Effectiveness and safety of apremilast in biologic-naïve patients with moderate psoriasis treated in routine clinical practice in Greece: the APRAISAL study.

BACKGROUND: Apremilast is an oral phosphodiesterase-4 inhibitor indicated for patients with moderate-to-severe chronic plaque psoriasis and active psoriatic arthritis. OBJECTIVES: To examine the effectiveness of apremilast on Dermatology Life Quality Index (DLQI), Psoriasis Area and Severity Index (PASI) and nail, scalp and palmoplantar involvement, when administered prior to biologics. METHODS: This 52-week real-world study included biologic-naive adults with moderate psoriasis (psoriasis-involved body surface area 10% to <20%, or PASI 10 to <20 and DLQI 10 to <20). Apremilast was initiated ≤7 days before enrolment. Data from the first 100 eligible patients who completed 24 weeks (W24) of observation (or were prematurely withdrawn) are presented in this interim analysis using the last-observation-carried-forward imputation method. RESULTS: Eligible patients (mean age: 49.9 years; 71.0% males; median disease duration: 8.0 years) were consecutively enrolled between April and October 2017, by 18 dermatology specialists practising in hospital outpatient settings in Greece. Baseline DLQI (median: 12.0) and PASI (median: 11.7) scores improved (P < 0.001) at all postbaseline timepoints (Weeks 6, 16 and 24; W24 median decreases: 9.0 and 9.4 points respectively). At W24, DLQI ≤5, DLQI 0 or 1, and PASI-75 response rates were 63.0%, 25.0% and 48.0% respectively. The Nail Psoriasis Severity Index score in patients with baseline nail involvement (n = 57) decreased at all postbaseline timepoints (P < 0.001; W24 median decrease: 20.0 points). At W24, 50.0% and 51.7% of patients with baseline scalp (n = 76) and palmoplantar (n = 29) involvement respectively achieved postbaseline Physician's Global Assessment (PGA) score of 0 or 1 if baseline score was ≥3, or 0 if baseline score was 1 or 2. The adverse drug reaction rate was 21.0% (serious: 2.0%). CONCLUSIONS: These interim results indicate that through 24 weeks, apremilast improved quality of life and reduced disease severity in biologic-naive patients with moderate plaque psoriasis, while demonstrating safety consistent with the known safety profile.

Effect of classical music on light-plane anaesthesia and analgesia in dogs subjected to surgical nociceptive stimuli.

The objectives of this prospective, randomized, blinded, crossover, experimental study were to detect the potential anaesthetic- and analgesic-sparing effects of classical music provided to dogs undergoing skin surgery, and to investigate the role of substance P as an intraoperative pain indicator. Twenty dogs were included, each subjected to three different treatments: Chopin music, Mozart music and no music. They were premedicated with acepromazine, butorphanol and meloxicam and anaesthetized with propofol and isoflurane. Fentanyl was used as rescue analgesia. The anaesthetic depth was monitored by using the bispectral index along with standard anaesthetic monitoring, and autonomic nervous system responses were used to monitor the adequacy of analgesia. Furthermore, measurements of substance P serum concentration were carried out. Dogs exposed to music required less isoflurane and fentanyl. Furthermore, a statistically significant effect of time on substance P concentration was observed regardless of exposure to music, and there was a significant interaction effect between different timepoints and the type of acoustic stimulus. Classical music seems to have an isoflurane and fentanyl sparing effect on dogs undergoing minor surgery. Following surgical stimulation, the serum substance P concentration increases rapidly, and thus appears to be a potentially useful pain indicator.

Efficacy and safety of a hypertonic nasal wash solution containing sea algae extracts in patients that underwent surgical correction of a deviated nasal septum and radiofrequency turbinate volume reduction.

OBJECTIVE: The objective of this study was to evaluate efficacy and safety of a Hypertonic Seawater Solution (2.3% NaCl) containing brown and blue-green Algae (HSS-A) in comparison to Isotonic Saline Solution (ISS) regarding the improvement of nasal breathing in patients that have undergone surgical correction of a deviated nasal septum and radiofrequency turbinate volume reduction. PATIENTS AND METHODS: A total of 101 individuals were enrolled in the study (HSS-A: 57; ISS: 44). Nasal breathing was evaluated using a Peak Nasal Inspiratory Flow (PNIF) measurement device at four timepoints: prior to surgical intervention (up to 30 days pre-surgery) and at the 2nd, 10th and 20th postoperative days. On the 20th postoperative day, patients also answered a Nasal Surgical Questionnaire (NSQ) evaluating breathing ability and overall satisfaction from the use of both nasal sprays. RESULTS: No significant differences were observed in PNIF measurements between groups at different points. On the 20th postoperative day, NSQ analysis showed that ISS-treated patients had more frequently moderate nasal bleeding compared to the HSS-A group (85.7% vs. 14.3%, p=0.038). No other statistically significant differences were observed between groups. When NSQ parameters were evaluated in a binary mode, a trend for reduced crusting scores was seen in the HSS-A group (15.9% vs. 35.5% in ISS, p=0.053). No safety concerns were reported throughout the study. CONCLUSIONS: In patients that have undergone surgical correction of a deviated nasal septum and radiofrequency turbinate volume reduction, PNIF values did not differ significantly in patients receiving HSS-A and ISS solutions. Nasal bleeding was more frequent in ISS patients versus HSS-A. Overall, both solutions provided symptomatic relief and use satisfaction in the absence of side effects.

Efficacy and safety of a hypertonic seawater nasal irrigation solution containing algal and herbal natural ingredients in patients with COVID-19.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of using a hypertonic seawater nasal irrigation solution comprising natural ingredients (HSS-Plus) with the aim of reducing viral load and ameliorating nasal symptoms in cases of COVID-19. PATIENTS AND METHODS: This single-center, prospective, single-arm, low-intervention study evaluated daily use of HSS-Plus in patients admitted to the Sotiria Hospital, Athens, Greece for a period of up to 10 days or until hospital discharge. Viral load measurements in nasopharyngeal swabs were performed on days 0 (baseline), 3 and 6, and on the final day of participation (day 10 ± 2; hospital discharge). In addition, study participants were asked to rate the severity of nasal and other symptoms using Visual Analog Scales (VAS) at the same time points. At the final day, the patients also assessed the perceived use benefit of HSS-Plus. RESULTS: 47 patients were enrolled in the study; 93.6% had a decrease in viral load of at least > 0.5 log10 on day 10 (p<0.001). Compared to values before nasal irrigation, viral load in nasopharyngeal swabs increased immediately after nasal lavage on days 3 (p=0.037) and 6 (p=0.010), indicating efficient removal of viral particles from the nasal cavity. Mean VAS symptoms' total score was reduced from 27.57 ± 15.63 at baseline to 6.73 ± 6.59 after 10 days (p<0.001). Similar reductions were also evident for individual symptoms at all time points (p<0.005). No adverse events were reported in the study. CONCLUSIONS: HSS-Plus nasal irrigation is an effective and safe method for reducing viral load and providing symptom relief in patients with COVID-19.

Clinical, dermoscopic and histological assessment of melanocytic lesions: a comparative study of the accuracy of the diagnostic methods.

BACKGROUND:   Worldwide, the incidence of melanoma is increasing, while late diagnosis is related to poor prognosis. A significant risk marker for melanoma is the presence of atypical nevi; therefore, it is of outstanding importance to make accurate clinical classification of common benign nevi, atypical nevi, and melanomas. The non-invasive method of dermoscopy allowed for the visualization of structures invisible to the naked eye and undoubtedly advanced the assessment of melanocytic lesions to a new dimension. This study aimed to evaluate the sensitivity and specificity of naked-eye examination and dermoscopy in diagnosing melanocytic lesions compared to the histopathological results, constituting the gold standard of diagnosis. MATERIAL AND METHODS: One hundred eighteen melanocytic lesions were clinically evaluated via the naked eye and dermoscopic examination, using Pattern Analysis Methodology, and afterward, they were excised. The histopathological results were correlated with the findings. RESULTS: According to the final histopathological analysis, 63 common benign nevi, 41 dysplastic nevi, and 14 cutaneous melanomas were excised in total. Clinical examination via the naked eye showed 78.2 % sensitivity and 71.4 % specificity in identifying the clinical atypia, while dermoscopy demonstrated 89.1 % sensitivity and 93.7 % specificity. CONCLUSIONS: The results of the present study indicate a higher sensitivity and specificity of dermoscopy in evaluating and diagnosing melanocytic lesions compared to the naked-eye examination. HIPPOKRATIA 2021, 25 (4):156-161.

JAK inhibitors in chronic plaque psoriasis: What is known so far.

Janus kinase (JAK) inhibitors are novel small molecules with a mechanism of action in multiple signaling pathways that allows their application in a broad spectrum of autoimmune and autoinflammatory diseases. As far as the field of dermatology is concerned, chronic plaque psoriasis is currently one of the most studied indications regarding the potential use of JAK inhibitors. The purpose of this review is to provide a summarized overview of the existing information on the efficacy and safety of JAK inhibitors in plaque psoriasis, with a focus on tofacitinib, ruxolitinib, baricitinib, peficitinib and filgotinib. Although the published data on the therapeutic benefit of these agents in the therapy of this chronic condition are promising, further prospective studies and real-life data are necessary in order to sufficiently evaluate their role as an adequate treatment option for psoriatic patients.

The role of IL-17 and IL-17 receptor inhibitors in the management of generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a severe psoriasis form that can be refractory to several systemic treatments. The role of interleukin (IL)-17/ T-helper 17 (Th17) axis inhibitors in the therapy of GPP is not fully established. The objective of this paper is to summarize the existing information on the efficacy and safety of secukinumab, ixekizumab and brodalumab in GPP. Articles published in the English language and derived from the databases MEDLINE (PubMed), Embase and Scopus were assessed for this study. Although the existing data on the potential therapeutic benefit of these agents in the treatment of GPP are encouraging, further studies are needed so as to provide sufficient evidence for their use in this serious condition.

Pyogenic granuloma: complete remission under occlusive imiquimod 5% cream.

An 82-year-old man was referred to our department for evaluation and treatment of a recurrent pyogenic granuloma on his right hand. After previous histopathological confirmation of the clinical diagnosis, he had been treated twice with electrocautery, but the lesion recurred 10 and 8 days later, respectively. After a 3-week topical application of imiquimod 5% cream twice daily under occlusion, complete remission of the lesion was achieved. Apart from an erythematous reaction in the apparently normal surrounding skin, the patient experienced no local or systemic side-effects. Since discontinuation of treatment he has been followed up for 8 months, and there has been no recurrence.

Peripheral large nerve fibre function in patients with chronic plaque psoriasis.

Accumulating evidence suggests the involvement of neurogenic inflammation in the pathogenesis of psoriasis. Moreover, the concomitant occurrence of peripheral neuropathy has been reported in several psoriatic patients. Thus, the aim of the present study was to answer the question whether an impairment of peripheral large nerve fibre function may exist in psoriasis. Thirty-two patients with severe and generalized chronic plaque psoriasis and 32 sex- and age-matched healthy controls were evaluated by detailed clinical neurological and standard neurophysiological examination. The latter included motor nerve conduction study of one nerve in the upper and one in the lower extremities and sensory nerve conduction study of one nerve in the upper and two in the lower extremities. Neurological examination failed to demonstrate any clinical evidence of large fibre neuropathy. Furthermore, all values of the examined neurophysiological parameters were within normal limits; comparisons of the corresponding mean values in the patient and the control group showed no statistically significant differences. These findings demonstrate no measurable abnormalities of the peripheral large nerve fibres in psoriatic patients and therefore an association of psoriasis with peripheral large fibre neuropathy cannot be suggested.

Qualitative and quantitative alterations of cell surface carbohydrate residues during epidermal morphogenesis.

The purpose of this study was to investigate the carbohydrate residue composition of cell surface in the developing epidermis and to define the chronological sequence of its alterations in human fetuses from the 10th to the 20th weeks of gestation and at the 23rd week of gestation, using a panel of six biotinylated lectins: Concanavalin A, Ulex europaeus agglutinin-I, Ricinus communis agglutinin-I, Peanut agglutinin, Wheat germ agglutinin, and Dolichos biflorus agglutinin. Distinct qualitative and quantitative alterations in the expression of cell surface carbohydrate residues were found during epidermal morphogenesis prior to keratinization (10th to 20th weeks). At the 23rd week of gestation, the already keratinized fetal human epidermis revealed a pattern of cell surface glycosylation very similar to that of the adult human epidermis. Further studies are now warranted to answer the question regarding whether the glycosylation pattern in the developing human epidermis is disturbed in fetuses with genodermatoses and whether these disturbances might be important for prenatally diagnosing the latter.

Heterogeneous fluoroimmunoassays using fluorescein as label with measurement of the fluorescence signal directly onto the solid-phase.

A heterogeneous fluoroimmunoassay approach with measurement of the fluorescence signal directly onto the solid support is described. Fluorescein was employed as fluorescent label whereas plastic microtitration wells were used as solid carriers. The influence of the type of the plastic wells on the proposed approach was investigated. Different types of commercially available plastic microtitration wells (white-opaque, black, and transparent) were tested. The solid supports were judged on the grounds of the maximum fluorescence signal, the precision, and the sensitivity they provided in a model non-competitive assay for mouse IgG. Among the solid supports tested, the white-opaque wells provided the most promising results with respect to the parameters in question. This support was also used for the development of a competitive fluoroimmunoassay for the determination of total thyroxin in human serum samples in order to assess the validity of the proposed approach under real immunoassay conditions. The assay developed had appropriate analytical characteristics for the determination of thyroxin and the serum sample values obtained were well correlated with those determined by a commercial solid-phase radioimmunoassay.

Stiff-person syndrome associated with oral isotretinoin treatment.

We describe a patient with severe nodulocystic acne who developed disabling muscle stiffness and painful superimposed spasms of the neck, back and upper limbs 10 days after the onset of oral isotretinoin treatment. The muscle hyperactivity condition, which revealed the clinical and electromyographic features of the stiff-person syndrome, gradually resolved 2 weeks after drug withdrawal.

Group B streptococcus infection rate unchanged by gestational diabetes.

OBJECTIVE: Group B streptococcal colonization in pregnancy has been associated with adverse perinatal outcomes, including intra-amniotic infection, postpartum endometritis, and neonatal sepsis. We sought to determine whether gestational diabetes increases the risk of maternal and neonatal morbidity from group B streptococcal colonization. METHODS: Gestational diabetic and nondiabetic women who underwent vaginal or anogenital culture for group B streptococcus colonization in pregnancy were followed up for pregnancy outcome. Antibiotic prophylaxis was not routinely given. Major perinatal morbidity included intraamniotic infection, endometritis, and neonatal sepsis. Potential confounding variables included induction of labor, cesarean delivery, prematurity, maternal antibiotic use, and prolonged rupture of membranes. RESULTS: We compared 446 gestational diabetic women to 1,046 nondiabetic women for outcome. Overall, 12% were colonized with group B streptococcus, with no difference in colonization rates between gestational diabetic (12%) and nondiabetic (12%) women. There were no differences in intraamniotic infection rates between gestational diabetic and nondiabetic women, whether group B streptococcus positive (16% compared with 13%) or group B streptococcus negative (10% compared with 11%). Likewise, endometritis did not differ (6-9%) regardless of diabetes or group B streptococcus status. Neonatal sepsis was higher in group B streptococcus-positive women overall (3% compared with 1%, odds ratio 3.71, 95% confidence interval 1.23, 10.81), but did not differ between diabetic and nondiabetic pregnancies. CONCLUSION: Gestational diabetes does not alter the perinatal morbidity associated with group B streptococcal colonization in pregnancy.

Radioimmunoassay of free thyroxine (T4) using 125I-labeled T4-IgG complex with very large molecular weight.

We describe a double-antibody radioimmunoassay for the determination of free thyroxine (FT4) in serum using a 125I-labeled T4-IgG conjugate of very large molecular weight (approximately 1,000,000) as tracer. The binding of this conjugate to the anti-T4 antibody was found to be satisfactory and independent of the T4-binding protein concentration. The T4 sequestration by the antibody was limited and the sample dilution used in the final assay mixture was low. The results determined by the assay developed for samples from hypo-, hyper-, euthyroid subjects and from non-thyroidal-illness patients were well correlated with those obtained by a free T4-equilibrium dialysis kit (Nichols). The detection limit of the assay was 0.41 pmol/l and the range covered by assay standard solutions was 2.4-121 pmol/l. The FT4 concentrations in serum as determined by this assay were 9.6-31 pmol/l (mean 21 pmol/l) for 46 euthyroid serum samples; 6.7-47 pmol/l (mean 23.5 pmol/l) for 27 non-thyroidal illness; and 4.2-25.8 pmol/l (mean 11.6 pmol/l) for 19 pregnant women.