Very Rapid Improvement in Extended Nitric Oxide Parameters Is Associated With Clinical and Functional Improvement in Patients With Chronic Rhinosinusitis With Nasal Polyps Treated With Dupilumab.

BACKGROUND AND OBJECTIVE: Dupilumab, an anti-IL-4 receptor a monoclonal antibody, was recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate-to-severe asthma. Onset of its clinical effects is rapid. CRSwNP is characterized by extended type 2 inflammatory involvement that can be assessed using extended nitric oxide analysis. We investigated whether dupilumab was associated with a rapid improvement in extended nitric oxide parameters, lung function, and clinical outcomes in patients with CRSwNP. METHODS: Consecutive patients with CRSwNP and an indication for dupilumab were evaluated for extended nitric oxide analysis (exhaled, FeNO; bronchial, JawNO; alveolar, CalvNO; nasal, nNO) and lung function 15 and 30 days after initiation of treatment and for clinical outcomes (nasal polyps score [NPS], quality of life questionnaires, visual analog scale [VAS] for the main symptoms, and the Asthma Control Test [ACT]) 30 days after initiation of treatment. RESULTS: We enrolled 33 patients. All extended nitric oxide and lung function parameters improved significantly after 15 days of treatment, remaining stable at 30 days. Scores on the NPS, VAS for the main RSwNP symptoms, quality of life questionnaires, and the ACT improved significantly 30 days after initiation of treatment. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway areas. This is associated with improved lung function and clinical parameters in patients with CRSwNP.

Correlation Between Cervical Spine Sagittal Alignment and Clinical Outcome After Standalone Intersomatic Titanium Cage CeSPACE for Cervical Anterior Discectomy and Fusion in Cervical Degenerative Disk Diseases.

The aim of this study was to determine the relationship between cervical spine sagittal alignment and clinical outcomes after using a standalone intersomatic titanium cage CeSPACE for anterior cervical discectomy and arthrodesis. We present our clinical experience in a group of 180 patients with a mean follow-up for at least 2 years. Patients were evaluated by clinical and radiological assessment preoperatively, immediately after surgery and at regular follow-up. There were 97 male and 83 female patients (average age: 56.6 years) who were preoperatively affected by cervical radiculomyelopathy that was due to spondylosis or cervical disk herniation and who underwent surgical treatment. All patients underwent an anterior discectomy and interbody fusion through the positioning of one or more levels of the CeSPACE device. Compared with the preoperative scores, improvement was seen in postoperative visual analog scale (VAS) scores and Neck Disability Index (NDI) values. The standalone intersomatic titanium cage CeSPACE for anterior cervical discectomy and arthrodesis improved radiculomyelopathy and increased the probability of cervical kyphotic alignment. However, cervical sagittal alignment after surgery was not significantly associated with clinical outcomes in terms of postoperative improvement in VAS scores and NDI values. Similarly, the change in cervical sagittal alignment was not related to visual analog scale scores or Neck Disability Index values.

An investigation into the cytotoxic effects of microbubbles and their constituents on osteosarcoma and bone marrow stromal cells.

BACKGROUND: Ultrasound-responsive microbubbles offer a means of achieving minimally invasive, localised drug delivery in applications including regenerative medicine. To facilitate their use, however, it is important to determine any cytotoxic effects they or their constituents may have. The aim of this study was to test the hypothesis that phospholipid-shelled microbubbles are non-toxic to human bone-derived cells at biologically-relevant concentrations. METHODS: Microbubbles were fabricated using combinations of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dibehenoyl-sn-glycero-3-phosphocholine (DBPC), polyoxyethylene(40) stearate (PEG40S) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene-glycol)-2000] (DSPE-PEG2000). Microbubble size and concentration were measured as a function of time and temperature by optical microscopy. Effects on MG63 osteosarcoma and human bone marrow stromal cells (BMSCs) were measured for up to 72 h by assay for viability, metabolic activity and proliferation. RESULTS: DBPC:DSPE-PEG2000 microbubbles were significantly more stable than DSPC:PEG40S microbubbles under all conditions tested. Serum-containing medium had no detrimental effect on microbubble stability, but storage at 37 °C compared to at 4 °C reduced stability for both preparations, with almost complete dissolution of microbubbles at times ≥24 h. DSPC:PEG40S microbubbles had greater inhibitory effects on cell metabolism and growth than DBPC:DSPE-PEG2000 microbubbles, with PEG40S found to be the principle inhibitory component. These effects were only evident at high microbubble concentrations (≥20% (v/v)) or with prolonged culture (≥24 h). Increasing cell-microbubble contact by inversion culture in a custom-built device had no inhibitory effect on metabolism. CONCLUSIONS: These data indicate that, over a broad range of concentrations and incubation times, DBPC:DSPE-PEG2000 and DSPC:PEG40S microbubbles have little effect on osteoblastic cell viability and growth, and that PEG40S is the principle inhibitory component in the formulations investigated.

A case of Leishmania infection with focal splanchnic involvement without systemic symptoms: a potential anti-inflammatory role for vitamin D.

CASE REPORT: We report the case of a 59 year-old woman with persistent nausea, hyporexia, fatigue and mild abdominal discomfort. The patient was hospitalized upon suspicion of malignancy due to multiple hepatic and splenic nodules found on an abdominal ultrasound. Hypercalcemia emerged at initial diagnostic workup, which was considered secondary to iatrogenic vitamin D intoxication. After an adequate management of hypercalcemia and normalization of serum calcium level, all symptoms presented by the patient completely regressed. In order to characterize splanchnic lesions, several biochemistry, microbiology and radiological tests were performed, including two bioptic specimens of a focal hepatic lesion. Eventually, a diagnosis of leishmanial infection was made. The patient started a specific anti-leishmanial treatment, and the focal hepatic and splenic lesions progressively disappeared. CONCLUSION: To our knowledge, this is the first reported case of asymptomatic leishmanial infection with a widespread focal splanchnic involvement. The anti-inflammatory effect of vitamin D could be related to this atypical presentation of visceral leishmaniasis without systemic symptoms.

Very rapid improvement of extended nitric oxide parameters, associated with clinical and functional betterment, in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) treated with Dupilumab.

BACKGROUND AND OBJECTIVE: Background: Dupilumab, an anti-IL-4 receptor alpha monoclonal antibody, has been recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate to severe asthma, demonstrating a rapid onset of clinical effects. CRSwNP is characterized by an extended type-2 inflammatory involvement that can be assessed by extended nitric oxide analysis. Objective: In this study we investigated whether Dupilumab is associated with a rapid improvement in extended nitric oxide parameters, lung function and clinical outcomes in patients with CRSwNP. METHODS: : Consecutive patients with CRSwNP and indication to be treated with Dupilumab were evaluated for extended nitric oxide analysis (exhaled, FENO; bronchial, JawNO and alveolar, CalvNO components; nasal, nNO) and lung function 15 and 30 days after treatment initiation, and for clinical outcomes (nasal polyps score, NPS; quality of life questionnaires; visual analogue scales, VAS, for main symptoms, asthma control test, ACT) after 30 days of treatment initiation. RESULTS: 33 patients were enrolled. All extended nitric oxide and lung function parameters significantly improved after 15 days of treatment remaining stable at 30 days. NPS, VAS for main CRSwNP symptoms, quality of life questionnaires and ACT significantly improved after 30 days of treatment initiation. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway districts and this is associated with improved lung function and clinical parameters in patients with CRSwNP.

Vitamin D and disease severity in bronchiectasis.

BACKGROUND: Bronchiectasis is a complex respiratory disease characterised by permanent dilatation of bronchi. Vitamin D plays a role in infective disease by modulating the inflammation. Patients affected by bronchiectasis are frequently Vitamin D deficient and it correlates with lung function decline. We want to understand if there is a correlation between Vitamin D and clinical and radiological severity of bronchiectasis. METHODS: We included 57 patients (17 males/40 female with mean age 60 ±â€¯12 years) between October 2017 and March 2018. We excluded patients with cystic fibrosis, traction bronchiectasis and reporting Vitamin D supplementation. Bronchiectasis severity index (BSI) and Bhalla score were calculated, blood inflammatory markers and Vit. D were measured and lung function tests were performed. RESULTS: Vitamin D is deficient in 64% of patients, sufficient in 36% and normal in 7%. Mean BSI is 7.5 ±â€¯5 and mean Bhalla score is 16 ±â€¯4. Vitamin D levels correlate with Bhalla score (R2 = 0.68, p < 0.001) and BSI (R2 = 0.58, p < 0.0001). The correlation appears to be stronger than other markers of inflammation such as ESR and CRP [R2 = 0.33, p = 0.001 and R2 = 0.39, p = 0.001 respectively]. CONCLUSIONS: We consider Vitamin D as a good predictor of clinical and radiological severity of bronchiectasis.

[Modalities for access to networks of palliative care and pain management in Lazio: level of information for health personnel aware of the Policlinico Tor Vergata]. / Modalità per l'accesso alle reti di cure palliative e terapia del dolore nel Lazio: grado di informazione del personale sanitario del Policlinico Tor Vergata.

Law no. 38 of 2010 introduces for the first time protection for access to Palliative Care and Pain Management. It was interesting to evaluate the level of knowledge among health care workers at the Policlinico Tor Vergata, procedures relating to such access through the administration of a questionnaire. The questionnaire divided into a general part and the two sections (A and B) The general part concerns the health operator respect to age, gender, profession, and his role within the operating unit of the hospital. The section A and B, is to understand if the operator knows Palliative Care, and Pain Therapy, as he became aware of the two arguments, and if they have been addressed during the university courses he attended. The analysis of the data examined show a general confusion distributed evenly among all professionals. Is greater knowledge of pain therapy compared to Palliative Care.

Detailed analysis of the E2-IgM complex in hepatitis C-related type II mixed cryoglobulinaemia.

Hepatitis C virus (HCV) plays a major role in the induction of type II mixed cryoglobulinaemia (MCII). The role of HCV proteins and virus-host interaction in the pathogenesis of MC remains to be defined. To address this issue, we have characterized, in detail, the monoclonal IgM and the viral component of circulating immune complexes in eight patients with HCV-associated MCII. The proportion of HCV-RNA compartmentalized in the cryoprecipitate (CP) varied greatly (10-80% of total HCV-RNA). The complementary determining region (CDR)3 sequences of monoclonal immunoglobulin M (IgM) VH and VK genes were highly homologous to rheumatoid factor and to antibodies against HCV-E2. Furthermore, the CDR3 sequences in some of our MCII patients were highly similar to those described in HCV-positive patients with non-Hodgkin's lymphoma (NHL). From these results, it appears that, as in the case of NHL, the IgM-rheumatoid factor (RF) production in MCII patients is antigen driven, namely by E2. However, the limited number of mutations in VH and VK genes with respect to the germline and their distribution showed that the B-cell response in these cases was prevented from undergoing affinity maturation. Furthermore, in patients with monoclonal IgM and definite compartmentalization of HCV in either CP or supernatant, a highly homogeneous E2-hypervariable region (HVR)1 sequence distribution was found (90-100% identical clones), a feature of the quasispecies frequently associated with an impaired humoral immune response to HCV. These findings suggest that in patients with HCV-associated MCII, maturation of monoclonal B lymphocytes may be blocked in a primitive stage preventing serious damaging effects because of the auto-reactivity of their secreted immunoglobulins.

[Multinodular goiter as an organ disease: study of continual nodulogenesis. Biological bases indicating total thyroidectomy]. / Il gozzo multinodulare come malattia d'organo: studio della nodulogenesi incessante. Basi biologiche per l'indicazione alla tiroidectomia totale.

Multinodular goitre is a very common pathology among people especially female adult and represents more than 90% of the thyroid surgery. We analyzed 37 patients, demonstrating that the whole gland is progressively affected by an incessant nodulogenesis and we confirm the necessity of total thyroidectomy in order to eliminate any persistent pathology.

Estudo da involuçäo uterina por meio da ultra-sonografia (modo-B) em cadelas submetidas a cesariana / Ultrasonographyc study of the postpartum uterine involution in bitches after cesaerean section

Utilizaram-se 15 cadelas gestantes submetidas a cesariana e posteriormente a exames ultra-sonográficos seriados, em modo B (tempo real), para averiguaçäo do diâmetro uterino nos dias 0, 3, 7, 14 e 21 pós-cesariana, com o objetivo de verificar a influência do ato cirúrgico na involuçäo uterina. Os resultados (média e desvio-padräo, em centímetros) registrados para os dias estudados foram, respectivamente: 3,99+0,71; 3,27+0,51; 2,60+0,54; 2,01+0,34; 1,28+0,24. A involuçäo uterina pós-cesariana seguiu o mesmo padräo do puerpério do parto normal, assim como as características das imagens ultra-sonográficas. O parto cesariana näo influenciou no padräo de involuçäo uterina

Rayleigh scattering and redistribution of radiation in He I plasmas: measurements and calculations.

Conditions for which Rayleigh scattering and redistribution of radiation can be observed are examined. The competition between the relaxation processes and spontaneous emission is shown to determine the conditions for partial redistribution. We investigate specific cases in the singlet and triplet He I atomic system for plasma parameters reachable experimentally in a well diagnosed magnetic multipole source. Partial redistribution on the 2 1S-4 1P at 396.5 nm, 2 1P-5 1D at 438.8 nm, 2 3P-5 3D at 402.6 nm, 2 3P-4 3D at 447.2 nm and 2 3P-4 3S at 471.3 nm fine structure transitions is observed employing a dye laser pumping the He I plasma. We make use of a previously developed two-photon formalism based on the frequency fluctuation model to calculate radiative redistribution functions. Results of the partial redistribution measurements are presented, augmented by a comparison with calculations. This allows us to confirm available electron-atom elastic collision rates to within 20%.

Estudo ultra-sonográfico da involuçäo uterina pós-parto em cadelas / Ultrasonography study of the post-partum uterine involution in bitches

Utilizando-se 15 cadelas no pós-parto, säo descritas as características da involuçäo uterina e determinado o diâmetro do útero, por meio de exames seriados de ultra-som em modo B (tempo real), no período de zero a 28 dias pós-parto. O diâmetro uterino declina progressivamente, sem influência da ordem de parto ou tamanho da ninhada. As características ultra-sonográficas do útero säo melhor visualizadas na primeira semana pós-parto e a qualidade da imagem diminui com o progresso da involuçäo. Pela técnica usada sao visualizadas apenas três camadas constituintes da parede uterina

Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized study.

PURPOSE: Because interferon gave promising results in the management of metastatic renal cell carcinoma in the 1980s, a multicentric randomized controlled trial was planned to compare adjuvant recombinant interferon alfa-2b (rIFNalpha2b) with observation after radical nephrectomy in patients with Robson stages II and III renal cell carcinoma. Overall and event-free survival were to be evaluated together with prognostic factors. PATIENTS AND METHODS: Overall and event-free survival curves for 247 patients (124 controls and 123 treated) were estimated by the Kaplan-Meier method and compared using the log-rank test. Cox's multiple regression models were adopted to perform a joint analysis of treatment and prognostic factors. RESULTS: The 5-year overall and event-free survival probabilities were 0.665 and 0.671, respectively, for controls and 0.660 and 0.567, respectively, for the treated group; the differences were not statistically significant (2P = .861 for overall and 2P = .107 for event-free survival with the log-rank test). Regarding prognostic factors, only grade, pT, and pN demonstrated a significant prognostic role. First-order interactions of treatment with pT and pN category were investigated; a significant interaction was found between pN and treatment. A harmful effect of rIFNalpha2b in the 97 treated pN0 patients and a protective effect in the 13 treated pN2/pN3 patients were statistically significant. CONCLUSION: Adjuvant rIFNalpha2b is not indicated after radical nephrectomy for renal cell carcinoma. The protective effect in the small group of pN2/pN3 patients requires further investigation.

Nd:YAG laser surgery for the excision of pilonidal cysts: a comparison with traditional techniques.

BACKGROUND AND OBJECTIVE: Nd:YAG laser photothermal ablation has been accepted as a treatment modality for hemorrhoidal disease. There is little reported on its use in treating pilonidal disease. We hypothesized that laser would be an excellent tool for pilonidal cystectomy, facilitating improved outcome and patient satisfaction. STUDY DESIGN/MATERIALS AND METHODS: A 5-year retrospective study was performed comparing Nd:YAG laser to the standard surgical technique. A telephone questionnaire addressing the length of time the cyst was debilitating both preoperatively and postoperatively as well as length of convalescent time before return to work was administered. Pain was assessed by using an analog pain scale. RESULTS: Operative time for the traditional pilonidal cystectomy was 20 minutes longer than Nd:YAG laser cystectomy. Postoperative hospital stay was similar. Laser patients returned to work an average of 2.4 days earlier, and their postoperative pain was less than those treated traditionally. CONCLUSION: In an era when the medical consumer makes decisions based on the efficacy of treatment by using criteria such as pain, length of hospitalization, and speed of return to work, Nd:YAG lasers have emerged as a surgical tool that can fulfill these criteria for certain procedures. Patient postoperative satisfaction after laser excision was greater when compared with those who had traditional excisions. Postoperative pain was less, as was the pain experienced during the first week of recovery. Cost for both was comparable.

Haplotype HLA-B8-DR3 confers susceptibility to hepatitis C virus-related mixed cryoglobulinemia.

Our aim was to investigate whether host genetic factors are involved in the onset of hepatitis C virus (HCV)-related mixed cryoglobulinemia (MC). We studied 25 consecutive patients presenting with a full-blown clinical picture of MC by physical examination, blood chemistry, assessment of cryoglobulins and their composition, nonorgan-specific autoantibodies, antibodies to HCV, serum HCV RNA, and HLA polymorphism. Biopsies of liver, bone marrow, and minor salivary glands were also performed in a number of patients. HLA results were compared with those of normal controls and patients with chronic HCV infection without MC and negative for autoimmune phenomena (pathological controls). Type II MC was found in 14 of 25 patients (56%), and type III MC was found in the remaining 11 (44%). All patients were positive for antibodies to HCV and/or serum HCV RNA. HLA-B8 was found in 40% (10 of 25) of patients compared with 10. 1% (38 of 377) of normal controls (P = .00003, Pcorrected = .0005, relative risk [RR] 5.9) and 6.7% (2 of 30) of pathological controls (P = .007, Pcorrected = not significant). As for class II HLA molecules, only DR3 was significantly more frequent in MC patients (40%, 10 of 25) than in normal controls (15.1%, 57 of 377; P = .003, Pcorrected = .03, RR 3.7). Odds ratio (OR) for the risk of developing MC was calculated in patients positive for B8 and/or DR3, and the highest OR (8.2) was observed in individuals possessing both. The results suggest that the development of HCV-related MC is associated with HLA-B8 and DR3 markers.

Calcific chronic lateral epicondylitis: a histological and ultrastructural study.

Fragments of insertion tissue from right arm common extensor muscle have been collected from a 25-year patient with chronic lateral epicondylitis. Specimens, processed for light (LM) and electron (EM) microscopy, evidentiated a variety of degenerative alterations, such as focal hyalinosis, lipoidosis, collagen fiber redistribution, calcifications and vascular changes. Evidence of collagen normal function maintenance and turnover have been also observed in tenocytes.

Isolated peripheral enthesitis and/or dactylitis: a subset of psoriatic arthritis.

OBJECTIVE: To identify isolated peripheral enthesitis and/or dactylitis as a subset of psoriatic arthritis (PsA) and to define the clinical characteristics of these patients. METHODS: We examined 401 unselected patients with PsA seen in 3 Italian rheumatological centers over a 6 month period. The diagnosis of PsA was based upon the clinical experience of a rheumatologist. The clinical features of patients with PsA were assessed by clinical examination and review of the patients' charts, evaluating the presence of peripheral arthritis, spinal involvement, dactylitis, and enthesitis. A series of 483 rheumatological patients without psoriasis and spondyloarthropathy (European Spondylarthropathy Study Group criteria) seen consecutively in a one month period constituted the control group. RESULTS: 14 patients (3.5%) presented isolated episodes of peripheral enthesitis and/or dactylitis. No patient developed peripheral arthritis and/or axial involvement during the followup period (median 30 mo; range 3-72 mo). 10/14 patients (71%) presented at least one episode of finger and/or toe dactylitis. 5 of these 10 patients (50%) had additional episodes of peripheral enthesitis (Achilles tendinitis, plantar fasciitis, and posterior tibial tendinitis). Episodes of Achilles tendinitis and/or plantar fasciitis were present in 8/14 patients (57%). 3 of these 8 patients (37%) had associated peripheral enthesitis in other sites as well: lateral epicondyle, insertion of the patella tendon into the inferior pole of the patella, femoral quadriceps, and posterior tibial tendons. An additional case had posterior tibial tendinitis and 2 episodes of toe dactylitis. None of these 14 cases presented radiological evidence of sacroiliitis and only one of the 13 typed was HLA-B27 positive. 12 patients (2.4%) of the control group had episodes of peripheral enthesitis (11 plantar fasciitis and one Achilles tendinitis). No patient had episodes of dactylitis. The frequency of isolated Achilles tendinitis and/or dactylitis was significantly higher in patients with PsA compared to controls (3.5 vs 0.2%; p = 0.001). CONCLUSION: In some patients PsA can occur only with peripheral enthesitis, particularly Achilles tendinitis, and/or dactylitis. These patients may represent a subset of PsA, not defined by Moll and Wright and spondyloarthritis classification criteria, and poorly recognized in the studies on PsA.

[Role of hyperbaric oxygen in the treatment of necrotizing infections of the soft tissues]. / Ruolo dell'ossigeno iperbarico nel trattamento delle infezioni necrotizzanti dei tessuti molli.

The Authors report their experience in the treatment of soft tissue necrotizing infections. The correct "timing" of the association of surgery, antibiotics and hyperbaric oxygen therapy is stressed. The good clinical results obtained in the patients examined confirm the usefulness of an early treatment modulated according to the needs of each single patient.

Kindled seizure-induced c-fos and prodynorphin mRNA expressions are unrelated in the rat brain.

Levels of mRNA for c-fos and prodynorphin were studied by in situ hybridization in adjacent coronal sections taken from kindled rats 30-60 min after the last seizure. Within this time frame, expression of both genes was induced in multiple brain areas. Anatomical colocalization of the induced gene expressions was found in the hippocampus. Induction of c-fos in the dentate gyrus was bilateral and symmetrical in a subgroup of rats, ipsilateral in another subgroup and absent in a third subgroup. However, no relative increase was observed in the ipsilateral compared with the contralateral prodynorphin expression in the dentate gyrus when c-fos expression was induced ipsilaterally only. These observations suggest that, at variance with other experimental situations, Fos is not involved in the mechanisms of kindled seizure-induced activation of prodynorphin transcription in the rat forebrain.