Development of a pediatric differentiated thyroid carcinoma registry within the EuRRECa project: rationale and protocol.

Background: Although differentiated thyroid carcinoma (DTC) is the most frequent endocrine pediatric cancer, it is rare in childhood and adolescence. While tumor persistence and recurrence are not uncommon, mortality remains extremely low. Complications of treatment are however reported in up to 48% of the survivors. Due to the rarity of the disease, current treatment guidelines are predominantly based on the results of small observational retrospective studies and extrapolations from results in adult patients. In order to develop more personalized treatment and follow-up strategies (aiming to reduce complication rates), there is an unmet need for uniform international prospective data collection and clinical trials. Methods and analysis: The European pediatric thyroid carcinoma registry aims to collect clinical data for all patients ≤18 years of age with a confirmed diagnosis of DTC who have been diagnosed, assessed, or treated at a participating site. This registry will be a component of the wider European Registries for Rare Endocrine Conditions project which has close links to Endo-ERN, the European Reference Network for Rare Endocrine Conditions. A multidisciplinary expert working group was formed to develop a minimal dataset comprising information regarding demographic data, diagnosis, treatment, and outcome. We constructed an umbrella-type registry, with a detailed basic dataset. In the future, this may provide the opportunity for research teams to integrate clinical research questions. Ethics and dissemination: Written informed consent will be obtained from all participants and/or their parents/guardians. Summaries and descriptive analyses of the registry will be disseminated via conference presentations and peer-reviewed publications.

Monkeypox in humans: a new outbreak.

Infection caused by Monkeypox Virus (MPVX) has small rodents as its natural reservoir and both monkeys and humans are occasional hosts. The causative agent is an Orthopoxvirus (MPVX) that was isolated in monkeys in 1958 and proved capable of passing to humans in 1970. It remained contained in Africa, causing isolated episodes of infection, until 2003 when an outbreak occurred in the United States following importation of animals from that continent. Since then, anecdotal cases have continued to be reported outside Africa, usually very clearly linked to travelers to those countries, but in May 2022, a broad outbreak of this disease has begun, now affecting several continents, with the emergence of human cases of MPVX (H-MPVX) infection mainly among Men that have Sex with Men (MSM). The disease has an incubation time ranging from 5 to 15 days and is characterized by the presence of pustules, fever, malaise and headache. The presence of significant regional lymphadenopathy is a differential feature with episodes of classical smallpox. Proctitis and pharyngitis, with minimal skin lesions, may be another form of presentation. Diagnosis can be confirmed by PCR testing of lesions or by demonstration of MPVX in other body fluids or tissues, although in the appropriate epidemiologic setting the clinical picture is highly suggestive of the disease. Effective drug treatment has been developed as part of programs to protect against potential bioterrorist agents and smallpox vaccinees are known to have high protection against monkeypox. New vaccines are available, but neither the drugs nor the vaccines are yet freely available on the market. The prognosis of the disease appears, at least in adults in developed countries, to be good, with very low mortality figures and much less aggressive behavior than that described in classical smallpox. Isolation measures, essential for the control of the outbreak, have been published by the health authorities.

Value of syndromic panels in the management of severe community-acquired pneumonia.

Community-acquired pneumonia requiring hospital admission is a prevalent and potentially serious infection, especially in high-risk patients (e.g., those requiring ICU admission or immunocompromised). International guidelines recommend early aetiological diagnosis to improve prognosis and reduce mortality. Syndromic panels that detect causative pathogens by molecular methods are here to stay. They are highly sensitive and specific for detecting the targets included in the test. A growing number of studies measuring their clinical impact have observed increased treatment appropriateness and decreased turnaround time to aetiological diagnosis, need for admission, length of hospital stay, days of isolation, adverse effects of medication and hospital costs. Its use is recommended a) per a pre-established protocol on making the diagnosis and managing the patient, b) together with an antimicrobial stewardship programme involving both the Microbiology Service and the clinicians responsible for the patient, and c) the final evaluation of the whole process. However, we recall that microbiological diagnosis with traditional methods remains mandatory due to the possibility that the aetiological agent is not included among the molecular targets and to determine the antimicrobial susceptibility of the pathogens detected.

Severe renal failure and thrombotic microangiopathy induced by malignant hypertension successfully treated with spironolactone.

Malignant hypertension can cause thrombotic microangiopathy (TMA) characterized by hemolytic anemia and thrombocytopenia. On the other hand, severe hypertension is sometimes associated with hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP). Distinguishing these entities is important because of therapeutic implications. Plasmapheresis should be initiated as soon as possible if we are dealing with TTP. We describe the case of a 30-year-old man referred to our hospital with malignant hypertension, severe renal failure and TMA: haemoglobin=9g/dL, total bilirubin=0.4mg/dL, haptoglobin≤10mg/dL, platelet count=59,000/µL and schistocytes on peripheral smear. He required initiation of hemodialysis. Additionally, we considered that the possible cause of TMA was malignant hypertension according to the presence of hypertensive retinopathy and thrombocytopenia which remitted only with blood pressure control, hence, plasmapheresis was not given. Renal function did not improve and the patient remained chronic hemodialysis. Intensive therapy for hypertension with a combination of antihypertensive drugs including spironolactone successfully lowered his blood pressure without developing hyperkalemia.

Missed diagnosis of Clostridium difficile infection; a prospective evaluation of unselected stool samples.

BACKGROUND: Clostridium difficile infection (CDI) is the leading cause of hospital-acquired diarrhoea in developed countries, however a high proportion of CDI episodes go undiagnosed, either because physicians do not request identification of toxigenic C. difficile or microbiologists do not perform the appropriate tests. OBJECTIVE: To investigate the clinical characteristics of patients with CDI within a non-selected population and to determine risk factors for clinical underdiagnosis. METHODS: We conducted a prospective study in which systematic testing for toxigenic C. difficile on all diarrhoeic stool samples was performed regardless of the clinician's request. Patients aged >2 years positive for toxigenic C. difficile and diarrhoea were enrolled (Jan-June 2013) and monitored at least 2 months after their last episode. RESULTS: We identified 204 cases of CDI, of which three-quarters were healthcare-associated. Most cases were mild to moderate (83.8%), the recurrence rate was 16.2%, and CDI-related mortality was low (2.5%). A significant proportion (12.7%) of CDI cases would have been missed owing to lack of clinical suspicion. Community-acquired cases and young age were risk factors for clinical underdiagnosis. CONCLUSION: Our data support the introduction of a systematic search for toxigenic C. difficile in all diarrhoeic stools from inpatients and outpatients older than 2 years.

Recurrent infection in the left thumb.

INTRODUCTION: Infections of the hand may be associated with lymphangitis and lymphadenitis. In most cases, bacterial infections are responsible but these may be also due to viral infections. MATERIAL AND METHODS: We describe a clinical case of a recurrent infection in the left thumb of a health male. Bacterial and viral cultures were performed. RESULTS: Herpes simplex virus (HSV) type 2 was isolated on viral culture and on direct fluorescent antibody testing; so, the final diagnosis was herpetic whitlow. CONCLUSIONS: Herpetic whitlow should be considered in cases of recurrent finger infections.

[Positron emission tomography-computed tomography with (18)F-fluorodeoxyglucose in patients with recurrent differentiated thyroid carcinoma and negative radioiodine scan. Diagnostic performance and relation with tyroglobulin levels]. / La tomografía por emisión de positrones-tomografía computarizada con (18)F-fluordesoxiglucosa en los pacientes con cáncer diferenciado de tiroides en recurrencia y rastreo con radioyodo negativo. Rendimiento diagnóstico y relación con los niveles de tiroglobulina.

OBJECTIVE: To assess the diagnostic performance of (18)F-FDG PET-CT scan and its relation to serum thyroglobulin (Tg) levels in patients with differentiated thyroid carcinoma with suspicion of persistence or recurrence of the disease and negative radioiodine scans. MATERIALS AND METHODS: This is a retrospective analysis of 35 PET-CT studies in 25 patients (17 women, average age 48.8±15.2 years). The results were confirmed by histology or by ultrasonography and clinical follow-up. We analyzed the relationship between the diagnostic performance of the PET-CT scans and three levels of Tg: ≤2ng/ml; between 2 and 10 ng/ml, and >10ng/ml. RESULTS: We obtained 26 true-positives (TP), one false-positive (FP), 3 true-negatives (TN) and 5 false-negatives (FN). Of the 18 patients with PET-CTs classified as TP, 3 showed lesions at the post-thyroidectomy bed, 15 showed lymph node metastases and 5 were distant metastases. Sensitivity was 83.9% (95%CI: 69.3%-98.4%) and specificity was 75% (95%CI: 20%-100%). Regarding the three intervals of Tg, PET-CT scan showed TP rates of 37.5%, 83% and 100% in patients with Tg levels <2ng/ml, between 2 and 10ng/ml, and >10ng/ml, respectively. CONCLUSIONS: (18)F-FDG PET-CT demonstrates high diagnostic yield in local disease and distant lesions for the population of patients with differentiated thyroid carcinoma and persistence of the disease with negative radioiodine scans at Tg levels above 2ng/ml.

[Comparative study of the susceptibility to daptomycin and other antimicrobials against Staphylococcus spp. resistant to methicillin and Enterococcus spp. using Wider, E-test, and microdilution methods]. / Estudio comparativo de Wider, E-test y microdilución para la determinación de la sensibilidad a daptomicina y otros tres antimicrobianos de aislamientos clínicos de Staphylococcus spp. resistentes a meticilina y Enterococcus spp.

The human and material costs of inappropriate antimicrobial therapy are high. This study was designed to search for a rapid, simple and effective antimicrobial susceptibility test capable of identifying the best treatment strategy against microorganisms causing hospital infections showing resistance or reduced susceptibility to the more traditional antibiotics. The tests compared were the E-test, an automated test (Wider) and broth microdilution ( as the reference test), to determine the susceptibility to vancomycin, teicoplanin, linezolid and daptomycin of clinical isolates of methicillin resistant Staphylococcus aureus (MRSA), methicillin resistant coagulase negative Staphylococcus spp. and Enterococccus spp. The E-test and Wider methods showed good agreement with the reference method indicating their reliability for routine susceptibility testing of staphylococci and enterococci against vancomycin, teicoplanin, linezolid and daptomycin. Notwithstanding, when faced with a serious enterococcal infection, the MIC of daptomycin should be more accurately determined using a reference technique such as broth microdilution.

Susceptibility of 228 non-fermenting gram-negative rods to tigecycline and six other antimicrobial drugs.

The aim of the study was to determine the in vitro activity of tigecycline and 6 other antimicrobial drugs used in clinical practice against 228 clinical isolates of nonfermenting Gram-negative rods (NFGNRs) including Acinetobacter spp., Stenotrophomonas maltophilia, and Pseudomonas aeruginosa. Minimum inhibitory concentrations (MICs) were determined according to the recommendations of the Clinical and laboratory Standards institute. for tigecycline, we used the criteria approved by the fDA. Almost 50% of the clinical isolates of Acinetobacter spp. were resistant to piperacillin/tazobactam, ciprofloxacin, gentamicin, and ceftazidime. Strains of this microorganism were more susceptible to imipenem, and even more susceptible to colistin and tigecycline; no strains were resistant to tigecycline. Stenotrophomonas maltophilia showed even greater resistance to the drugs tested. Thus, all strains were resistant to imipenem and a large percentage (82.6%) were resistant to piperacillin/tazobactam. Resistance to the other agents tested was also high, with the exception of tigecycline, with only 3 resistant strains (MIC >8 microg/ml). Tigecycline, on the other hand, was scarcely active against Pseudomonas aeruginosa, which bears efflux pump systems such as MexXy-OprM. Almost 90% of strains were resistant to ciprofloxacin; only 8% were resistant to gentamicin; over half were colistin-intermediate or -resistant, and finally, approximately half of the strains were susceptible to the 3 beta-lactams studied. In conclusion, NFGNRs present variable susceptibility patterns, although they are generally highly resistant to antimicrobial agents including those considered more specific. Tigecycline, which showed good activity against most of the strains examined, broadens the spectrum of drugs available for the treatment of infections caused by these complex microorganisms.

Decline in the workload associated with the serodiagnosis of syphilis in a general hospital: 1994-2004.

Syphilis re-emergence is a cause of concern. Our objective was to quantify the laboratory workload, incident cases and patient follow-up that syphilis has generated for 11 years in a large teaching hospital. An ecologic study including all samples submitted for syphilis serodiagnosis at our hospital from January 1994 to December 2004 was undertaken. Our laboratory processed 58,832 samples for syphilis serodiagnosis. From 1994 to 2004, the number of samples submitted for syphilis testing dropped by 11% (95% confidence interval [CI] 10-12, p<0.001). Syphilis was diagnosed in 443 patients. The incidences were 11, 3 and 8 per 100,000 inhabitants/year in 1994, 2000 and 2004, respectively. Only 42% (185) of patients had repeat tests and in 79% (146) of cases, the 1-year follow-up data were missing. The median follow-up was 9 months (interquartile range [IQR] 3-26). We detected a reduction in the effort to detect syphilis, despite an increase in its incidence and the low cost of syphilis screening. Efforts should be intensified to improve physician compliance with syphilis screening and follow-up guidelines.

[Adrenal cortex scintigraphy with and without dexamethasone suppression in the study of primary aldosteronism]. / Gammagrafía suprarrenal cortical con frenación y supresión de la frenación con dexametasona en el estudio del hiperaldosteronismo primario.

AIM OF THE STUDY: To evaluate the diagnostic performance and efficacy of adrenal scintigraphy in primary aldosteronism following the protocol that combines adrenal suppression scintigraphy plus non-suppression study. METHODS AND PROCEDURES: 20 patients referred to our service with the suspicion of primary aldosteronism were studied by combined scintigraphy. Thirteen men and 7 women, mean age of 52 years, aged from 31 to 73 years, were included. Uptake of free iodine by the thyroid was inhibited by oral Lugol 5 % administration. Dexamethasone 4 mg per day was administered from day 7 to the third day of detection, when administration was stopped. Adrenal scintigraphy was performed after intravenous injection of I-131-norcolesterol (37 MBq). Images were taken at 24 and/or 48 hours and on the third day. Afterwards, dexamethasone administration was stopped and late images on 5th and/or 7th days were obtained. The scintigraphic result was confirmed with the final clinical evaluation (FCE) of the patient. RESULTS: 11 patients presented pathological studies, 9 adenomas (8TP + 1FP) and 2 bilateral adrenal hyperplasia (2TP); 7 normal scintigraphies (6TN and 1 non-conclusive FCE) and 2 non-conclusive scintigraphies (1 incidentaloma and 1 non-conclusive FCE). Normal adrenal glands were visualized in all cases on the 5th and/or 7th day scintigraphy. CONCLUSION: The study of adrenal functionalism by the combined protocol of adrenal suppression study plus later non-suppression study made it possible to identify with high precision primary aldosteronism and to confirm the function of normal adrenal glands.

Semiquantitative culture of open surgical wounds for diagnosis of surgical site infection.

The aim of this study was to assess the performance of a semiquantitative culture method and traditional qualitative culture for the diagnosis of surgical site infections resulting in an open wound. Results were correlated with the definitions for the diagnosis of SSI proposed by the Centers for Disease Control and Prevention, Atlanta, Ga., USA. The sensitivity, specificity, positive and negative predictive values of the qualitative culture method were 96%, 61%, 84% and 89%, respectively. For the semiquantitative technique with a breakpoint of 15 colony forming units/plate these values were 91%, 96%, 98% and 83%, respectively. Analysis of the receiver operating characteristic curve revealed an area under the curve of 94.44% (95% confidence interval, 88.5%-99%) for the semiquantitative method. This result indicates that our easy-to-perform semiquantitative culture technique for open surgical wounds correlates better with the diagnosis of SSI than the traditional qualitative method.

Catheter-related infections: diagnosis and intravascular treatment.

The diagnosis of catheter-related infections relies on the presence of clinical manifestations of infection and the evidence of colonization of the catheter tip by bacteria, mycobacteria, or fungi. The reference method to confirm the latter requires the withdrawal of the catheter for culturing, which frequently turns out to be inconvenient, unnecessary and costly. New methods try to avoid these drawbacks and to assess the presence of tip colonization without withdrawal. Comparative quantitative blood cultures with a marked increase (> or = 5) in colony counts between blood obtained from the catheter lumen and from a peripheral vein simultaneously is one of those methods. It has a high sensitivity (>80%) and specificity (94-100%) but it is cumbersome and requires both an easy backflow of blood in the catheter and the existence of bacteremia. Cytocentrifugation and acridine orange staining of blood withdrawn from an infected catheter lumen has a sensitivity and a specificity of over 90% for the diagnosis of tip colonization. 'Superficial cultures' comprise the semiquantitative culture of the hub, of the skin surrounding the catheter entrance and of the first subcutaneous portion (1 cm) of the catheter after swabbing. The sensitivity of this method is >90%, specificity is >80%, and positive and negative predictive values for catheters (considering together those with and without clinical data of infection) are 66 and 97%, respectively. Endoluminal brushing has proved to be an impractical and unreliable procedure, at least in our experience. New methods based on the speed of bacterial growth to detectable levels of micro-organisms in conventional blood cultures are a new and interesting way of assessing catheter-related infections. Moreover, as the use of antimicrobial-coated catheters becomes more prevalent, the existing definitions of catheter colonization and catheter-related infection may need to be modified, because such coatings may lead to false-negative culture results. Many catheter infections, diagnosed without catheter withdrawal, can be handled nowadays with the so-called 'antibiotic lock-in technique', which consists in 'locking' the infected catheter lumen with a solution containing antibiotics. A high proportion of infected catheters, mainly those with coagulase-negative staphylococci, can be maintained in place and sterilized with this technique, including catheters in patients with therapeutic failure after receiving conventional intravenous antibiotic therapy. New diagnostic and therapeutic techniques may avoid the unnecessary withdrawal of thousands of efficient, difficult to replace and expensive intravascular lines.

Standard provocative manoeuvres in patients with and without left bundle branch block studied with myocardial SPECT.

BACKGROUND: The objective of this study was to determine the prevalence of anterior and septal defects in patients with left bundle branch block (LBBB), and to assess the diagnostic accuracy of myocardial single photon emission computed tomography (SPECT) with technetium compounds in patients with and without LBBB using standard provocative manoeuvres. METHODS: Five hundred and nine consecutive patients (456 without LBBB and 53 with LBBB) without previous infarction who had a coronary angiography performed within <3 months of the scintigraphic study were retrospectively evaluated. The same stress procedures were followed in all patients. (1) Only exercise when it was sufficient; and (2) exercise + simultaneous administration of dypiridamole if exercise was insufficient. Only reversible defects were considered positive and > or =50% of coronary stenosis was considered significant. RESULTS: Prevalence of reversible anterior and septal defects was low (33% and 12%, respectively) in patients with LBBB. Although lower values of global sensitivity (81%) and specificity (73%) were obtained in these patients, there were no significant differences with respect to the patients without LBBB (89% and 86%, respectively). Specificity values for the diagnosis of stenosis of left anterior descending (78%), left circumflex (96%) and right coronary artery (74%) in patients with LBBB were lower, but without significant statistical differences with respect patients without LBBB (90%, 96% and 82%, respectively). CONCLUSIONS: Myocardial SPECT with technetium compounds, using standard provocation manoeuvres, can be used in patients with LBBB with only a mild decrease in diagnostic accuracy as compared to patients without LBBB.

Environmental surveillance and other control measures in the prevention of nosocomial fungal infections.

The steady world-wide increase in the number of severely immunocompromised patients in most hospitals has made the control and prevention of nosocomial systemic fungal infections a critical quality-of-care standard. Early diagnosis and antifungal prophylaxis of these infections are complicated, so avoiding the acquisition of the pathogen in the case of Aspergillus and minimizing the predisposing risk factors in the case of Candida are more effective approaches. The maintenance of good air quality in critical areas in hospitals is mandatory to reduce the incidence of invasive aspergillosis. We review the currently available Center for Disease Control recommendations and report our own experiences in the field. The indications and problems of fungal environmental and patient surveillance are also discussed.

Catheter-related infections: diagnosis and intravascular treatment.

The diagnosis of catheter-related infections relies on the presence of clinical manifestations of infection and the evidence of colonization of the catheter tip by bacteria, mycobacteria or fungi. The reference method to confirm the latter requires the withdrawal of the catheter for culturing, which frequently turns out to be inconvenient, unnecessary and costly. New methods try to avoid these inconveniences and to assess the presence of tip colonization without withdrawal. One of these methods uses quantitative blood cultures with a jump (> or = 5) in colony counts between blood obtained from the catheter lumen and simultaneously from a peripheral vein. It has a high sensitivity (>80%) and specificity (94%-100%) but is cumbersome and requires both an easy backflow of blood in the catheter and the existence of bacteremia. Cytocentrifugation and acridine orange staining of blood withdrawn from an infected catheter lumen has a sensitivity and a specificity of over 90% for the diagnosis of tip colonization. "Superficial cultures" consist in the semiquantitative culture of the hub, of the skin surrounding the catheter entrance and of the first (1 cm) subcutaneous portion of the catheter after swabbing. Sensitivity of this method is >90% and specificity is >80%, and positive and negative predictive values for catheters (considering together those with and without clinical data of infection) are 66% and 97%, respectively. Endoluminal brushing has turned out to be an impractical and unreliable procedure, at least in our experience. New methods based on the speed of bacterial growth to detectable levels of microorganisms in conventional blood cultures are a new and interesting way of assessing catheter-related infections. Besides, as use of antimicrobial-coated catheters becomes more prevalent, the existing definitions of catheter colonization and catheter-related infection may need to be modified, because such coatings may lead to false-negative culture results. Many catheter infections, diagnosed without catheter withdrawal, can be handled nowadays with the so-called "antibiotic lock-in technique", which consists in locking the infected catheter lumen with a solution containing antibiotics. A high proportion of infected catheters, mainly those with coagulase-negative staphylococci, can be maintained in place and sterilized with this technique, including catheters in patients with therapeutic failure after receiving conventional intravenous antibiotic therapy. New diagnostic and therapeutic techniques may avoid the unnecessary withdrawal of thousands of efficient, difficult to replace and expensive intravascular lines.

Criteria used when initiating antifungal therapy against Candida spp. in the intensive care unit.

Invasive candidiasis is a life threatening complication for intensive care unit (ICU) patients. The infection is difficult to recognise so that treatment may be delayed or even not given. Risk factors for candidiasis include the use of antimicrobial agents, central intravascular devices (mainly Hickmann catheters), recurrent gastrointestinal perforations, surgery for acute pancreatitis or splenectomy and renal dysfunction or haemodialysis. Therapy against Candida spp is recommended in ICU patients with endophthalmitis or chorioretinitis possibly caused by Candida spp., in symptomatic patients with risk factors for invasive candidiasis especially if two or more anatomical sites are colonised and for asymptomatic high-risk surgical patients (with recent abdominal surgery or recurrent gastrointestinal perforations or anastomotic leakages). The isolation of Candida from any site poses an increased risk but there are a few microbiological data that might help to establish the predictive value of a particular isolate. These include the site of isolation, the number of culture positive, noncontigous sites, the density of colonisation and the species isolated. Antifungals should be started when Candida spp. are recovered from blood cultures or from usually sterile body fluids, abscesses or wounds in burns patients. They should also be considered in patients with a colonisation index >0.5 or a corrected colonization index >0.4 or when the isolate is identified as Candida tropicalis.

[Should cefminox substitute cefoxitin in infectionscaused by bacteria susceptible to both drugs?] / ¿Debe sustituir cefminox a cefoxitinaen en las infecciones por bacterias sensibles a ambos?

We studied the in vitro activity of cefminox (MIC by agar dilution) and cefoxitin against 477 facultative Gram-positive and Gram-negative isolates which were recovered from clinical specimens and identified by standard methods. Cefminox has proved to be 4-16 times more active than cefoxitin against enteric Gram-negative bacilli commonly involved in cholecystitis, secondary peritonitis, intraabdominal abscesses and gynecological infections. On the contrary, cefoxitin has proved to be four times more active against Gram-positive cocci. Both have been ineffective against Enterobacter spp., Pseudomonas aeruginosa and Acinetobacter spp. The microbiological activity and pharmacokinetic parameters of cefminox make it one of the first choice treatments for community-acquired intraabdominal and pelvic infections with the presence of anaerobes.