Mid-term radiological results of intra-articular penetration of the screw used in scaphoid surgery.

Background and Aim: Headless cannulated compression screw is often used in scaphoid fracture and nonunion surgery. In the volar and dorsal surgical approach, when adequate fluoroscopic imaging is not performed, the screw may protrude beyond the scaphoid bone and penetrate into the joint. When the length of the screw is too long, and it is noticed intraoperatively, it is replaced with a shorter screw. However, there is no clear consensus in the literature about the way to be followed when screw penetration is noticed in the postoperative period. Materials and Methods: The cases in which cannulated screw penetrated the radioscaphoid, scapholunate, and scaphotrapeziotrapezoid joint on postoperative radiographs were included in this study. Sixteen patients (13 men and 3 women) were included. The mean postoperative follow up time was 35.1 months. There was scaphotrapeziotrapezoid joint penetration in seven cases, scapholunate joint penetration in two cases, and radioscaphoid joint penetration in seven cases. Results: Osteoarthritis developed in the scapholunate joint in two cases and in the radioscaphoid joint in two cases. Early revision surgery or waiting for the fracture to heal and removing the screw, or not performing secondary surgery are among the options. In this study, mid term radiological results of screws penetrating radioscaphoid, scapholunate, and scaphotrapeziotrapezoid joints were examined. It was observed that it may cause osteoarthritis development in radioscaphoid and scapholunate joints, but it did not cause osteoarthritis development in scaphotrapeziotrapezoid joint. Conclusion: In the early postoperative period, revision surgery is recommended to prevent the development of osteoarthritis of screws penetrating the radioscaphoid and scapholunate joint.

Defining tetrahydrobiopterin responsiveness in phenylketonuria: Survey results from 38 countries.

BACKGROUND: A subset of patients with phenylketonuria benefit from treatment with tetrahydrobiopterin (BH4), although there is no consensus on the definition of BH4 responsiveness. The aim of this study therefore was to gain insight into the definitions of long-term BH4 responsiveness being used around the world. METHODS: We performed a web-based survey targeting healthcare professionals involved in the treatment of PKU patients. Data were analysed according to geographical region (Europe, USA/Canada, other). RESULTS: We analysed 166 responses. Long-term BH4 responsiveness was commonly defined using natural protein tolerance (95.6%), improvement of metabolic control (73.5%) and increase in quality of life (48.2%). When a specific value for a reduction in phenylalanine concentrations was reported (n = 89), 30% and 20% were most frequently used as cut-off values (76% and 19% of respondents, respectively). When a specific relative increase in natural protein tolerance was used to define long-term BH4 responsiveness (n = 71), respondents most commonly reported cut-off values of 30% and 100% (28% of respondents in both cases). Respondents from USA/Canada (n = 50) generally used less strict cut-off values compared to Europe (n = 96). Furthermore, respondents working within the same center answered differently. CONCLUSION: The results of this study suggest a very heterogeneous situation on the topic of defining long-term BH4 responsiveness, not only at a worldwide level but also within centers. Developing a strong evidence- and consensus-based definition would improve the quality of BH4 treatment.

Prenatal Diagnosis of Organic Acidemias at a Tertiary Center.

The aim of this study was to share our experience in the prenatal diagnosis (PND) of organic acidemias (OAs) in our clinic. This study consisted of 10 cases in whom an invasive prenatal diagnostic test (IPNDT) was performed by a single physician for the PND of OAs. Median maternal age, parity, gestational week of IPNDT, prenatal test indications, OA types, method of IPNDT, IPNDT results and gestational outcomes were evaluated. Targeted mutation analysis was performed in fetal DNA for the specific mutations by using polymerase chain reaction (PCR) and direct Sanger sequencing. The diagnosis was confirmed by genetic targeted mutation analysis after birth. Median maternal age, parity and gestational week of IPNDT values were 30 (range 21-35), one (range 0-4) and 11.5 (range 11-17), respectively. Indications for IPNDT were mother being a carrier of the disease for one case (10.0%) and at least one child with OA in the family for nine cases (90.0%). Organic acidemia types investigated were maple syrup urine disease (MSUD), methylmalonic acidemia (MMA) and isovaleric acidemia (IVA) in five (50.0%), three (30.0%) and two (20.0%) patients, respectively. Chorion villus sampling (CVS) was done in seven (70.0%) patients and amniocentesis was performed in three (30.0%) patients. Eight fetuses (80.0%) were found to be healthy and two fetuses (20.0%) were found to be affected (one case with IVA and one case with MMA). The two pregnancies (20.0%) with affected fetuses were terminated. Prenatal diagnosis of OAs is critical. Appropriate prenatal counseling should be given to families with known risk factors.

An update on serine deficiency disorders.

Serine deficiency disorders are caused by a defect in one of the three synthesising enzymes of the L-serine biosynthesis pathway. Serine deficiency disorders give rise to a neurological phenotype with psychomotor retardation, microcephaly and seizures in newborns and children or progressive polyneuropathy in adult patients. There are three defects that cause serine deficiency of which 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency, the defect affecting the first step in the pathway, has been reported most frequently. The other two disorders in L-serine biosynthesis phosphoserine aminotransferase (PSAT) deficiency and phosphoserine phosphatase (PSP) deficiency have been reported only in a limited number of patients. The biochemical hallmarks of all three disorders are low concentrations of serine in cerebrospinal fluid and plasma. Prompt recognition of affected patients is important, since serine deficiency disorders are treatable causes of neurometabolic disorders. The use of age-related reference values for serine in CSF and plasma can be of great help in establishing a correct diagnosis of serine deficiency, in particular in newborns and young children.

Adipocytokine levels of colon cancer patients before and after treatment.

AIMS AND BACKGROUND: In the present study, we investigated the associations between pre- and post-treatment levels of adiponectin, ghrelin, resistin, visfatin and leptin levels in malign and benign groups. METHODS AND STUDY DESIGN: 20 malign colon carcinoma groups and 20 benign groups were included in this study. Serum levels of leptin, adiponectin, resistin, ghrelin, and visfatin were measured by Elisa kits (Milipore Corporation, Billerica, MA, USA). RESULTS: In the malign group, serum ghrelin (71.90±23.7) levels significantly decreased (p<0.05) when compared to those in the benign (88.00±16.9) group. However, serum resistin (4.92±2.2, 3.39±1.1) levels increased statistically significantly (p<0.05). In the malign group, serum visfatin (0.85±0.6, 0.83±0.5), adiponektin (60.31±23.1, 56.39±25.9) and leptin (3.08±1.4, 3.74±1.3) levels were not statistically significantly different from those in the benign group. In the malign treatment group, serum adiponectin (102.64±50.3, 66.64±27.0) levels were increased significantly (p<0.05); however, serum visfatin (1.17±0.9, 0.68±0.3), ghrelin (85.52±29.5, 82.18±18.0), leptin (5.65±2.8, 3.16±1.1), and resistin (5.96±2.8, 5.65±1.7) levels did not change significantly (p<0.05) compared to those in the respective benign treatment group. CONCLUSIONS: We showed that adipocytokines were involved in the carcinogenic process. The present results suggest that resistin and ghrelin may be important biomarkers of colon cancer. Furthermore, an in vitro study will also be necessary to evaluate the direct function of these adipocytokines in cancer cells. In addition, it will be appropriate to conduct new studies with a large number of patients at different stages (Tab. 1, Fig. 2, Ref. 24).

Secondary hemophagocytosis in 3 patients with organic acidemia involving propionate metabolism.

Hemophagocytic lymphohistiocytosis (HLH) may develop secondary to infections, malignancies, immune deficiency syndromes, and rheumatologic and metabolic disorders. Associations between HLH and inborn errors of metabolism, including lysinuric protein intolerance, multiple sulfatase deficiency, galactosemia, Gaucher disease, Pearson syndrome, and galactosialidosis, have previously been reported in the literature. In this report the authors present 3 children with disorders of propionate metabolism--1 with methylmalonic acidemia and 2 with propionic acidemia--who developed secondary HLH during their metabolic attacks. All patients fulfilled the 5 HLH criteria of the Histiocyte Society. Familial HLH was ruled out by molecular analysis. Plasma exchange was performed for 2 of them. Unfortunately 1 died of multiorgan failure despite intensive therapy. This is the first report of such an association.

Diffusion-weighted magnetic resonance imaging for the detection of ischemic brain lesions in coronary artery bypass graft surgery: relation to extracorporeal circulation and heparinization.

AIM: Cognitive decline is a well recognized complication after on-pump coronary artery bypass graft (CABG) surgery. We investigated whether the design of extracorporeal circulation (ECC) and the extent of perioperative heparinization have an impact on neurological dysfunction. METHODS: Sixty-three CABG surgery patients were randomly perfused with an uncoated ECC-set (group A) or with two different heparin-coated ECC-sets (groups B and C). In groups A and B, systemic heparin was given in doses of 400 IU/kg body weight, whereas group C received 150 IU/kg body weight. ECC sets in group C included a diagonal pump and low priming as opposed to roller pumps in groups A and B. Furthermore, in group C blood contact to surfaces other than endothelium and heparin coated material was eliminated. Brain lesions were detected by diffusion-weighted magnetic resonance imaging (DWI). Neurological complications were assessed clinically until discharge (manifest motoric, sensitive or cognitive disturbance). Biochemical coagulation and inflammation parameters were measured pre-, peri-, and postoperatively. RESULTS: No major neurological events were observed in either group until discharge. DWIs showed 61 new lesions in 19 of 45 patients who terminated all MRI study procedures. Number and volume of the lesions did not differ between groups (P>0.05). Biochemical and inflammatory parameters showed the expected time courses and variations between groups. CONCLUSION: Ischemic brain lesions are frequently observed in CABG surgery patients but are neither associated with clinically relevant neurological complications nor with ECC set-up and intraoperative heparin dosage. DWI may help in the development of new surgical strategies to reduce postoperative brain damage.

Management of spaghetti wrist under WALANT technique.

This study aimed to evaluate the effectiveness of the WALANT technique in managing spaghetti wrist lacerations. Thirteen consecutive patients with spaghetti wrist laceration were operated on under WALANT technique and followed prospectively. All patients were operated on by the same hand surgeon in a university hospital setting. At the final follow-up, arterial patency, tendon repair, nerve regeneration, handgrip strength and overall patient satisfaction were assessed. All patients were male, with a mean age of 23.8 ± 7.7 years (range, 18-42). The mean waiting time from admission to operation was 33.6 ± 5.1 min (range, 26-42). The operation lasted a mean 119.6 ± 33.8 min (range, 75-185). Mean time from admission to discharge was 269.3 ± 35.0 min (range, 225-341). Mean VAS for intraoperative pain was 1.0 ± 0.9 points (range, 0-3). Patients were followed up for at least 6 months: mean 9.8 ± 1.6 months (range, 7-12). Ten of the 12 repaired arteries were patent and 2 were occluded at the final follow-up. Six of the 17 repaired nerves were evaluated as excellent, 9 as good and 2 as fair on 2-point discrimination test. Total active range of motion was perfect in 6 patients, good in 6, and fair in 1. Grip strength was averaged 86.8% (range, 76.9-93.5%) of the contralateral value. All patients were either very satisfied (n: 9) or satisfied (n: 4). The WALANT technique can be used for spaghetti wrist lacerations involving the tendons, arteries and nerves, with favorable outcome. Major arterial anastomosis can be performed without any surgical limitation.

Correction to: PKU dietary handbook to accompany PKU guidelines.

An amendment to this paper has been published and can be accessed via the original article.

PKU dietary handbook to accompany PKU guidelines.

BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism caused by deficiency in the enzyme phenylalanine hydroxylase that converts phenylalanine into tyrosine. MAIN BODY: In 2017 the first European PKU Guidelines were published. These guidelines contained evidence based and/or expert opinion recommendations regarding diagnosis, treatment and care for patients with PKU of all ages. This manuscript is a supplement containing the practical application of the dietary treatment. CONCLUSION: This handbook can support dietitians, nutritionists and physicians in starting, adjusting and maintaining dietary treatment.

Peripheral neuropathy in a patient with D-2-hydroxyglutaric aciduria.

D-2-hydroxyglutaric aciduria (D-2-HGA; OMIM 600721) is a rare autosomal recessive neurometabolic disorder with a wide clinical spectrum. The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy with hypotonia, delayed cerebral visual development, cardiomyopathy and facial dysmorphic features. The mild phenotype has a more variable clinical expression with hypotonia and developmental delay. We present peripheral neuropathy as an additional clinical and electrophysiological feature in a 16-year-old boy with a homozygous missense mutation in exon 3 of the D-2-hydroxyglutarate dehydrogenase gene (D2HGDH) at position c.458T>C. This mutation results in replacement of a methionine residue, which was highly conserved during evolution, by threonine (p.Met153Thr).

Evaluation of risk factors and severity of a life threatening surgical emergency: Fournier's gangrene (a report of 15 cases).

BACKGROUND: Fournier's gangrene is a rare, rapidly progressive, necrotising fasciitis of the external genitalia and perineum with high morbidity and mortality. PATIENTS & METHODS: 15 patients with Fournier's gangrene were enrolled. Gender, age, aetiology, predisposing factors, symptomatology, associated diseases, hospital stay, FGSI, and body surface area were analysed. RESULTS: Ten males and five females were enrolled in the study. The mean age was 54 years (range 23-81). E. coli and acinetobacter were the common organisms cultured. All patients were treated with a common approach of resuscitation, broad-spectrum antibiotics, and wide surgical excision. Common predisposing factors included diabetes mellitus (73.3%), poor personal hygiene (60%), obesity (33.3%), psychosis (20%) and decubitus ulcers (13.2%). Whereas five (33.3%) patients developed synergistic gangrene of the scrotum secondary to anorectal disease, five (33.3%) had a urological source of infection. Mean BSA and FSGI scores were 15.93 +/- 3.13 and 6.02 +/- 0.95, respectively. Serum glucose > 140 mg/dl, the existence of septic shock on admission, the spread of gangrene to the perineum and abdominal wall (Groups C and D), BSA > or = 24 cm2, a cutaneous source of infection and FGSI scores > or = 7 were factors affecting mortality rates with statistical significance (p < 0.05). There was a direct correlation between the culture of mixed type micro-organisms and the cutaneous source of infection (p < 0.05). The extent of gangrene correlated with higher FGSI scores (> or = 7) (p < 0.05). Mortality and morbidity rates were as 20% (n = 3) and 60% (n = 9). CONCLUSION: Aggressive surgical debridement and combined antibiotherapy are essential in the management of Fournier's gangrene. FGSI and BSA are useful to assess the severity and prognosis of the disease.

Does maternal knowledge impact blood phenylalanine concentration in Turkish children with phenylketonuria?

The aim of this study was to compare the level of maternal knowledge and the blood phenylalanine (Phe) control in phenylketonuria (PKU; OMIM 261600). The study was conducted on 144 children (81 boys, 63 girls) with PKU, aged between 1 and 15 years, at Hacettepe University Ihsan Dogramaci Children's Hospital, Metabolism and Nutrition Unit. All subjects were treated with a low-Phe diet using a Phe-exchange system. A 20-question multiple-choice questionnaire was applied to the mothers to determine their knowledge about PKU and its dietary treatment. Questions in the test consisted of the knowledge about the disease (6 questions), general dietary knowledge (14 questions) and knowledge about specific exchange within the dietary questions (6 questions). The median blood Phe concentration for the previous 3-year period was used as an indicator of metabolic control. Eighty-seven children had a median blood Phe concentration above the MRC Working Party Guidelines. There was a negative correlation between maternal knowledge about exchange and median blood Phe concentration in the child (p<0.05). Maternal knowledge about a standard 15 mg Phe exchange system is correlated with dietary compliance as measured by blood Phe concentrations in our subjects. We would like to implement an easier method of measuring Phe exchanges to improve dietary knowledge in the mothers.

Heparin-coated extracorporeal circulation in combination with low dose systemic heparinization reduces early postoperative blood loss in cardiac surgery.

AIM: According to a recently performed meta-analysis, heparin-bonded circuits do not reduce blood loss in cardiac surgery patients compared to nonheparin-bonded circuits within the first 24 h postoperatively. We investigated the effects of heparin-coated circuits in combination with a reduced systemic heparin dose on early postoperative blood loss (first 12 h), platelet function, and postoperative complications. METHODS: Patients who underwent their first coronary artery bypass graft surgery were included in a randomized prospective study. Group A (n=149) was perfused with an uncoated extracorporeal circulation (ECC)-set and groups B (n=152) and C (n=149) with heparin-coated ECC-sets. In groups A and B, conventional dose systemic heparin was given, whereas group C received low dose systemic heparin. Blood loss was assessed within the first 12 h postoperatively. Moreover, biochemical parameters of pro-coagulant activity and immunological function were measured. RESULTS: None of the pro-coagulant activity markers and immunological parameters measured differed preoperatively or postoperatively between study groups. However, intraoperative platelet counts and maximal intraoperative concentrations of platelet factor 4, ss-thromboglobulin, and poly-morpho-nuclear (PMN)-elastase were lowest in group C, whereas group C also had the highest concentrations of thrombin-antithrombin complex (P<0.018-0.001). Blood loss within the first 12 h postoperatively was 457 +/- 204 mL in group A, 431 +/- 178 mL in group B, and 382 +/- 188 mL in group C (P<0.01). Complication rates and 30-day mortality did not differ between study groups. CONCLUSION: The combined use of heparin-coated circuits and low dose systemic heparinization is able to reduce early postoperative blood loss without enhancing the risk of complications.

Defects in the E2 lipoyl transacetylase and the X-lipoyl containing component of the pyruvate dehydrogenase complex in patients with lactic acidemia.

Three patients with chronic lacticacidemia and deficiency of the pyruvate dehydrogenase complex demonstrated in cultured skin fibroblasts showed abnormalities on Western blotting with anti-pyruvate dehydrogenase complex antiserum which were not located in the E1 (alpha and beta) component of the complex. One of these patients had an enzymatically demonstrable deficiency in the E2 dihydrolipoyl transacetylase segment of the complex and very low observable E2 protein component on Western blotting of fibroblast proteins. The other two patients had abnormalities observable in the X component but no observable reduction in either E1, E2, or E3 enzymatic activities. One patient appeared to have a missing X component while the other had two distinct bands where X should be on Western blotting of fibroblast proteins. All three patients appeared to have severe clinical sequelae resulting from these defects. This is the first time that defects in either the E2 or the X component of the pyruvate dehydrogenase complex have been observed in the human population.

Audiologic findings in children with biotinidase deficiency in Turkey.

OBJECTIVE: Biotinidase deficiency is an autosomal recessively inherited disorder characterized by neurological and cutaneous features, including sensorineural hearing loss. Although many features of the disorder are reversible following treatment with biotin, the hearing loss appears to be irreversible. In the present study, hearing status of patients with biotinidase deficiency is characterized in a Turkish population. METHODS: Subjective and objective audiologic tests were performed on 20 children with profound biotinidase deficiency. RESULTS: Sensorineural hearing loss occurs in approximately 55% of the children with biotinidase deficiency. The hearing loss varies in severity from mild to profound hearing loss. In children diagnosed immediately after birth because they had an older sibling with the disorder, statistically significant differences were found between ABR results and age of diagnosis (p<0.05). Greater prolongation in ABR latencies were observed in the late-diagnosed children compared to that in the early-diagnosed children (p<0.05). CONCLUSION: Early diagnosis is important to prevent peripheral and central hearing loss. Children with biotinidase deficiency who have hearing loss are likely at increased risk for having speech and language problems. If hearing aids do not provide sufficient amplification, cochlear implantation may be indicated in these children. Therefore, it is important to test the hearing thresholds of these children with hearing aids and evaluate their language development.

Serum her-2/neu and survivin levels and their relationship to histological parameters in early-stage breast cancer.

This study was conducted to investigate the serum levels of her-2/neu and survivin in patients with early-stage breast cancer and their relationship with known histological parameters. Forty-one patients with early-stage breast cancer were investigated. Serum samples were collected from patients on their first admission before adjuvant chemotherapy, and from healthy controls. Serum her-2/neu and survivin levels were determined using an enzyme-linked immunosorbent assay. There was no difference in the levels of serum her-2/neu and survivin between the breast cancer patients and the control group. Serum her-2/neu concentration showed moderate correlations with disease stage and the Ki-67 level, and the serum survivin level showed a moderate correlation with progesterone receptor concentration. Serum levels of her-2/neu and survivin were not significantly related to age and histological parameters in patients with early-stage breast cancer. However, much research continues on the prognostic value of serum her-2/neu and survivin levels, and important new knowledge may ultimately emerge.

A Turkish case with molybdenum cofactor deficiency.

Molybdenum cofactor deficiency (MIM 252150) is a rare progressive neurodegenerative disorder with about 100 cases reported worldwide. We have identified a male with molybdenum cofactor deficiency and analyzed the molybdenum cofactor synthesis (MOCS)1 gene, MOCS2 gene, MOCS3 gene and GEPH gene. We homozygously identified the CGA insertion after A666 of the MOCS1 gene which produces arginine insertion at codon 222 of MOCS1A. The parents, his brother and his sister who did not have any symptoms were heterozygous for the same mutation. This region was highly conserved in various species. The N-terminal part of MOCS1 a protein is suggested to form the central core of the protein and be composed of an incomplete [(alpha/beta)6] triosephosphate isomerase (TIM) barrel with a lateral opening that is covered by the C-terminal part of the protein. The insertion is located in the loop connecting the fifth beta strand to the sixth alpha helices of the TIM barrel structure. This arginine insertion would induce the conformation change and the lack of the activity.

Papillary fibroelastoma of the ascending aorta presenting with cardiogenic shock.

We describe an uncommon case of a 58-year-old woman who presented with cardiogenic shock. The echocardiography examination revealed a papillary fibroadenoma located in the ascending aorta which was subsequently surgically treated.

High cystine in platelets from patients with nephropathic cystinosis: a chemical, ultrastructural, and functional evaluation.

AIM: To investigate the morphology and function of platelets in nephropathic cystinosis (NC). METHODS: Seven patients (mean age, 6.5 years; SD, 20 months) with NC were investigated. Their platelets were examined by transmission electron microscopy (TEM) and the characteristics of the dense granules (DGs) were determined by mepacrine labelling and the uranaffin reaction. Bleeding time, turbidometric aggregation, and luminescence aggregation were studied and intraplatelet cystine was measured. RESULTS: Increased intraplatelet cystine, primary and secondary aggregation defects, and the absence of ATP release were demonstrated. TEM revealed DGs of various shapes and sizes and lamellary or amorphous cytoplasmic inclusions. Viscous material had been released into the vacuolar spaces and enlarged open canalicular system. Mepacrine labelling revealed that the numbers of DGs/platelet were comparable between the patients and the controls (mean, 2.9 (SD, 0.22) v 3.32 (0.18); p = 0.34). The uranaffin reaction revealed that the numbers of type 1, 3, and 4 DGs were comparable between the patients and the controls, but that there were fewer type 2 DGs in the patients (mean, 8.5 (SD, 1.95) v 17.22 (1.58); p = 0.01). TEM for platelet aggregation revealed a lack of induction and/or defective execution and/or delayed transmission. The patients' intraplatelet cystine concentrations were higher than the controls (mean, 1.56 (SD, 0.84) v 0.08 (0.01) nmol/mg protein; p = 0.009). CONCLUSIONS: This is the first report to demonstrate raised intraplatelet cystine, abnormal platelet ultrastructural findings, and defective aggregation in NC.