Swiss Patient Research Articles

Cardiomeds a m-health application for self-management supporting Swiss patient with heart failure: a two-stage usability study (Preprint)

Cardiomeds a m-health application for self-management supporting Swiss patient with heart failure: a two-stage usability study (Preprint)

Novel CRYGC Mutation in Conserved Ultraviolet-Protective Tryptophan (p.Trp131Arg) Is Linked to Autosomal Dominant Congenital Cataract

Congenital cataract (CC), the most prevalent cause of childhood blindness and amblyopia, necessitates prompt and precise genetic diagnosis. The objective of this study is to identify the underlying genetic cause in a Swiss patient with isolated CC. Whole exome sequencing (WES) and copy number variation (CNV) analysis were conducted for variant identification in a patient born with a total binocular CC without a family history of CC. Sanger Sequencing was used to confirm the variant and segregation analysis was used to screen the non-affected parents. The first de novo missense mutation at c.391T>C was identified in exon 3 of CRYGC on chromosome 2 causing the substitution of a highly conserved Tryptophan to an Arginine located at p.Trp131Arg. Previous studies exhibit significant changes in the tertiary structure of the crystallin family in the following variant locus, making CRYGC prone to aggregation aggravated by photodamage resulting in cataract. The variant can be classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) criteria (PP3 + PM1 + PM2 + PS2; scoring 10 points). The identification of this novel variant expands the existing knowledge on the range of variants found in the CRYGC gene and contributes to a better comprehension of cataract heterogeneity.

First Report of a Low-Frequency Mosaic Mutation in the Hydroxymethylbilane Synthase Gene Causing Acute Intermittent Porphyria.

Acute porphyrias are a group of monogenetic inborn errors of heme biosynthesis, characterized by acute and potentially life-threatening neurovisceral attacks upon exposure to certain triggering factors. Biochemical analyses can determine the type of acute porphyria, and subsequent genetic analysis allows for the identification of pathogenic variants in the specific gene, which provides information for family counselling. In 2017, a male Swiss patient was diagnosed with an acute porphyria while suffering from an acute attack. The pattern of porphyrin metabolite excretion in urine, faeces, and plasma was typical for an acute intermittent porphyria (AIP), which is caused by inherited autosomal dominant mutations in the gene for hydroxymethylbilane synthase (HMBS), the third enzyme in the heme biosynthetic pathway. However, the measurement of HMBS enzymatic activity in the erythrocytes was within the normal range and Sanger sequencing of the HMBS gene failed to detect any pathogenic variants. To explore the molecular basis of the apparent AIP in this patient, we performed third-generation long-read single-molecule sequencing (nanopore sequencing) on a PCR product spanning the entire HMBS gene, including the intronic sequences. We identified a known pathogenic variant, c.77G>A, p.(Arg26His), in exon 3 at an allelic frequency of ~22% in the patient's blood. The absence of the pathogenic variant in the DNA of the parents and the results of additional confirmatory studies supported the presence of a de novo mosaic mutation. To our knowledge, such a mutation has not been previously described in any acute porphyria. Therefore, de novo mosaic mutations should be considered as potential causes of acute porphyrias when no pathogenic genetic variant can be identified through routine molecular diagnostics.

Psychiatric reaction of an intensive care unit survivor in the context of coronavirus disease 2019: a case report

BackgroundThe coronavirus disease 2019 pandemic has had a serious impact on global mental health, particularly in intensive care unit survivors. Given the lethal potential and unpredictability of coronavirus disease 2019, a high risk of posttraumatic stress disorder was identified in the beginning of the crisis. There are insufficient details in current literature and no official guidelines available for the treatment and follow-up of acute stress disorder and the prevention of posttraumatic stress disorder for intensive care unit survivors in the context of coronavirus disease 2019.Case presentationWe hereby describe a 67-year-old Swiss patient presenting a psychiatric reaction in the context of coronavirus disease 2019. He was admitted to the intensive care unit due to severe acute respiratory distress syndrome from severe acute respiratory syndrome coronavirus 2 and intubated for 13 days. Afterwards, there was a severe worsening of acute renal failure prompting hemodialysis, and he developed delirium. Psychiatric liaison was requested 4 days post-intubation because the patient presented residual symptoms of delirium, false memories about the real context of his medical care, and ideas of persecution toward medical caregivers. He suffered from a very strong peritraumatic reaction, then developed an acute stress disorder linked with his care on the intensive care unit. We looked for strategies to prevent progression from acute stress disorder to posttraumatic stress disorder. We proceeded to the following therapeutic interventions: intensive psychiatric follow-up, intensive care unit diary, and low-dose antipsychotic treatment. The aim of our psychotherapeutic approach was to allow him to increase his feeling of security and to cope with the reality of his traumatic experience. He showed clinical improvement in his mental state after 3 months, despite several predictive factors of evolution to post-intensive care unit posttraumatic stress disorder.ConclusionThis case report illustrates how a delusional clinical presentation after intensive care in the context of coronavirus disease 2019 can hide psychotraumatic symptoms. It is important to highlight that the intensive care unit diary completed by the intensive care team and the follow-up by the psychiatric liaison team helped the patient reconstruct an appropriate and coherent account. Further studies are needed to determine the psychiatric effects of coronavirus disease 2019 and to assess early and appropriate psychiatric intervention for patients hospitalized for coronavirus disease 2019 to prevent posttraumatic stress disorder.

The GERMELATOX-A (Dermatologic Cooperative Oncology Group): Study attitude of German melanoma patients towards toxicity during adjuvant treatment.

e21597 Background: Trials of adjuvant treatment with immune checkpoint inhibitors like PD1-antibodies (ICI) or targeted therapy with BRAF/MEK inhibitors (TT) in high-risk melanoma patients demonstrate a significant improvement in recurrence-free survival (RFS) with a very similar relative risk reduction. Both treatment modalities are characterized by specific side effects. Therefore the decision for or against a treatment modality is very often driven by the risk for toxicity. This study addressed for the first time the attitudes and preferences of German and Swiss patients and physicians for adjuvant treatment with ICI and TT. Methods: In this multicenter study („GERMELATOX-A“) patients with low-risk melanoma (pT1a, AJCC stage I, familiar with cancer diagnosis but no adjuvant treatment planned), and dermatooncologists from 11 German and 1 Swiss skin cancer centers were asked to fill out a questionnaire. Here, side effect scenarios typical for each ICI and TT with mild-to-moderate or severe toxicity and also melanoma recurrence leading to cancer death were described. We asked patients and physicians about the reduction in melanoma relapse (relapse-free survival, RFS) and the survival increase (overall survival, OS) at 5 yrs they would expect to tolerate defined side-effects. Results: Data were obtained from 136/107 patients/physicians, respectively (median age: 59 yrs/32 yrs, 56.2%/67.6% female).Overall, by visual analog scale, patients valued a melanoma relapse worse than all scenarios of side-effects during adjuvant treatment with ICI or TT. In general patients required higher risk reductions for DFS and OS for both ICI and TT and their drug related side effects compared to physicians to accept this treatment. In case of severe side effects, patients needed a 20% higher reduction of relapse rate at 5 yrs for ICI compared to TT (71.4%/50.0%). Physicians required identical relapse reduction rates for ICI and TT in case of severe side effects (42.9%). Conclusions: This study demonstrated a pronounced variation of German and Swiss patient preferences on adjuvant treatment related to drug class specific side effects and outcomes and a clear difference between patients' and physicians' attitudes. This difference might influence decision making for adjuvant treatment options and should therefore also be investigated in further trials for current adjuvant treatment modalities. As adjuvant melanoma treatment with ICI and TT will possibly be implemented in earlier stages soon, precise knowledge of the patient perspective can be helpful for the process of decision making.

From Diagnosis to Satisfaction in Multiple Sclerosis: A Swiss Patient Survey Highlighting the Importance of the First Diagnostic Consultation

Background: An early treatment start with disease modifying therapies (DMT) and long-term adherence is crucial in the treatment of people with multiple sclerosis (PwMS) to prevent future disability. Objectives: To gain information on the diagnostic process, decision making, treatment start and adherence with regard to DMT as well as satisfaction in PwMS in Switzerland to optimize management of PwMS. Methods: A survey was conducted between June 2017 and March 2018 in six hospital-based MS centres and eight private practices in Switzerland. PwMS according to the 2010 McDonald criteria, aged 18–60 years, having a clinical isolated syndrome, relapsing remitting MS, or secondary progressive MS were eligible. The survey contained 40 questions, covering participants’ background and circumstances, treatment decisions, therapy start, treatment adherence, and satisfaction (EKNZ Req-2016-00701). Results: 212 questionnaires were returned for analysis. Of these, 125 (59.0%) were answered by patients treated by practice-based neurologists and 85 (40.1%) by patients treated in hospitals. That PwMS were satisfied overall with current medical care, that they were free of relapses and disease progression, and that they were able to live independently were the main goals of patients. Satisfaction was reflected by an early therapy start and a high adherence to DMT in our cohort. The treating neurologist played a major role in this regard. Furthermore, a satisfactory first diagnostic consultation (FDC) was crucial for successful long-term patient care positively influencing an early treatment start, longer duration of the initial therapy, as well as adherence to treatments and general satisfaction. Conclusion: The treating neurologist and especially a satisfactory FDC play a major role for the successful long-term treatment of PwMS. Detailed information on various aspects of the disease and time with the treating neurologist seems to be of major importance.

Do anti-psoriatic drugs work better in women than men?

Linked Article:Maul etal. Br J Dermatol 2021; 185:1160-1168. Psoriasis is a chronic, scaly skin condition affecting about 2·5% of the population. It has a negative impact on people's quality of life, more so in women. It is usually treated with creams but is sometimes severe enough to need strong medicines, which are not always effective. This study examines differences between men and women in their responses to treatment. The 5346 adult patients were identified from Swiss and German patient registries; 60% were male. The men were heavier than women (average 91 kg versus 78 kg). At the start of treatment men had worse psoriasis whereas women had worse quality of life scores. All received systemic medicines, including non-biologics (methotrexate, fumaric acid esters, ciclosporin, acitretin or apremilast) or biologics (adalimumab, etanercept, infliximab, ustekinumab or secukinumab). They were followed up for up to a year after starting treatment and women showed better improvements on two scales called the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) than men. These results might reflect better drug adherence in women, or their lower bodyweight - where the same dose is used for men and women, women will receive a higher dose per kilogram of body tissue. Also, because of hormonal factors, women's bodies contain a higher proportion of fat, which may allow the drug to spread more easily through the body. Finally, women experience their psoriasis more negatively than men and so there was more room for improvement in DLQI. These findings indicate a need for more personalized treatment, taking gender into account.

Repatriation of a patient with COVID-19 contributed to the importation of an emerging carbapenemase producer

ObjectivesPatients hospitalised abroad can become colonised with multidrug-resistant bacteria and import them to their home countries. In this study, we characterised an OXA-484 carbapenemase-producing Escherichia coli strain from a Swiss patient infected by SARS-CoV-2 and repatriated from India.MethodsAt admission to Switzerland (April 2021), the patient undertook a nasopharyngeal swab to search for SARS-CoV-2 and a rectal swab to detect multidrug-resistant bacteria. Both SARS-CoV-2 and E. coli isolates were whole-genome sequenced and analysed for phylogenetic relatedness.ResultsThe patient was infected with the SARS-CoV-2 B.1.617.2 lineage (VOC Delta), a lineage that began to be reported across Switzerland at that time. He was also colonised with a sequence type 410 (ST410) E. coli strain (L3452210II) producing OXA-484, a single amino acid variant of OXA-181. The blaOXA-484 gene was carried by a 51.5 kb IncX3 plasmid identical to those described in blaOXA-181-harbouring ST410 E. coli strains. Core genome analysis showed that L3452210II was identical (ΔSNV ≤23) to two ST410 OXA-484 producers recently reported in Qatar and Germany, but differed from other ST410 OXA-181 producers reported worldwide.ConclusionThe patient was infected by an emerging SARS-CoV-2 variant and also imported an E. coli producing OXA-484, an OXA-48-like carbapenemase not yet reported in Switzerland. The genetic background of L3452210II indicated that blaOXA-484 shared the same plasmid as blaOXA-181, but its bacterial host differed from most of the pandemic OXA-181-producing ST410 strains reported previously. This case description underlines that the COVID-19 crisis can contribute to the worldwide spread of emerging carbapenemase producers.

Power to the patient: How EUPATI (CH) is changing the face of patient education

The European Patients’ Academy on Therapeutic Innovation (EUPATI) is an independent, non-profit foundation committed to changing the face of patient engagement through education. It provides training for patients and patient representatives on medicines research and development (R&D). EUPATI Switzerland (EUPATI CH) is the official Swiss EUPATI National Platform and acts as a central point for inquiries and cooperation for patient empowerment and involvement in medicines R&D in Switzerland. After successfully launching the increasingly popular annual Swiss Patient Forum (SPF) in 2017, EUPATI CH is currently developing a Swiss training module for Swiss patients and patient representatives who wish to be involved in patient engagement activities and who are interested in learning about the Swiss legal and ethical framework for clinical R&D in one of Switzerland’s national languages.

Critical Incident Reporting zu Medikationsfehlern mit Masseinheiten und Berechnungen

IntroductionMedication safety is an important hot spot of patient safety. This fact prompted the Swiss Patient Safety Foundation to conduct its annual CIRRNET (Critical Incident Reporting & Reacting NETwork) reporting month on the topic of “Units of measurement of medicines and calculation errors in prescription/dispensing (mg, g, mmol etc.)”. MethodsDuring the CIRRNET reporting month 2018, the CIRS (Critical Incident Reporting System) managers of the health institutions participating in CIRRNET forwarded all incident reports on the topic to the CIRRNET database. The archive was also searched for usable reports on the same topic. The reports were analysed according to the type of medication involved (type of application and medication class according to ATC codes), the process stage affected (prescription, preparation, administration and documentation) and the error category. ResultsOf the 110 reports analysed, 27 reports originated directly from the reporting month, 83 reports were additionally extracted from the archive. 67 reports (60 %) concerned intravenously administered medications and analgesics (opioids and non-opioids, such as NSAIDs) were the most frequently affected/involved medication class with 21 reports (18 %). The process step preparation/calculation was the one where most of the errors analysed occurred. With a total of 48 reports (44 %), most of the errors analysed were classified here. Regarding error categories, it becomes apparent that the categories “Derivation of the amount to be administered (volume/number of single doses) from strength or concentration” with 33 (30 %), “Unit of measurement ml – mg” with 20 (18 %) and “Dose/volume per time” with 14 reports (13 %) were reported most frequently. ConclusionErrors concerning units of measurement or the calculation of medication have been numerously reported by the CIRRNET institutions. Often, these were cases in which, for example, the volume of a drug to be administered was derived incorrectly. Such calculations are demanding, prone to error and represent a system problem. Therefore, good solution strategies need to be implemented in order to sustainably improve medication safety and thus patient safety.

Conidiobolus pachyzygosporus invasive pulmonary infection in a patient with acute myeloid leukemia: case report and review of the literature

BackgroundConidiobolus spp. (mainly C. coronatus) are the causal agents of rhino-facial conidiobolomycosis, a limited soft tissue infection, which is essentially observed in immunocompetent individuals from tropical areas. Rare cases of invasive conidiobolomycosis due to C. coronatus or other species (C.incongruus, C.lamprauges) have been reported in immunocompromised patients. We report here the first case of invasive pulmonary fungal infection due to Conidiobolus pachyzygosporus in a Swiss patient with onco-haematologic malignancy.Case presentationA 71 year-old female was admitted in a Swiss hospital for induction chemotherapy of acute myeloid leukemia. A chest CT performed during the neutropenic phase identified three well-circumscribed lung lesions consistent with invasive fungal infection, along with a positive 1,3-beta-d-glucan assay in serum. A transbronchial biopsy of the lung lesions revealed large occasionally septate hyphae. A Conidiobolus spp. was detected by direct 18S rDNA in the tissue biopsy and subsequently identified at species level as C. pachyzygosporus by 28S rDNA sequencing. The infection was cured after isavuconazole therapy, recovery of the immune system and surgical resection of lung lesions.ConclusionsThis is the first description of C. pachyzygosporus as human pathogen and second case report of invasive conidiobolomycosis from a European country.

Novel truncating mutations of MYO18B causing congenital myopathy in a Swiss patient

Congenital myopathies (CMs) are a group of rare inherited myopathies most commonly presenting in infancy with hypotonia and weakness. They have been classified on the basis of distinctive myopathologic features. Mutations in more than 25 genes can cause CM.1

Should MMMT still be treated with adjuvant taxane-based combination chemotherapy?

BackgroundMalignant mixed Mullerian tumors of endometrial (MMMT-E) and ovarian (MMMT-O) origin are associated with poor prognosis. Suggestively epithelial-driven tumors, their treatment has shifted from anthracycline or ifosfamide-based towards taxane-based chemotherapy. It remains unclear whether this change associates with better outcomes.Patients and methodsA conjoined Australian and Swiss patient cohort of MMMT-E (N = 103) and MMMT-O (N = 17) was compared to patients with adenocarcinoma of the endometrium (EC, N = 172) and ovary (OC, N = 189). Clinicopathological characteristics, FIGO stage, first-line treatment, and patient outcomes were analyzed. The generated hypothesis was verified in an US-American cohort with high-grade serous ovarian cancer (HGSOC, N = 1290) and MMMT-O (N = 450) using immunohistochemistry and next-generation sequencing.ResultsEarly stage I/II MMMT-E showed a survival plateau after 2.5 years, with no recurrence or death observed afterwards. Relapse-free survival was significantly worse in MMMT-E treated with platinum/taxanes (P = 0.024) compared to non-taxane regimen. Hypothesizing that also MMMT-O might benefit from an adjuvant non-paclitaxel regimen, a second independent cohort of MMMT-O and HGSOC patients was examined. p53 mutations dominated in both cancers with comparable frequency. PI3KCA and KRAS mutations were less frequent: they were more frequent in MMMT-O than in HGSOC (P = 0.015 and P = 0.018, respectively). MMMT-O responded better to a combination of carboplatin with anthracyclines than with taxanes (73.9% vs. 39.4%).ConclusionEarly stage I/II MMMT-E patients have excellent prognosis if no recurrence has appeared within the first 2.5 years. In MMMT-E, platinum/anthracycline or ifosfamide regimen associated with better outcomes than platinum/taxanes regimens. This might also apply to MMMT-O.

Case Study: More Patient Safety by Design - System-based Approaches for Hospitals.

Since the publication of the report "To Err Is Human: Building a Safer Health System" by the US Institute of Medicine in 2000, much has changed with regard to patient safety. Many of the more recent initiatives to improve patient safety target the behavior of health care staff (e.g., training, double-checking procedures, and standard operating procedures). System-based interventions have so far received less attention, even though they produce more substantial improvements, being less dependent on individuals' behavior. One type of system-based intervention that can benefit patient safety involves improvements to hospital design. Given that people's working environments affect their behavior, good design at a systemic level not only enables staff to work more efficiently; it can also prevent errors and mishaps, which can have serious consequences for patients. While an increasing number of studies have demonstrated the effect of hospital design on patient safety, this knowledge is not easily accessible to clinicians, practitioners, risk managers, and other decision-makers, such as designers and architects of health care facilities. This is why the Swiss Patient Safety Foundation launched its project, "More Patient Safety by Design: Systemic Approaches for Hospitals," which is presented in this chapter.

Patient-to-patient: Talking about medical devices

How will the regulatory changes taking place for medical devices affect patients – those who carry the true risks or benefits of having them in or on their bodies? For a down-to-earth patient perspective, European Patients’ Academy (EUPATI) fellow Estelle Jobson met with Karen Topaz Druckman, President of the Swiss patient association, HHT Swiss, to ask her some questions. Karen’s views represent years in patient advocacy including patient input.

Improved Glycemic Control with Insulin Glargine 300U/mL (Toujeo®) in Patients with Type 2 Diabetes: Real-World Effectiveness in Switzerland.

IntroductionInsulin glargine 300 U/mL (Gla-300, Toujeo®) is a long-acting, once-daily basal insulin with improved—more stable and smoother—pharmacokinetic and pharmacodynamic profiles compared to insulin glargine 100 U/mL (Gla-100) and insulin degludec (IDeg). These properties have been shown to translate into an effective HbA1c reduction with the advantage of a lower risk of hypoglycemia in randomized controlled trials of Gla-300 versus Gla-100. In this study, we assessed the effectiveness and safety of Gla-300 under real-world conditions in Switzerland.MethodsThe prospective, observational, open-label, multicenter study TOP-2 explored the effectiveness of Gla-300 in adult patients with type 2 diabetes (T2D) uncontrolled (HbA1c 7.5–10%) on their previous basal insulin in Germany, Austria, and Switzerland. The primary endpoints were the percentages of patients achieving a fasting plasma glucose (FPG) of ≤ 6.1 mmol/L after 6 and 12 months. Secondary endpoints included changes in HbA1c, FPG, body weight, and insulin dose as well as hypoglycemia incidence and safety. Here we report the results for the Swiss patient cohort after 12 months of treatment with insulin glargine 300 U/mL.ResultsThe 62 patients (33 men) had a mean age of 65 years, a mean diabetes duration of 14 years, a mean body mass index (BMI) of 31 kg/m2, and were mainly switched from Gla-100 (44%) to Gla-300. The most common concomitant oral anti-diabetes therapy was metformin (65%). The mean individual HbA1c target chosen by the investigators was 7.4%. After 12 months of therapy, Gla-300 significantly reduced mean HbA1c from 8.2% to 7.6% (p < 0.0001). Likewise, Gla-300 significantly reduced mean FPG from 9.1 mmol/L to 7.4 mmol/L (p < 0.0001). At study end, 32% of patients achieved FPG ≤ 6.1 mmol/L, 55% achieved FPG ≤ 7.2 mmol/L , and 57% achieved their individual HbA1c target. Gla-300 was uptitrated to a mean dose of 40 units per day. Symptomatic hypoglycemia incidence after 12 months was low at 9.7% and a rate of 0.23 events per patient year. Body weight remained stable and was not significantly altered during the study.ConclusionUpon switching basaI insulin to Gla-300, overall glucose control significantly improved and glycemic targets were achieved with a low rate of hypoglycemia in T2D patients under real-world conditions in Switzerland.FundingSanofi–Aventis (Suisse) SA.

Prurigo pigmentosa after fat-reduced diet, treated with doxycycline

Prurigo pigmentosa is arare inflammatory skin disease of unknown origin, mostly described in the ethnic Japanese population. Etiology and pathogenesis are not completely known. Tetracyclines or dapsone are the therapy of choice. A17-year-old Swiss patient with Turkish parents presented with pruritic rash on the neck and trunk, which started after a diet. Under therapy with doxycycline over 5weeks, complete healing with slight reticular hyperpigmentation was observed.

Congenital malformations, palliative care and postnatal redirection to more intensive treatment – a review at a Swiss tertiary center

Purpose: The so-called lethal malformations pose ethical challenges. Most affected fetuses die before or at birth. Live-born neonates commonly receive palliative care. If the postnatal course is better than expected, redirection towards more treatment may occur. We aimed to analyze this in a Swiss patient cohort. Materials and methods: Over 6 years, fetal malformation was suspected in 1113 cases. We identified patients prenatally assigned to palliative care, assessed pre- and postnatal diagnoses, and outcomes. Results: Fourteen neonates received palliative care. Eleven patients received palliative care following late termination of pregnancy, for three, palliative care was planned and the fetus died during delivery, for two, the outcome was unknown (incomplete documentation). Genetic testing was performed in 50%. The predominant diagnostic group was central nervous system malformations (33%), followed by chromosomal aberrations (20%) and renal anomalies (17%). One child assigned to palliative care was resuscitated. Antenatal findings were anhydramnios and pulmonary hypoplasia. Postnatally, respiration was better than expected. The neonate was admitted to intensive care, died on day one. Conclusions: Nervous system malformations seem to be a major criterion for foregoing life-sustaining interventions. Redirection towards more treatment is rare. This may reflect precise prenatal prognostication; a degree of self-fulfilling prophecy cannot be excluded.

Increased Prevalence of Flammer Syndrome in Patients with Retinitis Pigmentosa.

"Retinitis pigmentosa" refers to a group of degenerative eye diseases with a genetic background. Flammer syndrome encompasses a set of symptoms and signs, mainly but not exclusively related to dysregulation of blood vessels. The purpose of the present study was to determine, with the help of a questionnaire, whether symptoms of Flammer syndrome occur more often in patients with retinitis pigmentosa than in controls. 76 patients with retinitis pigmentosa (members of the Swiss patient organization for retinitis pigmentosa) and 274 control subjects answered a questionnaire (Flammer Syndrome Questionnaire) on 15 symptoms and signs of Flammer syndrome. Seven of 15 symptoms and signs of Flammer syndrome were significantly more often positive in retinitis pigmentosa patients than in controls. Six additional symptoms and signs occurred non-significantly more often and 2 non-significantly less often in patients with retinitis pigmentosa. Retinitis pigmentosa patients suffer significantly more often from symptoms and signs of the Flammer syndrome than control subjects. This includes low body mass index, low blood pressure, feeling cold, migraine, increased smell perception and perfectionism. The reason for this association between retinitis pigmentosa and Flammer syndrome and the potential implications need to be determined.

Frequency and Pathophysiology of Acute Liver Failure in Ornithine Transcarbamylase Deficiency (OTCD).

BackgroundAcute liver failure (ALF) has been reported in ornithine transcarbamylase deficiency (OTCD) and other urea cycle disorders (UCD). The frequency of ALF in OTCD is not well-defined and the pathogenesis is not known.AimTo evaluate the prevalence of ALF in OTCD, we analyzed the Swiss patient cohort. Laboratory data from 37 individuals, 27 females and 10 males, diagnosed between 12/1991 and 03/2015, were reviewed for evidence of ALF. In parallel, we performed cell culture studies using human primary hepatocytes from a single patient treated with ammonium chloride in order to investigate the inhibitory potential of ammonia on hepatic protein synthesis.ResultsMore than 50% of Swiss patients with OTCD had liver involvement with ALF at least once in the course of disease. Elevated levels of ammonia often correlated with (laboratory) coagulopathy as reflected by increased values for international normalized ratio (INR) and low levels of hepatic coagulation factors which did not respond to vitamin K. In contrast, liver transaminases remained normal in several cases despite massive hyperammonemia and liver involvement as assessed by pathological INR values. In our in vitro studies, treatment of human primary hepatocytes with ammonium chloride for 48 hours resulted in a reduction of albumin synthesis and secretion by approximately 40%.ConclusionIn conclusion, ALF is a common complication of OTCD, which may not always lead to severe symptoms and may therefore be underdiagnosed. Cell culture experiments suggest an ammonia-induced inhibition of hepatic protein synthesis, thus providing a possible pathophysiological explanation for hyperammonemia-associated ALF.