Report on a study of fires with smoke gas development : determination of blood cyanide levels, clinical signs and laboratory values in victims.

BACKGROUND: This is a report on an international non-interventional study of patients exposed to fires with smoke development in closed rooms. The objective of the study was to document clinical symptoms, relevant laboratory values and blood cyanide concentrations from fire victims in order to confirm or rule out presumptive correlations between the individual parameters. MATERIALS AND METHODS: The study was conducted in five European countries with patients being included if they presented with the characteristic clinical signs, such as soot deposits and altered neurological status. Venous blood samples were taken from victims prior to administration of an antidote in all cases and determination of cyanide concentration was performed in a central laboratory using high performance liquid chromatography. RESULTS: Data from 102 patients (62 % male, average age 49 years) were included in the evaluation with no blood samples being available for analysis from 2 patients. In 25 patients the blood cyanide concentration was below the limit of detection of 1.2 µmol/l. Cyanide levels between 1.2 and 10 µmol/l were measured in 54 patients, 7 patients had values between 10 and 20 µmol/l, 4 patients between 20 and 40 µmol/l while levels above 40 µmol/l were determined in 10 patients. The results of the study could not demonstrate that the cyanide level was influenced either by the interval between smoke exposure and blood sampling or the duration presence at the fire scene. The following clinical signs or laboratory values were recorded as relevant for increased and possibly toxic cyanide levels: respiratory arrest, dyspnea, resuscitation requirement, tracheal intubation, respiratory support measures, low Glasgow coma scale (GCS) score and respiratory frequency. A correlation between cyanide concentration and the total amount of soot deposits on the face and neck, in the oral cavity and in expectoration was confirmed. A correlation between cyanide and carboxyhemoglobin (COHb) levels in the blood of fire victims was also confirmed. CONCLUSIONS: As long as it is not possible to immediately determine the blood cyanide concentration in patients exposed to fire with smoke development, a decreased GCS score, soot deposits particularly in expectoration, dyspnea and convulsions are to be regarded as risk markers for intoxication. In their presence immediate administration of hydroxocobalamin as an antidote is recommended.

Pharmacokinetics of obidoxime in patients poisoned with organophosphorus compounds.

OBJECTIVES: Reactivation of inhibited acetylcholinesterase (AChE) with oximes is a causal therapy of intoxication with organophosphorus compounds (OPs). Maximal oxime effects are expected when effective doses are administered as soon as possible and as long as reactivation can be anticipated. An obidoxime plasma level in the range of 10-20 microM was estimated as appropriate. The achievement of this target was assessed in 34 severely OP-poisoned patients. METHODS: After admission to the intensive care unit (ICU) the obidoxime regimen (250 mg i.v. as bolus, followed by 750 mg/24h) was started and maintained as long as reactivation was possible. Plasma concentrations of obidoxime were determined by HPLC. RESULTS: A total amount of 2269+/-1726 mg obidoxime was infused over 65 h+/-55 h resulting in a steady state plasma concentration of 14.5+/-7.3 microM. Obidoxime was eliminated with t(1/2(1)) 2.2 and t(1/2(2)) 14 h. The volumes of distribution amounted to 0.32+/-0.1L/kg (V((1))) and 0.28+/-0.12 (V((2)))L/kg. Postmortem examination of tissue in one patient showed obidoxime accumulation in cartilage, kidney and liver and pointed to brain concentrations similar to plasma concentration. CONCLUSIONS: Using the suggested obidoxime regimen, the targeted plasma concentration could be achieved. Obidoxime was eliminated biphasically and was well tolerated. This result allows the recommendation of using this definite regimen for adults also in case of mass casualties.

[Lead intoxication in a group of workers in Germany]. / Gruppenvergiftung mit Blei am Arbeitsplatz.

HISTORY AND ADMISSION FINDINGS: Seventeen East-European workers with a suspected lead-intoxication presented themselves to the Department of Toxicology. All of them had worked on the renovation of pylons of a high-tension line. The old paint, known to contain lead was removed with needle descalers. The patients had blood lead concentrations between 325 and 1124 microg/l, but no specific symptoms. The workers neglected the protective measures at their working-place. INVESTIGATIONS: 12 of 17 workers had lead-concentrations above 400 microg/l (Reference < 90 microg/l). 10 of 17 patients showed an increased level of free protoporphyrins and all workers showed a decreased activity of delta-aminolaevulinacid-dehydratase (ALAD). TREATMENT AND COURSE: Patients with lead-concentration above 700 microg/l were treated with the chelating agent meso-2,3-dimercaptosuccinic acid (DMSA) 3 x 200 mg/d for nine days. The patients with lead concentrations between 400 and 700 microg/l were treated which DMSA 3 x 100 mg/d. After the DMSA-treatment the lead-concentrations had dropped (p < 0.001). During the DMSA-therapy one patient had to be treated in the hospital because of a generalised allergic exanthema. CONCLUSION: We report seventeen patients with high lead concentration in their blood due to occupational exposure. The high blood lead levels showed that the workers had not been protected adequately. This examplifies that occupational lead exposure still occurs, also in Germany. By patients with unspecific symptoms connected with lead exposure a biomonitoring for lead is necessary.

Monitoring of neuromuscular transmission in organophosphate pesticide-poisoned patients.

Thirty-four adult patients with severe organophosphorus compounds (OP) poisoning requiring artificial ventilation were enrolled in a clinical study and received atropine and obidoxime (250 mg i.v., followed by 750 mg/24 h) as antidotal treatment. Here, we re-analyzed the cholinesterase status (red blood cell acetylcholinesterase (RBC-AChE) activity, reactivatability of RBC-AChE, and plasma butyrylcholinesterase (Pl-BChE) activity) in relation to the neuromuscular transmission (NMT) data. When RBC-AChE activity ranged between 100% and 30% NMT was unimpaired after tetanic stimulation with frequencies up to 50 Hz. A further decrease in RBC-AChE activity was accompanied by a marked disturbance of NMT, being strongly impaired at AChE activities <5% of normal. Higher stimulation frequencies (>30 Hz) facilitated the discrimination of the types of impairment. The neuromuscular transmission was the best quantified by using the ratio of the ninth to the first amplitude, while the standard method was less discriminative. At RBC-AChE levels higher than 40% of normal weaning from the ventilator may be considered. Completely aged RBC-AChE as indicated by loss of reactivatability loses its guidance function. Then, steadily increasing Pl-BChE activity suggests lack of circulating poison. One-week later, neuromuscular transmission may be largely normal and patients could be weaned from the respirator if other complications are not withstanding.

Acute effects of sulfur mustard injury--Munich experiences.

Sulfur mustard (SM) is a strong vesicant agent which has been used in several military conflicts. Large stockpiles still exist to the present day. SM is believed to be a major threat to civilian populations because of the persistent asymmetric threat by non-state actors, such as terrorist groups, its easy synthesis and handling and the risk of theft from stockpiles. Following an asymptomatic interval of several hours, acute SM exposure produces subepidermal skin blisters, respiratory tract damage, eye lesions and bone marrow depression. Iranian victims of SM exposure during the Iran-Iraq (1984-1988) war were treated at intensive care units of 3 Munich hospitals. All 12 patients were injured following aerial attacks with SM filled bombs, which exploded in a distance between 5 and 30m. All patients soon noted an offensive smell of garlic, addle eggs or oil roasted vegetables. No individual protective equipment was used. Eye itching and skin blistering started 2h after SM exposure. Some patients complained of nausea, dizziness and hoarseness. 4h after exposure, most patients started vomiting. Eye symptoms worsened and most patients suffered from temporary blindness due to blepharospasm and lid oedema. Additionally, pulmonary symptoms such as productive cough occurred. Patients were transferred to Munich 4-17 days after SM exposure. On admission all patients showed significant skin blistering and pigmentation. Conjunctivitis and photophobia were the major eye symptoms. Pulmonary symptoms, including productive cough were persistent. Bronchoscopy revealed massive inflammation of the trachea with signs of necrosis. 3 patients needed tracheotomy. Chest X-ray did not yield abnormal observations. This presentation summarizes the experience of treating SM victims in Munich and discusses therapeutic implications.

Acute renal failure by ingestion of Cortinarius species confounded with psychoactive mushrooms: a case series and literature survey.

Mushrooms of the Cortinarius species are nephrotoxic and can cause severe acute renal failure. The toxic effect is due to orellanine. It is suspected that the cytotoxic damage is caused by the production of oxygen-free radicals. Renal pathology shows tubular necrosis with interstitial nephritis. In addition to accidental intoxications as a consequence of mushroom meals, recent cases are often due to voluntary abuse of natural drugs like magic mushrooms. We report 4 current cases of acute renal failure from intoxication by Cortinarius species by confusing it with psychoactive fungi. Typical for the Cortinarius poisoning is the long latency period from ingestion until the onset of clinical symptoms (3 - 20 days). Diagnosis is based on microscopical identification of the mushroom spores, and detection of the orellanine toxin in leftover mushrooms. In renal biopsy tissue, orellanine is detectable by thin-layer chromaography technique up to 6 months after poisoning. There is no causative therapy, and treatment is symptomatic with adequate hemodialysis. In cases of otherwise unexplained acute renal failure, intoxication with nephrotoxic mushrooms should be considered.

[Amanita poisoning--comparison of silibinin with a combination of silibinin and penicillin]. / Knollenblätterpilzvergiftung. Silibinin und Kombination von Silibinin und Penicillin im Vergleich.

BACKGROUND AND AIMS: Current treatment of amatoxin poisoning includes the administration of silibinin and penicillin in combination or silibinin alone. The aim of this study was to compare both therapeutic regimes. PATIENTS AND METHODS: Of 604 patients with the suspected diagnosis of amatoxin poisoning 367 were retrospectively analysed: 118 patients had received silibinin alone and 249 patients silibinin in combination with penicillin. Logistic regression analyses were applied to investigate the efficacy of both therapeutic regimens by comparing death and liver transplantation rates. A potentially independent effect on outcome of age, sex, year of treatment, latency period of symptoms and start of silibinin therapy was taken into account. RESULTS: In the group who had received the combination of silibinin and penicillin 8.8% died or underwent liver transplantation compared to 5.1% in the group of those who had received silibinin alone. The risk of death or organ transplantation was thus reduced by nearly 40% in the latter group (adjusted odds ratio: 0.58; 95% CI: 0.21-1.57; p=0.28). A longer latency period (< or =12h vs. >12h) was associated with a significant reduction of this risk (adjusted OR.: 6.10; 95% CI:1.77-21.3; p=0.004). A later start of silibinin therapy (>24h vs. < or = 24h) was associated with a tendency toward an increased frequency of death or organ transplantation (adjusted OR.: 3.0; 95% CI: 0.96-9.20; p=0.059). CONCLUSIONS: A lower death and transplantation rate was observed in the silibinin treatment group than in group treated with silibinin combined with penicillin. However, this difference was not statistically significant. The high risk ratio relating to the time-dependent effect of silibinin suggests its efficaciousness in the treatment of amatoxin poisoning. The latency period was assessed as an independent prognostic factor.

Cerebellar effects after consumption of edible morels (Morchella conica, Morchella esculenta).

Morchella esculenta and Morchella conica are well known edible morels, which seldom induce clinical symptoms. We report six persons who developed cerebellar effects 6-12 hours after consumption of these mushrooms. The symptoms were self-limited and disappeared after one day.

Withdrawal from high-dose tranylcypromine.

A 34-year-old man with a history of multiple substance abuse (now abstinent for six years) became addicted to tranylcypromine, consuming up to 240 mg/day. After discontinuing the drug, he developed thrombocytopenia (52,000/ul) and delirium; there were no other anticholinergic signs. The delirium was unresponsive to haloperidol and diazepam. Intravenous administration of physostigmine (2 mg) on hospital day 6 resulted in prompt, but temporary, clearing of the delirium. Following a recurrence of the delirium after 30 minutes, he was started on an intravenous infusion of physostigmine (2 mg/hr) with good results. Physostigmine administration did not produce any cholinergic signs. By hospital day 8, he did not require any more physostigmine. Thrombocytopenia resolved on hospital day 9 without therapeutic intervention. On hospital day 10, the patient was asymptomatic and left the hospital on his own recognizance.

Treatment of health complaints attributed to amalgam.

The aim of the present study was to compare the reduction of subjective complaints by 3 treatment strategies in 90 "amalgam patients" whose complaints could not be explained by a medical or psychological disorder. The individuals were randomly assigned either to removal of dental amalgam only (removal group), or removal in combination with a "biological detoxification" therapy with high doses of vitamins and trace elements (removal-plus group), or participation in a health promotion program without removal of dental amalgam (no-removal group). Between baseline and month 12, the sum score of main complaints decreased by 3.5 (SD=2.2) points on average in the removal group as well as in the removal-plus group, and by 2.5 (SD=2.4) points in the no-removal group (p=0.152). Both removal groups showed a significant decrease in steady-state levels of inorganic mercury compared with the no-removal group. Thus, all 3 interventions were associated with clinically relevant improvements.

Blood and urine mercury levels in adult amalgam patients of a randomized controlled trial: interaction of Hg species in erythrocytes.

UNLABELLED: Parts of the population are permanently exposed to low levels of Hg degrees and Hg(II) from dental amalgam. It was the aim (1) to investigate the internal exposure to amalgam-related mercury from the kinetics of inorganic Hg in plasma and erythrocytes after amalgam removal, and (2) to estimate the amalgam-related absorbed dose. Dietary coexposure was monitored by determination of blood organic-Hg. Postremoval steady-state Hg concentrations were measured for 18 months. Eighty-two patients had been randomized into three groups: (A) removal of the fillings; (B) removal and non-specific detoxification, and (C) a health promotion program without removal. After amalgam removal, inorganic Hg dropped rapidly in plasma and red cells, stabilizing at 27% of preremoval levels after 60 days. Concentrations of organic Hg in plasma remained unchanged, indicating no change in dietary uptake of organic Hg. The concentration of organic Hg in red cells of group A was in the early postremoval phase lower and in the late postremoval phase higher than the preremoval control (p<0.01 for low-high difference). A protracted increase in organic Hg was also found in red cells of group B after 60 days. Thus, the effect of removal on organic Hg levels in the combined group A+B was compared with the values of group C in a linear mixed effects (LME) model which showed a significant increase with time in group A+B (p=0.028). In all groups, time profiles of urinary concentration and excretion of total-Hg were very similar to those of inorganic-Hg levels in plasma. From extrapolations of blood and urine data it was estimated that the amalgam-related inhalation and ingestion of Hg species were within the limits proposed by WHO, ATSDR and EPA. The integrated daily Hg dose absorbed from amalgam was estimated up to 3 microg for an average number of fillings and at 7.4 for a high amalgam load. CONCLUSIONS: This is the first study on adult amalgam patients which continuously monitored the postremoval decline of inorganic Hg and the coexposure from dietary organic Hg in a randomized-controlled-trial design. The integrated daily dose of 7.4 microg absorbed from a high amalgam load is well below the tolerable dose of 30 microg (WHO, 1990). The unexpected postremoval increase in erythrocyte organic Hg, which is associated with the depletion of cellular inorganic Hg, might result from binding of organic Hg to cellular sites previously occupied by inorganic Hg.

Dysfunctional cognitions in idiopathic environmental intolerances (IEI)--an integrative psychiatric perspective.

Idiopathic environmental intolerances (IEI) - formerly multiple chemical sensitivities (MCS) - are characterized by diffuse symptoms reported after exposure to low doses of everyday chemicals. Previous theories about the origin of IEI have emphasized either biological or psychological factors, neglecting a probable interplay. Many have suggested classifying IEI as a somatoform or an anxiety disorder, irrespective of some incongruities. By focusing on dysfunctional cognitions we discuss obvious parallels of IEI with somatoform disorders, and also indicate overlaps with anxiety and delusional disorders. To propose a hypothetical psycho-neurobiological basis of IEI, recent evidence about cortically represented symptoms in the absence of peripheral stimuli is briefly summarized. We conclude that IEI can serve as an illustrative example for the impact of cognitive, representational processes in symptom generation.

[The influence of diet on mental health]. / Uber den möglichen Einfluss der Ernährung auf die psychische Gesundheit.

The influence of nutritional factors on brain metabolism and the course of mental illness are increasingly being addressed in international research. It is a matter of discussion whether dietary habits, e.g., the amount of fish or vegetables, have an effect on the incidence of certain illnesses. Furthermore an optimized or supplemented diet could offer therapeutic possibilities; one example is the role of polyunsaturated fatty acids as an add-on therapy in affective disorders. The limitations of psychopharmacotherapy (drug interactions, side effects, noncompliance) underline the theoretical and practical relevance of nutrition in mental illness, the more so as mentally ill patients (especially when demented, anorectic, depressed, or schizophrenic) are at higher risk of malnutrition anyway. Even if the therapeutic evidence is still limited and the effects may be relatively weak, nutritional assessment and an optimized diet can be recommended for every patient.

Lessons to be learnt from organophosphorus pesticide poisoning for the treatment of nerve agent poisoning.

The increasing threat of nerve agent use for terrorist purposes against civilian and military population calls for effective therapeutic preparedness. At present, administration of atropine and an oxime are recommended, although effectiveness of this treatment is not proved in clinical trials. Here, monitoring of intoxications with organophosphorus (OP) pesticides may be of help, as their actions are closely related to those of nerve agents and intoxication and therapy follow the same principles. To this end, the clinical course of poisoning and the effectiveness of antidotal therapy were investigated in patients requiring artificial ventilation being treated with atropine and obidoxime. However, poisoning with OP pesticides shows extremely heterogeneous pictures of cholinergic crisis frequently associated with clinical complications. To achieve valuable information for the therapy of nerve agent poisoning, cases resembling situations in nerve agent poisoning had to be extracted: (a) intoxication with OPs forming reactivatable OP-AChE-complexes with short persistence of the OP in the body resembling inhalational sarin intoxication; (b) intoxication with OPs resulting rapidly in an aged OP-AChE-complex resembling inhalational soman intoxication; (c) intoxications with OPs forming a reactivatable AChE-OP complex with prolonged persistence of the OP in the body resembling percutaneous VX intoxication. From these cases it was concluded that sufficient reactivation of nerve agent inhibited non-aged AChE should be possible, if the poison load was not too high and the effective oximes were administered early and with an appropriate duration. When RBC-AChE activity was higher than some 30%, neuromuscular transmission was relatively normal. Relatively low atropine doses (several milligrams) should be sufficient to cope with muscarinic symptoms during oxime therapy.

[Poisoning by the autumn crocus plant]. / Verwechslungsgefahr im Frühjahr: Bärlauch und Herbstzeitlose. Warnen Sie lhre Patienten vor dem tödlichen Salat!

Confirmed cases of poisoning resulting from the ingestion of Colchicum autumnale in mistake for Allium ursinum were analysed retrospectively. The study included 32 patients between 27 and 90 years. The severity of the intoxication was graded on the basis of the poisoning severity score (PSS). All the patients developed diarrhea and/or vomiting after a latency period of between 2 and 24 h. All those patients with a latency of > 9 h suffered only mild poisoning. If the leaves were boiled before being eaten, 64% of the patients suffered moderate, severe or fatal poisoning; when the leaves were eaten raw, only 33%. It is presumed that heating may promote the liberation of colchicines from the plant. Eight of the nine patients with severe or fatal poisoning were older than 65 years. A possible cause of the more serious course in the elderly may be a decrease in renal clearance. In addition, a diminished sense of smell may allow the absence of the typical garlic smell and taste of Allium ursinum to go unrecognised.

[Lethal sepsis and multi-organ failure after accidental injection of urine in a drug addict]. / Letal verlaufende Sepsis und Multiorganversagen nach akzidenteller Urin-Injektion bei einer drogenabhängigen Patientin.

HISTORY AND ADMISSION FINDINGS: A 33-year-old drug addict injected accidentally into the femoral vein 5 ml urine (kept in the refrigerator for 1 week for unanticipated drug-screening) which she mis-took for methadone. Soon after injection she was found confused with shivering. On admission she had a blood pressure of 90/60 mmHg, heart rate of 120/min and fever of 40 degrees C. INVESTIGATIONS: Laboratory tests showed consumption coagulopathy (DIC) as well as leukopenia. Blood cultures were positive for E.coli and Klebsiella pneumoniae. Infection with hepatitis C and HIV was excluded. Echocardiography revealed good ventricular function without signs of endocarditis. DIAGNOSIS AND TREATMENT: The patient developed a fulminant Gram-negative sepsis with DIC and multi-organ failure. She was intubated and mechanically ventilated. Acute renal failure required haemodialysis and ultrafiltration. Septic shock was treated with fluids and high doses of vasopressors. DIC was effectively treated with tranexamic acid, PPSB complex and fresh frozen plasma. The further course was complicated by septic emboli to the myocardium, liver, kidney and spleen. Laparotomy because of an acute abdomen revealed perforation of terminal ileum (mainly due to ischemic bowel lesions) requiring partial resection. The patient was weaned on day 18 with an initially uneventful further course. On day 25 the patient had a cardiac arrest with at first successful resuscitation but electromechanical dissociation proved fatal on day 26. CONCLUSION: Although serious systemic inflammation associated with i. v.-injection in drug addicts is rare, one has to be aware of severe complications with septic emboli. To our knowledge it is the first published case of i. v.-injection of urine followed by sepsis and multi-organ failure. Aggressive interdisciplinary treatment is required.

[The development of a toxic megacolon due to Amanita phalloides poisoning. A rare complication]. / Die Entwicklung eines toxischen Megakolons bei Knollenblätterpilzvergiftungen - Eine ungewöhnliche Komplikation -

HISTORY: A 71-year-old previously healthy man consumed a mushroom meal containing Amanita phalloides, which he had confused with Agaricus campestris. Approximately 8 hours later, typical gastrointestinal symptoms began with copious loss of fluids. Treatment with penicillin G was initiated followed by a continuous silibinin infusion before the patient was transferred to our toxicological department. Other than a transient tachycardia and diffuse pain on abdominal palpation clinical examination was without abnormal findings. INVESTIGATIONS: Laboratory findings showed severe hepatic damage with 100-fold increased transaminases, elevation of serum creatinine, hyperbilirubinemia and a serious disturbance of coagulation. Infection with HIV, hepatitis- and CMV as well as pathogenic enteric bacteria and antibiotic-associated pseudo-membranous colitis were excluded. 11 days after the mushroom meal x-ray of abdomen showed a 6 cm dilatation of the small intestine and an 8 cm dilatation of the colon. DIAGNOSIS AND TREATMENT: Although clinical condition and laboratory findings nearly fulfilled transplantation criteria, hepatic injury resolved during intensive care therapy. Intractable diarrhea, dilatation of the intestine on x-ray as well as other findings met criteria of toxic megacolon. Therapy with antibiotics and systemic steroids was ineffective, so the patient needed decompression by a catheter, which was placed by colonoscopy. 30 days after the serious amanita poisoning complicated by development of toxic megacolon, the patient's condition resolved without sequelae and he was discharged. CONCLUSIONS: In addition the well known complications of amanita-poisoning, such as hepatic failure, encephalopathy and multi-organ failure, involvement of other organs like bone marrow, pancreas, kidney and gastrointestinal tract (except for the initial cholera-like gastroenteritis) are not well documented in the literature. Uncommon complications like toxic megacolon require an empirical approach.

[Multiple chemical sensitivity. Is the patient suffering as a result of environmental pollutants or psychological problems?]. / V. a. Multiple Chemical Sensitivity. Leidet Ihr Patient an Umweltgiften oder an der Seele?

Multiple chemical sensitivity (MCS) poses a medical challenge. Proposed etiologies are as numerous as they are contradictory, direct and indirect costs are high, and patient suffering considerable. In the absence of objective diagnostic criteria, estimation of its prevalence is difficult. Nevertheless, establishment of the diagnosis is frequently strikingly uncritical. We support an holistic approach that gives consideration both to psychological and physical aspects, as well as taking account of the high level of comorbidity, and we warn against "over-diagnosis". Therapeutical approaches should consider carefully the risk of avoidance and social withdrawal.

[Psychiatric aspects of multiple chemical sensitivity (MCS)]. / Psychiatrische Aspekte der Multiple Chemical Sensitivity (MCS).

Patients with multiple chemical sensitivity (MCS) react to low levels of common environmental chemicals with various health complaints. The etiology and pathogenesis of MCS is not clear. Objective criteria for diagnosis are lacking. Usually there are no pathological somatic findings, while psychiatric morbidity is considerably high. Somatoform, mood and anxiety disorders are diagnosed most frequently. A subgroup of MCS patients may suffer from a special form of somatoform disorders related to the environment. Critics of a psychogenic model of MCS argue that psychiatric diagnoses are descriptive, and causality can not be derived from them. However, clinicians are expected to evaluate the most probable cause of the complaints and give therapeutic recommendations. There are promising therapeutic concepts for somatoform and other psychiatric disorders, but not for MCS. Double-blind challenge tests, but also therapy evaluation studies could contribute to a better understanding of the pathogenesis of MCS in the future.