Randomized controlled trial of 8 weeks' vs 12 weeks' interval between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer.

AIM: The aim was to compare the pathological complete response (pCR) rate at 8 compared to 12 weeks' interval between completion of neoadjuvant chemoradiotherapy (CRT) and surgery in patients with locally advanced rectal cancer. METHOD: This was a randomized trial which included a total of 330 patients from two institutions. Patients with locally advanced (T3-4N0M0, TxN+M0) rectal cancer were randomized into 8- and 12-week interval groups. All the patients received long-course CRT (45 Gy in 1.8 Gy fractions and concomitant oral capecitabine or 5-fluorouracil infusion). Surgery was performed at either 8 or 12 weeks after CRT. The primary end-point was pCR. Secondary end-points were sphincter preservation, postoperative morbidity and mortality. RESULTS: Two-hundred and fifty-two patients (n = 125 in the 8-week group, n = 127 in the 12-week group) were included. Demographic and clinical characteristics were similar between groups. The overall pCR rate was 17.9% (n = 45): 12% (n = 15) in the 8-week group and 23.6% (n = 30) in the 12-week group (P = 0.021). Sphincter-preserving surgery was performed in 107 (85.6%) patients which was significantly higher than the 94 (74%) patients in the 12-week group (P = 0.016). Postoperative mortality was seen in three (1.2%) patients overall and was not different between groups (1.6% in 8 weeks vs 0.8% in 12 weeks, P = 0.494). Groups were similar in anastomotic leak (10.8% in 8 weeks vs 4.5% in 12 weeks, P = 0.088) and morbidity (30.4% in 8 weeks and 20.1% in 12 weeks, P = 0.083). CONCLUSION: Extending the interval between CRT and surgery from 8 to 12 weeks resulted in a 2-fold increase in pCR rate without any difference in mortality and morbidity.

First report of carglumic acid in a patient with citrullinemia type 1 (argininosuccinate synthetase deficiency).

WHAT IS KNOWN AND OBJECTIVE: Carglumic acid is a structural analogue of human N-acetylglutamate, which has become an alternative therapeutic option for hyperammonaemia in organic acidaemias such as isovaleric acidaemia, methylmalonic acidaemia and propionic acidaemia, and it has been suggested in other urea cycle disorders such as ornithine transcarbamylase deficiency and carbamoyl phosphate synthetase 1 deficiency. CASE DESCRIPTION: A male newborn was diagnosed with citrullinemia after serum amino acid analyses revealed markedly elevated citrulline concentration together with homozygous p.Gly390Arg mutation in ASS1 gene. The ammonia concentration decreased and blood gas analysis normalized after peritoneal dialysis was performed for three days. Also, sodium benzoate, L-arginine and parenteral nutrition with glucose and lipid therapy were initiated. Until 1 year of age, low adherence to sodium benzoate therapy due to unpleasant taste caused hyperammonaemic episodes and obligated us to initiate carglumic acid (100 mg/kg/day) therapy. During treatment with carglumic acid, the median ammonia level was 45.6 µmol/L. The patient's treatment was switched from carglumic acid to sodium phenylbutyrate when he was 4.5 years old. Currently, the patient is 6.5 years old and remains under follow-up with sodium phenylbutyrate, L-arginine and protein-restricted diet. Plasma ornithine level was found to be significantly lower during the carglumic acid treatment compared to other treatments (P=.039). Also, glutamic acid was found to be higher during the sodium benzoate treatment period compared to other treatment periods (P=.024). WHAT IS NEW AND CONCLUSION: To the best of our knowledge, this is the first report describing the long-term use of carglumic acid in a patient with argininosuccinate synthetase deficiency.

Functionalized imidazolium and benzimidazolium salts as paraoxonase 1 inhibitors: Synthesis, characterization and molecular docking studies.

Paraoxonase (PON) is a key enzyme in metabolism of living organisms and decreased activity of PON1 was acknowledged as a risk for atherosclerosis and organophosphate toxicity. The present study describes the synthesis, characterization, PON1 inhibitory properties and molecular docking studies of functionalized imidazolium and benzimidazolium salts (1a-5g). The structures of all compounds were elucidated by IR, NMR, elemental analysis and structures of compounds 2b and 2c were characterized by single-crystal X-ray diffraction. Compound 1c, a coumarin substituted imidazolium salt showed the best inhibitory effect on the activity of PON1 with good IC50 value (6.37 µM). Kinetic investigation was evaluated for this compound and results showed that this compound is competitive inhibitor of PON1 with Ki value of 2.39 µM. Molecular docking studies were also performed for most active compound 1c and one of least active compound 2c in order to determine the probable binding model into active site of PON1 and validation of the experimental results.

Evaluation of the intraocular pressure in obese adolescents.

AIM: The aim of this study was to evaluate the intraocular pressure (IOP) levels of children with normal and high Body Mass Index (BMI) and to find out the potential correlation between glaucoma and obesity. METHODS: Thirty obese and thirty healty children were enrolled in this study. Physical examinations and anthropometric measurements of all patients and controls were performed. Obesity was defined as a BMI exceeding the 95th percentile for the patients according to age and sex. All participants were underwent a complete eye examination. The results of these measurements were considered for statistical analysis. RESULTS: Mean age was 13.5±2.1 years in obese group and 13.3±2.0 years in control group. Mean BMIs were 28.1±3.9 kg/m2 and 19.7±1.2 kg/m2 in obese and control groups, respectively. No significant difference was found in mean IOP levels of both right and left eyes between two groups (P=0.837 and P=0.755, respectively). There was no significant difference in cup/disc ratios of each eyes and mean central corneal thickness of both right and left eyes between obese patients and controls. In visual field analysis, no statistically significant difference in mean false negativeness and mean false positiveness were found between two groups. There were not also any significant correlations in both mean deviation of each eyes (P=0.78 and P=0.94, respectively) and pattern standart deviation of right and left eyes (P=0.89 and P=0.90, respectively) between obese cases and controls. CONCLUSION: In this study, there were no significant difference in IOP measurements, central corneal thicknesses, cup/disc ratios and visual field parameters between obese and normal children. No significant correlation was found between obesity and glaucoma or elevated IOP in children.

Cytoreductive surgery (SRC) and hyperthermic intraperitoneal chemotherapy (HIPEC) for treatment of peritoneal carcinomatosis: Our initial experience and technical details.

OBJECTIVE: The aim of this study is to present our initial experience in peritoneal carcinomatosis treatment and the technical details of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the light of current literature. MATERIAL AND METHODS: Data of 27 consecutive patients who were treated with CRS and HIPEC for peritoneal carcinomatosis in Medical Park Samsun Hospital, between November 2012 and September 2014 were retrospectively reviewed. Treatment indication and management were evaluated at the multidisciplinary oncology council. All patients underwent CRS and HIPEC with the aim of complete cytoreduction. Patients with unresectable disease and/or palliative surgery were excluded from analysis. Perioperative complications were classified according to Clavien-Dindo classification, and HIPEC-related side effects were identified using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) criteria. Demographic, clinical and histopathological data of the patients were analyzed. RESULTS: The mean age was 54 (32-72). Nineteen patients were female. The origin of peritoneal carcinomatosis was colorectal cancer in 12 patients, ovarian cancer in 12 patients, gastric cancer in 2 patients and pseudomyxoma peritonei in 1 patient. The mean Peritoneal Carcinomatosis Index was 12 (3-32), with a mean operative time of 420 (300-660) minutes. Perioperative morbidity, HIPEC-related toxicity and perioperative mortality were observed in eight (30%), one (3.7%) and four patients (14.8%), respectively. During a mean follow up of 13 (1-22) months, overall and disease-free survival rates were 95.8% and 82.6%, respectively. Two patients with colorectal cancer (after 9 and 12 months) and one patient with ovarian cancer (after 11 months) had intra-abdominal recurrence. One patient with ovarian cancer had liver metastases 13 months after surgery, and underwent resection of segments 6-7. The remaining patients are being followed-up without any recurrence. CONCLUSION: Cytoreductive surgery and HIPEC have favorable results in the treatment of patients with peritoneal carcinomatosis. Compatible with the literature, surgical outcomes of the presented series are encouraging for this treatment modality that have been recently popularized in our country. Careful perioperative evaluation, proper patient selection and multidisciplinary approach are essential for success in curative treatment of peritoneal carcinomatosis.

The prognostic impact of the log odds of positive lymph nodes in colon cancer.

AIM: This study aimed to investigate the prognostic impact of the log odds of positive lymph nodes (LODDS) in colon cancer. METHOD: Four hundred and forty patients with colon cancer were divided into three each groups according to their lymph node ratio (LNR) and LODDS. Survival analysis was performed. RESULTS: The 5-year overall survival (OS) rate was 70.2%. In univariate analysis age, pT and pN stage, tumour grade, lymphatic, venous and perineural invasion, surgical margin clearance, LNR and LODDS were significantly associated with OS. In multivariate analysis age, surgical margins, perineural invasion and LODDS were found to be independent prognostic factors. In subgroup analysis of patients with an inadequate number of examined lymph nodes (NELN) (n = 76) and node-negative patients (n = 210), LODDS retained its prognostic value, whereas the impact of LNR was not statistically significant (P = 0.063). The overall survival rates of node-negative patients in the LODDS groups 0, 1 and 2 were 81%, 74.2% and 50%, respectively (P = 0.020). LNR and LODDS classifications were both significantly associated with survival in Stage III colon cancer, but only LODDS was an independent prognostic factor. CONCLUSION: Conventional TNM staging for nodes (pN) and LNR status cannot reliably classify node-negative patients into homogeneous groups. LODDS provides more valuable information than LNR independently of the NELN.

Evaluation of serum xenin and ghrelin levels and their relationship with nonalcoholic fatty liver disease and insulin resistance in obese adolescents.

AIM: Xenin is a peptide of the neurotensin/xenopsin/xenin family secreted from gastric cells and other tissues. The first aim of this study was to investigate the serum xenin and ghrelin levels in obese children and compare the patients with healthy controls. The second aim was to compare the xenin levels in patients with nonalcoholic fatty liver disease (NAFLD) and also with insulin resistance with the patients without these complications. METHODS: 62 obese adolescents (27 with NAFLD) and 32 healthy controls were enrolled in the study. Obesity was defined as a body mass index exceeding the 95th percentile for the patients' age and sex. NAFLD was diagnosed via ultrasonographic examination. The insulin resistance was calculated by a homeostasis model assessment (HOMA-IR) index. Serum xenin and ghrelin levels were assessed by enzyme-linked immunosorbent assay. RESULTS: The mean serum xenin concentration was significantly higher in obese adolescents than the healthy peers (68.15 ± 0.63 vs 16.54 ± 0.07 pg/mL, p = 0.000). Serum xenin levels were not different between the patients with and without NAFLD and also between the patients with and without IR (p > 0.05). There was a positive correlation between xenin levels and relative weight (r = 0.663, p < 0.001) and HOMA-IR (r = 0.612, p < 0.001). Ghrelin was negatively correlated with relative weight (r = -0.283, p < 0.05). CONCLUSION: In this study, serum xenin levels of both groups of obese patients were found higher than controls. On the other hand, xenin levels were not different in patients with and without NAFLD. High levels of xenin may be in relation with obesity.

Case report: Pai syndrome with multiple ventricular septal defect and without cleft palate.

Pai syndrome is described as the association of a midline cleft lip, midline facial polyps, and lipoma of the central nervous system. However, only a few patients present the full triad, and most exhibit a wide spectrum of phenotypic variability. Its entire clinical spectrum is still poorly delineated and the etiology remains unknown. In this report, a newborn was presented with congenital nasal septal lipoma, lipoma of the corpus callosum, multiple ventricular septal defect, and additional minor facial dysmorphism. This entity, multiple ventricular septal defect, which has never been reported in PS. Cytogenetic analysis showed normal male 46, XY karyotype. Chromosomal microarray analysis (750 K array) was also unremarkable. This case draws attention with the presence of multiple ventricular septal defect in Pai syndrome and is important in terms of providing phenotypic diversity. To our knowledge, this is also the first genetically evaluated case of Pai syndrome from Turkey.

Identification of seven novel SMPD1 mutations causing Niemann-Pick disease types A and B.

Niemann-Pick disease (NPD) types A and B are autosomal, recessively inherited, lysosomal storage disorders caused by deficient activity of acid sphingomyelinase (E.C. 3.1.4.12) because of mutations in the sphingomyelin phosphodiesterase-1 (SMPD1) gene. Here, we present the molecular analysis and clinical characteristics of 15 NPD type A and B patients. Sequencing the SMDP1 gene revealed eight previously described mutations and seven novel mutations including four missense [c.682T>C (p.Cys228Arg), c.1159T>C (p.Cys387Arg), c.1474G>A (p.Gly492Ser), and c.1795C>T (p.Leu599Phe)], one frameshift [c.169delG (p.Ala57Leufs*20)] and two splicing (c.316+1G>T and c.1341delG). The most frequent mutations were p.Arg610del (21%) and p.Gly247Ser (12%). Two patients homozygous for p.Arg610del and initially classified as phenotype B showed different clinical manifestations. Patients homozygous for p.Leu599Phe had phenotype B, and those homozygous for c.1341delG or c.316+1G>T presented phenotype A. The present results provide new insight into genotype/phenotype correlations in NPD and emphasize the difficulty of classifying patients into types A and B, supporting the idea of a continuum between these two classic phenotypes.

Association of cardiometabolic risks with body composition in hemodialysis patients.

OBJECTIVE: High body fat ratio is known as one of the main reasons that increase the risk of cardiovascular disease. This study examined the relationship between body composition and cardiometabolic risks in hemodialysis (HD) patients. PATIENTS AND METHODS: This study was conducted with chronic kidney disease (CKD) patients who received HD treatment between March 2020 and September 2021. Anthropometric measurements of the individuals and their body composition analyses were performed using the bioelectrical impedance analysis (BIA) method. Framingham risk scores were calculated in order to determine the cardiometabolic risk factors of individuals. RESULTS: According to the Framingham risk score, 15.96% of individuals were found to have a high cardiometabolic risk. The lean-fat tissue index (LTI)/(FTI), body shape index (BSI) and visceral adiposity index (VAI) (female-male) values of individuals with high risk according to the Framingham risk score were found to be 11.34±2.29, 13.52±2.88, 8.50±3.89, 9.60±3.07, 0.086±0.024, respectively. The effect of anthropometric measurements in estimating the Framingham risk score was examined using the linear regression analysis. The regression analysis performed with BMI, LTI, VAI values, it was determined that 1-unit increase in VAI increased the Framingham risk score by 1,468 units (OR: 0.951-1.952) (p=0.002). CONCLUSIONS: It has been discovered that indices indicating adipose tissue increase the Framingham risk score in HD patients, independent of BMI. It is recommended to evaluate the ratios showing body fat ratio in cardiovascular diseases.

Multiple factors influencing mortality in hemodialysis patients.

OBJECTIVE: Both decreased food intake and elevated inflammation contribute to malnutrition in hemodialysis (HD) patients. Malnutrition, inflammation, anthropometric measurements, and other comorbidity factors were investigated in this study as potential indicators of mortality in HD patients. PATIENTS AND METHODS: By measuring geriatric nutritional risk index (GNRI), malnutrition inflammation score (MIS), and prognostic nutritional index (PNI), 334 HD patients' nutritional status was assessed. Through the use of four different models and logistic regression analysis, the predictors of each individual's survival status were examined. The models were matched using the Hosmer-Lemeshow test. On the survival of patients, the effects of malnutrition indices in Model 1, anthropometric measurements in Model 2, blood parameters in Model 3, and sociodemographic characteristics in Model 4 were investigated. RESULTS: Five years later, 286 individuals were still on hemodialysis. Patients who had a high GNRI value had a lower mortality rate in Model 1. The body mass index (BMI) value of the patients was found to be the best predictor of mortality in Model 2, and it was found that patients with high muscle percentage had a lower mortality risk. The difference in urea level measured at the beginning and end of hemodialysis was found to be the most potent predictor of mortality in Model 3, although C-reactive protein (CRP) level was also discovered to be one of the best predictors for this model. The final model, Model 4, revealed that mortality was lower in women than in men and that income status was a reliable predictor of mortality estimation. CONCLUSIONS: The best indicator of mortality in hemodialysis patients is the malnutrition index.

Effects of infliximab against carbon tetrachloride-induced spleen toxicity in rats.

OBJECTIVE: Carbon tetrachloride (CCl4) is a non-polar molecule used in industry in grain curing, insect-killing and especially in the production of chlorofluorocarbons. It is estimated that an average of 70,000 industry workers in Europe are exposed to this toxic compound. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley rats were randomly allocated into four groups: control group (saline only, Group I), infliximab (INF) group (Group II), CCl4 group (Group III) and CCl4+INF group (Group IV). RESULTS: While there was an increase in the numerical density of CD3, CD68, and CD200R positive T lymphocytes and macrophages in the CCl4 administration group (p=0.000), this was not the case in the CCl4+INF administration group (p=0.000). CONCLUSIONS: TNF-α inhibitors have a protective effect against CCl4-induced spleen toxicity/inflammation as seen by the reduction in CD3, CD68, CD200R positive T lymphocytes and macrophages.

(E,E)-N'-{4-[(2-Benzoyl-hydrazin-1-yl-idene)meth-yl]benzyl-idene}benzo-hydrazide.

In the title compound, C(22)H(18)N(4)O(2), the mol-ecules lie across an inversion centre. The dihedral angle between the mean planes of the central and terminal benzene rings is 66.03 (2)°. The mol-ecule displays trans and anti conformations about the C=N and N-N bonds, respectively. In the crystal, N-H⋯O hydrogen bonds, with the O atoms of C=O groups acting as acceptors, link the mol-ecules into a chain along [101].

(E)-4-Hy-droxy-N'-(2-hy-droxy-5-iodo-benzyl-idene)benzohydrazide methanol monosolvate.

In the title compound, C(14)H(11)IN(2)O(3)·CH(4)O, the dihedral angle between the benzene rings is 33.2 (3)°. The mol-ecule displays trans and anti conformations about the C=N and N-N bonds, respectively. There is an intra-molecular O-H⋯N(azomethine) hydrogen bond. Inter-molecular N-H⋯O and O-H⋯O hydrogen bonds consolidate mol-ecules into a three-dimensional architecture.

3-Amino-4-[4-(dimethyl-amino)-phen-yl]-4,5-dihydro-1,2,5-thia-diazole 1,1-dioxide.

The title compound, C(10)H(14)N(4)O(2)S, exists in the amine tautomeric form. The dihedral angle between the benzene and thia-diazo-lidine rings is 66.54 (19)°. In the crystal, mol-ecules are linked by N-H⋯O and N-H⋯N hydrogen bonds into a layer parallel to the ac plane. The layers are further linked by C-H⋯O hydrogen bonds.

(E)-N'-(2-Hy-droxy-benzyl-idene)furan-2-carbohydrazide.

In the title compound, C(12)H(10)N(2)O(3), the dihedral angle between the benzene ring and the furan ring is 16.12 (13)°. The conformation is stabilized by an intra-molecular O-H⋯N hydrogen bond. Inter-molecular N-H⋯O hydrogen bonds with the keto group as acceptor lead to strands along [001]. The mol-ecule displays a trans configuration with respect to the C=N and N-N bonds.

Different patterns of hepatocellular carcinoma-related malign thrombosis in 18F-FDG PET/CT. / Los principales patrones de la trombosis maligna relacionada con el carcinoma hepatocelular en la 18F-FDG PET/TC.

Tumor thrombus is an intravascular malign tumor extension that may occur in various types of cancer. Hepatocellular carcinomas (HCC) are common causes of malign thrombus. The presence of a malign thrombus due to HCC has a dismal prognosis, which affects treatment choices. We present three cases of tumor thrombi due to advanced HCC detected by 18F-FDG PET/CT.

Health-related quality of life of school-age children with familial Mediterranean fever.

OBJECTIVES: To describe and compare the parent proxy-reported and child self-reported physical and psychosocial HRQOL of school age children who have FMF with healthy peers. METHODS: The Pediatric Quality of Life Inventory 4.0 (Peds QL 4.0) Generic Core Scales was used to measure HR-QOL. Fifty-one patients and 81 healthy peers were enrolled in the study. Patients were grouped according to their ages as : 1) Children (8-12 years) and 2) Adolescents (13-18 years). An accompanying parent completed the parent proxy-report of the Peds QL 4.0. RESULTS: Peds QL scores of children (8-12 years) with FMF were significantly lower than healthy peers for physical and psychosocial functioning for both child self-report and parent proxy-report. The parent proxy-report and child self-reported Peds QL scores of adolescent patients (13-18 years) with FMF were lower than the healthy group for physical, emotional and school functioning; however no significant difference was detected regarding the social functioning. Adolescents with FMF had significantly higher social scores when compared to the younger age group (8-12 years) with FMF, 92.6 +/- 8.5 and 82.2 +/- 17.6, respectively (p=0.028). The scores of physical, emotional and school functioning were similar in both groups (p=0.73, p=0.93, and p=0.028). Correlations among child self-report subscales and proxy-report subscales were all significant and varied from moderate to high. CONCLUSION: This study suggested that assessment of HRQOL has potential clinical implications for the healthcare needs of children and adolescents with FMF. Given the degree of reported impairment in their health-related quality of life, individualized counseling and interventions are needed.

1-(4-Chloro-3-fluoro-phen-yl)-2-[(3-phenyl-isoquinolin-1-yl)sulfan-yl]ethanone.

In the title compound, C(23)H(15)ClFNOS, the isoquinoline system and the 4-chloro-3-fluoro-phenyl ring are aligned at 80.4 (1)°. The dihedral angle between the isoquinoline system and the pendant (unsubstituted) phenyl ring is 19.91 (1)°.

Weaning practices in phenylketonuria vary between health professionals in Europe.

BACKGROUND: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. METHODS: A cross sectional questionnaire (survey monkey®) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. RESULTS: Weaning started at 17-26 weeks in 85% (n = 81/95) of centres, >26 weeks in 12% (n = 11/95) and < 17 weeks in 3% (n = 3/95). Infant's showing an interest in solid foods, and their age, were important determinant factors influencing weaning commencement. 51% (n = 48/95) of centres introduced Phe containing foods at 17-26 weeks and 48% (n = 46/95) at >26 weeks. First solids were mainly low Phe vegetables (59%, n = 56/95) and fruit (34%, n = 32/95).A Phe exchange system to allocate dietary Phe was used by 52% (n = 49/95) of centres predominantly from Northern and Southern Europe and 48% (n = 46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods.A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n = 39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n = 35/95) at infant age > 1y mainly from Southern Europe. 53% (n = 50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. CONCLUSIONS: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.