In Alzheimer’s disease (AD), angiotensin II receptor blockers (ARBs) could reduce cerebrovascular dysfunction, while angiotensin-converting enzyme inhibitors (ACEis) might increase brain amyloid-β by suppressing effects of the angiotensin-converting enzyme 1, an amyloid-β-degrading enzyme. However, ACEis could benefit patients with AD by reducing the amyloidogenic processing of the amyloid precursor protein, by central cholinergic and anti-inflammatory mechanisms, and by peripheral modulation of glucose homeostasis. We aimed to investigate whether the ACE insertion/deletion polymorphism is associated with clinical changes in patients with AD, while considering apolipoprotein E (APOE)-ϵ4 carrier status and blood pressure response to angiotensin modulators.

Consecutive outpatients with late-onset AD were screened with cognitive tests and anthropometric measurements, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic associations were estimated for 1 year, taking APOE-ϵ4 carrier status and genotypes of the ACE insertion/deletion polymorphism into account, along with treatment with ACEis or ARBs.

For 193 patients (67.4% women, 53.4% APOE-ϵ4 carriers), the ACE insertion/deletion polymorphism was in Hardy–Weinberg equilibrium (p = 0.281), while arterial hypertension was prevalent in 80.3% (n = 124 used an ACEi, n = 21 used an ARB). ARBs benefitted mostly APOE-ϵ4 carriers concerning caregiver burden variations, cognitive and functional decline. ACEis benefitted APOE-ϵ4 non-carriers concerning cognitive and functional decline due to improved blood pressure control in addition to possible central mechanisms. The ACE insertion/deletion polymorphism led to variable response to angiotensin modulators concerning neurological outcomes and blood pressure variations.

Angiotensin modulators may be disease-modifiers in AD, while genetic stratification of samples is recommended in clinical studies.

The purpose of the present study was to evaluate the efficacy and safety of (−)-OSU6162 in doses up to 30 mg b.i.d. in patients suffering from mental fatigue following stroke or traumatic brain injury (TBI).

This 4 + 4 weeks double-blind randomised cross-over study included 30 patients afflicted with mental fatigue following a stroke or head trauma occurring at least 12 months earlier. Efficacy was assessed using the Mental Fatigue Scale (MFS), the Self-rating Scale for Affective Syndromes [Comprehensive Psychopathological Rating Scale (CPRS)], the Frenchay Activity Index (FAI), and a battery of neuropsychological tests. Safety was evaluated by recording spontaneously reported adverse events (AEs).

There were significant differences on the patients’ total FAI scores (p = 0.0097), the subscale FAI outdoor scores (p = 0.0243), and on the trail making test (TMT-B) (p = 0.0325) in favour of (−)-OSU6162 treatment. Principal component analysis showed a clear overall positive treatment effect in 10 of 28 patients; those who responded best to treatment had their greatest improvements on the MFS. Reported AEs were mild or moderate in severity and did not differ between the (−)-OSU6162 and the placebo period.

The most obvious beneficial effects of (−)-OSU6162 were on the patients’ activity level, illustrated by the improvement on the FAI scale. Moreover, a subgroup of patients showed substantial improvements on the MFS. Based on these observed therapeutic effects, in conjunction with the good tolerability of (−)-OSU6162, this compound may offer promise for treating at least part of the symptomatology in patients suffering from stroke- or TBI-induced mental fatigue.

Do patients with acute illness admitted to the hospital and treated with liberal oxygen therapy compared with those treated with conservative oxygen therapy have differences in mortality and morbidity?

Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet 2018;391(10131):1693–705.

To analyse the existing literature to assess the potential benefits or harms of supplemental oxygen use in acutely ill patients.

To review the history of moist therapy used to regenerate traumatic tympanic membrane perforations.

Literature review.

The literature on topical agents used to treat traumatic tympanic membrane perforations was reviewed, and the advantages and disadvantages of moist therapy were analysed.

A total of 76 studies were included in the analysis. Topical applications of certain agents (e.g. growth factors, Ofloxacin Otic Solution, and insulin solutions) to the moist edges of traumatic tympanic membrane perforations shortened closure times and improved closure rates.

Dry tympanic membrane perforation edges may be associated with crust formation and centrifugal migration, delaying perforation closure. On the contrary, moist edges inhibit necrosis at the perforation margins, stimulate proliferation of granulation tissue and aid eardrum healing. Thus, moist perforation margins upon topical application of solutions of appropriate agents aid the regeneration of traumatic tympanic membrane perforations.

Wound healing after endoscopic sinus surgery may result in adhesion formation. Hyaluronic acid may prevent synechiae development. A systematic review was performed to evaluate the current evidence on the clinical efficacy of hyaluronic acid applied to the nasal cavity after sinus surgery.

Studies using hyaluronic acid as an adjunct treatment following endoscopic sinus surgery for chronic rhinosinusitis were identified. The primary outcome was adhesion formation rates. A meta-analysis was performed on adhesion event frequency. Secondary outcome measures included other endoscopic findings and patient-reported outcomes.

Thirteen studies (501 patients) met the selection criteria. A meta-analysis of adhesion formation frequency on endoscopy demonstrated a lower risk ratio in the hyaluronic acid intervention group (42 out of 283 cases) compared to the control group (81 out of 282) of 0.52 (95 per cent confidence interval = 0.37–0.72). Hyaluronic acid use was not associated with any significant adverse events.

Hyaluronic acid appears to be clinically safe and well tolerated, and may be useful in the early stages after sinus surgery to limit adhesion rate. Further research, including larger randomised controlled trials, is required to evaluate patient- and clinician-reported outcomes of hyaluronic acid post sinus surgery.

Sinonasal undifferentiated carcinoma is a rare aggressive tumour arising from the Schneiderian epithelium lining the sinonasal tract. Although considered the cornerstone of therapy, surgical resection can only be performed in a limited number of patients. This report describes the experience of treating sinonasal undifferentiated carcinoma with a multimodality approach.

The treatment charts of sinonasal undifferentiated carcinoma patients treated at a tertiary care centre from 2004 to 2012 were retrospectively reviewed.

A total of 16 sinonasal undifferentiated carcinoma patients with a median age at diagnosis of 47.5 years (range 8–65 years) were included: 19 per cent had neck nodal metastasis at presentation. Four patients (25 per cent) underwent surgery: of these, two had post-operative radiotherapy, one had pre-operative radiotherapy and one had adjuvant chemotherapy alone. Six patients (38 per cent) received definitive radiotherapy: five had received neoadjuvant chemotherapy to reduce tumour size and help in radiotherapy planning, while four (25 per cent) received palliative radiotherapy. The median follow up was 10.4 months (range 1–42.5 months). The estimated median progression-free survival time was 29.3 months. One- and three-year progression-free survival rates were 77 per cent and 41 per cent, respectively.

Surgery is the best treatment option for sinonasal undifferentiated carcinoma, although most patients require post-operative radiotherapy for advanced disease and close tumour margins. Definitive radiotherapy with or without chemotherapy may be suitable for patients with inoperable locally advanced disease. Elective nodal irradiation to address the high nodal involvement rates should be considered to improve the survival rate.

The Fontan circulation is the optimal treatment for patients with univentricular hearts. These patients are at high risk of circulatory failure. There is no consensus on the optimal drug treatment for the prevention of failure of the Fontan circulation. The aim of this systematic review was to provide an overview of evidence for drug therapy used in the prevention of Fontan circulatory failure.

We searched the Embase database for articles that reported drug therapy in Fontan patients. Studies published between 1997 and 2014 were included if efficacy or safety of medication was assessed, drug therapy aimed to prevent or treat failure of the Fontan circulation, and if the full text was available. Case reports were excluded.

A total of nine studies were included with a total of 267 Fontan patients; four studies evaluated the medication sildenafil, one iloprost, three bosentan, and one enalapril. Among all, two sildenafil studies reported improvement in exercise capacity, one in exercise haemodynamics, and one in ventricular performance. In the largest study of bosentan, an increase in exercise capacity was found. Enalapril did not result in improvements.

The studies analysed in this review suggest that bosentan, sildenafil, and iloprost may improve exercise capacity at the short term. Given the limitations of the studies, more, larger, placebo-controlled studies with longer follow-up periods are needed to better understand which drug therapies are effective in the prevention of failure of the Fontan circulation.

The management of Bell's palsy has been the subject of much debate, with corticosteroids being the preferred medication. However, evidence also supports the use of antiviral drugs for severe cases and even decompression surgery in patients who, despite medical treatment, are not recovering.

A literature review was conducted on the management of Bell's palsy.

This paper describes the background, statistical evidence, study results and pathophysiological theories that support more aggressive treatment for patients with severe palsy and those who have inadequate recovery.

Combination therapy including antiviral medication significantly improves outcomes in patients with severe Bell's palsy. Decompression should be considered in patients who have not recovered with drug treatment.

Neuralgic amyotrophy is a polyneuropathy that classically involves the brachial plexus. This paper reports an unusual clinical manifestation associated with vocal fold paralysis.

A 36-year-old male presented with hoarseness and progressive weakness of the right shoulder and upper arm muscles. Laryngoscopy revealed a limited adduction of the right vocal fold.

Subsequent speech therapy did not improve the symptoms. Therefore, vocal fold augmentation by application of hyaluronic acid in the right vocal fold was performed.

Vocal fold augmentation with resorbable material seems to be a more effective transient treatment than speech therapy alone for patients with neuralgic amyotrophy and laryngeal involvement.