Pyroclastic Dust from Arequipa-Peru Decorated with Iron Oxide Nanoparticles and Their Ecotoxicological Properties in Water Flea D. magna.

A novel magnetic composite made of Peruvian pyroclastic dust material decorated with maghemite nanoparticles was synthesized and characterized using a variety of analytic techniques. The 13 nm maghemite nanoparticles were grown on the pyroclastic dust using the conventional coprecipitation chemical route. A short-term acute assay was developed to study the ecotoxicological behavior of the water flea, Daphnia magna. A 24 h-lethal concentration (LC50) value equal to 123.6 mg L-1 was determined only for the magnetic composite. While the pyroclastic dust material did not exhibit a lethal concentration, it caused morphologically significant changes (p < 0.05) for heart and tail parameters at high concentrations. Morphologies exposed to the magnetic composite above the 24 h-LC50 revealed less tolerance and significant changes in the body, heart, antenna, and eye. Hence, it affects biomarker growth and swimming. The reproduction rate was not affected by the raw pyroclastic dust material. However, the number of individuals showed a decrease with increasing composite concentrations. The present study indicates the LC50 value, which can be used as a reference concentration for in-situ water cleaning with this material without damaging or changing the Daphnia magna ecosystem.

Genomic characterisation of hormone receptor-positive breast cancer arising in very young women.

BACKGROUND: Very young premenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained. PATIENTS AND METHODS: Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the Suppression of Ovarian Function Trial (SOFT) to determine genomic drivers that are enriched in young premenopausal women. Genomic alterations were characterised using next-generation sequencing from a subset of 1276 patients (deep targeted sequencing, n = 1258; whole-exome sequencing in a young-age, case-control subsample, n = 82). We defined copy number (CN) subgroups and assessed for features suggestive of homologous recombination deficiency (HRD). Genomic alteration frequencies were compared between young premenopausal women (<40 years) and older premenopausal women (≥40 years), and assessed for associations with distant recurrence-free interval (DRFI) and overall survival (OS). RESULTS: Younger women (<40 years, n = 359) compared with older women (≥40 years, n = 917) had significantly higher frequencies of mutations in GATA3 (19% versus 16%) and CN amplifications (CNAs) (47% versus 26%), but significantly lower frequencies of mutations in PIK3CA (32% versus 47%), CDH1 (3% versus 9%), and MAP3K1 (7% versus 12%). Additionally, they had significantly higher frequencies of features suggestive of HRD (27% versus 21%) and a higher proportion of PIK3CA mutations with concurrent CNAs (23% versus 11%). Genomic features suggestive of HRD, PIK3CA mutations with CNAs, and CNAs were associated with significantly worse DRFI and OS compared with those without these features. These poor prognostic features were enriched in younger patients: present in 72% of patients aged <35 years, 54% aged 35-39 years, and 40% aged ≥40 years. Poor prognostic features [n = 584 (46%)] versus none [n = 692 (54%)] had an 8-year DRFI of 84% versus 94% and OS of 88% versus 96%. Younger women (<40 years) had the poorest outcomes: 8-year DRFI 74% versus 85% and OS 80% versus 93%, respectively. CONCLUSION: These results provide insights into genomic alterations that are enriched in young women with HR+HER2- EBC, provide rationale for genomic subgrouping, and highlight priority molecular targets for future clinical trials.

Time-resolved study of nonlinear photoemission in radio-frequency photoinjectors.

Photoemission is one of the fundamental processes that describes the generation of charged particles from materials irradiated by photons. The continuous progress in the development of ultrashort lasers allows investigation into the dynamics of the process at the femtosecond timescale. Here we report about experimental measurements using two ultrashort ultraviolet laser pulses to temporally probe the electrons release from a copper cathode in a radio-frequency photoinjector. By changing their relative delay, we studied how the release mechanism is affected by two-photon photoemission when tens of GW/cm2 intensities are employed. We evaluated the limits it poses on the achievable beam brightness and analyzed the resulting emission yield in terms of the electronic temperature by modeling the cathode as a two-temperature system.

Phase II study of eribulin in combination with gemcitabine for the treatment of patients with locally advanced or metastatic triple negative breast cancer (ERIGE trial). Clinical and pharmacogenetic results on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC).

BACKGROUND: The combination of a microtubule inhibitor (eribulin) with a nucleoside analog (gemcitabine) may synergistically induce tumor cell death, particularly in triple negative breast cancer (TNBC) characterized by high cell proliferation, aggressive behavior, and chemo-resistance. PATIENTS AND METHODS: This is an open-label, multicenter phase II study evaluating the combination of eribulin (0.88 mg/m2) plus gemcitabine (1000 mg/m2) on days 1 and 8 of a 21-day cycle as either first- or second-line treatment of locally advanced or metastatic TNBC. The primary endpoint was the objective response for evaluable patients. A prospective, molecular correlative study was carried out to assess the role of germinal BRCA pathogenic variants and single nucleotide polymorphisms (SNPs) in predicting efficacy and toxicity of the combination regimen. RESULTS: From July 2013 to September 2016, 83 evaluable patients were enrolled. They received a median number of six cycles of treatment. An overall response rate (ORR) of 37.3% (31 patients) was observed, with a complete response rate of 2.4% and a partial response rate of 34.9%; the clinical benefit rate was 48.8%. With a median follow-up of 28.8 months, the median response duration was 6.6 months, the median progression-free survival (PFS) was 5.1 months, and the median overall survival (OS) was 14.5 months. The most common grade 3-4 adverse events were aminotransferase elevation (in 25% of the patients) and neutropenia (in 23.8%). Women with BRCA1/2 pathogenic variants were associated with worse ORR, PFS, and OS than BRCA1/2 wild-type carriers. CYP3A4 and FGD4 SNPs were associated with increased risk of liver toxicity. Three different SNPs in CDA∗2, RRM1, and CYP2C8 genes were significantly associated with poorer OS. CONCLUSIONS: The combination of eribulin and gemcitabine showed promising activity and a moderate toxicity profile in metastatic TNBC. BRCA status and pharmacogenetics tests may help identify patients with high probability of response with negligible toxicity. EUDRACT NUMBER: 2012-003505-10.

The management of emergency spinal surgery during the COVID-19 pandemic in Italy.

AIMS: The current pandemic caused by COVID-19 is the biggest challenge for national health systems for a century. While most medical resources are allocated to treat COVID-19 patients, several non-COVID-19 medical emergencies still need to be treated, including vertebral fractures and spinal cord compression. The aim of this paper is to report the early experience and an organizational protocol for emergency spinal surgery currently being used in a large metropolitan area by an integrated team of orthopaedic surgeons and neurosurgeons. METHODS: An organizational model is presented based on case centralization in hub hospitals and early management of surgical cases to reduce hospital stay. Data from all the patients admitted for emergency spinal surgery from the beginning of the outbreak were prospectively collected and compared to data from patients admitted for the same reason in the same time span in the previous year, and treated by the same integrated team. RESULTS: A total of 19 patients (11 males and eight females, with a mean age of 49.9 years (14 to 83)) were admitted either for vertebral fracture or spinal cord compression in a 19-day period, compared to the ten admitted in the previous year. No COVID-19 patients were treated. The mean time between admission and surgery was 1.7 days, significantly lower than 6.8 days the previous year (p < 0.001). CONCLUSION: The structural organization and the management protocol we describe allowed us to reduce the time to surgery and ultimately hospital stay, thereby maximizing the already stretched medical resources available. We hope that our early experience can be of value to the medical communities that will soon be in the same emergency situation. Cite this article: Bone Joint J 2020;102-B(6):671-676.

A rare case of cervical junction ligamentous cyst.

Ligamentous cyst is a cystic formation arising from degeneration of ligamentous structures all around the spinal cord. They can cause spinal cord compression, like synovial cyst. Unlike synovial cyst, there is no spinal instability in pathogenesis of ligamentous cyst. Differential diagnosis through pre-operative MRI is difficult and intraoperative findings plus histopathology are crucial to achieve a diagnosis. In this case report, we deal with a rare case of cervical junction ligamentous cyst. A 59-year-old Caucasian female was admitted in our ward with left-sided hemiparesis, cervical pain, and upper limb diffused paresthesias, due to an oval-shaped formation into ALL, of 13 mm in maximum diameter, with peripheral contrast enhancement. The patient underwent, under general anesthesia, a surgery through a posterolateral suboccipital approach which aimed to decompress the spinal cord and to drain the cyst with total removal of the compression by emptying the cyst and fulfilling it with muscle graft and glue. No posterior fixation was needed. After the surgery, symptoms improved and a post-operative MRI scan demonstrated the good result of the surgery.

Exposure to reversine affects the chondrocyte morphology and phenotype in vitro.

Articular chondrocytes derived from osteoarthritic tissues (OA HAC) show a severely reduced chondrogenic commitment. This impairment undermines their use for tissue-engineered cartilage repair, which relies on cell proliferation and growth to meet therapeutic needs, but also on efficient cell plasticity to recover the chondrogenic phenotype. Reversine (Rev), a 2,6-disubstituted purine inhibitor of spindle-assembly checkpoints, was described to convert differentiated mesenchymal cells to their undifferentiated precursors. We hypothesized that Rev exposure could divert OA HAC to more plastic cells, re-boosting their subsequent commitment. HAC were enzymatically released from OA cartilage specimens, expanded for 2 weeks and treated with 5 µm Rev in dimethylsulphoxide (DMSO) or with DMSO alone for 6 days. Cell growth was assessed using the AlamarBlueTM assay. Cytoskeletal structure, endoproliferation and caspase-3-immunopositivity were assayed by epifluorescence microscopy. The OA HAC chondrogenic performance was evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) for glyceraldehyde-3-phosphate dehydrogenase, Sox9, Aggrecan (Agg), type II collagen (Col2), Ki67, cyclinD1, transforming growth factor-ß1 (TGF-ß1), -2 and -3, interleukin-1ß (IL-1ß) and -6 , SMAD3 and -7, and vascular endothelial growth factor. Rev-treated OA HAC recovered polygonal morphology and reduced Ki67 expression and proliferation. Cell-cycle impairment accounted for altered cytoskeletal organization, endoproliferation and apoptosis, whereas a compensatory mechanism sustained the increased cyclinD1 transcript levels. Sox9, Agg and TGFs were overexpressed, but not Col2. IL transcripts were massively downregulated. These events were dose-related and transient. Overall, in spite of a higher Rev-induced transcriptional activity for extracellular matrix components and in spite of a Rev-treated cell phenotype closer to that of the three-dimensional native articular chondrocyte, Rev effects seem unleashed from a full regained chondrogenic potential.

Metronomic Chemotherapy in Triple-Negative Metastatic Breast Cancer: The Future Is Now?

Triple-negative breast cancer (TNBC) shows a very bad prognosis, even in early stages of disease. Metronomic chemotherapy refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen with no prolonged drug-free breaks that leads to antitumor activity. In the present article, we review preclinical and clinical data of metronomic administration of chemotherapy agents with or without biological agents in TNBC cell lines and patients, contextually reporting data from the VICTOR-2 study in the subgroup of patients with TNBC, in order to stimulate new ideas for the design of clinical trials in this subset of patients.

Metronomic chemotherapy with oral vinorelbine (mVNR) and capecitabine (mCAPE) in advanced HER2-negative breast cancer patients: is it a way to optimize disease control? Final results of the VICTOR-2 study.

PURPOSE: The VICTOR-1 study demonstrated that the all-oral metronomic combination of vinorelbine and capecitabine is highly active and well tolerated in hormone receptor-positive/HER2-negative patients. The VICTOR-2 study was designed to confirm these results. METHODS: Patients received mVNR 40 mg three times a week and mCAPE 500 mg three times a day, continuously. The primary endpoint was the clinical benefit rate (CBR); secondary endpoints were toxicity, objective response rate (ORR), and progression-free survival (PFS). RESULTS: Eighty patients were evaluable for the primary efficacy analysis. Median age was 65.3 years; most patients had HR-positive tumors (65 %). The CBR was 45.7 % (95 % CI 28.8-63.4) and 51.1 % (95 % CI 35.8-66.3) in first- and ≥ second-line therapy, respectively. The ORR was 35.5 % in first-line (95 % CI 19.2-54.6) and 25.6 % in ≥second-line (95 % CI 13.5-41.2). The median duration of response was 11.3 and 6.4 months and PFS rates at 1 year were 24.3 and 22.2 %, respectively. In triple-negative breast cancer patients (N = 28, 35 %) a lower, but clinically relevant CBR (35.7, 95 % CI 18.6-55.9) was observed. The main toxicities per cycle were non-febrile neutropenia (1.1 %), hand-foot syndrome (1.0 %), nausea and vomiting (1.0 %), leucopenia (0.8 %), fatigue (0.7 %), and diarrhea (0.4 %). CONCLUSION: The VICTOR-2 study confirms the clinical activity of mVNR and mCAPE in HER2-negative breast cancer patients, suggesting that the easy schedule of administration, which requires monthly blood tests and limits patients' dependence on hospitals, and the low cost of the drugs are valuable elements, even for countries with limited access to innovative or expensive drugs.

Use of serum levels of high sensitivity troponin T, galectin-3 and C-terminal propeptide of type I procollagen at long term follow-up in heart failure patients with reduced ejection fraction: Comparison with soluble AXL and BNP.

BACKGROUND: Prognostic biomarkers are needed to improve the management of the heart failure (HF) epidemic, being the brain natriuretic peptides the most valuable. Here we evaluate 3 biomarkers, high sensitivity troponin T (hs-TnT), galectin-3 (Gal-3) and C-terminal propeptide of type I procollagen (CICP), compare them with a recently described new candidate (sAXL), and analyze their relationship with BNP. METHODS: HF patients with reduced ejection fraction (n=192) were included in this prospective observational study, with measurements of candidate biomarkers, functional, clinical and echocardiographic variables. A Cox regression model was used to determine predictors for clinical events, i.e. all-cause mortality and heart transplantation. RESULTS: Hs-TnT circulating values were correlated to clinical characteristics indicative of more advanced HF. When analyzing the event-free survival at a mean follow-up of 3.6years, patients in the higher quartile of either BNP, hs-TnT, CICP and sAXL had increased risk of suffering a clinical event, but not Gal-3. Combination of high sAXL and BNP values had greater predictive value (HR 6.8) than high BNP alone (HR 4.9). In a multivariate Cox regression analysis, BNP, sAXL and NYHA class were independent risk factors for clinical events. CONCLUSIONS: In this HF cohort, hs-TnT is a good HF marker and has a very significant prognostic value. The prognostic value of CICP and sAXL was of less significance. However, hs-TnT did not add predictive value to BNP, while sAXL did. This suggests that elevated troponin has a common origin with BNP, while sAXL could represent an independent pathological mechanism.

A New Quantitative Approach to Assessing Noncompliance With Medical Recommendations in Heart Transplant Recipients.

BACKGROUND: Failure of compliance with medical regimen is one of the major risk factors associated with morbidity and mortality in heart transplant (HT) recipients. Nevertheless, to date, there is no specific, gold-standard, comprehensive set of tools for assessing compliance in these patients. OBJECTIVE: The objective of the present study was to develop a specific instrument for the assessment of noncompliance with medical recommendations in HT recipients. METHODS: This prospective observational study used a nonprobability sampling method, which was performed from January 2006 to December 2012. All of the patients met clinical criteria for being included on the waiting list for a HT. We designed a scale for measuring the compliance degree at 12 months after heart transplantation. This scale included the most important aspects of the medical regimen, using nine discrete quantitative variables. The total score was described as the patient's Noncompliance Factor (NCF). The results were analysed by mean, ranks, and percentages. RESULTS: The sample was constituted of 61 participants who underwent surgical HT intervention and completed the 12-month follow-up assessment. The overall incidence of noncompliance was around 30% and only 43.1% of the recipients had an acceptable degree of compliance. CONCLUSIONS: The overall incidence of noncompliance in HT recipients is high and this can generate worse clinical outcomes. Evaluation by specific screening instruments like the one proposed in the present study can be useful for a systematic detection of this phenomenon.

Cancer Incidence in Heart Transplant Recipients With Previous Neoplasia History.

Neoplasm history increases morbidity and mortality after solid organ transplantation and has disqualified patients from transplantation. Studies are needed to identify factors to be considered when deciding on the suitability of a patient with previous tumor for heart transplantation. A retrospective epidemiological study was conducted in heart transplant (HT) recipients (Spanish Post-Heart Transplant Tumor Registry) comparing the epidemiological data, immu-nosuppressive treatments and incidence of post-HT tumors between patients with previous malignant noncardiac tumor and with no previous tumor (NPT). The impact of previous tumor (PT) on overall survival (OS) was also assessed. A total of 4561 patients, 77 PT and 4484 NPT, were evaluated. The NPT group had a higher proportion of men than the PT group (p < 0.001). The incidence of post-HT tumors was 1.8 times greater in the PT group (95% confidence interval [CI] 1.2-2.6; p < 0.001), mainly due to the increased risk in patients with a previous hematologic tumor (rate ratio 2.3, 95% CI 1.3-4.0, p < 0.004). OS during the 10-year posttransplant period was significantly lower in the PT than the NPT group (p = 0.048) but similar when the analysis was conducted after a first post-HT tumor was diagnosed. In conclusion, a history of PT increases the incidence of post-HT tumors and should be taken into account when considering a patient for HT.

Cost-Effectiveness of Highly Sensitive Cardiac Troponin T to Rule Out Acute Rejection After Heart Transplantation.

BACKGROUND: Endomyocardial biopsy (EMB) remains the gold standard for detecting acute rejection (AR) after heart transplantation (HTx). Non-invasive detection of AR thus far remains a challenge. Several studies have demonstrated that highly sensitive cardiac troponin T (hs-cTnT) concentrations have a low positive predictive value for diagnosing AR. Nevertheless, hs-cTnT proved to be useful for ruling out AR after HTx. An hs-cTnT concentration <17 ng/L, a value close to that used for rule-in or rule-out myocardial infarction, was associated with a 100% negative predictive value of AR. However, the cost-effectiveness of a strategy with the use of hs-cTnT for ruling out AR in HTx patients remains to be proven. METHODS: The cost-effectiveness of hs-cTnT determination for ruling out AR was assessed, comparing the costs of hs-cTnT measurements in 305 blood samples obtained at the time of EMB. Eighteen samples were excluded because the EMB was not assessable. RESULTS: Hs-cTnT determination cost 16.00€ per sample, whereas EMB cost 1752.00€ per biopsy; cost estimations included direct and indirect (30%) charges. Thirty-nine (13.6%) of the 287 blood samples presented hs-cTnT concentrations <17 ng/L; in none of them was an AR >2R degree found in the EMB. The cost of the assessment in the 287 blood samples and biopsies was of 4592.00€ for hs-cTnT and 502,824.00€ for EMB. Hs-cTnT systematic measurement would have avoided 39 EMB, with a saving of 68,328.00€, which represents the 13.5% of the total budget expended in these cases. CONCLUSIONS: The use of hs-cTnT values to rule out the need of EMB for AR diagnosis after HTx appears to be a cost-effective procedure.

Two-Color Radiation Generated in a Seeded Free-Electron Laser with Two Electron Beams.

We present the experimental evidence of the generation of coherent and statistically stable two-color free-electron laser radiation obtained by seeding an electron beam double peaked in energy with a laser pulse single spiked in frequency. The radiation presents two neat spectral lines, with time delay, frequency separation, and relative intensity that can be accurately controlled. The analysis of the emitted radiation shows a temporal coherence and a shot-to-shot regularity in frequency significantly enhanced with respect to the self-amplified spontaneous emission.

Clinical features and outcomes of tuberculosis in transplant recipients as compared with the general population: a retrospective matched cohort study.

There are no previous studies comparing tuberculosis in transplant recipients (TRs) with other hosts. We compared the characteristics and outcomes of tuberculosis in TRs and patients from the general population. Twenty-two TRs who developed tuberculosis from 1996 through 2010 at a tertiary hospital were included. Each TR was matched by age, gender and year of diagnosis with four controls selected from among non-TR non-human immunodeficiency virus patients with tuberculosis. TRs (21 patients, 96%) had more factors predisposing to tuberculosis than non-TRs (33, 38%) (p <0.001). Pulmonary tuberculosis was more common in non-TRs (77 (88%) vs. 12 TRs (55%); p 0.001); disseminated tuberculosis was more frequent in TRs (five (23%) vs. four non-TRs (5%); p 0.005). Time from clinical suspicion of tuberculosis to definitive diagnosis was longer in TRs (median of 14 days) than in non-TRs (median of 0 days) (p <0.001), and invasive procedures were more often required (12 (55%) TRs and 15 (17%) non-TRs, respectively; p 0.001). Tuberculosis was diagnosed post-mortem in three TRs (14%) and in no non-TRs (p <0.001). Rates of toxicity associated with antituberculous therapy were 38% in TRs (six patients) and 10% (seven patients) in non-TRs (p 0.014). Tuberculosis-related mortality rates in TRs and non-TRs were 18% and 6%, respectively (p 0.057). The adjusted Cox regression analysis showed that the only predictor of tuberculosis-related mortality was a higher number of organs with tuberculosis involvement (adjusted hazard ratio 8.6; 95% CI 1.2-63). In conclusion, manifestations of tuberculosis in TRs differ from those in normal hosts. Post-transplant tuberculosis resists timely diagnosis, and is associated with a higher risk of death before a diagnosis can be made.

Dosimetry of very high energy electrons (VHEE) for radiotherapy applications: using radiochromic film measurements and Monte Carlo simulations.

Very high energy electrons (VHEE) in the range from 100-250 MeV have the potential of becoming an alternative modality in radiotherapy because of their improved dosimetry properties compared with MV photons from contemporary medical linear accelerators. Due to the need for accurate dosimetry of small field size VHEE beams we have performed dose measurements using EBT2 Gafchromic® film. Calibration of the film has been carried out for beams of two different energy ranges: 20 MeV and 165 MeV from conventional radio frequency linear accelerators. In addition, EBT2 film has been used for dose measurements with 135 MeV electron beams produced by a laser-plasma wakefield accelerator. The dose response measurements and percentage depth dose profiles have been compared with calculations carried out using the general-purpose FLUKA Monte Carlo (MC) radiation transport code. The impact of induced radioactivity on film response for VHEEs has been evaluated using the MC simulations. A neutron yield of the order of 10(-5) neutrons cm(-2) per incident electron has been estimated and induced activity due to radionuclide production is found to have a negligible effect on total dose deposition and film response. Neutron and proton contribution to the equivalent doses are negligible for VHEE. The study demonstrates that EBT2 Gafchromic film is a reliable dosimeter that can be used for dosimetry of VHEE. The results indicate an energy-independent response of the dosimeter for 20 MeV and 165 MeV electron beams and has been found to be suitable for dosimetry of VHEE.

Robot-assisted or conventional laparoscoic rectopexy for rectal prolapse? Systematic review and meta-analysis.

AIM: The use of robotic technology has proved to be safe and effective, arising as a helpful alternative to standard laparoscopy in a variety of surgical procedures. However the role of robotic assistance in laparoscopic rectopexy is still not demonstrated. METHODS: A systematic review of the literature was carried out performing an unrestricted search in MEDLINE, EMBASE, the Cochrane Library, and Google Scholar up to 30th June 2014. Reference lists of retrieved articles and review articles were manually searched for other relevant studies. We meta-analyzed the data currently available regarding the incidence of recurrence rate of rectal prolapse, conversion rate, operative time, intra-operative blood loss, post-operative complications, re-operation rate and hospital stay in robot-assisted rectopexy (RC) compared to conventional laparoscopic rectopexy (LR). RESULTS: Six studies were included resulting in 340 patients. The meta-analysis showed that the RR does not influence the recurrence rate of rectal prolapse, the conversion rate and the re-operation rate, whereas it decreases the intra-operative blood loss, the post-operative complications and the hospital stay. Yet, the RR resulted to be longer than the LR. Post-operative ano-rectal and the sexual functionality and procedural costs could not meta-analyzed because the data from included studies about these issues were heterogeneous and incomplete. CONCLUSION: The meta-analysis showed that the RR may ensure limited improvements in post-operative outcomes if compared to the LR. However, RCTs are needed to compare RR to LR in terms of short-term and long-term outcomes, specially investigating the functional outcomes that may confirm the cost-effectiveness of the robotic assisted rectopexy.

The falling incidence of hematologic cancer after heart transplantation.

BACKGROUND: A number of changes in the management of heart transplantation (HT) patients have each tended to reduce the risk of post-HT hematologic cancer, but little information is available concerning the overall effect on incidence in the HT population. METHODS: Comparison of data from the Spanish Post-Heart-Transplantation Tumour Registry for the periods 1991-2000 and 2001-2010. RESULTS: The incidence among patients who underwent HT in the latter period was about half that observed in the former, with a particularly marked improvement in regard to incidence more than five yr post-HT. CONCLUSIONS: Changes in HT patient management have jointly reduced the risk of hematologic cancer in the Spanish HT population. Long-term risk appears to have benefited more than short-term risk.

Toxoplasmic encephalitis associated with meningitis in a heart transplant recipient.

Toxoplasma gondii is an opportunistic pathogen that causes neurologic and extraneurologic manifestations in immunosuppressed patients. Encephalitis and intracranial mass lesions are easily recognized as typical manifestations of toxoplasmosis. However, meningitis caused by T. gondii is a rare condition with very few cases described in the literature. We present the case of a heart transplant recipient who developed toxoplasmic encephalitis associated with meningitis. After an extensive review of the medical literature, we found only 1 case of meningitis in solid organ transplant recipients and <25 cases in immunosuppressed patients, such as patients infected with human immunodeficiency virus or those with Hodgkin's disease. In this report, we consider toxoplasmosis in the differential diagnosis of meningitis in immunocompromised individuals.

AXL receptor tyrosine kinase is increased in patients with heart failure.

BACKGROUND: AXL is a membrane receptor tyrosine kinase highly expressed in the heart and has a conspicuous role in cardiovascular physiology. The role of AXL in heart failure (HF) has not been previously addressed. METHODS AND RESULTS: AXL protein was enhanced 6-fold in myocardial biopsies of end-stage HF patients undergoing heart transplantation compared to controls from heart donors (P<0.0001). Next, we performed a transversal study of patients with chronic HF (n=192) and a group of controls with no HF (n=67). sAXL and BNP circulating levels were quantified and clinical and demographic data were collected. sAXL levels in serum were higher in HF (86.3 ± 2.0 ng/mL) than in controls (67.8 ± 2.0 ng/mL; P<0.0001). Also, sAXL correlated with several parameters associated with worse prognosis in HF. Linear regression analysis indicated that serum creatinine, systolic blood pressure and atrial fibrillation, but not BNP levels, were predictive of sAXL levels. Cox regression analysis indicated that high sAXL values at enrollment time were related to the major HF events (all-cause mortality, heart transplantation and HF hospitalizations) at one year follow-up (P<0.001), adding predictive value to high BNP levels. CONCLUSIONS: Myocardial expression and serum concentration of AXL is elevated in HF patients compared to controls. Furthermore, peripheral sAXL correlates with parameters associated with the progression of HF and with HF events at short term follow-up. All together these results suggest that sAXL could belong to a new molecular pathway involved in myocardial damage in HF, independent from BNP.