[Updated AWMF Guideline on the Diagnosis and Treatment of Langerhans cell Histiocytosis in Children and Adolescents]. / Aktualisierte AWMF Leitlinie zur Diagnostik und Therapie der Langerhanszell Histiozytose (LCH) im Kindes- und Jugendalter.

Langerhans cell Histiocytosis is a rare neoplastic disease, which occurs mainly in children and adolescents. The disease may affect any organ, and therefore, the clinical symptoms vary widely. Some patients have a spontaneous remission of the disease, whereas others experience a rapid and potentially lethal clinical course. The therapeutic approach depends on the extent of the disease, and reaches from a watch-and-wait strategy to chemotherapy with the standard drugs vinblastine and prednisone. The identification of mutations in the MAPK-pathway resulted in growing interest in targeted therapy using compounds such as the BRAF inhibitors. Chronic relapses and permanent sequelae are important problems of LCH and are the focus of current research.

Performance of the beta-glucan test for the diagnosis of invasive fusariosis and scedosporiosis: a meta-analysis.

The (1→3)-ß-D-glucan (BDG) is a component of the fungal cell wall that can be detected in serum and used as an adjunctive tool for the diagnosis of invasive mold infections (IMI) in patients with hematologic cancer or other immunosuppressive conditions. However, its use is limited by modest sensitivity/specificity, inability to differentiate between fungal pathogens, and lack of detection of mucormycosis. Data about BDG performance for other relevant IMI, such as invasive fusariosis (IF) and invasive scedosporiosis/lomentosporiosis (IS) are scarce. The objective of this study was to assess the sensitivity of BDG for the diagnosis of IF and IS through systematic literature review and meta-analysis. Immunosuppressed patients diagnosed with proven or probable IF and IS, with interpretable BDG data were eligible. A total of 73 IF and 27 IS cases were included. The sensitivity of BDG for IF and IS diagnosis was 76.7% and 81.5%, respectively. In comparison, the sensitivity of serum galactomannan for IF was 27%. Importantly, BDG positivity preceded the diagnosis by conventional methods (culture or histopathology) in 73% and 94% of IF and IS cases, respectively. Specificity was not assessed because of lacking data. In conclusion, BDG testing may be useful in patients with suspected IF or IS. Combining BDG and galactomannan testing may also help differentiating between the different types of IMI.

IF and IS are severe fungal infections for which diagnosis is often delayed. This meta-analysis shows that beta-glucan testing in serum had a sensitivity of about 80% for IF/IS and could detect the disease earlier compared to conventional diagnostic tests.

Adult-type and Pediatric-type Diffuse Gliomas : What the Neuroradiologist Should Know.

The classification of diffuse gliomas into the adult type and the pediatric type is the new basis for the diagnosis and clinical evaluation. The knowledge for the neuroradiologist should not remain limited to radiological aspects but should be based additionally on the current edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS). This classification defines the 11 entities of diffuse gliomas, which are included in the 3 large groups of adult-type diffuse gliomas, pediatric-type diffuse low-grade gliomas, and pediatric-type diffuse high-grade gliomas. This article provides a detailed overview of important molecular, morphological, and clinical aspects for all 11 entities, such as typical genetic alterations, age distribution, variability of the tumor localization, variability of histopathological and radiological findings within each entity, as well as currently available statistical information on prognosis and outcome. Important differential diagnoses are also discussed.

Characterization of MRI White Matter Signal Abnormalities in the Pediatric Population.

(1) Background and Purpose: The aim of this study was to retrospectively characterize WMSAs in an unselected patient cohort at a large pediatric neuroimaging facility, in order to learn more about the spectrum of the underlying disorders encountered in everyday clinical practice. (2) Materials and Methods: Radiology reports of 5166 consecutive patients with standard brain MRI (2006-2018) were searched for predefined keywords describing WMSAs. A neuroradiology specialist enrolled patients with WMSAs following a structured approach. Imaging characteristics, etiology (autoimmune disorders, non-genetic hypoxic and ischemic insults, traumatic white matter injuries, no final diagnosis due to insufficient clinical information, "non-specific" WMSAs, infectious white matter damage, leukodystrophies, toxic white matter injuries, inborn errors of metabolism, and white matter damage caused by tumor infiltration/cancer-like disease), and age/gender distribution were evaluated. (3) Results: Overall, WMSAs were found in 3.4% of pediatric patients scanned at our and referring hospitals within the ten-year study period. The majority were found in the supratentorial region only (87%) and were non-enhancing (78% of CE-MRI). WMSAs caused by autoimmune disorders formed the largest group (23%), followed by "non-specific" WMSAs (18%), as well as non-genetic hypoxic and ischemic insults (17%). The majority were therefore acquired as opposed to inherited. Etiology-based classification of WMSAs was affected by age but not by gender. In 17% of the study population, a definite diagnosis could not be established due to insufficient clinical information (mostly external radiology consults). (4) Conclusions: An "integrated diagnosis" that combines baseline demographics, including patient age as an important factor, clinical characteristics, and additional diagnostic workup with imaging patterns can be made in the majority of cases.

[Severe courses of meningitis and encephalitis in children and adolescents]. / Schwer verlaufende Meningitis und Enzephalitis bei Kindern und Jugendlichen.

Bacterial meningitis and viral encephalitis are infectious diseases of the central nervous system (CNS), mostly with severe sequelae up to a fatal outcome. Despite progress in prevention by vaccination, the global impact of bacterial meningitis is enormous. Before the coronavirus disease 2019 (COVID-19) pandemic, the incidence of viral encephalitis in childhood was increasing also due to the growing incidence of emerging pathogens, such as enterovirus (EV)-A71 and West Nile virus in temperate climates as well as the wider use of immunosuppressive treatment and stem cell transplantation in childhood. The following article summarizes the data on the frequency and clinical signs of infectious CNS diseases and presents the current treatment recommendations.

Magnetic Resonance Imaging as the Primary Imaging Modality in Children Presenting with Inflammatory Nontraumatic Atlantoaxial Rotatory Subluxation.

Inflammatory nontraumatic atlantoaxial rotatory subluxation (AAS) in children is an often-missed diagnosis, especially in the early stages of disease. Abscess formation and spinal cord compression are serious risks that call for immediate surgical attention. Neither radiographs nor non-enhanced computed tomography (CT) images sufficiently indicate inflammatory processes. Magnetic resonance imaging (MRI) allows a thorough evaluation of paraspinal soft tissues, joints, and ligaments. In addition, it can show evidence of vertebral distraction and spinal cord compression. After conducting a scoping review of the literature, along with scientific and practical considerations, we outlined a standardized pediatric MRI protocol for suspected inflammatory nontraumatic AAS. We recommend contrast-enhanced MRI as the primary diagnostic imaging modality in children with signs of torticollis in combination with nasopharyngeal inflammatory or ear nose and throat (ENT) surgical history.

Central Nervous System Mold Infections in Children with Hematological Malignancies: Advances in Diagnosis and Treatment.

The incidence of invasive mold disease (IMD) has significantly increased over the last decades, and IMD of the central nervous system (CNS) is a particularly severe form of this infection. Solid data on the incidence of CNS IMD in the pediatric setting are lacking, in which Aspergillus spp. is the most prevalent pathogen, followed by mucorales. CNS IMD is difficult to diagnose, and although imaging tools such as magnetic resonance imaging have considerably improved, these techniques are still unspecific. As microscopy and culture have a low sensitivity, non-culture-based assays such as the detection of fungal antigens (e.g., galactomannan or beta-D-glucan) or the detection of fungal nucleic acids by molecular assays need to be validated in children with suspected CNS IMD. New and potent antifungal compounds helped to improve outcome of CNS IMD, but not all agents are approved for children and a pediatric dosage has not been established. Therefore, studies have to rapidly evaluate dosage, safety and efficacy of antifungal compounds in the pediatric setting. This review will summarize the current knowledge on diagnostic tools and on the management of CNS IMD with a focus on pediatric patients.

Abusive head trauma: experience improves diagnosis.

PURPOSE: The diagnosis of abusive head trauma (AHT) is complex and neuroimaging plays a crucial role. Our goal was to determine whether non-neuroradiologists with standard neuroradiology knowledge perform as well as neuroradiologists with experience in pediatric neuroimaging in interpreting MRI in cases of presumptive AHT (pAHT). METHODS: Twenty children were retrospectively evaluated. Patients had been diagnosed with pAHT (6 patients), non-abusive head trauma-NAHT (5 patients), metabolic diseases (3 patients), and benign enlargement of the subarachnoid spaces (BESS) (6 patients). The MRI was assessed blindly, i.e., no clinical history was given to the 3 non-neuroradiologists and 3 neuroradiologists from 2 different institutions. RESULTS: Blindly, neuroradiologists demonstrated higher levels of sensitivity and positive predictive value in the diagnosis of pAHT (89%) than non-neuroradiologists (50%). Neuroradiologists chose correctly pAHT as the most probable diagnosis 16 out of 18 times; in contrast, non-neuroradiologists only chose 9 out of 18 times. In our series, the foremost important misdiagnosis for pAHT was NAHT (neuroradiologists twice and non-neuroradiologists 5 times). Only victims of motor vehicle accidents were blindly misdiagnosed as pAHT. No usual household NAHT was not misdiagnosed as pAHT. Neuroradiologists correctly ruled out pAHT in all cases of metabolic diseases and BESS. CONCLUSION: MRI in cases of suspected AHT should be evaluated by neuroradiologists with experience in pediatric neuroimaging. Neuroradiologists looked beyond the subdural hemorrhage (SDH) and were more precise in the assessment of pAHT and its differential diagnosis than non-neuroradiologists were. It seems that non-neuroradiologists mainly assess whether or not a pAHT is present depending on the presence or absence of SDH.

Pediatric CNS imaging and long-term effects of irradiation in pediatric oncology patients.

BACKGROUND: The aim of this study was to evaluate post-irradiation changes in the central nervous system (CNS) detected using magnetic resonance (MR) imaging. METHODS: Magnetic resonance images of 15 children with CNS tumors treated through whole-brain irradiation over 10 years were reviewed retrospectively. Variables such as age at the time of irradiation, total radiation dose, treatment length, and time interval between irradiation and MR changes, were evaluated. RESULTS: All patients included in the study had imaging abnormalities of the CNS. Eight patients (53%) developed CNS abnormalities within a short period of time - only a few months after irradiation (mean 4.8 months). Seven patients (47%) developed CNS abnormalities within a long time interval after treatment (mean 4.6 years). In almost all patients, a T2 increase in supra- and infratentorial white matter was observed. Follow-up examinations showed nine patients (60%) with cerebellar atrophy. CONCLUSIONS: In this sample of pediatric patients who underwent whole-brain irradiation, the time receiving irradiation was not related to the severity of the MR changes. A correlation between the age of the child or the length of the radiotherapy and the extent of the changes could not be confirmed. However, we observed a trend towards stronger brain parenchymal degeneration with cystic changes in the younger age group of children in our sample. Older children who received irradiation seem to be more susceptible to vascular dysplasia with cavernous hemangiomas and microbleeding.

Invasive Mold Infection of the Central Nervous System in Immunocompromised Children.

Background: Due to the difficulties in the definite diagnosis, data on brain imaging in pediatric patients with central nervous system (CNS)-invasive mold infection (IMD) are scarce. Our aim was to describe brain imaging abnormalities seen in immunocompromised children with CNS-IMD, and to analyze retrospectively whether specific imaging findings and sequences have a prognostic value. Methods: In a retrospective study of 19 pediatric patients with proven or probable CNS-IMD, magnetic resonance imaging (MRI)-findings were described and analyzed. The results were correlated with outcome, namely death, severe sequelae, or no neurological sequelae. Results: 11 children and 8 adolescents (11/8 with proven/probable CNS-IMD) were included. Seven of the patients died and 12/19 children survived (63%): seven without major neurological sequelae and five with major neurological sequelae. Multifocal ring enhancement and diffusion restriction were the most common brain MRI changes. Diffusion restriction was mostly seen at the core of the lesion. No patient with disease limited to one lobe died. Perivascular microbleeding seen on susceptibility weighted imaging (SWI) and/or gradient-echo/T2* images, as well as infarction, were associated with poor prognosis. Conclusions: The presence of infarction was related to poor outcome. As early microbleeding seems to be associated with poor prognosis, we suggest including SWI in routine diagnostic evaluation of immunocompromised children with suspected CNS-IMD.

The role of magnetic resonance imaging in the diagnosis of central nervous system involvement in children with acute lymphoblastic leukemia.

PURPOSE: Acute lymphoblastic leukemia (ALL) is the most frequent malignancy in childhood. As central nervous system (CNS) involvement requires an intensified CNS-targeted therapy, timely diagnosis is essential. The aim of this retrospective analysis was to evaluate whether cranial magnetic resonance imaging (MRI) examinations findings correlate with cerebrospinal fluid (CSF) analysis on CNS involvement and whether MRI examinations reveal incidental findings with a clinical consequence. METHODS: All pediatric patients with ALL at our institution between 1998 and 2016 were identified. Patients were divided into two groups: de novo and relapsed ALL. Both groups were analyzed separately for the presence of CNS involvement. Incidental findings were also evaluated. RESULTS: Two hundred fifteen patients with de novo ALL and 31 with relapsed ALL were identified. In the de novo group, no patient was diagnosed CNS positive based on MRI results alone. In relapsed patients, only one patient had a positive MRI with negative CSF results and no neurological symptoms, thus was classified CNS positive solely on the basis of the MRI. In both groups, no patient showed an incidental finding that required therapy. CONCLUSION: In our study, MRI examinations do not improve the detection of CNS involvement compared with CSF analysis alone. In addition, the analysis of incidental findings does not add value to the performance of an MRI examination performed prior to treatment. Overall, MRI prior to treatment in pediatric patients with ALL is not necessary.

European Society of Paediatric Radiology 2019 strategic research agenda: improving imaging for tomorrow's children.

The European Society of Paediatric Radiology (ESPR) research committee was established to initiate, drive forward and foster excellence in paediatric imaging, paediatric image-guided intervention and radiation protection research, by facilitating more evidence-based standards, protocols and multi-institutional collaborations. The ESPR Strategic Research Agenda outlines our current research approach, highlighting several areas of paediatric imaging where the society can help guide current and future research, and emphasizing those areas where early research ("seed") funding may need to be allocated by this and other societies as precursors to larger grant applications. The key aims are to evaluate normal variation in order to be able to confidently diagnose disease states, develop robust image-based classification systems to aid diagnosis and treatment monitoring, and help develop evidence-based clinical guidelines using current literature and experience to identify knowledge gaps. For this reason, the development of evidence-based imaging pipelines, broken down step-by-step to include diagnosis, classification and clinical effectiveness, should be the end goal for each disease entity for each affected child. Here, we outline the 2019 ESPR Strategic Research Agenda along three points in the clinical imaging pipeline: clinical referral, disease diagnosis and evolution, and clinical therapeutic evaluation and effectiveness. Through multicentre trials, using existing high-level experience and expertise, and nurturing the next generation of researchers, we will be able to achieve these aims.

Pontine tumor in a neonate: case report and analysis of the current literature.

Tumors of the central nervous system represent the largest group of solid tumors found in pediatric patients. Pilocytic astrocytoma is the most common pediatric glioma, mostly located in the posterior fossa. The majority of brainstem tumors, however, are classified as highly aggressive diffuse intrinsic pontine gliomas (DIPGs) and their prognosis is dismal.The authors report on the case of a neonate in whom MRI and neuropathological assessment were used to diagnose DIPG. Before initiation of the planned chemotherapy, the tumor regressed spontaneously, and the newborn exhibited a normal neurological development. Meanwhile, Illumina Human Methylation450 BeadChip analysis reclassified the tumor as pilocytic astrocytoma of the posterior fossa.In conclusion, the authors advocate not initiating immediate intensive therapy in newborns with brain tumors, even with classical appearance of a DIPG; rather, they would like to encourage a biopsy to define the best individual therapeutic approach and avoid ineffective chemotherapy.

Overweight among children and adolescent with type I diabetes mellitus: prevalence and associated factors.

OBJECTIVES: Describe the overweight frequency (overweight and obesity) and identify the factors associated with this in children and adolescents with type 1 diabetes mellitus (T1DM) treated at a University Children's Hospital in Rio de Janeiro. METHODS: This is an analytical cross-sectional study, which included patients diagnosed with T1DM who had complete anthropometric data (weight and height) and excluded those using drugs with effect on weight gain, genetic syndromes, celiac disease, hypothyroidism, renal failure and other chronic diseases, and pregnant women. The data collection was referring to the last consultation, and with respect to laboratory tests, the most recent data was collected. The dependent variable was the overweight, defined as Z score ≥1. The independent variables were gender, age, insulin dose, duration of disease, lipid profile, glycated hemoglobin, type of prescribed food planning, and place of residence. A logistic regression model was built for each outcome studied, considering significant associations those with p < 0.05. RESULTS: The study included 195 patients with a mean age of 10.6 (±3.8) years, and 49.7 % (n = 97) aged less than 10 years. The overweight frequency was 40 % (n = 78). The age ≥10 years (OR 0.41; 95 % CI 0.20-0.86; p = 0.019) and the dose of insulin/kg ideal weight (OR 3.38; 95 % CI 1:55-7:39; p = 0.002) were considered the variables associated with overweight. CONCLUSIONS: There was a high prevalence of overweight, which explains strategies for promoting healthy eating habits and changing lifestyle with a focus on children and adolescents with diabetes.

Paediatric patients with sudden vision impairment - An overview of MRI findings.

PURPOSE: Sudden visual impairment in children occurs sporadically but, when present, needs urgent attention. Optimal management strategies and timely recognition are required. Often psychogenic disorders are the cause in school-age children; however, this is a diagnosis of exclusion. Therefore, MRI plays an important role in ruling out pathology along the optic pathways or helping with the diagnosis of underlying life threatening diseases, such as hydrocephalus or intracranial mass. The purpose of this study was first to evaluate non-traumatic (tumoural and non-tumoural) causes of acute vision impairment; and, second, to assess whether conventional cerebral and orbital MR imaging is helpful for children with sudden visual impairment. PATIENTS AND METHODS: We retrospectively analysed the MRI scans and clinical findings of 95 children (47 male, 48 female; median age: 12.5 years, range: from 2 to 17 years) who presented symptoms of monocular or bilateral acute vision impairment. RESULTS: Patients with acute visual impairment were usually older than 7 years. In 36% of the patients a correlation between the MRI findings and the clinical symptoms was found. The most common causes of visual impairment were: infectious diseases (16%), migraine (12%), autoimmune diseases (11%), optic nerve neuritis with unknown aetiology (8%), neoplasms (8%), idiopathic intracranial hypertension (5%) and orthostatic hypotension (4%). Still, in 23% of the patients the cause remained unclear. CONCLUSION: Acute vision impairment is frequently caused by infectious diseases, migraine, autoimmune diseases or tumours in children. MRI is highly recommended, especially in the case of children younger than 5 years of whom clinical assessment can be difficult.

A novel reconstruction tool (syngo DynaCT Head Clear) in the post-processing of DynaCT images to reduce artefacts and improve image quality.

BACKGROUND: Latest generations of flat detector (FD) neuroangiography systems are able to obtain CT-like images of the brain parenchyma. Owing to the geometry of the C-arm system, cone beam artifacts are common and reduce image quality, especially at the periphery of the field of view. An advanced reconstruction algorithm (syngo DynaCT Head Clear) tackles these artifacts by using a modified interpolation-based 3D correction algorithm to improve image quality. MATERIALS AND METHODS: Eleven volumetric datasets from FD-CT scans were reconstructed with the standard algorithm as well as with the advanced algorithm. In a two-step data analysis process, two reviewers compared dedicated regions of the skull and brain in both reconstruction modes using a 5-point scale (1, much better; 5, much worse; advanced vs standard algorithm). Both reviewers were blinded to the reconstruction mode. In a second step, two additional observers independently evaluated image quality of the 3D data (non-comparative evaluation) in dedicated regions also using a 5-point scale (1, not diagnostically evaluable; 5, good quality, perfectly usable for diagnosis) for both reconstruction algorithms. RESULTS: Both in the comparative evaluation of dedicated brain regions and in the independent analysis of the FD-CT datasets the observers rated a better image quality if the advanced algorithm was used. The improvement in image quality was statistically significant at both the supraganglionic (p=0.018) and the infratentorial (p=0.002) levels. CONCLUSIONS: The advanced reconstruction algorithm reduces typical artifacts in FD-CT images and improves image quality at the periphery of the field of view.

Absence of biochemical evidence at an early age delays diagnosis in a patient with a clinically severe peroxisomal biogenesis disorder.

Analysis of the plasma levels of very long chain fatty acids (VLCFA) is a primary screening method for peroxisomal disorders and usually identifies severe peroxisomal biogenesis defects reliably. We report a patient presenting with typical facial stigmata, a treatment resistant seizure disorder and polymicrogyria, whose plasma VLCFA levels were within normal limits until the age of 18 months. Only thereafter an elevation was found. Subsequent enzymatic and molecular genetic analysis revealed compound heterozygous mutations in the PEX6 gene. In conclusion, normal VLCFA levels do not necessarily exclude global peroxisomal biogenesis defects and the analysis should be repeated subsequently. Persisting clinical suspicion justifies further enzymatic and molecular evaluation.

Analysis of T2 signal intensity helps in the differentiation between high and low-grade brain tumours in paediatric patients.

PURPOSE: Previous studies hypothesized that the analysis of magnetic resonance intensity of the solid portion in paediatric tumours can provide pre-surgical information about the histopathology. Classically, high signal-intensity in T2weighted (T2w) images identifies low-grade tumours, while anaplasia is characterized by T2 hypointensity. We aimed to investigate if T2w signal intensities can pre-operatively distinguish between low-grade and high-grade brain tumours in paediatric patients. METHODS: Two raters, blinded to the histological diagnosis, rated the signal intensity of MR images (T2w) from 36 children with newly diagnosed brain tumours, 17 children with low-grade brain tumours and 19 children with high-grade brain tumours were included in this study. Relative T2 values were obtained by dividing the T2w values of the solid portion of the tumour by the T2w values of the vitreous humour. RESULTS: The best cut-off point to distinguish low and high-grade paediatric brain tumours was 0.8. If the signal intensity was less than or equal to 0.8 the tumour was expected to be a high-grade tumour with a sensitivity of 100%. Prediction of a low-grade tumour was more uncertain with a sensitivity of 70.5%. Overall, 86% of the tumours would have been predicted correctly. CONCLUSION: Our data suggest that T2w signal intensities of the solid portion of brain tumours in paediatrics can pre-operatively differentiate between low-grade and high-grade tumours. In addition, T2 hypointensity may be helpful in targeting stereotactic biopsy.

Evaluation of the perforators of the anterior communicating artery (AComA) using routine cerebral 3D rotational angiography.

BACKGROUND: Damage to perforating branches of the anterior communicating artery (AComA) is a known complication of surgical or interventional treatment procedures for AComA aneurysm leading to neurologic deficits. In spite of the clinical relevance of these AComA branches, they have not been systematically analyzed using imaging techniques and most of our knowledge is based on post-mortem injection studies or neurosurgical reports. We therefore analyzed three-dimensional rotational angiography (3DRA) images of the AComA, and propose a first imaging definition of the microvascular structures surrounding the AComA. METHODS: Reconstructed 3D data derived from standard-of-care rotational angiography acquisitions (5 s DSA) were retrospectively analyzed. 20 patients undergoing selective cerebral angiography and 3DRA for therapy assessment were included in our study. 3DRA datasets were reconstructed and displayed using the volume rendering technique (VRT). Additionally, multiplanar reformatted CT-like cross-sectional images (MPR) were used to evaluate the number, size, and origin of the perforators of the AComA. RESULTS: Perforating branches of the AComA could be demonstrated in all cases with large interindividual variations in vessel visibility. MPRs appeared to be superior to total VRT volumes in the visualization of the perforating branches of the AComA. CONCLUSIONS: 3DRA can be used to visualize perforating branches of the AComA in vivo. Since damage to these perforators may result in neurologic deficits, visualization of these vessels prior to surgery or endovascular aneurysm treatment could help in the planning of therapeutic interventions. Further refinement of current imaging techniques will be necessary, however, to increase the reliability of small vessel angiography.

Determination of the worst case for cleaning validation of equipment used in the radiopharmaceutical production of lyophilized reagents for 99mTc labeling

ABSTRACT Cleaning validation, a requirement of the current Good Manufacturing Practices (cGMP) for Drugs, consists of documented evidence that cleaning procedures are capable of removing residues to predetermined acceptance levels. This report describes a strategy for the selection of the worst case product for the production of lyophilized reagents (LRs) for labeling with 99mTc from the Instituto de Pesquisas Energéticas e Nucleares (IPEN-CNEN/São Paulo). The strategy is based on the calculation of a "worst case index" that incorporates information about drug solubility, cleaning difficulty, and occupancy rate in the production line. It allowed a reduction in the required number of validations considering the possible manufacturing flow of a given product and the subsequent flow, thus facilitating the process by reducing operation time and cost. The products identified as "worst case" were LRs PUL-TEC and MIBI-TEC.

RESUMO A validação de limpeza é uma exigência dos atuais regulamentos de Boas Práticas de Fabricação de Medicamentos (BPF) e consiste na evidência documentada, que demonstra que os procedimentos de limpeza removem os resíduos em níveis de aceitação pré-determinados. Este estudo apresenta uma estratégia para escolha do produto "pior caso" da linha de produção de reagentes liofilizados para marcação com 99mTc do Instituto de Pesquisas Energéticas e Nucleares (IPEN-CNEN/São Paulo). A estratégia baseia-se no cálculo de um índice denominado "índice para pior caso," que utiliza informações de solubilidade dos fármacos, dificuldade de limpeza dos equipamentos e ocupação dos produtos na linha de produção. A estratégia adotada proporcionou a diminuição no número de validações necessárias, considerando-se as possibilidades de sequências de fabricação de um determinado produto e do produto subsequente, possibilitando a simplificação do processo e redução no tempo e nos custos das atividades envolvidas. Os produtos indicados como pior caso foram os reagentes liofilizados (RL) PUL-TEC e MIBI-TEC.