Comprehensive evaluation of patients with primary hyperoxaluria type 1: A nationwide study.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is characterized by increased endogenous oxalate production and deposition as calcium oxalate crystals. The main manifestations are nephrocalcinosis/nephrolithiasis, causing impaired kidney function. We aimed to evaluate the clinical characteristics and overall outcomes of paediatric PH1 patients in Turkey. METHODS: This is a nationwide, multicentre, retrospective study evaluating all available paediatric PH1 patients from 15 different paediatric nephrology centres in Turkey. Detailed patient data was collected which included demographic, clinical and laboratory features. Patients were classified according to their age and characteristics at presentation: patients presenting in the first year of life with nephrocalcinosis/nephrolithiasis (infantile oxalosis, Group 1), cases with recurrent nephrolithiasis diagnosed during childhood (childhood-onset PH1, Group 2), and asymptomatic children diagnosed with family screening (Group 3). RESULTS: Forty-eight patients had a mutation consistent with PH1. The most common mutation was c.971_972delTG (25%). Infantile oxalosis patients had more advanced chronic kidney disease (CKD) or kidney failure necessitating dialysis (76.9% vs. 45.5%). These patients had much worse clinical course and mortality rates seemed to be higher (23.1% vs. 13.6%). Patients with fatal outcomes were the ones with significant comorbidities, especially with cardiovascular involvement. Patients in Group 3 were followed with better outcomes, with no kidney failure or mortality. CONCLUSION: PH1 is not an isolated kidney disease but a systemic disease. Family screening helps to preserve kidney function and prevent systemic complications. Despite all efforts made with traditional treatment methods including transplantation, our results show devastating outcomes or mortality.

Follow-The-Leader Mechanisms in Medical Devices: A Review on Scientific and Patent Literature.

Conventional medical instruments are not capable of passing through tortuous anatomy as required for natural orifice transluminal endoscopic surgery due to their rigid shaft designs. Nevertheless, developments in minimally invasive surgery are pushing medical devices to become more dexterous. Amongst devices with controllable flexibility, so-called Follow-The-Leader (FTL) devices possess motion capabilities to pass through confined spaces without interacting with anatomical structures. The goal of this literature study is to provide a comprehensive overview of medical devices with FTL motion. A scientific and patent literature search was performed in five databases (Scopus, PubMed, Web of Science, IEEExplore, Espacenet). Keywords were used to isolate FTL behavior in devices with medical applications. Ultimately, 35 unique devices were reviewed and categorized. Devices were allocated according to their design strategies to obtain the three fundamental sub-functions of FTL motion: steering, (controlling the leader/end-effector orientation), propagation, (advancing the device along a specific path), and conservation (memorizing the shape of the path taken by the device). A comparative analysis of the devices was carried out, showing the commonly used design choices for each sub-function and the different combinations. The advantages and disadvantages of the design aspects and an overview of their performance were provided. Devices that were initially assessed as ineligible were considered in a possible medical context or presented with FTL potential, broadening the classification. This review could aid in the development of a new generation of FTL devices by providing a comprehensive overview of the current solutions and stimulating the search for new ones.

A possibly new autoinflammatory disease due to compound heterozygous phosphomevalonate kinase gene mutation.

BACKGROUND: Mevalonate kinase (MVK) plays a role in cholesterol and non-sterol isoprenoid biosynthesis and its deficiency-related diseases are caused by bi-allelic pathogenic mutations in the MVK gene, (MVK), which leads to rare hereditary autoinflammatory diseases. The disease may manifest different clinical phenotypes depending on the degree of the deficiency in the enzyme activity. The complete deficiency of the enzyme activity results in the severe metabolic disease called mevalonic aciduria, while a partial deficiency results in a broad spectrum of clinical presentations called hyper-immunoglobulin D syndrome (HIDS). Serum immunoglobulin (Ig) D and urine mevalonic acid levels may be increased during inflammatory attacks of HIDS. CASE PRESENTATION: Herein, for the first time in the literature, we present a 6-year-old male patient who suffered from recurrent episodes of fever, polyarthritis, skin rash, diarrhea, abdominal pain, and inflammatory bowel disease-like manifestations with elevated levels of serum IgD, and urine mevalonic acid. Eventually we detected compound heterozygous mutations in the phosphomevalonate kinase (PMVK) gene coding the second enzyme after mevalonate kinase in the mevalonate pathway. CONCLUSION: For patients presenting with HIDS-like findings, disease exacerbations and persistent chronic inflammation, and having high urinary mevalonic acid and serum IgD levels, raising suspicion in terms of MVK deficiency (MVKD), it is recommended to study all mevalonate pathway enzymes, even if there is no mutation in the MVK gene. It should be kept in mind that novel mutations might be seen such as PMVK gene.

A Patient with a Novel RARS2 Variant Exhibiting Liver Involvement as a New Clinical Feature and Review of the Literature.

Pontocerebellar hypoplasia (PCH) is a heterogeneous neurodevelopmental disorder that is characterized by decreased brainstem and cerebellum volume. Pontocerebellar hypoplasia type 6 (PCH6) is a mitochondrial disease associated with autosomal recessive inheritance that results from mutations in the RARS2 gene. In this case report, we describe a new clinical presentation with a novel RARS2 pathogenic variant. We report here on 2 siblings who presented with neonatal lactic acidosis, microcephaly, growth retardation, persistent seizures, and cholestasis with a previously undefined RARS2 pathogenic variant. In our literature review, we evaluated the clinical features and pathogenic variants of 34 patients reported in 16 publications since the initial identification of RARS2 pathogenic variants in PCH6 in 2007. Both siblings were detected with c.1564G>A (p.Val522Ile), a novel homozygous pathogenic variant of the RARS2 gene. Imaging revealed advanced cerebral atrophy and cerebellar hypoplasia, while the basal ganglia and pons were preserved. At follow-up, the elevations in liver function test results and cholestasis had regressed while the LDH and GGT elevations persisted. Both siblings showed microcephaly on follow-up and started to suffer seizures. Severe developmental delay and nutritional problems were observed, and both died in infancy. RARS2 pathogenic variant is a mitochondrial disease that causes severe mental, motor, and developmental retardation, as well as short life expectancy. Our patients are the first cases with liver involvement in PCH6 and a novel homozygous RARS2 pathogenic variant to be reported in the literature. This additional phenotype can be considered as making a valid contribution to the literature.

Addressing the need for patient-friendly medical communications: adaptation of the 2019 recommendations for the management of MPS VI and MPS IVA.

BACKGROUND: Patients are the most important stakeholders in the care of any disease and have an educational need to learn about their condition and the treatment they should receive. Considering this need for patient-focused materials, we present a directed approach for mucopolysaccharidosis (MPS) VI and MPS IVA, a pair of rare, inherited diseases that affects multiple organs and parts of the body. Independent guidelines on the treatment of these diseases were recently published, providing evidence- and expertise-driven recommendations to optimize patient management. However, while healthcare providers may have the training and knowledge to understand these guidelines, patients and their caregivers can find the technical content challenging. Hence, we aimed to develop plain language summaries (PLS) of the MPS VI and MPS IVA guidelines with patients as the primary audience. RESULTS: A review of the guidelines by an expert team identified six domains of information relevant to patients: The multidisciplinary team, regular tests and check-ups, disease-modifying and supportive treatments, general anesthetics, ear-nose-throat/respiratory care, and surgeries. This information was adapted into a series of infographics specific to either MPS VI or MPS IVA, designed to appeal to patients and clearly present information in a concise manner. CONCLUSIONS: The use of patient-friendly materials, like the infographics we have developed, has the potential to better inform patients and engage them in their care. We issue a "call to arms" to the medical community for the development of similar PLS materials in rare diseases intended to inform and empower patients.

Co-Occurring Atypical Galactosemia and Wilson Disease.

Introduction: Classic galactosemia is a disorder of the galactose metabolism and is inherited as an autosomal recessive disease. It is caused by a complete or severe deficiency of galactose-1-phosphate uridyltransferase (GALT), and in rare cases, atypical galactosemia can manifest at older ages. Wilson disease (WD) is a disorder of the copper metabolism that, like galactosemia, is inherited as an autosomal recessive disease. Hepatic, neurological, or psychiatric symptoms can be seen, independently or in combination, and symptoms vary from family to family. We present here a patient diagnosed with both WD and galactosemia. Case Presentation: A 6-year-old girl was referred to our center with elevated transaminase levels and hepatosplenomegaly. The child, birthweight of 2,200 g, was born to first-degree consanguineous parents after a full-term uneventful pregnancy and was hospitalized in the neonatal period due to indirect hyperbilirubinemia, gastrointestinal bleeding, diarrhea lasting 2 weeks, and elevated liver enzymes. Hepatosplenomegaly was evident at the time of admission, a cataract was detected, and a neuropsychiatric evaluation revealed borderline mental capacity, as well as cognitive and speech retardation. Metabolic investigations revealed no specific findings other than trace positivity of reducing substances in the urine. A liver biopsy revealed copper accumulation in hepatocytes and low ceruloplasmin levels. Although WD was suspected in the patient, this diagnosis did not explain the intellectual disability, behavioral disorder, or cataract findings. A genetic analysis revealed homozygous mutations in the ATP7B and GALT genes. The galactose-1-phosphate uridyltransferase enzyme level was found to be low, and the patient was diagnosed with coexisting WD and galactosemia. Conclusion: Coexistences of rare genetically transmitted diseases can be seen in countries where consanguineous marriages are common (Saudi Arabia, Iran, Pakistan, etc.), as in our country, Turkey.

The Role of Minimally Invasive Surgery in Gastric Cancer.

OBJECTIVE: This study aims to investigate the efficacy and safety of minimally invasive surgery (MIS) in gastric cancer and to compare MIS versus open gastrectomy (OG) in terms of early mortality and morbidity, long-term oncological outcomes, and recurrence rates. METHODS: A total of 75 patients who underwent MIS or OG for gastric cancer at Koç University School of Medicine between December 2014 and December 2019 were retrospectively analyzed. Postoperative complications and disease-specific survival were compared between surgical approaches. RESULTS: Of the patients, 44 were treated with MIS and 31 with OG. In the MIS group, 33 patients underwent laparoscopic surgery, and 11 patients underwent robotic gastrectomy. Duration of operation was significantly longer in the MIS group than in the OG group (p<0.0001). The median amount of blood loss was 142.5 (range, 110 to 180) mL in the MIS group and 180.4 (range, 145 to 230) mL in the OG group (p<0.706). The median number of lymph node dissection was 38.9 (range, 15 to 66) and 38.7 (range, 12 to 70) in the MIS and OG groups, respectively (p<0.736). The median length of hospitalization, twelve days in the OG group and nine days in the MIS group. Median follow-up was 19.1 (range, 2 to 61) months in the MIS group and 22.1 (range, 2 to 58) months in the OG group. The median OS and DFS rates were 56.8 months and 39.6 months in the MIS group, respectively (log-rank; p=0.004) and 31.6 months and 23.1 months in the OG group, respectively (log-rank; p=0.003). CONCLUSION: Our study results suggest that, despite its technical challenges, MIS is an effective and safe method in treating gastric cancer with favorable early mortality and morbidity rates and long-term oncological outcomes, and acceptable recurrence rates.

Expanding the clinical spectrum of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency with Turkish cases harboring novel HMGCS2 gene mutations and literature review.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS) deficiency is a very rare autosomal recessive inborn error of ketone body synthesis and presents with hypoketotic hypoglycemia, metabolic acidosis, lethargy, encephalopathy, and hepatomegaly with fatty liver precipitated by catabolic stress. We report acute presentation of two patients from unrelated two families with novel homozygous c.862C>T and c.725-2A>C mutations, respectively, in HMGCS2 gene. Affected patients had severe hypoketotic hypoglycemia, lethargy, encephalopathy, severe metabolic and lactic acidosis and hepatomegaly after infections. Surprisingly, molecular screening of the second family showed more affected patients without clinical findings. These cases expand the clinic spectrum of this extremely rare disease.

Overdiscrete echo-planar spectroscopic imaging with correlated higher-order phase correction.

PURPOSE: To introduce a robust methodology for fast 1 H MRSI of the brain at 3T with improved SNR and reduced phase-related artifacts. METHOD: An accelerated acquisition scheme using echo-planar spectroscopic imaging (EPSI) was combined with the overdiscrete reconstruction framework. This approach enables the interleaved acquisition of a water reference scan at each phase encoding step, maximizing its correlation with the water-suppressed measurement. Moreover, a generalized high-order phase correction was incorporated into the reconstruction pipeline. The spatial-temporal phase correction term was estimated from the reference scan and interpolated to high resolution using a polynomial basis. The method was implemented at 3T and validated with phantom and in vivo experiments. RESULTS: The methodology showed the elimination of spectral artifacts generated by phase disturbances and achieved mean SNR gains in vivo of 3.18 and 1.19 compared to standard reconstructions with corrections performed at nominal and high resolution, respectively. EPSI scans with interleaved water acquisition showed to be robust to system instabilities and potentially to patient motion. Moreover, phase distortions were effectively corrected in a single step, avoiding additional reference measurements and post-processing steps. CONCLUSION: The overdiscrete reconstruction framework with high-order phase correction allowed to effectively correct for distortions, related to B0 inhomogeneities, B0 drift, eddy currents, and system vibrations. Furthermore, the presented reconstruction method, combined with EPSI acquisitions, demonstrated improved measurement stability, substantial SNR enhancement, better spectral linewidth, and effective artifact removal.

Hematologic Findings of Inherited Metabolic Disease: They are More Than Expected.

Inherited metabolic diseases are pathologic conditions that generally develop as a result of impairment of the production or breakdown of protein, carbohydrate, and fatty acids. Early determination of hematological findings has a positive effect on the prognosis of metabolic diseases. Three hundred eighteen patients who were being followed-up within the previous 6 months at Department of Pediatric Nutrition and Metabolism, Gazi University, Turkey, were included in the study. The hematological findings were classified under 7 main groups: anemia of chronic disease, iron deficiency anemia, vitamin B12 deficiency anemia, hemophagocytosis, leukocytosis, and thrombocytosis. Nine hundred twenty-two hematological examinations of the 319 patients were included in the study, and 283 hematological findings were determined, 127 anemia of chronic disease, 81 iron deficiency anemia, 56 cytopenia, and 4 vitamin B12 deficiency anemia. Leukocytosis (n=1), thrombocytosis (n=5), and hemophagocytosis (n=9) were also observed. It was determined that, although anemia of chronic disease and nutritional anemia are the most common hematological findings, these may be diagnosed late, whereas neutropenia, thrombocytopenia, pancytopenia, and hemostasis disorders may be diagnosed earlier. Our study is the most comprehensive one in the literature, and we think it would positively contribute to the monitoring and prognosis of congenital metabolic diseases.

Patient With Niemann-Pick Type C Presenting With a Jaw Mass Characterized With Lymph Node Involvement by Niemann-Pick Cells.

Niemann-Pick type C disease (NPC) is an autosomal recessive disorder resulting in accumulation of unesterified lysosomal cholesterol. An 8-year-old girl with NPC disease had a painless, rigid, and fixed mass measuring 3 cm in diameter located on the left angular region of mandibula. The mass biopsy showed lipid-laden phagocytic cells infiltrating the lymph node consistent with Niemann-Pick cells. In NPC, accumulation of cholesterol in tissues could be seen not only in reticuloendothelial and nervous systems, but also in all systems. Our case is important for it being the first case of NPC with submandibular lymphadenopathy characterized with NPC cell infiltration.

Smartphones and Programmable Shunts: Are These Indispensable Phones Safe and Smart?

OBJECTIVE: This study aimed to determine whether smartphones affect programmable shunts. METHODS: iPhone 5S (Apple Inc., Cupertino, CA, USA) and Samsung Galaxy S5 (Samsung Electronics, Gumi, South Korea) smartphones were chosen for this study. For both phones, magnetic field mapping was performed with 3-dimensional magnetic scanning systems constructed with high-precision motorized stages, and a Hall effect sensor was used to measure the flux density on the smartphone surface. The distance (h) between the distal outlet of the reservoir and the rugby ball of the Strata valve (Medtronic Inc., Minneapolis, MN, USA) was measured using highly sensitive microanalysis optical method. During optical microanalysis, while keeping a 3-cm distance between the valve and the magnetic generator, the h value (µm) was recorded for different magnetic flux densities (MFDs). Then, direct x-ray radiography was performed for radiologic assessment after each process under different magnetic fields. For analysis of the Codman Certas valve (Codman Neuro, Raynham, MA, USA), the magnet orientation and the angle between the magnet with the tantalum ball were measured with the same optical analysis. RESULTS: Maximum MFDs found 62 G for iPhone 5S and 61 G for Samsung Galaxy S5. When the magnetic generator formed a current at 0, 30, 60, and 90 G, the h values of the Strata valve adjusted to 100 mm H2O opening pressure were 320, 280, 190, and 175 µm, respectively. When the magnetic generator was removed from the environment, the h value returned to 320 µm. In direct graphs taken after each optical analysis at different Gauss values, substitution was not observed at the indicator. The angle in the Codman Certas valve was 123.9°, 112.5°, and 103.6° at the magnetic flux densities of 0, 60, and 90 G, respectively. When the magnetic field was removed (0 G), the angle was still 103.6°, suggesting an irreversible effect in the shunt construct. CONCLUSIONS: Smartphones exert reversible effects on Strata programmable valves without producing remarkable radiologic findings and irreversible effects on Codman Certas valves.

Deriving effective vaccine allocation strategies for pandemic influenza: Comparison of an agent-based simulation and a compartmental model.

Individuals are prioritized based on their risk profiles when allocating limited vaccine stocks during an influenza pandemic. Computationally expensive but realistic agent-based simulations and fast but stylized compartmental models are typically used to derive effective vaccine allocation strategies. A detailed comparison of these two approaches, however, is often omitted. We derive age-specific vaccine allocation strategies to mitigate a pandemic influenza outbreak in Seattle by applying derivative-free optimization to an agent-based simulation and also to a compartmental model. We compare the strategies derived by these two approaches under various infection aggressiveness and vaccine coverage scenarios. We observe that both approaches primarily vaccinate school children, however they may allocate the remaining vaccines in different ways. The vaccine allocation strategies derived by using the agent-based simulation are associated with up to 70% decrease in total cost and 34% reduction in the number of infections compared to the strategies derived by using the compartmental model. Nevertheless, the latter approach may still be competitive for very low and/or very high infection aggressiveness. Our results provide insights about potential differences between the vaccine allocation strategies derived by using agent-based simulations and those derived by using compartmental models.

Molecular analysis of the AGXT gene in patients suspected with hyperoxaluria type 1 and three novel mutations from Turkey.

Primary hyperoxaluria type 1 (PH1) is a rare, autosomal recessive disease, caused by the defect of AGXT gene encoding hepatic peroxisomal alanine glyoxylateaminotransferase (AGT). This enzyme is responsible for the conversion of glyoxylate to glycine. The diagnosis of PH1 should be suspected in infants and children with nephrocalcinosis or nephrolithiasis. Early diagnosis and treatment is crucial in preventing disease progression to end stage kidney disease (ESKD). In this study, AGXT gene sequence analyses were performed in 82 patients who were clinically suspected (hyperoxaluria and nephrolithiasis or nephrocalcinosis with or without renal impairment) to have PH1. Disease causing mutations have been found in fifteen patients from thirteen families (18%). Novel mutations have been found (c.458T>A (p.L153X), c.733_734delAA (p.Lys245Valfs*11), c.52 C>T (p.L18F)) in three of 13 families. There were 3-year lag time between initial symptoms and the time of PH1 is suspected; additionally, 5.5-year lag time between initial symptoms and definitive diagnosis. Consanguinity was detected in 77% of the patients with mutation. After genetic diagnosis, one patient received combined kidney and liver transplantation. AGXT gene sequencing is now the choice of diagnosis of PH1 due to its non-invasive nature compared to liver enzyme assay. Early diagnosis and accurate treatment in PH1 is important for better patient outcomes.

Lumbar Disc Surgery with Epidural Anesthesia: Review of 700 Cases.

AIM: Lumbar disc surgery can be performed under general anesthesia or regional anesthesia methods. There are long-standing discussions between neurosurgeons, orthopedic surgeons and anesthesiologists concerning the use of epidural anesthesia in lumbar surgery. The results of this study's 700 lumbar disc surgery cases operated with epidural anesthesia in our clinic between September 2006 and December 2011 will contribute to these discussions. MATERIAL AND METHODS: This study included 700 patients underwent lumbar disc surgery with epidural anesthesia, which consisted of 388 males (55%) and 312 females (45%). Forty-two of these cases had recurrence disc herniation and only 11 of 42 cases were operated in our department. RESULTS: Eleven of 700 cases had dural injury and were repaired intraoperatively by primary sutures and tissue sealants. Infection of the incision site developed in six patients, who healed with appropriate antibiotic treatment with no problems. In addition to those 700 cases, 22 patients received general anesthesia in which we started with epidural anesthesia. Microdiscectomies were performed in 578 of 700 cases, and open surgery in 122 cases. CONCLUSION: This study showed that epidural anesthesia seems more advantageous for some patients since it does not have some of the risks that general anesthesia bears.

Convection-reaction equation based magnetic resonance electrical properties tomography (cr-MREPT).

Images of electrical conductivity and permittivity of tissues may be used for diagnostic purposes as well as for estimating local specific absorption rate distributions. Magnetic resonance electrical properties tomography (MREPT) aims at noninvasively obtaining conductivity and permittivity images at radio-frequency frequencies of magnetic resonance imaging systems. MREPT algorithms are based on measuring the B1 field which is perturbed by the electrical properties of the imaged object. In this study, the relation between the electrical properties and the measured B1 field is formulated for the first time as a well-known convection-reaction equation. The suggested novel algorithm, called "cr-MREPT," is based on the solution of this equation on a triangular mesh, and in contrast to previously proposed algorithms, it is applicable in practice not only for regions where electrical properties are relatively constant but also for regions where they vary. The convective field of the convection-reaction equation depends on the spatial derivatives of the B1 field, and in the regions where its magnitude is low, a spot-like artifact is observed in the reconstructed electrical properties images. For eliminating this artifact, two different methods are developed, namely "constrained cr-MREPT" and "double-excitation cr-MREPT." Successful reconstructions are obtained using noisy and noise-free simulated data, and experimental data from phantoms.

Microwave-assisted preparation of azachalcones and their N-alkyl derivatives with antimicrobial activities.

Two new azachalcones were prepared by both Claisen-Schmidt condensation and a simple environmentally trendy microwave-assisted method. Ten new N-alkyl (C6,8,10,12,14)-substituted azachalconium bromides (3a-e, 4a-e) were prepared from compounds 1 and 2 with corresponding alkyl halides. The antimicrobial activities of all the compounds were tested against Enterococcus faecalis, Yersinia pseudotuberculosis, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus micro-organisms.

Is the elapsed time following the placement of a ventriculoperitoneal shunt catheter an individual risk factor for shunt fractures?

In this study, we examined whether the resistance of peritoneal catheters against the retraction force changed over time following shunt placement, and the role of this resistance in shunt fracture is discussed. We investigated peritoneal catheters removed from patients treated with a ventriculoperitoneal shunt because of hydrocephalus; previously, patients underwent shunt revision. The maximum tension, maximum elongation and elongation percentages of the peritoneal catheters were measured. The mean and maximum tension values of the revised peritoneal catheters were increased compared to the unused catheters. The maximum elongation and elongation rates were significantly decreased. The changes in the maximum elongation, elongation rate and tension values were unrelated to the time elapsed after catheter insertion. This finding indicates that the time elapsed following peritoneal catheter placement was not an individual factor based on the strength of the response of the organism to the foreign body and the mechanical trauma exposed in shunt fractures.