Antibiotics versus placebo in adults with CT-confirmed uncomplicated acute appendicitis (APPAC III): randomized double-blind superiority trial.

BACKGROUND: Non-operative management of uncomplicated acute appendicitis is an option, but omission of antibiotics from the regimen has not been tested. METHODS: A double-blind, placebo-controlled, superiority RCT in adults with CT-confirmed uncomplicated acute appendicitis was designed to compare placebo with antibiotics (intravenous ertapenem followed by oral levofloxacin and metronidazole). The primary endpoint was treatment success (resolution resulting in discharge without appendicectomy within 10 days); secondary outcomes included pain scores, complications, hospital stay, and return to work. RESULTS: From May 2017 to September 2020, 72 patients with a mean(s.d.) age of 37.5 (11.1) years were recruited at five hospitals. Six were excluded after randomization (5 early consent withdrawals, 1 randomization protocol violation), 35 were assigned to receive antibiotics, and 31 to receive placebo. Enrolment challenges (including hospital pharmacy resources in an acute-care surgery setting) meant that only the lowest sample size of three predefined scenarios was achieved. The 10-day treatment success rate was 87 (95 per cent c.i. 75 to 99) per cent for placebo and 97 (92 to 100) per cent for antibiotics. This clinical difference of 10 (90 per cent c.i. -0.9 to 21) per cent was not statistically different for the primary outcome (1-sided P = 0.142), and secondary outcomes were similar. CONCLUSION: The lack of antibiotic superiority statistically suggests that a non-inferiority trial against placebo is warranted in adults with CT-confirmed mild appendicitis. Registration number: EudraCT 2015-003634-26 (https://eudract.ema.europa.eu/eudract-web/index.faces), NCT03234296 (http://www.clinicaltrials.gov).

Appendicitis was the most common reason for emergency surgery, but we now know that mild and severe acute appendicitis are two different diseases. Severe appendicitis still necessitates removal of the appendix but antibiotics alone are an option for mild disease. This small study found that most cases of mild appendicitis to resolve even without antibiotics. Larger studies (more patients) would be needed to show that omitting antibiotics is safe and no worse than antibiotic therapy for milder acute appendicitis.

Oral Doxycycline Compared to Intravenous Ceftriaxone in the Treatment of Lyme Neuroborreliosis: A Multicenter, Equivalence, Randomized, Open-label Trial.

BACKGROUND: Lyme neuroborreliosis (LNB) is often treated with intravenous ceftriaxone even if doxycycline is suggested to be noninferior to ceftriaxone. We evaluated the efficacy of oral doxycycline in comparison to ceftriaxone in the treatment of LNB. METHODS: Patients with neurological symptoms suggestive of LNB without other obvious reasons were recruited. The inclusion criteria were (1) production of Borrelia burgdorferi-specific antibodies in cerebrospinal fluid (CSF) or serum; (2) B. burgdorferi DNA in the CSF; or (3) an erythema migrans during the past 3 months. Participants were randomized in a 1:1 ratio to receive either oral doxycycline 100 mg twice daily for 4 weeks, or intravenous ceftriaxone 2 g daily for 3 weeks. The participants described their subjective condition with a visual analogue scale (VAS) from 0 to 10 (0 = normal; 10 = worst) before the treatment, and 4 and 12 months after the treatment. The primary outcome was the change in the VAS score at 12 months. RESULTS: Between 14 September 2012 and 28 December 2017, 210 adults with suspected LNB were assigned to receive doxycycline (n = 104) or ceftriaxone (n = 106). The per-protocol analysis comprised 82 patients with doxycycline and 84 patients with ceftriaxone. The mean change in the VAS score was -3.9 in the doxycycline group and -3.8 in the ceftriaxone group (mean difference, 0.17 [95% confidence interval, -.59 to .92], which is within the prespecified equivalence margins of -1 to 1 units). Participants in both groups improved equally. CONCLUSIONS: Oral doxycycline is equally effective as intravenous ceftriaxone in the treatment of LNB. CLINICAL TRIALS REGISTRATION: NCT01635530 and EudraCT 2012-000313-37.

18F-FDG positron emission tomography/computed tomography of cardiac implantable electronic device infections.

BACKGROUND: The diagnosis of cardiac implantable electronic device (CIED) infection is challenging because of its variable presentations. We studied the value of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the detection of CIED infection. METHODS AND RESULTS: Thirty patients with suspected CIED infection underwent 18F-FDG-PET/CT. The control group was ten patients with asymptomatic CIED who underwent cancer-related 18F-FDG-PET/CT. 18F-FDG-PET/CT was evaluated visually, semiquantitatively as maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR). Final diagnosis of CIED infection was based on clinical and bacteriological data. 18F-FDG-PET/CT was visually positive in all 9 patients with recent (≤ 8 weeks) implantation of CIED, but only 4 had confirmed CIED infection. 18F-FDG-PET/CT was true positive in 9 out of 21 cases with remote implantation of CIED and false positive in 3 (14.3%) cases. 18F-FDG-PET/CT was also false positive in 3 (30%) cases of control group. The SUVmax of the pocket area was significantly higher in patients with CIED infection than in the control group (4.8 ± 2.4 vs 2.0 ± .8, P < .001). By using the cut-off value of TBR ≥ 1.8, sensitivity of 18F-FDG-PET/CT for the diagnosis of CIED infection in patients with remote implantation was 90% and specificity 73%, PPV 75%, and NPV 89%. CONCLUSIONS: 18F-FDG-PET/CT is a sensitive but nonspecific method in the diagnosis of CIED infection.

Maternal risk factors for congenital limb deficiencies: A population-based case-control study.

BACKGROUND: Risk factors for congenital limb deficiencies are poorly understood. OBJECTIVE: To investigate risk factors for congenital limb deficiencies. METHODS: We conducted a nationwide population-based case-control (1:5) study in Finland, using national registers on congenital anomalies, births, and induced abortions, cross-linked with data on maternal prescription medicine use obtained from the registers on Reimbursed Drug Purchases and Medical Special Reimbursements. Five hundred and four children with limb deficiencies (241 isolated, 181 syndromic, and 82 other associated anomalies) were identified, and 2,520 controls were matched to cases on residence and year of pregnancy. Non-syndromic cases (n = 323) were subdivided into longitudinal (n = 120), transverse (n = 123), intercalary (n = 24), mixed (n = 18), and unknown (n = 38) deficiencies. RESULTS: Pregestational diabetes was associated with all limb deficiencies (adjusted odds ratio [OR] 12.71, 95% confidence interval [CI] 2.37, 68.25) and with isolated (OR 11.42, 95% CI 2.00, 64.60) deficiencies. Primiparity was associated with increased risk of congenital limb deficiencies among all cases (OR 1.49, 95% CI 1.15, 1.93), isolated cases (OR 1.46, 95% CI 1.09, 1.96), and among cases with longitudinal (OR 1.90, 95% CI 1.24, 2.90) and transverse deficiencies (OR 1.75, 95% CI 1.13, 2.70). Young maternal age (<25 years) was associated with all congenital limb deficiencies (OR 1.40, 95% CI 1.02, 1.90) and transverse deficiencies (OR 1.76, 95% CI 1.05, 2.96). Advanced maternal age (≥35 years) was associated with syndromic (OR 1.82, 95% CI 1.19, 2.78) and transverse deficiencies (OR 1.94, 95% CI 1.06, 3.57). Maternal antiepileptic medication was associated with all (OR 5.77, 95% CI 1.75, 19.04) and with isolated cases (OR 3.83, 95% CI 1.02, 14.34). CONCLUSIONS: It is important that pregnant women taking medications, especially antiepileptics, or women with pregestational diabetes are carefully monitored with regard to the occurrence and risk of limb deficiencies in the fetus.

The value of combined positron emission tomography/magnetic resonance imaging to diagnose inflammatory bowel disease: a prospective study.

BACKGROUND: The clinical utility of positron emission tomography/magnetic resonance imaging (PET/MRI) in comparison to standard work-up with patients with known or suspected inflammatory bowel disease (IBD) is unknown. PURPOSE: To evaluate the value of 18F-fluorodeoxyglucose (18F-FDG) PET/MRI in the diagnostics of IBD and further compare the data obtained using PET/MRI to histological findings. MATERIALS AND METHODS: Ten patients with relapse in IBD or with symptoms of suspected IBD were recruited either from a gastroenterology outpatient clinic or from a hospital ward. Intestinal inflammation was assessed with histology and 18F-FDG PET/MRI. Maximum standard uptake values (SUVmax) were calculated in six regions of the intestine (small bowel, ascending, transverse, descending and sigmoid colon, and rectum) and compared to histological analysis of inflammation activity. RESULTS: The study showed that both the inflammation activity (P = 0.008) and the region of the biopsy in the intestine (P = 0.015) had a significant effect on SUV. SUVs obtained from severe inflammation activity emerged significantly from the background (P = 0.006). In addition, the SUVs obtained from moderate inflammation raised from background, but the difference was not statistically significant (P = 0.083), while SUVs of mild inflammation were at the same level with SUVs of normal bowel wall (P = 0.988). CONCLUSION: 18F-FDG PET/MRI is a promising method of detecting especially severe inflammatory bowel lesions. More data are required to define its sensitivity and specificity.

Effect of Oral Moxifloxacin vs Intravenous Ertapenem Plus Oral Levofloxacin for Treatment of Uncomplicated Acute Appendicitis: The APPAC II Randomized Clinical Trial.

Importance: Antibiotics are an effective and safe alternative to appendectomy for managing uncomplicated acute appendicitis, but the optimal antibiotic regimen is not known. Objective: To compare oral antibiotics with combined intravenous followed by oral antibiotics in the management of computed tomography-confirmed uncomplicated acute appendicitis. Design, Setting, and Participants: The Appendicitis Acuta (APPAC) II multicenter, open-label, noninferiority randomized clinical trial was conducted from April 2017 until November 2018 in 9 Finnish hospitals. A total of 599 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were enrolled in the trial. The last date of follow-up was November 29, 2019. Interventions: Patients randomized to receive oral monotherapy (n = 295) received oral moxifloxacin (400 mg/d) for 7 days. Patients randomized to receive intravenous antibiotics followed by oral antibiotics (n = 288) received intravenous ertapenem (1 g/d) for 2 days followed by oral levofloxacin (500 mg/d) and metronidazole (500 mg 3 times/d) for 5 days. Main Outcomes and Measures: The primary end point was treatment success (≥65%) for both groups, defined as discharge from hospital without surgery and no recurrent appendicitis during 1-year follow-up, and to determine whether oral antibiotics alone were noninferior to intravenous and oral antibiotics, with a margin of 6% for difference. Results: Among 599 patients who were randomized (mean [SD] age, 36 [12] years; 263 [44%] women), 581 (99.7%) were available for the 1-year follow-up. The treatment success rate at 1 year was 70.2% (1-sided 95% CI, 65.8% to ∞) for patients treated with oral antibiotics and 73.8% (1-sided 95% CI, 69.5% to ∞) for patients treated with intravenous followed by oral antibiotics. The difference was -3.6% ([1-sided 95% CI, -9.7% to ∞]; P = .26 for noninferiority), with the confidence limit exceeding the noninferiority margin. Conclusion and Relevance: Among adults with uncomplicated acute appendicitis, treatment with 7 days of oral moxifloxacin compared with 2 days of intravenous ertapenem followed by 5 days of levofloxacin and metronidazole resulted in treatment success rates greater than 65% in both groups, but failed to demonstrate noninferiority for treatment success of oral antibiotics compared with intravenous followed by oral antibiotics. Trial Registration: ClinicalTrials.gov Identifier: NCT03236961; EudraCT Identifier: 2015-003633-10.

The Accuracy of Low-dose Computed Tomography Protocol in Patients With Suspected Acute Appendicitis: The OPTICAP Study.

OBJECTIVE: To compare diagnostic accuracy of contrast enhanced low-dose computed tomography (CT) accomplished in the OPTICAP trial phantom phase to standard CT in patients with suspected acute appendicitis. BACKGROUND: Increasing use of CT as the gold standard in diagnosing acute appendicitis has raised concerns regarding radiation exposure. Unenhanced low-dose CT protocols have shown similar diagnostic accuracy with standard CT for diagnosing appendicitis. To our knowledge, there are no other trials in which the same patient with suspected acute appendicitis underwent both standard and low-dose CT allowing interpatient comparison. METHODS: OPTICAP is an interpatient protocol sequence randomized noninferiority single-center trial performed at Turku University Hospital between November, 2015 and August, 2016. Sixty patients with suspected acute appendicitis and body mass index <30 kg/m were enrolled to undergo both standard and low-dose contrast enhanced CT scans, which were categorized as normal, uncomplicated or complicated appendicitis by 2 radiologists in blinded manner. All patients with CT confirmed appendicitis underwent appendectomy to obtain histopathology. RESULTS: The low-dose protocol was not inferior to standard protocol in terms of diagnostic accuracy; 79% [95% confidence interval (CI) 66%-89%) accurate diagnosis in low-dose and 80% (95% CI 67%-90%) in standard CT by primary radiologist. Accuracy to categorize appendicitis severity was 79% for both protocols. The mean radiation dose of low-dose CT was significantly lower compared with standard CT (3.33 and 4.44 mSv, respectively). CONCLUSION: Diagnostic accuracy of contrast enhanced low-dose CT was not inferior to standard CT in diagnosing acute appendicitis or distinguishing between uncomplicated and complicated acute appendicitis in patients with a high likelihood of acute appendicitis. Low-dose CT enabled significant radiation dose reduction.

Vein Harvest Wound Healing after Bypass Surgery for Critical Limb Ischemia.

BACKGROUND: Lower-limb revascularization surgery, especially when performed using the great saphenous vein, predisposes patients to major surgical trauma on initially ischemic tissue. Vein harvest wounds (VHWs) after infrainguinal revascularization heal slowly. This study's aim was to assess the factors associated with VHW healing after infrainquinal bypass surgery for critical limb ischemia (CLI). METHODS: A retrospective patient record study was conducted. All patients with CLI who underwent infrainguinal bypass surgery with autologous vein graft between January 1, 2015, and December 31, 2017, in the Turku University Hospital, were included. Follow-up data were collected until February 28, 2018. The following data was collected from the patient files; risk factors, ankle-brachial indices (ABIs), systolic toe pressures (STPs), the presence of an ischemic ulcer, VHW dehiscence, and the time when the VHW was completely healed. Procedures with outflow vessels at either popliteal or tibial artery were analyzed separately. Descriptive and univariate statistical analyses were performed. RESULTS: Altogether, 195 patients were operated on for CLI, of whom 133 (68.2%) patients had ischemic ulcers. The mean follow-up time was 535.0 days (range 3.0-1143.0 days). The mean ABI improvement was 0.49 (P = 0.00), and STP improvement, 39.9 mm Hg (P = 0.00). The median time taken when VHW was healed was 48.0 days (95% confidence interval [CI], 39.4-56.6) in patients without ischemic ulcers and 82.0 days (95% CI, 59.7-104.3) in patients with ischemic ulcers, P = 0.03. VHW in patients who underwent popliteal artery bypass (62 days, 95% CI, 12.9-93.0) healed faster than VHW in those who underwent tibial artery bypass (132 days, 95% CI, 48.0-93.0), P = 0.02. Risk factors and the preoperative or postoperative ABIs or STPs had no effect on VHW healing time. CONCLUSIONS: VHW healing was remarkably slower after revascularization surgery in patients with an ischemic foot ulcer than in those without ischemic ulcers.

The long-term learning effect related to the repeated use of the Finnish matrix sentence test and the Finnish digit triplet test.

Objectives: To assess are there learning-related improvements in the speech reception thresholds (SRTs) for the Finnish matrix sentence test (FMST) and the Finnish digit triplet test (FDTT) in repeated use over 12 months.Design: Test sessions were scheduled at 0, 1, 3, 6 and 12 months, and each session included five FMST measurements and four FDTT measurements. The within-session and inter-session improvements in SRTs were analysed with a linear mixed model.Study sample: Fifteen young normal-hearing participants.Results: Statistically significant mean improvements of 2.0 dB SNR and 1.2 dB SNR were detected for the FMST and the FDTT, respectively, over the 12-month follow-up period. For the FMST, majority of the improvement occurred during the first two test sessions. For the FDTT, statistically significant differences were detected only in comparison to the first test session and to the first test measurement of every session over the 12-month follow-up.Conclusions: Repeated use of the FMST led to significant learning-related improvements, but the improvements appeared to plateau by the third test session. For the FDTT, the overall improvements were smaller, but a significant within-session difference between the first and consecutive FDTT measurements persisted throughout the test sessions.

Borrelia burgdorferi Infection in Biglycan Knockout Mice.

BACKGROUND: Borrelia burgdorferi sensu lato spirochetes (Borrelia) causing Lyme borreliosis are able to disseminate from the initial entry site to distant organs in the host. Outer-surface adhesins are crucial in the bacterial dissemination and adhesion to various tissues. Two well-characterized Borrelia adhesins, decorin-binding proteins A and B, have been shown to bind to 2 host receptors, decorin and biglycan. However, the role of biglycan in Borrelia infection has not been characterized in vivo. METHODS: We infected biglycan knockout (KO) and wild-type (WT) C3H mice with strains representing 3 Borrelia genospecies, Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii. The infection was monitored by measuring joint swelling, Borrelia culture, polymerase chain reaction analysis, and serologic analysis. The host immune responses were analyzed by histological scoring of the inflammation in tissues and by cytokine profiling. RESULTS: B. burgdorferi sensu stricto and B. garinii established long-term infection in mice of both genotypes, while B. afzelii failed to disseminate in KO mice. Further, the B. burgdorferi sensu stricto-infected KO mice had persistent inflammation in the joints. CONCLUSIONS: The dissemination and tissue colonization of Borrelia and the inflammatory response of the host differ in a mouse biglycan expression- and Borrelia genospecies-dependent manner.

Association between Deep Gray Matter Changes and Neurocognitive Function in Mild Cognitive Impairment and Alzheimer's Disease: A Tensor-Based Morphometric MRI Study.

BACKGROUND: Atrophy of the deep gray matter (DGM) has been associated with a risk of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) and the degree of cognitive impairment. However, specific knowledge of the associations between degenerative DGM changes and neurocognitive functions remains limited. OBJECTIVE: To examine degenerative DGM changes and evaluate their association with neurocognitive functions. METHOD: We examined DGM volume changes with tensor-based morphometry (TBM) and analyzed the relationships between DGM changes and neurocognitive functions in control (n = 58), MCI (n = 38), and AD (n = 58) groups with multiple linear regression analyses. RESULTS: In all DGM areas, the AD group had the largest changes in TBM volume. The differences in TBM volume changes were larger between the control group and the AD group than between the other pairs of groups. In the AD group, volume changes of the right thalamus were significantly associated with episodic memory, learning, and semantic processing. Significant or trend-level associations were identified between bilateral caudate nucleus changes and episodic memory as well as semantic processing. In the control and MCI groups, very few significant associations emerged. CONCLUSIONS: Atrophy of the DGM structures, especially the thalamus and caudate nucleus, is related to cognitive impairment in AD. DGM atrophy is associated with tests reflecting both subcortical and cortical cognitive functions.

Pregnancy and perinatal outcomes after transfer of binucleated or multinucleated frozen-thawed embryos: a case-control study.

Blastomere multinucleation in human embryos is a common phenomenon, but data on its effect on pregnancy outcome and the health of newborns are scarce. In this case-control study, we assessed pregnancy and perinatal outcomes from 136 binucleated and multinucleated frozen-thawed embryo transfer cycles against a control group of 136 non-binucleated and multinucleated frozen embryo transfer cycles. Clinical pregnancy and live birth rates were lower among the case group (29.4% versus 44.1%, P = 0.012; 22.1% versus 36.0%, P = 0.011, respectively), but perinatal outcomes (gestational week at delivery, birth weight, placental weight and occurrence of congenital anomalies) were similar. Live birth rates among patients receiving embryos with multinucleation compared with binucleation was not significantly different (24.7% versus 13.2%). Consequently, frozen-thawed cleavage-stage embryos with bi- or multinucleation have lower than normal but still acceptable implantation potential and ability to produce healthy pregnancies and newborns. The study is limited by its retrospective nature. Time-lapse monitoring would be a more sensitive method of detecting multinucleation. Controls and cases were matched only by age at the time of oocyte retrieval, and other characteristics were only interpreted statistically. Although larger than previously reported, the number of cases is limited.

Reversibility of myocardial metabolism and remodelling in morbidly obese patients 6 months after bariatric surgery.

AIMS: To study myocardial substrate uptake, structure and function, before and after bariatric surgery, to clarify the interaction between myocardial metabolism and cardiac remodelling in morbid obesity. METHODS: We studied 46 obese patients (age 44 ± 10 years, body mass index [BMI] 42 ± 4 kg/m2 ), including 18 with type 2 diabetes (T2D) before and 6 months after bariatric surgery and 25 healthy age-matched control group subjects. Myocardial fasting free fatty acid uptake (MFAU) and insulin-stimulated myocardial glucose uptake (MGU) were measured using positron-emission tomography. Myocardial structure and function, and myocardial triglyceride content (MTGC) and intrathoracic fat were measured using magnetic resonance imaging and magnetic resonance spectroscopy. RESULTS: The morbidly obese study participants, with or without T2D, had cardiac hypertrophy, impaired myocardial function and substrate metabolism compared with the control group. Surgery led to marked weight reduction and remission of T2D in most of the participants. Postoperatively, myocardial function and structure improved and myocardial substrate metabolism normalized. Intrathoracic fat, but not MTGC, was reduced. Before surgery, BMI and MFAU correlated with left ventricular hypertrophy, and BMI, age and intrathoracic fat mass were the main variables associated with cardiac function. The improvement in whole-body insulin sensitivity correlated positively with the increase in MGU and the decrease in MFAU. CONCLUSIONS: In the present study, obesity and age, rather than myocardial substrate uptake, were the causes of cardiac remodelling in morbidly obese patients with or without T2D. Cardiac remodelling and impaired myocardial substrate metabolism are reversible after surgically induced weight loss and amelioration of T2D.

Impact of sphincter lesions and delayed sphincter repair on sacral neuromodulation treatment outcomes for faecal incontinence: results from a Finnish national cohort study.

PURPOSE: The aim of this multicentre study was to analyse the effects of patent sphincter lesions and previous sphincter repair on the results of sacral neuromodulation (SNM) treatment on patients with faecal incontinence (FI). METHODS: Patients examined by endoanal ultrasound (EAUS) with FI as the indication for SNM treatment were included in the study. Data was collected from all the centres providing SNM treatment in Finland and analysed for differences in treatment outcomes. RESULTS: A total of 237 patients treated for incontinence with SNM had been examined by EAUS. Of these patients, 33 had a history of previous delayed sphincter repair. A patent sphincter lesion was detected by EAUS in 128 patients. The EAUS finding did not influence the SNM test phase outcome (p = 0.129) or the final treatment outcome (p = 0.233). Patient's history of prior sphincter repair did not have a significant effect on the SNM test (p = 0.425) or final treatment outcome (p = 0.442). CONCLUSIONS: Results of our study indicate that a sphincter lesion or previous sphincter repair has no significant effect on the outcome of SNM treatment. Our data suggests that delayed sphincter repair prior to SNM treatment initiation for FI is not necessary.

Motor skills in association with physical activity, sedentary time, body fat, and day care attendance in 5-6-year-old children-The STEPS Study.

PURPOSE: This study examined how motor skills are associated with physical activity (PA), sedentary time, body fat, and day care attendance among young children. Also, the motor skills of healthy weight children were compared to those who were overweight or obese. METHODS: The study population consisted of five to six years old children (n = 111; 45 boys) who participated in the longitudinal STEPS Study carried out in Southwest Finland in 2013-2014. Motor skills were measured with the Bruininks-Oseretsky test, second edition (BOT-2) including fine manual control, manual coordination, body coordination, and strength and agility. Moderate-to-vigorous intensity PA (MVPA) and sedentary time were objectively measured with hip-worn accelerometers. Body mass index (BMI) was calculated based on measured weight and height. Body fat percentage (BF%) was measured using segmental multifrequency bio impedance analysis. Day care attendance was measured with parental questionnaires. Linear regression analyses were adjusted by age, sex, and parental education. RESULTS: Day care attendance was positively associated with body coordination and strength and agility. Lower BF% in girls was associated with higher strength and agility scores. There were no associations between manual coordination or fine manual control and the explanatory variables. Objectively measured MVPA and sedentary time showed no associations with motor skills. Overweight children had significantly lower scores in all motor skill composites (P < 0.05) than healthy weight children, except in fine manual control where the association was non-significant (P = 0.202). CONCLUSIONS: Early prevention of overweight and obesity may be of importance and day care attendance may be beneficial for motor skill development.

Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial.

Importance: Short-term results support antibiotics as an alternative to surgery for treating uncomplicated acute appendicitis, but long-term outcomes are not known. Objective: To determine the late recurrence rate of appendicitis after antibiotic therapy for the treatment of uncomplicated acute appendicitis. Design, Setting, and Participants: Five-year observational follow-up of patients in the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotic therapy, in which 530 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were randomized to undergo an appendectomy (n = 273) or receive antibiotic therapy (n = 257). The initial trial was conducted from November 2009 to June 2012 in Finland; last follow-up was September 6, 2017. This current analysis focused on assessing the 5-year outcomes for the group of patients treated with antibiotics alone. Interventions: Open appendectomy vs antibiotic therapy with intravenous ertapenem for 3 days followed by 7 days of oral levofloxacin and metronidazole. Main Outcomes and Measures: In this analysis, prespecified secondary end points reported at 5-year follow-up included late (after 1 year) appendicitis recurrence after antibiotic treatment, complications, length of hospital stay, and sick leave. Results: Of the 530 patients (201 women; 329 men) enrolled in the trial, 273 patients (median age, 35 years [IQR, 27-46]) were randomized to undergo appendectomy, and 257 (median age, 33 years, [IQR, 26-47]) were randomized to receive antibiotic therapy. In addition to 70 patients who initially received antibiotics but underwent appendectomy within the first year (27.3% [95% CI, 22.0%-33.2%]; 70/256), 30 additional antibiotic-treated patients (16.1% [95% CI, 11.2%-22.2%]; 30/186) underwent appendectomy between 1 and 5 years. The cumulative incidence of appendicitis recurrence was 34.0% (95% CI, 28.2%-40.1%; 87/256) at 2 years, 35.2% (95% CI, 29.3%-41.4%; 90/256) at 3 years, 37.1% (95% CI, 31.2%-43.3%; 95/256) at 4 years, and 39.1% (95% CI, 33.1%-45.3%; 100/256) at 5 years. Of the 85 patients in the antibiotic group who subsequently underwent appendectomy for recurrent appendicitis, 76 had uncomplicated appendicitis, 2 had complicated appendicitis, and 7 did not have appendicitis. At 5 years, the overall complication rate (surgical site infections, incisional hernias, abdominal pain, and obstructive symptoms) was 24.4% (95% CI, 19.2%-30.3%) (n = 60/246) in the appendectomy group and 6.5% (95% CI, 3.8%-10.4%) (n = 16/246) in antibiotic group (P < .001), which calculates to 17.9 percentage points (95% CI, 11.7-24.1) higher after surgery. There was no difference between groups for length of hospital stay, but there was a significant difference in sick leave (11 days more for the appendectomy group). Conclusions and Relevance: Among patients who were initially treated with antibiotics for uncomplicated acute appendicitis, the likelihood of late recurrence within 5 years was 39.1%. This long-term follow-up supports the feasibility of antibiotic treatment alone as an alternative to surgery for uncomplicated acute appendicitis. Trial Registration: ClinicalTrials.gov Identifier: NCT01022567.

Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss at 5 Years Among Patients With Morbid Obesity: The SLEEVEPASS Randomized Clinical Trial.

Importance: Laparoscopic sleeve gastrectomy for treatment of morbid obesity has increased substantially despite the lack of long-term results compared with laparoscopic Roux-en-Y gastric bypass. Objective: To determine whether laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass are equivalent for weight loss at 5 years in patients with morbid obesity. Design, Setting, and Participants: The Sleeve vs Bypass (SLEEVEPASS) multicenter, multisurgeon, open-label, randomized clinical equivalence trial was conducted from March 2008 until June 2010 in Finland. The trial enrolled 240 morbidly obese patients aged 18 to 60 years, who were randomly assigned to sleeve gastrectomy or gastric bypass with a 5-year follow-up period (last follow-up, October 14, 2015). Interventions: Laparoscopic sleeve gastrectomy (n = 121) or laparoscopic Roux-en-Y gastric bypass (n = 119). Main Outcomes and Measures: The primary end point was weight loss evaluated by percentage excess weight loss. Prespecified equivalence margins for the clinical significance of weight loss differences between gastric bypass and sleeve gastrectomy were -9% to +9% excess weight loss. Secondary end points included resolution of comorbidities, improvement of quality of life (QOL), all adverse events (overall morbidity), and mortality. Results: Among 240 patients randomized (mean age, 48 [SD, 9] years; mean baseline body mass index, 45.9, [SD, 6.0]; 69.6% women), 80.4% completed the 5-year follow-up. At baseline, 42.1% had type 2 diabetes, 34.6% dyslipidemia, and 70.8% hypertension. The estimated mean percentage excess weight loss at 5 years was 49% (95% CI, 45%-52%) after sleeve gastrectomy and 57% (95% CI, 53%-61%) after gastric bypass (difference, 8.2 percentage units [95% CI, 3.2%-13.2%], higher in the gastric bypass group) and did not meet criteria for equivalence. Complete or partial remission of type 2 diabetes was seen in 37% (n = 15/41) after sleeve gastrectomy and in 45% (n = 18/40) after gastric bypass (P > .99). Medication for dyslipidemia was discontinued in 47% (n = 14/30) after sleeve gastrectomy and 60% (n = 24/40) after gastric bypass (P = .15) and for hypertension in 29% (n = 20/68) and 51% (n = 37/73) (P = .02), respectively. There was no statistically significant difference in QOL between groups (P = .85) and no treatment-related mortality. At 5 years the overall morbidity rate was 19% (n = 23) for sleeve gastrectomy and 26% (n = 31) for gastric bypass (P = .19). Conclusions and Relevance: Among patients with morbid obesity, use of laparoscopic sleeve gastrectomy compared with use of laparoscopic Roux-en-Y gastric bypass did not meet criteria for equivalence in terms of percentage excess weight loss at 5 years. Although gastric bypass compared with sleeve gastrectomy was associated with greater percentage excess weight loss at 5 years, the difference was not statistically significant, based on the prespecified equivalence margins. Trial Registration: clinicaltrials.gov Identifier: NCT00793143.

Accuracy of 837 pedicle screw positions in degenerative lumbar spine with conventional open surgery evaluated by computed tomography.

BACKGROUND: The spatial and directional accuracy of the positioning of pedicle screws in the lumbosacral spine with conventional open surgery assessed by computed tomography (CT) has been published in several studies, systematic reviews and meta-analyses with a short-term follow-up. Inaccurate pedicle screw insertion may cause neurologic symptoms and weakens the construct. METHODS: The data of 147 patients operated on with transpedicular screw fixation based on anatomical landmarks, supported by fluoroscopy, by a senior neurosurgeon in our clinic between 2000 and 2010 were analyzed retrospectively. The accuracy of the pedicle screw position was assessed by using postoperative CT images and graded in 2-mm increments up to 6 mm by two independent surgeons and partly by an independent radiologist. RESULTS: A total of 837 lumbosacral pedicle screws were inserted in 147 randomly selected patients by a senior neurosurgeon. A mean accuracy of 85.7% of the screws being inside the pedicles was identified by the surgeon observers, with 3.3% being perforated 4 mm or more outside the pedicles. Postoperative neurologic symptoms were observed on the side corresponding to the breach in an average of 25.9% of patients with pedicle perforations, and 89.2% of the misplaced screws were either medially or inferiorly inserted. CONCLUSIONS: Screw application reached a mean accuracy of 85.7% based on anatomical landmarks supported by fluoroscopy, warranting computer-assisted navigation for increased accuracy. Our results of 24 patients (16.3%) with the breached screws indicate that the direction of the breach may be more important than the absolute deviation in causing new neurologic symptoms.

Cerebrospinal fluid cytokines in Lyme neuroborreliosis.

BACKGROUND: Lyme neuroborreliosis (LNB) is one of the manifestations of Lyme disease. Although it is known that immune reaction of LNB patients is dominated by Th1 and Th2 responses and patients have elevated numbers of B cells in their cerebrospinal fluid (CSF), not all the cells involved in inflammation and cytokine secretion have been characterized. The current diagnostics of LNB is based on intrathecal production of antibodies. In recent years, the measurement of chemokine CXCL13 concentration from the CSF has been introduced as a new promising diagnostic tool for LNB to complement the antibody-based diagnostic methods. A few other cytokines have also been analyzed as possible diagnostic markers. However, multiplex analyses simultaneously evaluating the concentrations of a large number of different cytokines in the CSF of LNB patients have been lacking thus far. Extensive cytokine profiling CSF samples of LNB patients would also help in understanding the complex immunopathogenesis of LNB. METHODS: CSF samples were analyzed from 43 LNB patients, 19 controls, 18 tick-borne encephalitis patients, and 31 multiple sclerosis patients. In addition, CSF samples from 23 LNB patients obtained after the antibiotic treatment were examined. Altogether, the concentrations of 49 different cytokines were determined from all of the samples. The concentrations of 48 different cytokines were analyzed by magnetic bead suspension array using the Bio-Plex Pro Human Cytokine 21- and 27-plex panels, and the concentration of CXCL13 was analyzed by an ELISA based method. RESULTS: Distinct cytokine profiles which were able to distinguish LNB patients from controls, tick-borne encephalitis patients, multiple sclerosis patients, and LNB patients treated with antibiotics were identified. LNB patients had elevated concentrations of all major T helper cell type cytokines (Th1, Th2, Th9, Th17, and Treg) in their CSF. CONCLUSIONS: Despite the great differences in the CSF cytokine profiles of different patient groups, CXCL13 still remained as the best marker for LNB. However, IL-1ra might also be helpful as a marker for the antibiotic treatment response. Concerning the immunopathogenesis, this is the first report suggesting the involvement of Th9 cells in the immune response of LNB.

Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial.

IMPORTANCE: An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis. OBJECTIVE: To compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography (CT). DESIGN, SETTING, AND PARTICIPANTS: The Appendicitis Acuta (APPAC) multicenter, open-label, noninferiority randomized clinical trial was conducted from November 2009 until June 2012 in Finland. The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan. Patients were randomly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period. INTERVENTIONS: Patients randomized to antibiotic therapy received intravenous ertapenem (1 g/d) for 3 days followed by 7 days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times per day). Patients randomized to the surgical treatment group were assigned to undergo standard open appendectomy. MAIN OUTCOMES AND MEASURES: The primary end point for the surgical intervention was the successful completion of an appendectomy. The primary end point for antibiotic-treated patients was discharge from the hospital without the need for surgery and no recurrent appendicitis during a 1-year follow-up period. RESULTS: There were 273 patients in the surgical group and 257 in the antibiotic group. Of 273 patients in the surgical group, all but 1 underwent successful appendectomy, resulting in a success rate of 99.6% (95% CI, 98.0% to 100.0%). In the antibiotic group, 70 patients (27.3%; 95% CI, 22.0% to 33.2%) underwent appendectomy within 1 year of initial presentation for appendicitis. Of the 256 patients available for follow-up in the antibiotic group, 186 (72.7%; 95% CI, 66.8% to 78.0%) did not require surgery. The intention-to-treat analysis yielded a difference in treatment efficacy between groups of -27.0% (95% CI, -31.6% to ∞) (P = .89). Given the prespecified noninferiority margin of 24%, we were unable to demonstrate noninferiority of antibiotic treatment relative to surgery. Of the 70 patients randomized to antibiotic treatment who subsequently underwent appendectomy, 58 (82.9%; 95% CI, 72.0% to 90.8%) had uncomplicated appendicitis, 7 (10.0%; 95% CI, 4.1% to 19.5%) had complicated acute appendicitis, and 5 (7.1%; 95% CI, 2.4% to 15.9%) did not have appendicitis but received appendectomy for suspected recurrence. There were no intra-abdominal abscesses or other major complications associated with delayed appendectomy in patients randomized to antibiotic treatment. CONCLUSIONS AND RELEVANCE: Among patients with CT-proven, uncomplicated appendicitis, antibiotic treatment did not meet the prespecified criterion for noninferiority compared with appendectomy. Most patients randomized to antibiotic treatment for uncomplicated appendicitis did not require appendectomy during the 1-year follow-up period, and those who required appendectomy did not experience significant complications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01022567.