Ultrasound exploration in the work-up of unexplained fever in the immunocompromized host: preliminary observations.

In immunocompromized hosts, febrile episodes have an unknown origin (FUO) in about fifty per cent of cases. In this preliminary study we evaluated the role of abdominal and pleural ultrasound (US) examination for early detection of infectious sites. US exploration was performed in a cohort of 14 consecutive FUO patients early after fever onset, at patients’ bedside, by a hematologist trained in diagnostic ultrasound, and it was repeated at neutrophil recovery. US exploration showed abnormal abdominal findings in 7 and pleural effusion in 3 patients. In all cases but one the abnormality was found at the first US examination. Abdominal and pleural US exploration is a low-cost, easy to use tool for the work-up of FUO in the immunocompromized host that proved to be effective in identifying the infection site in about 50% of patients

Spleen sizing by ultrasound scan and risk of pneumococcal infection in patients with chronic GVHD: preliminary observations.

Encapsulated bacteria infections (EBI) can cause severe complications after BMT, usually occurring in patients with chronic GVHD (cGVHD) and attributed to functional hyposplenism. Using ultrasound (US) scan, we measured spleen size in 22 patients transplanted from HLA identical siblings, with or without cGVHD. No patient had received TBI, spleen irradiation or penicillin prophylaxis. Results were correlated with occurrence of EBI during a mean follow-up of 55 months (range 7-93). In the group without cGVHD, the difference between pre- and post-BMT spleen longitudinal diameters was not significant, and no patient developed EBI. In the cGVHD group, post-BMT spleen longitudinal diameters were significantly smaller than those pre-BMT (9.1 ± 1.6 vs 12.3 ± 2.2; P = 0.0005). Out of four patients with cGVHD who showed a major spleen size reduction, two developed a severe infection (an overwhelming sepsis and a pneumococcal meningitis). In our small series, we found a borderline relationship between spleen size reduction and duration of cGVHD (P = 0.06), as well as an increased risk of life-threatening infection in patients with extensive cGVHD and hyposplenism as detected by US scan. We conclude that US scan may be useful to detect spleen size reduction following allogeneic BMT and that penicillin prophylaxis is to be strongly recommended in patients with extensive cGVHD and spleen size reduction, even in those who have not received total body or spleen irradiation

Ultrasound scan to detect acalculous cholecystopathy in immunocompromised hosts with unexplained fever.

We found a significant prevalence of acalculous cholecystopathy in a group of patients with hematologic malignancies and unexplained fever. Ultrasound scan (US) detected a case of acute cholecystitis, two of gallbladder overdistension and biliary sludge, and one of striated gallbladder wall thickening. US proved effective in early identification of abdominal infection site

Intravenous itraconazole for treating invasive pulmonary aspergillosis in neutropenic patients with acute lymphoblastic leukemia.

Aspergillus infection is associated with a high mortality rate in immunocompromised hosts; more effective drugs for this infection are needed. Oral itraconazole has been studied in neutropenic fungus-infected patients. Using a novel formulation (intravenous) of itraconazole, we successfully treated severe necrotizing pneumonias due to Aspergillus species occurring during a postchemotherapy prolonged aplastic phase in two patients with acute lymphoblastic leukemia

Endothelial cell activation by SARS-CoV-2 spike S1 protein: A crosstalk between endothelium and innate immune cells

Background. Emerging evidences suggest that in severe COVID-19, multi-organ failure is associated with a hyperinflammatory state (the so-called “cytokine storm”) in combination with the development of a prothrombotic state. The central role of endothelial dysfunction in the pathogenesis of the disease is to date accepted, but the precise mechanisms underlying the associated coagulopathy remain unclear. Whether the alterations in vascular homeostasis directly depend upon the SARS-CoV-2 infection of endothelial cells or, rather, occur secondarily to the activation of the inflammatory response is still a matter of debate. Here, we address the effect of the SARS-CoV-2 spike S1 protein on the activation of human lung microvascular endothelial cells (HLMVEC). In particular, the existence of an endothelium-macrophage crosstalk in the response to the spike protein has been explored. Methods and Results. The effect of the spike protein is addressed in human lung microvascular endothelial cells (HLMVEC), either directly or after incubation with a conditioned medium (CM) of human monocyte-derived macrophages (MDM) previously activated by the spike S1 protein (CM-MDM). Both MDM and HLMVEC are activated in response to the S1 protein, with an increased expression of pro-inflammatory mediators. However, when HLMVEC are exposed to CM-MDM, an enhanced cell activation occurs in terms of the expression of adhesion molecules, pro-coagulant markers, and chemokines. Under this experimental condition, ICAM-1 and VCAM-1, the chemokines CXCL8/IL-8, CCL2/MCP1, and CXCL10/IP-10 as well as the protein tissue factor (TF) are markedly induced. Instead, a decrease of thrombomodulin (THBD) is observed. Conclusion. Our data suggest that pro-inflammatory mediators released by spike-activated macrophages amplify the activation of endothelial cells, likely contributing to the impairment of vascular integrity and to the development of a pro-coagulative endothelium

Small bowel infarction by Aspergillus.

Primary gut involvement by Aspergillus is a rare and often fatal complication of intensive antileukemic therapy. We describe the case of an adult patient affected by acute leukemia who developed a small bowel fungal thromboembolism without radiographic evidence of lung involvement during the post-induction aplastic phase. The diagnosis was made histologically at laparotomy performed for small bowel perforation. The patient died a week later in spite of amphotericin-B treatment and neutrophil recovery. Anti- Aspergillus prophylaxis and early introduction of amphotericin-B in the treatment of febrile neutropenia is probably advisable in all cases of AML

Liver nodular regenerative hyperplasia after bone marrow transplant.

We report an unusual liver disease which may occur after bone marrow transplantation, i.e. the collapse of hepatic lobuli followed by regenerative islets: the resulting clinical picture may mimic GvHD or a viral disease, but histology is diagnostic, showing nodular regeneration in the absence of inflammation or fibrosis

Combined treatment with amphotericin-B and granulocyte transfusion from G-CSF-stimulated donors in an aplastic patient with invasive aspergillosis undergoing bone marrow transplantation.

Granulocyte transfusions from G-CSF stimulated donors were added to standard anti-infective treatment in preparation for and during allogeneic bone marrow transplantation in a young man affected by very severe acute aplastic anemia and invasive aspergillosis. Nine concentrates with a mean neutrophil content of 18.7x109/L (2.6x 108/kg patient b.w.) were transfused before and after marrow infusion. An impressive clinical improvement was noticed after each granulocyte transfusion, although this was not always paralleled by a neutrophil increase in the peripheral blood. Engraftment (N>0.5x109/L and PIt >25x109/L) was verified at +16 and +40 days, respectively. The patient is currently in complete hematological and microbiological remission 14 months after transplantation. Granulocyte apheresis from G-CSF stimulated donors provides a high number of activated neutrophils. At the dose given (300 μg/day) donor tolerance to G-CSF was excellent. This new approach is indicated when life-threatening infections develop in patients exposed to prolonged severe neutropenia

High number of circulating CD34+ cells in patients with myelophthisis.

Hematopoietic Stem Cells High number of circulating CD34+ cells in patients with myelophthisis Six patients with bone marrow micrometastases from solid cancers presented with increased numbers of circulating CD34+ cells; the CD34+ cell counts were very high in some cases. By contrast, no patient with metastatic cancer without bone marrow involvement showed raised numbers of circulating hemopoietic progenitors. haematologica 2005; 90:976-977 (http:/

Post-transplant cerebral toxoplasmosis diagnosed by magnetic resonance imaging.

Cerebral toxoplasmosis is a rare late complication in allogeneic bone marrow transplanted patients. Neuroradiological findings may suggest the correct diagnosis. We report a patient in whom cerebral magnetic resonance imaging (MRI) showed a lesion characteristic of toxoplasmosis. Anti- toxoplasma treatment led to clinical and radiological improvement. MRI seems to be a valid tool for detection and follow-up of cerebral toxoplasmosis