Irreversible Brain Death Research Articles

Explainable and Interpretable Model for the Early Detection of Brain Stroke Using Optimized Boosting Algorithms.

Background/Objectives: Stroke stands as a prominent global health issue, causing con-siderable mortality and debilitation. It arises when cerebral blood flow is compromised, leading to irreversible brain cell damage or death. Leveraging the power of machine learning, this paper presents a systematic approach to predict stroke patient survival based on a comprehensive set of factors. These factors include demographic attributes, medical history, lifestyle elements, and physiological metrics. Method: An effective random sampling method is proposed to handle the highly biased data of stroke. The stroke pre-diction using optimized boosting machine learning algorithms is supported with explainable AI using LIME and SHAP. This enables the models to discern intricate data patterns and establish correlations between selected features and patient survival. Results: The performance of three boosting algorithms is studied for stroke prediction, which include Gradient Boosting (GB), AdaBoost (ADB), and XGBoost (XGB) with XGB achieved the best outcome overall with a training accuracy of 96.97% and testing accuracy of 92.13%. Conclusions: Through this approach, the study seeks to uncover actionable insights to guide healthcare practitioners in devising personalized treatment strategies for stroke patients.

Prolong Submersion in the Swimming Pool without Neurological Outcome

Abstract Drowning can be defined as a chain of events of respiratory disability due to submersion or immersion in liquid with sequelae such as irreversible brain damage, heart failure, and death. The main organ in a drowning subject is the brain, which has almost zero energy and oxygen stores and hence needs a continuous supply of blood to fulfill its need for oxygen and loss of laryngospasm. This leads to massive aspiration, lung atelectasis, and edema. This unique and miracle case was a child submerged in a swimming pool for a prolonged period without receiving CPR, traveling from the drowning place to the present hospital around 30 km. The patient came from a small village where there were no facilities of ambulance inbuilt basic facilities or advanced life support. He was on a mechanical ventilator in the pediatric intensive care unit in the present institute. He was unconscious on admission. Recovered from all complications and was discharged without any neurological abnormalities. A 13-year-old boy was admitted to the pediatric emergency department with a history of drowning in a swimming pool; he was a nonswimmer and went with his friends who were swimmers, where he accidentally fell into the water without notice from other friends. After not finding him around, his friends searched for him. They found him immersed in water at the bottom of the pool for about 10–15 min, not receiving cardiopulmonary resuscitation (CPR) as nobody was trained. The primary diagnosis was drowning without neurological complications. Therapeutic interventions included a mechanical ventilator, intravenous antibiotics, intravenous steroids, chest physiotherapy. On discharge patient had no neurological complication except limping of right foot. After 1 month of follow up, central nervous system examination was within the normal limits. No limping was seen. No neurological deficit was observed. Drowning is a common etiology of accidental mortality in the pediatric age group. Most victims not treated with CPR at the site develop permanent neurological deficits. Proper and effective management can improve many complications caused due to drowning. Guidelines should be strictly followed in private/public swimming pools to have all duties of lifeguards who are trained in CPR. Drowning patients should be managed in hospitals with well-equipped mechanical ventilators, including trained staff.

Taste-masked formulation of sodium phenylbutyrate (ACER-001) for the treatment of urea cycle disorders

Urea cycle disorders (UCDs) are a group of rare inherited metabolic diseases caused by a deficiency of one of the enzymes or transporters that constitute the urea cycle. Defects in these enzymes lead to acute accumulation (hyperammonemic crises, HAC) or chronically elevated levels (hyperammonemia) of ammonia in the blood and/or various tissues including the brain, which can cause persistent neurological deficits, irreversible brain damage, coma, and death. Ongoing treatment of UCDs include the use of nitrogen-scavenging agents, such as sodium phenylbutyrate (salt of 4-phenylbutyric acid; NaPBA) or glycerol phenylbutyrate (GPB). These treatments provide an alternative pathway for nitrogen disposal through the urinary excretion of phenylacetylglutamine. ACER-001 is a novel formulation of NaPBA with polymer coated pellets in suspension, which is designed to briefly mask the unpleasant bitter taste of NaPBA and is being developed as a treatment option for patients with UCDs. Four Phase 1 studies were conducted to characterize the bioavailability (BA) and/or bioequivalence (BE) of ACER-001 (in healthy volunteers) and taste assessment relative to NaPBA powder (in taste panelists). ACER-001 was shown to be bioequivalent to NaPBA powder under both fed and fasting conditions. Lower systemic exposure of phenylacetate (PAA) and phenylbutyrate (PBA) was observed when ACER-001 was administered with a high-fat meal relative to a fasting state suggesting that the lower doses of PBA administered under fasting conditions may yield similar efficacy with potentially fewer dose dependent adverse effects relative to higher doses with a meal. ACER-001 appeared to be adequately taste-masked, staying below the aversive taste threshold for the first 3min after the formulation was prepared and remaining palatable when taken within 5min.

Organspende nach irreversiblem Hirnfunktionsausfall

The prerequisites for post-mortem organ donation in Germany include the determination of irreversible loss of brain function, consent to organ donation, and the exclusion of medical contraindications. In addition, mainly because of the shortage of donor organs in Germany and the sometimes controversial social and media discussions on the topic of organ donation, all physicians involved in the donation process must be familiar with the relevant laws, guidelines, and procedural instructions. This applies especially to those who are to carry out the verification of irreversible brain death. Only then, can they act safely in this challenging situation and serve as competent consultants for all involved.

CD4+ T Cells Are Required for Production of Disease-Causing Antibodies in an Alloantigen-Specific Murine Model of Fetal/Neonatal Alloimmune Thrombocytopenia

Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT) occurs when maternal antibodies specific for fetal platelet alloantigens cross the placenta and clear a baby's platelets, causing thrombocytopenia that is unpredictably severe and associated with irreversible brain damage and death. Of the 37 human platelet alloantigens (HPAs) implicated in FNAIT, HPA-1a, which resides on the integrin β3 subunit, is among the most clinically significant. Indirect evidence in humans implicates CD4+ T cells in production of FNAIT-causing HPA-1a-specific antibodies; however, whether CD4+ T cells are required for disease induction, and might therefore be manipulated to prevent disease development, is not known. We employed a novel CRISPR-Cas9-generated humanized transgenic mouse expressing the HPA-1a alloantigen to examine the requirement for CD4+ T cells in development of FNAIT. CD4+ T cells and B cells were purified separately from wild-type BALB/c donor mice that had been immunized, intraperitoneally with adjuvant, with platelets from HPA-1a-transgenic mice, in which HPA-1a-specific B and CD4+ T cells are generated. Donor B cells, either alone or with CD4+ T cells, were adoptively transferred into sub-lethally irradiated Rag1-deficient BALB/c recipient mice. Recipients were immunized with HPA-1a-transgenic platelets, and HPA-1a-specific antibodies were quantified in sequential blood samples collected from recipients. Adoptive transfer of B cells alone from HPA-1a-immunized mice resulted in transient production by Rag1-deficient recipients of only very low levels of HPA-1a-specific antibodies, whereas adoptive transfer of both B and CD4+ T cells resulted in sustained production of high levels of HPA-1a-specific antibodies. These results convincingly demonstrate that, in our mouse model, CD4+ T cells are required for B cell production of the HPA-1a-specific antibodies that cause FNAIT. The phenotypes and functions of CD4+ T cells that are generated in HPA-1a-incompatible pregnancies, and that initiate and amplify production of FNAIT-causing antibodies, are under investigation.

Statistical analysis of the social aspect of organ donation in determining brain death in the Republic of Kazakhstan

The article discusses the social problems of donation in the Republic of Kazakhstan when estab- lishing irreversible brain death in potential donors. The purpose of the article is to identify the social problems of organ donation in the Republic of Kazakhstan when establishing irreversible brain death by conducting statistical and comparative analysis. The article’s theoretical bases are the concepts of “altru- istic relations”, “gift economy”, “gift exchange theory”, “inheritance”. The data for the statistical analysis and research were provided by RSE on PCV “Republican center for coordination of transplantation and high-tech medical services” of the Ministry of health Of the Republic of Kazakhstan, the database of the Ministry of Digital Development, Innovation and Aerospace Industry of the Republic of Kazakhstan. So, based on the information above, the number of people on the waiting list, including those who died due to the lacking donor organs, the number of people who became donors after being diagnosed with brain death, and the number of living people who became donors are revealed. Moreover, evaluation of the significance and the role of the donor whose brain death is detected, has been given for society, people’s lives on the waiting list. Furthermore, the degree of interaction between recipient and donor in case of concluded brain death, the reasons for the low number of donors after the brain death in the Republic of Kazakhstan were discussed. In addition, the article considers the importance and benefits of multi-organ donation for society. Key words: irreversible brain death, multi-organ donor, «Eurotransplant» model, coordination cen- ter, waiting list, potential donor.

Long-Term Effects of Biliverdin Reductase a Deficiency in Ugt1-/- Mice: Impact on Redox Status and Metabolism.

Accumulation of neurotoxic bilirubin due to a transient neonatal or persistent inherited deficiency of bilirubin glucuronidation activity can cause irreversible brain damage and death. Strategies to inhibit bilirubin production and prevent neurotoxicity in neonatal and adult settings seem promising. We evaluated the impact of Bvra deficiency in neonatal and aged mice, in a background of unconjugated hyperbilirubinemia, by abolishing bilirubin production. We also investigated the disposal of biliverdin during fetal development. In Ugt1−/− mice, Bvra deficiency appeared sufficient to prevent lethality and to normalize bilirubin level in adults. Although biliverdin accumulated in Bvra-deficient fetuses, both Bvra−/− and Bvra−/−Ugt1−/− pups were healthy and reached adulthood having normal liver, brain, and spleen histology, albeit with increased iron levels in the latter. During aging, both Bvra−/− and Bvra−/−Ugt1−/− mice presented normal levels of relevant hematological and metabolic parameters. Interestingly, the oxidative status in erythrocytes from 9-months-old Bvra−/− and Bvra−/−Ugt1−/− mice was significantly reduced. In addition, triglycerides levels in these 9-months-old Bvra−/− mice were significantly higher than WT controls, while Bvra−/−Ugt1−/− tested normal. The normal parameters observed in Bvra−/−Ugt1−/− mice fed chow diet indicate that Bvra inhibition to treat unconjugated hyperbilirubinemia seems safe and effective.

Noninvasive Detection of Intracranial Hypertension by Novel Ultrasound Time-Harmonic Elastography.

A method for measuring intracranial pressure (ICP) noninvasively has long been sought after in neurology and neurosurgery. Treatment failure in individuals presenting with unspecific symptoms such as headache, gait disturbance, or visual impairment occurring in response to increased ICP can lead to irreversible brain injury, progressive disability, and death. Guidelines for diagnostic ICP measurement recommend intracranial placement of pressure tip catheters or lumbar puncture (LP) despite their invasiveness and possible complications. As ICP fluctuations are closely associated with changes in brain stiffness, ultrasound elastography could be a valid method to detect ICP noninvasively and with short examination times. In this pilot study, we have investigated the use of time-harmonic shear waves, introduced into the brain by an external shaker, and measured in real-time by transtemporal ultrasound, for deducing a noninvasive imaging marker sensitive to elevated ICP. To this end, we developed cerebral ultrasound time-harmonic elastography for the noninvasive quantification of shear wave speed (SWS) as a surrogate marker of cerebral stiffness in a short examination time of a few minutes. We found that SWS in patients enrolled for LP with confirmed intracranial hypertension was 1.81 ± 0.10 m/s, distinguishing them from healthy volunteers with excellent diagnostic accuracy (1.55 ± 0.08 m/s; P < 0.001; area under the curve, 0.99). Interestingly, values in symptomatic patients decreased to normal stiffness immediately after LP (1.56 ± 0.06 m/s, P < 0.001). Moreover, invasively measured opening pressure correlated with SWS measured before LP and liquid volume drained through the spinal tap with the SWS difference between the 2 measurements. Collectively, our results suggest a tight link between cerebral stiffness and ICP and demonstrate that intracranial hypertension can be detected noninvasively within short examination times, opening avenues for diagnostic applications of cerebral ultrasound time-harmonic elastography in neurology and emergency medicine.

Irreversible brain death-Part 2. Spinalization phenomena

Spinal automatisms and reflexes, peripheral neurogenic and myogenic reactions are common in patients with irreversible brain death. They are therefore compatible and are even understood by experienced investigators as confirmation of irreversible brain death. This article provides an overview of the phenomenology of irreversible brain death and discusses it from a neuropathological perspective. Furthermore, irreversible brain death is described in order to distinguish it from pathological movements and motor reactions in comatose patients or patients with disturbed consciousness due to severe brain disorders.

Diagnostik des irreversiblen Hirnfunktionsausfalls

In Germany, postmortem organ donation requires adiagnosis of irreversible brain death (BD) in strict compliance with the guidelines of the German Medical Association. Identification of factors that have alimiting effect on the initiation and execution of BD diagnostics. Identification of potential for improvement. Anonymous survey of transplantation officials in hospitals in Berlin, Brandenburg and Mecklenburg-Western Pomerania. There is considerable heterogeneity with respect to the frequency of BD diagnostics and hospital-specific procedures, including the use of an existing consultation service. The local availability of qualified doctors and of suitable ancillary diagnostic tests has astructurally limiting effect. This is especially true for pediatric patients. Potential for improvement was seen in the identification of affected patients, the motivation of staff and the role of transplantation officials. According to the recently amended German Transplantation Act, acentrally organized consultation service for BD diagnostics must be implemented as soon as 2021. Recommendations can be derived from the present survey and from the experience of the regionally established consultation service. In addition to neurological and neurosurgical expertise, qualified pediatricians and mobile ancillary instrumental diagnostics should also be provided. Expert advice from neurointensive care physicians should be available at an early stage in order to identify potentially affected patients. The highly variable participation of hospitals in organ donation, despite the availability of an expert diagnostic service free of charge, points to an important role of additional factors, some of which may be nonmedical in nature.

Midazolam and isoflurane combination reduces late brain damage in the paraoxon-induced status epilepticus rat model

Organophosphates (OPs) are widely used as pesticides and have been employed as warfare agents. OPs inhibit acetylcholinesterase, leading to over-stimulation of cholinergic synapses and can cause status epilepticus (SE). OPs poisoning can result in irreversible brain damage and death. Despite termination of SE, recurrent seizures and abnormal brain activity remain common sequelae often associated with long-term neural damage and cognitive dysfunction. Therefore, early treatment for prevention of seizures is of high interest. Using a rat model of paraoxon poisoning, we tested the efficacy of different neuroprotective and anti-epileptic drugs (AEDs) in suppressing early seizures and preventing brain damage. Electrocorticographic recordings were performed prior, during and after injection of 4.5 LD50 paraoxon, followed by injections of atropine and toxogonin (obidoxime) to prevent death. Thirty minutes later, rats were injected with midazolam alone or in combination with different AEDs (lorazepam, valproic acid, phenytoin) or neuroprotective drugs (losartan, isoflurane). Outcome measures included SE duration, early seizures frequency and epileptiform activity duration in the first 24 -hs after poisoning. To assess delayed brain damage, we performed T2-weighted magnetic resonance imaging one month after poisoning. SE duration and the number of recurrent seizures were not affected by the addition of any of the drugs tested. Delayed brain injury was most prominent in the septum, striatum, amygdala and piriform network. Only isoflurane anesthesia significantly reduced brain damage. We show that acute treatment with isoflurane, but not AEDs, reduces brain damage following SE. This may offer a new therapeutic approach for exposed individuals.

Communication with relatives

Communication with relatives is acentral part of the decision-making process. In the absence of the patient's direct consent to apotential organ donation, the next of kin must provide information about apotential wish to donate and give permission in the context of an extended consent solution. At the same time, family members must also cope with the death of aloved one. To determine how relatives can be optimally supported during the decision-making process. Narrative review. In the context of potential or confirmed irreversible brain death, communication with family members or legal representatives serves to deliver bad news as well as to determine whether the patient had awish to donate his/her organs and to clarify the resultant steps. Communication strategies such as the SPIKES or VALUE models provide emotional and cognitive support for relatives and strengthen clinicians' communication skills. Clinicians' behavior towards patients, deceased, and next of kin may influence relatives' decision-making; respectful and competent behavior seems to contribute towards relatives granting permission for organ donation. Clinicians must be trained and skilled in communication strategies which are used in critical situations to provide emotional support to relatives during the organ donation decision-making process. Relatives are more likely to achieve asatisfying and sustainable decision if astrong relationship exists between clinicians and relatives based on information giving, openness, trust, and empathy.

How Harvard Defined Irreversible Coma.

The Harvard criteria for the definition of irreversible coma or brain death were a product of a multidisciplinary committee chaired by anesthesiologist Beecher. The Harvard criteria included unreceptivity, unresponsiveness, no movements or breathing, no reflexes with further delineation of brainstem reflexes, and a flat electroencephalogram (repeated after 24h with no change). The apnea test involved disconnection of the ventilator for 3min. Hypothermia or any other central nervous system depressant had to be excluded. The Harvard criteria (and what followed) have been a bane for bioethicists from day one. This historical vignette explains, criticizes, and celebrates this landmark publication for its courage to tackle the topic. The Harvard criteria resulted in more studies and more criteria gradually complicating matters until the American Academy of Neurology in 1995 provided the necessary simplicity.

Ghost in the Machine: Historical Aspects of Irreversible Brain Injury and Brain Death (P2.469)

Ghost in the Machine: Historical Aspects of Irreversible Brain Injury and Brain Death (P2.469)

Cosmetic tourism for breast augmentation: a systematic review.

The medical tourism industry, and in particular cosmetic tourism for breast augmentation, is becoming an increasingly popular global phenomenon. The objective of this study is to determine the extent of medical literature and the patient risk profiles associated with cosmetic tourism for breast augmentation both locally and abroad. OVID MEDLINE, OVID Embase, Cochrane Central and Proquest electronic databases. The search was conducted through to April 2017. Studies pertaining entirely or partly to cosmetic tourism for breast augmentation were considered for inclusion. Exclusion criteria included non-English articles, studies relating to non-cosmetic or non-implant breast augmentation, and studies that did not separately report on findings associated with breast augmentation abroad. We identified 17 observational studies. Common destinations included Europe, South America and South East Asia. Infectious complications were common. Wound dehiscence and aesthetic dissatisfaction also featured. Catastrophic outcomes such as sepsis, intubation and ventilation, radical bilateral mastectomy, irreversible hypoxic brain injury and death were also reported. There were expectations that home country health systems would treat complications and provide non-medically indicated revision procedures. The burden on home country health systems was evident from a public health perspective. Determining the extent of cosmetic tourism for breast augmentation, including outcomes and complications, will help to inform Australian patients who this seek procedure abroad. Furthermore, it will aid in better understanding the health system implications and may help to guide future research and public health interventions both locally and internationally.

Bilirubin-Induced Neurotoxicity and Environmental Impacts on Hyperbilirubinemia Development

Hyperbilirubinemia (also known as jaundice), caused by the accumulation of unconjugated bilirubin, is one of the most common clinical diagnoses in both premature and term newborns. Owing to the fact that bilirubin is metabolized solely through glucuronidation by UDP-glucuronosyltransferase (UGT) 1A1, it is now known that immaturity of UGT1A1 in combination with overproduction of bilirubin during the developmental stage acts as a bottleneck to bilirubin elimination and predisposes the infant to high TBS levels. While neonatal jaundice is mostly benign, excessively high levels of serum bilirubin in a small percentage of newborns can cause acute or chronic bilirubin-induced neurologic dysfunction (BIND), potentially progressing to acute encephalopathy leading to irreversible brain damage and death. As a series of hereditary UGT1A1 mutations have been identified that are associated with UGT1A1 deficiency, new evidence has verified that developmental expression of UGT1A1 is a tightly controlled event, and both genetic polymorphisms and developmental regulation of UGT1A1 are major contributing factors determining the severity of hyperbilirubinemia and bilirubin-induced neurotoxicity. This review recapitulates the progress that has been made in recent years in understanding etiology and physiopathology of severe hyperbilirubinemia, investigating molecular mechanisms underlying bilirubin-induced encephalopathy, and searching for potential therapies for treating pathologic hyperbilirubinemia. Several animal models have been developed to make it possible to examine bilirubin-induced neurotoxicity from multiple directions. Moreover, environmental factors that may alleviate or worsen the condition of hyperbilirubinemia are discussed.

Rac1 contributes to cerebral ischemia reperfusion-induced injury in mice by regulation of Notch2

Background: Cerebral ischemia–reperfusion (IR) injury is a complex pathological process that can cause irreversible brain damage, neuronal injury or death from brain ischemia. Rac1 GTPase is involved in cellular protection from IR injury. However, the mechanism of protection and the molecules affected by Rac1 remain to be defined. Methods and results: C57BL/6 mice were subjected to middle cerebral artery occlusion for 1h, followed by 24-h reperfusion. In this in vivo model of cerebral IR injury, mice treated with the Rac GTPase inhibitor NSC23766 or Rac1 small interfering RNA (siRNA) had better short-term (72h) neurologic scores, less infarction volume, higher production of antioxidant enzymes, lower lipid peroxide, and reduced apoptosis compared with a vehicle-treated group or a control-siRNA group. However, long-term (14day) neurologic scores were worse for the two treatments compared to controls. Microarray and quantitative polymerase chain reaction (PCR) revealed that Notch2 was downregulated under NSC23766 treatment. Notch2 protein levels decreased with NSC23766 and Rac1 siRNA in vitro and in vivo. Cell survival increased with the Notch signaling inhibitor DAPT or Notch2 siRNA and NICD2 attenuated the NSC23766 effect. In addition, immunoblotting showed that DAPT and Notch2 siRNA changed the levels of apoptosis-regulating proteins. NFkB mediated Rac1, which regulated Notch2 in an oxygen glucose deprivation model. Both inhibitors of Notch2 and Rac1 enhanced neural stem cell differentiation. Conclusions: This study demonstrated the importance of Rac1 regulation of Notch2 in mediating cerebral IR-induced production of injurious reactive oxygen species and cell death in vitro and in vivo in the short term. Targeted inhibition of Rac1 or Notch2 is new avenue for in vivo therapy aimed at protecting organs at risk from IR injury.

KNOWLEDGE, ATTITUDES AND NURSING PRACTICES ON CARDIORESPIRATORY ARREST IN NEONATAL INTERMEDIATE CARE UNIT: A QUALITATIVE STUDY IN THE NORTHEAST OF BRAZIL

Introduction: the cardiorespiratory arrest (CRA) in neonates is rarely a sudden event. It is the result of progressive deterioration of respiratory and circulatory functions, leading to irreversible brain damage and death, if appropriate measures are not immediately taken by professionals with specific knowledge. Objective : to analyze the knowledge, attitudes and practices of nursing professionals on cardiorespiratory arrest in a neonatal intermediate care unit. MethodS : Qualitative study of exploratory and descriptive approach, conducted in October 2012 in Cajazeiras, Paraiba, Brazil. Five nurses and three nurse technicians participated. The instrument used was a structured, adapted and validated questionnaire. Results : the nursing professionals knew the definition and how to identify the early signs and symptoms of CRA and recognized the difference between CRA in neonates and adults. Professionals reported changes in care CRA protocol. The careful handling of the newborn, especially the head and neck and heating prior to resuscitation maneuvers were the main actions reflecting basic knowledge to effect the cardiopulmonary ressucitation (CPR) maneuvers. Referring to the sequence of the CPR, questions emerged. Few professionals knew about the correct sequence of the implementation of CPR maneuvers recommended for infants. 100% (n = 8) of the participants demonstrated to know the Advanced Support technical life in neonatology, held with the presence of a doctor. Turning to the main medications administered during CPR in newborns, the adrenaline was the drug of choice, followed by atropine, bicarbonate and dobutamine. Given the factors that hinder the performance of the nursing staff to the CRA victim, professionals reported insecurity, lack of technical skills, difficulty in practice / performance of certain procedures; deficit of practical / theoretical knowledge and inexperience to act on the steps of CPR. Conclusion : it was found that there is no protocol to guide the nursing team in cases of CRA, since they act in a heterogeneous manner. There is also a lack of knowledge of current clinical protocols, on performing certain procedures, primary assessment and chest compressions, according to the new guidelines proposed by the American Heart Association which may lead to a poor quality of care.

Jahi McMath and the Ethics of the Brain Death Standard

How does one account for “the discrepancy” between the evidence of total and irreversible brain death and the current evidence of recovered brain function? This is the question that is raised by recent legal action in the case of 13-year old Jahi McMath, certified dead on the basis of neurological criteria but maintained in mechanical ventilation and medical/nursing care since then at the insistence of the parents who claim she is alive. In this brief discussion, the medical and legal issues are reviewed. Here the argument is advanced that this is not a case that means there should be a re-evaluation of the neurological criteria for determination of brain death. Instead, this case is to be understood as the exception that proves the rule. DOI: http://dx.doi.org/10.3329/bioethics.v5i3.21533 Bangladesh Journal of Bioethics 2014; 5(3):18-22

Occurrence of giant focal forms of congenital hyperinsulinism with incorrect visualization by (18) F DOPA-PET/CT scanning.

Congenital hyperinsulinism (CHI) is a rare disease characterized by severe hypoglycaemic episodes due to pathologically increased insulin secretion from the pancreatic beta cells. When untreated, CHI might result in irreversible brain damage and death. Currently, two major subtypes of CHI are known: a focal form, associated with local distribution of affected beta cells and a nonfocal form, affecting every single beta cell. The identification of focal forms is important, as the patients can be cured by limited surgery. (18) F DOPA-PET/CT is an established non-invasive approach to differentiate focal from nonfocal CHI. The purpose of this study was to identify possible limitations of (18) F DOPA-PET/CT scan in patients with focal forms nonfocal CHI. A retrospective chart review of 32 patients (from 2008 through 2013) who underwent (18) F DOPA-PET/CT and partial pancreatectomy for focal CHI at the reference centres in Berlin, Germany and London, UK. In most cases (n=29, 90·7%), (18) F DOPA-PET/CT was sufficient to localize the complete focal lesion. However, in some patients (n=3, 9·3%), (18) F DOPA-PET/CT wrongly visualized only a small portion of the focal lesion. In this group of patients, a so-called 'giant focus' was detected in histopathological analysis during the surgery. Our data show that in most patients with focal CHI (18) F DOPA-PET/CT correctly predicts the size and anatomical localisation of the lesion. However, in those patients with a 'giant focal' lesion (18) F DOPA-PET/CT is unreliable for correct identification of 'giant focus' cases.