Simultaneous Bilateral Total Knee Arthroplasty in Elderly: Are There Factors that Can Influence Safety and Clinical Outcome?

Objective: The aim of this study was to look for preoperative patients' related factors correlating with worse clinical outcomes in a cohort of elderly patients undergoing simultaneous bilateral total knee arthroplasty (SiBTKA) to search for risk factors, which may influence clinical outcomes and safety. Subjects and Methods. The hospital database was mined searching for patients older than 70 years that underwent SiBTKA for severe bilateral knee osteoarthritis (OA) between 2012 and 2016. Preoperative clinical information, Oxford Knee Score (OKS), and Knee Injury and Osteoarthritis Outcome Score (KOOS) prior to surgery were recorded. The OKS and the KOOS were submitted again after a minimum of 5 years of follow-up (FU). Results: An improvement was observed in all clinical scores at last FU. The major complication rate was 5.4%. No patients' clinical data showed correlation with perioperative complications or need for transfusions. Functional scores at the last FU were negatively affected by age at surgery and positively affected by preoperative clinical scores. Discussion. In the setting of severe symptomatic bilateral knee OA, SiBTKA seems to be effective in improving symptoms at midterm follow-up, with acceptable rates of perioperative complications in patients older than 70. Higher age at surgery and lower preoperative functional scores are associated with worse clinical outcomes at FU. This could assist surgeons in advising patients that delay of surgical treatment could worsen outcomes.

Multiparametric MR imaging of the prostate at 1.5-T without endorectal coil using an 8 channel pelvic phased array: Is it still a viable option?

INTRODUCTION: The purpose of our work was to evaluate the feasibility of prostate multiparametric MR imaging at 1.5-T without endorectal coil using an 8 channel pelvic phased array coil. MATERIAL AND METHODS: A total of 154 patients who underwent mp-MRI were retrospectively included. Patients received a standardized mp-MRI, compliant with 2012 European Society of Uro-Radiology guidelines, with 1·5 T magnetic field strength and an 8 channel pelvic phased-array coil. Two blinded readers graded the image quality of mp-MRI on a three-point scale and they scored the prostate lesions according to PI-RADS v2. All PI-RADS of 4 or 5 underwent biopsy. A third radiologist and a pathologist verified the correspondence between the MRI images and the results of the biopsy. RESULTS: 64 (41.6%) patients showed a Pi-rads of 4 or 5. At biopsy, 79.7% showed a Gleason score ≥7, 12.5% showed a Gleason score of 6 and 7.8% showed a negative biopsy. In the group of Pi-rads ≤ 3, 12 patients underwent a biopsy with the following results: negative biopsy in 33.3%, atypical Small Acinar Proliferation in 16.7%, prostatic intraepithelial neoplasia in 25% and indolent PCa 25%. Mp-MRI in the identification of clinically significant cancer provided a low percentage of false positive (7.8%) while in 79.7% of cases it was capable to detect clinically significant prostate cancer. In 92.2% of patients mp-MRI identified a prostate cancer with a Gleason score ≥6. The inter-reader agreement was excellent in defining both the quality of the examination and the PI-RADS category (k = 0.83 and k = 0.70, respectively). CONCLUSIONS: mp-MRI at 1.5-T without endorectal coil using an 8 channel phased array is an appropriate tool for early detection of clinically significant prostate cancer. IMPLICATIONS FOR PRACTICE: 8 channel pelvic phased array is still an appropriate tool for early detection of clinically significant prostate cancer and for obtaining a reduction in overdiagnosis of indolent PCa.

Relevance of TH2 Markers in the Assessment and Therapeutic Management of Severe Allergic Asthma: A Real-Life Perspective.

BACKGROUND: Although blood eosinophils are currently recognized as the main clinical marker of TH2-type inflammation, their relevance in identifying asthma severity remains a matter of debate. METHODS: Our retrospective real-life study on severe asthmatics included in the NEONet Italian database aimed to investigate the relevance of blood eosinophil count and fractional exhaled nitric oxide (FeNO) in the clinical assessment of severe asthma and their role as potential predictors of responsiveness to anti-IgE therapy. The cut-off values chosen were 300 eosinophils/mm3 and FeNO of 30 ppm. RESULTS: We evaluated 132 adult patients. No significant differences were observed between the groups (high and low baseline eosinophil counts) in terms of demographic data, total IgE, lung function, patient-reported outcomes, or nasal comorbidities. The Asthma Control Test score and Asthma Quality of Life Questionnaire scores were poorer in patients with FeNO ≥30 ppb than in patients with FeNO <30 ppb. In the high FeNO subgroup, more frequent hospital admissions and a higher number of working days lost in the previous year were registered. A combined score including both eosinophils and FeNO did not improve the accuracy of the individual parameters. In the high-eosinophil subgroup, the proportion of responders to omalizumab was greater and increased at each follow-up time point. CONCLUSIONS: Our findings show that blood eosinophil count is not an unequivocal marker of asthma severity, whereas a higher FeNO level is associated with more frequent hospital admissions and more working days lost. Blood eosinophils seem to act as a predictor of response to omalizumab.

Relevance of TH2 markers in the assessment and therapeutic management of severe allergic asthma: a real-life perspective

BACKGROUND: Although blood eosinophils are currently recognized as the main clinical marker of TH2-type inflammation, their relevance in identifying asthma severity remains a matter of debate. METHODS: Our retrospective real-life study on severe asthmatics included in the NEONet Italian database aimed to investigate the relevance of blood eosinophil count and fractional exhaled nitric oxide (FeNO) in the clinical assessment of severe asthma and their role as potential predictors of responsiveness to anti-IgE therapy. The cut-off values chosen were 300 eosinophils/mm3 and FeNO of 30 ppm. RESULTS: We evaluated 132 adult patients. No significant differences were observed between the groups (high and low baseline eosinophil counts) in terms of demographic data, total IgE, lung function, patient-reported outcomes, or nasal comorbidities. The Asthma Control Test score and Asthma Quality of Life Questionnaire scores were poorer in patients with FeNO ≥30 ppb than in patients with FeNO <30 ppb. In the high FeNO subgroup, more frequent hospital admissions and a higher number of working days lost in the previous year were registered. A combined score including both eosinophils and FeNO did not improve the accuracy of the individual parameters. In the high-eosinophil subgroup, the proportion of responders to omalizumab was greater and increased at each follow-up time point. CONCLUSIONS: Our findings show that blood eosinophil count is not an unequivocal marker of asthma severity, whereas a higher FeNO level is associated with more frequent hospital admissions and more working days lost. Blood eosinophils seem to act as a predictor of response to omalizumab

ANTECEDENTES: Aunque los eosinófilos en la sangre actualmente son reconocidos como el principal marcador clínico de la inflamación Th2, su relevancia en la identificación de la gravedad del asma sigue siendo un tema de debate. MÉTODOS: Nuestro estudio retrospectivo de la vida real sobre asmáticos graves, incluido en la base de datos italiana de NEONet, tuvo como objetivo investigar la relevancia del recuento de eosinófilos en sangre y el FeNO en la evaluación clínica del asma grave y su función como posible factor predictivo de la capacidad de respuesta al tratamiento con anti-IgE. Como valores de corte se eligieron 300 eosinófilos/mm3en sangre y 30 ppm para FeNO. RESULTADOS: En total se evaluaron 132 pacientes adultos. No se pudieron observar diferencias significativas entre los grupos de eosinófilos basales altos y bajos, en términos de datos demográficos, IgE total, función pulmonar, resultados informados por el paciente (PRO) o comorbilidades nasales. Los pacientes con ≥ FeNO 30 ppb mostraron una puntuación de ACT peor y una puntuación AQLQ más baja en comparación con los de FeNO <30 ppb. En el subgrupo de FeNO alto, se registraron ingresos hospitalarios con más frecuencia y un mayor número de días de trabajo perdidos en el último año. Una puntuación combinada que incluye tanto a los eosinófilos como el FeNO no mejoró la precisión de los parámetros individuales. En el subgrupo de eosinófilos altos, la proporción de pacientes que respondieron al tratamiento con omalizumab fue mayor y aumentó significativamente en cada punto de tiempo de seguimiento. CONCLUSIONES: De acuerdo con nuestros hallazgos, los eosinófilos en sangre no representan un marcador unívoco de la gravedad del asma, mientras que un nivel más alto de FeNO se asocia con más ingresos hospitalarios y más días de trabajo perdidos. Los eosinófilos de la sangre parecen actuar como predictores de la respuesta del tratamiento al omalizumab

Autologous and micro-fragmented adipose tissue for the treatment of diffuse degenerative knee osteoarthritis.

BACKGROUND: Chondral lesions of the knee represent a challenge for the orthopaedic surgeon. Several treatments have been proposed with variable success rate. Recently, new therapeutic approaches, such as the use of mesenchymal stem cells, have shown promising results. The adipose tissue is a good source of these naturally occurring regenerative cells, due to its abundance and easy access. In addition, it can be used to provide cushioning and filling of structural defects. The 1-year safety and outcome of a single intra-articular injection of autologous and micro-fragmented adipose tissue in 30 patients affected by diffuse degenerative chondral lesions was evaluated. METHODS: Micro-fragmented adipose tissue was obtained using a minimal manipulation technique in a closed system. The safety of the procedure was evaluated by recording type and incidence of any adverse event. The clinical outcomes were determined using the KOOS, IKDC-subjective, Tegner Lysholm Knee, and VAS pain scales taken pre-operatively and at 12 months follow-up. A level of at least 10 points of improvement in the scores has been selected as cut-off representing a clinically significant difference. RESULTS: No relevant complications nor clinical worsening were recorded. A total median improvement of 20 points has been observed in IKDC-subjective and total KOOS, and a higher percentage of success was found in VAS pain and Tegner Lysholm Knee, where the total median improvement was 24 and 31 points, respectively. CONCLUSION: The results of this study show the safety and feasibility of using autologous and micro-fragmented adipose tissue in patients affected by diffuse degenerative chondral lesions. The technique is safe, minimally invasive, simple, one-step, with low percentage of complications, and compliant with the regulatory panorama.

SANI-Severe Asthma Network in Italy: a way forward to monitor severe asthma.

Even if severe asthma (SA) accounts for 5-10% of all cases of the disease, it is currently a crucial unmet need, owing its difficult clinical management and its high social costs. For this reason several networks, focused on SA have been organized in some countries, in order to select these patients, to recognize their clinical features, to evaluate their adherence, to classify their biological/clinical phenotypes, to identify their eligibility to the new biologic therapies and to quantify the costs of the disease. Aim of the present paper is to describe the ongoing Italian Severe Asthma Network (SANI). Up today 49 centres have been selected, widespread on the national territory. Sharing the same diagnostic protocol, data regarding patients with SA will be collected and processed in a web platform. After their recruitment, SA patients will be followed in the long term in order to investigate the natural history of the disease. Besides clinical data, the cost/benefit evaluation of the new biologics will be verified as well as the search of peculiar biomarker(s) of the disease.

A novel technique for combined medial collateral ligament and posterior oblique ligament reconstruction: technical note.

PURPOSE: In the last year, we have performed a new technique for combined medial collateral ligament (MCL) and posterior oblique ligament (POL) reconstruction in chronic setting of anterior cruciate ligament and MCL complex deficiency. Autogenous semitendinosus tendon with the tibial attachment preserved has been used for the medial/posteromedial compartment reconstruction. We describe the operative technique. METHODS: Between January and December 2014, 12 consecutive patients with multiligamentous injuries underwent concomitant MCL/POL using a novel technique. The usefulness of the novel technique is the semitendinosus sling on the semimembranosus tendon and the POL fixation with the knee in full extension. RESULTS: An ideal anteroposterior and rotational stability avoiding the medial compartment over constraint was achieved, in the immediate after surgery, due to the sequence of the bundle fixations and to the semitendinosus sling below the semimembranosus tendon. CONCLUSIONS: This technique is easily reproducible and useful and restores the medial stability immediately after surgery.

Pattern of airway inflammation and remodelling in mild persistent atopic asthma and in mild persistent asthma related to gastroesophageal reflux.

BACKGROUND: The increase of basement membrane thickness (BMAT) represents a structural feature described as commonly characterizing airway remodelling in asthma, even if the non-atopic condition had been investigated only episodically from this point of view. Gastrooesophageal-reflux is a pathological condition which can frequently cause and/or sustain asthma in non-atopic individuals. OBJECTIVES: The aim of the study was to measure BMT; some inflammatory mediators in BAL; cys-leucotrienes (LTE4) in urine; e-NO, and BHR to Methacholine (MCh) in mild atopic and in mild non-atopic, GER-related asthma. METHODS: After their informed consent, 25 mild atopic (40.9 years +/- 13.1 sd, FEV1 = 95.9% pred. +/- 12.9 sd) and 39 non-atopic, GER-related asthmatics (57.3 years +/- 14.2 ds, FEVY1 = 101.3% pred. +/- 12.2 sd), nonsmoker and of a comparable asthma duration, underwent measurements of basal lung function and bronchial response to MCh (PD20 FEV1); endobronchial biopsies and BAL (in the right middle lobe), and a 24-h gastroesophageal pHmetry. RESULTS: Atopic GER-related asthma showed two distinct patterns of airway inflammation. The eosinophilic contribution to airway inflammation was systematically prevailing in the former group, such as: EOS = 10.7% +/- 13.4 sd vs 2.0% +/- 2.8 sd, p = 0.001; ECP = 344.9 mcg/l +/- 635.9 sd vs 59.2 mcg/l +/- 75.1 sd, p = 0.001. CONCLUSIONS: Data from the present study are suggesting that persistent mild atopic and mild GER-related asthma seem to represent two distinct phenotypes of asthma in terms of airway remodelling, and in particular of BMT involvement.

Reference urinary LTE4 levels in normal individuals: a pilot study.

UNLABELLED: The definition of reference normal values for urinary LTE4 still represents an open question. AIM: to assess the influence of gender and age on urinary LTE4 levels in normal individuals. METHODS: after their informed consent, urinary LTE4 was measured in 124 well matched, non smoker, non atopic subjects (mean age 49.5 y +/- 20.1 sd; range 4-85 y, 57 m;) without any clinically evident disease and not taking any drug for several months. In all subjects, urine were collected in the morning, and processed by an immunoenzimatic method (Cayman Chem, Mi, USA) via the Triturus system (Grifols, Spain). STATISTICS: t test, anova, linear regression, assuming p < 0.05. RESULTS: mean urinary LTE4 were 57.3 pg/ml in males (mean age 51.2 y +/- 21.3 sd) and 57.0 pg/ml in females (mean age 48.1 y + 19.1 sd), p = ns. Linear regression showed no relationship between urinary LTE4 levels and subjects' age in the whole sample of subjects. When subjects were divided according to 4 different classes of age (0-14; 15-40; 41-60; > 60), anova proved that mean urinary LTE4 levels were significantly different in the different classes of age, being higher in younger subjects (67.1 pg/ml +/- 33.4 sd; 69.8 pg/ml +/- 27.5 sd; 57.1 pg/ml +/- 25.4 sd, and 45.1 pg/ml +/- 24.9, respectively) (anova p < .002; Welch test p < .005). CONCLUSIONS: 1) gender does not affect urinary LTE4 levels in normals; 2) mean urinary LTE4 concentrations tend to a slight, but significant, decrease with the increase of the subjects' age, and this is clear in those over-60; 3) reference values for younger and older normal subjects (such as, under- and over-60 years) should be assumed accordingly.

Laparoscopic treatment of bowel endometriosis in infertile women.

BACKGROUND: The purpose of the study was to determine the influence of bowel endometriosis on fertility, and to study whether its removal improves fecundity in women with endometriosis-associated infertility. METHODS: Three groups of infertile patients were included in the study. Group A (60 women) consisted of patients who underwent surgery for endometriosis with colorectal segmental resection. In group B, 40 patients with evidence of bowel endometriosis underwent endometriosis removal without bowel resection. Group C consisted of 55 women who underwent surgery for moderate or severe endometriosis with at least one endometrioma and deep infiltrating endometriosis but without bowel involvement. The women were clinically evaluated before laparoscopy and then at 1 month, at 6 months and at each year up to 4 years after surgery. Main outcome measures were surgical complications as well as post-operative pregnancy rate, time to conception and monthly fecundity rate. RESULTS: The monthly fecundity rates (MFR) in groups A, B and C were 2.3, 0.84 and 3.95%, respectively. The difference in the MFR between groups was significant (P < 0.05). CONCLUSIONS: The presence of bowel infiltration by endometriosis seems to negatively influence the reproductive outcome in women with endometriosis-associated infertility. The complete removal of endometriosis with bowel segmental resection seems to offer better results in terms of post-operative fertility.

Cultural and linguistic testing of the Handling Questionnaire: a specific instrument for assessing the patient's acceptability of dry powder inhalers.

The testing and checking phases of a questionnaire are briefly described in this paper, identifying the common errors due to incorrect formulation of questions and the main issues. The theoretical methods for "testing" a questionnaire has been examined in the first section, in the second section the testing process for a specific questionnaire for assessing the patient's acceptability of a dry powder device (the Handling Questionnaire) has been described, together with the grading of improvement achieved.

PIKO-1, an effective, handy device for the patient's personal PEFR and FEV1 electronic long-term monitoring.

BACKGROUND AND AIM: Subjects with airway obstruction are strongly recommended to monitor their lung function, which is particularly variable in asthma. Unlike PEFR, other personal measurements (such as FEV1) are still difficult to perform. PIKO-1 is the first electronic device for both PEFR and FEV1 personal check, but its precision has not yet been assessed. The aim of this study was to compare PEFR and FEV1 values from PIKO-1 and from a conventional spirometer in subjects with airway obstruction. METHODS: In total, 352 subjects (217 men; 47.6 +/- 19.0 years; 72.6 +/- 15.0 kg; 168.1 +/- 11.9 cm) performed sequential measurements using a PIKO-1 device and a spirometer. Wilcoxon signed-rank test and sign test were used as statistical tests. RESULTS: Mean FEV1 values from the spirometer and PIKO-1, respectively, were 2.9 L +/- 1.1 and 3.0 L +/- 1.1, and mean PEFR values were 466.1 L/min +/- 164.5 SD and 426.3 L/min +/- 151.6 SD. PIKO-1 proved to overestimate FEV1 values by 4% (p<0.0001) and to underestimate PEFR values by 8% (p<0.000) systematically. CONCLUSIONS: The precision of both PIKO-1 measurements (such as FEV1 and PEFR) have been assessed. PEFR and FEV1 measures should be reset by two different constants. Nevertheless, PIKO-1 is a suitable and reliable device for the personal monitoring of obstructive patients in real life.

The therapeutic effects of inhaled long-acting beta2-adrenergics (LABA) and corticosteroids (ICS) are not affected by their inhalation sequence in moderate/persistent asthma.

UNLABELLED: Bronchial asthma is defined as "a chronic inflammatory disease of the airways involving many cells" and inhaled corticosteroids have therefore become the fundamental drugs for the long-term management of the disease. In moderate and severe persistent asthma the use of a long-acting bronchodilator is recommended in order to control symptoms and to enhance the efficacy of corticosteroids. Although not based on scientific evidence, it has been assumed that the, 2 adrenergic and the inhaled steroid should be administered in a strict inhalation sequence: the bronchodilatator first and then the steroid. The aim of the study was to assess the effects of this assumption experimentally, common indeed since long ago. MATERIALS AND METHODS: Twelve subjects with moderate-persistent asthma (7 males, aged 18-64, basal FEV1 = 65.59% pred. +/- 7.59 ds; reversibility = + 14.8% +/- 8.3 ds from baseline after Salbutamol 200mg), symptomatic despite the regular home treatment with Fluticasone p. 250mg bid and beta 2 short-acting prn for over 6 weeks, were initially treated with combined SM/FP 50/250mg bid from an unique Diskus" device, for 6 weeks. After this initial phase, the treatment continued according to a randomised, double-blind, cross-over design: all subjects received the same drugs, from two different Diskus" inhalers, and according to two different sequences of administration: 1) SM first and FP 20' later for 4 weeks, and then FP first and SM 20' later for a further 4 weeks; 2) vice versa. No wash-out period was included between these two phases of cross-over treatment. FEV1 (% pred.); morning PEF (L/min), the use of short-acting beta 2 as required (n/week); the number of awakenings at night (n/week), and the daytime asthma symptom score were measured. STATISTICS: The t paired test and anova (Duncan test) were used for statistical comparisons: a p<0.05 was accepted as the minimum level of significance. RESULTS: After the first six weeks of treatment with combined Salmeterol/Fluticasone, 50/250 mg FEV1 changed from 69.6% pred. +/- 7.59 ds to 79.8% pred. +/- 10.1 ds (p>0.005), whilst the morning PEF changed from 282.2 l/min : 64.1 ds to 333.4 l/min +/- 55.5 ds (p<0.02). Furthermore, the consumption of beta 2 adrenergic prn dropped from 4.4 (no./week) +/- 7.3 ds to 1.2 +/- 0.9 ds (p<0.001); the number of night-time awakenings decreased from 1.6 (no./week) +/- 0.2 ds to 0.2 +/- 0.3 ds (p<0.001), and the daytime symptom score changed from 3.4 +/- ds 0.8 to 1.9 +/- 0.7 ds (p<0.001). This therapeutic performance was maintained over the two subsequent 4-week periods of treatment from two distinct devices independently of the inhalation sequence. In particular, by both using salmeterol first or using fluticasone first, the therapeutic effects proved quite identical: FEV1: 80.7 % pred. +/- 9.5 ds and 80.3 +/- 7.4 ds; morning PEF: 336.5 l/min +/- 55.4 ds and 338.6 l/min +/- 67.1 ds; consumption of beta 2 adrenergic as required: 0.9 (no./week) +/- 0.6 ds and 0.9 (no./week) +/- 0.8 ds; number of awakenings: 0.3 (no./week) +/- 0.3 and 0.2 (no./week) +/- 0.3 ds; day-time/night-time symptom score: 1.7 +/- 0.5 ds and 1.8 +/- 0.6 ds, respectively (anova = ns). CONCLUSIONS: Both in terms of lung function and of clinical outcomes the efficacy of SM and FP administration proved completely independent of the particular sequence for their separate inhalation and quite superimposable to thatachieved b y their combined inhalation from an unique device.

Nasal and bronchial tolerability of Rofecoxib in patients with aspirin induced asthma.

UNLABELLED: Aspirin (ASA) and several other nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclo-oxygenase (COX) enzyme both isoforms 1 and 2, and can precipitate asthmatic attacks in aspirin-induced asthmatics. Rofecoxib (R) is a novel and specific COX-2 inhibitor which is caracterized by an highly selective COX-2 inhibition, and can be presumed as non cross-reactive with ASA. Aim of the study was to assess the bronchial and the nasal response to R in AIA. MATERIALS AND METHODS: Nineteen subjects with AIA (21-54 years, 7 m, mean FEV1 85.1% pred. +/- 5.4 sd) performed two oral provocation tests: one with increasing doses of ASA and one other of R at a time interval of 2 weeks, according to a randomized, cross-over design. The bronchial and the nasal responses were measured by serial measures of FEV1, and of nasal resistences by acoustic rhinomanometry, respectively. STATISTICS: Anova for trends was used, and p<0.05 accepted. RESULTS: Mean ASA PD20 was 68.3 mg +/- 12.4 sd. ASA induced a significant broncho-constriction in all patients with AIA: basal FEV1 dropped from 88.9% pred. +/- 6.2sd to 70.1% pred. +/- 6.9sd after 60 min. (Anova p = 0.001). Despite ASA, R was well tolerated: basal FEV1 remained unchanged during the period of observation following the R 25mg ingestion. ASA also precipitated a significant nasal response with increased nasal resistances (anova p < 0.001) and reduced volumes (anova p < 0.001). The nasal function was unchanged following R 25mg. CONCLUSIONS: Despite ASA, Rofecoxib, largely due to its highly specificity for COX-2, proved a drug particularly safe in treating patients with AIA.

Gliomatosis cerebri and pituitary adenoma: case report and literature review.

The diagnosis of Gliomatosis cerebri (GC) is known to be difficult and is still a matter of debate. We describe an in vivo case of GC associated with a pituitary tumor. A 47-year-old woman presented with short-term memory loss. A MRI revealed the presence of a pituitary enhancing tumor and a diffuse lesion involving the brain. A left pterional craniotomy with partial temporal lobectomy and removal of the pituitary lesion were performed in order to obtain diagnosis. The histological analyses showed a pituitary non-functioning tumor and a GC consisting of neoplastic oligodendrocytes and astrocytes. Both lesions showed nuclear immunoreactivity for progesterone receptors (PGr) and estrogen receptors (EGr). This result could suggest there is a common receptor substrate in these tumors. In this case hormones could constitute a common step in tumorigenesis of both lesions.

Thymus changes in anti-MuSK-positive and -negative myasthenia gravis.

Morphologic findings of thymuses from 32 anti-acetylcholine receptor (AChR)-negative myasthenia gravis patients, 12 with and 20 without antibodies against the muscle-specific kinase (MuSK), were compared with those from 30 AChR-positive subjects. In contrast with the high frequency of thymic hyperplastic changes in AChR-positive patients, in MuSK-positive subjects histologic alterations were minimal, arguing against an intrathymic disease pathogenesis. Since hyperplastic changes were seen in 35% of MuSK-negative patients, the thymus could be involved in some of these cases.

Regulation of human cytotoxic T lymphocytes development by the synergistic effect of IL-7 and sCD23.

The present study was undertaken to investigate the interaction of IL-7 and sCD23 on human peripheral blood T cell activation and CTL differentiation. Purified T lymphocytes were stimulated with mitogen plus IL-2 and subcultured for 7 days with IL-7 and/or sCD23. The combination of IL-7 and sCD23 synergistically enhanced the proliferation of both CD4+ and CD8+. T cells. CD8+ T cells, however, were usually more responsive to IL-7 and sCD23. This synergy was observed on both subsets of T cells. Furthermore, these cytokines synergistically augment the CTL activity of CD8+ T cells in both mitogen- and antigen-activated T cells. MAbs anti-IL-2 or anti-IL-2R (CD25) and anti-IL-12 had no effect on T cell proliferation and CD8+ cytotoxic activity induced by IL-7 and sCD23. We analyzed the effect on IFN-gamma induction by CD8+ T cells and found that IL-7 alone was incapable of inducing detectable levels of IFN-gamma production, but together with sCD23 it enhanced the production of IFN-gamma. We also found that IFN-gamma was not required for enhanced CTL activity of CD8+ T cells, because rabbit anti-IFN-gamma did not block the synergistic effects of either cytokine. The data demonstrate that the synergistic stimulatory activity of IL-7 and sCD23 may be of significance in the human CTL development and provide an alternative mechanism of stimulating T cells for use in immunotherapy.

Modulation of TCR usage in HIV-1 infection is regulated by IL-7 and sCD23.

The purpose of this study is to elucidate the effect of interleukin-7 (IL-7) and soluble CD23 (sCD23) on Phorbol12 Myristate13 Acetate (PMA) activated CD4+ TCR alpha beta+ cells of HIV-1 infected subjects. CD23 and IL-7R were detectable on activated CD4+ T cells of these subjects by FACS. Addition on IL-7 (1000 U/ml), at the onset of cultures, resulted in a significant increase of CD23 expression. We also demonstrated that T cells proliferation and CD23 expression in the presence of exogenous IL-7 occur in an IL-2 independent manner. Addition of IL-7 and sCD23 to activated CD4+ cells of HIV-1 infected subjects induced a proliferative response of TCR alpha beta cells. In contrast, addition of either sCD23 or IL-7 to activated CD4+ T cells did not result in an increase of TCR alpha beta expression. The data provide direct evidence that sCD23 in combination with IL-7 induce proliferation of activated CD4+ T cells of HIV-1 infected subjects to augment TCR alpha beta expression. These results support the possibility that IL-7 plus sCD23 might play an important role in the modulation of TCR alpha beta expression in HIV infection.

Interleukin 7 and sCD23 synergize in the induction of human T cell activation in HIV-1-infected subjects.

The role played by CD23 in retroviral infections is still unclear. The synergistic effects of interleukin 7 (IL-7) and sCD23 on T cell proliferation and the generation of HIV-1-specific cytotoxic T lymphocytes (CTL) in mitogen- and antigen-stimulated systems were examined. Addition of IL-7 and sCD23 at the onset of culture resulted in a marked augmentation of T cell proliferation and cytotoxic activity. Studies of CTL development in purified mitogen CD8+ T cells demonstrated that IL-7 and sCD23 could act directly on the CD8+ lymphocyte subset to augment cytotoxicity. The data demonstrate that IL-7 and sCD23 synergistically augmented CTL activity independently of IL-2 and IL-12. We analyzed the effects on IFN-gamma production by CD8+ T cells and found that IL-7 alone did not induce detectable levels of IFN-gamma production, but together with sCD23, it synergistically enhanced the production of IFN-gamma. We also found that IFN-gamma appeared not to be required for the enhanced CD8+ CTL activity because rabbit anti-IFN-gamma antibody did not block the synergistic effects of IL-7 and sCD23. These results indicate that IL-7 and sCD23 can exert major upregulatory effects on human CTL development and suggest that these effects are both proliferative and differentiative.