Outpatient treatment of pneumonia in a setting with and without an infectious disease doctor.

AIM: To compare the outpatient treatment of community acquired pneumonia (CAP) by infectious disease doctors (IDDs) and doctors of other specialties (nIDDs). METHODS: We retrospectively identified 600 outpatients with CAP: 300 treated by IDDs and 300 by nIDDs in two tertiary hospitals during 2019. The two groups were compared in terms of adherence to guidelines, antibiotic group prescription, frequency of combined treatment, and treatment duration. RESULTS: IDDs prescribed significantly more first-line treatment (P<0.001) and alternative treatment (P=0.008). NIDDs prescribed more reasonable (P<0.001) and unnecessary (P=0.002) second-line treatment, and inadequate treatment (P=0.004). IDDs significantly more frequently prescribed amoxicillin (P<0.001) for typical and doxycycline (P=0.045) for atypical CAP, while nIDDs significantly more frequently prescribed amoxicillin-clavulanate (P<0.001) for typical and fluoroquinolones for both typical (P<0.001) and atypical (P<0.001) CAP. No significant differences were found in the frequency of combined treatment, which exceeded 50% in both groups, or in treatment duration. CONCLUSIONS: Outpatient treatment of CAP in the absence of IDDs meant more broad-spectrum antibiotic prescription and more disregard for national guidelines. Our results highlight the need for antibiotic stewardship, especially in settings with no IDDs.

Encephalitis with Autoantibodies against the Glutamate Kainate Receptors GluK2.

OBJECTIVE: The objective of this study was to report the identification of antibodies against the glutamate kainate receptor subunit 2 (GluK2-abs) in patients with autoimmune encephalitis, and describe the clinical-immunological features and antibody effects. METHODS: Two sera from 8 patients with similar rat brain immunostaining were used to precipitate the antigen from neuronal cultures. A cell-based assay (CBA) with GluK2-expressing HEK293 cells was used to assess 596 patients with different neurological disorders, and 23 healthy controls. GluK2-ab effects were determined by confocal microscopy in cultured neurons and electrophysiology in GluK2-expressing HEK293 cells. RESULTS: Patients' antibodies precipitated GluK2. GluK2 antibody-specificity was confirmed by CBA, immunoprecipitation, GluK2-immunoabsorption, and GluK2 knockout brain immunohistochemistry. In 2 of 8 samples, antibodies reacted with additional GluK2 epitopes present in GluK1 or GluK3; in both, the reactivity was abrogated after GluK2 immuno-absorption. Six of 8 patients developed acute encephalitis and clinical or magnetic resonance imaging (MRI) features of predominant cerebellar involvement (4 presenting as cerebellitis, which in 2 patients caused obstructive hydrocephalus), and 2 patients had other syndromes (1 with cerebellar symptoms). One of the samples showed mild reactivity with non-kainate receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors [AMPAR] and N-methyl-D-aspartate receptors [NMDAR]) leading to identify 6 additional cases with GluK2-abs among patients with anti-AMPAR (5/71) or anti-NMDAR encephalitis (1/73). GluK2-abs internalized GluK2 in HEK293 cells and neurons; these antibody-effects were reversible in neurons. A significant reduction of GluK2-mediated currents was observed in cells treated with patients' GluK2 serum following the time frame of antibody-mediated GluK2 internalization. INTERPRETATION: GluK2-abs associate with an encephalitis with prominent clinicoradiological cerebellar involvement. The antibody effects are predominantly mediated by internalization of GluK2. ANN NEUROL 2021;90:107-123.

Association between surgical indications, operative risk, and clinical outcome in infective endocarditis: a prospective study from the International Collaboration on Endocarditis.

BACKGROUND: Use of surgery for the treatment of infective endocarditis (IE) as related to surgical indications and operative risk for mortality has not been well defined. METHODS AND RESULTS: The International Collaboration on Endocarditis-PLUS (ICE-PLUS) is a prospective cohort of consecutively enrolled patients with definite IE from 29 centers in 16 countries. We included patients from ICE-PLUS with definite left-sided, non-cardiac device-related IE who were enrolled between September 1, 2008, and December 31, 2012. A total of 1296 patients with left-sided IE were included. Surgical treatment was performed in 57% of the overall cohort and in 76% of patients with a surgical indication. Reasons for nonsurgical treatment included poor prognosis (33.7%), hemodynamic instability (19.8%), death before surgery (23.3%), stroke (22.7%), and sepsis (21%). Among patients with a surgical indication, surgical treatment was independently associated with the presence of severe aortic regurgitation, abscess, embolization before surgical treatment, and transfer from an outside hospital. Variables associated with nonsurgical treatment were a history of moderate/severe liver disease, stroke before surgical decision, and Staphyloccus aureus etiology. The integration of surgical indication, Society of Thoracic Surgeons IE score, and use of surgery was associated with 6-month survival in IE. CONCLUSIONS: Surgical decision making in IE is largely consistent with established guidelines, although nearly one quarter of patients with surgical indications do not undergo surgery. Operative risk assessment by Society of Thoracic Surgeons IE score provides prognostic information for survival beyond the operative period. S aureus IE was significantly associated with nonsurgical management.

Influence of the timing of cardiac surgery on the outcome of patients with infective endocarditis and stroke.

BACKGROUND: The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. METHODS: Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. RESULTS: Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). CONCLUSIONS: There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.

Extracorporeal membrane oxygenation in COVID-19: Results of the Croatian Extracorporeal Membrane Oxygenation Referral Center.

At the beginning of the COVID-19 pandemic, the role of extracorporeal membrane oxygenation (ECMO) was uncertain and the outcomes of ECMO-treated patients were unfavorable. During the pandemic, medical community realized that carefully selected patients may benefit from ECMO support. The goal of the study was to present the outcomes of ECMO-treated patients with severe COVID-19 ARDS referred to the respiratory ECMO hub in Croatia and to determine variables that influenced the outcome. Our study included all adult patients with confirmed COVID-19 ARDS that required ECMO treatment, in the period between February 2020 and April 2022. All ECMO circuits were veno-venous with femoro-jugular configuration, with drainage at the femoral site. A total of 112 adult patients with COVID-19 induced ARDS were included in the study. All patients had veno-venous ECMO treatment and 34 survived. Surviving patients were discharged home either from the hospital or from a designated rehabilitation facility. The mortality was associated with the incidence of nosocomial bacteremia, occurrence of heparin induced thrombocytopenia and acute renal failure. In order to reduce the mortality in COVID-19 ECMO patients, the treatment should be started as soon as criteria for ECMO are met. Furthermore, complications of the procedure should be detected as soon as possible. However, despite even the optimal approach, the mortality in COVID-19 ECMO patients will surpass that of non-COVID-19 ARDS ECMO patients, mostly due to poor resolving and long lasting ARDS with longer ECMO runs and ensuing infectious complications.

Extracorporeal membrane oxygenation for the treatment of ARDS in Covid-19 and influenza patients: Does etiology matter?

At the beginning of the COVID 19 pandemic, the outcome of patients treated with ECMO was discouraging. Subsequently, it became clear that a certain group of patients may benefit from ECMO treatment. The primary objective of this study was to compare the outcome of ECMO treatment in COVID-19 and influenza patients referred to a tertiary care center. A total of 119 adult patients required ECMO treatment following ARDS secondary to H1N1 (49) and SARS-CoV-2 (70) in the referral ECMO Center based in Zagreb between October 2009 and October 2021. Our study revealed a significantly higher mortality in COVID-19 patients compared to H1N1 influenza when the onset of ARDS was severe enough to require ECMO support. Based on these results and current knowledge, we argue that ECMO treatment for ARDS in COVID-19 patients is more challenging compared to H1N1 influenza patients. Therefore, referral to the most experienced ECMO centers should be considered. Additionally, patient selection and timing for ECMO treatment play a key role in relation to outcome. Mortality rate in COVID-19 patients requiring ECMO treatment may be used as a reference frame for ECMO centers to ensure best possible care and outcome.

Severe West Nile Virus Neuroinvasive Disease: Clinical Characteristics, Short- and Long-Term Outcomes.

West Nile Virus Neuroinvasive Disease (WNV NID) requires prolonged intensive care treatment, resulting in high mortality and early disability. Long-term results are lacking. We have conducted an observational retrospective study with a prospective follow-up of WNV NID patients treated at the Intensive Care Unit (ICU), University Hospital for Infectious Diseases, Zagreb, Croatia, 2013-2018. Short-term outcomes were vital status, length of stay (LOS), modified Rankin Scale (mRS), and disposition at discharge. Long-term outcomes were vital status and mRS at follow-up. Twenty-three patients were identified, 78.3% males, median age 72 (range 33-84) years. Two patients (8.7%) died in the ICU, with no lethal outcomes after ICU discharge. The median ICU LOS was 19 days (range 5-73), and the median hospital LOS was 34 days (range 7-97). At discharge, 15 (65.2%) patients had moderate to severe/mRS 3-5, 6 (26.0%) had slight disability/mRS 2-1, no patients were symptom-free/mRS 0. Ten (47.6%) survivors were discharged to rehabilitation facilities. The median time to follow-up was nine months (range 6-69). At follow-up, seven patients died (30.5%), five (21.7%) had moderate to severe/mRS 3-5, one (4.3%) had slight disability/mRS 2-1, six (26.1%) had no symptoms/mRS 0, and four (17.4%) were lost to follow-up. Briefly, ten (43.5%) survivors improved their functional status, one (4.3%) was unaltered, and one (4.3%) aggravated. In patients with severe WNV NID, intensive treatment in the acute phase followed by inpatient rehabilitation resulted in significant recovery of functional status after several months.

A fatal Mycobacterium chelonae infection in an immunosuppressed patient with systemic lupus erythematosus and concomitant Fahr's syndrome.

We present a case of systemic Mycobacterium chelonae infection in an immunosuppressed patient with systemic lupus erythematosus (SLE), idiopathic hypoparathyroidism, and hypothyroidism. The patient was treated for 3 months for skin infection with clarithromycin monotherapy. Since her condition deteriorated, the antibiotic therapy was switched to intravenously administered clindamycin, cloxacillin, and meropenem. Due to further deterioration and isolation of M. chelonae from the blood culture, antimicrobial therapy was changed to azithromycin and amikacin. Drug-test sensitivity was performed, and the isolate was susceptible to clarithromycin only. The patient's deteriorating status prevented orally administered medication with clarithromycin (parenteral formulation is not registered in Croatia). The same antibiotic regime was continued until the isolation of Pseudomonas aeruginosa and Candida albicans. In addition, extensive calcifications in her brain were found on a computed tomography (CT) scan, which suggested Fahr's syndrome. Despite all measures and supportive care, the patient developed multiorgan failure and eventually died. There has been an increase in the number of infections by rapidly growing mycobacteria, but only a few cases of severe systemic infection with M. chelonae have been described. If the infection is diagnosed early and a patient is treated with appropriate drugs, dissemination can be avoided despite immunosuppression. For serious skin, bone, and soft-tissue disease, a minimum of 4 months of a combined drug therapy is necessary. This is the first report of M. chelonae infection in Croatia and the first-described M. chelonae infection in a patient with concomitant Fahr's syndrome.

A retrospective comparison between influenza and COVID-19-associated ARDS in a Croatian tertiary care center.

BACKGROUND: Since the beginning of the Corona virus disease 2019 (COVID-19) pandemic the new Severe acute respiratory syndrome coronoavirus 2 (SARS-CoV­2) virus has been repeatedly compared to the influenza virus; however, the comparison of invasively mechanically ventilated patients with acute respiratory distress syndrome (ARDS) caused by these viruses is very scarce. The purpose of this study was to compare clinical course and laboratory parameters between the most severely ill flu and COVID 19 patients treated with invasive mechanical ventilation (IMV). METHODS: The study was conducted at the intensive care unit (ICU) of the tertiary care hospital in Zagreb, Croatia in the period between November 2018 and July 2020. Investigation included 72 adult patients requiring IMV due to influenza or SARS-CoV­2 virus infection and 42 patients had influenza and 30 had SARS-CoV­2 virus infection and the comparison between two etiological groups was conducted. RESULTS: Invasively mechanically ventilated patients with COVID 19 and influenza differ in certain aspects. COVID 19 patients are older, male, have lower C-reactive protein (CRP) levels and have less need for extracorporeal membrane oxygenation (ECMO) support. In other measured variables, including mortality, the difference between influenza or SARS-CoV­2 etiology was not significant. CONCLUSION: High mortality of IMV patients with influenza and COVID 19 with 55% and 63%, respectively, challenges and urges medical and especially ICU community to expand our quest for further treatments, especially since ECMO use that is scarcely required in COVID 19 patients probably has limited impact in reducing mortality in COVID 19 patients.

Rapid, multimodal, critical care knowledge-sharing platform for COVID-19 pandemics.

In many areas of the world, critical care providers caring for COVID-19 patients lacked specific knowledge and were exposed to the abundance of new and unfiltered information. With support from the World Health Organization, we created a multimodal tele-education intervention to rapidly share critical care knowledge related to COVID-19 targeting providers in a region of Southeastern Europe. We delivered 60-minute weekly interactive tele-education sessions over YouTubeTM between March 2020 and May 2020, supplemented by a dedicated webpage. The intervention was reinforced using a secure social media platform (ViberTM), providing continuous rapid knowledge exchange among faculty and learners. A high level of engagement was observed, with over 2000 clinicians participating and actively interacting over a 6-week period. Surveyed participants were highly satisfied with the intervention. Tele-education interventions using social media platforms are feasible, low-cost, and effective methods to share knowledge during the COVID-19 pandemic.

Acute motor axonal neuropathy associated with pandemic H1N1 influenza A infection.

BACKGROUND: Guillain-Barre syndrome (GBS) is a well known entity that has many infectious agents reported as antecedent events. The spectrum of GBS includes acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor sensory axonal neuropathy (AMSAN), and some other variants like Miller-Fisher syndrome (MFS). METHODS: Patient with AMAN variant of GBS after severe bilateral pneumonia and ARDS due to the novel pandemic H1N1 influenza A virus is presented. RESULTS: 28-year-old white female was admitted to our Intensive Care Unit during the influenza pandemic because of severe ARDS due to bilateral pneumonia. The course of the disease was complicated with the new onset tetraplegia due to the AMAN variant of GBS. Treatment with plasma exchange was conducted and the patient had satisfactory recovery. CONCLUSION: We report a case of AMAN variant of GBS associated with proven H1N1 influenza A infection. This virus has not been reported previously as the agent of antecedent infection that induced this disorder. Risk factors for other causes of ICU neuromuscular weakness are usually present in the ICU patients and should not be the reason for reluctance in active quest for GBS. Once the diagnosis of GBS is established or suspected the treatment with plasma exchange or intravenous immune globulin is indicated.

Cauda equina arachnoiditis - a rare manifestation of West Nile virus neuroinvasive disease: A case report.

BACKGROUND: Data regarding the neuroradiology features of the West Nile virus neuroinvasive disease (WNV NID) is rather scarce. To contribute to the knowledge of the WNV NID, we present a patient with a combination of encephalitis and acute flaccid paresis, with cauda equina arachnoiditis as the main magnetic resonance (MR) finding. CASE SUMMARY: A 72-year-old female patient was admitted due to fever, headache and gait instability. During the first several days she developed somnolence, aphasia, urinary incontinence, constipation, and asymmetric lower extremities weakness. Cerebrospinal fluid analysis indicated encephalitis. Native brain computed tomography and MR were unremarkable, while spinal MR demonstrated cauda equina enhancement without cord lesions. Virology testing revealed WNV IgM and IgG antibodies in serum and cerebrospinal fluid, which confirmed acute WNV NID. The treatment was supportive. After two months only a slight improvement was noticed but cognitive impairment, loss of sphincter control and asymmetric inferior extremities weakness remained. The patient died after a month on chronic rehabilitation. CONCLUSION: Cauda equina arachnoiditis is a rare, but possible neuroradiological feature in acute flaccid paresis form of WNV NID.

Association Between Cardiac Surgery and Mortality Among Patients With Infective Endocarditis Complicated by Sepsis and Septic Shock.

BACKGROUND: Sepsis and septic shock are common presentations of infective endocarditis (IE), but little is known about clinical characteristics in this group of patients, use of surgical treatment, and their associations with outcome. We sought to determine the influence of cardiac surgery (CS) on the outcome of patients with IE in different stages of sepsis severity. METHODS: Two hundred ninety four patients with definite IE native or prosthetic valve IE admitted between 2000 and 2011. Prospective evaluation using multivariable logistic regression to evaluate clinical characteristics and outcomes (in-hospital and 1-year mortality) in surgically and medically treated patients stratified by severity of sepsis and using new Sepsis-3 definitions. RESULTS: The presence of sepsis or septic shock during IE showed a statistical relationship with increased in-hospital mortality (odds ratio [OR] 8.915, P < 0.001 and OR 35.969, P < 0.001, respectively) after adjusting for other risk factors of poor outcomes (neurological complications, congestive heart failure, and Staphylococcus aureus IE). Surgical treatment had a positive influence on in-hospital mortality in patients with sepsis or septic shock and IE (OR 5.157, P < 0.001) as well as on 1-year survival (hazard ratio 3.092, P < 0.001). CONCLUSIONS: The presence of sepsis or septic shock as defined in Sepsis-3 definitions is associated with unfavorable outcomes in patients with IE. Surgical treatment has a positive effect on outcomes (in-hospital mortality and 1-year survival) in patients with IE and sepsis or septic shock.

Nosocomial blood stream infections in patients treated with venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome.

BACKGROUND: The incidence of complication rates in patients treated with venovenous extracorporeal membrane oxygenation (VV ECMO) remains substantial and impacts the results of any future trial dealing with ECMO efficacy. Of these complications blood stream infections (BSI) are less well studied. Our objective was to report influence of BSI in ARDS patients treated with VV ECMO. METHODS: One-hundred adult patients with ARDS treated with VV ECMO at the tertiary care hospital in Zagreb, Croatia between the October of 2009 and the June of 2016 were prospectively included in the study. RESULTS: In 35% of patients an episode of the nosocomial BSI during VV ECMO treatment was detected. ECMO duration of more than 250 hours and significant bleeding episode independently increase the possibility of acquiring BSI during an ECMO run (odds ratio 3.189, 95% confidence limits 1.108-9.180 and odds ratio 3.378, 95% confidence limits 1.055-10.869 respectively). BSI occurrence had no effect on mortality. CONCLUSIONS: Our study found that BSI incidence increases with the duration of an ECMO run and bleeding complications with no effect on hospital mortality. Further studies of BSI in this risk group should address the problem of rapid diagnosis and appropriate antimicrobial therapy in an era of growing multiresistance.

[Long term survival after Rhodococcus equi pneumonia in a patient with human immunodeficiency virus infection in the era of highly active antiretroviral therapy: case report and review]. / Dugorocno prezivljavanje nakon pneumonije uzrokovane Rhodococcus equi bolesnika zarazenog virusom humane imunodeficijencije u eri vrlo ucinkovitog antiretrovirusnog lijecenja: prikaz bolesnika i pregled literature.

Before highly active antiretroviral therapy (HAART) has become available, antibiotic treatment was usually unable to eradicate Rhodococcus (R.) equi infection in HIV-infected patients, although some clinical improvement could be observed in most cases. There are limited data on the outcome of treatment of R. equi pneumonia in the HAART era. We report on a 52-year-old HIV-infected man who presented in poor general condition with an extensive lung cavitation lesion caused by R. equi. The patient recalled exposure to horses on several occasions. R. equi was cultured from the sputum and the isolate was sensitive to imipenem vancomycin, co-trimoxazole, erythromycin, azithromycin, ciprofloxacin and rifampicin. The CD4+ lymphocyte count was 5 cells/mm3 (0.9%) and his plasma HIV-1 RNA viral load was 101000 copies/mL. The patient was successfully treated with a combination of antibiotics that included azithromycin both as part of an initial and suppressive regimen together with antiretroviral treatment. Surgery was not needed and the patient had no relapse for more than five years after the diagnosis and for more than 3 years of suppressive therapy discontinuation. Our literature search revealed 27 patients treated for R. equi infection in the HAART era. However, details on antimicrobial treatment were given in only 3 cases. The optimal drug regimen and duration of treatment for R. equi pneumonia have not yet been established. Because drug resistance may occur during single agent therapy, it has been suggested that at least two antibiotics to which R. equi is susceptible be given. The recommended choices usually include imipenem, antipseudomonal aminoglycosides, erythromycin or azithromycin, vancomycin, rifampin, and levofloxacin. To our knowledge this is the first documented case of long term remission of R. equi pneumonia in an HIV-infected man treated with azithromycin as part of his antibiotic regimen and HAART.

First molecular analysis of West Nile virus during the 2013 outbreak in Croatia.

This is the second subsequent year of West Nile neuroinvasive disease (WNND) outbreak in Croatia. Between July and October 2013, 22 patients presented with symptoms of WNND: all with meningitis and 18 additionally with encephalitis. In contrast to 2012, where six autochthonous infections were confirmed in eastern Croatia, the majority of this year's cases occurred in and around the city of Zagreb, where no West Nile virus infections have been observed before. Viral RNA was recovered from two patients and phylogenetic analyses revealed West Nile virus lineage 2. This represents the first molecular characterization and phylogenetic analysis of the circulating West Nile virus strain in Croatia.

Dexamethasone for adult community-acquired bacterial meningitis: 20 years of experience in daily practice.

UNLABELLED: The aim of the study was to assess adjunctive intravenous dexamethasone in adult community-acquired bacterial meningitis (BM) in daily practice. Analysis of consecutive patients (1990-2009) with acute community-acquired bacterial meningitis in a single centre in Zagreb, Croatia, N = 304. Adjusted relative risks [RR, dexamethasone vs. no dexamethasone (control)] of Glasgow Outcome Scale (GOS) = 1 (death) and GOS = 5 (full recovery) at discharge/end of specific treatment were estimated considering demographics; co-morbidity; BM pathogenesis and on-admission characteristics, and cerebrospinal fluid (CSF) inflammation markers; causative agent and antibiotic use. Two hundred forty (79%) patients had proven BM (43.1% Streptococcus pneumoniae, any other agent ≤ 8.2%). No independent effects of dexamethasone on GOS = 1 or GOS = 5 were observed in the entire cohort (dexamethasone n = 119, control n = 185; RR = 1.06, 95% CI 0.77-1.45 and RR = 0.99, CI 0.83-1.20, respectively), microbiologically proven disease (dexamethasone n = 104, control n = 136; RR = 0.97, CI 0.69-1.38 and RR = 1.03, CI 0.82-1.28), pneumococcal disease (dexamethasone n = 71, control n = 60; RR = 0.95, CI 0.53-1.70 and RR = 0.82, CI 0.57-1.18), and also in other BM, subgroups based on consciousness disturbance, CSF markers, prior use of antibiotics and timing of appropriate antibiotic treatment. CSF markers did not predict the outcomes. CONCLUSIONS: Our experience does not substantiate the reported benefits of adjunctive dexamethasone in adult BM. Socio-economic and methodological factors do not seem to explain this discrepancy. Empirical use of dexamethasone in this setting appears controversial.

Novel observations during extracorporeal membrane oxygenation in patients with ARDS due to the H1N1 pandemic influenza.

We report four patients with novel observations during extracorporeal membrane oxygenation support (ECMO). ECMO was initiated because of severe ARDS due to the primary H1N1 pandemic influenza pneumonia. Two patients had excessive conjugated hyperbilirubinemia and two had unproportional depletion of the coagulation factor IX. Pathogenetic mechanisms and clinical relevance of the noticed phenomena are discussed.

Correlation of clinical symptoms and laboratory findings in children with milk allergy.

Food hypersensitivities can be divided into toxic and nontoxic, and the latter can further be subdivided into immune and nonimmune hypersensitivities. Cow's milk allergy or intolerance occurs in 5-15% of infants, mostly during the first year of life, or occasionally later. The symptoms may involve different organ systems, especially the gastrointestinal system, skin, and respiratory system. For the diagnosis of cow's milk protein allergy/intolerance, double-blind, placebo-controlled food challenge has been used as a gold standard. Since the test suffers from some drawbacks, many reports have pointed to the need for novel and simpler diagnostic procedures and criteria. In our study, clinical symptoms and laboratory findings of patients with cow's milk protein allergy were compared to assess the possible correlation between particular laboratory findings, clinical picture, and the organ system predominantly involved. There were no significant differences in the levels of IgE, cow's milk protein specific IgE, eosinophilia, prick test results, rectal mucosa biopsy histology, and atopy incidence in patient families among the children with gastrointestinal, cutaneous, and combined gastrointestinal and cutaneous symptoms. Improvement in the symptoms with dietary therapy irrespective of clinical presentation and type of hypersensitivity underlying the symptoms in all these patients strongly suggests that clinical response should be a basic criterion for the diagnosis of cow's milk protein allergy.