9)/L. Group 2 consisted of 20 patients, platelet levels above 400 x 10(9)/L. Measurements of plasma viscosity were performed using Brookfield viscometer. RESULTS: Mean plasma viscosity was found as 1.05 ± 0.08 mPa.s. in Group 1, and 1.03 ± 0.06 mPa.s. in Group 2. Mean plasma viscosity was not statistically different. White blood cell count was significantly higher in Group 2. Vitamin B12 levels were significantly higher in Group 2, while folic acid levels were higher in Group 1 (p=0.011 and p=0.033). Plasma viscosity was correlated with erythrocyte sedimentation rate (r=0.512 p=0.002) in Group 1 and inversely correlated with vitamin B12 (r=-0.480 p=0.032) in Group 2. CONCLUSION: Despite the significant difference between groups in terms of platelet count, no significant difference was detected in plasma viscosity and this finding could be explained as the following; 1-These platelets were not thrombocythemic platelets; 2-Similar to the theory about leukocytes, higher platelet counts - even non-thrombocythemic - may increase plasma viscosity; 3-Evaluating platelet count alone is not sufficient and the associating red-cell deformability should also be taken into account; and 4-Although other diseases that could affect viscosity are excluded, some definitely proven literature criteria such as fibrinogen, hyperlipidemia, and the inflammatory process should also be evaluated by laboratory and clinical measures.

Flow cytometric evaluation of cell cycle regulators (cyclins and cyclin-dependent kinase inhibitors) expressed on bone marrow cells in patients with chronic myeloid leukemia and multiple myeloma.

OBJECTIVE: The aim of this study was to use flow cytometry to analyze the expression of cell cycle-regulating elementswith low and high proliferative signatures in patients with malignant diseases. MATERIAL AND METHODS: Cyclin D, E, A, and B, and cyclin-dependent kinase inhibitor (CDKI) p16 and p21 levels weremeasured via flow cytometry in patients with chronic myeloid leukemia (CML) (n = 16) and multiple myeloma (MM)(n = 13), and in controls (n = 15). RESULTS: The distributions of the cell cycle S phase were 10, 63%, 6, 72% and 3, 59%; for CML, MM and controlpatients, respectively. Among all the cyclins expressed during the S phase, cyclin D expression was the lowest in the CMLpatients. Distribution of cyclins and CDKIs during the G2/M phase was similar in the MM and control groups, whereascyclin expression was similar during all 3 phases in the MM and CML groups. CONCLUSION: Elevated cyclin expression during cell cycle phases in the CML and MM patients was not associatedwith elevated CDKI expression. This finding may increase our understanding of the mechanisms involved in theetiopathogenesis of hematological malignancy.

Capsular Invasion Matters Also in "Papillary Patterned" Tumors: A Study on 121 Cases of Encapsulated Conventional Variant of Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy. Some PTCs with classical papillae can be totally or partially encapsulated, and these tumors are called "encapsulated" (conventional) variant of papillary thyroid carcinoma. We aimed to investigate the clinicopathological features of this variant, comparing with non-encapsulated conventional type PTC. Among 823 thyroidectomy specimens with PTC diagnosed between 2015 and 2018, 121 tumors from 105 patients (12.75%) were reclassified as encapsulated conventional PTC. In 76 patients, tumors were unifocal. Size, cystic changes, background thyroiditis, psammoma bodies, cervical lymph node metastasis at presentation, capsular/vascular invasion, and immunohistochemical BRAF-V600E expression were evaluated. Ninety-two non-encapsulated conventional PTCs served as control group. Encapsulated cases were predominantly women (73.3%), 56.4% were microcarcinomas, 97.5% had cystic changes, 81.4% were BRAF-V600E positive, and 36.8% of unifocal encapsulated tumors had cervical lymph node metastasis. Thyroiditis and psammoma bodies were detected in nearly half of the encapsulated PTCs. Fourteen percent of the unifocal tumors showed total encapsulation, whereas capsular and vascular invasion was detected in 85.5% and 5.8%, respectively. Encapsulated cases did not show any significant difference from the control group, except for prominent cystic changes (p < 0.001). Relationship between lymph node metastasis at presentation and capsular invasion was statistically significant (p = 0.001), and metastasis was more frequent in cases with extensive capsular invasion (no/minimal invasion versus extensive invasion, p < 0.001). Cystic changes are very common, and this feature deserves mentioning as a morphological characteristic of encapsulated conventional PTCs. As in encapsulated "follicular" variant of PTC, capsular invasion status is important in evaluating papillary patterned encapsulated PTC for predicting lymph node metastasis. Total examination of the tumor capsule and inclusion of capsular invasion status in pathology reports are recommended.

[Therapy with omalizumab in patients with severe persistent allergic asthma: a real life data in Turkey]. / Agir allerjik astimli hastalarda anti-IgE (omalizumab) tedavisi: Gerçek yasam verileri.

Omalizumab is a biologic agent, which has been shown to be effective in clinical trials in allergic, severe asthmatics. The aim of this study was to evaluate the clinical, functional effectiveness, and side effects of omalizumab in real-life conditions respectively. A total of 18 patients (female/male: 11/7) were included to the study. The mean ± SD age, total IgE, disease duration were 41.8 ± 11.2 years, 255.1 ± 197.3 kU/L, 12.8 ± 9.4 years, respectively. Eight patients had isolated mite, seven patients had mite + other inhalant allergen, three patients had only other allergen sensitivity. Mean duration of omalizumab treatment (months ± SD) was 15.1 ± 8.6 (min-max 1-29) months. Omalizumab dose was 150 mg/month in five patients, 300 mg/month in five, 300 mg/15 days in three, 375 mg/15 days in four, 225 mg/15 days in one patient. Data at the date of last visit were compared with one year prior to omalizumab treatment. Mean systemic steroid dose reduced by 83% (14.7 ± 14.6 vs. 3.2 ± 8 mg), number of other asthma medications reduced by 28% (3.6 ± 1.3 vs. 2.5 ± 1.3) (p< 0.05). FEV1% values (53.5 ± 21.2 vs. 64.5 ± 23.5) did not significantly change. Mean numbers of exacerbations (20 ± 57.6 vs. 0.4 ± 0.7), emergency visits (16.5 ± 46.1 vs. 0.4 ± 1.2), hospitalizations (2.1 ± 2.6 vs. 0.1 ± 0.3) decreased by 93%, 95%, 86%, respectively (p< 0.05). ACT scores increased by 94% (10.4 ± 3.4 vs. 20.4 ± 5.7) (p< 0.05). Fifteen patients (88%) were stated as responsive to treatment with omalizumab. Eleven patients (64.8%) stated that their expectations are met, three patients (17.6%) stated that their expectations are close to being met, three patients (17.6%) stated that their expectations are not met. A local side effect was seen in one patient. In conclusion, our data has shown that omalizumab is effective, and safe in severe allergic asthmatics under real-life conditions.

Doppler ultrasonography findings in ocular Behçet's disease.

The aim of this prospective study was to determine and compare the orbital Doppler ultrasonography parameters of patients with Behçet's disease (with or without ocular involvement) with those of healthy subjects. We evaluated ophthalmic artery (OA), central retinal artery, posterior ciliary artery (PCA), central retinal vein, and superior ophthalmic vein (SOV) flow velocities and resistance indices (RIs). Detection of the decreased flow velocities in the OA and SOV and the increased RI in the OA and PCA might allow the identification of active period of patients with Behçet's disease.

Significance of inducible nitric oxide synthase expression in benign and malignant breast epithelium: an immunohistochemical study of 151 cases.

The role of calcium independent inducible nitric oxide synthase (iNOS) in breast carcinoma is controversial, and the implications of iNOS expression on prognosis are not known. In this study, we aimed to investigate the significance of immunohistochemical iNOS expression in 100 invasive ductal carcinomas. In addition, 11 normal breast tissues, 20 cases of usual ductal hyperplasias (UDHs) and 20 fibroadenomas were included. We found that 78% of malignant and 75% of benign cases showed iNOS immunoreactivity. However, the intensity and the quantity of iNOS expression were significantly higher in the cancer group when compared with benign breasts (P<0.001), suggesting a role of iNOS in breast carcinogenesis. We were unable to show a correlation between iNOS expression and tumor grade, axillary lymph node status, and estrogen receptor expression. In 50 axilla negative cases having 5--12 years follow-up, disease free survival (DFS) rate was significantly lower in cases showing strong iNOS expression (P=0.05). As strong iNOS expression was correlated with short DFS, we concluded that further studies would be necessary to elucidate if iNOS expression might be a useful prognostic marker in breast carcinoma, especially in the axilla negative group.

Neuroendocrine differentiation in colorectal carcinomas: assessing its prognostic significance.

AIMS AND BACKGROUND: There is evidence that colorectal carcinomas with extensive neuroendocrine features have a substantially worse prognosis than those without, but the frequency and clinical significance of neuroendocrine features in conventional carcinomas has not been settled since few studies have been performed, with conflicting results. The aim of the study was to investigate neuroendocrine differentiation in colorectal carcinomas in relation to its prognostic significance. METHODS: In 50 patients with colorectal carcinoma, the extent and intensity of staining with each of the three antibodies (chromogranin A, neuron-specific enolase and synaptophysin) were determined and correlated with the histologic type, grade, stage of the tumor and survival time ot the patients. RESULTS: We observed chromogranin A expression in 38%, neuron-specific enolase expression in 26%, and synaptophysin expression in 6% of the tumors. Chromogranin A was the most frequently and strongly expressed marker in our study. Of the three antibodies studied, only chromogranin A positivity was correlated with grade and stage of the tumors and was associated with a decreased effect on survival. CONCLUSIONS: Our results show that chromogranin A is the most sensitive and specific neuroendocrine marker. Chromogranin A positivity appears to bear a poor prognosis in patients with colorectal cancers.

Serrated lesions of the appendix: do they differ from their colorectal counterparts?

BACKGROUND/AIMS: The aim of this study is, therefore, to classify appendiceal serrated polyps in a large case series with respect to the recent World Health Organization classification using diagnostic criteria provided for colorectal serrated polyps. MATERIALS AND METHODS: A total of 960 appendix specimens diagnosed between 2005 and 2010 were reviewed retrospectively, and cases presenting with a polyp with serrated morphology were classified with reference to the recent World Health Organization criteria. Histologic criteria comprised architectural features of the crypts, including serration, branching, basal dilatation, inverted T- or L-shaped crypts together with cytologic features comprising a mucin pattern, dysplasia, in terms of pseudostratification and nuclear atypia, mitoses in the upper crypts, and cytoplasmic eosinophilia. RESULTS: A total of 71 cases (7.39%) were diagnosed as serrated polyps, including 36 (50.7%) hyperplastic polyps, 33 (46.48%) sessile serrated adenoma/polyps, and 2 (2.81%) traditional serrated adenomas. There were 32 males and 39 females with an age range of 2 to 82 years. Histology revealed that the majority of both hyperplastic polyps (63.9%) and sessile serrated adenomas/polyps (74.3%) involved the entire appendiceal circumference. Basal dilatation (94.3%), basal serration (94.3%), T-/L-shaped crypts (94.3%), and ectopic crypts (68.6%) were significantly more commonly observed in sessile serrated adenomas/polyps compared to hyperplastic polyps. Dysplasia was observed in 31.4% of sessile serrated adenomas/polyps, while hyperplastic polyps did not show dysplasia. CONCLUSION: The results of the present study suggest that appendiceal serrated polyps, despite bearing many similarities with their colorectal counterparts, may have some special features due to the anatomic uniqueness of the organ itself and also the polyps arising from its mucosal lining.

Serrated polyps of the colon: how reproducible is their classification?

For several years, the lack of consensus on definition, nomenclature, natural history, and biology of serrated polyps (SPs) of the colon has created considerable confusion among pathologists. According to the latest WHO classification, the family of SPs comprises hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The term SSA/P with dysplasia has replaced the category of mixed hyperplastic/adenomatous polyps (MPs). The present study aimed to evaluate the reproducibility of the diagnosis of SPs based on currently available diagnostic criteria and interactive consensus development. In an initial round, H&E slides of 70 cases of SPs were circulated among participating pathologists across Europe. This round was followed by a consensus discussion on diagnostic criteria. A second round was performed on the same 70 cases using the revised criteria and definitions according to the recent WHO classification. Data were evaluated for inter-observer agreement using Kappa statistics. In the initial round, for the total of 70 cases, a fair overall kappa value of 0.318 was reached, while in the second round overall kappa value improved to moderate (kappa = 0.557; p < 0.001). Overall kappa values for each diagnostic category also significantly improved in the final round, reaching 0.977 for HP, 0.912 for SSA/P, and 0.845 for TSA (p < 0.001). The diagnostic reproducibility of SPs improves when strictly defined, standardized diagnostic criteria adopted by consensus are applied.

Mucins in the colorectal neoplastic spectrum with reference to conventional and serrated adenomas.

BACKGROUND/AIMS: Alterations in expression of mucins and aberrant expression of various types of mucin genes were observed in colorectal adenomas and carcinomas, though their significance in neoplastic transformation of colorectal epithelium is yet to be determined. The aim of this study was to determine expression of MUC1, MUC2, MUC5AC, and MUC6 through conventional adenoma-carcinoma sequence and polyps involved in the "serrated" pathway of the colorectum using tissue array technique. METHODS: In this study, a total of 172 cases including 100 colorectal polyps [8 hyperplastic polyps, 10 sessile serrated adenomas, 19 tubular, 37 tubulovillous, and 26 villous adenomas], 16 adenomas with intramucosal carcinoma, 28 conventional colorectal cancers, and 28 normal mucosae were examined. Tissue array blocks were prepared and sections were stained immunohistochemically for MUC1, MUC2, MUC5AC, and MUC6. RESULTS: Expression of MUC1 significantly increased in close correlation with the neoplastic process and reached its highest values in intramucosal carcinomas and conventional colorectal cancers (p<0.001). In contrast, MUC2 expression showed a significant decrease in intramucosal carcinoma and conventional colorectal cancer groups (p<0.001). Sessile serrated adenomas exhibited the highest MUC5AC expression while adenomatous polyps showed an increase in MUC5AC expression in parallel with neoplastic progression (p<0.001). Hyperplastic polyps seemed to lie between normal mucosa and sessile serrated adenomas in terms of mucin expression, suggesting that they are morphologically and histogenetically linked. CONCLUSIONS: Upregulation of MUC1 and MUC6 through the adenoma-carcinoma sequence together with downregulation of MUC2 and MUC5AC at the neoplastic end of the spectrum seem to follow the steps of malignant transformation.

The significance of beta-catenin, E-cadherin, and P-cadherin expressions in neoplastic progression of colorectal mucosa: an immunohistochemical study.

BACKGROUND AND STUDY AIMS: The purpose of the current study was to investigate the role of beta-catenin, E-cadherin and P-cadherin in colorectal carcinogenesis using tissue array method. PATIENTS AND METHODS: Core tissue biopsies were taken from paraffin-embedded tissue blocks of 167 cases including 26 normal mucosae (NM), 99 colorectal polyps (10 hyperplastic polyps (HP), 8 traditional serrated (TSA), 17 tubular (TA), 37 tubulovillous (TVA), and 27 villous adenomas (VA)), 14 adenomas with intramucosal carcinoma (ACA), and 28 colorectal cancers (CCA). Immunohistochemistry was performed using antibodies to beta-catenin, E-cadherin, and P-cadherin. Distribution of positivity was assessed using percentage expression while an arbitrary grading scale was used for staining intensity. RESULTS: beta-catenin expression was cytoplasmic, membranous, and nuclear. Both E-cadherin and P-cadherin expressions were confined to cytoplasmic-membranous compartments. Membranous expression of beta-catenin significantly decreased in CCA (p < 0.01). Nuclear beta-catenin expression significantly increased in close correlation with neoplastic sequence reaching its highest expression in ACA and CCA (p < 0.001). Polyps with intraepithelial neoplasia (IEN) showed significantly higher nuclear beta-catenin expression in parallel with increasing grades of IEN (p < 0.001). E-cadherin and P-cadherin expression increased in polyps, whereas a significant decrease in their expression was observed in CCA (p < 0.001) while E-cadherin expression significantly increased in CCA compared to NM (p < 0.001), no such difference was observed in P-cadherin expression. CONCLUSIONS: Nuclear beta-catenin expression correlating with the grade of IEN in polyps and carcinomas supports its role in colorectal carcinogenesis. E-cadherin and P-cadherin expressions in adenomas suggest that these molecules might have role in adenoma formation though not necessarily be involved in neoplastic progression.