CONGENITAL HYPERINSULINISM – NOVEL INSIGHTS INTO ETIOLOGY, DIAGNOSIS AND TREATMENT

Kongenitalni hiperinzulinizam (KHI) najčešći je uzrok tvrdokornih hipoglikemija u novorođenačkom i ranome dojenačkom razdoblju. Iako je bolest razmjerno rijetka s pojavnosti od oko 1 : 25 000–50 000 živorođene djece, bolest se ne smije podcijeniti zbog trajnih neuroloških oštećenja do kojih dolazi ako se bolest brzo ne otkrije i ne započne promptno liječiti. Uzrok su mutacije nekog od 7 gena, ključnih u regulaciji inzulinske sekrecije u b-stanicama gušterače. Odmah nakon postavljanja dijagnoze nužno je u terapiju uvesti antihipoglikemike koji djeluju specifično na -stanice gušterače. Kod teških neonatalnih oblika nerijetko postoji rezistencija na antihipoglikemike. Tada preostaje kirurško liječenje prije kojeg je potrebno odrediti histološki oblik bolesti, što se danas uspješno postiže kombinacijom genskog testiranja i scintigrafske pretrage. Kirurškim se zahvatom najčešće postiže izlječenje kod fokalnog KHI, dok difuzni oblik ima lošiju prognozu. Ovaj je tekst pregled novijih spoznaja o KHI, kojim želimo naglasiti važnost što ranijeg postavljanja dijagnoze kao preduvjeta uspješnoga ciljanog liječenja bolesti, koje je posljednjih godina obogaćeno novim mogućnostima.Congenital hyperinsulinism (CHI) is a major cause of persistent hypoglycemia in the neonatal and early infancy periods. Althought the disease is relatively rare with incidence of about 1: 25 000–50 000 live births, the importance of the disease should not be underestimated. Namely, prompt recognition and management of patients with CHI is essential, if permanent neurological impairment is to be avoided. CHI is caused by mutations in one of the 7 genes involved in the regulation of insulin secretion in pancreatic b-cells. It is important to introduce specific medical therapy as soon as diagnosis is established. Severe, neonatal forms of CHI are often resistant to medications, thus they require surgical procedure. The preoperative genetic testing and scintigraphy are indicated to distinguish histological subtypes of the disease (focal vs. diffuse CHI). Patients with focal disease are usually cured after pancreatic resection, while diffuse disease has much worse prognosis. This manuscript offers novel insights into CHI and emphasizes the role of early diagnosis as crucial for succesful treatment that was recently enriched with novel options

ARBITRATION IN INTERNATIONAL LAW

Međunarodni je spor svako neslaganje tvrdnji ili zahtjeva između dviju međunarodnih osoba ili više njih. Za rješavanje svakog spora treba upotrijebiti prikladno sredstvo, a koje će to prikladno sredstvo biti ovisi o vrsti spora i željama stranaka. Razlikuju se sredstva čija primjena rezultira donošenjem obvezujuće odluke, te ona sredstva čija primjena ne rezultira obvezujućom odlukom. Pregovori, posredovanje, istraga i mirenje su sredstva mirnog rješavanja sporova čiji doseg je ograničen na pronalaženje kompromisnog rješenja ili utvrđivanja činjenica bitnih za spor, koji ne obvezuju stranke. Među sredstva mirnog rješavanje međunarodnih sporova čije rješenje ima obvezujući učinak ubrajamo izravnanje, arbitražu, te rješavanje sporova pred međunarodnim sudovima. Arbitraža je sredstvo mirnog rješavanja međunarodnih sporova koje rezultira donošenjem obvezujućeg i konačnog pravorijeka koji ima značaj presude. Mnoge se stranke odlučuju upravo za arbitražu jer je arbitražni postupak brži i fleksibilniji, one mogu same imenovati arbitre te mogu ugovoriti tajnost postupka.The international dispute is any disagreement between a claim or a request between two or more international persons. To resolve any dispute, appropriate means should be used, and that appropriate means will depend on the type of dispute and the wishes of the parties. Funds whose application results in the passing of a binding decision and those resources whose application does not result in a binding decision are different. Negotiations, mediation, investigation and conciliation are the means of peaceful resolution of disputes whose scope is limited to finding a compromise solution or finding facts relevant to the dispute that are not binding on the parties. Among the funds for the peaceful resolution of international disputes whose solution has a binding effect, we include equalization, arbitration, and settlement of disputes before international courts. Arbitration is a means of peaceful resolution of international disputes resulting in the passing of a binding and final award that has the significance of the verdict. Many parties decide for arbitration because the arbitration process is faster and more flexible, they can name arbiters and can negotiate the secrecy of the proceedings

Surgical Treatment of Moderate Hallux Valgus: A Comparison of Distal Chevron Metatarsal Osteotomy With and Without Lateral Soft-Tissue Release

Purpose: The purpose of the study was to determine if lateral soft tissue release (LSTR) has either a beneficial or a detrimental effect on the outcome of distal chevron first metatarsal osteotomy (DCMO) in the treatment of moderate hallux valgus. Methods: We compared the effect of different surgical treatments in two groups of patients: Group I (23 patients, 25 feet, average age of 55 (from 43-77 years of age) was subjected to DCMO only, while Group II (18 patients, 23 feet, average age of 59 (from 52-70 years of age) was subjected to DCMO with LSTR. The American Orthopedic Foot and Ankle Society's Hallux Metatarsophalangeal- Interphalangeal (AOFAS Hallux MTP-IP) scale survey was conducted postoperatively, followed by the brief survey on postoperative patient satisfaction. The patient follow-up period was from 18-24 months after surgical treatment, on average. Results: After surgical intervention, both groups of patients presented with an improved hallux valgus angle, but there was no significant difference between the groups. However, Group II showed significant improvements in medial sesamoid bone position and patient satisfaction scores as compared to Group I. Conclusion: Our mid-term follow-up of surgical treatments for moderate hallux valgus deformity suggests that both procedures provide good postoperative results. However, according to our results, DCMO with LSTR provides better results than procedures without LSTR

Influence of Various Factors on Functional Dyspepsia

Aim of the research is to establish the prevalence of dyspepsia in Osjecˇko-baranjska County, to establish its specific characteristics and to determine the effect of demographic, anthropometric, and socioeconomic factors. It is a cross- sectional and case control study conducted in 2010 on systematic sample of 900 subjects between 20 and 69 years of age. Every subject was sent an invitation letter and a Rome III diagnostic questionnaire for one of the disorders. A scoring algorithm was used to confirm or exclude the diagnosis of functional dyspepsia (FD). The chi-square test, t-test and logistic regression were used for analysis. Prevalence of dyspepsia was recorded in 16, 56 %, of subjects. There is no statistically significant difference in prevalence of dyspepsia male and female. The prevalence of dyspepsia increases with age. Correlation with the place of birth was proven. There is no correlation between the current place of residence (rural area and town) and dyspepsia. There is a correlation with marital status. Correlation between stool forms was proven. There were a greater number of subjects that had at least one alarm symptom or some of the psychosocial factors and they often suffered from a chronic disease. The risk for dyspepsia increases with age, body mass index (BMI), and poorer health. Logistic regression showed the following as statistically significant for dyspepsia: place of birth and self-assessment of one’s health. FD presents a significant health problem. Rome III survey questionnaire proved to be an acceptable method for diagnosin this functional disorder in clinical-consilliary and primary health care for persons showing signs of alarm and needing further diagnostic treatment

Kongenitalni hiperinzulinizam - novosti o nastanku, dijagnosticiranju i liječenju bolesti [Congenital hyperinsulinism - novel insights into etiology, diagnosis and treatment]

Congenital hyperinsulinism (CHI) is a major cause of persistent hypoglycemia in the neonatal and early infancy periods. Althought the disease is relatively rare with incidence of about 1:25 000-50 000 live births, the importance of the disease should not be underestimated. Namely, prompt recognition and management of patients with CHI is essential, if permanent neurological impairment is to be avoided. CHI is caused by mutations in one of the 7 genes involved in the regulation of insulin secretion in pancreatic beta-cells. It is important to introduce specific medical therapy as soon as diagnosis is established. Severe, neonatal forms of CHI are often resistant to medications, thus they require surgical procedure. The preoperative genetic testing and scintigraphy are indicated to distinguish histological subtypes of the disease (focal vs. diffuse CHI). Patients with focal disease are usually cured after pancreatic resection, while diffuse disease has much worse prognosis. This manuscript offers novel insights into CHI and emphasizes the role of early diagnosis as crucial for succesful treatment that was recently enriched with novel options

ORAI1 mutations abolishing store-operated Ca

BACKGROUND: Store-operated Ca OBJECTIVE: We performed molecular and immunologic analysis of patients with CID, anhidrosis, and ectodermal dysplasia of unknown etiology. METHODS: We performed DNA sequencing of the ORAI1 gene, modeling of mutations on ORAI1 crystal structure, analysis of ORAI1 mRNA and protein expression, SOCE measurements, immunologic analysis of peripheral blood lymphocyte populations by using flow cytometry, and histologic and ultrastructural analysis of patient tissues. RESULTS: We identified 3 novel autosomal recessive mutations in ORAI1 in unrelated kindreds with CID, autoimmunity, ectodermal dysplasia with anhidrosis, and muscular dysplasia. The patients were homozygous for p.V181SfsX8, p.L194P, and p.G98R mutations in the ORAI1 gene that suppressed ORAI1 protein expression and SOCE in the patients\u27 lymphocytes and fibroblasts. In addition to impaired T-cell cytokine production, ORAI1 mutations were associated with strongly reduced numbers of invariant natural killer T and regulatory T (Treg) cells and altered composition of γδ T-cell and natural killer cell subsets. CONCLUSION: ORAI1 null mutations are associated with reduced numbers of invariant natural killer T and Treg cells that likely contribute to the patients\u27 immunodeficiency and autoimmunity. ORAI1-deficient patients have dental enamel defects and anhidrosis, representing a new form of anhidrotic ectodermal dysplasia with immunodeficiency that is distinct from previously reported patients with anhidrotic ectodermal dysplasia with immunodeficiency caused by mutations in the nuclear factor κB signaling pathway (IKBKG and NFKBIA)

Guidelines for treatment of atopic dermatitis

Atopijski dermatitis česta je, kronično recidivirajuća upalna bolest kože karakterizirana složenom etiopatogenezom i raznolikim kliničkim fenotipom. Klinička slika može biti različita, a bolest je obilježena ponavljajućim dermatitisom, izraženim svrbežom i značajnim utjecajem na kvalitetu života oboljele osobe i cijele obitelji. Dijagnoza se postavlja na temelju kliničke slike prema standardiziranim dijagnostičkim kriterijima, a procjena težine bolesti prema standardiziranim instrumentima za procjenu težine bolesti. Liječenje treba prilagoditi svakom bolesniku, a cilj liječenja je smanjiti simptome svrbeža, obnoviti oštećenu kožnu barijeru, spriječiti egzacerbaciju bolesti, spriječiti odnosno liječiti komplikacije i komorbiditete te smanjiti negativni utjecaj bolesti na kvalitetu života. Zahvaljujući napretku u razumijevanju etiopatogeneze, terapijske mogućnosti su zadnjih godina značajno napredovale. Hrvatsko dermatovenerološko društvo Hrvatskoga liječničkog zbora predstavlja smjernice za dijagnostiku i liječenje atopijskog dermatitisa. Smjernice su rezultat konsenzusa hrvatskih stručnjaka za atopijski dermatitis koji su kritički proučili mjerodavnu znanstvenu literaturu, koja se temelji na najboljim dokazima.Atopic dermatitis is a common, chronically recurrent inflammatory skin disease characterized by a complex etiopathogenesis and a variable clinical phenotype. The clinical presentation is heterogeneous, and the disease is characterized by a recurrent dermatitis, intense itching and a significant impact on the quality of life of patients and their family. The diagnosis is based on the clinical presentation according to the standardized diagnostic criteria, while the assessment of disease severity of the disease is based on the standardized tools for disease severity assessment. Treatment should be tailored to each patient profile, and the goal of the treatment is focused on decreasing symptoms and renewing damaged skin barrier, preventing the exacerbation of the disease and preventing or treating the complications and comorbidities, and decreasing the negative influence of the disease on the patient’s quality of life. Due to progress in understanding the etiopathogenesis, treatment options have significantly expanded in the past years. The Croatian Society of Dermatovenerology of the Croatian Medical Association is presenting guidelines for diagnosis and treatment of atopic dermatitis. These guidelines are the result of consensus of Croatian experts based on critical analysis of relevant, evidence-based scientific literature

Guidelines for treatment of atopic dermatitis

Atopijski dermatitis česta je, kronično recidivirajuća upalna bolest kože karakterizirana složenom etiopatogenezom i raznolikim kliničkim fenotipom. Klinička slika može biti različita, a bolest je obilježena ponavljajućim dermatitisom, izraženim svrbežom i značajnim utjecajem na kvalitetu života oboljele osobe i cijele obitelji. Dijagnoza se postavlja na temelju kliničke slike prema standardiziranim dijagnostičkim kriterijima, a procjena težine bolesti prema standardiziranim instrumentima za procjenu težine bolesti. Liječenje treba prilagoditi svakom bolesniku, a cilj liječenja je smanjiti simptome svrbeža, obnoviti oštećenu kožnu barijeru, spriječiti egzacerbaciju bolesti, spriječiti odnosno liječiti komplikacije i komorbiditete te smanjiti negativni utjecaj bolesti na kvalitetu života. Zahvaljujući napretku u razumijevanju etiopatogeneze, terapijske mogućnosti su zadnjih godina značajno napredovale. Hrvatsko dermatovenerološko društvo Hrvatskoga liječničkog zbora predstavlja smjernice za dijagnostiku i liječenje atopijskog dermatitisa. Smjernice su rezultat konsenzusa hrvatskih stručnjaka za atopijski dermatitis koji su kritički proučili mjerodavnu znanstvenu literaturu, koja se temelji na najboljim dokazima.Atopic dermatitis is a common, chronically recurrent inflammatory skin disease characterized by a complex etiopathogenesis and a variable clinical phenotype. The clinical presentation is heterogeneous, and the disease is characterized by a recurrent dermatitis, intense itching and a significant impact on the quality of life of patients and their family. The diagnosis is based on the clinical presentation according to the standardized diagnostic criteria, while the assessment of disease severity of the disease is based on the standardized tools for disease severity assessment. Treatment should be tailored to each patient profile, and the goal of the treatment is focused on decreasing symptoms and renewing damaged skin barrier, preventing the exacerbation of the disease and preventing or treating the complications and comorbidities, and decreasing the negative influence of the disease on the patient’s quality of life. Due to progress in understanding the etiopathogenesis, treatment options have significantly expanded in the past years. The Croatian Society of Dermatovenerology of the Croatian Medical Association is presenting guidelines for diagnosis and treatment of atopic dermatitis. These guidelines are the result of consensus of Croatian experts based on critical analysis of relevant, evidence-based scientific literature