Efficacy and Reliability of T-Cell-Depleted Haploidentical Stem Cell Transplantation in Hematologic Disorders: A Retrospective Study.

BACKGROUND: A promising recent strategy for haploidentical transplantation is the depletion of T lymphocytes based on the selective elimination of T cells by manipulation, which enables a very low incidence of nonrelapse mortality and graft-vs-host disease. It is more expensive than conventional unmanipulated methods and requires dedicated transplant centers and sufficient stem cell processing facilities. This retrospective study aimed to evaluate the relapse, survival, and clinical data of the patients and to analyze the outcomes of the technique. METHODS: The study included 56 adult patients who underwent haploidentical stem cell transplantation via αß T-cell depletion. RESULTS: The median age of the patients at the time of hematopoietic stem cell transplantation was 41.5 years (range, 20-70 years); 22 patients (39.3%) were women. After the transplantation, half of the patients (50.0%) needed immunosuppressive drugs, and 17.9% of the patients experienced a post-transplant relapse. The mortality rate was 55.4%, and nonrelapse mortality was 25.0%. The 100-day mortality rate was 19.6%. The median overall days was 1101 days (142-3813 days), whereas the median progression-free overall was 302.5 days (11-2479 days). Being older (age >40), having hypertension, having acute liver graft-vs-host disease, and having systemic fungal infection were found as risk factors that significantly increased mortality (with 3.5-, 2.8-, 3.7-, and 2.7-fold increases, respectively). CONCLUSION: To conclude, T-cell-depleted hematopoietic stem cell transplantation is an effective and reliable technique that has the potential to decrease morbidity and improve relapse-free survival, especially for young patients requiring haploidentical donor transplantation for hematologic malignancy.

In Silico Analysis of a De Novo OTC Variant as a Cause of Ornithine Transcarbamylase Deficiency.

Ornithine transcarbamylase deficiency (OTCD) is the most common X-linked hereditary disorder of urea cycle disorders that is caused by neonatal hyperammonemia. OTC gene sequence variations are common causes of OTCD. The current study presents a 28-month-old baby girl proband with phenotypical characteristics of OTCD such as irritability, somnolence, intermittent vomiting, and high levels of serum ammonium. Whole-exome sequencing revealed a de novo c.275G>A p.(Arg92Gln) variant within the OTC gene. In silico analysis revealed a possible differential affinity between wild-type and mutant OTCase, while Arg92Gln decreases the binding ability of OTCase to the substrate, which can disrupt the urea cycle and explains the molecular pathogenicity of clinical hyperammonemia. In light of the fact that the genotype and phenotype correlation of OTCD is still uncertain, the present in silico analysis outcome can enhance our knowledge on this complicated, rare, and severe genetic disorder.

The Effect of Gene Mutations on Metastasis and Overall Survival in Metastatic and Nonmetastatic Colon Cancers.

OBJECTIVE: It is known that many genes are associated with colon cancer. We aimed to investigate the effect of gene mutations on metastasis and overall survival in metastatic and non metastatic colon cancers. METHODS: A total of 50 patients with metastatic (n=25) and non metastatic (n=25) diagnosed with colon cancer between 2010 and 2018 were included in the study. APC, MUTYH, RAD50, MEN1, ATM, PALB2, NSH2, BRCA1, BRCA2, MLH1, BRIP1, TP53, PTEN, BARD1, MSH6, PMS2, NBN, and FAM175A gene mutations were evaluated using the next generation sequencing method. The effect of gene mutations on metastasis and overall survival were evaluated. RESULTS: The mean age of patients with colon cancer without distant metastasis was 48.64±14.72 years and for patients with distance metases was 56.68±11.65. The mean survival time of colon cancer patients with distant organ metastasis after the metastasis date was 104.36±58.59 weeks. The presence of APC, MUTYH, and TP53 genetic mutations was observed with a higher rate in metastatic colon cancer (p<0.05). CONCLUSION: We showed that APC, MUTYH, and TP53 mutations are associated with distant organ metastasis.

The tendency of reduced periodontal destruction in acromegalic patients showing similar inflammatory status with periodontitis patients.

PURPOSE: Evaluate periodontal status of acromegalics through clinical and biochemical variables. METHODS: Demographics, hormone and metabolic variables, periodontal variables, gingival crevicular fluid (GCF) volume, and content data were collected from 30 patients with acromegaly, 30 patients with periodontitis, and 20 healthy subjects and comparatively analyzed. RESULTS: GH differences between acromegaly (2.56 ± 4.86) and periodontitis (0.53 ± 0.95) (p < 0.001) were statistically significant. IGF-1 was lowest at periodontitis (113.31 ± 45.01) and lower (152.11 ± 45.56) at healthy group compared with acromegalics (220.38 ± 167.62) (p < 0.05). GH and IGF-1 had positive correlation (p < 0.05). IGF-1 and CAL had negative (p < 0.01) correlation except healthy group that showed the same correlation at the opposite direction (p < 0.05). Besides similar plaque and gingival indices with periodontitis, acromegalics showed relatively less CAL and GCF volume but except CAL, all their periodontal variables were higher than healthy subjects. GCF GH and prolactin showed higher values in acromegalics while healthy subjects showed relatively high interleukin-1, -10 and carboxyterminal telopeptide of type I collagen compared with others. CONCLUSION: Acromegalics have a tendency of slowed periodontal destruction with an influence of GH and IGF-1 to the inflammation- and collage metabolism-related mechanisms rather than bone-associated ones. However, this information must be confirmed with further studies exploring the mechanisms possibly bonded to others.

An adolescent case of extensive Behçet`s disease successfully treated with Infliximab.

Isiyel E, Bakkaloglu S, Oguz D, Yenicesu I, Boyunaga Ö, Özdemir Y, Damar Ç, Kandur Y, Akçaboy M, Aslan AT, Sismanlar T, Hasanoglan E, Buyan N. An adolescent case of extensive Behçet`s disease successfully treated with Infliximab. Turk J Pediatr 2019; 61: 585-588. Cardiac involvement is an uncommon and life-threatening complication of Behçet`s Disease. We present a 14-year-old boy, admitted to our hospital for recurrent hemoptysis. In his radiologic evaluation, a right ventricular thrombus and pulmonary arterial aneurysm were identified. He was diagnosed with Behçet`s Disease, and then he received prednisone and cyclophosphamide. However, his cardiac thrombus enlargened. After his treatment was replaced with infliximab, the pulmonary aneurysms regressed, and the cardiac thrombus disappeared. In conclusion, infliximab should be considered as a reliable option for vascular Behçet`s Disease resistant to conventional treatment.

Isolated acute lupus pneumonitis as the initial presentation of systemic lupus erythematosus in an 8-year-old girl.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease which has broad pleuropulmonary manifestations. One of the rare and mortal complications is acute lupus pneumonitis, which is reported very rarely, especially in childhood. Herein, we report an 8-year-old girl with isolated acute lupus pneumonitis as the initial presentation that required a lung biopsy for diagnosis. Although she had improvement with the administration of steroids, steroid treatment was reduced due to the drug's side effects resulting in the addition of azathioprine and mycophenolate mofetil to the treatment regimen. After the new regimen failed to result in clinical improvement, hydroxychloroquine treatment was started and a significant improvement was observed. Acute lupus pneumonitis is an uncommon manifestation of SLE and diagnosis may be difficult in patients without other organ involvement.

Oxygen plasma modification of polyurethane membranes.

Polyurethane membranes were prepared under nitrogen atmosphere by using various proportions of toluene diisocyanates (TDI) and polypropylene-ethylene glycol (P) with addition of no other ingredients such as catalysts, initiator or solvent in order to achieve medical purity. Effects of composition on mechanical properties were examined. In general, modulus and UTS values demonstrated an increase and PSBR demonstrated a decrease as the TDI/Polyol ratio of the polymer increased. Elastic modulus, ultimate tensile strength (UTS) and per cent strain before rupture (PSBR) values were found to be in the range of 1.4-5.4 MPa, 0.9-1.9 MPa, and 60.4-99.7%, respectively. Surfaces of the membranes were modified by oxygen plasma applying glow-discharge technique and the effect of applied plasma power (10 W or 100 W, 15 min) on surface hydrophilicity and on the attachment of Vero cells were studied. Water contact angle values of the plasma modified surfaces varied between 67 degrees and 46 degrees, demonstrating a decrease as the applied plasma power was increased. The unmodified material had 42-45 cells attached per cm(2). It was observed that as the applied power increased the number of attached cells first increased (60-70 cells/cm(2) at 10 W) and then decreased (27-40 cells/cm(2) at 100 W). These demonstrated that surface properties of polyurethanes can be modified by plasma-glow discharge technique to achieve the optimum levels of cell attachment.