Retrospective study of gross and histopathologic lesions associated with closed chest cardiopulmonary resuscitation in dogs.

OBJECTIVES: To investigate and characterise the incidence of iatrogenic complications secondary to closed chest cardiopulmonary resuscitation in dogs. MATERIALS AND METHODS: Necropsy reports and histologic sections of tissues were retrospectively examined from 180 dogs that had received closed chest cardiopulmonary resuscitation to determine lesions associated with resuscitation. RESULTS: The most common complication was pulmonary haemorrhage (81/163, 49.7%, 95% confidence interval: 42.1 to 57.3), although only nine dogs had pulmonary haemorrhage of at least moderate severity. Liver fractures occurred in 16 of 180 cases (8.9%, 95% confidence interval: 5.5 to 14.0). Blood loss of >15% of blood volume into the abdomen and/or thorax occurred in 13 of 180 cases (7.2%, 95% confidence interval: 4.2 to 12.1). CLINICAL SIGNIFICANCE: Significant haemorrhage secondary to cardiopulmonary resuscitation may decrease the chances of achieving the return of spontaneous circulation or may cause or compound ischemic damage to critical organs if the return of spontaneous circulation is achieved. Following successful cardiopulmonary resuscitation, animals should be screened for cavitary or pulmonary haemorrhage, as significant haemorrhage could be a factor in recurrence of cardiac arrest.

Refractory and 17p-deleted chronic lymphocytic leukemia: improving survival with pathway inhibitors and allogeneic stem cell transplantation.

Refractory/early relapsed and 17p deletion/p53 mutation (del(17p)/TP53mut)-positive chronic lymphocytic leukemia (CLL) has been conventionally considered a high-risk disease, potentially eligible for treatment with allogeneic stem cell transplantation (alloSCT). In this multicenter retrospective analysis of 157 patients, we compared the outcomes of patients with high-risk CLL treated with alloSCT, a B-cell receptor pathway inhibitor (BCRi), and both. Seventy-one patients were treated with BCRis, 67 patients underwent reduced-intensity conditioning alloSCT, and 19 received alloSCT with a BCRi before and/or after transplantation. Inverse probability of treatment weighting analyses were performed to compare the alloSCT and no-alloSCT groups; in the 2 groups, 5-year OS, PFS, and cumulative incidence of nonrelapse mortality (NRM) and relapse were 40% versus 60% (P = .096), 34% versus 17% (P = .638), 28% versus 5% (P = .016), and 38% versus 83% (P = .005), respectively. Patients treated with alloSCT plus BCRi had a 3-year OS of 83%. The 3-year OS and NRM by year of alloSCT, including patients treated with BCRi, were 53% and 17% in 2000 to 2007, 55% and 30% in 2008 to 2012, and 72% and 18% in 2013 to 2018. In conclusion, the combination of pathway inhibitors and alloSCT is feasible and may further improve the outcome of high-risk CLL patients.

Fear of cancer recurrence in haematological cancer patients: exploring socio-demographic, psychological, existential and disease-related factors.

PURPOSE: This study aims to explore the relation between the dimension of fear of cancer recurrence (FCR) in haematological cancer patients relapse-free for at least 2 years and socio-demographic, related to the disease, psychological and existential factors. METHODS: A sample of 75 haematological cancer patients agreed to participate in the study through a self-reported online questionnaire (51.9% males). A total of 70.1% had a low recurrence risk. The questionnaire included socio-demographic (gender, age, civil status, level of education and number of children), related to the disease (diagnosis, therapeutic line and years since diagnosis), psychological (anxiety and depression), existential (purpose in life; PIL) factors and Fear of Cancer Recurrence Concerns Inventory (FCRI). Simple and multiple linear regressions were conducted for the analyses, and we performed some preliminary analysis on the reliability of the FCRI. FINDINGS: A total of 53.3% of participants showed clinical levels of FCR on the severity dimension, which was higher than found in previous research in other cancer patients. The coping strategies, triggers, severity and psychological distress dimensions showed higher mean values. Women, patients with indolent non-Hodgkin lymphomas, years since diagnosis, anxiety and purpose in life are significantly related to one or more dimensions of FCRI. IMPLICATIONS: It is important that the clinicians have at their disposal multiple possibilities to help patients cope with haematological cancer. If future research will confirm the results of this study, the negative correlation between FCR and PIL can suggest indications for planning interventions based on a salutogenic approach.

Microwave thermal ablation using CT-scanner for predicting the variation of ablated region over time: advantages and limitations.

This study aims at investigating in real-time the structural and dynamical changes occurring in an ex vivo tissue during a microwave thermal ablation (MTA) procedure. The experimental set-up was based on ex vivo liver tissue inserted in a dedicated box, in which 3 fibre-optic (FO) temperature probes were introduced to measure the temperature increase over time. Computed tomography (CT) imaging technique was exploited to experimentally study in real-time the Hounsfield Units (HU) modification occurring during MTA. The collected image data were processed with a dedicated MATLAB tool, developed to analyse the FO positions and HU modifications from the CT images acquired over time before and during the ablation procedures. The radial position of a FO temperature probe (rFO) and the value of HU in the region of interest (ROI) containing the probe (HUo), along with the corresponding value of HU in the contralateral ROI with respect to the MTA antenna applicator (HUc), were determined and registered over time during and after the MTA procedure. Six experiments were conducted to confirm results. The correlation between temperature and the above listed predictors was investigated using univariate and multivariate analysis. At the multivariate analysis, the time, rFO and HUc resulted significant predictive factors of the logarithm of measured temperature. The correlation between predicted and measured temperatures was 0.934 (p  < 0.001). The developed tool allows identifying and registering the image-based parameters useful for predicting the temperature variation over time in each investigated voxel by taking into consideration the HU variation.

Cortical malformations and COL4A1 mutation: Three new cases.

AIM: The COL4A1 gene (13q34) encodes the α1 chain of type IV collagen, a crucial component of the basal membrane. COL4A1 mutations have been identified as a cause of a multisystem disease. Brain MRI in COL4A1-mutated patients typically shows vascular abnormalities and white matter lesions. Cortical malformations (specifically schizencephaly) have also recently been described in these patients, suggesting that these, too, could be part of the phenotypic spectrum of COL4A1 mutations. The aim of our work was to retrospectively evaluate COL4A1-mutated subjects diagnosed at our centers in order to assess the frequency and define the type of cortical malformations encountered in these individuals. METHOD: We retrospectively reviewed MRI data of 18 carriers of COL4A1 mutations diagnosed in our centers between 2010 and 2016. RESULTS: We identified polymicrogyria in two patients, and schizencephaly in the mother of a further patient. INTERPRETATION: Our findings confirm that cortical malformations should be considered to fall within the phenotypic spectrum of COL4A1 mutations and show that not only schizencephaly but also polymicrogyria can also be found in mutated individuals. Although further studies are needed to clarify the underlying pathogenetic mechanism, independently of this, the timing of the brain damage could be the crucial factor determining the type of lesion.

Dielectric properties of muscle and adipose tissue-mimicking solutions for microwave medical imaging applications.

The aim of the present study was to synthesize mixture solutions which can accurately mimic the dielectric properties of biological tissues, specifically muscle and adipose tissues between 500 MHz and 50 GHz. Mixtures utilizing concentrations of bovine serum albumin (BSA) dissolved in phosphate buffered saline (PBS) and Ringer's solutions were synthesized to mimic in vivo and ex vivo muscle tissues. Solutions consisting of concentrations of peanut oil and Triton X-100 (TX) in PBS and Ringer's solutions were also synthesized to mimic in vivo and ex vivo adipose tissue. Results were then analysed and compared to measured dielectric properties of in vivo and ex vivo biological tissues from another previous study. Good agreement with said dielectric property measurements were obtained since the solutions from this study yielded low RMSE and RMSRE values. This implied that such solutions can be utilized in the construction of human body phantoms for narrowband and ultra-wideband microwave devices for near field breast cancer imaging.

Stroke-like events after brain radiotherapy: a large series with long-term follow-up.

BACKGROUND AND PURPOSE: Patients with a history of brain radiotherapy can experience acute stroke-like syndromes related to the delayed effects of brain radiation, including stroke-like migraine attacks after radiation therapy syndrome, peri-ictal pseudoprogression and acute late-onset encephalopathy after radiation therapy syndrome. The aim of this study was to collect evidence on the long-term outcome and treatment of these conditions, whose knowledge is undermined by their rarity and fragmented description. METHODS: Cases were collected, both prospectively and retrospectively, amongst six neuro-oncology departments. Inclusion criteria were as follows: (i) history of brain radiotherapy (completed at least 6 months before the acute episode); (ii) new onset of acute/subacute neurological symptoms; (iii) exclusion of all etiologies unrelated to brain irradiation. A review of current literature on stroke-like syndromes was performed to corroborate our findings. RESULTS: Thirty-two patients with acute neurological conditions attributed to the delayed effects of radiation were identified, including 26 patients with stroke-like syndromes. Patients with stroke-like syndromes commonly presented with a mosaic of symptoms, including focal deficits (77%), encephalopathy (50%), seizures (35%) and headache (35%). Seventy-three percent of them had acute consistent magnetic resonance imaging alterations. Treatment included high-dose steroids in 65% of cases. Twenty-two patients recovered completely (85%). Sixteen patients (62%) experienced relapses (median follow-up 3.5 years). A literature review identified 87 additional stroke-like cases with similar characteristics. CONCLUSIONS: Stroke-like events related to brain irradiation may be associated with permanent sequelae. Steroids are often administered on empirical grounds, as they are thought to accelerate recovery. Relapses are common, highlighting the need to elaborate adequate prevention strategies.

Early reduction of serum TARC levels may predict for success of ABVD as frontline treatment in patients with Hodgkin Lymphoma.

BACKGROUND: Many efforts have been made to predict prognosis of newly diagnosed Hodgkin Lymphoma (HL) patients. Objective of this study was to investigate the association between early reduction of Thymus and Activation-Regulated Chemokine after the first ABVD cycle (TARC-1) and prognosis of HL patients. METHODS: Serum samples of 116 HL patients were collected at baseline, after every ABVD cycle and during follow-up. The 99th centile of TARC distribution in a group of 156 independent healthy subjects (800pg/ml) was considered as cut-off for discriminating between abnormal and normal TARC values. FINDINGS: 101 patients out of 116 had baseline TARC above 800pg/ml (median value 27515pg/ml (IQR, 11001-68139)) and were the object of this analysis. TARC-1 significantly decreased to a median value of 556pg/ml (IQR, 378-977pg/ml). TARC-1 values below 800pg/ml were associated with success of therapy (p=0.0003) and PET-2 negativity (p=0.001). TARC-1≤800pg/ml identified a population with a significantly higher 5-years PFS in the whole cohort (90.1% vs 55.6%; p<0.0001) and in both subgroups of advanced (p=0.003) and early stage patients (p=0.021). At multivariable analysis, TARC-1 was significant independent predictor of PFS (p=0.0035). INTERPRETATION: Early reduction of TARC serum levels can predict success of treatment, being associated with achievement of interim PET-2 negative and favorable long-term outcome in HL patients receiving ABVD as front-line therapy.

Treatment planning in microwave thermal ablation: clinical gaps and recent research advances.

Microwave thermal ablation (MTA) is a minimally invasive therapeutic technique aimed at destroying pathologic tissues through a very high temperature increase induced by the absorption of an electromagnetic field at microwave (MW) frequencies. Open problems, which are delaying MTA applications in clinical practice, are mainly linked to the extremely high temperatures, up to 120 °C, reached by the tissue close to the antenna applicator, as well as to the ability of foreseeing and controlling the shape and dimension of the thermally ablated area. Recent research was devoted to the characterisation of dielectric, thermal and physical properties of tissue looking at their changes with the increasing temperature, looking for possible developments of reliable, automatic and personalised treatment planning. In this paper, a review of the recently obtained results as well as new unpublished data will be presented and discussed.

Adult polyglucosan body disease: clinical and histological heterogeneity of a large Italian family.

Adult Polyglucosan Body Disease (APBD) is a rare inherited leukodystrophy associated with axonal polyneuropathy, mainly reported in persons of Ashkenazi-Jewish descent. We describe three Italian siblings at disease onset, presenting in their fifties with a combination of pyramidal and ataxic signs, mild demyelinating neuropathy on neurophysiological investigation (1/3 cases) and transient symptoms (1/3). A leucoencephalopathy with infratentorial lesions without enhancement and medullary/spine atrophy was demonstrated on brain/spine MRI (3/3). Muscle biopsy was normal in 2/3; both muscle and nerve biopsy showed polyglucosan bodies in the sibling with polyneuropathy. This indicated a need for GBE1 sequencing, which revealed a novel missense mutation (c.1064G>A; p.Arg355His) and one previously described (c.1604A>G; p.Tyr535Cys) in all siblings. We highlight that peripheral neuropathy, deemed as disease hallmark, may be missing and that transient symptoms are confirmed as early disease manifestations. The pattern of damage at neuro-imaging described recurs irrespective of clinical presentation, constituting a unifying diagnostic clue.

Adult polyglucosan body disease in a patient originally diagnosed with Fabry's disease.

Adult polyglucosan body disease is a rare autosomal recessive disease, caused by glycogen branching enzyme gene mutations, characterised by urinary dysfunction, spastic paraplegia with vibration sense loss, peripheral neuropathy, and cognitive impairment. Fabry's disease is an X-linked lysosomal storage disorder caused by α-galactosidase A gene mutations; neurological manifestations include cerebrovascular accidents, small-fibre neuropathy and autonomic dysfunction. Here, we report the case of a 44-year-old Sicilian male with stroke-like episodes, hypohidrosis and mild proteinuria, which led to the diagnosis of Fabry's disease after a hemizygous mutation (p.Ala143Thr) in α-galactosidase A gene was detected. Subsequently, he developed progressive walking difficulties and dementia, which were considered atypical for Fabry's disease. Therefore, we performed additional investigations that eventually led to the diagnosis of adult polyglucosan body disease caused by two novel missense mutations (p.Asp413His and p.Gly534Val) in the glycogen branching enzyme gene. Recently, the pathogenic role of the p.Ala143Thr mutation in causing Fabry's disease has been questioned. This case underlines the importance of performing further investigations when facing with atypical features even in the presence of a genetic diagnosis of a rare disease.

CT and MRI of brain tumors.

Imaging plays a crucial role in the management of patients with brain tumors. The technical improvement of computed tomography (CT) and magnetic resonance (MRI) with the development of, new imaging techniques strongly improved the detection and characterization of brain tumors. For the optimal therapeutic management of the oncologic patient not only the recognition of the lesion is needed, but also the exclusion of other diseases that can mimic brain tumors. The preoperative assessment of malignancy and of relationships of the tumor with surrounding eloquent structures are also necessary to allow the correct choice of therapy and to warn surgeons of possible risks of the surgical approach. This article is an overview of the current state of neuroimaging of the most frequent brain tumors including CT and MRI, perfusion weighted imaging (PWI), diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS) and functional MRI based on blood oxygen level (fMRI BOLD). Indeed, in the last years, a transition took place from a purely anatomy-based radiology to one that incorporates functional, hemodynamic, metabolic, cellular, and cytoarchitectural alterations. Neuroimaging has evolved into a comprehensive diagnostic tool that allows the characterization of morphologic as well as biologic alterations to diagnose and grade brain tumors and to monitor and assess treatment response and patient prognosis.

Novel POMGNT1 point mutations and intragenic rearrangements associated with muscle-eye-brain disease.

Congenital muscular dystrophies due to defects in genes encoding proteins involved in α-dystroglycan (α-DG) glycosylation are a heterogeneous group of muscle disorders variably associated with central nervous system and eye abnormalities. One of the more severe is muscle-eye-brain disease (MEB). Mutations in genes coding for proven or putative glycosyltransferases (POMT1, POMT2, POMGnT1, fukutin, FKRP, and LARGE), the DPM3 gene encoding a DOL-P-Man synthase subunit, and the DAG1 gene encoding α-dystroglycan, have been associated with altered α-DG glycosylation. We report new POMGnT1 mutations and evaluate protein expression in 3 patients and 2 foetuses with variably severe MEB features. We identify two new point mutations (c.643C>T, c.1863delC), one new intragenic rearrangement (deletion of exons 2-8), and a new intron retention (between exons 21 and 22) resulting from a known point mutation c.1895+1G>T. Our study provides further evidence that rearrangements of the POMGnT1 gene are relatively common. Importantly, if heterozygous, they can be missed on standard genomic DNA sequencing. POMGNT1 protein analysis in 3 patients showed that the severity of the phenotype does not correlate with protein expression. Cerebral MRI is important for identifying MEB and α-dystroglycanopathy phenotypes in children and foetuses, and hence for directing the genetic analysis.

Cranial mediastinal liposarcoma in a horse.

A 23-year-old Anglo-Arabian mare was presented with tachypnea, dyspnea, and pitting edema of the ventral thoracic subcutis. On necropsy, a tan to red, friable, irregularly shaped mass (23 × 20 × 18 cm) occupied the cranial mediastinum. Histologically, the mass was classified as a liposarcoma and was composed of short interlacing bundles of spindle-shaped to irregularly rounded cells with discrete, variably sized, clear cytoplasmic vacuoles, which were stained with oil red O in frozen sections of formalin-fixed tissue.

Challenges for the next decade: allogeneic stem cell transplantation in chronic lymphocytic leukemia.

Although hematopoietic stem cell transplantation (allogeneic SCT (allo-SCT)) is the treatment of choice for many aggressive hematological malignancies, the role of allo-SCT in chronic lymphocytic leukemia (CLL) is still a matter of debate and can be considered one of the more important challenges for the next decade. In the era of novel drugs and humanized antibodies, the long-term outcome of patients has improved, and a critical reappraisal of autologous and allo-SCT in CLL treatment is warranted.

Rhabdomyosarcoma in 8 horses.

This multi-institutional report describes 8 cases of rhabdomyosarcoma in horses. Four neoplasms were in the tongue and other areas of the mouth or head, 2 were in the abdominal wall, and 1 each was in right shoulder muscles and heart. Four rhabdomyosarcomas that were less than 10 cm in diameter were treated by surgical excision or radiation with no recurrence. Two neoplasms greater than 10 cm in diameter in the abdominal wall and the right shoulder were considered inoperable and led to decisions to euthanize the horses. Two neoplasms were incidental findings at necropsy. All the neoplasms were classified as embryonal except for 1 pleomorphic rhabdomyosarcoma. These 8 cases were evaluated with 9 published case reports of equine rhabdomyosarcoma. For all cases, the most common sites were limb muscles (5/17) and tongue (4/17). Metastasis was reported in 4 of the previously published cases; none was found in this study.