Major Variation in the Incidence of Appendicitis Before, During and After Pregnancy: A Population-Based Cohort Study.

BACKGROUND: Previous studies indicate a low incidence of appendicitis in third-trimester pregnancy, suggesting a protecting effect of pregnancy. This large population-based cohort study analyzes the association of appendicitis with pregnancy in more detail. The aim of the study was to investigate the incidence of appendicitis and negative appendectomy before, during and after pregnancy. METHODS: Cross-linking between two Swedish health registries provided data on appendectomy for all women in Sweden giving birth between 1973 and 2013. We analyzed the incidence rates (IR) of perforated and non-perforated appendicitis and negative appendectomy before, during and after pregnancy, and secular trends during the study period. Standardized incidence ratios (SIR) were estimated using age-, sex- and period-specific IR from the background population in Sweden. RESULTS: Some 3,888,452 pregnancies resulted in birth during the study period. An appendectomy was registered for 27,575 women in the interval starting one year before and ending two years after pregnancy. The incidence of appendicitis varied substantially during and after pregnancy. SIR for perforated appendicitis was 0.47 (95% CI 0.38-0.59) in the third trimester, 3.89 (2.92-5.18) peripartum, 2.20 (1.89-2.55) in the puerperium and 1.27 (1.19-1.36) in the year postpartum. The pattern was similar for non-perforated appendicitis. Negative appendectomy decreased postpartum. Incidence rate of non-perforated appendicitis and negative appendectomy decreased for both pregnant and non-pregnant women during the study period. CONCLUSIONS: The findings in this study suggest a protecting effect of pregnancy on the development of appendicitis, which is followed by a rebound effect after birth.

Randomized clinical trial of Appendicitis Inflammatory Response score-based management of patients with suspected appendicitis.

BACKGROUND: The role of imaging in the diagnosis of appendicitis is controversial. This prospective interventional study and nested randomized trial analysed the impact of implementing a risk stratification algorithm based on the Appendicitis Inflammatory Response (AIR) score, and compared routine imaging with selective imaging after clinical reassessment. METHOD: Patients presenting with suspicion of appendicitis between September 2009 and January 2012 from age 10 years were included at 21 emergency surgical centres and from age 5 years at three university paediatric centres. Registration of clinical characteristics, treatments and outcomes started during the baseline period. The AIR score-based algorithm was implemented during the intervention period. Intermediate-risk patients were randomized to routine imaging or selective imaging after clinical reassessment. RESULTS: The baseline period included 1152 patients, and the intervention period 2639, of whom 1068 intermediate-risk patients were randomized. In low-risk patients, use of the AIR score-based algorithm resulted in less imaging (19·2 versus 34·5 per cent; P < 0·001), fewer admissions (29·5 versus 42·8 per cent; P < 0·001), and fewer negative explorations (1·6 versus 3·2 per cent; P = 0·030) and operations for non-perforated appendicitis (6·8 versus 9·7 per cent; P = 0·034). Intermediate-risk patients randomized to the imaging and observation groups had the same proportion of negative appendicectomies (6·4 versus 6·7 per cent respectively; P = 0·884), number of admissions, number of perforations and length of hospital stay, but routine imaging was associated with an increased proportion of patients treated for appendicitis (53·4 versus 46·3 per cent; P = 0·020). CONCLUSION: AIR score-based risk classification can safely reduce the use of diagnostic imaging and hospital admissions in patients with suspicion of appendicitis. Registration number: NCT00971438 ( http://www.clinicaltrials.gov).

Short-term complications and long-term morbidity of laparoscopic and open appendicectomy in a national cohort.

BACKGROUND: Laparoscopic appendicectomy has been proposed as the standard for surgical treatment of acute appendicitis, based on controversial evidence. This study compared outcomes after open and laparoscopic appendicectomy in a national, population-based cohort. METHODS: All patients who underwent open or intended laparoscopic appendicectomy in Sweden between 1992 and 2008 were identified from the Swedish National Patient Register. The outcomes were analysed according to intention to treat with multivariable adjustment for confounding factors and survival analytical techniques where appropriate. RESULTS: A total of 169 896 patients underwent open (136 754) or intended laparoscopic (33 142) appendicectomy. The rate of intended laparoscopic appendicectomy increased from 3·8 per cent (425 of 11 175) in 1992 to 32·9 per cent (3066 of 9329) in 2008. Laparoscopy was used most frequently in middle-aged patients, women and patients with no co-morbidity. The rate of conversion from laparoscopy to open appendicectomy decreased from 75·3 per cent (320 of 425) in 1992 to 19·7 per cent (603 of 3066) in 2008. Conversion was more frequent in women and those with perforated appendicitis, and the rate increased with age and increasing co-morbidity. After adjustment for co-variables, compared with open appendicectomy, laparoscopy was associated with a shorter length of hospital stay (by 0·06 days), a lower frequency of negative appendicectomy (adjusted odds ratio (OR) 0·59; P < 0·001), wound infection (adjusted OR 0·54; P = 0·004) and wound rupture (adjusted OR 0·44; P = 0·010), but higher rates of intestinal injury (adjusted OR 1·32; P = 0·042), readmission (adjusted OR 1·10; P < 0·001), postoperative abdominal abscess (adjusted OR 1·58; P < 0·001) and urinary infection (adjusted OR 1·39; P = 0·020). Laparoscopy had a lower risk of postoperative small bowel obstruction during the first 2 years after surgery, but not thereafter. CONCLUSION: The outcomes of laparoscopic and open appendicectomy showed a complex and contrasting pattern and small differences of limited clinical importance. The choice of surgical method therefore depends on the local situation, the surgeon's experience and the patient's preference.

Possible transmission of Candida albicans on an intensive care unit: genotype and temporal cluster analyses.

BACKGROUND: Nosocomial transmission of Candida spp. has not been fully explored and previous studies have shown conflicting results. AIM: To evaluate the possible nosocomial transmission of Candida spp. on an intensive care unit (ICU). METHODS: A prospective study was conducted for a period of 19 months, including all patients on our ICU with growth of Candida spp. from surveillance and directed cultures. Molecular typing with repetitive sequence-based polymerase chain reaction was used to define genotype relationships between the Candida albicans and Candida glabrata isolates. Candida isolates obtained from blood cultures taken from patients in our county outside the ICU were used as a reference. Temporal cluster analysis was performed to evaluate genotype distribution over time. FINDINGS: Seventy-seven patients with 78 ICU stays, representing 12% of all ICU stays, were found to harbour 180 isolates of Candida spp. Molecular typing revealed 27 C. albicans genotypes and 10 of C. glabrata. Possible clustering, indicated by overlapping stays of patients with indistinguishable candida genotypes, was observed on seven occasions with C. albicans and on two occasions with C. glabrata. Two C. albicans genotypes were found significantly more often in the ICU group compared with the reference group. Moreover, C. albicans genotypes isolated from more than one patient were significantly more often found in the ICU group. Temporal cluster analysis revealed a significantly increased number of pairs with indistinguishable genotypes at a 21-day interval, indicating clustering. CONCLUSION: This study indicates possible transmission of C. albicans between ICU patients based on genotyping and temporal cluster analysis.

Survival and prognostic factors in patients with small bowel carcinoid tumour.

BACKGROUND: Previous studies of small bowel carcinoid tumours usually presented overall or relative survival. This study, in addition, evaluated disease-specific survival in a cohort of patients in a geographically defined population. METHODS: Patients diagnosed with carcinoid of the jejunum or ileum in Jönköping County between 1960 and 2005 were eligible for inclusion. Available tumour specimens were re-examined to confirm the diagnosis. Medical records and pathology reports were reviewed in detail. RESULTS: A total of 145 patients were included in the study. One hundred and thirty-five patients underwent surgery in connection with the diagnosis. Resection was considered complete (R0) in 74 patients (54·8 per cent). Only two localized tumours recurred, whereas no patient with distant metastases was cured. Patients with regional metastases who underwent R0 resection had a better survival than patients with incomplete resection (P = 0·005), and a majority of patients remained recurrence-free. Median overall survival was 7·2 years and median disease-specific survival 12·3 years. In multivariable analysis, age 61-74 years (hazard ratio (HR) 3·78, 95 per cent confidence interval 1·86 to 7·68), age 75 years or more (HR 3·96, 1·79 to 8·74), distant metastases (HR 14·44, 1·59 to 131·36) and incomplete tumour resection (HR 2·71, 1·11 to 6·61) were associated with worse disease-specific survival. Later time period of diagnosis (HR 0·45, 0·24 to 0·84) was associated with better disease-specific survival. CONCLUSION: Age, disease stage and complete resection were identified as independent prognostic factors for survival in patients with small bowel carcinoid tumours. The importance of achieving R0 resection is therefore emphasized.

Different cytokine profiles in patients with a history of gangrenous or phlegmonous appendicitis.

Appendicitis is one of the most common and costly acute abdominal states of illnesses. Previous studies suggest two types of appendicitis which may be different entities, one which may resolve spontaneously and another that progresses to gangrene and perforation. Gangrenous appendicitis has a positive association to states of Th1 mediated immunity whereas Th2 associated immune states are associated with lower risk of appendicitis. This study investigated the inflammatory response pattern in patients previously appendicectomized for gangrenous (n = 7), or phlegmonous appendicitis (n = 8) and those with a non-inflamed appendix (n = 5). Peripheral blood mononuclear cells were analysed with ELISPOT analysis for number of spontaneous or antigen/mitogen stimulated IFN-gamma, IL-4, IL-10 and IL-12 secreting cells or with ELISA for concentration of spontaneous or antigen/mitogen stimulated IFN-gamma, IL-5 and IL-10. Spontaneously IL-10 secreting cells/100,000 lymphocytes were increased in the gangrenous group compared to the phlegmonous group (P = 0.015). The median concentration of IL-10 secreted after Tetanus toxoid (TT)-stimulation were higher in the gangrenous group and the control group, than the phlegmonous group (P = 0.048 and P = 0.027, respectively). The median concentration of TT induced IFN-gamma secretion was higher for the gangrenous group compared to both the phlegmonous group and the control group (P = 0.037 and P = 0.003). Individuals with a history of gangrenous appendicitis demonstrated ability to increased IL-10 and IFN-gamma production. The increased IFN-gamma may support the notion of gangrenous appendicitis as an uncontrolled Th1 mediated inflammatory response and increased IL-10 may speculatively indicate the involvement of cytotoxic cells in the progression to perforation.

Meta-analysis of the clinical and laboratory diagnosis of appendicitis.

BACKGROUND: The importance of specific elements in the clinical diagnosis of appendicitis is controversial. This review analyses the diagnostic value of elements of disease history, clinical findings and laboratory test results in suspected appendicitis. METHODS: A systematic Medline search was made of all published studies on the clinical and laboratory diagnosis of appendicitis in patients admitted to hospital with suspected disease. Meta-analyses of receiver-operator characteristic (ROC) areas, and positive and negative likelihood ratios, of 28 diagnostic variables described in 24 studies are presented. RESULTS: Inflammatory response variables (granulocyte count, proportion of polymorphonuclear blood cells, white blood cell count and C-reactive protein concentration), descriptors of peritoneal irritation (rebound and percussion tenderness, guarding and rigidity) and migration of pain were the strongest discriminators, with ROC areas of 0.78 to 0.68. The discriminatory power of the inflammatory variables was particularly strong for perforated appendicitis, with ROC areas of 0.85 to 0.87. Appendicitis was likely when two or more inflammatory variables were increased and unlikely when all were normal. CONCLUSION: Although all clinical and laboratory variables are weak discriminators individually, they achieve a high discriminatory power when combined. Laboratory examination of the inflammatory response, clinical descriptors of peritoneal irritation, and a history of migration of pain yield the most important diagnostic information and should be included in any diagnostic assessment.

Small bowel obstruction after appendicectomy.

BACKGROUND: This study analysed the risk of surgically treated small bowel obstruction after open appendicectomy. METHODS: This was a historical cohort study of 245 400 patients who underwent open appendicectomy and population-based matched controls, identified by linkage of computer registries. Analyses were made with the life-table technique, Kaplan-Meier plots and Cox proportional hazards regression analysis. RESULTS: The cumulated risk of surgically treated small bowel obstruction after appendicectomy was 0.41 per cent after 4 weeks, 0.63 per cent after 1 year and 1.30 per cent after 30 years of follow-up, compared with 0.003 per cent at 1 year and 0.21 per cent after 30 years of follow-up among the non-operated controls. The highest risk was found after operation for other diagnoses (adjusted hazard ratio 5.2 (95 per cent confidence interval 4.6-5.8)), followed by operation for perforated appendicitis (adjusted hazard ratio 3.5 (3.1-3.8)), non-specific abdominal pain (adjusted hazard ratio 2.6 (2.3-3.0)) and mesenteric lymphadenitis (adjusted hazard ratio 2.4 (2.0-2.8)) compared with operation for non-perforated appendicitis. The relation with age was J shaped, with the lowest risk at 20-39 years. Women had a slightly lower risk than men. CONCLUSION: The risk of postoperative small bowel obstruction needing surgical treatment after open appendicectomy is lower than previously thought. Perforated appendicitis, negative appendicectomy and high age are the risk factors.

An oligomer from flaxseed composed of secoisolariciresinoldiglucoside and 3-hydroxy-3-methyl glutaric acid residues.

A straight-chain oligomeric structure composed of five secoisolariciresinoldiglucoside (SDG) residues interconnected by four 3-hydroxy-3-methyl glutaric acid (HMGA) residues (molecular weight ca. 4000 Da) was assigned to the main lignan of flaxseed on the basis of nuclear magnetic resonance spectroscopy (NMR).

Identification of a sucrose diester of a substituted beta-truxinic acid in oats.

A novel compound, 4,4'-dihydroxy-3,3'-dimethoxy-beta-truxinic acid esterified to sucrose through the fructosyl 3-and 6-carbons (1), was isolated from oat grains (Avena sativa L.). Its structure was determined by a combination of mass spectrometry and 1-D and 2-D NMR. The amounts of 1 in groats of six different oat cultivars ranged from 101 to 150 microg g(-1) (dry wt). None was detected in the hulls. The free diacid, 4,4'-dihydroxy-3,3'-dimethoxy-beta-truxinic acid (2), could not be detected in groats nor in hulls.

Mortality after appendectomy in Sweden, 1987-1996.

OBJECTIVE: To study mortality after appendectomy. SUMMARY BACKGROUND DATA: The management of patients with suspected appendicitis remains controversial, with advocates of early surgery as well as of expectant management. Mortality is not known. METHODS: The authors conducted a complete follow-up of deaths within 30 days after all appendectomies in Sweden (population 8.9 million) during the years 1987 to 1996 (n = 117,424) by register linkage. The case fatality rate (CFR) and the standardized mortality ratio (SMR) were analyzed by discharge diagnosis. RESULTS: The CFR was 2.44 per 1,000 appendectomies. It was strongly related to age (0.31 per 1,000 appendectomies at 0-9 years of age, decreasing to 0.07 at 20-29 years, and reaching 164 among nonagenarians) and diagnosis at surgery (0.8 per 1,000 appendectomies after nonperforated appendicitis, 5.1 after perforated appendicitis, 1.9 after appendectomies for nonsurgical abdominal pain, and 10.0 for those with other diagnoses). The SMR showed a sevenfold excess rate of deaths after appendectomy compared with the general population. The relation to age was less marked (SMR of 44.4 at 0-9 years, decreasing to 2.4 in patients aged 20-29 years. and reaching 8.1 in nonagenarians). The SMR was doubled after perforation compared with nonperforated appendicitis (6.5 and 3.5, respectively). Nonsurgical abdominal pain and other diagnoses were associated with a high excess rate of deaths (9.1 and 14.9, respectively). The most common causes of deaths were appendicitis, ischemic heart diseases and tumors, followed by gastrointestinal diseases. CONCLUSIONS: The CFR after appendectomy is high in elderly patients. The excess rate of death for patients with nonperforated appendicitis and nonsurgical abdominal pain suggests that the deaths may partly be caused by the surgical trauma. Increased diagnostic efforts rather than urgent appendectomy are therefore warranted among frail patients with an equivocal diagnosis of appendicitis.

Appendectomy and protection against ulcerative colitis.

BACKGROUND: A history of appendectomy is rare in patients with ulcerative colitis. This suggests a protective effect of appendectomy or that appendicitis and ulcerative colitis are alternative inflammatory responses. We sought to characterize this inverse relation further. METHODS: We studied a cohort of 212,963 patients who underwent appendectomy before the age of 50 years between 1964 and 1993 and a cohort of matched controls who were identified from the Swedish Inpatient Register and the nationwide census. The cohort was followed until 1995 for any subsequent diagnosis of ulcerative colitis. RESULTS: Patients who underwent appendectomy for appendicitis and mesenteric lymphadenitis had a low risk of ulcerative colitis (for patients with perforated appendicitis, the adjusted hazard ratio was 0.58 [95 percent confidence interval, 0.38 to 0.87]; for those with nonperforated appendicitis it was 0.76 [95 percent confidence interval, 0.65 to 0.90]; and for those with mesenteric lymphadenitis it was 0.57 [95 percent confidence interval, 0.36 to 0.89]). In contrast, patients who underwent appendectomy for nonspecific abdominal pain had the same risk of ulcerative colitis as the controls (adjusted hazard ratio, 1.06; 95 percent confidence interval, 0.74 to 1.52). For the patients who had appendicitis, an inverse relation with the risk of ulcerative colitis was found only for those who underwent surgery before the age of 20 years (P<0.001). CONCLUSIONS: Appendectomy for an inflammatory condition (appendicitis or lymphadenitis) but not for nonspecific abdominal pain is associated with a low risk of subsequent ulcerative colitis. This inverse relation is limited to patients who undergo surgery before the age of 20 years.

Incidence of appendicitis during pregnancy.

BACKGROUND: The aetiology and pathogenesis of appendicitis remains unknown. A relation with female sex hormones has been proposed because of a lower incidence among women and incidence variations during the menstrual cycle, but studies have given inconsistent results. Pregnancy constitutes a period of dramatic increases in levels of female sex hormones, but the incidence of appendicitis during childbearing is not known. METHODS: Case-control study of pregnancy status at the time of appendectomy of 53 058 women and of 53 058 population-based age-matched controls. Cases and controls were identified by linkage of the Swedish Inpatient Register and the nation-wide census. Pregnancy status at the time of operation was obtained by linkage with the Swedish Fertility Register. Differences in pregnancy status were analysed using conditional logistic regression and expressed as odds ratios (OR) with 95% CI. RESULTS: Fewer patients than expected with appendicitis were pregnant compared with the controls, especially in the third trimester (OR = 0.49, 95% CI : 0.30-0.79 for perforated and OR = 0.33, 95% CI : 0.28-0.39 for non-perforated appendicitis). CONCLUSIONS: The reduced incidence of appendicitis suggests a protective effect of pregnancy, especially in the third trimester.

Why does the clinical diagnosis fail in suspected appendicitis?

OBJECTIVE: To identify systematic errors in surgeons' estimations of the importance of diagnostic variables in the decision to explore patients with suspected appendicitis. DESIGN: Prospective case series. SETTING: Two emergency departments, Sweden. PATIENTS: 496 patients with suspected appendicitis on admission, of whom 194 had a correct operation for appendicitis and 59 had a negative exploration. MAIN OUTCOME MEASURES: Predictors of a negative exploration expressed as the odds ratio (OR) for negative exploration. Variables influence on the decision to operate, expressed as the OR for operation, compared with the true diagnostic importance, expressed as the OR for appendicitis. RESULTS: Predictors of negative explorations were high ratings in variables describing pain and tenderness (patient's perceived pain, abdominal tenderness, rebound tenderness, guarding or rectal tenderness), weak or absent inflammatory response, female sex, long duration of symptoms and absence of vomiting, with OR of 1.8-3.0. Pain and tenderness had too strong an influence on the decision to operate whereas the lack of an inflammatory response, no vomiting, and long duration of symptoms were not given enough attention. There was no sex difference in the proportion of patients with non-surgical abdominal pain (NSAP) who were operated on, but NSAP was more common and appendicitis less common among women, leading to a larger proportion of negative appendicectomies among women. CONCLUSION: Negative explorations in patients with suspected appendicitis are related to systematic errors in the clinical diagnosis with too strong an emphasis on pain and tenderness, and too little attention paid to duration of symptoms and objective signs of inflammation. Rectal tenderness is not a sign of appendicitis. The risk of diagnostic errors is similar in men and women.

Repeated clinical and laboratory examinations in patients with an equivocal diagnosis of appendicitis.

In-hospital observation with repeated clinical examinations is commonly used in patients with an equivocal diagnosis of appendicitis. It is not known if repeated measurements of temperature and laboratory examinations have any diagnostic importance in this situation. The importance of repeated measurements of the body temperature, white blood cell (WBC) and differential cell counts, C-reactive protein concentration (CRP) and of the surgeon's repeated assessments was prospectively analyzed in 420 patients with an equivocal diagnosis of appendicitis at admission who were reexamined after a median of 6 hours of observation. The final diagnosis was appendicitis in 137 patients. After observation the inflammatory response was increasing among patients with appendicitis and decreasing among patients without appendicitis. The variables discriminating power for appendicitis consequently increased, from an area under the receiver operating characteristic (ROC) curve of 0.56 to 0.77 at admission, to 0.75 to 0.85 after observation. The ROC area of the surgeons' clinical assessment increased from 0.69 to 0.89. The WBC and differential cell counts were the best discriminators at the repeat examination. The change in the variables between the observations had weak discriminating power and had no additional importance in addition to the actual level at the repeat examination. To conclude, the diagnostic information of the temperature and laboratory examinations increased after observation. Repeated controls of the body temperature and laboratory examinations are therefore useful in the management of patients with equivocal signs of appendicitis, but the result of the examinations must be integrated with the clinical assessment.

Diagnostic value of disease history, clinical presentation, and inflammatory parameters of appendicitis.

The clinical diagnosis of appendicitis needs to be improved, as up to 40% of explorations for suspected appendicitis are unnecessary. The use of body temperature and laboratory examinations as diagnostic aids in the management of these patients is controversial. The diagnostic power of these variables compared to that of the disease history and clinical findings is not well studied. In this study we prospectively assessed and compared the diagnostic value of 21 elements of the history, clinical findings, body temperature, and laboratory examinations in 496 patients with suspected appendicitis. The diagnostic value of each variable was compared from the area under the receiver operating characteristic (ROC) curve and the likelihood ratios (LR). Logistic regression was used to analyze the diagnostic value of a combination of variables and to analyze independent relations. No single variable had sufficiently high discriminating or predicting power to be used as a true diagnostic test. The inflammatory variables (temperature, leukocyte and differential white blood cell (WBC) counts, C-reactive protein) had discriminating and predicting powers similar to those of the clinical findings (direct and rebound abdominal tenderness and guarding). Anorexia, nausea, and right-sided rectal tenderness had no diagnostic value. The leukocyte and differential WBC counts, C-reactive protein, rebound tenderness, guarding, and gender were independent predictors of appendicitis with a combined ROC area of 0. 93 for appendicitis. This showed that inflammatory variables contain important diagnostic information, especially with advanced appendicitis. They should therefore always be included in the diagnostic workup in patients with suspected appendicitis.