Highlights • Tenofovir (TDF) is increasingly used to treat CHB patients worldwide. • We describe two cases of TDF-induced Fanconi syndrome in CHB patients. • Fanconi syndrome reverted after TDF ...withdrawal while HBV was suppressed by ETV. • Glomerular and tubular function should be carefully monitored in patients under TDF. • Several factors, including age and ADV exposure, may increase the risk of this complication.
Sofosbuvir (SOF)-based regimens have been associated with renal function worsening in HCV patients with estimated glomerular filtration rate (eGFR) ≤ 45 ml/min, but further investigations are ...lacking.
To assess renal safety in a large cohort of DAA-treated HCV patients with any chronic kidney disease (CKD).
All HCV patients treated with DAA in Lombardy (December 2014–November 2017) with available kidney function tests during and off-treatment were included.
Among 3264 patients 65% males, 67% cirrhotics, eGFR 88 (9–264) ml/min, CKD stage was 3 in 9.5% and 4/5 in 0.7%. 79% and 73% patients received SOF and RBV, respectively. During DAA, eGFR declined in CKD-1 (p < 0.0001) and CKD-2 (p = 0.0002) patients, with corresponding rates of CKD stage reduction of 25% and 8%. Conversely, eGFR improved in lower CKD stages (p < 0.0001 in CKD-3a, p = 0.0007 in CKD-3b, p = 0.024 in CKD-4/5), with 33–45% rates of CKD improvement. Changes in eGFR and CKD distribution persisted at SVR. Baseline independent predictors of CKD worsening at EOT and SVR were age (p < 0.0001), higher baseline CKD stages (p < 0.0001) and AH (p = 0.010 and p < 0.0001, respectively).
During DAA, eGFR significantly declined in patients with preserved renal function and improved in those with lower CKD stages, without reverting upon drug discontinuation.
We report the case of a 64 year old male patient with a history of ischemic heart disease who underwent surgery for an abdominal mass. The histological diagnosis was highly malignant non-Hodgkin's ...lymphoma. After surgery the patient was admitted to our Department and received 6 courses of chemotherapy according to the COP schedule, followed by radiotherapy to the left upper abdominal region and ipsilateral lung base. The patient achieved partial remission. One month later he began to complain of left axillary lymphadenomegaly, polydipsia and polyuria. A NMR brain scan showed a hypophyseal mass. The patient was treated with DDAVP and chemotherapy with the PRO-MACE protocol; the polyuria and lymphadenomegaly disappeared and the size of the hypophyseal mass reduced markedly. The clinical picture was, therefore, attributed to a hypophyseal localization of the non-Hodgkin's lymphoma, which is a very rare manifestation of lymphomatous spread to the central nervous system. Our case is also interesting because it shows that a favorable outcome can be obtained with chemotherapy, provided that the latter is sufficiently aggressive. This is not necessarily the case with radiotherapy which may also be followed by late and severe neurologic sequelae.
Modulation of cytoplasmic Ca++ concentration is a mechanism common to signal transduction pathways regulating many cellular phenomena, including the interactions of tumors with the hemostatic system. ...We have investigated the pro-aggregating and pro-coagulant activities of human tumor cell lines cultured in vitro and the ability of different platelet agonists to induce Ca++ transients in these cells. Cells of a malignant mesothelioma line activated platelets by a thrombin-dependent mechanism; on the contrary, HeLa cells, derived from a uterine cervical cancer, possessed ADP-dependent pro-aggregating activity, and DND-IA melanoma cells did not stimulate platelet aggregation. All cell lines showed a tissue-factor-like procoagulant property, more pronounced in mesothelioma cells. Furthermore, ADP was able to induce a transient increase in cytoplasmic Ca++ concentration in tumor cells from all lines; collagen showed this effect in mesothelioma cells and in HeLa cells, and thrombin was effective only in mesothelioma cells. PAF never induced Ca++ fluxes in any of the cell lines investigated. Finally, the calcium-channel blocker verapamil inhibited agonist-induced Ca++ transients in tumor cells and in vitro tumor-cell growth. These data may help to identify new possible mechanisms of the 2-way interaction of tumors with the hemostatic system.
Two paintings by the Neapolitan Renaissance painter Colantonio were studied with two non-invasive techniques to enrich the technical–scientific documentation. Infrared reflectography (IR) and x-ray ...fluorescence (XRF) analyses were performed on Saint Jerome in the studio and Saint Francis delivering the Rule, paintings preserved in the Museo e Real Bosco di Capodimonte. The IR scanning was performed to look beyond the visible layers of the paint for the preparatory drawings and pentimenti, or changes made during the painting process. The XRF technique was applied in many points to determine the elemental composition and enable the identification of pigments and materials used in paint and in the preparatory layers. Elemental XRF mapping was also carried out on a region of particular interest. Results provide an initial overview and hypothesis of color palette and techniques used by the artist.
Preemptive strategies in neutropenic patients based on serum galactomannan (GM) -guided triggering of diagnostic work-up may be time-consuming and expensive when applied to the entire population. We ...have assessed the feasibility of a clinically driven diagnostic strategy without GM screening.
Patients with neutropenic fever underwent a baseline diagnostic work-up (BDWU; three blood cultures and other examinations as indicated). An intensive diagnostic work-up (IDWU; GM for 3 days, chest computed tomography and other examinations as indicated) was reserved for patients with 4 days of persisting or relapsing fever or with other clinical findings possibly related to an invasive fungal diseaser (IFD). Antifungal therapy was administered to patients diagnosed with IFD and empirically (negative IDWU) only to those with persisting neutropenic fever and worsening clinical conditions.
Of 220 neutropenia episodes, fever occurred in 159 cases and recurred in 28 cases. Overall, 49 IFDs were diagnosed (two by BDWU and 47 by IDWU) during 48 episodes (21.8%). Diagnostic-driven therapy was administered to 48 patients with IFDs; one patient with zygomycosis died without treatment. Only one patient received empirical therapy. IDWU was required in 40% of neutropenia episodes, and only 1.4 mean blood samples per neutropenia episode were tested for GM. Our strategy allowed a 43% reduction in antifungal treatments compared with a standard empirical approach. At 3-month follow-up, 63% of patients with IFD survived, and no undetected IFDs were found.
A clinically driven diagnostic approach in selected neutropenia episodes offered effective antifungal control and reduced the exposure to unnecessary antifungal treatment.
Mucormycosis is the third cause of invasive mycosis after candidiasis and aspergillosis in AML patients, representing a poor prognostic factor associated with a high rate of fatal outcome. We report ...a case of a patient with AML and a concomitant pulmonary mucormycosis at diagnosis, who obtained a complete remission both of her AML and of the fungal infection. The incidence of the infection at the onset of leukemia is extremely unusual, and, to our knowledge, the sporadic cases reported in the literature are included in heterogeneous series retrospectively examined. In our case, Liposomal Amphotericin B as single agent appeared incapable of controlling the infection, so anti-infective therapy was intensified with posaconazole and simultaneously antileukemic treatment with 5-azacitidine was started, with the understanding that the only antifungal treatment would not have been able to keep the infection under control for a long time if not associated with a reversal of neutropenia related to the disease. We observed a progressive improvement of the general conditions, a healing of pneumonia and a complete remission of the leukemic disease, suggesting that a careful utilization of the new compounds available today, in terms of both antifungal and antileukemic treatment, may offer a curative chance a patient who would have otherwise been considered unfit for a potentially curative therapeutic strategy.
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