Akuutin umpilisäketulehduksen diagnostiikka : diagnostinen pisteytys ja leikkausta edeltävän viiveen merkitys

Background and aims: Diagnostic scoring is a method for stratifying patients according to the probability of appendicitis, and therefore works as an excellent basis for a diagnostic algorithm. This study aimed at developing a new diagnostic score, the Adult Appendicitis Score (AAS), and validating its routine use as an integral part of a new diagnostic algorithm. Diagnostic accuracy of the imaging studies depends on the pre-test probability of the disease. This study aimed to assess how accurate the imaging was in various AAS-stratified pre-test probability groups. The effect of in-hospital delay on the risk of perforation is controversial. The research in this thesis aimed to further clarify the matter. Patients and methods: The study enrolled 1737 patients with acute right lower quadrant abdominal pain. The first data collection of 829 patients was used to develop the AAS and compare it with two previously published scores as well as with the clinical assessment. The validation study of AAS enrolled 908 patients in two university hospitals. The negative appendectomy rate was compared between the first and second patient cohort. Patients that had diagnostic imaging were stratified into three probability-of-appendicitis groups according to the AAS, and the diagnostic accuracy of ultrasound (US) and computed tomography (CT) were compared between the score groups. To find the best marker to detect pre-hospital perforations, laboratory results and two previously published diagnostic scores were analyzed. The effects of total duration of symptoms, pre-hospital delay, and in-hospital delay on the risk of perforation were analyzed. Results: After the AAS was developed and incorporated into a new diagnostic algorithm the negative appendectomy rate decreased from 18.2% to 8.2%. With a specificity of 93%, the AAS stratified half of all patients with appendicitis into the high-probability group. The probability of appendicitis was only 7% for the low-probability group. The AAS outperformed both the clinical assessment and two previously published scores. The diagnostic accuracy of imaging depended on the pre-test probability of appendicitis. When compared to the two other groups allocated by the AAS, in the low-probability group a positive CT and US findings yielded lower post-test probability for appendicitis. More false than true positive US results were found in the low-probability group. C-reactive protein (CRP) was the best marker for pre-hospital perforation. For patients with CRP values less than 99 mg/l longer in-hospital delay increased the perforation risk whereas the duration of pre-hospital delay showed no difference between patients with uncomplicated and complicated appendicitis. For patients with CRP values 99 mg/l or more, the in-hospital delay did not increase the perforation risk. Conclusions: The AAS provides an accurate method to stratify patients according to their probability of appendicitis. After the score was implemented into clinical routine, it led to a dramatic reduction in the negative appendectomy rates. When the AAS stratifies the patient to have a low probability of appendicitis, the benefits of imaging are questionable. False positive imaging results can even induce negative appendectomies. Most perforations in acute appendicitis occur as pre-hospital events. However, some of the perforations can be avoided by minimizing the in-hospital delay.Akuutti umpilisäketulehdus on tavallinen äkillisen vatsakivun syy. Vaikka umpilisäketulehduksen oireet ovat hyvin tunnettuja, tehdään edelleen myös turhia leikkauspäätöksiä. Uuden, väitöstutkimuksen yhteydessä kehitetyn, diagnostisen pisteytyksen käyttöönoton havaittiin vähentävän merkittävästi turhien umpilisäkepoistojen osuutta. LL Henna Sammalkorven tuoreessa väitöstutkimuksessa kehitettiin uusi aikuisten potilaiden tutkimisessa hyödynnettävä diagnostinen pisteytys, Adult Appendicitis Score. Pisteytyksellä potilaat, joilla epäillään umpilisäketulehdusta, jaotellaan kolmeen ryhmään umpilisäketulehduksen todennäköisyyden mukaan. Uuden pisteytyksen kehittämistä varten prospektiivisesti kerätty aineisto sisälsi 829 Meilahden sairaalassa umpilisäkkeen tulehduksen epäilyn vuoksi tutkittua potilasta. Aiempaa tarkempi pisteytys luotiin analysoimalla potilaiden oireita, tutkimuslöydöksiä ja laboratoriokoevastauksia. Uusi pisteytys oli tarkempi kuin päivystävien kirurgien arvio tai kumpikaan vertailussa mukana olleista aiemmin julkaistusta pisteytyksistä. Pisteytys on otettu rutiinikäyttöön osana uutta umpilisäkkeen tulehduksen diagnostista ohjeistusta Meilahden sairaalassa. Pisteytyksen käytän vaikutusta diagnostiikan tarkkuuteen tutkittiin 908 potilaan aineistossa Meilahdessa ja Kuopion Yliopistollisessa Sairalassa. Ennen uuden pisteytyksen käyttöönottoa 18,2 prosentissa Meilahden sairaalassa umpilisäkkeen tulehduksen epäilyn vuoksi tehdyissä leikkauksissa umpilisäke ei ollut tulehtunut. Uuden pisteytyksen käyttöönoton jälkeen luku laski 8,2 prosenttiin , Henna Sammalkorpi kuvaa tilannetta. Uuden pisteytyksen ohella tutkimuksessa selvitettiin sairaalaan saapumisen ja umpilisäkkeen poiston välisen aikavälin vaikutusta puhkeamariskiin. Tutkimuksessaan LL Henna Sammalkorpi havaitsi, että umpilisäkkeen puhkeaman todennäköisyyttä parhaiten kuvaava muuttuja on C-reaktiivinen proteiini, CRP. Potilailla, joiden CRP oli yli 99 jo sairaalaan tullessa, ei sairaalassa aiheutunut viive lisännyt puhkeaman todennäköisyyttä, sillä umpilisäke oli todennäköisimmin jo puhjennut ennen sairaalaan tuloa. Niillä potilaista, joiden CRP oli alle 99 sairaalassa aiheutunut viive lisäsi puhkeamariskiä. Mikäli sairaalassaoloaika ennen leikkausta kasvoi alle 6 tunnista yli 12 tuntiin, puhkeamariski kaksinkertaistui. Näin ollen osalla potilaista puhkeama voidaan välttää tarjoamalla potilaille viivytyksetöntä diagnostiikkaa ja hoitoa

Performance of imaging studies in patients with suspected appendicitis after stratification with adult appendicitis score

Background: Diagnostic scoring is used to stratify patients with suspected appendicitis into three groups: high, intermediate, and low probability of appendicitis. The stratification can be used for selective imaging to avoid the harms of radiation without compromising diagnostic accuracy. The aim was to study how stratification by Adult Appendicitis Score affects diagnostic performance of imaging studies. Methods: Analysis of 822 patients who underwent diagnostic imaging for suspected appendicitis was made. Adult Appendicitis Score was used to stratify patients into groups of high, intermediate, and low probability of appendicitis. Diagnostic performance of computed tomography (CT) and ultrasound (US) was compared between these patient groups. Results: After scoring, pre-test probability of appendicitis ranged from 9-16% in low probability group to 75-79% in high probability group in patients who underwent US or CT. Post-test probability of appendicitis after positive CT was 99, 91, and 75% in high probability, intermediate probability and low probability groups, respectively, p <0.001. After positive US the respective probabilities were 95, 91 and 42%, p <0.001. Conclusion: Diagnostic imaging has limited value in patients with low probability of appendicitis according to Adult Appendicitis Score.Peer reviewe

A new adult appendicitis score improves diagnostic accuracy of acute appendicitis - a prospective study

Peer reviewe

Bile Reflux is a Common Finding in the Gastric Pouch After One Anastomosis Gastric Bypass

INTRODUCTION: Data on postoperative bile reflux after one anastomosis gastric bypass (OAGB) is lacking. Bile reflux scintigraphy (BRS) has been shown to be a reliable non-invasive tool to assess bile reflux after OAGB. We set out to study bile reflux after OAGB with BRS and endoscopy in a prospective series (RYSA Trial). METHODS: Forty patients (29 women) underwent OAGB between November 2016 and December 2018. Symptoms were reported and upper gastrointestinal endoscopy (UGE) was done preoperatively. Six months after OAGB, bile reflux was assessed in UGE findings and as tracer activity found in gastric tube and esophagus in BRS (follow-up rate 95%). RESULTS: Twenty-six patients (68.4%) had no bile reflux in BRS. Twelve patients (31.6%) had bile reflux in the gastric pouch in BRS and one of them (2.6%) had bile reflux also in the esophagus 6 months postoperatively. Mean bile reflux activity in the gastric pouch was 5.2% (1-21%) of total activity. De novo findings suggestive of bile reflux (esophagitis, stomal ulcer, foveolar inflammation of gastric pouch) were found for 15 patients (39.5%) in postoperative UGE. BRS and UGE findings were significantly associated (P = 0.022). Eight patients experienced de novo reflux symptoms at 6 months, that were significantly associated with BRS and de novo UGE findings postoperatively (P = 0.033 and 0.0005, respectively). CONCLUSION: Postoperative bile reflux in the gastric pouch after OAGB is a common finding in scintigraphy and endoscopy. The long-term effects of bile exposure will be analyzed in future reports after a longer follow-up. TRIAL REGISTRATION: Clinical Trials Identifier NCT02882685.Peer reviewe

MARC1 variant rs2642438 increases hepatic phosphatidylcholines and decreases severity of non-alcoholic fatty liver disease in humans

Non peer reviewe

The PNPLA3-I148M Variant Confers an Antiatherogenic Lipid Profile in Insulin-resistant Patients

Context: The I148M (rs738409-G) variant in PNPLA3 increases liver fat content but may be protective against cardiovascular disease. Insulin resistance (IR) amplifies the effect of PNPLA3-I148M on liver fat. Objective: To study whether PNPLA3-I148M confers an antihyperlipidemic effect in insulin-resistant patients. Design: Cross-sectional study comparing the impact of PNPLA3-I148M on plasma lipids and lipoproteins in 2 cohorts, both divided into groups based on rs738409-G allele carrier status and median HOMA-IR. Setting: Tertiary referral center. Patients: A total of 298 obese patients who underwent a liver biopsy during bariatric surgery (bariatric cohort: age 49 +/- 9 years, body mass index [BMI] 43.2 +/- 6.8 kg/m(2)), and 345 less obese volunteers in whom liver fat was measured by proton magnetic resonance spectroscopy (nonbariatric cohort: age 45 +/- 14 years, BMI 29.7 +/- 5.7 kg/m(2)). Main Outcome Measures: Nuclear magnetic resonance profiling of plasma lipids, lipoprotein particle subclasses and their composition. Results: In both cohorts, individuals carrying the PNPLA3-I148M variant had significantly higher liver fat content than noncarriers. In insulin-resistant and homozygous carriers, PNPLA3-I148M exerted a distinct antihyperlipidemic effect with decreased very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) particles and their constituents, and increased high-density lipoprotein particles and their constituents, compared with noncarriers. VLDL particles were smaller and LDL particles larger in PNPLA3-I148M carriers. These changes were geometrically opposite to those due to IR. PNPLA3-I148M did not have a measurable effect in patients with lower IR, and its effect was smaller albeit still significant in the less obese than in the obese cohort. Conclusions: PNPLA3-I148M confers an antiatherogenic plasma lipid profile particularly in insulin-resistant individuals.Peer reviewe

Assessment of Lifestyle Factors Helps to Identify Liver Fibrosis Due to Non-Alcoholic Fatty Liver Disease in Obesity

Only some individuals with obesity develop liver fibrosis due to non-alcoholic fatty liver disease (NAFLD-fibrosis). We determined whether detailed assessment of lifestyle factors in addition to physical, biochemical and genetic factors helps in identification of these patients. A total of 100 patients with obesity (mean BMI 40.0 ± 0.6 kg/m2) referred for bariatric surgery at the Helsinki University Hospital underwent a liver biopsy to evaluate liver histology. Physical activity was determined by accelerometer recordings and by the Modifiable Activity Questionnaire, diet by the FINRISK Food Frequency Questionnaire, and other lifestyle factors, such as sleep patterns and smoking, by face-to-face interviews. Physical and biochemical parameters and genetic risk score (GRS based on variants in PNPLA3, TM6SF2, MBOAT7 and HSD17B13) were measured. Of all participants 49% had NAFLD-fibrosis. Independent predictors of NAFLD-fibrosis were low moderate-to-vigorous physical activity, high red meat intake, low carbohydrate intake, smoking, HbA1c, triglycerides and GRS. A model including these factors (areas under the receiver operating characteristics curve (AUROC) 0.90 (95% CI 0.84–0.96)) identified NAFLD-fibrosis significantly more accurately than a model including all but lifestyle factors (AUROC 0.82 (95% CI 0.73–0.91)) or models including lifestyle, physical and biochemical, or genetic factors alone. Assessment of lifestyle parameters in addition to physical, biochemical and genetic factors helps to identify obese patients with NAFLD-fibrosis

Käypä hoito -suosituksen fibroosilaskureiden toimivuus lihavien rasvamaksatautipotilaiden edenneen fibroosin selvittelyssä

JOHDANTO : Rasvamaksatautipotilaiden edenneen fibroosin tunnistaminen on tärkeää vakavien maksakomplikaatioiden ehkäisyssä. Käypä hoito -suosituksessa käytetään Fibrosis-4- (FIB-4) ja NAFLD Fibrosis Score (NFS) -fibroosilaskureita kaksiportaisesti. Selvitimme, miten Käypä hoito -algoritmin kaksiportainen seulonta toimii edenneen fibroosin selvittelyssä verrattuna yleisesti suositellun pelkän FIB-4:n käyttöön. MENETELMÄT : Tutkimukseen osallistui 401 lihavaa potilasta, joille tehtiin kliinisen tutkimuksen lisäksi maksabiopsia. Potilaille laskettiin FIB-4- ja NFS-riskipisteet, ja niiden osuvuutta tunnistaa maksabiopsialla varmistettu edennyt fibroosi arvioitiin. TULOKSET : Maksabiopsiassa ilmeni rasvamaksatauti 64 %:lla ja edennyt fibroosi 5 %:lla potilaista. Käypä hoito -algoritmi ohjasi jatkotutkimuksiin 76 potilasta eli merkitsevästi vähemmän kuin pelkkä FIB-4 (129 potilasta, p < 0,001). Algoritmi ja pelkkä FIB-4 tunnistivat edenneen fibroosin yhtä hyvin (18/20 vs 15/20 potilasta, p = 0,41). PÄÄTELMÄT : Käypä hoito -algoritmin mukainen lihavien potilaiden edenneen fibroosin kaksiportainen seulonta vähentää turhia lähetteitä jatkotutkimuksiin verrattuna pelkän FIB-4:n käyttöön.Peer reviewe

Hydroxysteroid 17-beta dehydrogenase 13 variant increases phospholipids and protects against fibrosis in nonalcoholic fatty liver disease

Carriers of the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) gene variant (rs72613567:TA) have a reduced risk of NASH and cirrhosis but not steatosis. We determined its effect on liver histology, lipidome, and transcriptome using ultra performance liquid chromatography-mass spectrometry and RNA-seq. In carriers and noncarriers of the gene variant, we also measured pathways of hepatic fatty acids (de novo lipogenesis [ONLI and adipose tissue lipolysis [ATL] using (H2O)-H-2 and H-2-glycerol) and insulin sensitivity using H-3-glucose and euglycemic-hyperinsulinemic clamp) and plasma cytokines. Carriers and noncarriers had similar age, sex and BMI. Fibrosis was significantly less frequent while phospholipids, but not other lipids, were enriched in the liver in carriers compared with noncarriers. Expression of 274 genes was altered in carriers compared with noncarriers, consisting predominantly of downregulated inflammation-related gene sets. Plasma IL-6 concentrations were lower, but DNL, ATL and hepatic insulin sensitivity were similar between the groups. In conclusion, carriers of the HSD17B13 variant have decreased fibrosis and expression of inflammation-related genes but increased phospholipids in the liver. These changes are not secondary to steatosis, ONL, ATL, or hepatic insulin sensitivity. The increase in phospholipids and decrease in fibrosis are opposite to features of choline-deficient models of liver disease and suggest HSD17B13 as an attractive therapeutic target.Peer reviewe

The PNPLA3-I148M variant increases polyunsaturated triglycerides in human adipose tissue

Background & Aims The I148M variant in PNPLA3 is the major genetic risk factor for non-alcoholic fatty liver disease (NAFLD). The liver is enriched with polyunsaturated triglycerides (PUFA-TGs) in PNPLA3-I148M carriers. Gene expression data indicate that PNPLA3 is liver-specific in humans, but whether it functions in adipose tissue (AT) is unknown. We investigated whether PNPLA3-I148M modifies AT metabolism in human NAFLD. Methods Profiling of the AT lipidome and fasting serum non-esterified fatty acid (NEFA) composition was conducted in 125 volunteers (PNPLA3(148MM/MI), n = 63; PNPLA3(148II), n = 62). AT fatty acid composition was determined in 50 volunteers homozygous for the variant (PNPLA3(148MM), n = 25) or lacking the variant (PNPLA3(148II), n = 25). Whole-body insulin sensitivity of lipolysis was determined using [H-2(5)]glycerol, and PNPLA3 mRNA and protein levels were measured in subcutaneous AT and liver biopsies in a subset of the volunteers. Results PUFA-TGs were significantly increased in AT in carriers versus non-carriers of PNPLA3-I148M. The variant did not alter the rate of lipolysis or the composition of fasting serum NEFAs. PNPLA3 mRNA was 33-fold higher in the liver than in AT (P <.0001). In contrast, PNPLA3 protein levels per tissue protein were three-fold higher in AT than the liver (P <.0001) and nine-fold higher when related to whole-body AT and liver tissue masses (P <.0001). Conclusions Contrary to previous assumptions, PNPLA3 is highly abundant in AT. PNPLA3-I148M locally remodels AT TGs to become polyunsaturated as it does in the liver, without affecting lipolysis or composition of serum NEFAs. Changes in AT metabolism do not contribute to NAFLD in PNPLA3-I148M carriers.Peer reviewe