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The article presents a case study of a 76-year-old man, who was diagnosed with congenital FVII deficiency treated. The patient was treated with plasma‐derived FVII (pdFVII) to prevent bleeding associated with coronary artery bypass grafting (CABG) for coronary heart disease (CHD). The patient underwent coronary angiography to treat acute coronary syndrome. It also examines the risk of diabetes and hypertension for patient with CHD.

The article presents a case study of a 56-year-old man with severe haemophilia A and severe aortic valve stenosis who was successfully treated with percutaneous transluminal aortic valve implantation (TAVI). It explains that Haemophilia is a sex-linked recessive inherited disease that only affects males caused by the deficiency of coagulation factor VIII. It implies that transluminal aortic valve implantation has rapidly become an important treatment option for selective patients.

Extramedullary plasmacytoma (EMP) and solitary bone plasmacytoma (SBP) represent a disease continuum through a multistage process of cell differentiation, survival, proliferation, and dissemination, strictly related to multiple myeloma (MM), the second most common hematological malignancy. Herein, we report two cases of recurrent oral plasmacytoma progressed to MM, in which the first clinical sign of a more widespread disease was limited to the mouth. Based on our experience, we recommend a strict workup for the differential diagnosis between EMP, SBP, and MM for patients with oral plasmacytoma, including radiological exam of the skeleton, magnetic resonance imaging (MRI) of the bone, and positive emission tomography (FDG-PET). MRI and possibly PET can all be used to more sensitively detect EM plasmacytoma sites. [ABSTRACT FROM AUTHOR]

The reliability of endoscopic ultrasonography (EUS) in follow-up management of gastric lymphomas has not been clearly validated. We conducted a retrospective analysis on 23 patients, 12 affected by mucosa-associated lymphoid tissue (MALT) lymphoma, eight by diffuse large B-cell lymphoma, and three by high-grade lymphoma with low-grade component, all treated with a stomach-conservative approach. One hundred and twenty matched evaluations with both EUS and endoscopy with biopsy (E-Bx) were performed, according to validated guidelines and clinical judgment. At a median follow-up of 87 months ranged between 9.5 and 166 months, the analysis of progression-free survival and disease-free survival showed a strict relationship between the persistence of EUS abnormalities and the clinical outcome in patients with MALT lymphoma (p = 0.0079; p = 0.02) but not in patients with high-grade lymphoma. In conclusion, EUS evaluation does not seem reliable in follow-up management of high-grade lymphomas, although it could have a great clinical impact in the management of MALT lymphoma. [ABSTRACT FROM AUTHOR]

Background Although the stomach is the most frequent site of intestinal lymphomas, few data are available on both clinical endoscopic presentation of gastric lymphoma and possible differences between low-grade and high-grade lymphomas. Methods Clinical, histological and endoscopic records of consecutive patients with primary low-grade or high-grade lymphoma diagnosed were retrieved. Symptoms were categorized as ‘alarm’ or ‘not alarm’. The endoscopic findings were classified as ‘normal’ or ‘abnormal’. Results Overall, 144 patients with primary gastric lymphoma were detected, including 74 low-grade and 70 high-grade lymphoma. Alarm symptoms, particularly persistent vomiting and weight loss, were more frequently present in patients with high-grade lymphoma than in those with low-grade lymphoma (54% vs. 28%; P = 0.002). Low-grade lymphomas presented as ‘normal’ appearing mucosa (20% vs. 0%; P = 0.0004) or petechial haemorrhage in the fundus (9% vs. 0%; P = 0.02) more frequently than high-grade lymphomas, being also more often confined to the antrum (47% vs. 27%, P = 0.03) and associated with Helicobacter pylori infection (88% vs. 52%, P < 0.0001). On the contrary, high-grade lymphomas presented more commonly as ulcerative type (70% vs. 52%; P = 0.03), being also more frequently diagnosed in stage >I when compared with low-grade lymphomas (70% vs. 21%, P < 0.0001). Conclusions The overall prevalence of alarm symptoms is quite low and may be absent in more than 70% of patients with low-grade lymphoma. [ABSTRACT FROM AUTHOR]

ABSTRACT The leaf hydraulic conductance (K [sub L] ) was measured in Prunus laurocerasus L. and Juglans regia L. in which previous measurements had revealed different impacts of dehydration on K [sub L] . Leaves of P. laurocerasus lost 8% of their K [sub L] at water potentials (Ψ [sub L] ) of -2.0 MPa. Leaflets of J. regia showed K [sub L] losses of 40% at Ψ [sub L] = -1.0 MPa. When major veins were blocked using cyanoacrylate to simulate their embolism, the K [sub L] of P. laurocerasus was reduced by 57% but that of J. regia leaflets was reduced by 80%. Such differences were hypothesized to be due to different axial-to-radial permeabilites of major veins. Infiltration of leaves with Phoxine B revealed that P. laurocerasus major veins were largely leaky in the radial direction whereas those of J. regia leaflets showed prevailing axial water transport. Differences between species in terms of axial-to-radial water permeability were confirmed by measurements of changes of hydraulic resistance along the midrib. The two hydraulic models are discussed in terms of leaf vulnerability to embolism and plant adaptation to dry habitats. [ABSTRACT FROM AUTHOR]

Abstract Vulnerability to cavitation of leaf minor veins and stems of Laurus nobilis L. was quantified together with that of leaflets, rachides and stems of Ceratonia siliqua L. during air-dehydration of 3-year-old branches. Embolism was estimated by counting ultrasound acoustic emissions (UAE) and relating them to leaf water potential (ΨL). The threshold ΨL for cavitation was less negative in L. nobilis than in C. siliqua according to the known higher drought resistance of the latter species. Leaf minor vein cavitation was also quantified by infiltrating leaves with fluorescein at different dehydration levels and observing them under microscope. Distinct decreases in the functional integrity of minor veins were observed during leaf dehydration, with high correlation between the two variables. The relationship between leaf conductance to water vapour (gL) and ΨL showed that stomata of L. nobilis closed in response to stem and not to leaf cavitation. However, in C. siliqua, gL decreased in coincidence to the leaf cavitation threshold, which was, nevertheless, very close to that of the stem. The hypothesis that stem cavitation acts as a signal for stomatal closure was confirmed, while the same role for leaf cavitation remains an open problem. [ABSTRACT FROM AUTHOR]

Brassica comprises very variable species, both morphologically and genetically. Among these species, the Sicilian populations of Brassica sect. Brassica, species related to kale crops form a complex group. The genetic relationships among 15 populations occurring in Sicily and one from Calabria, representing the existing diversity, have been investigated using random amplified polymorphic DNA (RAPD) markers. This assay, carried out with 22 arbitrary primers, generated 236 polymorphic fragments, 21 of which were specific for single populations (mainly Brassica insularis, Brassica incana and Brassica macrocarpa). Jaccard’s genetic distances were computed and the phylogenic tree was established using the UPGMA algorithm. The dendrogram obtained showed four branches grouping: (1) B. incana populations; (2) B. insularis and B. macrocarpa, occurring in small islands around Sicily; (3) B. rupestris populations; and (4) B. villosa populations. Within B. rupestris, only B. rupestris subsp. brevisiliqua was clustered in the B. villosa group. The classification obtained is discussed with regard to the morphological, ecological and geographical data. [ABSTRACT FROM AUTHOR]

ABSTRACT Plant water relations, xylem anatomy and the hydraulic architecture of 1-year-old twigs of Spartium junceum, both healthy and affected by a phytoplasm disease, were studied. The disease causes twigs to be either shortened (witches broom disease, WBD) or flat (fasciate disease, FD). WBD twigs show a sevenfold increase in total leaf area, smaller and shorter xylem conduits, a higher stomatal conductance (gl) and a decline of minimum leaf water potentials (Ψl) below the turgor loss point. FD twigs had nearly twice the leaf area of the healthy controls as well as high gl values and Ψl values below the turgor loss point. Moreover, significant differences between healthy and affected twigs in stem stomatal conductance (gs) and in the total stem area were recorded. Affected twigs die back under drought stress, which is explained by a pronounced loss of hydraulic conductivity of the infected stems (40 and 60%) in FD and WBD as well as by the unfavourable ratio of weighted conduit radius (Σr4) to total surface area (At), so that the efficiency of the stem in supplying the whole transpiring area with water is strongly reduced. [ABSTRACT FROM AUTHOR]

The article discusses the case of a patient with haemophilia A treated using high-titre factor VIII inhibitors. Topics covered include the effective management of bleeding conditions in hemophilia A patients. Also mentioned is the impact of percutaneous transluminal angioplasty (PTA) with stent implication on patients.

Background and Objectives. Few therapeutic options are presently available for patients with multiple myeloma (MM) who relapse after autologous or allogeneic stem cell transplantation, or for patients who are refractory to conventional chemotherapy and not eligible for salvage high-dose therapy. Thalidomide, a glutamic acid derivative with anti-angiogenic properties, has been recently proposed as an effective therapy for patients with advanced refractory disease. The aim of this study was to evaluate the activity of thalidomide in a large series of MM patients. Design and Methods. From October 1999 to January 2001, 65 patients (46 males/19 females) from 8 Italian institutions were treated with thalidomide. Twenty-six patients had relapsed after autologous stem cell transplantation, either single (n = 12) or double (n= 12); 38 patients had shown disease progression after greater than or equal to 2 lines of conventional chemotherapy, 2 patients had relapsed after allotransplant, one single patient had not received previous treatment. Sixty-one (93.8%) patients were in stage 111, median beta2 microglobulin was 2.9 mg/L, and median bone marrow plasma cell infiltration was 50%. Thalidomide was initially administered at a dose of 100 mg/day; if well tolerated, the dose was to be increased serially by 200 mg every other week to a maximum of 800 mg/day. Results. The median administered dose of thalidomide was 400 mg/day. WHO grade> II toxic effects were constipation (52%), lethargy (34%), skin rash (11%), peripheral neuropathy (14%) and leukopenia (3%). Sixty patients are presently evaluable for response; of these, 17 (28.3%) showed greater than or equal to 50% reduction in serum or urinary M protein concentration and 11 (18.3%) showed greater than or equal to 25% tumor reduction, for a total response rate averaging 46.6%. After a median of 8 months' follow-up, 15/28 patients are alive and progression-free (at 2 to 16 months), 12 patients have relapsed, and 1 patient... [ABSTRACT FROM AUTHOR]

The ELOQUENT-3 trial demonstrated the superiority of the combination of elotuzumab, pomalidomide, and dexamethasone (EloPd) in terms of efficacy and safety, compared to Pd in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor. The present study is an 18-month follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloPd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 17.7 months, 213 patients (66.4%) experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 7.5 and 19.2 months, respectively. The updated multivariate analysis showed a significant reduction of PFS benefit magnitude both in advanced International Staging System (ISS) (II and III) stages and previous exposure to daratumumab cases. Instead, advanced ISS (II and III) stages and more than 2 previous lines of therapy maintained an independent prognostic impact on OS. Major adverse events included grade three-fourths neutropenia (24.9%), anemia (13.4%), lymphocytopenia (15.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 19.3% and 8.7%, respectively. A slight increase in the incidence of neutropenia and lymphocytopenia was registered with longer follow-up. In conclusion, our real-world study still confirms that EloPd is a safe and possible therapeutic choice for RRMM. Nevertheless, novel strategies are desirable for those patients exposed to daratumumab., (© 2024 John Wiley & Sons Ltd.)

Daratumumab-based regimens are the new standard of care for newly diagnosed patients with AL amyloidosis based on the results of the ANDROMEDA study. However, real-world data on daratumumab efficacy in upfront therapy in unselected patients are scanty. In the framework of a prospective observational study, we investigated the efficacy and safety of daratumumab in 88 newly diagnosed patients, including subjects with IIIb cardiac stage (26%) or myeloma defining events (29%). Daratumumab was administered with bortezomib in 50 (56%) patients, lenalidomide in 31 (35%), and monotherapy in 7 (8%). The rate of serious adverse events was low (16%). The overall hematologic response rate was 75% with 52 (59%) patients attaining at least a very good partial response (VGPR) at six months. Amongst patients evaluable for organ response, the rate of cardiac and renal responses at 6 months was 31% and 21%, respectively. Comparing stage IIIb patients with the remaining ones, the rate of profound hematologic response was not significantly different (≥VGPR 57% vs. 59%, p 0.955) likewise the rate of cardiac (33% vs. 30%, p 0.340) and renal (40% vs. 16%, p 0.908) responses. Daratumumab-based regimens demonstrated to be safe and effective in treatment-naïve AL amyloidosis even in advanced stage disease., (© 2024 John Wiley & Sons Ltd.)

The treatment scenario for newly-diagnosed transplant-ineligible multiple myeloma patients (NEMM) is quickly evolving. Currently, combinations of proteasome inhibitors and/or immunomodulatory drugs +/- the monoclonal antibody Daratumumab are used for first-line treatment, even if head-to-head comparisons are lacking. To compare efficacy and safety of these regimens, we performed a network meta-analysis of 27 phase 2/3 randomized trials including a total of 12,935 patients and 23 different schedules. Four efficacy/outcome and one safety indicators were extracted and integrated to obtain (for each treatment) the surface under the cumulative ranking-curve (SUCRA), a metric used to build a ranking chart. With a mean SUCRA of 83.8 and 80.08 respectively, VMP + Daratumumab (DrVMP) and Rd + Daratumumab (DrRd) reached the top of the chart. However, SUCRA is designed to work for single outcomes. To overcome this limitation, we undertook a dimensionality reduction approach through a principal component analysis, that unbiasedly grouped the 23 regimens into three different subgroups. On the bases of our results, we demonstrated that first line treatment for NEMM should be based on DrRd (most active, but continuous treatment), DrVMP (quite "fixed-time" treatment), or, alternatively, VRD and that, surprisingly, melphalan as well as Rd doublets still deserve a role in this setting., (© 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

In combination with lenalidomide and dexamethasone (KRd), Carfilzomib has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) on ASPIRE trial. Efficacy and safety of the triplet are still the object of investigation by many groups to confirm ASPIRE results in the setting of RRMM treated in real-life who don't meet trial restrictive inclusion criteria. Therefore, we report a retrospective multicenter analysis of 600 RRMM patients treated with KRd between December 2015 and December 2018. The median age was 64 years (range 33-85), and the median number of previous therapies was two (range 1-11). After a median of 11 KRd cycles, the overall response rate was 79.9%. The median progression-free survival (PFS) was 22 months, and the 2-year probability of PFS was 47.6%. Creatinine clearance<30 ml/min, >1 line of previous therapy, and high-risk FISH were all associated with a poor prognosis in multivariate analysis. The median overall survival (OS) was 34.8 months; the 2-year probability of OS was 63.5%. At multivariate analysis, creatinine clearance<30 ml/min, >1 line of previous therapy, and high-risk FISH were significantly associated with poor prognosis. After a median follow-up of 16 months (range 1-50), 259 withdrew from therapy. The main discontinuation reason was progressive disease (81.8%). Seventy-four patients (12.3%) discontinued therapy for toxicity. The most frequent side effects were hematological (anemia 49.3%, neutropenia 42.7%, thrombocytopenia 42.5%) and cardiovascular (hypertension 14.5%, heart failure 2.5%, arrhythmias 3.6%). Our study confirms the safety and efficacy of KRd in the real-life setting of RRMM patients and encourages its use in clinical practice., (© 2022 John Wiley & Sons Ltd.)

The combination of elotuzumab, lenalidomide, and dexamethasone (EloRd) enhanced the clinical benefit over Rd with a manageable toxicity profile in the ELOQUENT-2 trial, leading to its approval in relapsed/refractory multiple myeloma (RRMM). The present study is a 3-year follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloRd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 36 months (range 6-55), 236 patients experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 18.4 and 34 months, respectively. The updated multivariate analyses showed a significant reduction of PFS and OS benefit magnitude only in cases with International Staging System stage III. Major adverse events included grade 3/4 neutropenia (18.5%), anemia (15.4%), lymphocytopenia (12.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 33.9% and 18.9%, respectively. No new safety signals with longer follow-up have been observed. Of 319 patients, 245 (76.7%) reached at least a partial remission. A significantly lower response rate was found in patients previously exposed to lenalidomide. In conclusion, our study confirms that EloRd is a safe and effective regimen for RRMM patients, maintaining benefits across multiple unfavorable subgroups., (© 2022 John Wiley & Sons Ltd.)

The impact of ruxolitinib therapy on evolution to blast phase (BP) in patients with myelofibrosis (MF) is still uncertain. In 589 MF patients treated with ruxolitinib, we investigated incidence and risk factors for BP and we described outcome according to disease characteristics and treatment strategy. After a median follow-up from ruxolitinib start of 3 years (range 0.1-7.6), 65 (11%) patients transformed to BP during (93.8%) or after treatment. BP incidence rate was 3.7 per 100 patient-years, comparably in primary and secondary MF (PMF/SMF) but significantly lower in intermediate-1 risk patients (2.3 vs 5.6 per 100 patient-years in intermediate-2/high-risk patients, P < .001). In PMF and SMF cohorts, previous interferon therapy seemed to correlate with a lower probability of BP (HR 0.13, P = .001 and HR 0.22, P = .02, respectively). In SMF, also platelet count <150 × 10 9 /l (HR 2.4, P = .03) and peripheral blasts ≥3% (HR 3.3, P = .004) were significantly associated with higher risk of BP. High-risk category according to dynamic International Prognostic Score System (DIPSS) and myelofibrosis secondary to PV and ET Collaboration Prognostic Model (MYSEC-PM predicted BP in patients with PMF and SMF, respectively. Median survival after BP was 0.2 (95% CI: 0.1-0.3) years. Therapy for BP included hypomethylating agents (12.3%), induction chemotherapy (9.2%), allogeneic transplant (6.2%) or supportive care (72.3%). Patients treated with supportive therapy had a median survival of 6 weeks, while 73% of the few transplanted patients were alive at a median follow-up of 2 years. Progression to BP occurs in a significant fraction of ruxolitinib-treated patients and is associated with DIPSS and MYSEC-PM risk in PMF and SMF, respectively., (© 2020 John Wiley & Sons Ltd.)

We provide a long-term evaluation of patients enrolled in the EORTC/GIMEMA AML-10 trial which included a total of 2157 patients, 15-60 years old, randomized to receive either daunorubicin (DNR, 50 mg/m 2 ), mitoxantrone (MXR, 12 mg/m 2 ), or idarubicin (IDA, 10 mg/m 2 ) in addition to standard-dose cytarabine and etoposide for induction chemotherapy and intermediate dose cytarabine for consolidation. Younger patients who reached complete remission with complete (CR) or incomplete (CRi) recovery were then scheduled to receive an allogeneic hematopoietic stem cell transplantation (HSCT). That was if they had a HLA-identical sibling donor; in all other cases, an autologous HSCT had to be administered. At an 11-year median follow-up, the 5-year, 10-year and 15-year overall survival (OS) rates were 33.2%, 30.1% and 28.0%, respectively. No significant difference between the three randomized groups regarding OS was observed (P = .38). In young patients, 15-45 years old, no treatment difference (P = .89) regarding OS was observed, while in patients 46-60 years old, MXR and IDA groups had a trend for a longer OS as compared to the DNR group (P = .029). Among younger patients without a favorable MRC cytogenetic risk subgroup who achieved a CR/CRi after induction chemotherapy, those with a HLA-identical sibling donor had higher 10-year and 15-year OS rates than those without. In older patients who reached CR/CRi, the long-term outcomes of those with or without a donor was similar. In conclusion, long-term outcomes of the study confirmed similar OS in the three randomized groups in the whole cohort of patients., (© 2020 Wiley Periodicals, Inc.)

Hodgkin Lymphoma (HL) is associated with deep microenvironment re-shaping and myeloid dysfunction. Given that only limited data are available regarding the role of Brentuximab Vedotin (BV) as single agent in transplant-naive relapsed/refractory (R/R) patients and its off-target effects on immune system, we evaluated the amount of regulatory T-cells (T-regs), myeloid-derived suppressor cells (MDSC) subpopulations, and their functional marker, serum arginase-1 (s-Arg-1), in peripheral blood of 15 consecutive R/R HL patients. After a median of four BV cycles, the overall response rate (complete response + partial response) was 47%, with 4 (27%) complete metabolic remissions. BV reduced the absolute number of three MDSC subtypes and s-Arg-1 levels. Patients with baseline s-Arg-1 ≥200 ng/ml had inferior progression-free survival at 36 months compared to those with low s-Arg-1. T-regs dysfunction was recovered by BV: absolute T-regs count was increased after treatment with BV, independently of metabolic response achieved, with a significant reduction of CD30 + T-regs. Our data disclose off-target effects of BV in the microenvironment that could explain its deep and durable clinical efficacy., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)