Multicenter Evaluation of the Clinical Performance and the Neutralizing Antibody Activity Prediction Properties of 10 High-Throughput Serological Assays Used in Clinical Laboratories.

As the coronavirus disease 2019 (COVID-19) pandemic second wave is emerging, it is of the upmost importance to screen the population immunity in order to keep track of infected individuals. Consequently, immunoassays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high specificity and positive predictive values are needed to obtain an accurate epidemiological picture. As more data accumulate about the immune responses and the kinetics of neutralizing-antibody (nAb) production in SARS-CoV-2-infected individuals, new applications are forecast for serological assays such as nAb activity prediction in convalescent-phase plasma from recovered patients. This multicenter study, involving six hospital centers, determined the baseline clinical performances, reproducibility, and nAb level correlations of 10 commercially available immunoassays. In addition, three lateral-flow chromatography assays were evaluated, as these devices can be used in logistically challenged areas. All assays were evaluated using the same patient panels in duplicate, thus enabling accurate comparison of the tests. Seven immunoassays examined in this study were shown to have excellent specificity (98 to 100%) and good to excellent positive predictive values (82 to 100%) when used in a low (5%)-seroprevalence setting. We observed sensitivities as low as 74% and as high as 95% at ≥15 days after symptom onset. The determination of optimized cutoff values through receiver operating characteristic (ROC) curve analyses had a significant impact on the diagnostic resolution of several enzyme immunoassays by increasing the sensitivity significantly without a large trade-off in specificity. We found that spike-based immunoassays seem to be better correlates of nAb activity. Finally, the results reported here will add to the general knowledge of the interlaboratory reproducibility of clinical performance parameters of immunoassays and provide new evidence about nAb activity prediction.

Evolution of and risk factors for psychological distress in patients with psoriasis: the PSYCHAE study.

Psychological distress (PD) is common in patients with psoriasis but little is known about its evolution. The aim of this study is to assess the evolution of PD in psoriasis. For this purpose, 1,505 psoriatic patients, who had been previously enrolled in the PSYCHAE study, an observational multicenter Italian study, were re-evaluated after 6 and 12 months. Minor and major PD were assessed using the General Health Questionnaire (GHQ) and Brief Symptoms Inventory (BSI) questionnaires and coping using Brief COPE questionnaire. Minor PD was present in 46 percent of patients but halved during the study. Female gender, surface area, topical steroids, methotrexate, self-distraction, venting and behavioral disengagement were risk factors for minor PD; cyclosporine and humor were protective. Major PD was present in 11 percent of patients and remained stable. Female gender, venting, religion, behavioral disengagement and emotional support were risk factors for major PD; instrumental support was protective. In conclusion, the results obtained suggest that major PD remained stable after 12 months and that coping was a predictor of its evolution.

Effect of etretinate on chemotaxis of neutrophils from patients with pustular and vulgar psoriasis.

The chemotactic activities of neutrophil granulocytes of patients with pustular and vulgar psoriasis were evaluated before and after treatment with etretinate. Control values before treatment were significantly different from those of vulgar psoriasis group but not from the pustular psoriasis group. The difference between the 2 groups with psoriasis was significant. Etretinate causes a significant reduction in neutrophil chemotaxis in pustular psoriasis patients and a less pronounced reduction in those with vulgar psoriasis.

Factors secreted by untreated psoriatic monocytes enhance neutrophil functions.

Monocytes stimulated with bacterial lipopolysaccharides (LPS) release mediators that induce increased responses of human granulocytes. Recently we showed that psoriatic monocytes can stimulate neutrophil chemotaxis, phagocytosis, and O2- production without addition of LPS and this effect is inhibited by cyclosporin A. We have now investigated the presence of cytokines in supernatants from cultures of psoriatic monocytes (resting monocytes). These cells were cultured for 24 h in endotoxin-free medium. Normal human neutrophils were then incubated for 1 h with the resulting supernatants (sMS, or conditioned media). The sMS from unstimulated psoriatic monocytes significantly enhanced neutrophil chemotaxis and superoxide anion production. The enhancing factors are protein in nature and require ongoing protein synthesis, demonstrated by the facts that the activity in conditioned medium is labile to heat denaturation at 100 degrees C for 10 min, is not produced by monocytes cultured in the presence of puromycin, and is proteinase sensitive. Additional evidence suggested that extremes of pH inhibit activity. None of the conditioned media treated in these ways activated neutrophils. The neutrophil function-enhancing factors derived from psoriatic monocytes are in part cytokines, including TNF and GM-CSF. The support for this conclusion is the higher level of TNF and GM-CSF in media conditioned by psoriatic monocytes than in media conditioned by normal human monocytes, the inhibition of TNF production and neutrophil stimulating activity by cyclosporin A, and the inhibition of neutrophil stimulating activity in conditioned media preincubated with anti-TNF and anti-GM-CSF antibodies. It is concluded that psoriatic monocytes spontaneously produce higher than normal levels of TNF alpha, GM-CSF, and, perhaps, other cytokines that might be responsible for the enhanced activity of psoriatic neutrophils.

Posttransplantation cutaneous B-cell lymphoma with monoclonal Epstein-Barr virus infection, responding to acyclovir and reduction in immunosuppression.

Posttransplantation lymphoproliferative disorders (PTLDs) represent an important complication of solid organ transplantation. The main causative factor of PTLDs seems to be the intensity and type of immunosuppressive therapy and the frequent occurrence of Epstein-Barr virus infection. PTLDs that are disseminated at diagnosis or present late after transplantation generally share an unfavorable prognosis and are unlikely to regress in response to reduction in immunosuppressive therapy. We describe a case of cutaneous B-cell lymphoma occurring 4 years after heart transplantation in which molecular analysis revealed a monoclonal pattern of Epstein-Barr virus infection and immunoglobulin gene rearrangement. In spite of its monoclonal nature and late occurrence, the lymphomatous lesions regressed completely after antiviral treatment and a reduction in immunosuppressive therapy.

Macular skin lesion and monoclonal lymphoplasmacytoid infiltrates. Occurrence in primary Waldenström's macroglobulinemia.

Macular skin lesions and extensive, heavy lymphoplasmacytoid cell infiltrates of the dermis were observed in a patient with primary IgM-kappa Waldenström's macroglobulinemia. Direct immunofluorescent microscopy on tissue sections disclosed that the lymphoplasmacytoid cells had a monoclonal IgM-kappa origin.

Immunohistological evaluation of basal cell carcinoma immunoinfiltrate during intralesional treatment with alpha 2-interferon.

We investigated the peritumoral and intratumoral immune infiltrate in 6 basal cell carcinomas (BCCs) treated with recombinant alpha 2b-interferon. Each BCC was injected intralesionally three times a week for 3 weeks with 1.5 x 10(6) IU of interferon per injection (total dose 13.5 x 10(6) IU). The immunohistological study was done before the start of interferon therapy and 15 days afterwards, using a series of monoclonal antibodies and an immunocytochemical technique. Before therapy the infiltrate consisted mainly of CD3+ (T) cells, with prevalence of CD4+ (helper/inducer) T cells. The percentage of T cells expressing interleukin-2 receptor (CD25+ cells) was higher in the tumor nests than in the peritumoral infiltrate (20% and 11% respectively). CD1+ (Langerhans) cells and CD14b+ cells (monocytes/macrophages) were present in the peritumoral infiltrate in all cases (9% +/- 5% and 14% +/- 7% respectively). Very few CD56+ (natural killer), CD15+ (granulocytes) and CD20+ (B) cells were observed in the peritumoral infiltrate and none at all in tumor nests. After 15 days of interferon therapy, we observed an increase in peritumoral and intratumoral CD4+ cells. There was a decrease in the number of CD25+ cells and of CD1+ cells in the peritumoral infiltrate. The number of intratumoral CD25+ increased. No variations were seen in CD14b, CD15, CD20, and CD56 positive cells. Eight weeks after completion of therapy, two BCCs were cleared and the remaining four showed clinical and histological improvement. These results may indicate a direct effect of interferon against BCC; in addition the immunohistological findings suggest that intralesional interferon enhances T cell mediated immune response, especially in tumor nests.(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind crossover comparison of flecainide and slow-release mexiletine in the treatment of stable premature ventricular complexes.

In 24 patients with stable premature ventricular contractions (PVCs) greater than or equal to 100/h, Lown class greater than or equal to 2 the relative anti-arrhythmic efficacy of flecainide 150 mg twice daily and slow-release mexiletine 360 mg twice daily was evaluated in a double-blind placebo-controlled randomized crossover study. All the patients had normal ventricular function. Criteria of efficacy were: reduction greater than or equal to 70% of PVCs or reduction greater than or equal to 50% with abolition of Lown class greater than 2 arrhythmias or suppression of non-sustained ventricular tachycardias (nSVT). Twenty-two patients completed the study protocol. The placebo phases showed comparable results and no carry over effect. The criteria of efficacy were fulfilled in 20 of the 22 patients (91%) on flecainide and in 12 of the 22 (55%) on mexiletine. The absolute reductions of PVCs, couplets and nSVT obtained on flecainide and mexiletine, in comparison to the placebo, were statistically significant (p less than 0.01 for flecainide, p less than 0.05 for mexiletine). Flecainide was superior to mexiletine in overall PVC reduction (p less than 0.05). In the 17 patients with couplets the reduction obtained with flecainide was superior to mexiletine (p less than 0.05). Both drugs were highly effective on nSVT. At steady state, the mean plasma levels of both drugs were within the range of clinical efficacy. The drugs were well tolerated and no patient withdrew because of side-effects. It was concluded that at the dosages employed flecainide was superior to mexiletine in reducing premature ventricular contractions and in abolishing couplets. The efficacy of both drugs for non-sustained ventricular tachycardias was comparable. Both drugs were highly effective by comparison with the placebo.

Plasma neuropeptide levels in psoriasis.

The immune system is important in the pathogenesis of psoriasis and emotional stress has precipitated psoriasis in many patients. Neuropeptides, alpha-Melanocyte stimulating hormone (alpha-MSH), beta-endorphin, met-enkephalin and substance P (SP) act as immunomodulators, and their secretion increases during periods of stress. To see whether these neuropeptides themselves might be related to psoriasis and/or to the aggressiveness of the disease, we evaluated the plasma neuropeptide levels in 13 patients with active psoriasis (patients with new lesions and/or pre-existing lesions that had become larger during the month before the study), in 11 patients with stable psoriasis and in 10 healthy controls. Plasma concentrations of neuropeptides were evaluated by RIA (immunoradiometric assay for beta-endorphin). Data were compared by the Student t-test for unpaired data. There were no significant differences between the plasma levels of any of the neuropeptides between active psoriatic patients and stable psoriatic patients, nor between the plasma levels of neuropeptides of psoriatic patients and those of control subjects. It seems unlikely that circulating neuropeptide levels are of primary importance in the manifestation of the psoriatic skin lesions.

Topical calcipotriol (MC 903) for psoriasis: a clinical study.

Calcipotriol, a non-calcemic vitamin D3 analogue, inhibits the proliferation and is necessary for final differentiation of keratinocytes. The aim of the present study was to determine the efficacy and tolerability of calcipotriol ointment in patients treated for 6 weeks. Twenty patients with chronic plaque-type psoriasis were treated twice daily with calcipotriol ointment 50 ng/g. After 6 weeks' treatment there was a marked and statistically significant decrease in the PASI score values for 17 patients, no improvement was seen in 1 patient and local adverse events occurred in 2. Hypercalcemia or other laboratory abnormalities did not develop in any patient.

Topical calcipotriol for psoriasis--an immunohistologic study.

The aim of the present study was to investigate the distribution of Langerhans cells and T cells in the lesions and also the phenotypic expression of markers of activation on lesional T cells and keratinocytes, before and after 2 weeks of topical treatment of 7 psoriatic patients with calcipotriol. Before treatment, the infiltrate was composed mainly of T cells and there was decreased expression of CD1 on the intra-epidermal Langerhans cells. ICAM-1 and EGF receptor were present throughout the epidermis, but keratinocytes expressing Transferrin receptor were detected only in the basal layer. After 14 days of calcipotriol therapy, there were significantly fewer CD4T cells in the dermis and an increased number of intraepidermal CD1 + Langerhans cells. ICAM-1 expression on lesional keratinocytes was reduced in all patients, but the expression of EGF receptor was decreased in 3 patients only, and Transferrin receptor expression on keratinocytes had not changed. All these changes were concurrent with moderate clinical improvement of the lesions. The results suggest that in the early stages of the clinical response to calcipotriol there is an immunomodulating effect of the drug associated with variable decreases in keratinocyte expression of markers of activation.

Experience with psoriasis in a psychosomatic dermatology clinic.

We studied 179 psoriatic patients by semistructured colloquia and psychometric tests and determined their cutaneous psycho-neurophysiological profiles by biofeedback methods. The Paykel scale for stressful events showed that 72% of psoriatics had experienced significant stressful events about one month before the appearance of the psoriasis. The Zung test for anxiety and depression showed a high level of anxiety in the psoriatic patients. 64% of the patients who were treated by BFBtraining had a decrease in their PASI index for severity and the extent of the disease and also fewer recurrences at the one-year follow-up. The results of the World Experience Inventory indicated difficulties related to body image and to relationships with others. Psoriasis influenced the sexuality of the patients. It is always difficult when one is afflicted by ill health to enjoy life and the general scores of SWL (Satisfaction with Life), were significantly lower than those of a control group.

[Clinical framework of psoriatic arthropathy. Proposal of an evaluation protocol]. / Inquadramento clinico dell'artropatia psoriasica. Proposta di un protocollo di valutazione.

Psoriatic arthropathy is an inflammatory seronegative arthritis characterized by an involvement of peripheral or axial joints in association with psoriasis. In this study the clinical features of both skin and joints have been observed simultaneously by a rheumatologist and a dermatologist. We have finally proposed a clinical protocol based on PASI to evaluate psoriasis and on a simple subset classification to estimate joint involvement.

[Laser flow cytofluorimetry in the study of papilloma virus-induced lesions]. / La laser-citofluorimetria a flusso nello studio delle lesioni indotte da papillomavirus.

HPV insertion into the genome can cause permanent changes in cellular DNA that disturb the regulation of cell proliferation. Most HPV-induced epithelial proliferative disease are benign, but not all. We have studied both types of lesion by automated laser flow cytometry to see if there were any permanent changes in the DNA that might serve as reliable prognostic indicators. There were 101 lesions of interest to the dermatologist, stomatologist and gynecologist. Although fluctuations in yields of cells make it difficult to formulate definite conclusions, since many results are heterogeneous and hard to summarize, we found dysplastic and metaplastic lesions always to be hyper- or hypodiploid and to our surprise two cases of common wart were hyperdisploid and another hypodiploid. This present study shows that laser flow cytometry can detect changes in the genome of lesions known to become malignant when the histological degree of transformation still indicates only a preneoplastic condition. This raises the problem of how we should label lesions like common warts, since laser flow cytometry clearly shows that they have net changes, though slight, in DNA content.

[Growth factors in the pathogenesis of progressive systemic sclerosis]. / I fattori di crescita nella patogenesi della sclerosi sistemica progressiva.

Scleroderma is a connective tissue disorder characterized by vascular lesions, fibrosis and inflammation. The pathogenesis of this disease is not clear. A vascular lesion, possibly caused by deposition of immune complexes or by release of cytotoxic factors, seems to be at the origin of the disease. As a consequence, platelet adhesion and activation might occur in sclerodermic patients. The observation that platelet might release, upon aggregation, a potent mitogenic factor, named Platelet Derived Growth Factor (PDGF) has focused interest on platelets as the potential mediators of the fibrotic process, characteristic of systemic scleroderma. We found an increased mitogenic activity in plasma derived serum (PDS) of a group of patients with progressive systemic sclerosis (PSS), as compared to control subjects. The activity was inhibited by incubation with anti-PDGF IgG's, suggesting that abnormal PDGF levels might indeed be present in plasma of PSS patients.

Muscle belly union associated with simultaneous medial rectus recession for treatment of myopic myopathy: results in 33 eyes.

PURPOSE: To describe the results achieved using muscle belly union associated with the recession of the ipsilateral medial rectus muscle to treat myopic myopathy and restore the normal anatomical relationship of superior and lateral rectus (LR). METHODS: A retrospective, nonrandomized study performed on 33 eyes of 26 patients who underwent muscle belly union between January 2004 and October 2012. We preoperatively and postoperatively recorded: best-corrected visual acuity; refraction; intraocular pressure; complete orthoptic assessment, including the angle of deviation and maximal abduction measured using the Goldmann perimeter. Pictures of the eyes in all gaze directions were taken before and after the surgical treatment. Anatomical relationships between muscle cone and eye globe were preoperatively analyzed using magnetic resonance imaging (MRI). Surgical complications were noted. RESULTS: The follow-up period was 6 months. Preoperative mean BVCA was 0.97 ± 0.96 logMAR (ranging from 0.1 to 3 logMAR) and no changes were detected during postoperative controls. Preoperative mean hypotropia and esotropia were, respectively, 10.2 ± 3.9 prism diopters (PD) and 46.2 ± 15.5 PD. Postoperative mean hypotropia was 2.48 ± 2.00 PD (P<0.001) and mean esotropia was 7.36 ± 9.09 PD (P<0.001). A statistical incrementation of mean maximal abduction (P<0.001) was also noticed. CONCLUSIONS: Muscle belly union-coupled with the recession of the ipsilateral medial rectus muscle when considered convenient-is the elective surgical technique in myopic myopathy, when a downward displacement of LR muscle is shown on MRI with coronal sections.

Different underlying neurocognitive deficits in developmental dyslexia: a comparative study.

The aim of this study was to investigate the role of several specific neurocognitive functions in developmental dyslexia (DD). The performances of 60 dyslexic children and 65 age-matched normally reading children were compared on tests of phonological abilities, visual processing, selective and sustained attention, implicit learning, and executive functions. Results documented deficits in dyslexics on both phonological and non-phonological tasks. More stringently, in dyslexic children individual differences in non-phonological abilities accounted for 23.3% of unique variance in word reading and for 19.3% in non-word reading after controlling for age, IQ and phonological skills. These findings are in accordance with the hypothesis that DD is a multifactorial deficit and suggest that neurocognitive developmental dysfunctions in DD may not be limited to the linguistic brain area, but may involve a more multifocal cortical system.