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This multicentre observational study evaluated the feasibility, efficacy and toxicity of antifungal combination therapy (combo) as treatment of proven or probable invasive fungal diseases ( IFDs) in patients with haematological malignancies. Between January 2005 and January 2010, 84 cases of IFDs (39 proven and 45 probable) treated with combo were collected in 20 Hematological Italian Centres, in patients who underwent chemotherapy or allogeneic haematopoietic stem cell transplantation for haematological diseases. Median age of patients was 34 years (range 1-73) and 37% had less than 18 years. Acute leukaemia was the most common underlying haematological disease (68/84; 81%). The phase of treatment was as follows: first induction in 21/84 (25%), consolidation phase in 18/84 (21%) and reinduction/salvage in 45/84 (54%). The main site of infection was lung with or without other sites. The principal fungal pathogens were as follows: Aspergillus sp. 68 cases (81%), Candida sp. six cases (8%), Zygomycetes four cases (5%) and Fusarium sp. four cases (5%). The most used combo was caspofungin+voriconazole 35/84 (42%), caspofungin + liposomal amphotericin B (L-AmB) 20/84 (24%) and L-AmB+voriconazole 15/84 (18%). The median duration of combo was 19 days (range 3-180). The overall response rate ( ORR) was 73% (61/84 responders) without significant differences between the combo regimens. The most important factor that significantly influenced the response was granulocyte ( PMN) recovery ( P 0.009). Only one patient discontinued therapy (voriconazole-related neurotoxicity) and 22% experienced mild and reversible adverse events (hypokalaemia, ALT/ AST increase and creatinine increase). The IFDs-attributable mortality was 17%. This study indicates that combo was both well tolerated and effective in haematological patients. The most used combo regimens were caspofungin + voriconazole ( ORR 80%) and caspofungin + L-AmB ( ORR 70%). The ORR was 73% and the mortality IFD related was 17%. PMN recovery during combo predicts a favourable outcome. Clinical Trials Registration: NCT00906633. [ABSTRACT FROM AUTHOR]

We report two cases of invasive zygomycoses occurring in severely immunocompromised patients with haematological malignancies that were successfully treated with liposomal amphotericin B and surgical debridement, followed by oral administration of posaconazole. These cases demonstrated that an early instituted, aggressive and combined therapeutic approach results in a recovery from invasive fungal infection, without any relapse of infection, thanks to secondary prophylaxis using posaconazole. [ABSTRACT FROM AUTHOR]

Contents The μ-opioid receptor (MOR) is expressed in bovine, human, equine and canine oocytes, and in seasonal breeders, it is expressed with higher intensity during the anoestrous phase. Supplementation of in vitro maturation (IVM) medium with opioid agents, agonists or antagonists, was shown to affect oocyte maturation in several species such as rat, bovine and equine. This study reports the effects of supplementing IVM medium with naloxone (Nx), an opioid antagonist, on nuclear and cytoplasmic maturation rate of oocytes recovered from anoestrous bitches. Cytoplasmic maturation was examined in terms of mitochondrial (mt) distribution. In order to confirm the receptor-mediated action of Nx, in oocytes of anoestrous bitches, MOR expression was analyzed by Western blot. Cumulus–oocyte complexes, recovered from the ovaries of bitches in anoestrous, were cultured in vitro and Nx was added at the concentrations of 1 × 10−6, 1 × 10−8 and 1 × 10−10 m. The rate of oocytes resuming meiosis after culture in presence of 1 × 10−6 m Nx (29%) was significantly higher than that of oocytes of control group (12%; p < 0.05). However, treatment with Nx did not affect mt distribution pattern. In denuded oocytes and in corresponding cumulus cells, a doublet of 65 and 50 kDa was observed. We conclude that, in oocytes of anoestrous bitches, MOR is expressed and Nx significantly improves nuclear maturation rate. Further studies should be performed to elucidate the expression of other opioid receptors, such as δ and κ, and possible interactive effects of their antagonists on canine oocyte maturation. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) therapies differ in efficacy, side effects, route, frequency, and duration of administration. We assessed patient preferences for treatment attributes and evaluated associations with disease stage, treatment line, and socio-demographic characteristics in a cross sectional, observational study conducted at 16 Italian hematology centers. Study visits occurred between February and July 2020; 401 adult patients with CLL (201 Watch and Wait (W&W), 200 treated) participated in a discrete choice experiment (DCE), composed of 8 choices between pairs of treatment profiles with different levels of 5 attributes of currently available CLL treatments (length of response, route and duration of administration, risk of side effects including diarrhea, infections, or organ damage). Health-related quality of life was assessed with the EQ-5D-5L, EORTC QLQ-C30 and QLQ CLL-16. Previously treated patients had longer disease duration (7 vs. 5 years), higher prevalence of serious comorbidities (45.5% vs. 36.2%) and high-risk molecular markers (unmutated IGHV 55.6% vs. 17.1%; TP53 mutation 15.2% vs. 4.0%). Health-related quality of life scores were similar between groups. In the DCE, W&W patients rated "possible occurrence of infections" highest (relative importance [RI] = 36.2%), followed by "treatment and relevant duration" (RI = 28.0%) and "progression-free survival (PFS)" (RI = 16.9%). Previously treated patients rated "treatment and relevant duration" highest (RI = 33.3%), followed by "possible occurrence of infections" (RI = 28.8%), "possible occurrence of organ damage" (RI = 19.4%), and "PFS" (RI = 9.8%). Concern over infection was rated highest overall; unexpectedly PFS was not among the most important criteria in either group, suggesting that the first COVID-19 pandemic wave may have influenced patient preferences and concerns about CLL therapy options., (© 2023 Abbvie SRL and The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the western world. In Italy, venetoclax was approved for use in patients with CLL as monotherapy in 2017 and in combinations in 2019. As a result of this delayed approval, there are relatively few real-world studies from Italian clinical practice and much of the data are in heavily pretreated patients. We have collected the available studies in Italian routine practice. Three studies confirm the effectiveness and tolerability of this agent in patients with relapsed/refractory CLL and high-risk disease characteristics, many of whom had received prior B-cell receptor signaling treatment. Addition of rituximab to venetoclax produced more complete responses in patients with relapsed/refractory CLL, while higher disease burden and progression while receiving a prior Bruton's tyrosine kinase inhibitor were both associated with poorer outcomes in patients treated with venetoclax. Venetoclax was well-tolerated with low discontinuation rates. No studies of venetoclax plus obinutuzumab for the first-line treatment of patients with CLL were available due to the short time since approval in Italy. Several cohorts addressed the impact of COVID-19 on patient management and outcomes, suggesting that treated patients and those in clinical observation had similar rates of COVID-19-related hospital admission, intensive care unit admission, and mortality. Overall, the responses and tolerance to venetoclax observed in the Italian real-world setting confirm the tolerability and effectiveness of venetoclax regimens in high-risk patients., (© 2023 Abbvie S.R.L and The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

Zygomycosis is an invasive infection that can occur particularly in patients with haematological malignancy. The causative fungi are members of the order Mucorales, and individual species within this group require a high level of laboratory skill to be identified. Zygomycosis can present as rhinocerebral, pulmonary, or disseminated disease, with a rapid clinical course. The optimal management of these cases requires early diagnosis, aggressive antifungal therapy and, when possible, surgical debridement. Founded on clinical experience, but without the benefit of comparative studies, liposomal amphotericin B has become the therapeutic agent of choice. Posaconazole is an orally administered triazole with a demonstrated in vitro and in vivo activity against most Zygomycetes that is comparable to that of amphotericin B. Studies on salvage therapy with posaconazole have yielded promising results, and successful case reports are also available. As an adjuvant approach, iron chelation with deferasirox has shown promising results, although clinical experience is still limited.

In this modification of the title compound, 5-(4-[(2-pyridylamino)sulfonyl]phenyldiazenyl)salicylic acid, C(18)H(14)N(4)O(5)S, the molecule is present in the amide tautomeric form. Two azo-bridged phenyl rings render the bulk of the molecule planar, with the carboxylic acid group at one terminal and the pyridylamino residue at the other. The repeating unit in the crystal is a centrosymmetric dimer containing two identical R-2/2-(8) hydrogen-bonded ring systems, each involving the carboxylic acid and pyridylamino moieties. Additional stabilization is due to an intramolecular hydrogen bond between the 2-hydroxyl group and the carbonyl O atom of the carboxylic acid group, as well as intermolecular pi-pi stacking.