Search

ObjectiveSepsis and septic shock are major challenges and economic burdens to healthcare, impacting millions of people globally and representing significant causes of mortality. Recently, a large number of quality improvement programs focused on sepsis resuscitation bundles have been instituted worldwide. These educational initiatives have been shown to be associated with improvements in clinical outcomes. We aimed to evaluate the impact of a multi-faceted quality implementing program (QIP) on the compliance of a “simplified 1-h bundle” (Sepsis 6) and hospital mortality of severe sepsis and septic shock patients out of the intensive care unit (ICU).MethodsEmergency departments (EDs) and medical wards (MWs) of 12 academic and non-academic hospitals in the Lombardy region (Northern Italy) were involved in a multi-faceted QIP, which included educational and organizational interventions. Patients with a clinical diagnosis of severe sepsis or septic shock according to the Sepsis-2 criteria were enrolled in two different periods: from May 2011 to November 2011 (before-QIP cohort) and from August 2012 to June 2013 (after-QIP cohort).Measurements and main resultsThe effect of QIP on bundle compliance and hospital mortality was evaluated in a before–after analysis. We enrolled 467 patients in the before-QIP group and 656 in the after-QIP group. At the time of enrollment, septic shock was diagnosed in 50% of patients, similarly between the two periods. In the after-QIP group, we observed increased compliance to the “simplified rapid (1 h) intervention bundle” (the Sepsis 6 bundle – S6) at three time-points evaluated (1 h, 13.7 to 18.7%, p = 0.018, 3 h, 37.1 to 48.0%, p = 0.013, overall study period, 46.2 to 57.9%, p

Purpose: Sinonasal mucoceles (SM) are benign, expansive neoformations which require surgical marsupialization to prevent severe complications. The present study reports the larger case history ever published: a 28-years expertise in the surgical management of SM., Methods: A retrospective study was conducted on patients surgically treated for SM at the Departments of Otorhinolaryngology of Varese and Pavia, between 1994 and 2022., Results: 398 patients were reported. An endoscopic endonasal marsupialization of SM was performed in 92,5% of cases. 7% of patients underwent a combined approach while 0,5% required an exclusive open surgery. The average follow-up after surgery was 10-60 months. SM overall recurrence was observed in 11,4% of cases., Conclusion: Endonasal endoscopic SM marsupialization is a feasible technique which allows the preservation of the anatomy and physiology avoiding the surgical invasiveness of the external approaches. The well-established surgical expertise in the endonasal endoscopy together with technological improvements widened the indication range of the exclusive endoscopic technique over the traditional open surgery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Intranasal corticosteroids (INCs) are the first line of therapy for chronic sinonasal conditions such as rhinitis and rhinosinusitis. Among these, one of the most frequently used is beclomethasone dipropionate (BDP). Over the years many studies have evaluated the efficacy of BDP as part of therapy for chronic rhinosinusitis (CRS) and allergic rhinitis (AR) along with nasal washes, which seems to be very well tolerated., Objective: To analyse the data in the literature regarding the various therapeutic regimens of BDP in different sinonasal disease and their efficacy and tolerability., Materials and Methods: Using different search engines, the posology, efficacy, and tolerability of BDP were reviewed and a total of 64 full-length articles were examined for eligibility. After applying inclusion and exclusion criteria, 4 articles were reviewed., Results: BDP is among the group of INCs with significant improvement of nasal symptoms and has good efficacy and safety., Conclusions: BDP nasal spray is one of the most frequently prescribed INC for rhinitis and rhinosinusitis. Treatment with BDP resulted in significant and clinically meaningful improvements in nasal symptoms associated with AR and CRS. BDP is well tolerated, and the safety profile is similar to that of placebo in most patients. These results, in conjunction with the significant benefit reported in subjects with CRS and AR, provide convincing evidence of the overall effectiveness of BDP for the treatment of the full spectrum of sinonasal disease., (Copyright © 2024 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Kaposi's sarcoma (KS) is an angioproliferative disease characterized by proliferation of neoplastic cells (spindle cells) mixed with endothelial and inflammatory cells. In this study we evaluated the role of the adhesive glycoprotein, fibronectin (FN) and its receptor alpha(5)beta(1) (FNR), and the proto-oncogene bcl-2, an anti-apoptotic protein. Significantly decreased serum levels of FN were noted in HIV-1-infected patients with KS, whereas serum levels of FNR were significantly increased in the same patients. Furthermore, increased FNR expression was observed on CD4 cells from KS patients. Serum levels of bcl-2 protein were significantly decreased in asymptomatic seropositive patients, whereas HIV-1-infected patients with KS showed increased serum levels of bcl-2. These results provide further information about interaction between integrins and the extracellular matrix and bcl-2 protein that can support cell survival either of neoplastic cells or endothelial and inflammatory cells.

Purpose: To assess the safety and efficacy of vinorelbine in patients with AIDS-related Kaposi's sarcoma (KS)., Patients and Methods: From December 1994 to May 1997, within the Italian Cooperative Group on AIDS and Tumors, we enrolled 36 patients with AIDS-related KS who experienced disease progression after one or more regimens of systemic chemotherapy. Patients were treated with vinorelbine 30 mg/m(2) every 2 weeks by intravenous bolus., Results: Of 35 assessable patients, three (9%) had a clinical complete response and 12 (34%) had a partial remission, for an overall objective response rate of 43% (95% confidence interval, 26% to 61%). For the 15 patients with objective responses, the median duration of response from the beginning of therapy until the development of progression was 176 days, whereas the median progression-free survival and the median survival durations for 35 assessable patients were 151 days and 216 days, respectively. Vinorelbine also induced responses in patients who had become resistant to regimens that included other vinca alkaloids. Overall, vinorelbine was well tolerated. Toxicity, including neurologic toxicity, was mild and reversible. Neutropenia was the most frequent dose-limiting toxicity., Conclusion: Vinorelbine is safe and effective in the treatment of patients with advanced KS who have been previously treated with one or more chemotherapy regimens.

The production of nitric oxide (NO) by macrophages is important for the killing of intracellular pathogens, such as Toxoplasma gondii. Gamma interferon (IFN-gamma) and lipopolysaccharide stimulate NO production. The aim of this study was to investigate the importance of NO, IFN-gamma and interleukin-12 (IL-12) in the host immune response in AIDS patients suffering from toxoplasmic encephalitis (TE). It was demonstrated that the production of NO, detected as nitrite/nitrate in the sera and in the cerebrospinal fluid (CSF) of 32 AIDS patients with TE, was normal. In addition, levels of IFN-gamma in the sera and in the CSF of patients with TE were not increased. In contrast, serum levels of IL-12 in these patients were significantly increased (6.5 +/- 7.1 pg/ml; P = 0.0368), compared to the control patients (1.7 +/- 3.5 pg/ml). Furthermore, increased but not significant levels of IL-12 were also observed in the CSF of patients with TE (2.2 +/- 4.7 pg/ml; controls: 0.5 +/- 1.9 pg/ml). The results of this study indicate that reactivation or recurrence of T. gondii infection in HIV-1-infected patients is probably due to a down-regulation of IFN-gamma along with a resulting non-optimal NO activity.

Objective: To describe the epidemiologic and clinical features of AIDS-associated Kaposi's sarcoma (KS) in women compared with men., Methods: In a retrospective study, within the Italian Cooperative Group on AIDS and Tumors (GICAT), we compared selected characteristics of 54 women and 108 men with AIDS-associated KS, matched by date of KS diagnosis and referral hospital. The chi2 test was used to test differences among proportions; the Kaplan-Meier method to estimate the survival time, and the Cox proportional hazard model was used to assess the role of gender, age, and CD4 cell count on death's risk., Results: KS occurred at an earlier age (p = .001), was associated with a more severe immunodeficiency (p = .03), more advanced stages of HIV disease (p = .05), and had more aggressive presentation and course in women than in men. At KS diagnosis, women had a significantly increased proportion of visceral disease (p = .009), in particular pulmonary involvement (p = .002) and atypical sites of involvement (p = .008). The number of deaths due to KS was significantly higher (p = .01) in female patients. Both the higher proportion of visceral disease and of KS-related deaths observed in women did not change after adjusting for CD4 cell count and age. Women showed a decreased overall survival compared with men (8.9 and 14.4 months, respectively; p = .07), and the CD4 cell count at diagnosis significantly influenced survival., Conclusions: This study suggests that KS is more aggressive and life threatening in female than in male patients. This peculiar clinical behavior may reflect an inherently more aggressive biology of KS in women, possibly mediated by the level of immunodeficiency.

To evaluate the efficacy and safety of Amphotericin B dissolved in dextrose (Amb) or in a lipid emulsion (Intralipid, Amb-IL) in AIDS patients with cryptococcal meningitis, we conducted a retrospective study in 30 AIDS patients with cryptococcal meningitis. A clinical complete resolution was obtained in 11 patients (55%) treated with Amb, and in six patients (60%) treated with Amb-IL. Intralipid did not decrease the infusion-related adverse effects, in particular nephrotoxicity and anaemia. Our results indicate that Amb-IL formulation is useful in the treatment of cryptococcal meningitis in AIDS patients, but it does not reduce the infusion-related adverse events.

Aims of the Study: a retrospective study was designed to evaluate efficacy and tolerance of trimethoprim-sulphamethoxazole (TMP-SMZ) in AIDS patients with cerebral toxoplasmosis (TE)., Patients and Methods: we reviewed 471 patients with AIDS, and we analysed 71 AIDS patients with TE, who received intravenous therapy with TMP-SMZ (TMP: 10 mg/kg/day, SMZ: 50 mg/kg/day) for 4 weeks., Results: 35 patients (49.2%) had a complete regression of clinical signs, and a complete resolution of radiological lesions was noted in 41 patients (57.7%). Improvement of clinical signs and radiological lesions were observed in 27 patients (38%), and in nine patients (12.6%), respectively. In contrast, nine patients (12.6%) did not show any clinical change, or worsened. Twenty-two patients (30.9%) suffered from adverse cutaneous reactions, whereas many patients had haematological toxicity., Conclusions: TMP-SMZ seems to be an efficient therapy for TE in AIDS patients, although further prospective, randomized therapeutic trials are required to confirm these results.

Apoptosis of CD4-positive T cells is considered to be involved in depletion of CD4-positive T cells in adult patients with HIV-1 infection. In this report we evaluated serum levels of soluble Fas/Apo-1 and circulating bcl-2 protein (an antiapoptotic molecule) in HIV-1-infected children, and 30 HIV-1 seronegative children. Significantly higher levels of Fas/Apo-1 were observed in 13 HIV-1-infected children than in non-infected control children (p < 0.001), whereas serum levels of bcl-2 were significantly decreased (p=0.002). Seronegative children born to HIV-infected mothers displayed significantly decreased (p < 0.05) serum levels of bcl-2. By contrast, children born to HIV-seronegative mothers and suffering from acute lower respiratory infection had normal levels of bcl-2 and Fas/Apo-1. These data suggest that upregulation of Fas/Apo-1 along with downregulation of bcl-2 protein may contribute to apoptosis in children with HIV-1 infection.

Objective: To compare the pharmacokinetics of foscarnet administered as an infusion twice daily (BID) or thrice daily (TID), and to compare the effects on the electrolyte balance, cardiac and renal functions over a 3-week induction treatment of Cytomegalovirus (CMV) retinitis., Methods: Pharmacokinetics/dynamics of foscarnet were investigated on treatment days 1, 14 and 21. Twelve AIDS patients with CMV retinitis completed the investigation period. Concentrations of foscarnet and electrolytes were assayed by high-performance liquid chromatography (HPLC) and by an ion-selective analyser, respectively., Results: The pharmacokinetics of the two regimens were essentially similar. Foscarnet plasma and creatinine clearances were 2.0 and 1.6 ml.min-1.kg-1, respectively, in the BID group at steady state (day 21). In the TID group the corresponding values were 1.8 and 1.7 ml.min-1.kg-1, respectively. In both regimens the elimination half-life of foscarnet was 2-3 h. Ionized calcium concentrations were transiently decreased and strongly inversely correlated to foscarnet plasma concentrations in both regimens with no significant differences between groups. A trend towards prolongation of the QTc interval was seen when data from both treatments were analysed together., Conclusion: Our data suggest comparable pharmacokinetics of foscarnet after intermittent administration BID or TID during a 3-week induction period.

Aims: To measure circulating concentrations of nitrite in patients with HIV-1 infection., Methods: Nitrite concentrations were measured using the Griess reaction adapted to microtitre plates in the serum of 10 asymptomatic HIV-1 positive patients, 33 patients with AIDS with cerebral disorders, 17 patients with AIDS with pulmonary involvement, and in eight patients with AIDS with other disorders. Nitrite concentrations were also measured in bronchoalveolar lavage (BAL) fluid and cerebrospinal fluid (CSF) of patients with AIDS with pulmonary involvement and cerebral disorders, respectively., Results: Increased serum concentrations of nitrite were observed in patients with pulmonary involvement, and in particular in serum and in BAL samples of patients with interstitial pneumonia (36.2 (26.2) mumol/l and 0.3 (0.4) mumol/l, respectively). Increased serum concentrations of nitrite were also noted in patients with retinitis caused by infection with cytomegalovirus. Serum nitrite concentrations were also raised in patients with cerebral toxoplasmosis, whereas normal serum concentrations were found in patients with HIV-1 encephalopathy and cryptococcal meningitis. Nitrite concentrations in CSF were not raised in patients with cerebral disorders., Conclusions: These results suggest that production of nitrite in patients with AIDS with concomitant opportunistic infections may be part of the host defense against opportunistic organisms.

Nitric oxide (NO) is a newly discovered gas that plays an important role in cell communication and host resistance to infection. The production of NO was examined in the sera of seven children infected with human immunodeficiency virus type 1 (HIV-1) and in the sera of 14 children who became seronegative for HIV-1 during the first year of life. In addition, we determined serum levels of various cytokines, such as interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, and gamma interferon (IFN-gamma), inasmuch as these cytokines are potent inducers of NO production. Production of NO, detected as circulating serum levels of nitrite, was measured with use of the Griess reagent. Serum levels of cytokines were determined by enzyme immunoassay. Increased serum levels of nitrite were observed in children with HIV-1 infection (0.4 +/- 0.2 mumol/L; P = .013), and in those who became seronegative for HIV-1 during the first year of life (0.5 +/- 0.3 mumol/L; P = .04). Furthermore, serum levels of IL-1 beta and TNF-alpha were significantly elevated in children with HIV-1 infection (37.5 +/- 23.6 pg/mL and 91.2 +/- 45.1 pg/mL, respectively). Prophylactic administration of intravenous immune globulin provoked a significant decrease of circulating levels of nitrite in children with HIV-1 infection. In conclusion, NO may play a role as a cytostatic or cytotoxic factor for invading microorganisms, and thus it is probably involved in limiting and/or eradicating infection.

Aim: To determine concentrations of fibronectin and fibronectin receptor in children with pertussis., Methods: Concentrations of circulating fibronectin and serum fibronectin receptor were detected in eight children affected by pertussis, eight children with acute upper or lower respiratory tract infections, and in 14 healthy control children. The single radial immunodiffusion technique and a solid phase enzyme immunoassay were used to detect circulating serum concentrations of fibronectin and fibronectin receptor., Results: On admission, a significant decrease in fibronectin was detected in children with pertussis (p = 0.0006). Significant and decreased concentrations of fibronectin were also observed in children with upper or lower respiratory tract infections (p = 0.0002). On the other hand, serum fibronectin receptor concentrations were significantly increased in patients with pertussis, whereas patients with upper or lower respiratory tract infections had normal circulating fibronectin receptor concentrations., Conclusions: Fibronectin deficiency in children with pertussis may be related to diffusion and deposition of this protein in bronchial and alveolar spaces to limit infection, while increased fibronectin receptor concentrations are probably the expression of T cell activation and cell-mediated immunity during Bordetella pertussis infection.

Meningeal involvement in leptospiral infection is quite common, usually mild and often overlooked. In contrast, cases of isolated involvement of the central nervous system, including aseptic meningitis, have been reported only rarely. A case of a patient with acute aseptic meningitis caused by Leptospira australis serovar bratislava is reported. This is believed to be the first report of aseptic meningitis due to Leptospira australis. This case indicates the need to consider human leptospirosis in the differential diagnosis of aseptic meningitis.

We found a significant increase in fibronectin receptor (FNR) levels in the sera of adult human immunodeficiency virus type 1 (HIV-1)-infected patients, especially in those with AIDS (1,026.9 +/- 583.9 ng/ml; P < 0.0001). In contrast, AIDS patients with neurologic disorders and HIV-1-seropositive patients showed normal levels of FNR in serum. In addition, HIV-1-infected children showed increased levels of FNR in serum (824.4 +/- 333.5 ng/ml; P = 0.03). We suggest that an increase of FNR levels in AIDS patients is related to enhanced expression of FNR on HIV-1-infected cells.

Serum levels of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in patients with acute viral hepatitis were investigated. Twelve patients suffering from acute viral hepatitis were studied; 8 patients presented with acute hepatitis B, 2 patients with acute hepatitis A, and 2 patients with acute hepatitis C. Serum levels of IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha were significantly increased in all patients with acute viral hepatitis. Decreased serum levels of all cytokines were noted in four patients with acute hepatitis B during the recovery phase of infection. In addition, IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha were undetectable at the end of a follow-up period of 6 months. Our study shows that increased levels of IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha are probably related to hepatitis activity and thus may have some role in hepatocytic injury.

Fibronectin (FN) is present in soluble and matrix forms in various body fluids and tissues, and has been shown to bind to several pathogens, including viruses. The interaction of FN with viral proteins of human immunodeficiency virus (HIV-1) was investigated by immunofluorescence technique using a cell line chronically infected with HIV-1 (H9-V). The results of this study showed that FN binds to HIV-1 infected cells, especially at FN concentration of 5 micrograms/ml. In addition, FN-pentapeptide has shown the ability to bind to HIV-1 infected cells. On the other hand, preincubation with antibodies against FN abolished the binding of FN to HIV-1 infected cells. Finally, FN has shown to bind to HIV-1 glycoproteins, including gp41 and gp120. In contrast, no binding to HIV-1 core proteins, including p15 and p24, was noted. We suggest that FN, in binding HIV-1 particles, may reduce viremia and thus may be involved in the clearance of viral proteins from the cells.

Aims: To evaluate the fibronectin concentrations in the cerebrospinal fluid of HIV-1 infected patients with central nervous system disorders., Methods: Fibronectin was determined by an immunoturbidimetric assay in 41 HIV-1 infected patients with AIDS dementia complex, progressive multifocal leucoencephalopathy, and opportunistic infections., Results: A significant decrease in fibronectin concentrations in the cerebrospinal fluid of patients with AIDS and dementia complex and progressive multifocal leucoencephalopathy was observed, as well as in those with opportunistic infections of the central nervous system (p < 0.0001). In particular, a significant decrease in fibronectin concentration in cerebrospinal fluid was observed in patients with cerebral toxoplasmosis and cryptococcal meningitis (p < 0.0001)., Conclusions: Because fibronectin can bind to several viruses, fungi, and protozoa, it is conceivable to suppose that the consumption of fibronectin in the cerebrospinal fluid of patients with neurological disorders may be related to the binding of fibronectin to HIV itself, or to viral proteins, or to organisms responsible for opportunistic infections.

Pertussis toxin (PT) has been previously shown to affect a wide variety of immune responses and to cause lymphocyte proliferation. In this study, we examined the effect of PT on cultured human peripheral blood lymphocytes and monocytes with the regard to the capability of this toxin to stimulate the production and release of various cytokines. PT was found to induce the production and release of Tumor Necrosis Factor alfa (TNF-alfa) and Interleukin-6 (IL-6) by both human lymphocytes and monocytes and IL-1 (IL-1B) beta by human monocytes in culture. Most activities of PT in vitro were achieved at the optimal concentration range of 1-0.01 microgram/ml, which is responsible for the adjuvant effect of PT in vivo. Since TNF-alfa, IL-1 beta and IL-6 are potent mediators of inflammation, the production and release of these cytokines by PT and Bordetella pertussis itself may play an important role in antibacterial defenses against such infection.

Objective: To determine serum levels of acute-phase proteins and interleukin 1B, interleukin 6, tumor necrosis factor alpha, and interleukin 8 in children with pertussis., Design: Cross-sectional study., Setting: Divisions of Infectious Diseases, Regional Hospital, and Pediatrics, University of Pavia, Varese, Italy., Participants: Eight children with pertussis, six with acute febrile infections, and eight healthy control children matched for sex, age, and time presentation over a 32-month study period., Interventions: None., Measurements/main Results: An immunoenzymatic assay was used to detect serum levels of all cytokines. Normal values of C-reactive protein, alpha 1-acid glycoprotein, and erythrocyte sedimentation rate were observed in the serum of patients with pertussis. The mean (+/- SD) detectable levels of tumor necrosis factor alpha (65.0 +/- 50.4 pg/mL) and interleukin 6 (32.3 +/- 17.8 pg/mL) were observed in the serum of patients with pertussis. In contrast, a nonsignificant increment of interleukin 1B levels (66.5 +/- 83.7 pg/mL) and interleukin 8 levels (12.7 +/- 17.8 pg/mL) was noted in the serum of the same patients. Increased and significant levels of all four cytokines were noted in most of the serum samples of patients with acute febrile infections., Conclusions: Acute-phase response is absent in patients with pertussis, whereas detectable and significant serum levels of tumor necrosis factor alpha and interleukin 6 were observed in some such patients.