Publications by authors named "Ebru Yilmaz"

105 Publications

The role of the rhinostomy ostium size on functional success in dacryocystorhinostomy.

Braz J Otorhinolaryngol 2021 Apr 10. Epub 2021 Apr 10.

Bandırma State Hospital, Ophthalmology Department.

Introduction: Endonasal and external dacryocystorhinostomy procedures have both been used for the treatment of post-saccular obstruction of the lacrimal system. Functional success of these surgeries depends on several factors.

Objective: To evaluate the status of the rhinostomy ostium with endonasal and external approaches in dacryocystorhinostomy operations and to determine the effect of ostium size on postoperative functional success.

Methods: The charts of the patients operated in our hospital between May 2017 and January 2019 were analyzed retrospectively (ethical approval number: 2018-12.04). The patients that were operated in the ophthalmology and otolaryngology departments were included in the study. Endoscopic rhinostomy ostium measurements, punctum lavage findings and complications were recorded at 8 weeks postoperative at the earliest.

Results: When the 64 patient charts were reviewed (76 operations), the mean ostium width was 1.85±1.11mm in the endonasal approach group and 3.60±2.24mm in the external approach group. The mean ostium areas in endonasal and external group were 14.61±16.66mm and 56.05±60.41mm, respectively. The ostium was anatomically patent and punctum lavages were negative in 11 patients (6 patients in the endonasal approach group and 5 patients in the external approach group) and these cases were considered as functional failures. The rhinostomy ostium was significantly wider in the external approach group, but this was considered ineffective on functional outcomes.

Conclusion: Lacrimal duct stenosis can be successfully treated with endonasal and external methods. Tear drainage may be insufficient even in the presence of a patent ostium. Therefore, functional success should also be considered when evaluating the overall success of dacryocystorhinostomy. An anatomically patent ostium is definitely required, while it is believed that ostium size does not affect functional surgical success.
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http://dx.doi.org/10.1016/j.bjorl.2021.03.006DOI Listing
April 2021

Over restrictive elimination of foods in children with food allergy.

Turk J Pediatr 2021 ;63(1):109-117

Divisions of Pediatric Allergy, Koc University School of Medicine, İstanbul, Turkey.

Background: Previous studies demonstrated critical deficits in diagnosis and management of childhood food allergy (FA), and recent developments in FA research support adopting a proactive approach in FA management. Our objective was to describe FA knowledge and management patterns of pediatricians.

Method: We applied a 24-item survey to 170 general pediatricians, pediatric allergists and pediatric gastroenterologists practicing in Turkey.

Results: Some IgE-mediated symptoms of FA such as cough, urticaria, wheezing and anaphylaxis were falsely recognized as symptoms of non-IgE-mediated FA by 30%, 29%, 25% and 19% of the participants, respectively. By contrast, 50% of the participants falsely recognized bloody stool, a finding of IgE-mediated FA. Most frequently and least frequently used diagnostic tools were specific IgE (30.5%) and oral food challenge test (1.7%), respectively. Maternal diet restrictions and infant diet restrictions were advised by 82% and 82%, respectively. Percentages of physicians eliminating only 1 food were 21%, 19%; 2 foods were 15%, 11%; 3 foods were 7%, 8%; 4-5 foods were 8%, 11%; 5 to 10 foods were 21%, 26%; and > 10 foods were 28%, 25% from the maternal and infant diet, respectively. Cow`s milk, cheese, butter, yoghurt, baked milk products and hen`s egg were the most commonly restricted items.

Conclusion: Overall, FA knowledge of pediatricians was fair. Pediatricians utilize an overly restrictive approach when advising diet eliminations in FA. Recent developments favor a more proactive approach to induce immune tolerance and need to be encouraged in pediatric clinical practice. Future educational efforts should focus on emphasizing the deleterious effects of injudicious and extensive eliminations.
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http://dx.doi.org/10.24953/turkjped.2021.01.013DOI Listing
January 2021

The Determination of the Efficacy of Neural Therapy in Conservative Treatment-resistant Patients With Chronic Low Back Pain.

Authors:
Ebru Yılmaz

Spine (Phila Pa 1976) 2020 Dec 28;Publish Ahead of Print. Epub 2020 Dec 28.

Department of Physical Medicine and Rehabilitation, Kocaeli Government Hospital, Kocaeli, Turkey.

Study Design: A randomized clinical trial.

Objective: The aim of this article is to determine the effectiveness of neural therapy (NT) in patients with chronic low back pain (LBP) who are resistant to medical and physical therapies.

Summary Of Background Data: Patients with LBP generally respond well to the treatment, whereas some cases do not improve via medical and physical therapies. Although trigger point injections (TPIs) may be an effective short-term treatment in selected patients with LBP, they are not recommended in patients with chronic LBP due to a long-lasting benefit not being demonstrated.

Methods: Fifty patients, who had inadequate functional recovery and pain relief, with chronic LBP were randomly divided into two groups: Group 1, only single TPI; Group 2, NT. NT including local-segmental treatment (intradermal injections) on the lumbosacral region, 5 mol/L injection (intradermal injections of the projection of the pelvic organs on the suprapubic region), pelvic plexus injection, i.v. injection (2 mL) for five sessions per a week. All patients in group 2 received the same kind of intervention every seance but interference field injections (injections into umbilicus for all patients and injections into scars resulting from vaccination and surgical operations such as cesarean section, if any) were also applied at the only first seance. The Visual Analog Scale (VAS) scores for current pain during activities and Roland Morris Disability Questionnaire (RMDQ) scores for disability were recorded at baseline and 1, 3, 6 months post-injection.

Results: The VAS and RMDQ scores at 3 and 6 months were significantly lower in Group 2 versus Group 1 (P < 0.05).

Conclusion: NT may be an alternative treatment option in patients with chronic LBP for pain relief and functional recovery in the long run.Level of Evidence: 2.
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http://dx.doi.org/10.1097/BRS.0000000000003909DOI Listing
December 2020

The Efficacy of Colchicine on Carotid Intima-Media Thickness: A Prospective Comparative Study.

J Stroke Cerebrovasc Dis 2021 Mar 30;30(3):105580. Epub 2020 Dec 30.

Department of Cardiology, Kocaeli Government Hospital, Gunes Street, 41300 Kocaeli, Turkey.

Objectives: Inflammation plays an important role in the development of atherosclerotic vascular disease, which is the leading cause of morbidity and mortality in the adult population. Several clinical trials have shown that suppression of the inflammatory response can delay or decrease the atherosclerotic process. The aim of this study was to investigate carotid intima-media thickness (CIMT) between patients with chronic disease history plus gout using colchicine and patients with cardiovascular risk factors.

Materials And Methods: In total, 102 patients (85 female, 17 male) were included. There were two groups in the study: Group 1 - patients with chronic diseases including cardiovascular risk factors plus gout using colchicine (0,5 mg twice a day); and Group 2 - patients with chronic diseases including cardiovascular risk factors only. All patients underwent ultrasonography for the measurement of CIMT. Additionally, the serum concentrations of C-reactive protein (CRP) and the levels of lipids such as cholesterol, triglyceride, LDL, HDL were measured.

Results: The mean age of patients was 62.35±6.68 years and 64.27±5.32 years in Group 1 and Group 2, respectively. There was also no statistically significant difference in the levels of lipids between groups (p>0.05). The value of CIMT and CRP in Group 1 and Group 2 were 0.98±0.20 and 0.26±0.14, 1.18±0.15 and 0.58±0.42, respectively. There was a statistically significant difference between groups (p<0.05). The colchicine group was found to have a statistically significant lowering of CIMT and CRP compared to the non-colchicine group.

Conclusions: It appears that colchicine in addition to statins and other standard treatments is an effective treatment for the interception of cardiovascular and cerebrovascular events in patients with cardiovascular risk factors.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105580DOI Listing
March 2021

Common Variable Immunodeficiency, Autoimmune Hemolytic Anemia, and Pancytopenia Associated With a Defect in IKAROS.

J Pediatr Hematol Oncol 2021 04;43(3):e351-e357

Department of Pediatrics, Division of Pediatric Hematology and Oncology & Pediatric HSCT Unit.

Objective: Mutations in IKZF1, which encodes Ikaros family zinc finger 1 (IKAROS) transcription factor, are associated with recurrent infections, cytopenia, autoimmune diseases, and hematologic malignancies. Diverse clinical phenotypes resulting from IKZF1 mutations include pulmonary fungal infections, cytopenia, autoimmune hemolytic anemia (AIHA), and malignancies. In this study, we aimed to assess the DNA-binding ability and pericentromeric (PC) localization of a variant of IKZF discovered in a patient.

Materials And Methods: DNA-binding ability of a pathogenic IKZF variant was tested using electrophoretic mobility shift assay and PC localization of the variant was assessed by immunofluorescent microscopy in NIH3T3 cells.

Results: Clinical features of a 3-month-old male infant who underwent hematopoietic stem cell transplantation because of an IKZF1 mutation-associated common variable immunodeficiency, AIHA, and pancytopenia are described. DNA studies revealed a heterozygous missense variant (IKZF1 NM_006060 c.427C>T; p.R143W). Cotransfection studies revealed that mutant R143W has a partial dominant-negative effect over PC targeting and DNA binding.

Conclusions: IKZF1 mutation must be kept in mind if neonatal AIHA, common variable immunodeficiency, and pancytopenia are observed.
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http://dx.doi.org/10.1097/MPH.0000000000001976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987842PMC
April 2021

Targeted CRISPR screening identifies PRMT5 as synthetic lethality combinatorial target with gemcitabine in pancreatic cancer cells.

Proc Natl Acad Sci U S A 2020 11 23;117(45):28068-28079. Epub 2020 Oct 23.

Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22903;

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most challenging cancers to treat. Due to the asymptomatic nature of the disease and lack of curative treatment modalities, the 5-y survival rate of PDAC patients is one of the lowest of any cancer type. The recurrent genetic alterations in PDAC are yet to be targeted. Therefore, identification of effective drug combinations is desperately needed. Here, we performed an in vivo CRISPR screen in an orthotopic patient-derived xenograft (PDX) model to identify gene targets whose inhibition creates synergistic tumor growth inhibition with gemcitabine (Gem), a first- or second-line chemotherapeutic agent for PDAC treatment. The approach revealed protein arginine methyltransferase gene 5 (PRMT5) as an effective druggable candidate whose inhibition creates synergistic vulnerability of PDAC cells to Gem. Genetic depletion and pharmacological inhibition indicate that loss of PRMT5 activity synergistically enhances Gem cytotoxicity due to the accumulation of excessive DNA damage. At the molecular level, we show that inhibition of PRMT5 results in RPA depletion and impaired homology-directed DNA repair (HDR) activity. The combination (Gem + PRMT5 inhibition) creates conditional lethality and synergistic reduction of PDAC tumors in vivo. The findings demonstrate that unbiased genetic screenings combined with a clinically relevant model system is a practical approach in identifying synthetic lethal drug combinations for cancer treatment.
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http://dx.doi.org/10.1073/pnas.2009899117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668168PMC
November 2020

The effect of COVID-19 pandemic on breast imaging: a clinical observations.

Diagn Interv Radiol 2020 Nov;26(6):603

Department of Radiology, Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey.

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http://dx.doi.org/10.5152/dir.2020.20644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664756PMC
November 2020

Dietary supplementation of black mulberry (Morus nigra) syrup improves the growth performance, innate immune response, antioxidant status, gene expression responses, and disease resistance of Nile tilapia (Oreochromis niloticus).

Fish Shellfish Immunol 2020 Dec 29;107(Pt A):211-217. Epub 2020 Sep 29.

Department of Fisheries, Faculty of Natural Resources, University of Zabol, Zabol, Iran.

The present study investigated the effects of black mulberry (Morus nigra) syrup supplementation on growth performance, hematological, serum biochemical, innate immune parameters, immune and antioxidant related gene expression responses, and disease resistance of Nile tilapia, Oreochromis niloticus. Five isonitrogenous and isoenergetic diets were formulated to contain black mulberry syrup at levels of 0%, 0.75%, 1.5%, 2.0%, and 3.0%. Fish were fed experimental diets for 60 days. Dietary black mulberry syrup increased activities of serum lysozyme, myeloperoxidase, superoxide dismutase and catalase, and increased the expression levels of immune-related genes (interleukin 1, beta, tumor necrosis factor, immunoglobulin M, interferon gamma and heat shock protein 70) in the spleen and antioxidant-related genes (superoxide dismutase, catalase and glutathione peroxidase) in the liver of fish fed especially with 1.5%, 2.0%, and 3.0% black mulberry syrup supplemented diets. Furthermore, at 2.0% incorporation level, growth performance increased. The findings of the present study indicate that Nile tilapia fed with diet containing 2.0% black mulberry might be adequate to improve the growth performance, innate immune parameters, antioxidant related gene expression responses, and disease resistance against Aeromonas veronii.
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http://dx.doi.org/10.1016/j.fsi.2020.09.041DOI Listing
December 2020

Y90 selective internal radiation therapy and peptide receptor radionuclide therapy for the treatment of metastatic neuroendocrine tumors: combination or not?

Nucl Med Commun 2020 Dec;41(12):1242-1249

Department of Nuclear Medicine.

Background: Peptide receptor radionuclide therapy and selective internal radiation therapy are effective radionuclide therapy modalities for unresectable metastatic neuroendocrine tumor patients that cannot be controlled with somatostatin analogs. The present study is intended to evaluate the therapeutic efficacy and toxicity of the combined therapy of selective internal radiation therapy and peptide receptor radionuclide therapy and stand-alone selective internal radiation therapy in patients with neuroendocrine tumor, a liver-dominant disease.

Methods: This cohort consists of 27 patients with metastatic neuroendocrine tumor and liver-dominant disease. They were grouped as the patients who were treated with selective internal radiation therapy for unresectable liver metastasis (n = 15) and the patients who received a combination of selective internal radiation therapy and peptide receptor radionuclide therapy (n = 12) for hepatic and extrahepatic metastasis. Treatment efficacy and treatment-associated toxicity were retrospectively assessed in both groups.

Results: The objective treatment response and stable disease were found in 13 patients (86.6%) in the selective internal radiation therapy group and eight patients (66.6%) in the selective internal radiation therapy + peptide receptor radionuclide therapy group. The median overall survival rate was found to be 34.9 months, in the selective internal radiation therapy group and 67.5 months in the selective internal radiation therapy + peptide receptor radionuclide therapy group (P = 0.217). The median progression-free survival data was not reached, and the mean values of progression-free survival were 53.1 ± 9.9 months in the selective internal radiation therapy group, and 27.2 ± 5.9 months in the selective internal radiation therapy + peptide receptor radionuclide therapy group (P = 0.561). Temporary lymphopenia was the most common side effect. Grade 1-2 hepatotoxicity was observed to be 6.6% in the selective internal radiation therapy group, while it was not observed in selective internal radiation therapy + peptide receptor radionuclide therapy group.

Conclusions: In the neuroendocrine tumors with liver-dominant metastatic disease, personalized selective internal radiation therapy and peptide receptor radionuclide therapy and their combinations result in increased survival rates. Selective internal radiation therapy alone could be an effective treatment in patients with liver-limited and -dominant disease.
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http://dx.doi.org/10.1097/MNM.0000000000001284DOI Listing
December 2020

Hepatitis-associated aplastic anemia in pediatric patients: single center experience.

Transfus Apher Sci 2020 Dec 3;59(6):102900. Epub 2020 Aug 3.

Department of Pediatric Gastroenterology, Hepatology and Nutrition, Erciyes University, Faculty of Medicine, Kayseri, Turkey.

Introduction: Hepatitis-associated aplastic anemia is a rare type of acquired aplastic anemia that occurs after hepatitis. This study investigated cases with hepatitis-associated aplastic anemia.

Methods: The files of patients with hepatitis-associated aplastic anemia who were followed up in our hospital between 2011-2019 were reviewed retrospectively.

Results: A total of 15 patients with hepatitis-associated aplastic anemia (10 males, 5 girls; mean age 10.26 ± 3.61 years) were analyzed. The mean duration between hepatitis and aplastic anemia was 5.06 ± 4.19 months. The majority of patients had mild hepatitis. The causes of hepatitis were detected only in six patients: three had hepatitis B, one had hepatitis A, one had autoimmune hepatitis and, one had a hydatid cyst. The cause of hepatitis was not found in nine patients. Only one patient with hepatitis-associated aplastic anemia developed spontaneous remission, and the others required immunosuppressive therapy and/or hematopoietic stem cell transplantation. Only one patient died because of sepsis. The other patients are still under follow-up and treatment.

Conclusion: Patients with hepatitis-associated aplastic anemia, mostly of unknown cause, can be successfully treated with immunosuppressive therapy and/or hematopoietic stem cell transplantation.
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http://dx.doi.org/10.1016/j.transci.2020.102900DOI Listing
December 2020

Presentation of multiple myeloma occurring in the humerus after strain: a case report.

Authors:
Ebru Yilmaz

Clin Rheumatol 2021 Jan 1;40(1):389-392. Epub 2020 Jul 1.

Department of Physical Medicine and Rehabilitation, Kocaeli Government Hospital, Gunes Street 41300, Kocaeli, Turkey.

Multiple myeloma (MM) is a malignant tumor originating from plasma cells that synthesize immunoglobulin in an abnormal amount and invade the bone marrow. The presenting symptoms have usually been severe bone pain, osteolytic bone damage and pathologic fractures, hypercalcemia, kidney damage, compromised immune function, and anemia. The patient age is typically over 40, with the majority of the cases diagnosed between ages 50 and 70. MM occurs in hematopoietic locations with red marrows; most common locations include the vertebrae, ribs, skull, pelvis, and proximal long bones. It often has extensive bone destruction with no reactive bone formation and a large soft tissue component similar to the lesion. In the literature, the presence of pathological fracture in the humerus is generally seen as the first clinical manifestation of MM. In this report, it is presented a case with MM occurring in the right humerus after strain and presenting only shoulder pain without pathologic fracture.
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http://dx.doi.org/10.1007/s10067-020-05256-4DOI Listing
January 2021

Extended clinical and immunological phenotype and transplant outcome in CD27 and CD70 deficiency.

Blood 2020 12;136(23):2638-2655

Dr von Hauner Children's Hospital, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.

Biallelic mutations in the genes encoding CD27 or its ligand CD70 underlie inborn errors of immunity (IEIs) characterized predominantly by Epstein-Barr virus (EBV)-associated immune dysregulation, such as chronic viremia, severe infectious mononucleosis, hemophagocytic lymphohistiocytosis (HLH), lymphoproliferation, and malignancy. A comprehensive understanding of the natural history, immune characteristics, and transplant outcomes has remained elusive. Here, in a multi-institutional global collaboration, we collected the clinical information of 49 patients from 29 families (CD27, n = 33; CD70, n = 16), including 24 previously unreported individuals and identified a total of 16 distinct mutations in CD27, and 8 in CD70, respectively. The majority of patients (90%) were EBV+ at diagnosis, but only ∼30% presented with infectious mononucleosis. Lymphoproliferation and lymphoma were the main clinical manifestations (70% and 43%, respectively), and 9 of the CD27-deficient patients developed HLH. Twenty-one patients (43%) developed autoinflammatory features including uveitis, arthritis, and periodic fever. Detailed immunological characterization revealed aberrant generation of memory B and T cells, including a paucity of EBV-specific T cells, and impaired effector function of CD8+ T cells, thereby providing mechanistic insight into cellular defects underpinning the clinical features of disrupted CD27/CD70 signaling. Nineteen patients underwent allogeneic hematopoietic stem cell transplantation (HSCT) prior to adulthood predominantly because of lymphoma, with 95% survival without disease recurrence. Our data highlight the marked predisposition to lymphoma of both CD27- and CD70-deficient patients. The excellent outcome after HSCT supports the timely implementation of this treatment modality particularly in patients presenting with malignant transformation to lymphoma.
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http://dx.doi.org/10.1182/blood.2020006738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735164PMC
December 2020

A prospective, comparative study of subacromial corticosteroid injection and subacromial corticosteroid injection plus suprascapular nerve block in patients with shoulder impingement syndrome.

Authors:
Ebru Yilmaz

Arch Orthop Trauma Surg 2021 May 30;141(5):733-741. Epub 2020 Apr 30.

Department of Physical Medicine and Rehabilitation, Kocaeli Government Hospital, Gunes Street 41300, Kocaeli, Turkey.

Introduction: Efforts are recently focused on the management of shoulder impingement syndrome (SIS) with a conservative and targeted approach because of its psychosocial impact, reduction in the quality of life, the cost to the economy and its negative effect on daily activities. Therefore, many studies have been designed to evaluate and compare the effectiveness of different treatments. The main purpose of this study was to identify the effect of combination of subacromial corticosteroid injection (SCI) and suprascapular nerve block (SSNB) on shoulder impingement syndrome (SIS).

Materials And Methods: 66 patients with SIS were randomly divided into two groups (33 patients per group): Group 1: SCI; Group 2: SCI plus SSNB. The estimation of the severity of pain by the visual analogue scale (VAS) and shoulder disability using quick DASH (Disabilities of the Arm, Shoulder and Hand) were assessed at baseline and 1, 3 months post-injection.

Results: The mean age of patients was 55.55 ± 10.42 years in Group 1 and 57.24 ± 12.75 years in Group 2. In steroid group, pre- and post-treatment (at 1 and 3 months) VAS/quickDASH scores were 8.64 ± 0.99/78.03 ± 9.24, 2.09 ± 0.84/15.58 ± 7.23 and 3.06 ± 1.12/25.06 ± 8.74, respectively. In steroid plus SSNB group, pre- and post-treatment (at 1 and 3 months) VAS/quickDASH scores were 8.45 ± 0.90/75.15 ± 9.86, 1.24 ± 0.43/10.88 ± 2.14 and 1.51 ± 0.56/15.51 ± 5.04, respectively. Both treatment groups showed a significant relief of pain at 1 and 3 months post-injection (p < 0.05). However, the VAS and quickDASH scores at 1 and 3 months were significantly lower in Group 2 versus Group 1 (p < 0.05).

Conclusion: The combination of SCI and SSNB seems to produce the long-term effect in pain relief and functional improvement.
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http://dx.doi.org/10.1007/s00402-020-03455-xDOI Listing
May 2021

Measurement of apparent diffusion coefficient in discrimination of benign and malignant axillary lymph nodes.

Pol J Radiol 2019 22;84:e592-e597. Epub 2019 Dec 22.

Altınbas University School of Medicine Bahcelievler Medical Park Hospital, İstanbul, Turkey.

Purpose: We aimed to determine the contribution of the apparent diffusion coefficient (ADC) value in the detection of axillary lymph node metastasis.

Material And Methods: Breast magnetic resonance of 58 patients, performed in the radiology clinic of our hospital between 2015 and 2017 were examined retrospectively, and 43 lymph nodes in 43 patients were included in the study. They were evaluated morphologically on T1W and T2W sequences, and the lymph nodes showing rounded shape, focal or diffuse cortical thickness of more than 3 mm, and partial or total effacement of fatty hilum were included in the study. Subsequently, their ADC values were measured.

Results: There were 43 lymph nodes, 20 of which were malignant and 23 of which were benign. While the mean ADC value of malignant axillary lymph nodes was 0.749 10 mm/s (0.48-1.342), it was 0.982 10 mm/s (0.552-1.986) for benign lymph nodes. When the ADC cut-off value was taken as ≤ 0.753 × 10 mm/s, its discrimination power between benign and malignant axillary lymph nodes was as follows: sensitivity - 60%; specificity - 91.3%; accuracy - 76.7%; positive predictive value - 85.7%; and negative predictive value - 72.4%.

Conclusions: There was no significant difference between mean ADC value of 12 lymphadenopathies (LAP) associated with inflammatory breast diseases (granulomatous mastitis and acute suppurative mastitis) and mean ADC value of metastatic lymph nodes. However, the ADC value of lymph nodes showing thickened cortex due to systemic inflammatory diseases was over 1, and there was a statistically significant difference when compared with metastatic lymph nodes.
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http://dx.doi.org/10.5114/pjr.2019.92315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016376PMC
December 2019

Phylogenetic Group/Subgroups Distributions, Virulence Factors, and Antimicrobial Susceptibility of Escherichia coli Strains from Urinary Tract Infections in Hatay.

Rev Soc Bras Med Trop 2020 7;53:e20190429. Epub 2020 Feb 7.

Department of Microbiology, Faculty of Veterinary Medicine, Hatay Mustafa Kemal University, TR-31060 Hatay, Turkey.

Introduction: Nosocomial and community acquired urinary tract infections (UTIs) are one of the most encountered infections in the world.

Methods: This study aimed to determine the antibiotic susceptibility, phylogeny, and virulence genes of 153 Escherichia coli strains isolated from UTIs. Antimicrobial susceptibility of the isolates to different classes of antimicrobials was determined by the VITEK-2 automated system. Presence of virulence genes and phylogenetic groups were investigated by PCR.

Results: Regarding susceptibility to antimicrobials, ampicillin resistance was most abundant (67.3%), followed by amoxicillin-clavulanic acid (50.9%); least abundant was resistance to amikacin (1.3%) and nitrofurantoin (1.3%). Multi drug resistance (MDR) was observed in 34.6% of the isolates, and all isolates were found to be susceptible to imipenem, meropenem and fosfomycine. The majority of the isolates belonged to the phylogenetic group B23 (35.9%), followed by A1 (20.9%), D1 (18.9%), D2 (12.4%), A0 (%5.9), B1 (3.9%) and B2 (1.9%). Among E. coli strains examined, 49% had iucD, 32.7% papE-F, 26.1% papC, 15% cnf2, 11.1% sfa, 7.8% cnf1, 1.3% afaE, 1.3% afaD, 1.3% hlyA, 0.7% f17a-A, 0.7% clpG and 0.7% eaeA genes.

Conclusions: Our research demonstrated that virulence factors were distributed among different phylogroup/subgroups, which play a role in UTIs pathogenesis in humans. For this reason, complex and detailed studies are required to determine the relationship between virulence factors and specific E. coli strains that cause UTIs in humans.
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http://dx.doi.org/10.1590/0037-8682-0429-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083342PMC
March 2020

IL-15 negatively regulates curdlan-induced IL-23 production by human monocyte-derived dendritic cells and subsequent Th17 response.

North Clin Istanb 2019 24;6(4):379-387. Epub 2019 Oct 24.

Department of Medical Biology, Erciyes University Faculty of Medicine, Betül-Ziya Eren Genome and Stem Cell Center (GENKOK), Kayseri, Turkey.

Objective: In this study, we aimed to assess the effects of long- and short-term IL-15 cytokine exposure of human monocyte-derived curdlan-matured dendritic cells (DCs) on the production of Th17 cell-polarizing cytokine IL-23 and subsequent Th17 cell activation.

Methods: Peripheral blood mononuclear cells (PBMCs) were purified using Ficoll-Paque from healthy donors. Monocytes were magnetically selected using CD14 Miltenyi beads and differentiated into DCs with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 for five days in the presence or absence of IL-15 (100ng/ml) for long-term exposure experiments. Then, DCs were matured with peptidoglycan (PGN), or curdlan for 24 hours. For short-term exposure experiments, IL-15 was added only during maturation of DCs. Then, DCs were characterized concerning the expression of MHC II and costimulatory molecules, production of cytokine subunits IL-23p19, IL-12p40, IL-12p35 and cytokine IL-23 via flow cytometry or real-time qPCR or ELISA. Finally, the phosphorylation of signaling molecules after curdlan stimulation was assessed using phospho-flow assays.

Results: IL-15 exposure suppressed IL-23 production by DCs. As a result, IL-15-exposed DCs suppressed IL-17 production by allogeneic T cells. Importantly, we observed a reduction in the surface Dectin-1 receptor levels by IL-15-exposed DCs. In line with these observations, curdlan stimulation resulted in reduced phosphorylation of ERK1/2, NF-kB p65 and AKT by human DCs exposed to IL-15 compared with controls. These results may explain why IL-15-exposed DCs produce less IL-23 after maturation with curdlan, which is a ligand of Dectin-1.

Conclusion: Short- or long-term exposure to IL-15 of human DCs during their differentiation or maturation programs DCs against Th17 cell polarization, which suggests that IL-15 availability may affect CD4+ T cell-mediated protective immunity to fungal infections.
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http://dx.doi.org/10.14744/nci.2019.38802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936942PMC
October 2019

Correction to: Long-term follow-up of a large cohort with focal epilepsy of unknown cause: deciphering their clinical and prognostic characteristics.

J Neurol 2020 Mar;267(3):848

Departments of Neurology and Clinical Neurophysiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

The original version of this article unfortunately contained a mistake.
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http://dx.doi.org/10.1007/s00415-019-09675-5DOI Listing
March 2020

Reflex epileptic features in patients with focal epilepsy of unknown cause.

Clin Neurol Neurosurg 2020 03 9;190:105633. Epub 2019 Dec 9.

Istanbul University, Istanbul Faculty of Medicine, Departments of Neurology and Clinical Neurophysiology Unit, Istanbul, Turkey.

Objectives: There is a gap of knowledge regarding reflex seizures in patients with focal epilepsy of unknown cause (FEUC). We aimed to evaluate the prevalence, demographic and clinical characteristics of reflex seizures in patients with FEUC to provide an insight to the underlying ictogenic mechanisms and to draw attention to this important but under-investigated topic.

Patients And Methods: After carefully questioning for reflex triggers, 186 patients diagnosed according to ILAE criteria and followed-up for a minimum of 5 years were included. The demographic and clinical properties as well as electrophysiological and neuroimaging data of these patients were reevaluated and compared to the patients without reflex seizures.

Results: The reflex seizure rate was 6.5 % in patients with FEUC. Patients with reflex features had lower monotherapy rates (p = 0.005) and higher major depression rates (p = 0.001) than patients without reflex features. The distribution of the patients according to their reflex triggers were as follows: hot-water induced (n = 3, 25 %), photosensitive (n = 2, 16.7 %), eating- induced (n = 2, 16.7 %), musicogenic (n = 2, 16.7 %), startle induced (n = 2, 16.7 %) and both musicogenic and startle type (n = 1, 8.3 %) respectively. The drug resistance rate of patients with reflex seizures was 25 % (n = 3). One patient with drug resistant reflex seizures showed benefit from epilepsy surgery and became seizure-free during last 3 years of follow-up.

Conclusion: A careful and thoroughly history taking specifically questioning and focusing on seizure inducing factors in patients with FEUC is needed to confirm the presence of reflex seizures in patients with FEUC, who had higher rates of polytherapy and major depression. Elaborative evaluation of reflex features in FEUC might contribute to effective seizure control, ensure new therapeutic approaches, enlighten the obscurity and the resulting anxiety of having a diagnosis of FEUC in epilepsy patients.
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http://dx.doi.org/10.1016/j.clineuro.2019.105633DOI Listing
March 2020

Complementary and Alternative Medicine Methods Used Among Turkish Pediatric Oncology Patients.

J Pediatr Nurs 2020 May - Jun;52:e103-e107. Epub 2019 Dec 9.

Department of Pediatric Oncology, Faculty of Medicine, Erciyes University, Kayseri, Turkey.

Purpose: Complementary and alternative medicine (CAM) methods are gradually becoming common in pediatric oncology. The aim of this study was to determine the current use of CAM methods by Turkish mothers for their children with cancer.

Design And Methods: The sample for this descriptive and cross-sectional study consisted of the mothers (n = 110) of children with cancer undergoing treatment in a hematology-oncology clinic and outpatient clinic. The data were collected using a questionnaire that included the CAM methods used by mothers for their children with cancer.

Results: Of 110 children, 65 (59.1%) were diagnosed with leukemia and 107 (97.3%) underwent chemotherapy. More than half of the mothers (53.6%) were using CAM methods. The most common CAM method was the use of natural products (93.2%), of which the most frequently used were carob, mulberry, and grape molasses. Mothers used CAM to support the treatment of their children with cancer and alleviate the side effects of chemotherapy and, in most cases, without previously consulting healthcare professionals about their use.

Conclusions: This study revealed that most mothers used CAM methods for their children.

Practice Implications: It is important that healthcare professionals are aware about the use of CAM methods in children with cancer to prevent any possible negative interaction between conventional (i.e., chemotherapy) and alternative treatments.
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http://dx.doi.org/10.1016/j.pedn.2019.11.013DOI Listing
April 2021

Long-term follow-up of a large cohort with focal epilepsy of unknown cause: deciphering their clinical and prognostic characteristics.

J Neurol 2020 Mar 2;267(3):838-847. Epub 2019 Dec 2.

Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Background And Purpose: Focal epilepsy of unknown cause (FEUC) is an under-investigated topic despite its remarkable frequency. We aimed to report the long-term follow-up findings along with the drug-response, 5 year remission rates and diagnostic changes to give an insight about the heterogeneous characteristics of FEUC.

Methods: Demographic, clinical, neurophysiological and imaging data of 196 patients diagnosed as FEUC according to ILAE criteria, with a minimum 5-year follow-up were evaluated in a tertiary epilepsy center. The drug resistance, 5 years of remission and relapse rates were investigated and the subgroups were compared statistically.

Results: The rate of drug resistance was 21.8% and status epilepticus (p < 0.001), abnormal neurological examination (p = 0.020), seizure onset before 10 years (p = 0.004) and a high initial seizure frequency (p = 0.006) were significant predictors of drug resistance. The rates of terminal 5-year remission, 5-year remission ever and relapse were 39.9%, 44.26% and 24.04%, respectively. There were 13 patients (6.6%) with a changed final diagnosis. Drug resistance (p = 0.004), pathological EEG (p = 0.034) and status epilepticus (p = 0.021) were negative variables for achieving remission. The lobar localization of seizures was not a predictor of remission or relapse. Onset after 10 years of age had a higher probability of achieving a 5-year remission according to Kaplan-Meier curves (p < 0.001).

Conclusions: Focal epilepsy of unknown cause has a benign electroclinical subgroup with favorable long-term course, lower drug resistance and higher 5 years of terminal remission and remission ever rates, when appropriately treated. Our findings might be valuable in terms of counseling and management of patients with FEUC at the first referral to epilepsy clinics.
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http://dx.doi.org/10.1007/s00415-019-09656-8DOI Listing
March 2020

Twenty children with non-Wilms renal tumors from a reference center in Central Anatolia, Turkey

Turk J Med Sci 2020 02 13;50(1):18-24. Epub 2020 Feb 13.

Division of Pediatric Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Erciyes University, Kayseri, Turkey

Background/aim: Non-Wilms renal tumors (NWRTs) are rarely encountered in children. The aim of this study is to determine the treatment strategies, prognosis, outcomes, and survival of children with NWRTs at Erciyes University in Kayseri, Turkey.

Materials And Methods: Medical records of all patients (n = 20) treated for NWRTs over a 23-year period (1995–2018) were reviewed retrospectively.

Results: There was male predominance (female/male: 7/13); the median age at diagnosis was 3.2 years old (0.1–13.5 years old). The major histological groups included mesoblastic nephroma (MBN), (n: 5, 25%), malignant rhabdoid tumor (MRT), (n: 5, 25%), renal cell carcinoma, (n: 3, 15%), inflammatory myofibroblastic tumor (n: 2, 10%), multilocular cystic renal tumors (n: 2, 10%), metanephric adenoma (n: 1, 5%), renal neuroblastoma (n: 1, 5%), and bilateral renal Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) (n: 1, 5%). All of the patients with NWRTs had radical nephrectomy except the child with bilateral renal ES/PNET. Six children died because of progressive disease; the mortality rate was 30% (n: 6).

Conclusion: We have made the first report of bilateral renal involvement of ES/PNET in the English medical literature. Physicians dealing with pediatric renal masses should be alert to the high mortality rate in children with MRT, MBN, and ES/PNET and they should design substantial management plans for NWRTs.
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http://dx.doi.org/10.3906/sag-1902-106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080372PMC
February 2020

Different Clinical Presentation of 3 Children With Familial Hemophagocytic Lymphohistiocytosis With 2 Novel Mutations.

J Pediatr Hematol Oncol 2020 10;42(7):e627-e629

Department of Pediatrics, Division of Pediatric Hematology and Oncology & Pediatric HSCT Unit, Faculty of Medicine.

Although familial hemophagocytic lymphohistiocytosis (FHL) generally manifest with a combination of unremitting fever, hepatosplenomegaly, and pancytopenia; unusual presentations should also be taken into account. Herein, we present 3 FHL cases with 2 novel mutations with different initial presentations. The first patient bearing a homozygous truncation mutation in UNC13D (c.2650C>T.p.Gln884Ter) presented with central nervous system involvement and skin rash. The patient responded to the HLH-2004 protocol, and allogenic hematopoietic stem cell transplantation was performed from her healthy sister. The second and third patients with homozygous splice site mutation (c.430-1G>A) in STXBP2 were siblings who presented at birth with fevers, elevated aspartate aminotransferase, alanine aminotransferase, and hyperferritinemia but did not fulfill FHL criteria. The last 2 infants died despite intervention. Hematologists should be vigilant about the different presentation of FHL in children.
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http://dx.doi.org/10.1097/MPH.0000000000001589DOI Listing
October 2020

IgE and IgG4 binding to lentil epitopes in children with red and green lentil allergy.

Pediatr Allergy Immunol 2020 02 4;31(2):158-166. Epub 2019 Nov 4.

Division of Pediatric Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: The consumption of lentil is common in the Mediterranean area and is one of the causes of IgE-mediated food allergy in many countries. Len c 1 is a well-defined allergen of lentil and approximately 80% of the patients with lentil allergy recognize the purified Len c 1 protein. We sought to identify IgE and IgG4 sequential epitopes of Len c 1 in patients with red and/or green lentil allergy. We also aimed to determine IgE and IgG4 binding differences between those patients who had outgrown or remained reactive to lentil.

Methods: Children with IgE-mediated lentil allergy were included in the study. We applied a microarray immunoassay to determine the characterization of positive IgE and IgG4 binding to Len c 1 epitopes in the patients' sera.

Results: The peptides specifically recognized by IgE and IgG4 antibodies were mainly detected between peptides 107 and 135 of Len c 1. The signal intensities of positive epitopes were significantly greater in reactive patients than tolerant ones (P = .008 for IgE and P = .002 for IgG4). Moreover, IgE and IgG4 antibodies bound largely the same sequential epitopes in patients who remained reactive or outgrew their allergy.

Conclusion: IgG4-binding epitopes in lentil allergy were identified and IgE and IgG4 binding to epitopes in both red and green lentils was compared. Our data regarding signal intensity differences between reactive and outgrown patients and overlap binding of IgE and IgG4 antibodies may be important for the development of more accurate diagnostic tests and understanding of natural tolerance development.
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http://dx.doi.org/10.1111/pai.13136DOI Listing
February 2020

Indoxyl sulfate associates with cardiovascular phenotype in children with chronic kidney disease.

Pediatr Nephrol 2019 12 19;34(12):2571-2582. Epub 2019 Aug 19.

Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University Children's Hospital Heidelberg, Heidelberg, Germany.

Background: Cardiovascular disease is the leading cause of death in children with chronic kidney disease (CKD). Serum levels of gut-derived uremic toxins increase with deterioration of kidney function and are associated with cardiac comorbidities in adult CKD patients.

Methods: Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) were measured by high-performance liquid chromatography in serum of children participating in the Cardiovascular Comorbidity in Children with CKD (4C) Study. Results were correlated with measurements of the carotid intima-media thickness (cIMT), central pulse wave velocity (PWV), and left ventricular mass index (LVMI) in children aged 6-17 years with initial eGFR of 10-60 ml/min per 1.73 m.

Results: The median serum levels of total IS and of pCS, measured in 609 patients, were 5.3 μmol/l (8.7) and 17.0 μmol/l (21.6), respectively. In a multivariable regression model, IS and pCS showed significant positive associations with urea and negative associations with eGFR and uric acid. Furthermore, positive associations of pCS with age, serum albumin, and non-Mediterranean residency and a negative association with glomerular disease were observed. By multivariable regression analysis, only IS was significantly associated with a higher cIMT SDS at baseline and progression of PWV SDS within 12 months, independent of other risk factors.

Conclusions: Serum levels of gut-derived uremic toxins IS and pCS correlated inversely with eGFR in children. Only IS was significantly associated with surrogate markers of cardiovascular disease in this large pediatric CKD cohort.
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http://dx.doi.org/10.1007/s00467-019-04331-6DOI Listing
December 2019

Effects of dietary anthocyanin on innate immune parameters, gene expression responses, and ammonia resistance of Nile tilapia (Oreochromis niloticus).

Authors:
Ebru Yilmaz

Fish Shellfish Immunol 2019 Oct 14;93:694-701. Epub 2019 Aug 14.

Department of Aquaculture, Faculty of Agriculture, Aydın Adnan Menderes University, Aydın, Turkey. Electronic address:

The present study investigated the effects of dietary anthocyanin on the growth performance, haematological, non-specific immune, and spleen gene expression responses of Nile tilapia, Oreochromis niloticus. Five experimental groups of fish with mean weights of 8.24 ± 0.64 g were used in the study; four of these were fed with diets incorporating anthocyanin (20 mg kg -, 40 mg kg, 80 mg kg and 160 mg kg), while the fifth was a control group without dietary anthocyanin. Growth performance and haematological parameters of tilapia were not affected by anthocyanin-supplemented diets (p > 0.05). Dietary anthocyanin significantly increased respiratory burst activity, phagocytic activity, phagocytic index, lysozyme activity, myeloperoxidase activity, serum total superoxide dismutase (T.SOD) activity, and serum catalase (CAT) activity (p < 0.05). The total immunoglobulin level was highest in the 80 mg kg group compared with the other groups (p < 0.05). In addition, with the anthocyanin-containing diets, the gene levels of interleukin 1, beta (IL-1β), interleukin 8 (IL-8), tumor necrosis factor (TNF-α), heat shock protein 70 (HSP70), and interferon gamma (IFN-γ) were increased in the fish spleen, and the gene levels of CAT, GPx, and SOD were also increased in fish liver (p < 0.05). At the end of the experiment, the fish were subjected to ammonia stress. The groups fed with 20 and 40 mg kg anthocyanin exhibited higher survival rates than the other groups. In summary, feeding Nile tilapia with anthocyanin-containing diets caused increases in the innate immune parameters, gene expression responses, and the survival rate of the fish subjected to ammonia stress.
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http://dx.doi.org/10.1016/j.fsi.2019.08.033DOI Listing
October 2019

A Pediatric Case of Idiopathic Hypereosinophilia Preceeding Precursor B-cell Lymphoblastic Lymphoma of Nasopharynx.

J Pediatr Hematol Oncol 2020 04;42(3):248-249

Department of Pediatric Hematology and Oncology, Kanuni Sultan Suleyman Traning and Research Hospital.

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http://dx.doi.org/10.1097/MPH.0000000000001561DOI Listing
April 2020

Investigation of Generalized EEG Paroxysms Accompanying Focal Epilepsies.

Clin EEG Neurosci 2019 Nov 28;50(6):413-422. Epub 2019 Jun 28.

1 Istanbul University, Istanbul, Turkey.

Interictal focal EEG features were frequently observed in generalized, epilepsies, but there is limited information about interictal, epileptiform/nonepileptiform generalized paroxysms in focal epilepsies. We aimed to report the frequency and associated factors of generalized EEG discharges in focal epilepsy with unknown cause (FEUC) and mesial, temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). A total of 200 patients (FEUC in 90 patients; MTLE-HS in 110 patients) were included. Generalized epileptiform (spike/sharp waves simultaneously in all regions) and nonspecific generalized discharges (paroxysmal slow waves) were investigated. All clinical and laboratory findings of 2 groups were compared with each other and with remaining control group, without generalized paroxysms, statistically. Generalized EEG features were present in 22 (11%; 4 males) patients; 9 in the FEUC group (10%; 2) and 13 in the MTLE-HS group (11.8%). Female gender ( < .021), febrile seizure ( < .034), precipitant factors ( < .025), and parental consanguinity ( < .033) were significantly higher in the group with generalized EEG findings. Monotherapy rates were lower in the MTLE-HS group ( < .05). The relationship of generalized EEG features with female gender and parental consanguinity may point out to a genetic property among focal epilepsies, while the relationship with febrile seizures and precipitant factors may be a clue about mechanisms with more extensive involvement of the neuronal networks.
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http://dx.doi.org/10.1177/1550059419841837DOI Listing
November 2019

The evaluation of the effectiveness of intra-articular steroid, tenoxicam, and combined steroid-tenoxicam injections in the treatment of patients with knee osteoarthritis.

Authors:
Ebru Yilmaz

Clin Rheumatol 2019 Nov 26;38(11):3243-3252. Epub 2019 Jun 26.

Department of Physical and Rehabilitation Medicine, Kocaeli Government Hospital, Kocaeli, Turkey.

Objective: Although intra-articular corticosteroid injections are widely applied in the treatment of knee osteoarthritis (OA), its effect is short term. Additionally, apart from oral use, tenoxicam is also applied as an intra-articular treatment option to minimize gastrointestinal side effects of NSAIDs. Clinical evidence suggests that the combined use of NSAIDs and corticosteroids is synergistic (especially macular edema after cataract surgery in ophthalmology). Therefore, the aim of this study is to determine whether the combination of intra-articular steroid and tenoxicam was more effective for a long period rather than only tenoxicam and steroid injection alone in OA treatment.

Methods: Ninety patients were randomly divided into three groups (30 patients per group): group 1, group 2, and group 3 were treated by intra-articular injection of tenoxicam, triamcinolone hexacetonide, and triamcinolone hexacetonide plus tenoxicam, respectively. Visual analog scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were enrolled at baseline and 1, 3, and 6 months post-injection.

Results: The mean age of patients was 68.07 ± 8.08, 65.83 ± 10.13, and 67.07 ± 6.01 in group 1, group 2, and group 3, respectively. In tenoxicam group, median pre- and post-treatment (at 1, 3, and 6 months) VAS/WOMAC scores were 7.30 ± 0.53/32.50 ± 3.79, 2.27 ± 0.98/10.83 ± 2.61, 6.73 ± 1.14/30.33 ± 5.93, and 7.03 ± 0.80/31.37 ± 4.38, respectively. In steroid group, median pre- and post-treatment VAS/WOMAC scores were 7.60 ± 0.49/34.33 ± 3.40, 1.37 ± 1.21/8.83 ± 2.70, 6.87 ± 1.35/30.80 ± 7.70, and 7.27 ± 0.86/32.83 ± 4.87, respectively. In steroid plus tenoxicam group, median pre- and post-treatment VAS/WOMAC scores were 7.57 ± 0.50/33.20 ± 3.66, 0.33 ± 0.47/6.67 ± 0.95, 0.93 ± 0.98/7.87 ± 1.96, and 1.97 ± 1.12/10.43 ± 3.70, respectively. VAS and WOMAC scores in 1 month after the injection significantly decreased in both groups compared to baseline (p < 0.01). Steroid plus tenoxicam group showed significantly improved VAS and WOMAC scores when compared to only steroid and tenoxicam group at follow-up 3 and 6 months (p < 0.01).

Conclusion: The combined therapy seems to produce a more effective result for a long period than monotherapy in reducing pain and improving functional recovery.

Key Points: • There is an evidence of short-term effects of intra-articular corticosteroid injection in treatment of knee OA; however, there is no consensus for the long-term benefit of this treatment yet. • Apart from oral use, tenoxicam is also applied as an intra-articular treatment option to minimize gastrointestinal side effects of NSAIDs. • Clinical evidence suggests that the combined use of NSAIDs and corticosteroids is synergistic (especially macular edema after cataract surgery in ophthalmology). • The combined therapy seems to produce a more effective result for a long period than alone therapy.
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http://dx.doi.org/10.1007/s10067-019-04641-yDOI Listing
November 2019

A Rare Case of Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS) Presenting With Hemophagocytosis Complicated With Hodgkin Lymphoma.

J Pediatr Hematol Oncol 2020 03;42(2):156-159

Department of Pediatrics, Division of Pediatric Immunology.

Gain of function mutations in the p110δ catalytic subunit of the phosphatidylinositol-3-OH kinase (PIK3CD) classified as activated phosphoinositide 3-kinase delta syndrome (APDS) are the cause of a primary immunodeficiency characterized by recurrent sinopulmonary infections, and lymphoproliferation. Previously, autoimmunity and Epstein-Barr virus-related B-cell lymphoma have been documented for patients with APDS; here, we present a case that extends the picture, as the patient shows the full diagnostic criteria of hemophagocytic lymphohistiocytosis at 6 months of age. He experienced Hodgkin lymphoma as a 2.5-year-old baby. Next-generation sequencing returned a de novo heterozygous missense variant in PIK3CD (LRG_191t1: c.3061G>A; p.Glu1021Lys), confirming the primary immunodeficiency. After 2 courses of ifosfamide, cisplatin, and etoposide combined with brentuximab, the patient successfully underwent allogeneic hematopoietic stem cell transplantation from his HLA full matched sister, and he has been well for 18 months after that. The hematologist treating Hodgkin lymphoma and/or hemophagocytic lymphohistiocytosis should be vigilant about the possible underlying immune deficiency, and they should consider APDS in their differential diagnosis.
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http://dx.doi.org/10.1097/MPH.0000000000001487DOI Listing
March 2020