Choice of Frontline Tyrosine-Kinase Inhibitor and Early Events in Very Elderly Patients With Chronic Myeloid Leukemia in Chronic Phase: A "Campus CML" Study.

OBJECTIVES: The study aimed to evaluate the utilization of frontline TKI therapy in a large cohort of elderly CP-CML patients. METHODS: A retrospective analysis was conducted on 332 CP-CML patients aged 75 years or older among 1929 diagnosed from January 2012 to December 2019 followed at 36 participating Hematology Centers involved in the "Campus CML" project. RESULTS: Among the patients analyzed, 85.8% received imatinib (IM) while 14.2% received second-generation TKIs (2G-TKI), 59.5% dasatinib, and 40.5% nilotinib. Most patients initiated IM at standard dose (67.3%) while 32.7% at reduced dose. A similar trend was observed with 2G-TKIs. The cumulative incidence of permanent TKI discontinuation at 12 months was 28.4%, primarily due to primary resistance (10.1%) and extra-hematologic toxicity (9.5%), with no significant difference between IM and 2G-TKI groups. Following the introduction of generic IM in Italy in 2018, IM usage increased significantly compared with 2G-TKIs. CONCLUSIONS: IM was in our Centers the preferred frontline therapy for older CP-CML patients, with increasing utilization after the introduction of generic formulations. However, 2G-TKIs are still used in a substantial proportion of patients, suggesting individualized physician assessments regarding patient suitability and expectations. Further investigation is needed to assess efficacy and safety of reduced TKI doses in this patient population.

Chiral Diketopyrrolo[3,4-c]pyrrole-1,2,3-1H-triazole Dyes with Highly Tuneable Properties in Solution and Thin Films.

We have studied the impact of achiral substituents on the chiral supramolecular architectures of diketopyrrolo[3,4-c]pyrrole-1,2,3-1H-triazole (DPP) dyes. We decorated the same chiral DPP motif with substituent groups on the nitrogen atoms of the lactam moiety: the hydrophobic n-octyl alkyl chain, the hydrophilic tri(ethylene glycol) (TEG) chain and the thermo-cleavable tert-butoxycarbonyl (t-Boc) carbamate group. In spite of having identical conjugated chromophore and chiral appendages, in aggregated form the three dyes displayed profoundly different optical, chiroptical, electrochemical and thermal features. ECD measurements revealed differences in the aggregation modes, which would be inaccessible by most other techniques. We found strong chiroptical features, which would have major implications in the context of chiral organic opto-electronics and in the development of other highly innovative technological applications.

Chiral Diketopyrrolo[3,4-c]pyrrole-1,2,3-1H-triazole Dyes with Highly Tuneable Properties in Solution and Thin Films.

Invited for the cover of this issue are the research groups of Lorenzo Di Bari at the University of Pisa and Gianluca Maria Farinola at the University of Bari Aldo Moro. The image depicts three diketopyrrolo[3,4-c]pyrrole-1,2,3-1H-triazole dyes with the same chiral appendage R* but different achiral substituent groups Y showing profoundly different features in their aggregated form. Read the full text of the article at 10.1002/chem.202300291.

Aggregation Modes of Chiral Diketopyrrolo[3,4-c]pyrrole Dyes in Solution and Thin Films.

The chiroptical features of chiral diketopyrrolo[3,4-c]pyrrole (DPP) derivatives have been only marginally investigated to date. In this regard, we have synthesized ad hoc four chiral DPP dyes, functionalized with enantiopure alkyl groups from natural sources either on the lactam moieties or on the terminal positions of the π-conjugated backbone, to promote an efficient self-assembly into chiral supramolecular structures. For each of them, the aggregation modes has been investigated by absorbance and ECD spectroscopies in conditions of solution aggregation and on thin films, considering the effects of deposition technique (drop casting vs. spin coating) and post-deposition operations (solvent and thermal annealing). The effect of the structure of lateral π-conjugated units attached to the central DPP scaffold, as well as that of the position of the alkyl chiral group, has been assessed. ECD revealed superior capability, compared to absorbance spectroscopy, to provide information on the aggregation modes and to detect the possible co-existence of multiple aggregation pathways.

The role of bone anabolic drugs in the management of periodontitis: a scoping review.

The aim of this scoping review was to summarise current knowledge about the effects of bone anabolic drugs on periodontitis, in order to identify new therapeutic strategies for preventing disease progression and reducing tooth loss. A technical expert panel (TEP) was established of 11 medical specialists, including periodontists and bone specialists that followed the PRISMA-ScR model to perform the scoping review and considered for eligibility both pre-clinical and clinical studies published in the English language up to September 2020. 716 items were initially found. After duplicate removal and screening of articles for eligibility criteria, 25 articles published between 2001 and 2019 were selected. Only studies concerning teriparatide, strontium ranelate, sclerostin antibodies and DKK1 antibodies met the eligibility criteria. In particular, only for teriparatide were there both clinical studies and experimental studies available, while for other bone anabolic drugs only animal studies were found. Available evidence about the use of bone anabolic drugs in periodontology demonstrates beneficial effects of these agents on biological pathways and histological parameters involved in periodontal tissue regeneration that suggest relevant clinical implications for the management of periodontitis.

Role of probiotics in adjunct to non-surgical periodontal therapy in patients with chronic periodontitis: a systematic review and meta-analysis.

The objective of this study was to establish the significance of probiotic usage, both as a preventive as well as a therapeutic strategy for the management of periodontal disease. It also substantiates the existing studies of single/combined bacterial strain for exhibiting variable ecological impact on oral bacteria. Data sources included literature searches of PubMed (MEDLINE), Scopus, Embase, CENTRAL and Web of science databases for placebo controlled randomized clinical trials of SRP with orally administered probiotics in any form as an adjunct. Data extraction was conducted and information from the included studies was tabulated according to the study designs, form of drug delivery, main outcomes, and clinical parameters. Data collected were based on the focused question outlined for the present systematic review. The reviewers cross-checked all extracted data. CAL and PD were assessed as the primary outcome to compare the effectiveness of adjunctive probiotic therapy in addition to SRP. Fourteen clinical studies were included and demonstrated efficacy in reducing periodontal probing depth (PPD) and gaining clinical attachment level (CAL), between probiotics and SRP/placebo. Adjunctive probiotic therapy in addition to SRP leads to decrease in probing depth and clinical attachment gain in chronic periodontitis patients. However, further high-quality randomized clinical trials with microbiological outcomes are required to fortify the conclusion.

Synthesis and Computational Study of Semicroconaines and Nonsymmetric Croconaines.

The synthesis of two new dye families of croconic acid derivatives, semicroconaine and nonsymmetric croconaine dyes, is reported for the first time. These compounds show strong absorption in the UV-visible and NIR, respectively. Semicroconaine dyes were obtained by a scalable and efficient condensation of croconic acid with aromatic heterocyclic methylene-active compounds. The subsequent reaction of the semicroconaine dyes with aromatic heterocyclic compounds affords nonsymmetric croconaines. The structure and electronic properties of the synthesized compounds have been investigated by preliminary theoretical calculations at DFT level of approximation.

Solvent-Free Pd-Catalyzed Heteroaryl-Aryl Coupling via C-H Bond Activation for the Synthesis of Extended Heteroaromatic Conjugated Molecules.

Direct arylation of thienopyrrolodione, diketopyrrolopyrroles, benzodithiophene derivatives, and fluorinated heteroarenes with functionalized aryl iodides is proven in solvent-free and non-anhydrous conditions. The reaction is performed in the presence of air and tolerates several functional groups on both the coupling partners, enabling a convenient synthesis of extended heteroaromatic conjugated molecules.

Stereochemical analysis of ß-keto sulfoxides by circular dichroism.

Three ß-keto sulfoxides (1-3) were synthesized in enantiopure form and investigated by means of circular dichroism (CD) spectroscopy, both in electronic and vibrational range (ECD, VCD), in combination with quantum chemical calculations. For compound 2, the X-ray structure was available; thus, the ECD in the solid state was also considered to reveal the differences between the molecular species in both states. Despite the simplicity of all ß-keto sulfoxides under investigation (29 atoms), reproducing even the major spectral VCD features failed for two compounds, making the use of VCD not ideal to assign their absolute configuration in a reliable way. We demonstrated, however, that the use of ECD spectroscopy, both in solution and solid state, can easily, unambiguously, and without any complication simulate all bands by applying the standard protocol for calculations. This study may stimulate the debate on the need of the use of two chiroptical methods simultaneously in the determination of absolute configurations.

Intensity and prevalence of depressive states in cancer inpatients: a large sample descriptive study.

In cancer patients, depression causes suffering during the whole disease trajectory and it also influences the personal perception of well-being as well as treatment adherence. Consequently, its better definition is needed for planning more tailored supportive programmes. This study was aimed to provide information on depressive state intensity and prevalence in an heterogeneous sample of cancer inpatients. In addition, associations were studied between depressive state and different socio-demographic and clinical factors. A total of 1,147 consecutive adult cancer inpatients completed the Center for Epidemiologic Studies Scale on Depression together with a form for collecting socio-demographic and clinical data. The mean score of depression was 16.9 (SD = 9.3). There were differences in depression intensity associated with gender (p < .001), age (p = .001) and cancer type (p < .001), but not with education level (p = .282) or marital status (p = .436). Of the entire sample 13.9% had depressive states; this percentage raised to 26.2% if a less stringent criterion was used. These data reinforce the importance of a clinical and research focus on depression in oncology. As differences according to gender, age and diagnosis exist in depression prevalence and intensity, tailored supportive intervention should be planned and verified for effectiveness and efficacy.

Stacked naphthyls and weak hydrogen-bond interactions govern the conformational behavior of P-resolved cyclic phosphonamides: a combined experimental and computational study.

P-Enantiomerically pure cyclic phosphonamides have been synthesized via a cyclization reaction of (S,S)-aminobenzylnaphthols with chloromethylphosphonic dichloride. The reaction is highly stereoselective and gives almost exclusively (S,S,SP)-cyclic phosphonamides in good yields. Analysis of the X-ray crystal structures shows clearly that the cyclization reaction forces the two naphthyl rings into a stable parallel displaced stacking assembly and indicates also the existence of intramolecular CH···π interactions and weak forms of intermolecular hydrogen bondings, involving the oxygen and the chlorine atoms. QM computations and NMR spectra in solution confirm the stacked molecular assembly as the preferred arrangement of the two naphthyl groups.