The role of body mass index in the development of thromboembolic events among cancer patients with PICCs: a systematic review.

OBJECTIVE: Peripherally inserted central catheters (PICC) guarantee a stable and safe vascular access to administer irritants or vesicants therapies. However, they may occasionally be affected by relevant thrombotic complications especially in patients with hypercoagulability such as oncological patients. Among the identification of independent risk factors, the role of body mass index (BMI) ≥25 kg/m2 is now emerging in literature with conflicting results. The aim of this systematic review is to analyze the available scientific literature in order to determine whether BMI could represent a risk factor in the development of thromboembolic event among cancer patients with PICCs. DATA SOURCES AND REVIEW METHODS: A scientific literature review was performed in Pubmed, Embase and Cinahl from Jan 1, 2010 to September 10, 2020 in which we identified 100 records. Of these, 88 were excluded and 14 were reviewed in full text. Among the reviewed records, 6 articles satisfied the inclusion criteria for analysis. These criteria included the English language, oncological patients with PICCs, the evaluation of catheter-related thrombosis as well as the stratification of patients according to BMI. Studies off topic and lacking data on PICC related complications among overweight and underweight patients were excluded. The includedstudies, judged with Newcastle-Ottawa Scale, was fair-lower quality. The primary endpoint was the relative risk (RR) of PICC-related thrombosis of overweight/obese vs normal weight/underweight (i.e., BMI ≥25 vs <25 kg/m2) in cancer patients. RESULTS: A total of 2431 patients were included in the analysis. Overall, 15.1% of patients developed PICC-related thrombosis within a median time of 23.2 days (range 11.0-42.5) after PICC implantation. Concerning BMI, 52.6% of the entire population was overweight/obese. We assessed the proportion of patients with PICC-related thrombotic events in the two groups, with 28% (95% CI, 12%-45%) of events registered in the overweight/obese patients cohort, and 13% (95% CI, 6%-19%) in the normal weight/underweight cohort. The pooled relative risk (RR) was 2.06 (95% CI, 1.21-3.49, p<0.001) in overweight/obese vs normal weight/underweight patients. CONCLUSION: This review showed a two-fold risk of thrombosis in overweight/obese compared to normal weight/underweight oncological patients with PICCs. Underweight condition could also play a role in thrombosis development, especially in nasopharyngeal and digestive system cancer. Future prospective studies are needed to achieve reliable results and produce useful conclusion.

Long term follow up in 183 high grade meningioma: A single institutional experience.

INTRODUCTION: Meningiomas are usually considered benign lesions, however a proportion of them shows a more aggressive behavior, defined high-grade meningiomas (HGM). Effective medical treatments are lacking, especially at the time of recurrence. METHODS: Through a retrospective analysis, we examined epidemiological, diagnostic, therapeutic, recurrence information and survival data of HGM treated at our institution between 2010 and 2018. RESULTS: 183 patients (105 females and 78 males), with median age of 58 years (25-88), were included; 168 were atypical, 12 anaplastic, 3 rhabdoid. Overall, m-PFS was 4.2 years, and m-OS was 10.3 years. Gross-total resection had a 5-year survival rate of 95% compared with subtotal/partial resection (86% and 67%) (p = 0.002). Higher expression of Ki-67/MIB-1 seems associated with higher risk of death (HR:1.06 with 95% CI, 1.00-1.12, p = 0.03). No statistically significant differences were seen in survival between the group managed with a wait-and-see strategy vs the group treated with RT while a difference on PFS was seen (4.1 years vs 5.2 years p = 0.03). After second recurrence, the most employed treatments were systemic therapies with a very limited effect on disease control. CONCLUSIONS: Data confirmed the aggressive behavior of HGM. The extent of resection seems to correlate with a favorable outcome regardless histological subtypes. The role of RT remains controversial, with no statistically significant impact on OS but a possible role on PFS. Recurrent HGM remains the real challenge, to date no chemotherapies are able to achieve disease control. Future research should focus on biological/molecular predictors in order to achieve a patient-tailored treatment.

Prospective observational study on the complications and tolerability of a peripherally inserted central catheter (PICC) in neuro-oncological patients.

PURPOSE: The use of central venous catheters with peripheral insertion (PICC) has increased rapidly in recent years, particularly in cancer patients. The benefits provided may occasionally be affected by relevant complications, such as infections and thrombotic events, especially in neuro-oncological patients. To date, the risk of PICC-related complications in this subset of patients is unknown, as is tolerability. As a primary objective, this study aimed to collect complications related to PICCs in primary neuro-oncological patients. As a secondary objective, the study aimed to evaluate PICC tolerability. METHODS: Neuro-oncological patients with PICCs that were placed as part of normal clinical practice at IRCCS Neurologico C. Besta were consecutively enrolled in the study. PICC-related complications were recorded immediately (during the procedure), early (within 1 week after PICC insertion), and late (1-3-5 months after PICC placement). At the same time points, all patients were also evaluated for tolerability through interviews with semi-structured, open-ended questions. RESULTS: Sixty patients were enrolled (41 males and 19 females, with a median age of 56.2 years). Excluding loss to follow-up, 33/49 patients developed at least one complication related to the PICC. Immediate complications mainly included hematoma (8), accidental arterial puncture (4), and primary malpositioning (3). Regarding early and late complications, 3 device-related infections, 8 thrombotic events, and 20 mechanical complications were registered. Semi-structured interviews revealed an overall positive experience with the device. The most negative impact was on hygiene habits, with 34 patients becoming caregiver-dependent. Over time, almost all patients became used to the device and perceived greater security during chemotherapy. A strongly negative issue was the difficulty of relying on competently trained healthcare personnel in outpatient setting. CONCLUSION: The results showed a nonnegligible increased thromboembolic risk in neuro-oncological patients with PICCs, almost double that in historical oncological populations. It is essential to extend the study to a greater number of patients to achieve reliable results and to identify patients at high risk. The device seems to be positively accepted by the majority of patients, without affecting activities of daily living.

Main changes in European Clinical Trials Regulation (No 536/2014).

The new Regulation (EU) No. 536/2014 for clinical trials of medicinal products for human is part of a European regulatory framework in which the European Commission has wished to give a strong impetus to scientific research and industrial progress. It is a new regulation that fills a series of regulatory gaps in the Clinical Trials through the creation of a uniform framework for the authorization of clinical trials by all interested Member States with a single assessment of the results. The Regulation thus facilitates cross-border cooperation to make the clinical tests wider and encourage the development of special treatments, for example for rare diseases, but above all streamlines the rules on clinical trials across European Union (EU), introducing simplified rules for experimentation so-called 'low level of intervention', on which much has been discussed and still arouses concern, providing for authorized medicines or used off-label in the presence of scientific evidence published on efficacy and safety and to benefit from they will be mainly the pediatric and oncological therapeutic areas. The applications and any communication will be submitted paperlessly via a new electronic EU portal. The complex processing procedures and shorter time limits are to be stressed in comparison to the previously valid regulations. This is a major challenge for all stakeholders, but on the other hand it should contribute to the future role of the EU in the development of innovative medicines.

The E3 ubiquitin ligase WWP1 sustains the growth of acute myeloid leukaemia.

The E3 ubiquitin ligase (E3) WWP1 is an oncogenic factor implicated in the maintenance of different types of epithelial cancers. The role of WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) in haematological neoplasms remains unknown. Acute myeloid leukaemia (AML) is characterized by the expansion of malignant myeloid cells blocked at different stages of differentiation. Here we report that the expression of WWP1 is significantly augmented in a large cohort of primary AML patients and in AML cell lines, compared with haematopoietic cells from healthy donors. We show that WWP1 inactivation severely impairs the growth of primary AML blasts and cell lines in vitro. In vivo, we observed a reduced leukaemogenic potential of WWP1-depleted AML cells upon transplantation into immunocompromised mice. Mechanistically, WWP1 inactivation induces the accumulation of its protein substrate p27Kip1, which ultimately contributes to G0/G1 cell cycle arrest of AML blasts. In addition, WWP1 depletion triggers the autophagy signalling and reduces survival of leukaemic cells. Collectively, our findings provide molecular insights into the anti-cancer potential of WWP1 inhibition, suggesting that this E3 is a promising biomarker and druggable target in AML.

Valor nutritivo da Coastcross-1 inoculada com Azospirillum brasilense / Nutritive value of Coastcross-1 inoculated with Azospirillum brasilense

Objetivou-se com este trabalho avaliar a taxa de produção de forragem e o valor nutritivo da Coastcross-1, inoculada com Azospirillum brasilense, fertilizada com diferentes doses de N e submetida ao regime de corte. O delineamento experimental foi o de blocos ao acaso, com três repetições, em esquema fatorial. Os fatores foram o uso da inoculação (não inoculada, inoculada somente no plantio e reinoculada no segundo ano), níveis de N (0, 100 e 200kg/ha/ano de N) e os períodos do ano. Avaliaram-se a taxa de produção e a composição botânica da forragem, a composição morfológica, o teor de proteína bruta, a digestibilidade in situ da matéria orgânica e os nutrientes digestíveis totais da Coastcross-1. A inoculação, quando não associada ao adubo nitrogenado, ocasionou aumento na taxa de produção de forragem, na participação da Coastcross-1 e na produção de nutrientes digestíveis totais. Houve redução nos teores de proteína bruta da Coastcross-1, quando a gramínea adubada com 200kg/ha/ano de N foi inoculada. A inoculação tem efeito positivo na Coastcross-1 não submetida à adubação nitrogenada.(AU)

The objective of this study was to evaluate the forage yield rate and nutritive value of Coastcross-1 inoculated with Azospirillum brasilense and fertilized with different levels of nitrogen subjected to cut. The experimental design was randomized blocks with three replications, in a factorial scheme. The factors were the inoculation (without inoculation, inoculated just in the implantation and reinoculated in the second year), levels of nitrogen (0, 100 and 200kg/ha/year of N) and periods of the year. Forage yield rate and botanical composition; morphological composition, crude protein content, in situ digestibility of organic matter and the total digestible nutrients of Coastcross-1 were evaluated. Inoculation increased the forage yield rate, Coastcross-1 contribution and production of total digestible nutrients, when the pasture was not fertilized with N. There was reduction in Coastcross-1 crude protein content when fertilized with 200kg/ha/yr of N. The inoculation has a positive effect on Coastcross-1 not submitted to nitrogen fertilization.(AU)

Extra central nervous system metastases from glioblastoma: a new possible trigger event?

Extra-cranial metastases of glioblastoma (GBM) represent a rare event, and the biological-genetic mechanisms involved in the pathogenesis have not yet been determined. We report the case of a young patient with multiple visceral and osseous metastases occurred after 4 years after first diagnosis of GBM. The strangeness as well as the rarity of this event does not allow to identify an effective treatment for GBM metastases, making the management of this ominous tumor an even greater challenge.

A case of medulloblastoma in adult patient affected by anaplastic oligoastrocytoma.

Medulloblastomas and high-grade gliomas (HGG) are two distinct brain tumor, with different peculiarities in terms of age of onset, localizations and prognosis. The coexistence of the two neoplasms in the same adult patient is an extremely rare event. We present the case of a woman treated with radio-chemotherapy for an HGG, who developed a cerebellar medulloblastoma 7 years later. Considering the poor prognosis of these tumors, the lack of knowledge about the mechanisms of onset as well as effective therapies, it is necessary to determine the exact role of irradiation and the presence of any potential molecular genetic abnormalities in the developing of the two tumors.

Safety and efficacy of primary central nervous system lymphoma treatment in elderly population.

Elderly patients represent an important subgroup in primary central nervous system lymphoma (PCNSL) that accounts for approximately half the cases. Furthermore age represents one of the heaviest prognostic factors and in some cases it has more effect on survival than therapies. We performed a retrospective analysis to assess the toxicity and the efficacy of high-dose methotrexate (HDMTX) chemotherapy in a PCNSL population older than 70 years. Seventeen consecutive immunocompetent patients older than 70 years, with histologically confirmed PCNSL, without systemic involvement, treated with HDMTX at our institution between May 2005 and April 2013, were retrospectively evaluated. Main outcome measures were acute toxicity and tumour response. No evidence of haematological toxicity was recorded in 47 % of patients and no deaths related to toxicity grade were reported. Patients achieved a partial response after 3 cycles of chemotherapy in 53 % of cases. The median overall survival (m-OS) from diagnosis was 20.9 months (range 5.2-34 months), with OS-12 of 58.8 % and an OS-24 of 45.4 %. Since there is no standard of care in the treatment of PCNSL in elderly population, it should be taken into account that elderly patients not always can be considered "fragile" and the general tendency to less treat to avoid severe toxicity should not be the rule.

Isthmocele in a retroflexed uterus: a report of an unrecognized case.

The term "isthmocele" refers to a niche on the anterior wall of the uterine isthmus or of the cervical canal at the site of a previous cesarean delivery scar. Such anatomic defect can cause many gynecologic sequelae that only recently have being identified and described. Hysteroscopy is commonly considered the gold standard for the diagnosis and also for the treatment, at least in the case of defects of small size. The authors described the case of a 37-year-old woman who underwent a cesarean section (CS) seven years before, with a long lasting history of menstrual irregularities, and pelvic pain increasing during menstruation at the hypogastric level. Magnetic resonance imaging (MRI) showed an exceptionally large isthmocele on the anterior wall of a retroflexed uterus which was otherwise misinterpreted as the uterine cavity filled with menstrual blood during a previous hysteroscopy (HSC). Although exceptional, this case highlights the possibility that a large sized isthmocele in a retroflexed uterus could be misinterpreted as the uterine cavity filled by menstrual blood at HSC. In this case MRI definitely clarified the diagnosis.

Clinical management of grade III oligodendroglioma.

Oligodendrogliomas represent the third most common type of glioma, comprising 4%-15% of all gliomas and can be classified by degree of malignancy into grade II and grade III, according to WHO classification. Only 30% of oligodendroglial tumors have anaplastic characteristics. Anaplastic oligodendroglioma (AO) is often localized as a single lesion in the white matter and in the cortex, rarely in brainstem or spinal cord. The management of AO is deeply changed in the recent years. Maximal safe surgical resection followed by radiotherapy (RT) was considered as the standard of care since paramount findings regarding molecular aspects, in particular co-deletion of the short arm of chromosome 1 and the long arm of chromosome 19, revealed that these subsets of AO, benefit in terms of overall survival (OS) and progression-free survival (PFS), from the addition of chemotherapy to RT. Allelic losses of chromosomes 1p and 19q occur in 50%-70% of both low-grade and anaplastic tumors, representing a strong prognostic factor and a powerful predictor of prolonged survival. Several other molecular markers have potential clinical significance as IDH1 mutations, confirming the strong prognostic role for OS. Malignant brain tumors negatively impacts on patients' quality of life. Seizures, visual impairment, headache, and cognitive disorders can be present. Moreover, chemotherapy and RT have important side effects. For these reasons, "health-related quality of life" is becoming a topic of growing interest, investigating on physical, mental, emotional, and social well-being. Understanding the impact of medical treatment on health-related quality of life will probably have a growing effect both on health care strategies and on patients.

MRI in the assessment of prolapsed pedunculated submucous leiomyomas: two case reports.

Uterine leiomyomas are the most common benign gynecological tumors affecting 20-30% of women in reproductive age. Despite their benignity, in some cases several symptoms may require surgical intervention. Submucosal leiomyomas are less frequent (5-10%), but are usually symptomatic. Approximately 2.5% of the myomas are pedunculated and can protrude in the cervical canal. Symptomatic leiomyomas can be treated either by hysterectomy or myomectomy, and these procedures can be performed with several techniques. Whenever possible, hysteroscopic myomectomy is better because it has many advantages, as it also preserves future fertility. Two interesting cases of prolapsed pedunculated submucous leiomyomas are reported in order to prove that magnetic resonance imaging (MRI) is essential to choose the most appropriate treatment and to perform an adequate presurgical planning, which must be based on an overall assessment of the leiomyoma's characteristics (number, location, size and presence or absence of a stalk) and the patient's characteristics.

Pedal and plantar loop angioplasty: technique and results.

Endovascular and subintimal approaches fails in obtaining a below-the-knee recanalization in 10-40% of cases, even in high-volume and expertise centers. The presence of long calcified occlusions, characterized by a complex anatomy, often necessitate the use of alternative techniques in order to obtain a direct blood flow to the foot arteries. Recanalization using pedal and plantar loop angioplasty could improve outcomes in the presence of a communication between the dorsal and plantar arch of the foot, if conventional techniques are not effective.

Update on treatment strategies for anaplastic glioma: a review of literature.

Anaplastic gliomas (AG) include 6-10% of all newly diagnoses of primary brain tumors. They have an unfavourable prognosis and, to date, there is not an established treatment universally recognized. Four recent randomized clinical trials were identified for a total of 1,170 patients (anaplastic-astrocytomas, anaplasticoligoastrocytoma, anaplastic-oligodendroglioma), in order to define the better sequence and timing of chemo-radiotherapy, Three studies compared radiotherapy (RT) treatment vs. radio-chemotherapy with procarbazine-lomustine-vincristine (PCV) or temozolomide (TMZ) or dibromodulcitol and bichloroethylnitrosurea (DBD/BCNU) and only one compared RT vs chemotherapy (CT) with PCV or TMZ. Results show no significant differences in terms of PFS/OS between RT/CT alone or combined treatment although a trend toward an improvement of OS was observed after RT + CT treatment (m-OS in RT + adjuvant PCV was 42.3 vs. 30.6 months in RT alone p=0.0003). Grade 3-4 mielotoxicity has been observed in almost all cases of patients treated with PCV + RT. None of four studies reviewed conducted a head to head comparison between PCV vs. TMZ. Only a study randomized patients to PCV/TMZ without however providing data in terms of PSF and OS between the two treatments. It found no significant differences in PFS from initial RT and adjuvant CT (PCV-TMZ) at progression compared to initial CT followed by RT at progression. The optimal treatment of AG should reasonably consider not only the histology as well as the molecular markers of the tumor, but also clinical conditions, age of patients, life expectancy, Karnofsky-performance-status and tumor resection to achieve in future the personalization of care.

Lung Metastasis after an Eighteen-Years-Long Disease-Free Period since Uterine Leiomyosarcoma Diagnosis.

Uterine leiomyosarcoma (ULMS) is an uncommon malignancy that accounts for one-third of uterine sarcomas and represents 1% of all uterine malignancies, with an incidence averaging 0.5-1/100,000/year. The prognosis is poor due to its intrinsic aggressiveness and its characteristic high metastatic potential with reported distant metastatic spread in lung, abdomen, soft tissue, and brain. We present the case of a 67-year-old woman with lung metastasis after eighteen years since uterine leiomyosarcoma diagnosis and its following surgical resection. The diagnosis of pulmonary metastases was obtained by reviewing the histology of the previous uterine tumor: the tumor cells were immunoreactive for CD10, PR, and smooth muscle actin (SMA), but negative for desmin, S100, CD34, CD 117, cytokeratins AE1AE3, CD68R, and ER. To our knowledge, this disease-free interval is the longest among previous reports of pulmonary metastasis of uterine leiomyosarcoma.

Safety of bevacizumab in patients with malignant gliomas: a systematic review.

Angiogenesis has recently become a major target for the development of new antineoplastic drugs. The most serious adverse events linked to angiogenesis inhibitors are venous or arterial thromboembolism and haemorrhage. Thus, there is need to define with more certainty the impact of these new drugs in terms of adverse effects in neurological patients. The aim of the study is to assess the risk of venous thromboembolism (VTE) and bleeding in patients with malignant gliomas treated with bevacizumab with or without concomitant anticoagulant therapy. A review of published literature was performed in Medline, from which 476 records were identified. A total of 27 full-text articles, including retrospective analyses, retrospective reviews, and open label trials, were assessed for eligibility. The investigated drugs included bevacizumab alone, bevacizumab plus chemotherapy with/without concomitant radiation therapy; only two articles dealt with bevacizumab in association with anticoagulant treatment. A total of 2,208 patients with malignant gliomas, were identified and included in the analysis. From data it appears that patients receiving bevacizumab had a major risk of developing VTE that increased when bevacizumab is associated with radio-chemotherapy (4.27 vs 7.46 %). Regarding bleeding, data showed that patients treated with anticoagulant had a significantly increased risk of severe central nervous system (CNS) bleeding compared to patients not receiving anticoagulant therapy (0.6 vs 8.2 %). The use of bevacizumab combined with chemo-radiotherapy seems to be associated with a higher risk for VTE compared to patients receiving antiangiogenic therapy alone. The associated use of anticoagulants and bevacizumab far increases the risk of developing CNS and non-CNS bleeding higher than grade 3, compared to patients receiving bevacizumab alone.

Reverse perfusion pattern in myocardial spect with 99mTc-sestaMIBI.

RATIONALE: The aim of our study was to investigate the myocardial perfusion deficit in rest images as compared to stress images in myocardial scintigraphy (MS). OBJECTIVES: The aim of this study is to investigate the reverse perfusion (RP) pattern in MS. METHODS AND RESULTS: 263 patients were enrolled in the study (72 females and 191 males; mean age 65.7 ± 9.5 years old). Mean body mass index (BMI) was of 27.6 ± 3.8 Kg/m2. 115 patients were positive for a previous history of myocardial infarction (MI). 142 patients reported a revascularization treatment (percutaneous transluminal coronary angioplasty, PTCA, cardiac stent placement, coronary artery bypass grafting, CABG). All the patients underwent MS following standard single day Stress/Rest protocol. In our series, 27 patients presented a RP pattern. We did not find statistically significant differences when considering age (p = 0.7988), sex (p = 0.0657), BMI (p = 0.8611), diabetes (p = 0.8259), dyslipidemia (p = 0.1464) or smoking status (p = 0.6829) in RP patients vs. non-RP patients. A history of MI is related to a RP pattern (p < 0.0001). A history of previous revascularization was not related with RP (p = 0.6868). DISCUSSION: The result of our study suggested that RP is probably related to artifacts of various origins. Further studies are necessary especially in microvascular dysfunction or a long history of disease.

Traumatic burst fracture with spinal channel involvement augmentation with bioactive strontium-hydroxyapatite cement.

In November 2011 a 75-year-old man was admitted to our emergency department with a low back pain caused by a traumatic L1 vertebral collapse with backward projection of posterior wall superior third. The indication for neurosurgical instrumentation was placed, although he refused the treatment. Hence he was treated conservatively without a significant improvement up to January 2012 when, still refusing surgery, he accepted to undergo percutaneous vertebroplasty with a novel bioactive injectable strontium-hydroxyapatite cement. Vertebroplasty was performed without complications. A CT scan, performed the day after the procedure, ruled out extravertebral cement leakage. Pain improvement was significant (preprocedure VAS 10, one-week VAS 4) with a gradual decrease up to three months when it stabilized at 2. CT examination after 1 year showed a good cement osseointegration with osteophytic spurs bridging the superior endplate of the level involved to the inferior one of the level above. The new bone ingrowing property of the strontium-hydroxyapatite containing cement permits to extend the treatment indication also to unstable collapses in which the risk of pseudoarthrosis is very high. In this reported case we evaluated the potential role of percutaneous vertebroplasty in traumatic burst fracture with spinal channel involvement.

An unusual case of bilateral granulomatous mastitis.

Idiopathic granulomatous mastitis (IGM) is an uncommon benign disorder of the breast. At clinical examination, IGM is characterized by an inflammatory process of the breast, usually unilateral. Possible clinical findings are palpable mass with erythematous skin, pain, sterile abscesses, fistula and nipple retraction. Mammography and ultrasound findings are not specific for IGM. Magnetic resonance imaging (MRI) is a useful tool for the differential diagnosis; it is also necessary to delineate the exact extension of the disease and to plan the correct treatment. Final diagnosis is histological. We described an unusual case of IGM with bilateral involvement in a patient with history of pacemaker implantation and IGM typical clinical symptoms. Mammography, ultrasound, and MRI examinations were performed to identify the inflammatory disorder and to plan the correct therapy. Imaging features were correlated with final histological diagnosis of IGM.