Long-term, durable, absolute Psoriasis Area and Severity Index and health-related quality of life improvements with risankizumab treatment: a post hoc integrated analysis of patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Risankizumab has demonstrated durable, high rates of efficacy in patients with moderate-to-severe plaque psoriasis as assessed by the achievement of relative Psoriasis Area and Severity Index (PASI) improvement and Dermatology Life Quality Index (DLQI) 0/1. OBJECTIVES: The aim of this post hoc analysis is to assess the achievement of absolute PASI thresholds and related improvements in health-related quality of life (HRQoL) in patients with moderate-to-severe plaque psoriasis treated with (i) risankizumab compared with ustekinumab, and (ii) long-term (>52 weeks to 172 weeks) risankizumab. METHODS: Data from patients randomised to 150 mg risankizumab or 45 or 90 mg ustekinumab in replicate randomised controlled trials UltIMMa-1 and UltIMMa-2 were analysed for the achievement of absolute PASI thresholds PASI ≤ 3, PASI ≤ 1, and PASI = 0, time to achieve these thresholds, and combined PASI and DLQI endpoints. Data from pat ients initially randomised to risankizumab who continued on risankizumab in the open-label extension study LIMMitless were analysed for the achievement of absolute PASI levels, mean DLQI scores, and DLQI 0/1. RESULTS: Significantly greater proportions of patients treated with risankizumab compared with ustekinumab achieved PASI ≤ 3, PASI ≤ 1, and PASI = 0, as well as combined endpoints for absolute PASI and DLQI [(PASI ≤ 3 and DLQI ≤ 5) or (PASI ≤ 1 and DLQI 0/1)]. The median time to first achieve PASI ≤ 3, PASI ≤ 1, and PASI = 0 was significantly lower for risankizumab-treated patients compared with ustekinumab-treated patients. Among patients treated with long-term risankizumab, more than 90% achieved PASI ≤ 3 though week 172 and more than 80% achieved DLQI 0/1. Low absolute PASI scores corresponded with low mean absolute DLQI scores through week 172 of continuous risankizumab treatment. CONCLUSIONS: Risankizumab treatment demonstrated high rates of rapid and durable efficacy as measured by absolute PASI thresholds and improvements in patient HRQoL.

Treatment options for demodex blepharitis: patient choice and efficacy.

BACKGROUND: Demodex mites are microscopic parasites that live around hair follicles or sebaceous glands and may cause chronic blepharitis. The aim of this outcome analysis was to assess the efficacy and patient preferences with regard to the currently recommended treatment options. METHODS: All patients with microscopic evidence for Demodex blepharitis were informed about the currently published treatments and instructed about daily lid hygiene. Additional topical treatment options included tea tree oil (TTO) 5%, a cleansing foam containing 0.02% TTO (Naviblef®), and metronidazole 2% ointment. Systemic treatment options included oral ivermectin 6 mg on day 1 and 14 and metronidazole 500 mg twice daily for 10 days. All patients were reviewed after 2 months for symptoms and for a mite count on 10 epilated lashes. RESULTS: Ninety-four of 96 patients with Demodex blepharitis opted for an additional treatment. The mean mite count after 2 months of treatment were 13.3 with 5% TTO (n=6), 12.0 with 0.02% TTO (n=38), 9.4 with metronidazole ointment (n=5), 12.8 with ivermectin (n=27) and 22.0 with oral metronidazole (n=5). CONCLUSION: While there are several published treatment options available, none of these options seem to be clearly effective in Demodex blepharitis.

Corneal cross-linking as supplementary treatment option in melting keratitis: a case series.

BACKGROUND: Corneal melting represents a serious condition that can result in corneal perforation and loss of vision. Treatment options include topical and systemic immunosuppression, cyanoacrylate gluing, and emergency keratoplasty, depending on the underlying disease and the stage of corneal melt. Recently, corneal cross-linking (CXL) has emerged as an additional treatment option. The present study evaluates whether CXL induces a clinical improvement in melting keratitis not responding to conventional treatment. HISTORY AND SIGNS: Six patients undergoing CXL for corneal melting of variable origin (including bacterial, fungal and Acanthamoeba keratitis) were reviewed retrospectively. THERAPY AND OUTCOME: Treatment parameters included riboflavin application following UV irradiation with a wavelength of 370 nm and an irradiance of 3 mW/cm2 for 30 minutes. Four patients with corneal melting due to contact lens-related infectious keratitis showed healing without any need for further interventions up to date. In two patients, CXL stabilized the melting cornea and facilitated additional surgical procedures. CONCLUSIONS: By stabilizing corneal collagen fibres, CXL seems to represent an effective option to re-establish corneal integrity in the event of pending perforations. In established perforations, CXL facilitates further emergency procedures by stiffening the tissue.

Brain activation and hypothalamic functional connectivity during human non-rapid eye movement sleep: an EEG/fMRI study.

Regional differences in sleep EEG dynamics indicate that sleep-related brain activity involves local brain processes with sleep stage specific activity patterns of neuronal populations. Macroscopically, it is not fully understood which cerebral brain regions are involved in the successive discontinuation of wakefulness. We simultaneously used EEG and functional MRI on 9 subjects (6 female: mean = 24.1 years, 3 male: mean = 26.0 years) and analyzed local blood oxygenation level dependent signal changes linked to the transition from wakefulness to different non-rapid eye movement (NREM) sleep stages (according to Rechtschaffen and Kales) of the first sleep cycles after 36 h of total sleep deprivation. Several brain regions throughout the cortex, the limbic lobe, the thalamus, the caudate nucleus, as well as midbrain structures, such as the mammillary body/hypothalamus, showed reduced activity during NREM sleep across all sleep stages. Additionally, we found deactivation patterns specific to NREM sleep stages compared with wakefulness suggesting that a synchronized sleeping state can be established only if these regions interact in a well-balanced way. Sleep stage 2, which is usually linked to the loss of self-conscious awareness, is associated with signal decreases comprising thalamic and hypothalamic regions, the cingulate cortex, the right insula and adjacent regions of the temporal lobe, the inferior parietal lobule and the inferior/middle frontal gyri. The hypothalamic region known to be of particular importance in the regulation of the sleep-wake cycle shows specific temporally correlated network activity with the cortex while the system is in the sleeping state, but not during wakefulness. We describe a specific pattern of decreased brain activity during sleep and suggest that this pattern must be synchronized for establishing and maintaining sleep.

Lactated Ringer's solution resuscitation causes neutrophil activation after hemorrhagic shock.

PURPOSE: To determine the degree of neutrophil activation caused by hemorrhagic shock and resuscitation. METHODS: Awake swine underwent 15-minute 40% blood volume hemorrhage, and a 1-hour shock period, followed by resuscitation with: group I, lactated Ringer's solution (LR); group II, shed blood; and group III, 7.5% hypertonic saline (HTS). Group IV underwent sham hemorrhage and LR infusion. Neutrophil activation was measured in whole blood using flow cytometry to detect intracellular superoxide burst activity. RESULTS: Neutrophil activation increased significantly immediately after hemorrhage, but it was greatest after resuscitation with LR (group I, 273 vs. 102%; p < 0.05). Animals that received shed blood (group II) and HTS (group III) had neutrophil activity return to baseline state after resuscitation. Group IV animals had an increase in neutrophil activation (259 vs. 129%; p < 0.05). CONCLUSION: Neutrophil activation occurring after LR resuscitation and LR infusion without hemorrhage, but not after resuscitation with shed blood or HTS, suggests that the neutrophil activation may be caused by LR and not by reperfusion.

Psychorehabilitation aspects in older age groups.

Throughout medical history, suggestion is the oldest and most common method of relieving human distress and treating physical disease. One of the oldest Egyptian documents, the Ebers Papyrus (1552 BC) states, "Lay your hands upon him to quiet the pain in the arms and say that the pain will disappear." The psychogenic and therapeutic potency of Native American trance dances are also well documented. In a North American tribe practicing ancient traditions, such dances were found to produce an altered feeling for time, loss of conscious control, drastic emotional outbreaks, illusions, hypersuggestibility, and a deep feeling of restored youthfulness (Jilek, 1982). These and other historical documents show the deep historical connection between somatic and mental processes. From the viewpoint of a neurologist or a psychiatrist, a combination of somatic illness, depressive syndromes, organic psychosyndromes, and multimorbidity is frequent in elderly patients (Kortus, 1992). Thus, integrated psychotherapy in geriatric rehabilitation is necessary and useful. Practical psychotherapeutic methods are discussed in this manuscript.

[Comparative analysis of mental health treatment of various groups of competitive athletes]. / Vergleichsanalyse zur psychohygienischen Betreuung unterschiedlicher Gruppen von Spitzensportlern.

1) There is sense and necessity of psychohygiene in sports. This could be stated with 3 compared groups, namely: a national team, a team of handicapped, a team of juveniles. 2) We have used a complex program with integrated autogenic training (this however, not in an isolated way). Earlier experiences (of last author) over many years and hundreds of sportives were integrated in our evaluation. 3) Its to our knowledge the first time in world literature that effectiveness of psychohygiene within sports could be proved with statistical significance using world cup points within comparable groups. 4) Only possible can be possible, and psychohygiene will help to optimate this goal but not overrun it. This is main differentiation against doping. The human and the humanity is the main goal and not the so-called "necessities" of sport dictatorship. Its a good sign that several of our candidates told us that our psychohygienic program has reached over their period of sports activities into their "normal" lives.

Amino acid residues lining the chloride channel of the cystic fibrosis transmembrane conductance regulator.

The cystic fibrosis transmembrane conductance regulator forms a chloride channel that is regulated by phosphorylation and intracellular ATP levels. The structure of the channel-forming domains is undetermined. To identify the residues lining this channel we substituted cysteine, one at a time, for 9 consecutive residues (91-99) in the M1 membrane-spanning segment. The cysteine substitution mutants were expressed in Xenopus oocytes. We determined the accessibility of the engineered cysteine to charged, sulfhydryl-specific methanethiosulfonate reagents added extracellularly. We assume that, among residues in membrane-spanning segments, only those lining the channel will be accessible to react with these hydrophilic reagents and that such a reaction would irreversibly alter conduction through the channel. Only the cysteines substituted for Gly-91, Lys-95, and Gln-98 were accessible to the reagents. We conclude that these residues are in the channel lining. The periodicity of these residues is consistent with an alpha-helical secondary structure.

Interleukin-6 in synovial fluid from patients with arthritis.

Synovial fluid and serum from patients with rheumatoid arthritis, other inflammatory arthritides, and traumatic arthritis were assayed for the presence of interleukin-6 (IL-6) by means of an IL-6-dependent mouse hybridoma cell line. The cytokine was detected in all the samples of synovial fluid (range 50-22000 U/ml). IL-6 in synovial fluid was positively correlated (r = 0.58, P = 0.03) with the erythrocyte sedimentation rate in patients with inflammatory arthritis. In serum, the concentration of IL-6 was slightly elevated in some patients with rheumatoid arthritis. The results demonstrate that IL-6 is released into synovial fluid in joints affected by arthritis, and there appears to be an association between the levels of IL-6 and disease activity.

Muscarinic binding in suicides.

Supersensitive muscarinic cholinergic receptors may underlie mood, neuroendocrine, and sleep disturbances in depression. To test this hypothesis, we examined muscarinic binding sites in the brains of suicides and controls in a matched-pair design, using the radioligand 3H-quinuclidinyl benzilate (QNB) and focusing on regions (frontal cortex, hypothalamus, and pons) mediating those functions. Receptor densities and binding affinities did not differ between suicide and control brains in any brain region studied, although there was a trend for both density and affinity to be lower in hypothalami from suicides. We discuss the implications of these findings for the cholinergic-adrenergic balance hypothesis of depression and the methodological limitations of our preliminary study.

Methadone, monoamine oxidase, and depression: opioid distribution and acute effects on enzyme activity.

Narcotic withdrawal is often accompanied by an atypical depression with responds to resumption of narcotics. We hypothesized that methadone might exert its antidepressant effects through monoamine oxidase (MAO) inhibition. The current study examined 3H-methadone distribution in rat brain and effects on regional MAO activity with acute doses (2.5 mg/kg) which approximate those found during chronic methadone maintenance in man. Limbic areas (amygdala, basomedial hypothalamus, caudate-putamen, hippocampus, preoptic nucleus), as well as pituitary and liver were assayed for MAO activity and methadone concentration. MAO activities did not differ significantly in acute methadone or saline-treated cage-mates at 1 or 24 hr. The concentrations of methadone at 1 hr ranged between 17 and 223 ng/100 mg wet wt tissue in the preoptic nucleus and pituitary, respectively. No significant correlation was found between change in MAO activity (MAO methadone/MAO saline) and methadone concentration in any region at 1 or 24 hr. This study does not support the hypothesis that methadone acts as an antidepressant through MAO inhibition, at least not following acute administration of this exogenous opioid.