The importance of schistocytes in a patient in VA-ECMO.

The presence of schistocytes can be responsible for spurious thrombocytosis and spuriously low red blood count (RBC). The hemoglobin concentration will be correct (as the method usually used, destroys the red cells and converts a substantial proportion of the hemoglobin to a stable pigment) but mean corpuscular hemoglobin (MCH) is falsely high. The platelets and RBC histograms of the full blood count analyzers play an important role in the identification of schistocytes and must be carefully analyzed before reporting the previously full blood count parameters. In patients in ECMO, where can be expected the presence of a small number of schistocytes, this evaluation is particularly important to avoid wrong clinical decisions.

Post-acute exercise cardiovagal modulation in older male adults with and without type 2 diabetes.

PURPOSE: We examined heart rate variability (HRV) and baroreflex sensitivity (BRS) disease- and age-related response at 10-and 60-min after an acute high-intensity interval (HIIE) and moderate continuous exercise (MICE) in older adults with and without type 2 diabetes mellitus (T2DM) and healthy young adults. METHODS: Twelve older male adults with (57-84 years) and without T2DM (57-76 years) and 12 healthy young male adults (20-40 years) completed an isocaloric acute bout of HIIE, MICE, and a non-exercise condition in a randomized order. Time and Wavelets-derived frequency domain indices of HRV and BRS were obtained in a supine position and offline over 2-min time-bins using Matlab. RESULTS: HIIE but not MICE reduced natural logarithm root mean square of successive differences (Ln-RMSSD) (d = - 0.85; 95% CI - 1.15 to - 0.55 ms, p < 0.001), Ln-high-frequency power (d = - 1.60; 95% CI - 2.24 to - 0.97 ms2; p < 0.001), and BRS (d = - 6.32; 95% CI - 9.35 to - 3.29 ms/mmHg, p < 0.001) in adults without T2DM (averaged over young and older adults without T2DM), returning to baseline 60 min into recovery. These indices remained unchanged in older adults with T2DM after HIIE and MICE. Older adults with T2DM had lower resting Ln-RMSSD and BRS than aged-matched controls (Ln-RMSSD, d = - 0.71, 95% CI - 1.16 to - 0.262 ms, p = 0.001; BRS d = - 3.83 ms/mmHg), 95% CI - 6.90 to - 0.76, p = 0.01). CONCLUSIONS: Cardiovagal modulation following acute aerobic exercise is intensity-dependent only in adults without T2DM, and appears age-independent. These findings provide evidence of cardiac autonomic impairments in older adults with T2DM at rest and following aerobic exercise.

Design study of a novel geometrical arrangement for an in-beam small animal positron emission tomography scanner.

Objective.We designed a geometrical solution for a small animal in-beam positron emission tomography (PET) scanner to be used in the project SIRMIO (Small animal proton irradiator for research in molecular image-guided radiation-oncology). The system is based on 56 scintillator blocks of pixelated LYSO crystals. The crystals are arranged providing a pyramidal-step shape to optimize the geometrical coverage in a spherical configuration.Approach.Different arrangements have been simulated and compared in terms of spatial resolution and sensitivity. The chosen setup enables us to reach a good trade-off between a solid angle coverage and sufficient available space for the integration of additional components of the first design prototype of the SIRMIO platform. The possibility of moving the mouse holder inside the PET scanner furthermore allows for achieving the optimum placement of the irradiation area for all the possible tumor positions in the body of the mouse. The work also includes a study of the scintillator material where LYSO and GAGG are compared with a focus on the random coincidence noise due to the natural radioactivity of Lutetium in LYSO, justifying the choice of LYSO for the development of the final system.Main results.The best imaging performance can be achieved with a sub-millimeter spatial resolution and sensitivity of 10% in the center of the scanner, as verified in thorough simulations of point sources. The simulation of realistic irradiation scenarios of proton beams in PMMA targets with/without air gaps indicates the ability of the proposed PET system to detect range shifts down to 0.2 mm.Significance.The presented results support the choice of the identified optimal design for a novel spherical in-beam PET scanner which is currently under commissioning for application to small animal proton and light ion irradiation, and which might find also application, e.g. for biological image-guidance in x-ray irradiation.

Significant nailfold capillary loss and late capillaroscopic pattern are associated with pulmonary arterial hypertension in systemic sclerosis.

OBJECTIVES: To evaluate differences in nailfold videocapillaroscopy (NVC) findings between systemic sclerosis-SSc patients with and without a diagnosis of pulmonary arterial hypertension (PAH). METHODS: 110 SSc patients were enrolled in this cross-sectional, case-control, multi-centre study. Patients were divided into cases (SSc-PAH confirmed by right hearth catheterization-RHC) and controls (SSc-nonPAH with low probability of PAH). NVC patterns (early, active, and late) and morphological parameters (microvascular density, non-specific abnormalities, giant capillaries, micro-haemorrhages, avascular areas) were considered using a semiquantitative scoring system. RESULTS: SSc-PAH patients showed higher frequencies of late pattern (p < 0.01), non-specific abnormalities (p < 0.01), lower capillary density (p < 0.01), higher avascular areas (p < 0.01), and a higher mean NVC score (p < 0.01). Contrarily, the early/active pattern (p < 0.01) and a higher rate of micro-haemorrhages (p = 0.04) were more frequent in non-PAH patients. By the multivariate analysis, SSc-PAH patients, compared to non-PAH, had more non-specific abnormalities (27/55, 49.1% vs 10/55, 18.2%, adjusted OR: 16.89, 95%CI: 3.06-93.16), a lower capillary density (grade 3, 20/55, 36.4% vs 5/55, 9.1%, adjusted OR: 38.33, 95%CI: 2.34-367.80), and avascular areas (18/55, 32.7% vs 10/55, 18.2%, adjusted OR: 16.90, 95%CI: 2.64-44.35). A correlation was found between the mean pulmonary arterial pressure-mPAP and avascular areas (p < 0.01), capillary density (p < 0.01), and non-specific abnormalities (p < 0.01). A clinical model including the NVC variables may be able to predict the diagnosis of PAH. CONCLUSIONS: Our results indicate that the distinctive peripheral microcirculatory injury of SSc, i.e capillary loss and morphological abnormalities, appear more severe and pronounced in patients with SSc-PAH.

Real life use of prostacyclin analog (iloprost), a multi-centric survey data from the Scleroderma study group Emilia Romagna (Sclero-RER) and review of the literature.

BACKGROUND AND AIM: Iloprost is recommend worldwide for the treatment of RP and the healing of DUs. The aim of this study is to report the regimens of Iloprost administered in different rheumatological centers within the same regional Health System Methods: A questionnaire exploring different items related to the use of Iloprost was developed and reviewed by three expert rheumatologists. The questionnaire was distributed as an online survey to all local SSc referral centers in Emilia-Romagna (Italy). Data are reported as percentage or median with interquartile range (IQR), as appropriate. An updated review of world literature on this topic was also carried out. RESULTS: All the invited centers completed the survey. There were both local (8) and university hospitals (4). The majority (58%) had a rheumatologist as head physician. All centers used Iloprost: a single monthly administration was the most common treatment (75%). The cycle lasted 1 [IQR 1-2] days with a 0.5-2.0 ng/Kg/min dose according to the drug tolerance of the patients. There were overall 68 spots (beds, reclining armchair, or simple armchair); 2.0 [1.5-4.0] patients were able to receive Iloprost at the same time. University Hospitals had more physicians at their disposal than local hospitals but less paramedic personnel (respectively: 1.8 vs 1.2 physicians, 1.5 vs 2.1 nurses). CONCLUSIONS: These observations were in line with the majority of previous studies reporting different regimens, comparing similar (but not identical) dose and schedule administration, however, despite differences being at times substantial, no standard infusion method is yet available.

Altered pathways of keratinization, extracellular matrix generation, angiogenesis, and stromal stem cells proliferation in patients with systemic sclerosis.

Objective: Systemic sclerosis is characterized by endothelial dysfunction, autoimmunity abnormalities, and fibrosis of the skin and internal organs. The pathogenetic mechanisms underlying systemic sclerosis vasculopathy are still not clarified. A complex cellular and extracellular network of interactions has been studied, but it is currently unclear what drives the activation of fibroblasts/myofibroblasts and the extracellular matrix deposition. Methods: Using RNA sequencing, the aim of the work was to identify potential functional pathways implied in systemic sclerosis pathogenesis and markers of endothelial dysfunction and fibrosis in systemic sclerosis patients. RNA-sequencing analysis was performed on RNA obtained from biopsies from three systemic sclerosis patients and three healthy controls enrolled in our University Hospital. RNA was used to generate sequencing libraries that were sequenced according to proper transcriptomic analyses. Subsequently, we performed gene set enrichment analysis of differentially expressed genes on the entire list of genes that compose the RNA-sequencing expression matrix. Results: Gene set enrichment analysis revealed that healthy controls were characterized by gene signatures related to stromal stem cells proliferation, cytokine-cytokine receptor interaction, macrophage-enriched metabolic network, whereas systemic sclerosis tissues were enriched in signatures associated with keratinization, cornification, retinoblastoma 1 and tumor suppressor 53 signaling. Conclusion: According to our data, RNA-sequencing and pathway analysis revealed that systemic sclerosis subjects display a discrete pattern of gene expression associated with keratinization, extracellular matrix generation, and negative regulation of angiogenesis and stromal stem cells proliferation. Further analysis on larger numbers of patients is needed; however, our findings provide an interesting framework for the development of biomarkers useful to explore potential future therapeutic approaches.

Recipient vessels for free flaps in advanced facial oncologic defects.

OBJECTIVES: To prospectively compare the results of microvascular flap reconstruction of midface and scalp advanced oncologic defects using superficial temporal versus cervical as recipient vessels. METHODS: This is a parallel group clinical trial with 1:1 allocation ratio of patients who underwent midface and scalp oncologic reconstruction with free tissue flap from April 2018 to April 2022 in a tertiary oncologic center. Two groups were analyzed: those in whom superficial temporal vessels were used as the recipient vessels (Group A) and those in whom cervical vessels were used as the recipient vessels (Group B). Patient gender and age, cause and localization of the defect, flap choice for reconstruction, recipient vessels, intraoperative outcome, postoperative course, and complications were recorded and analyzed. A Fisher's exact test was used to compare outcomes between the 2 groups. RESULTS: On the basis of the different recipient vessels, 32 patients were randomized into 2 groups, and of these 27 patients completed the study: Group A with superficial temporal recipient vessels (n = 12) and Group B with cervical recipient vessels (n = 15). There were 18 male and 09 female patients with an average age of 53.92 ±â€¯17.49 years. The overall flap survival rate was 88.89%. The overall complication rate for vascular anastomosis was 14.81%. The total flap loss rate in patients with superficial temporal recipient vessels was higher than the complication rate in those with cervical recipient vessels but with no statistical significance (16.67% vs. 6.66%, p = 0.569). Minor complications occurred in 05 patients without statistical significance between the groups (p = 0.342). CONCLUSION: In the group with superficial temporal recipient vessels, the postoperative rate of free flap complications was similar than the cervical recipient vessel group. Therefore the use of superficial temporal recipient vessels for midface and scalp oncologic reconstruction could be a reliable option.

Intra and inter-rater repeatability of brachial artery ultrasound estimates of flow-mediated slowing and flow-mediated dilation.

Flow-mediated slowing (FMS) is a non-invasive measure of endothelial function measured through reactive hyperemia-induced changes in pulse wave velocity (PWV). FMS is suggested to mitigate known pitfalls of flow-mediated dilation (FMD) including suboptimal repeatability and high-operator dependency. However, the few single-rater studies that examined FMS repeatability have shown controversial results and used only regional measurements of PWV, which might not reflect local brachial artery stiffness responses to reactive hyperemia. We assessed the inter- and intra-rater repeatability of ultrasound-based changes in local PWV (FMS) and diameter (FMD). Twenty-four healthy male participants aged 23-75 yr, were examined on two separate days. Reactive hyperemia-induced changes in PWV were calculated using a tailored R-script. The inter- and intra-rater repeatability were tested with the intraclass correlation coefficient (ICC), coefficient of variation (CV), and the Bland-Altman plot estimates. The inter-rater repeatability of FMS (bias: -0.08%; ICC: 0.85; 95% CI: 0.65 to 0.93; CV: 11%) and FMD (bias: -0.02%; ICC: 0.98; 95% CI: 0.97 to 0.99; CV: 7%) showed overall good repeatability over different days. The intra-rater repeatability of FMD (1st rater: bias: 0.27%; ICC: 0.90; 95% CI: 0.78 to 0.96; CV: 14%; 2nd rater: bias: 0.60%; ICC: 0.85; 95% CI: 0.64 to 0.94; CV: 18%) was better than FMS (1st rater: bias: -1.03%; ICC: 0.76; 95% CI: 0.44 to 0.91; CV: 21%; 2nd rater: bias:-0.49%; ICC: 0.70; 95% CI: 0.34 to 0.80; CV: 23%) but not different between raters. Ultrasound-based local measurements of PWV deceleration reactive hyperemia were repeatable among the raters.

Topical Cannabidiol in the Treatment of Digital Ulcers in Patients with Scleroderma: Comparative Analysis and Literature Review.

OBJECTIVE: To explore the effect of topical cannabidiol (CBD) in treating digital ulcers in patients with systemic sclerosis (SSc). METHODS: In total, 45 patients with SSc who had digital ulcers were consecutively enrolled between January 2019 and December 2019. Of the participants, 25 were treated with CBD during surgical debridement and 20 were treated with standard local therapy. A numeric rating scale for pain and Health Assessment Questionnaire Disability Index were administered at the baseline and at the end of treatment. RESULTS: Local treatment with CBD was significantly associated with lower pain scores, higher health assessment scores, and an increase in participants' total hours of sleep. Patients in the control group more frequently required additional analgesic therapy. CONCLUSIONS: Topical CBD may be a valuable tool to treat pain related to digital ulcers in patients with SSc.

Crystalline inclusions in chronic lymphocytic leukemia.

Crystalline inclusions in lymphocytes are unusual in chronic lymphocytic leukemia. They represent crystallized immunoglobulin (most frequently IgM-lambda) and their recognition facilitates the diagnosis of a lymphoproliferative disorder.

Recipient vessels for free flaps in advanced facial oncologic defects

Abstract Objectives To prospectively compare the results of microvascular flap reconstruction of midface and scalp advanced oncologic defects using superficial temporal versus cervical as recipient vessels. Methods This is a parallel group clinical trial with 1:1 allocation ratio of patients who underwent midface and scalp oncologic reconstruction with free tissue flap from April 2018 to April 2022 in a tertiary oncologic center. Two groups were analyzed: those in whom superficial temporal vessels were used as the recipient vessels (Group A) and those in whom cervical vessels were used as the recipient vessels (Group B). Patient gender and age, cause and localization of the defect, flap choice for reconstruction, recipient vessels, intraoperative outcome, postoperative course, and complications were recorded and analyzed. A Fisher's exact test was used to compare outcomes between the 2 groups. Results On the basis of the different recipient vessels, 32 patients were randomized into 2 groups, and of these 27 patients completed the study: Group A with superficial temporal recipient vessels (n = 12) and Group B with cervical recipient vessels (n = 15). There were 18 male and 09 female patients with an average age of 53.92 ± 17.49 years. The overall flap survival rate was 88.89%. The overall complication rate for vascular anastomosis was 14.81%. The total flap loss rate in patients with superficial temporal recipient vessels was higher than the complication rate in those with cervical recipient vessels but with no statistical significance (16.67% vs. 6.66%, p= 0.569). Minor complications occurred in 05 patients without statistical significance between the groups (p= 0.342). Conclusion In the group with superficial temporal recipient vessels, the postoperative rate of free flap complications was similar than the cervical recipient vessel group. Therefore the use of superficial temporal recipient vessels for midface and scalp oncologic reconstruction could be a reliable option.

Staphylococcal toxic shock syndrome.

Toxic Shock Syndrome (TSS) is a severe acute disease characterized by high fever, hypotension, rash, multiple organ dysfunction and desquamation during convalescence. TSS is caused by toxin-producing strains of Staphylococcus aureus or Streptococcus pyogenes. TSS remains a rare but severe disease. Early diagnosis is important because specific treatments with antitoxin effects must be started as soon as possible. This manuscript presents a set of images that illustrate the main findings in the peripheral blood film of a patient with TSS.

Molecular Pathways of Breast Cancer in Systemic Sclerosis: Exploratory Immunohistochemical Analysis from the Sclero-Breast Study.

Several authors reported an increased risk of cancer in SSc patients, including breast cancer (BC). Nevertheless, the mechanisms underlying this association have not yet been clarified. SSc and BC share several molecular pathways, which seem to play a common etiopathogenetic role. The previously published Sclero-Breast study demonstrated the development of BC with a good prognosis among these patients, which could be explained by an autoimmune background as a possible mechanism for limiting tumor extension. Here, we report the results of an IHC analysis of molecular pathways known to be common drivers for both diseases, with the aim to better define the mechanisms underlying a good prognosis of BC in patients affected by SSc. The analysis demonstrated higher TILs rates in all BC subgroups, with a high rate of PD-L1 expression especially in TNBC and HER2-positive BC, suggesting a less aggressive behavior in these patients compared to the general population. These results support a possible de-escalation strategy of cancer therapies in these fragile patients. These data could represent a starting point for future prospective studies based on the clinical application of these biomarkers with a larger sample size to promote a personalized and targeted oncological treatment for this specific subset of patients.