OBJECTIVE: Bilateral vestibular loss (BVL) is often diagnosed with great delay and an underlying cause is only identified in 50-80%. We measured horizontal and vertical semicircular canal function using the video-head-impulse test (vHIT) and hypothesized that specific vHIT-patterns may be linked to certain etiologies. METHODS: We retrospectively analyzed 109 BVL-patients linked to aminoglycoside vestibulotoxicity (n=16), Menière's disease (n=10), infectious inner-ear disorders (n=11), sensorineural hearing-loss (n=11), cerebellar-ataxia-neuropathy-vestibular-areflexia-syndrome (CANVAS, n=5), other causes (n=19) as well as those with unknown origin (n=47). Vestibulo-ocular reflex gains and cumulative saccade amplitudes were measured with vHIT, and the functional integrity of all semicircular canals was rated. RESULTS: Overall, anterior canal hypofunction (n=86/218) was identified significantly (p<0.001) less often than horizontal (n=186/218) and posterior (n=194/218) hypofunction. Preserved anterior canal function was associated with aminoglycoside vestibulotoxicity, Menière's disease and BVL of unknown origin, while no such sparing was found for inner-ear infections, CANVAS and sensorineural hearing loss. CONCLUSIONS: Semicircular canal function in BVL shows disease-specific dissociations, potentially related to reduced vulnerability or superior recovery of the anterior canals. SIGNIFICANCE: In patients with suspected BVL we recommend quantifying vHIT gains and saccade amplitudes for all semicircular canals as the pattern of canal hypofunction may help identifying the underlying disorder.

BackgroundOrthotopic liver transplantation (OLT) is a potential curative treatment in patients with hepatocellular carcinoma (HCC); however, treatment options for recurrent HCC after OLT are limited. Immune checkpoint inhibitors, such as nivolumab, an inhibitor of programmed cell death protein 1, have been successfully used for metastatic HCC but data on safety of nivolumab following solid organ transplantation are limited.MethodsWe report a 53-year-old woman with HCC who was treated with OLT. After 2 years, HCC recurred. Initial treatment with sorafenib was discontinued due to side effects and disease progression. Progressive HCC in the lung and lymph nodes was subsequently treated with nivolumab. One week after the first nivolumab dose, rapid progressive liver dysfunction was noted. Liver biopsy revealed severe cellular graft rejection prompting treatment with intravenous steroids and tacrolimus. Liver function continued to decline, leading to severe coagulopathy. The patient succumbed to intracranial hemorrhage.ResultsA systematic PubMed search revealed 29 cases treated with a checkpoint inhibitor following solid organ transplantation. Loss of graft was described in 4 (36%) of 11 cases with OLT and in 7 (54%) of 13 cases after kidney transplantation. However, cases with favorable outcome were also described. Eighteen cases with adverse events were identified upon searching the World Health Organization database VigiBase, including 2 cases with fatal outcome in liver transplant recipients due to graft loss.ConclusionExperience with checkpoint inhibitors in solid organ transplant recipients is limited. Published cases so far suggest severe risks for graft loss as high as 36% to 54%.

CHD risk associated with subclinical hypothyroidism did not differ by TPOAb status, suggesting that biomarkers of thyroid autoimmunity do not add independent prognostic information for CHD outcomes.

Voriconazole concentrations were determined in autopsy samples of eight patients who had been treated for a median of 7 days (interquartile range [IQR], 5 days). Voriconazole penetrates well into various tissues, with median levels of 6.26 μg/g ((interquartile range [IQR], 7.87 μg/g) in the lung, 3.41 μg/g (IQR, 16.72 μg/g) in the brain, 6.89 μg/g (IQR, 24.16 μg/g) in the liver, 6.47 μg/g (IQR, 6.19 μg/g) in the kidneys, 5.60 μg/g (IQR, 11.49 μg/g) in the spleen, and 7.55 μg/g (IQR, 16.91 μg/g) in the myocardium.

Caspofungin pharmacokinetics was assessed in 27 critically ill patients, including 7 on continuous venovenous hemofiltration (CVVH), 8 on continuous venovenous hemodialysis (CVVHD), and 13 not requiring continuous renal replacement therapy (CRRT). Caspofungin exposure during CRRT was very similar to that of the control group and comparable to that in healthy volunteers. Caspofungin clearance by CRRT was very low. Therefore, the standard dosage of caspofungin is probably adequate for critically ill patients undergoing CVVH or CVVHD.

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Drug-induced liver injury (DILI) is a potentially fatal adverse event with significant medical and economic impact. Many drugs, especially anti-infective, neurologic or pain-modifying substances, act as hepatotoxins. With cardiovascular toxicity, liver toxicity is one of the two leading causes for drug withdrawal from the market. The liver can be affected directly, in a predictable and dose-dependent manner, or idiosyncratically, independent of the dose and therefore unpredictable.Currently DILI is a diagnosis of exclusion that physicians have to bear in mind in patients with an unexplained increase of liver enzymes. The type of injury is categorized into hepatocellular, cholestatic, or mixed by the respective enzyme pattern of injury. Symptoms of affected patients can mimic any other liver disease.Therefore, new diagnostic and prognostic biomarkers for early liver injury are currently being evaluated in multi-centre clinical trials that are conducted by international consortia and other initiatives. Pharmacogenetic testing, next-generation sequencing, proteomics, metabolomics and mechanistic markers can help to preselect susceptible patient populations and tailor drug therapy to individual patients. Proposed DILI indicators that are under investigation include microRNAs, cytokeratin-18 (CK18), high mobility group box protein 1 (HMGB-1), and several other biomarkers. These developments can change clinical practice, and improve patients' safety and management. However, they have not been translated into clinical practice or approved for routine use yet. Management of DILI usually consists of initial withdrawal of the suspected drug and—if applicable—administration of specific antidotes, such as N-acetylcysteine. However, the overall management of DILI could change in the near future with the advent of novel diagnostic and prognostic DILI markers.

BackgroundCaring for patients with multimorbidity is common for generalists, although such patients are often excluded from clinical trials, and thus such trials lack of generalizability. Data on the association between multimorbidity and preventive care are limited. We aimed to assess whether comorbidity number, severity and type were associated with preventive care among patients receiving care in Swiss University primary care settings.MethodsWe examined a retrospective cohort composed of a random sample of 1,002 patients aged 50–80 years attending four Swiss university primary care settings. Multimorbidity was defined according to the literature and the Charlson index. We assessed the quality of preventive care and cardiovascular preventive care with RAND’s Quality Assessment Tool indicators. Aggregate scores of quality of provided care were calculated by taking into account the number of eligible patients for each indicator.ResultsParticipants (mean age 63.5 years, 44% women) had a mean of 2.6 (SD 1.9) comorbidities and 67.5% had 2 or more comorbidities. The mean Charlson index was 1.8 (SD 1.9). Overall, participants received 69% of recommended preventive care and 84% of cardiovascular preventive care. Quality of care was not associated with higher numbers of comorbidities, both for preventive care and for cardiovascular preventive care. Results were similar in analyses using the Charlson index and after adjusting for age, gender, occupation, center and number of visits. Some patients may receive less preventive care including those with dementia (47%) and those with schizophrenia (35%).ConclusionsIn Swiss university primary care settings, two thirds of patients had 2 or more comorbidities. The receipt of preventive and cardiovascular preventive care was not affected by comorbidity count or severity, although patients with certain comorbidities may receive lower levels of preventive care.