Interstitial lung disease in patients enrolled in early-phase clinical trials: the ILDE study.

BACKGROUND: Interstitial lung disease (ILD) encompasses a heterogeneous group of disorders sharing pathophysiological inflammatory mechanisms, leading to parenchymal distortions. The prevalence of ILD with new cancer drugs is underreported: the identification of potential determinants is priority. MATERIALS AND METHODS: ILDE is a retrospective study aimed at describing the clinical course and potential determinants of ILD in patients receiving experimental treatments. RESULTS: We identified 226 eligible patients, of whom 5.3% (n = 12) had ILD. In five patients, the diagnosis was radiological, while seven patients had initial cough, dyspnea, fatigue or fever. ILD was graded as grade 1 (G1) in four, G2 in five and G3 in three patients. The first occurrence of ILD resolved completely in 50% of patients (n = 6/12). No patient had fatal ILD. Eight patients (66.7%) resumed the treatment after the first episode of ILD, while four patients (33.3%) had to discontinue the therapy. Five out of six patients had resolved the first ILD episode and then resumed treatment, experiencing a second ILD episode (n = 5/6; 83.3%). The second ILD event was G1 in three patients and G2 in two patients, resulting in three patients who eventually discontinued the treatment (n = 3/5; 60%). Correlation analysis showed a higher risk of ILD in older patients (P = 0.051), those who had received previous chest radiation therapy (P = 0.047) or those receiving antibody-drug conjugates (P = 0.006). In a survival analysis adjusted for immortal time bias, ILD was not independently prognostic (hazard ratio 0.50, 95% confidence interval 0.23-1.09, P = 0.082). CONCLUSIONS: In ILDE, patients experiencing ILD had generally good outcomes, and many could resume the cancer treatments. Implementing best practices to prompt diagnosis and management of ILD is critical to treat a potentially severe adverse effect of new drugs, while not affecting patients' outcomes. Research efforts to identify risk factors is warranted, to implement risk-based monitoring schedules and develop ad hoc strategies to improve the cure rates of ILD.

Geographical differences in chronic obstructive pulmonary disease mortality trends by sex, Spain, 1980-2021.

BACKGROUND: To analyse changes in trends in mortality due to chronic obstructive pulmonary disease (COPD) in Spain by Autonomous Community (AC) and sex during the period 1980-2021.METHODS: Data on population and COPD death records (International Classification of Diseases, 10th edition, codes J40â-"J44 and J47) were retrieved from the National Institute of Statistics for the study period. Age-standardised mortality rates by AC and sex were assessed using joinpoint regression models.RESULTS: There were 562,668 deaths due to COPD (423,855 in men and 138,813 in women), with an average annual increase of 1.6%. COPD deaths in men increased in most ACs, except for Asturias (â-"0.5% per year). The Canary Islands (14% per year) and Madrid (6.5% per year) had the highest increases. In women, the figures show a wide range of values at the AC level (from a â-"1.4% decrease to 7.9% increase). Nationally, the sex ratio increased from 1980 to 2021. In men, six ACs showed a significant decrease, while in women only two ACs showed a significant decrease.CONCLUSION: A steady decrease in COPD mortality was observed in most ACs for men, while a different trend was observed in women in several ACs. Despite past and ongoing tobacco control initiatives, this condition remains a leading cause of death.

Automated Intelligent Microscopy for the Recognition of Decoy Cells in Urine Samples of Kidney Transplant Patients.

BACKGROUND: BK virus (BKV)-associated nephropathy is definitely involved in allograft failure after kidney transplant. Thus, the need for an early control of viral reactivation in immunocompromised patients is well established. Determination of urinary release of decoy cells (DC) and BK viral load in plasma and urine by polymerase chain reaction (PCR) usually precedes renal biopsy. The aim of the study is to assess viral reactivation by BKV-DNA PCR and DC detection in urinary sediment using automated intelligent microscopy. METHODS: Seventy-eight kidney transplant patients were analyzed for the presence of plasma BKV-DNA by quantitative TaqMan real-time PCR. Additionally, automated intelligent microscopy was used for urine sediment analysis, allowing to count cells with decoy feature, confirmed by phase contrast microscopic review. RESULTS: Plasma BKV-DNA PCR was detected in 14 (17.9%) patients. DC were identified in 19 (24.3%) urine sediments by automated analyzers and confirmed by microscopic observation. Two patients were BKV-DNA-positive/DC-negative; conversely, 7 subjects were DC-positive/BKV-DNA-negative. CONCLUSIONS: Plasma quantification of BK viral load is currently the best noninvasive method for the detection of viral reactivation. Nevertheless, automated methods to screen for the presence of DC in urine could facilitate early BK virus replication diagnosis and patient follow-up by quantitative and visual results.

Detection and quantification of EBV, HHV-6 and CMV DNA in the gastrointestinal tract of HIV-positive patients.

Human herpes viruses (HHVs) have been frequently detected in the gastrointestinal (GI) tract and may contribute to the development of gastric cancer. In the present study, the detection rate and viral load of Epstein Barr virus (EBV), HHV-6 and Cytomegalovirus (CMV) were assessed in the GI tract of human immunodeficiency virus (HIV) positive patients and of uninfected patients. The analysis revealed a significantly higher detection rate of EBV and HHV-6 in HIV-infected individuals than in uninfected subjects (88.5 vs 63%; p = 0.03). Moreover, EBV DNA load was significantly higher in the stomach of HIV patients than in controls. These data suggest that the HIV infection status may increase the persistence of these viruses in the GI compartment. Intriguingly, CMV DNA was undetectable in all biopsy specimens analyzed.

Multiplex polymerase chain reaction for the evaluation of cytomegalovirus DNA load in organ transplant recipients.

Because of the considerable impact of human cytomegalovirus (HCMV) infection, sensitive, specific, and standardized methods are required for rapid and accurate evaluation of viral load in monitoring transplant recipients. The aim of the present study was to evaluate the usefulness of a multiplex polymerase chain reaction (PCR) for the coamplification of HCMV-DNA and beta-globin genomic sequence in polymorphonuclear leukocytes (PMNL). Analysis and quantification of PCR products were carried out by a DNA enzyme immunoassay (DEIA), which is based on the hybridization of amplified DNA with a single-stranded DNA probe, which coats microtitre wells. Colorimetric detection of the DNA-antibody complex was carried out and optical density (O.D.) was recorded at 450/630 nm. To quantify HCMV/DNA load, a standard curve to which samples O.D. refer was obtained by amplifying serial dilutions of recombinant PGEM-3Z plasmid DNA containing a genomic fragment of glycoprotein B. 340 PMNL specimens from 102 solid organ recipients were tested for the detection of pp65 antigen and HCMV-DNA. The results showed a good correlation between viral load and clinical symptoms of HCMV infection; high specificity and predictive values for HCMV disease were found by PCR, using a cut-off limit of 10(3) genomic copies per 2 x 10(5) PMNL. These findings indicate that the system described is an efficient and reproducible diagnostic method easy to apply for routine diagnosis and therapeutic monitoring of transplanted patients.

Differential effect of human and murine polyclonal and monoclonal antisera on TNF-alpha production by human monocytes.

The capacity of human and murine polyclonal and monoclonal antibodies to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) release from human monocytes was investigated. Human pooled immunoglobulin G (IVIG), human IgM monoclonal antibody (HA-1A) directed against the lipid A moiety of LPS, and murine IgG monoclonal antibody (MT-1F) raised in mice against antibiotic-treated Escherichia coli O6:K- were either added simultaneously with LPS to monocytes or preincubated for 1 h at 37 degrees C before being added to monocytes. TNF-alpha content in the monocyte supernatants was then tested. Simultaneous addition of increasing concentrations of IVIG (from 0.3 to 2.5 mg/ml) and 10 micrograms/ml of LPS to monocytes induced an enhanced release of TNF-alpha by monocytes in a dose dependent fashion. Preincubation of IVIG with LPS abolished the additive effect, but did not inhibit LPS-induced TNF-alpha release by monocytes. The simultaneous addition of LPS and HA-1A to monocytes had no additive effect nor did it inhibit TNF-alpha release. On the other hand, inhibition of TNF-alpha release was observed when HA-1A was preincubated with LPS before being added to monocytes. In all instances MT-1F inhibited TNF-alpha release when the monocytes were stimulated with smooth type LPS, but not with LPS isolated from rough mutants.

Effect of intravenous immunoglobulin on opsonic activity and TNF production in patients at high risk for sepsis syndrome.

In a randomized double blind study, we analyzed the efficacy of IVIG in the infectious complications in patients at high risk of developing sepsis syndrome. Two groups of twenty patients were enrolled, one receiving 250 mg/Kg of IVIG on the first and seventh day after admission and the other receiving sterile saline as placebo. Serum samples were drawn before IVIG administration and 24, 48 and 72 hours afterwards. The same schedule was used for patients treated with placebo. Sera pooled from healthy donors served as controls. On all the samples, opsonic and bactericidal activity as well as C3, total IgG and serum TNF content were tested. IVIG did not significantly affect total IgG and C3 content. Similarly, opsonic and bactericidal activity tested against E. coli 06 :K-, E. coli 0111 and SAC I was not modified ranging within HPS values. Furthermore, IVIG administration did not change the TNF level. A lower incidence of bacteremia in IVIG treated patients was observed.

[Aneurysms of the abdominal aorta in elderly patients]. / Aneurismi dell'aorta addominale nei pazienti anziani.

Aneurysms of the abdominal aorta are often diagnosed in the over-75s. Although for many Authors the presence of risk factors such as cardiopathies, cerebrovascular problems, renal or respiratory insufficiency, which are clearly more frequent in elderly patients, represent a contraindication to the intervention of choice, personal experience has shown that surgery remains the best solution. In fact, in a group of patients operated on for aneurysm of the abdominal aorta in a heart, no significant differences in age-related mortality were observed. Surgery therefore remains the treatment of choice in the elderly too for it must also be remembered that the natural history of the disease has shown that, in a comparatively short time, the aneurysm ruptures and operating mortality is markedly higher.

Alpha interferon plus thymopentine in treatment of HBV and/or HDV positive patients undergoing liver transplant.

Infection by hepatitis B (HBV) and/or delta virus (HDV), is the most frequent acquired pathology in patients affected by end-stage hepatic disease, candidates for liver transplant. To reduce the risk of virus reactivation after surgery, we used alpha Interferon (IFN) therapy in patients who were HBV-DNA and/or HDV-RNA positives before transplant. Our protocol included alpha IFN at low dosage associated to a thymic hormone that seems to have a synergistic activity with IFN. We have evaluated in four patients, affected by post hepatitic end-stage liver disease, the outcome of HBV and HDV markers in relation to immunological response during treatment. Our interest has been focused on monocyte and natural killer cytotoxic activity. The data show that all patients, before starting therapy, had evidence of active phase viral replication. They also displayed low values of the immunological parameters tested. The study of viral markers showed decrease of HBV and HDV in all patients. The relation between viral markers and natural killer and monocyte cytotoxicity was very interesting; during the treatment we observed a marked increase of both activities. At the same time no relevant modifications in the other immunological parameters tested were found.

[Proposed new method of separation of Hb A2 for standardization of the screening of microcythemias]. / Proposta di un nuovo metodo di separazione dell'Hb A2 per l'unificazione dello screening delle microcitemie.

The AA. suggest a dose-method of Hb A2, which implies the adoption of tris-EDTA-Glycin tampon with a different concentration anode-cathode; the electrophoretic bands, obtained by cellulose acetate electrophoresis, are eluted in the same tampon, but it is suggested to use 15 cc of tampon for A fraction elution and 1.5 cc for A2 fraction elution. The lecture must be done by spectrophotometry to 415 nm. By using this method the normal values of Hb A2 ranges from 1.7% to 3.5% and so there isn't any confusion with pathologic values. The AA. compare this method with that recommend a densitometric lecture of the strips and with those that imply the adoption of cromathographic columns, and they underline its advantages. In conclusion, the AA. suggest the adoption of an unified method for microcytemic screening that could be used in all laboratories.