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Background and ObjectivesBreakdowns in clinician-family communication in neurologic intensive care units (neuroICUs) are common, particularly for goals-of-care decisions to continue or withdraw life-sustaining treatments while considering long-term prognoses. Shared decision-making interventions (decision aids [DAs]) may prevent this problem and increase patient-centered care, yet none are currently available. We assessed the feasibility, acceptability, and perceived usefulness of a DA for goals-of-care communication with surrogate decision makers for critically ill patients with severe acute brain injury (SABI) after hemispheric acute ischemic stroke, intracerebral hemorrhage, or traumatic brain injury.MethodsWe conducted a parallel-arm, unblinded, patient-level randomized, controlled pilot trial at 2 tertiary care US neuroICUs and randomized surrogate participants 1:1 to a tailored paper-based DA provided to surrogates before clinician-family goals-of-care meetings or usual care (no intervention before clinician-family meetings). The primary outcomes were feasibility of deploying the DA (recruitment, participation, and retention), acceptability, and perceived usefulness of the DA among surrogates. Exploratory outcomes included outcome of surrogate goals-of-care decision, code status changes during admission, patients' 3-month functional outcome, and surrogates' 3-month validated psychological outcomes.ResultsWe approached 83 surrogates of 58 patients and enrolled 66 surrogates of 41 patients (80% consent rate). Of 66 surrogates, 45 remained in the study at 3 months (68% retention). Of the 33 surrogates randomized to intervention, 27 were able to receive the DA, and 25 subsequently read the DA (93% participation). Eighty-two percent rated the DA's acceptability as good or excellent (median acceptability score 2 [IQR 2–3]); 96% found it useful for goals-of-care decision making. In the DA group, there was a trend toward fewer comfort care decisions (27% vs 56%, p = 0.1) and fewer code status changes (no change, 73% vs 44%, p = 0.02). At 3 months, fewer patients in the DA group had died (33% vs 69%, p = 0.05; median Glasgow Outcome Scale 3 vs1, p = 0.05). Regardless of intervention, 3-month psychological outcomes were significantly worse among surrogates who had chosen continuation of care.DiscussionA goals-of-care DA to support ICU shared decision making for patients with SABI is feasible to deploy and well perceived by surrogates. A larger trial is feasible to conduct, although surrogates who select continuation of care deserve additional psychosocial support.Clinical Trials RegistrationClinicaltrials.govNCT03833375.Classification of EvidenceThis study provides Class IV evidence that the use of a DA explaining the goals-of-care decision and the treatment options is acceptable and useful to surrogates of incapacitated critically ill patients with ischemic stroke, intracerebral hemorrhage, or traumatic brain injury.

Immune checkpoint inhibitors (CPIs) are highly effective in the treatment of various cancers. Immunotherapy enhances antitumor activity by relieving inhibition of T cells responsible for immune surveillance. However, overactivation of T cells leads to immune-related adverse events (irAE), of which cutaneous adverse events are the most common. Examples include pruritus and maculopapular eruption most commonly, psoriasis and bullous dermatoses less commonly, and, rarely, severe, life-threatening eruptions such as Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis. Many of these are autoimmune in nature, and these may present de novo or as recurrence of pre-existing disease. In order to maximize the therapeutic potential of CPIs, it is essential to recognize and effectively manage cutaneous irAE, which can otherwise lead to treatment interruption or discontinuation. This review summarizes the presentation and management of dermatologic adverse events secondary to immune dysregulation as a result of immune checkpoint inhibitor therapy, including the most common (maculopapular eruption, pruritus, lichenoid dermatitis, and vitiligo), less common (psoriasis, bullous pemphigoid, erythema multiforme, eczematous dermatitis, alopecia areata, and granulo-matous and neutrophilic dermatoses), and severe (acute generalized exanthematous pustulosis [AGEP], drug reaction with eosinophilia and systemic symptoms [DRESS], and Stevens-Johnson syndrome or toxic epidermal necrolysis [SJS/TEN]), as well as exacerbation of pre-existing cutaneous autoimmune disease (subacute cutaneous lupus erythematosus, dermatomyositis, eosinophilic fasciitis, leukocytoclastic vasculitis, and scleroderma-like reaction).

Glutathione (GSH) is the primary defense against oxidative stress through its role in reducing reactive oxygen species (ROS) in the body, and its levels have been shown to be lower in both metabolic disease and aging. In this study, we sought to determine whether GSH levels in the human brain are lower in older individuals and whether these levels are associated with metabolic changes that come with age, such as increasing insulin resistance. 14 young (age 30.1 ±3.2 years, BMI 26.1 ±0.8 kg/m2, A1c 5.3% ±0.1, HOMA-IR 1.6 mg(μU)/dL(mL) ±0.2) and 9 old (age 73.7 ±1.8, BMI 28.1 ±1.6, A1c 5.6 ±0.1, HOMA-IR 2.9 ±0.7) individuals underwent an oral glucose tolerance test as well as magnetic resonance spectroscopy (MRS) scanning at 4T for measurement of intracerebral GSH levels in the prefrontal cortex and striatum. Older individuals had higher levels of plasma ROS compared to younger individuals (P Disclosure J.J. Pach: None. D. Groskreutz: None. J. Leventhal: None. M. Knight: None. K. Jain: None. J. Hwa: None. L. Jiang: None. R. de Graaf: None. J. Hwang: None. Funding National Institutes of Health (P30AG021342)

Metabolic derangement triggered by a high fat diet has been associated with decreased brain glucose uptake in mice through downregulation of GLUT-1 expression at the blood-brain barrier. Likewise, a prior study by our group using 1H magnetic resonance spectroscopy (MRS) showed diminished change in brain glucose level during acute hyperglycemia in patients with obesity and diabetes. However, whether this reflected differences in absolute brain concentrations remains unknown. We utilized 13C MRS scanning at 4 Tesla to compare the rate of glucose transport (Tmax) and cerebral metabolic rate of glucose (CMRgl) in the occipital lobe during a 2-hour hyperglycemic clamp. Plasma glucose concentration of ∼180mg/dl was achieved using a variable 1-13C-glucose infusion. The study included 8 healthy lean (1M/7F, age 29 ± 5 years, BMI 21 ± 2 kg/m2, HgbA1c 5.4 ± 0.2%) and 6 obese participants (4M/2F, age 30 ± 3 years, BMI 33 ± 3 kg/m2, HgbA1c 5.5 ± 0.2%). Insulin and free fatty acids (FFA) levels were measured during the clamp. Despite nearly identical plasma glucose concentrations at steady state (lean 182.5 ± 9.0 mg/dL, obese 186.5 ± 13.5 mg/dL, P=0.55, averaged over time 60-120 minutes), the absolute brain glucose concentrations were 30% less in obese compared to lean participants (P=0.02). Moreover, using previously reported Michaelis-Menten Kt of 1.1 mM, the calculated Tmax/CMRgl at steady state were 37% less in obese participants (P=0.01), suggesting reduced glucose transport. A trend of higher insulin and FFA levels in obese participants during hyperglycemia was observed. In addition, FFA levels at steady state were negatively correlated with absolute brain glucose concentrations (r= -0.575, P=0.05). We conclude that obesity is associated with diminished absolute concentration of brain glucose during acute hyperglycemia, likely explained by reduced cerebral glucose transport capacity. These findings may have implications for understanding the impact of obesity on central regulation of feeding behavior as well as neurocognitive function. Disclosure F. Gunawan: None. L. Jiang: None. J. Leventhal: None. J.J. Pach: None. E. Sanchez Rangel: None. R. Belfort-DeAguiar: Research Support; Self; Silver Palate Kitchens, Inc. A. Coppoli: None. D.L. Rothman: None. R. Sherwin: Other Relationship; Self; ICON plc., IQVIA, MannKind Corporation. G.F. Mason: None. J.J. Hwang: None. Funding American Diabetes Association (1-17-ICTS-013 to J.J.H.)

Background Hyperglycemia leading to increased oxidative stress is implicated in the increased risk for the development of macrovascular and microvascular complications in patients with type 1 diabetes mellitus. Methods and Results A random subcohort of 349 participants was selected from the DCCT / EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) cohort. This included 320 controls and 29 cardiovascular disease cases that were augmented with 98 additional known cases to yield a case cohort of 447 participants (320 controls, 127 cases). Biosamples from DCCT baseline, year 1, and closeout of DCCT , and 1 to 2 years post‐ DCCT ( EDIC years 1 and 2) were measured for markers of oxidative stress, including plasma myeloperoxidase, paraoxonase activity, urinary F 2α isoprostanes, and its metabolite, 2,3 dinor‐8 iso prostaglandin F 2α . Following adjustment for glycated hemoblobin and weighting the observations inversely proportional to the sampling selection probabilities, higher paraoxonase activity, reflective of antioxidant activity, and 2,3 dinor‐8 iso prostaglandin F 2α , an oxidative marker, were significantly associated with lower risk of cardiovascular disease (−4.5% risk for 10% higher paraoxonase, P iso prostaglandin F 2α , P =0.0092). In contrast, the oxidative markers myeloperoxidase and F 2α isoprostanes were not significantly associated with cardiovascular disease after adjustment for glycated hemoblobin. There were no significant differences between DCCT intensive and conventional treatment groups in the change in all biomarkers across time segments. Conclusions Heightened antioxidant activity (rather than diminished oxidative stress markers) is associated with lower cardiovascular disease risk in type 1 diabetes mellitus, but these biomarkers did not change over time with intensification of glycemic control. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifiers: NCT 00360815 and NCT 00360893.

Hintergrund: Retinitis pigmentosa (RP) bezeichnet einen genetisch und klinisch heterogenen Formenkreis an dystrophischen Netzhauterkrankungen. Im Verlauf der Erkrankung kommt es zu zunehmenden Gesichtsfeldeinschrankungen bis hin zur Erblindung. Bisher ist keine Therapie etabliert. Durch zunehmendes Wissen uber die zugrunde liegenden genetischen und pathophysiologischen Veranderungen gibt es eine Reihe von neuen Therapieansatzen, von denen einige hier vorgestellt werden sollen. Methodik: Es wurde eine systematische Literaturrecherche in PubMed zu definierten Stichworten durchgefuhrt. Ergebnisse: Zu den neuen Therapieansatzen gehoren Gentherapie, pharmakologische Substanzen, Neuroprotektion, Elektrostimulation, retinale Implantate, Zelltransplantation und optogenetische Ansatze. Schlussfolgerung: In den letzten Jahren gab es einige Fortschritte in der Erforschung moglicher Therapieansatze bei dystrophischen Netzhauterkrankungen. Die Forschung ist in den einzelnen Bereichen unterschiedlich weit fortgeschritten. Obwohl es nach wie vor keine etablierte Therapie gibt, stehen die Chancen gut, dass in Zukunft zumindest einem Teil der RP-Patienten eine Therapie angeboten werden kann.

62 chronic schizophrenics, who after a psychotic exacerbation were stabilized again, were randomized on 3 different maintenance dosages of flupentixol-decanoate and observed for 12 months. 15 (24.2%) patients had a relapse independently of the dose. 34 of the 47 patients without relapse had complete documentations of the follow-up. After 3 to 6 months there was an obvious and constant clinical improvement as assessed by various test inventories. The BPRS-scores for psychopathology, negative and positive symptoms improved significantly between 14 to 18%. There was also significant reduction of negative symptoms assessed by SANS (22%) as well in the severity of illness (CGI) and an amelioration of psychosocial functioning (GAS, Strauss-Carpenter). At the end of trial 26.4% of the patients had mild involuntary movements (AIMS), 23.5% were on antiparkinson-medication. It is concluded that there could be an indication for flupentixol-decanoate in the long term maintenance therapy especially of chronic schizophrenics with negative symptoms and problems of compliance under oral medication.

Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of hereditary retinal disorders, which lead to progressive loss of vision and finally blindness. Yet there is no approved therapy. Advances in unravelling underlying genetic disorders and pathophysiological mechanisms offer new therapeutic approaches of which some are summarised in this review.We performed a systematic literature research for defined key words in PubMed.New approaches to therapy for RP include: gene therapy, pharmacological treatment, neuroprotection, electrical stimulation, retinal prostheses, retinal transplantation and optogenetic therapy.Recently there have been advances in new approaches for therapy of dystrophic retinal diseases. Advances in the different approaches are being made at different rates. Although there is no approved therapy yet, the future for treating RP at least in some patients looks promising.

Stargardt's disease is an autosomal recessive inherited juvenile macular degeneration and at present no acknowledged science-based therapy is available for these patients. Recently, reports have been published on the effectiveness of electrical stimulation in experimental animal models and in patients with neurodegenerative ocular disease, particularly retinitis pigmentosa. This study included 12 patients with Stargardt's disease who were randomized into one of three groups (n = 4) with 0% (sham), 66% or 150% of the individual electrically stimulated phosphene threshold. Outcome measures of the study were safety and efficacy of transcorneal electrical stimulation (TES) with DTL electrodes in subjective and objective parameters of visual function under therapy. In general TES was well tolerated and no adverse or serious events were noted. Neither Ganzfeld, multifocal ERG, OCT nor visual field testing showed statistically significant changes in any group.

Postimperative negative variation (PINV) was recorded during a warned reaction time paradigm in 16 chronic DSM-IIIR schizophrenics in remission. Clinical symptoms were assessed by BPRS, SANS and the anhedonia scale of the Chapman Questionnaire. Ten healthy controls were studied in the same manner. Over the fronto-central area we found a significantly elevated PINV amplitude with an altered topographical distribution in the patient group. The difference values 'PINV Cz-PINV Fz' were correlated negatively with primary negative symptoms of schizophrenia.

The hypothesis was tested that there are relationships between schizophrenic negative or deficit symptoms, the skin conductance nonresponding and an elevated amplitude of the postimperative negative variation (PINV). These variables were recorded in 16 chronic schizophrenics and 10 healthy controls. Clinical symptoms were assessed by the Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Frankfurt Complaint Questionnaire 3 and Chapman Questionnaire. In the patient group we found a significantly elevated PINV at Fz. Surprisingly, only one patient was a skin conductance nonresponder. PINV amplitude at Fz and the number of skin conductance responses to habituation were not correlated with negative or deficit symptoms inclding anhedonia. The hypothesis thus had to be rejected.

We undertook this study to evaluate the effects of needle acupuncture on cardiac autonomic nervous system (ANS) function in patients with minor depression or anxiety disorder. Patients (n = 36) were randomly distributed into a verum acupuncture (VA) group (needles were applied at classical acupuncture points, e. g. He7, Pe6, Du20, Bl62, Ex6) or a placebo (PL) group (needles were applied only epidermal at non-acupuncture points). Both groups underwent standardized measurements of the 5-minute resting heart rate variability (HRV), which were performed before the first and after the 9th acupuncture session of an acupuncture series, and also three times (before the start and 5, respectively, 15 minutes after needle application) during the third acupuncture session. Demographic data between the VA and PL group did not differ. Before the start of acupuncture there were also no significant differences in HRV data between these groups. Compared to PL the VA group showed a significant decrease of the mean resting heart rate both, 5 and 15 minutes after needle application, combined with a trend towards an increase of the high frequency (HF; 0.15 - 0.4 Hz) and a decrease of the low frequency (LF; 0.04 - 0.15 Hz) spectral power. The latter effects resulted in an overall significant decrease of the mean LF/HF ratio in VA compared to PL treated patients. This pattern of findings suggests that in patients with minor depression or anxiety only verum acupuncture 1.) leads to a relative increase of cardiovagal modulation of heart rate and 2.) facilitates the physiological regulatory ANS function in response to alterations of external or internal environment. Clinical implications of these findings are discussed.

The aim of the study was to evaluate myocardial perfusion in acute carbon monoxide poisoned patients using rest and stress Tc 99m-MIBI SPECT scintigraphy. There were 29 study patients (15 men and 14 women) aged from 14 to 46 years poisoned acutely with CO at home. Measurement of COHb, blood lactate level, duration of exposure and ECG examination were performed on admission to the Clinic. The enzymes activity (ALT, AST, CBK) were evaluated after 24 hours. The first rest Tc99m-MIBI SPECT was performed in all patients two to five days after intoxication. Fifteen of the patients underwent the control examination: stress and rest scintigraphy six months after CO exposure. Moving track exercise according to the Bruce protocol was used in each the patients. The control rest scintigraphy was performed 48 hours after exercise. Abnormal, differently intensified scans were noted in all the subjects: 5 patients had a I degree of pathological changes, 7 patients had II degree, 16--III degree and 1 patient had a IV degree of pathological changes. In 14 of the patients with pathological scintigraphic scans the normal EKG curves were noted. The mean COHb level was 35.0 +/- 7.22%, the blood lactate concentration was 4.4 +/- 3.7 mmol/L. The average duration of exposure was 108.4 +/- 163.9 min. Effort related ischemia was not noted in 10 of the patients who underwent control examination. An improvement in rest scintigraphic scans was stated in 12, and no changes were observed in 3 of the controlled patients. Deterioration was not found in any patient. No correlation between ECG results and scintigraphic image of myocardium was found. Tc 99m-MIBI SPECT scintigraphy is a more sensitive method than electrocardiography and measurement of enzymes activity for the evaluation of CO cardiotoxicity in acute poisoning. The method enables evaluation of the localization and disease extent.

That the problem of drug addiction is still growing up, so there is the necessity for widen of treatment panel for psychoactive substances abuse, especially for opiates. Because of the fact, that substituting treatment became to be popular in patients' opinion, more attention were paid on new medicine-buprenorphine. It is an agonist- antagonist of opiates' receptors. Buprenorphine has been successfully used in long-term treatment in United States and in Western Europe. Treatment with buprenorphine has been started in Poland in Toxicological Department in Kraków. This article shows outcomes of substituting treatment with buprenorphine in period from December 2000 to February 2001.

Methadone treatment programme for 50 opiate addicts has been conducted at the Department of Clinical Toxicology for a one year. The aim of the study was to evaluate the health state including psychological condition and also a social status of the opiate dependent patients after one year methadone maintenance medication. Also, considering the results of clinical examination, a trial of elaboration of system for dependence scoring was undertaken. An improvement of general health state of addicts was observed. No new cases of HIV positive patients were noted. An increase in number of addicts who start professional activity, and those who live in procreative families and even in formally confirmed marriage. A three pregnant women, and five who already gave birth to a child (one of them is completely drug free at present) were noted. A significant behavioural changes, reduced level of criminal activity and restored personal relationships with family were observed. A moderate psychopathological symptoms are still observed in patients with double diagnosis.

The study included 180 patients aged 18-79 (average 36) hospitalized for suicide attempts (drug intoxi-cations) in the Department of Clinical Toxicology CM UJ from March to December 2000. Examined group was composed of 49 men and 131 women. The following tests were used in this study: structured questionnaire, psychological tests: Beck Depression Inventory, Hamilton Depression Scale, Hopelessness Scale, Suicidal Intent Scale, Life Events Scale, SOC 29 (by Antonovsky). Besides, we used data from patients' history. The aim of our study is to analyse clinical data of suicidal attempters--after first and repeated suicidal attempts. We took into consideration the severity of coma, severity of intoxication, the kind of substances used in the attempt, the presence of alcohol, previous psychiatric treatment, cases of suicide among the patients' close friends or relatives and duration of hospitalization. Then the psychiatric diagnosis was stated. The analysis of severity of intoxication (divided into three stages: severe, moderate, and light according to the Poisoning Severity Score (PSS) indicated that in the group of repeated suicide attempters the percentage of severe intoxications was greater (9.2%) then in first time attempters. In the population of second time female attempters there is a greater percentage of persons who took neuroleptics (15.4%) compared to group first attempters (5.4%). In both groups the majority were taking anxiolytisc, sleep-inducing and mixed drugs. There was a greater percentage of persons drinking alcohol during the attempt among repeated suicidal attempters (38.8%) than among the first time attempters (26%). The percentage of persons with diagnosis of mental disease (treated in ambulatory or in hospital) is higher in the group of repeated suicide attempters (25.9%) then after first attempters (6.3%). In both groups a lot of persons had reactive depression, often associated with personality disorders, rarely endogenic depressions or psychosis. We observed that addiction to alcohol is often a problem in men who attempt suicide (I group--32.3%, II group--33.3%). The analysis of medical documentation indicated in the group of repeated suicide attempters a high percentage of people with cases of suicide among their close friends or relatives.

The blood clearance of Tc99m MIBI is rapid and biexponential, with an initial fast phase followed by a slow phase. The fundamental myocellular uptake mechanism involves passive distribution across plasma and mitochondrial membranes, and at equilibrium, sestamibi is sequestered within the mitochondria by the larger negative mitochondrial transmembrane potential. Reverse distribution into blood stream is stopped by the high membrane potential of the cardiac cells. Scintigraphic changes followed by the metabolic abnormalities in patients after acute carbon monoxide poisoning can be necrosis or only the transitory ischemia. It seems to detect accurately the extension of the early necrosis (unreversible) of the myocardium. Amiscan kit for the preparation of Tc99m-glucarate is being developed as a radiopharmaceutical diagnostic agent for the imaging of and diagnosis of acute myocardial necrosis. Cellular and subcellular uptake studies have shown that Tc99m-glucarate localizes in necrotic tissues binding primarily to the nucleoprotein sub-fractions and to a lesser extent to the DNA fractions. Glucarate is taken up rapidly by necrotic myocardium and cleared relatively rapidly from the circulation resulting in early, hight target-to-background ratios. In studies of Amiscan in patients with acute myocardial infarction, sensitivity was found to be 100% when Amiscan is administered within 9 hours of the onset of chest pain. In our preliminary study the scintigraphic scans using Tc99m-glucarate were performed in 10 patients after acute carbon monoxide poisoning. The study can confirm that some patients during acute CO poisoning have typical myocardial necrosis, but part of them have hibernating and/or stunned myocardium.

The patients hospitalised because of acute ethanol intoxication or ethanol withdrawal syndrome at the Kraków Department of Clinical Toxicology and Detoxification Ward of J. Babiński Specialistic Hospital in the years 1997-2000 were subjected to the study. A significant increase in number of ethanol related hospitalisation was noted at the Department of Clinical Toxicology (from 1381 patients in year 1997 up to 1771 in year 2000), and at the Detoxification Ward of Babiński Hospital from 369 in 1997 and 849 patients in 2000 respectively. A significant increase in number of ethanol dependent patients admitted to the Department of Clinical Toxicology because of acute ethanol intoxication and the patients hospitalised because of ethanol withdrawal syndrome or signs of delirium tremens was noted. The same and even stronger trends in hospitalisation, particularly of those ethanol addicts presenting clinical symptoms of acute ethanol intoxication were observed at the Detoxification Ward of Babiński Hospital.