XMEN disease caused by the novel MAGT1 p.(Trp136*) mutation may present with neuropsychiatric symptoms.

BACKGROUND: X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation defect (XMEN) disease is caused by MAGT1 loss-of-function (LOF) mutations. The disease commonly presents with respiratory symptoms. Although the central nervous system can be affected, the spectrum of neuropsychiatric symptoms is not completely understood. CASES: We describe a XMEN disease family presenting with atypical neuropsychiatric symptoms. The index, a previously healthy male, developed schizophrenia. Several years later, a novel hemizygous LOF MAGT1 c.407G > A, p.(Trp136X) LOF mutation and XMEN disease diagnosis was confirmed in his brother due to the burden of respiratory infections. Family screening also found the index to suffer from XMEN disease; the XMEN disease was concluded to contribute to the development of schizophrenia. CONCLUSIONS: Our case description demonstrates that the spectrum of XMEN disease clinical presentations can be variable, and the condition may also present with severe neuropsychiatric consequences. While respiratory infections are common among schizophrenia patients, the possibility of inborn errors in immunity should be considered whenever an unexplained personal or family history infection susceptibility is encountered. We recommend evaluating complete family history to exclude unusual monogenic disorders associated or presenting with psychiatric manifestations.

A Family With A20 Haploinsufficiency Presenting With Novel Clinical Manifestations and Challenges for Treatment.

BACKGROUND: Tumor necrosis factor α-induced protein 3 gene (TNFAIP3, also called A20) haploinsufficiency (HA20) leads to autoinflammation and autoimmunity. We have recently shown that a p.(Lys91*) mutation in A20 disrupts nuclear factor κB signaling, impairs protein-protein interactions of A20, and leads to inflammasome activation. METHODS: We now describe the clinical presentations and drug responses in a family with HA20 p.(Lys91*) mutation, consistent with our previously reported diverse immunological and functional findings. RESULTS: We report for the first time that inflammasome-mediated autoinflammatory lung reaction caused by HA20 can be treated with interleukin 1 antagonist anakinra. We also describe severe anemia related to HA20 successfully treated with mycophenolate. In addition, HA20 p.(Lys91*) was found to associate with autoimmune thyroid disease, juvenile idiopathic arthritis, psoriasis, liver disease, and immunodeficiency presenting with specific antibody deficiency and genital papillomatosis. CONCLUSIONS: We conclude that HA20 may lead to combination of inflammation, immunodeficiency, and autoimmunity. The condition may present with variable and unpredictable symptoms with atypical treatment responses.

Quality of Life and Patient Satisfaction at 7-Year Follow-up of Antibiotic Therapy vs Appendectomy for Uncomplicated Acute Appendicitis: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Long-term results support antibiotics for uncomplicated acute appendicitis as an alternative to appendectomy. To our knowledge, treatment-related long-term patient satisfaction and quality of life (QOL) are not known. Objective: To determine patient satisfaction and QOL after antibiotic therapy and appendectomy for treating uncomplicated acute appendicitis. Interventions: Open appendectomy vs antibiotics with intravenous ertapenem, 1 g once daily, for 3 days followed by 7 days of oral levofloxacin, 500 mg once daily, and metronidazole, 500 mg 3 times per day. Design, Setting, and Participants: This observational follow-up of the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotics included 530 patients age 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis who were randomized to undergo appendectomy (273 [52%]) or receive antibiotics (257 [49%]). The trial was conducted from November 2009 to June 2012; the last follow-up was May 9, 2018. The data were analyzed in February 2019. Main Outcomes and Measures: In this analysis, post hoc secondary end points of postintervention QOL (EQ-5D-5L) and patient satisfaction and treatment preference were evaluated. Results: Of the 530 patients enrolled in the trial (appendectomy group: 273 [174 men (64%)] with a median age of 35 years; (antibiotic group: 257 [155 men (60%)] with a median age of 33 years), 423 patients (80%) were available for phone interview at a median follow-up of 7 years; 206 patients (80%) took antibiotics and 217 (79%) underwent appendectomy. Of the 206 patients taking antibiotics, 81 (39%) had undergone appendectomy. The QOL between appendectomy and antibiotic group patients was similar (median health index value, 1.0 in both groups; 95% CI, 0.86-1.0; P = .96). Patients who underwent appendectomy were more satisfied in the treatment than patients taking antibiotics (68% very satisfied, 21% satisfied, 6% indifferent, 4% unsatisfied, and 1% very unsatisfied in the appendectomy group and 53% very satisfied, 21% satisfied, 13% indifferent, 7% unsatisfied, and 6% very unsatisfied in the antibiotic group; P < .001) and in a subgroup analysis this difference was based on the antibiotic group patients undergoing appendectomy. There was no difference in patient satisfaction after successful antibiotic treatment compared with appendectomy (cumulative odds ratio [COR], 7.8; 95% CI, 0.5-1.3; P < .36). Patients with appendectomy or with successful antibiotic therapy were more satisfied than antibiotic group patients who later underwent appendectomy (COR, 7.7; 95% CI, 4.6-12.9; P < .001; COR, 9.7; 95% CI, 5.4-15.3; P < .001, respectively). Of the 81 patients taking antibiotics who underwent appendectomy, 27 (33%) would again choose antibiotics as their primary treatment. Conclusions and Relevance: In this analysis, long-term QOL was similar after appendectomy and antibiotic therapy for the treatment of uncomplicated acute appendicitis. Patients taking antibiotics who later underwent appendectomy were less satisfied than patients with successful antibiotics or appendectomy. Trial Registration: Clinicaltrials.gov Identifier: NCT01022567.

Haploinsufficiency of A20 impairs protein-protein interactome and leads into caspase-8-dependent enhancement of NLRP3 inflammasome activation.

OBJECTIVES: TNFAIP3 encodes A20 that negatively regulates nuclear factor kappa light chain enhancer of activated B cells (NF-κB), the major transcription factor coordinating inflammatory gene expression. TNFAIP3 polymorphisms have been linked with a spectrum of inflammatory and autoimmune diseases and, recently, loss-of-function mutations in A20 were found to cause a novel inflammatory disease 'haploinsufficiency of A20' (HA20). Here we describe a family with HA20 caused by a novel TNFAIP3 loss-of-function mutation and elucidate the upstream molecular mechanisms linking HA20 to dysregulation of NF-κB and the related inflammasome pathway. METHODS: NF-κB activation was studied in a mutation-expressing cell line using luciferase reporter assay. Physical and close-proximity protein-protein interactions of wild-type and TNFAIP3 p.(Lys91*) mutant A20 were analysed using mass spectrometry. NF-κB -dependent transcription, cytokine secretion and inflammasome activation were compared in immune cells of the HA20 patients and control subjects. RESULTS: The protein-protein interactome of p.(Lys91*) mutant A20 was severely impaired, including interactions with proteins regulating NF-κB activation, DNA repair responses and the NLR family pyrin domain containing 3 (NLRP3) inflammasome. The p.(Lys91*) mutant A20 failed to suppress NF-κB signalling, which led to increased NF-κB -dependent proinflammatory cytokine transcription. Functional experiments in the HA20 patients' immune cells uncovered a novel caspase-8-dependent mechanism of NLRP3 inflammasome hyperresponsiveness that mediated the excessive secretion of interleukin-1ß and interleukin-18. CONCLUSIONS: The current findings significantly deepen our understanding of the molecular mechanisms underlying HA20 and other diseases associated with reduced A20 expression or function, paving the way for future therapeutic targeting of the pathway.

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.

Chest magnetic resonance imaging for pneumonia diagnosis in outpatients with lower respiratory tract infection.

We assessed whether magnetic resonance imaging (MRI) is applicable for diagnosing pneumonia among adult outpatients with lower respiratory tract infection.Patients were recruited prospectively when they had symptoms for ≤7 days and fever ≥37.8 °C. The patients underwent high-resolution computed tomography (HRCT), MRI and chest radiography, which were repeated 1 month later if necessary, to verify pneumonia. The duration of MRI examination was 3-4 min.Among 77 patients, HRCT, MRI and radiography identified 32 (41.6%), 30 (39.0%) and 23 (29.9%) cases of pneumonia, respectively (p=0.001). MRI missed two HRCT-identified pneumonia cases due to motion artefacts. Chest radiography resulted in four false-positive pneumonia findings and MRI resulted in none. When HRCT was used as a reference, MRI had a sensitivity of 0.938 (95% CI 0.799-0.983) and specificity of 0.978 (95% CI 0.884-0.996) for the diagnosis of pneumonia, whereas the sensitivity and specificity for chest radiography were 0.719 (95% CI 0.546-0.844) and 0.911 (95% CI 0.793-0.965), respectively.MRI is an accurate, fast and effective method for diagnosing outpatient pneumonia, with better accuracy compared with chest radiography and almost similar accuracy compared with HRCT.

Is preoperative distinction between complicated and uncomplicated acute appendicitis feasible without imaging?

BACKGROUND: One of the main aims of appendicitis research is the differential diagnostics between complicated and uncomplicated acute appendicitis that enable provision of the optimal treatment for each patient. METHODS: Data in the present study were collected prospectively in our randomized antibiotic treatment for uncomplicated acute appendicitis trial (APPAC) comparing surgery and antibiotic treatment for uncomplicated acute appendicitis (NCT01022567). We evaluated 705 patients who had acute appendicitis on computed tomography. Patients with uncomplicated acute appendicitis (n = 368) were compared with all complicated acute appendicitis patients (n = 337), and subgroup analyses were performed between uncomplicated acute appendicitis and an appendicolith appendicitis (CA1; n = 256) and uncomplicated acute appendicitis and perforation and/or abscess (CA2; n = 78). Age, sex, body temperature (°C), duration of symptoms, white blood cell count (E9/L), and C-reactive protein (mg/L) were recorded on admission. Receiver operating characteristic curves were calculated for white blood cell count, C-reactive protein, and temperature. RESULTS: CA2 patients had significantly greater C-reactive protein levels (mean 122 and 47, respectively, P < .001) and longer duration of symptoms than uncomplicated acute appendicitis patients; 81% of CA2 patients and 38% of uncomplicated acute appendicitis patients had symptoms >24 hours before admission (P < .001). In receiver operating characteristic analysis, C-reactive protein and temperature had clinically significant results only in comparison with uncomplicated acute appendicitis and CA2 (area under the curve >0.7), but no optimum cutoff points could be identified. CONCLUSION: In clinical decision making, neither clinical findings nor laboratory markers are reliable enough to estimate the severity of the acute appendicitis accurately or to determine the presence of an appendicolith. The current results emphasize the role of computed tomography in the differential diagnosis of complicated and uncomplicated acute appendicitis.

[Good specimens for the diagnosis and assessment of extent of lung cancer]. / Hyvä näytteenotto keuhkosyövän diagnostilkassa ja levinneisyyden arviossa.

In the diagnosis of lung cancer, tissue and cytologic specimens are needed for confirmation of the diagnosis, elucidation of the histologic type of lung cancer, determination of the extent of the cancer, and increasingly also for the molecular biological investigations required for the planning of drug therapy. The site and method of specimen collection are chosen multidisciplinarily on the basis of imaging studies, taking the clinical picture and patient safety into consideration. High-quality and quantitatively representative specimens are required for molecular biological analyses, and assessment of the response to drug therapy or modifying the treatment may require a new sample, which can be a tissue or cytologic specimen or a liquid biopsy.

Clinical and laboratory findings in the diagnosis of right lower quadrant abdominal pain: outcome analysis of the APPAC trial.

BACKGROUND: The current research on acute appendicitis aims to improve the diagnostics and to clarify to whom antibiotic treatment might be the treatment of choice. METHODS: The present study is a retrospective analysis of a prospectively collected data in our randomized multicenter trial comparing surgery and antibiotic treatment for acute uncomplicated appendicitis (APPAC trial, NCTO1022567). We evaluated 1321 patients with a clinical suspicion of acute appendicitis, who underwent computed tomography (CT). Age, gender, body temperature, pain scores, the duration of symptoms, white blood cell count (WBC) and C-reactive protein (CRP) were recorded on admission. RESULTS: CT confirmed the diagnosis of acute appendicitis in 73% (n=970) and in 27% (n=351) it revealed no or other diagnosis. Acute appendicitis patients had significantly higher WBC levels than patients without appendicitis (median 12.2 and 10.0, respectively, p<0.0001), whereas CRP levels did not differ between the two groups. Ideal cut-off points were assessed with receiver operating characteristic (ROC) curves, but neither these markers or neither their combination nor any clinical characteristic could accurately differentiate between patients with acute appendicitis and those without. The proportion of patients with normal WBC count and CRP was significantly (p=0.0007) lower in patients with acute appendicitis than in patients without appendicitis. CONCLUSIONS: Both clinical findings and laboratory tests are unable to reliably distinguish between patients with acute appendicitis and those without. If both WBC count and CRP are normal, acute appendicitis is very unlikely. The current results emphasize the role of CT imaging in patients with suspected acute appendicitis.

Effect of display type and room illuminance in chest radiographs.

OBJECTIVES: To compare diagnostic accuracy in the detection of subtle chest lesions on digital chest radiographs using medical-grade displays, consumer-grade displays, and tablet devices under bright and dim ambient light. METHODS: Five experienced radiologists independently assessed 50 chest radiographs (32 with subtle pulmonary findings and 18 without apparent findings) under bright (510 lx) and dim (16 lx) ambient lighting. Computed tomography was used as the reference standard for interstitial and nodular lesions and follow-up chest radiograph for pneumothorax. Diagnostic accuracy and sensitivity were calculated for assessments carried out in all displays and compared using the McNemar test. The level of significance was set to p < 0.05. RESULTS: Significant differences in sensitivity between the assessments under bright and dim lighting were found among consumer-grade displays in interstitial opacities with, and in pneumothorax without, Digital Imaging and Communication in Medicine-Grayscale Standard Display Function (DICOM-GSDF) calibration. Compared to 6 megapixel (MP) display under bright lighting, sensitivity in pneumothorax was lower in the tablet device and the consumer-grade display. Sensitivity in interstitial opacities was lower in the DICOM-GSDF calibrated consumer-grade display. CONCLUSIONS: A consumer-grade display with or without DICOM-GSDF calibration or a tablet device is not suitable for reading digital chest radiographs in bright lighting. No significant differences were observed between five displays in dim light. KEY POINTS: • Ambient lighting affects performance of consumer-grade displays (with or without DICOM-GSDF calibration). • Bright light decreases detection of pneumothorax on non-medical displays. • Bright light decreases detection of interstitial opacities on DICOM-GSDF-calibrated, consumer-grade displays. • Dim light is sufficient to detect subtle chest lesions from all displays.

[Update on current care guidelines. Current care guideline: Acute lower respiratory tract infection in adults]. / Kaypa hoite-suosituksen paivitystiivistelma. Alahengitystieinfektiot (aikuiset).

Pneumonia is recognised in patients suffering from acute cough or deteriorated general condition. Patients with acute cough without pneumonia-related symptoms or clinical findings do not benefit from antimicrobial treatment. Those with suspected or confirmed pneumonia are treated with antibiotics, amoxicillin being the first choice. Most patients with pneumonia can be treated at home. Those with severe symptoms are referred to hospital. Patients are always encouraged to contact his/her physician if the symptoms worsen or do not ameliorate within 2-3 days. Patients aged 50 years or older and smokers are controlled by thoracic radiography in 6-8 weeks.

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.

[Incidental finding as a diagnostic and therapeutic challenge]. / Radiologinen sattumalöydös.

Incidental findings have increased with imaging studies. On the average, an incidental finding is made for one out of four patients in connection with an imaging study. The finding may be a harmless change without any significance for the patient's prognosis or treatment. Most incidental findings are indeed benign. On the other hand, an incidental finding may necessitate further investigations, follow-up or even immediate treatment in case of a malignant or other life-threatening change. Ideally, collaboration between a radiologist and a clinician leads to the correct decisions.

[Hepatopulmonary syndrome]. / Hepatopulmonaalinen oireyhtymä.

Hepatopulmonary syndrome (HPS) is characterized by the triad of liver disease, intrapulmonary vascular dilatation and arterial deoxygenation. Mediating factors are tumor necrosis factor a, endothelin 1 and nitric oxide. Typical symptom is an increase in dyspnea while in standing position, orthodeoxia. In orthodeoxia hypoxemia accentuates while the partial pressure of oxygen in arterial blood decreases by 5% or more. The blood flow distribution to the lungs is changed as the pulmonary vascular tone is altered. Diagnosis is based on the evidence of liver disease, hypoxemia and pulmonary vascular shunt detected by the so-called bubble test. Liver transplantation is currently the only efficient therapeutic option.

[Diffuse alveolar damage DAD and organizing pneumonia OP]. / Diffuusi alveolivaurio ja organisoituva pneumonia.

Acute or subactute pulmonary damage can be either idiopathic or resulting from a known cause. The most common histologic types are diffuse acute alveolar damage (DAD) and organizing pneumonia (OP). Various kinds of infection, pulmonary drug reactions or acute exacerbations of interstitial lung diseases may cause DAD, often requiring intensive care. High-resolution computed tomography (HRTT) of the lungs is the most important diagnostic examination. Surgical lung biopsy is performed for few patients.

A prospective randomized controlled multicenter trial comparing antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis (APPAC trial).

BACKGROUND: Although the standard treatment of acute appendicitis (AA) consists of an early appendectomy, there has recently been both an interest and an increase in the use of antibiotic therapy as the primary treatment for uncomplicated AA. However, the use of antibiotic therapy in the treatment of uncomplicated AA is still controversial. METHODS/DESIGN: The APPAC trial is a randomized prospective controlled, open label, non-inferiority multicenter trial designed to compare antibiotic therapy (ertapenem) with emergency appendectomy in the treatment of uncomplicated AA. The primary endpoint of the study is the success of the randomized treatment. In the antibiotic treatment arm successful treatment is defined as being discharged from the hospital without the need for surgical intervention and no recurrent appendicitis during a minimum follow-up of one-year (treatment efficacy). Treatment efficacy in the operative treatment arm is defined as successful appendectomy evaluated to be 100%. Secondary endpoints are post-intervention complications, overall morbidity and mortality, the length of hospital stay and sick leave, treatment costs and pain scores (VAS, visual analoque scale). A maximum of 610 adult patients (aged 18-60 years) with a CT scan confirmed uncomplicated AA will be enrolled from six hospitals and randomized by a closed envelope method in a 1:1 ratio either to undergo emergency appendectomy or to receive ertapenem (1 g per day) for three days continued by oral levofloxacin (500 mg per day) plus metronidazole (1.5 g per day) for seven days. Follow-up by a telephone interview will be at 1 week, 2 months and 1, 3, 5 and 10 years; the primary and secondary endpoints of the trial will be evaluated at each time point. DISCUSSION: The APPAC trial aims to provide level I evidence to support the hypothesis that approximately 75-85% of patients with uncomplicated AA can be treated with effective antibiotic therapy avoiding unnecessary appendectomies and the related operative morbidity, also resulting in major cost savings.

[Diagnostics of lung cancers becoming more precise]. / Keuhkosyöpien tarkentuva diagnostiikka.

Nearly half of all lung cancers are adenocarcinomas falling into various subtypes. Other common types of lung cancer include squamous cell carcinoma and small cell carcinoma. The pathogenesis and molecular biology of lung cancer has been the subject of considerable research over the last few years, and new pharmacologic therapies have been developed. The histological classification of lung adenocarcinomas has been revised in 2011, and is already becoming established in replacing the WHO classification. The aim of the new classification is to make the diagnostics of lung cancer and assessment of treatment options more precise.

The occurrence of pneumonia diagnosis among neurosurgical patients: the definition matters.

BACKGROUND: Diagnosis of pneumonia in the hospital setting is a challenge due to the absence of a generally accepted pneumonia definition. METHODS: We prospectively evaluated six different clinical criteria for diagnosing pneumonia--physician's diagnosis (A), was compared to common methods, i.e., general surveillance method (B), consensus clinical criteria (C), and other three criteria (D, E, and F) among 390 neurosurgical patients treated in either the intensive care unit or the neurosurgical ward in a university hospital. RESULTS: The frequencies of pneumonia cases were: group A, 66 (16.9%); group B, 41 (10.1%); and group C, 55 (14.1%). Only 28 pneumonia cases were identified by all three criteria. The kappa values were: between A and B, 0.42 (95% confidence interval, CI; 0.27-0.57); between A and C, 0.49 (95% CI; 0.35-0.63); and between B and C, 0.68 (95% CI; 0.55-0.80). In group A, there were 34 false positive cases according to criterion B and 25 according to criterion C. Pneumonia cases were identified according to criterion D in 13 (3.3%), E in 35 (9.0%), and F in 51 (13.1%) cases, respectively. CONCLUSIONS: There was great variability in the presence of pneumonia among neurosurgical patients, depending on the criteria used. Our results support the idea that a more exact method for pneumonia diagnosis should be implemented to obtain more reliable results in this important infection of hospitalized patients, which is also used for benchmarking purposes. Furthermore, it seems important to treat all clinically suspected pneumonia cases whether or not the surveillance criteria are fulfilled.

Chest imaging findings in hospitalized patients with H1N1 influenza.

BACKGROUND: Previous studies have reported chest radiographic findings of consolidation and ground-glass opacity in patients with swine-origin influenza A (H1N1). However, most of these studies include both hospitalized and outpatients. PURPOSE: To evaluate initial chest radiographic and CT findings of hospitalized swine flu patients, adults and children, confirmed with a real-time reverse transcriptase polymerase chain reaction (PCR) assay for H1N1 virus. MATERIAL AND METHODS: All PCR-verified swine flu patients admitted to the Department of Emergency Medicine (October 1 to December 15, 2009) at Oulu University Hospital, in Northern Finland, who underwent frontal chest radiography within 24 hours of presentation and who were hospitalized, were included. The radiographs and CT scans were assessed for the presence of pneumonia and characterized by pattern and distribution. The patients' medical records were analyzed for demographics, underlying medical conditions, the admission to the intensive care unit (ICU), initiation of mechanical ventilation or non-invasive ventilation support (NIV) and death. RESULTS: Of 159 H1N1 influenza patients, 135 (85%) underwent chest radiographs at admission; 113 adults and 22 children. Findings of pulmonary infiltrates were detected in 62% (70/113) of adults and 64% (14/22) of children, being bilateral in 67% of adults and 64% of the children. The anatomic location of infiltrates was more often peripheral in adults; 42/70 (60%) vs. 4/14 (29%), P = 0.041, and diffuse among children; 9/14 (64%) vs. 26/70 (37%), P = 0.078. When the ICU and NIV patients were compared to less severe cases, on their chest radiographs four or five lobes were more often affected (65%, 11/17 vs. 34% 23/67, P = 0.029 ). The predominant radiographic findings were consolidation (93% of all patients, 91% of adults and 100% of children) and ground-glass opacity (74% of all, 77% of adults and 57% of children). Pulmonary emboli were detected by CT in 2/9 (22%) patients. CONCLUSION: The pandemic 2009 swine influenza causes common and widely distributed infiltrates on chest radiographs among hospitalized patients, which are not peculiar to usual respiratory viral infections, and these findings can not be differentiated from usual bacterial pneumonia.

[Diffuse pulmonary infiltrates--challenging diagnosis]. / Diffuusit keuhkoinfiltraatit--radiologiasta klinikkaan.

The diagnostics of diffuse pulmonary infiltrates is based on high-resolution computed tomography of the lungs. In typical cases, this technique can usually be applied to diagnose IPF, sarcoidosis and allergic alveolitis quite reliably. Radiological findings in several interstitial pulmonary diseases are, however, overlapping and the diseases may involve atypical manifestations. Analysis of tomographic images requires an experienced radiologist.