THE ROLE OF BIOLOGIC THERAPY IN THE TREATMENT OF EXTRAINTESTINAL MANIFESTATIONS AND COMPLICATIONS OF INFLAMMATORY BOWEL DISEASE

Ekstraintestinalne manifestacije javljaju se u oko 35 % bolesnika s upalnim bolestima crijeva. Najčešće su zahvaćeni koštanozglobni sustav, koža, oči te jetra i žučni sustav. Zahvaćenost koštano-zglobnog sustava se javlja u 5-10 % bolesnika s ulceroznim kolitisom (UC) i u 10-20 % bolesnika s Crohnovom bolešću (CB). Simptomi variraju od blage artralgije do teškog akutnog artritisa. Primarni sklerozirajući kolangitis (PSC), autoimuni hepatitis, bolesti gušterače, kolestaza, kolelitijaza i porast aminotransferaza smatraju se hepatobilijarnim manifestacijama. Najčešće se prepoznaje PSC, osobito kod bolesnika s UC (oko 7,5 %). Biološka terapija neučinkovita je u liječenju te nema utjecaja na prirodni tijek bolesti. Od kožnih manifestacija najčešće se javljaju nodozni eritem (3-20 %) i gangrenozna pioderma (0,5-20 %). Oftalmološki poremećaji javljaju se u 2-5 % bolesnika s upalnim bolestima crijeva. Tegobe variraju od blagog konjunktivitisa do teških upala očnih ovojnica. Infliksimab je u CB indiciran u liječenju spondiloartropatija, artritisa/artralgija, gangrenozne pioderme, nodoznog eritema te oftalmoloških manifestacija, osim optičkog neuritisa. Slične su indikacije za upotrebu adalimumaba, osim što nema indikacije u liječenju nodoznog eritema. Kod bolesnika s UC, infliksimab je indiciran u liječenju spondiloartropatija i gangrenozne pioderme. Komplikacije upalnih bolesti crijeva su fistule, stenoze I strikture crijeva, apscesi, perforacije, krvarenja iz probavnog sustava te nastanak karcinoma crijeva i drugih maligniteta. Liječenje anti-TNF lijekovima dokazano je učinkovito jedino u liječenju perianalnih fistula u bolesnika s CB.Extraintestinal manifestations occur in about 35% of patients with inflammatory bowel diseases (IBD). Most frequently affected are bones and joints, skin, eyes, liver and biliary ducts. Extraintestinal manifestations of IBD are divided in two groups: reactive manifestations which depend on activity of IBD – peripheral arthritis, erythema nodosum, aphthous stomatitis, episcleritis and other manifestations which are independent on activity of IBD – pyoderma gangrenosum, uveitis, axial arthropathy, primary sclerosing cholangitis (PSC). Most affected are bones and joints. Symptoms vary from mild arthralgia to severe arthritis with painful swallowing of joints. They occur in about 5-10% of patients with ulcerative colitis (UC) and in 10-20% of patients with Crohn’s disease (CD). Both peripheral and axial joints can be affected. According to available data, most patients with active IBD and concomitant arthritis have benefit from infliximab therapy. Infliximab is also effective in maintenance of remission in group of patients with spondyloarthropathy. Adalimumab showed similar efficacy in treatment of ankylosing spondylitis, but there are still no data about efficacy of adalimumab in treatment of patients with IBD and concomitant arthritis. Primary sclerosing cholangitis, autoimmune hepatitis, cholestasis, cholelithiasis and elevation of aminotransferase are also considered to be extraintestinal manifestations of IBD. Most frequent is PSC which affects usually patients with UC (7.5% of patients). Course of liver disease is completely independent on activity of IBD, and destruction of biliary ducts is usually irreversible and refractory on treatment and most of the patients need liver transplantation. Anti-TNF therapy is also ineffective in treatment of PSC and has no impact on disease course and outcome. However, there is no contraindication for anti-TNF therapy of concomitant active IBD in this group of patients. Erythema nodosum (EN) and pyoderma gangrenosum (PG) are usual skin manifestations of IBD. Erythema nodosum occurs in about 3-20%, and pyoderma gangrenosum in about 0.5-20% of patients with IBD. Infliximab is proven to be effective in treatment of PG,but there is still not enough evidence on efficacy of anti-TNF drugs in treatment of EN and other rare skin manifestations of IBD. About 2-5% of patients with IBD have also some ophthalmological disorder. Symptoms vary from mild conjunctivitis to severe inflammation of eye membranes – iritis, episcleritis, scleritis and uveitis. It seems that infliximab and adalimumab can diminish uveitis and scleritis in patients with different autoimmune disorders and IBD. According to guidelines of American Gastroenterology Association (AGA), in group of patients with CD, infliximab is indicated in treatment of spondyloarthropathies, arthritis, arthralgia, pyoderma gangrenosum, erythema nodosum, uveitis and other ophthalmological manifestations of IBD except optical neuritis which can worse or be consequence of anti-TNF treatment. Similar indications exist for use of adalimumab except in case of erythema nodosum. In group of patients with extraintestinal manifestations of UC, infliximab is indicated in treatment of spondyloarthropathies and pyoderma gangrenosum. Complications of IBD are fistulas (perianal and non-perianal), stenosis and strictures, abscesses, bowel perforations, gastrointestinal bleeding and development of different malignomas. Anti-TNF drugs are proven to be effective and indicated only for treatment of perianal fistulas in patients with Crohn’s disease. In group of patients with UC, there are only few case reports on beneficial effect of infliximab in treating chronic pouchitis and infliximab in treatment of these patients still cannot be recommended

Correlation between biometeorological forecast and the incidence of obstetric admissions in perinatal center during five years: A retrospective study of one center

Background and purpose: The aim of this study was to correlate obstetric admissions at a tertiary perinatal center with biometeorological forecast and weather conditions. Materials and methods: This retrospective study was conducted at the Department of Gynaecology and Obstetrics Clinical Hospital “Sveti Duh” over five years, from January 1, 2014 to December 31, 2018. The hospital’s emergency data was used for record of obstetric admissions on each day. The selected days were sorted in 4 groups based on biometeorological forecast. Results: In the observed period, there were a total of 18,072 obstetric admissions. There were 216 days with fifteen or more admissions. The results showed no significant difference between obstetric admission based on the biometeorological forecast one day before or three days before. Most hospitalization were on days with a favorable biometeorological forecast in the observed period, 68 days with more than fifteen admissions per day. The day before, the biometeorological forecast was mostly favorable or relatively favorable. Conclusion: Our retrospective single-center study did not show a significant difference between obstetric hospital admissions depending on biometeorological conditions, but the higher number of admissions during days with a favorable forecast is definitely the basis for future studies with larger dataset

Association of weather conditions and the day with extreme number of deliveries with spontaneous onset in a tertiary referral perinatal center

Background and purpose: The effect of weather on people’s well-being and health has been previously noticed and has been a subject of interest for medical professionals and laypeople throughout human history. There are many studies connecting gynecology and obstetrics with weather, some of them investigating the weather and physiological processes such as onset of labor.Materials and methods: In this paper we tried to find relationship between weather conditions and the day with extreme number of deliveries with spontaneous onset (contractions and/or rupture of membranes) in a tertiary referral perinatal center. It is still debatable whether we could connect the weather conditions with actual childbirth.Results: A case analysis shows that there could be a connection between the development of the weather situation and the extreme number of deliveries with spontaneous onset.Conclusion: Unfavorable biometeorological conditions were the result of weather conditions that affect people. In our case there was strong cold advection during the analyzed period, especially on the day with an extreme number of deliveries with spontaneous onset, and significant drop of barometric pressure

Postoji li povezanost komplikacija rane trudnoće s biometeorološkom prognozom?

The aim of our study was to connect the possible complications of early pregnancy (miscarriage and symptomatic ectopic pregnancy) up to the 12th week of gestation with biometeorological conditions while assuming a greater number of incidents with an unfavorable biometeorological forecast. We performed a retrospective observational study using medical data of a single medical center of Department of Gynecology and Obstetrics, Sveti Duh University Hospital and meteorological data from the Croatian Meteorological and Hydrometeorological Service in Zagreb. We tracked the number of visits to the gynecology and obstetrics emergency unit on a daily basis during 2017. Days with five or more visits were selected and underwent further analysis, during which the number of miscarriages and symptomatic ectopic pregnancies was noted. The information from the biometeorological forecast was then extracted and added to the database. Our results did not show a statistically significant difference between the groups determined by biometeorological forecast in the number of spontaneous abortions or ectopic pregnancy. Also, statistically significant results did not follow the expected trend of the increasing number of complications related to worse biometeorological forecast, or vice versa, a decreased number of complications with better forecast. Our single-center retrospective analysis of emergency unit visits related to weather conditions did not show a connection between the complications of early pregnancy and biometeorological conditions. However, different results could emerge in future studies. Considering the large and high-quality database collected for this study, efforts in researching the connection between other gynecologic pathologies and weather conditions will be feasible.Cilj ovoga istraživanja bio je povezati komplikacije rane trudnoće (spontani pobačaj i izvanmaternična trudnoća) do 12. tjedna gestacije s biometeorološkim uvjetima, očekujući veći broj incidenata u uvjetima nepovoljne biometeorološke prognoze. Proveli smo retrospektivno opservacijsko istraživanje koristeći medicinske podatke Klinike za ginekologiju i porodništvo Kliničke bolnice Sveti Duh i meteorološke podatke Državnoga hidrometeorološkog zavoda u Zagrebu. Zabilježili smo broj hitnih pregleda na Klinici za ginekologiju i porodništvo tijekom 2017. godine. Dani s pet ili više pregleda su zabilježeni, a zabilježen je i broj spontanih pobačaja i izvanmaterničnih trudnoća. Informacije o biometeorološkoj prognozi za obrađene dane su dodane prikupljenoj bazi podataka. Naši rezultati nisu pokazali statistički značajnu razliku između skupina određenih biometeorološkom prognozom u broju spontanih pobačaja i izvanmaterničnih trudnoća. Statistički značajne rezultate nisu pokazali ni očekivani porast broja komplikacija s lošijom biometeorološkom prognozom ili smanjen broj komplikacija povezanih s boljom biometeorološkom prognozom. Naša retrospektivna analiza nije pokazala povezanost posjeta hitnom prijmu s vremenskim prilikama, stoga ni povezenost komplikacija rane trudnoće s vremenskim uvjetima. Međutim, drugačiji rezultati se mogu dobiti u budućim istraživanjima. S obzirom na veliku i kvalitetnu bazu podataka prikupljenu u ovom istraživanju daljnja nastojanja u istraživanju povezanosti ginekološke patologije i vremenskih uvjeta uvelike su olakšana

Nutrition in Pancreatic Diseases

Pankreatitis je upalno stanje gušterače koje često iz svojeg akutnog oblika može prijeći u kroničnu bolest. Bolesnici s pankreatitisom imaju povećane nutritivne potrebe zbog upale, dok, s druge strane, zbog boli, mučnine i povraćanja pate od energijskog, proteinskog ili nutritivnog deficita. Hipokalcemija i hipomagnezemija mogu se pojaviti već u prvim fazama akutnog pankreatitisa. Bolesnici s dugotrajnim i prekomjernim unosom alkohola mogu, uz proteinsko-energijsku malnutriciju, imati i deficit vitamina i minerala: tiamina, folne kiseline, cinka, vitamina D, K, E, A i B12 te karotena. Osnovni cilj nutritivne njege bolesnika s pankreatitisom jest osigurati adekvatan unos energije. To je osobito važno u bolesnika s akutnim pankreatitisom u kojih se pokazalo da pravilna nutritivna njega može smanjiti komplikacije i skratiti vrijeme boravka u bolnici.Pancreatitis is inflammation of the pancreas that can be acute and often progress to chronic pancreatitis. Like in most diseases, patients with pancreatitis have a negative energy balance. They have an increased caloric expenditure due to inflammation and a decreased intake due to abdominal pain, nausea and vomiting. Hypocalcaemia and hypomagnesaemia can occur even with the first episode of acute pancreatitis. Patients with long-standing excessive alcohol intake may have thiamine and folate deficiencies in addition to protein-calorie malnutrition. Patients with chronic pancreatitis can have deficiency of fat-soluble vitamins, particularly vitamins D, E, A, K, β-carotene and B12. The basis of nutritional management in pancreatitis is to meet the energy needs of the patient through appropriate calorie administration. This is particularly important in acute pancreatitis because it may reduce complications and decrease hospital stays

ANTI–TNF THERAPY IN TREATMENT OF LUMINAL CROHN’S DISEASE

Intenzivna terapija primjenom anti-TNF lijekova infliksimaba i adalimumaba u luminalnoj Crohnovoj bolesti može biti učinkovitija od konvencionalne terapije u postizanju i održavanju kliničke remisije, zacijeljenju sluznice te postizanju i održavanju “duboke remisije”. Odluka o početku terapije anti-TNF lijekovima ovisi o nekoliko čimbenika: aktivnosti, težini, lokalizaciji i proširenosti bolesti, o fenotipu i ponašanju bolesti, o pridruženim bolestima i odgovoru na druge terapijske opcije te o mogućim komplikacijama. Sve je više dokaza da je rana intenzivna terapija luminalnog oblika Crohnove bolesti primjenom anti-TNF lijekova i imunosupresiva povezana s povećanom vjerojatnošću cijeljenja sluznice i održavanjem remisije bolesti bez steroida. Također, sve je vise podataka o kliničkim, epidemiološkim i laboratorijskim biljezima u času dijagnoze koji mogu predskazati nepovoljnu prognozu i nastanak teškog oblika bolesti te su bolesnici s nepovoljnim navedenim pokazateljima kandidati za rano započinjanje terapije anti-TNF lijekovima. Kandidati za anti-TNF terapiju su i bolesnici koji nisu odgovorili na konvencionalnu terapiju, bolesnici s umjerenim i teškim oblikom bolesti koji ne podnose steroide, bolesnici u kojih bi primjena steroida izazvala značajne neželjene učinke, bolesnici koji ne žele steroidnu terapiju te bolesnici s potrebom opetovanih ciklusa steroidne terapije.Biologic drugs directed against main proinflammatory mediator in inflammatory bowel disease (IBD) - tumor necrosis factor α (TNF α) – represent very effective and clinically proven therapy of IBD. Meta-analysis and daily clinical practice confirm efficacy of infliximab and adalimumab in induction and maintenance of remission without steroids in patients with luminal Crohn’s disease. Main therapeutic goals are reduction of complications, reduction of number of hospitalizations and surgical interventions and improvement of quality of life, work capacity and reproductive ability of patients. There are few very important issues that one must consider before starting an anti-TNF therapy in patients with luminal Crohn’s disease. First, it is necessary to identify patients who failed to respond to conventional drugs and who would benefit the most from early application of biologics. It is very important to exclude presence of strictures or other complications like intraabdominal fistulas and collections before starting anti-TNF therapy. Once we decide to start biologic therapy, it is important to apply adequate dose and regime of anti-TNF therapy and to change and adjust treatment to achieve and maintain remission in patients who lose response. In general, treatment recommendations depend on disease activity and severity, extension and localization of lesions, comorbidities and possible complications of disease and/or treatment. There are few clinical instruments and laboratory surrogates that help us to assess disease activity. Most used are Crohn’s Disease Activity Index (CDAI), Harvey – Bradshaw index (HBI), concentration of C-reactive protein (CRP) and fecal lactoferrin and calprotectin. In assessment of mucosal injury we rely on two complementary endoscopic indices of activity - Crohn’s Disease Endoscopic Index of Severity (CDEIS) and Simple Endoscopic Score for Crohn’s Disease (CD-SES). However, in time of diagnosis of Crohn’s disease available clinical, serological or laboratory markers do not have acceptably predictive value for future disease behavior and there are still no genetic indicator that could predict disease course. There are some clinical and epidemiologic factors that could be related to unfavorable disease course. Age less than 40 years, extended disease, need for steroid therapy early after diagnosis and perianal disease are considered to predict worse prognosis in patients with luminal Crohn’s disease. According to available data, it seems that early intensive therapy with anti-TNF drugs as monotherapy or in combination with immunosuppressive drugs in this group of patients increases possibility of induction of remission, mucosal healing and maintenance of steroid-free remission. Candidates for anti-TNF therapy are also patients who did not respond to conventional treatment, patients with moderate or severe disease who are intolerant to steroids, patients in whom we expect severe adverse effects from steroid treatment, patients who do not accept steroid treatment and patients with frequent relapses and need for steroids