Bio-nanocomposites films based on unmodified and modified thermoplastic starch reinforced with chemically modified nanoclays.

The use of polymers capable of being degraded by the action of microorganisms and/or enzymes without causing harmful effects is a strategy in waste management and environmental care. In this work, bio-nanocomposites based on thermoplastic starch (TPS) were synthesized by reactive extrusion using a twin-screw extruder. Two strategies were evaluated to reduce the disadvantages of TPS for packaging applications. First, starch was chemically modified producing the reaction of native starch with chemical reagents that introduce new functional groups to reduce the water adsorption. And two, nano-fillers were incorporated into TPS in order to enhance the mechanical and barrier properties, driving to materials with improved performance/cost ratio. The synergistic strategies of chemical modification and incorporation of modified nanoclays were also effective to reduce the dependence of properties of TPS with the environment humidity and the evolution thereof over time, which influences the performance during the service life of the product. Supplementary Information: The online version contains supplementary material available at 10.1007/s10853-023-08354-1.

Clinical use of biomarkers in breast cancer: Updated guidelines from the European Group on Tumor Markers (EGTM).

Biomarkers play an essential role in the management of patients with invasive breast cancer. For selecting patients likely to respond to endocrine therapy, both oestrogen receptors (ERs) and progesterone receptors (PRs) should be measured on all newly diagnosed invasive breast cancers. On the other hand, for selecting likely response to all forms of anti-HER2 therapy (trastuzumab, pertuzumab, lapatinib or ado-trastuzumab emtansine), determination of HER2 expression or gene copy number is mandatory. Where feasible, measurement of ER, PR and HER2 should be performed on recurrent lesions and the primary invasive tumour. Although methodological problems exist in the determination of Ki67, because of its clearly established clinical value, wide availability and low costs relative to the available multianalyte signatures, Ki67 may be used for determining prognosis, especially if values are low or high. In oestrogen receptor (ER)-positive, HER2-negative, lymph node-negative patients, multianalyte tests such as urokinase plasminogen activator (uPA)-PAI-1, Oncotype DX, MammaPrint, EndoPredict, Breast Cancer Index (BCI) and Prosigna (PAM50) may be used to predict outcome and aid adjunct therapy decision-making. Oncotype DX, MammaPrint, EndoPredict and Prosigna may be similarly used in patients with 1-3 metastatic lymph nodes. All laboratories measuring biomarkers for patient management should use analytically and clinically validated assays, participate in external quality assurance programs, have established assay acceptance and rejection criteria, perform regular audits and be accredited by an appropriate organisation.

A rare adverse reaction to ethambutol: drug-induced haemolytic anaemia.

Anti-tuberculosis drugs seldom cause serious haematological side effects. However, among these drugs, isoniazid and rifampicin, especially when administered intermittently, may very rarely be linked to acute autoimmune haemolytic anaemia. Ethambutol (EMB) can cause dose-related retrobulbar neuritis. In this paper, we present the first reported case of acute fatal autoimmune haemolytic anaemia due to EMB.

Effectiveness and safety of mouthpiece ventilation and nocturnal non-invasive ventilation in patients with kyphoscoliosis: Short and long-term outcomes after an episode of acute respiratory failure.

BACKGROUND: Kyphoscoliosis is a skeletal condition involving the hyperflexion of the thoracic spine. It is characterized by reduced chest wall compliance and impaired respiratory mechanisms leading to progressive hypo-ventilation. We evaluated the effectiveness and the safety of non-invasive ventilation (NIV) in patients after an episode of acute respiratory failure (ARF). METHODS: Eighteen patients with severe kyphoscoliosis who had been hospitalized for an episode of ARF were followed for 4 years. NIV was applied via mouthpiece (MPV) during the daytime and via mask during the night. The primary outcomes were changes in physiological and functional parameters as well as quality of life. Secondary outcomes were considered re-hospitalization and mortality rate after discharge. A set of control subjects was used for comparison. RESULTS: All patients showed a significant improvement in several clinical, physiological, functional and quality of life parameters. Four of them (22.2%) died during the four year follow-up period. In the uni-variate analysis patients who died had higher cardiac co-morbidity, lower MIP and SNIP, higher paCO2, and oxygen desaturation index at initial admission. CONCLUSIONS: Diurnal MPV associated with nocturnal NIV had significantly improved lung function, clinical outcomes and quality of life. It should be considered as a safe alternative to traditional administering of NIV.

Safety of vitamin K antagonist treatment for splanchnic vein thrombosis: a multicenter cohort study.

BACKGROUND: The treatment of splanchnic vein thrombosis (SVT) is challenging, due to the increased risk of bleeding and potentially life-threatening complications. Current recommendations are based on evidence from the treatment of venous thrombosis in usual sites, but small observational studies in SVT population suggest that the bleeding risk may offset the benefit of anticoagulant treatment in this setting. The aim of this study was to evaluate the safety of vitamin K antagonists (VKAs) in SVT patients. METHODS: We retrospectively included SVT patients treated with VKAs followed by 37 Italian anticoagulation clinics, until June 2013. The primary outcome was the incidence of major bleeding (MB), according to the ISTH definition, during VKA treatment. Vascular events, including both arterial and venous thrombosis, and mortality were also documented. RESULTS: Three hundred and seventy-five patients were included (median age 53 years; 54.7% males). During a median VKA treatment duration of 1.98 years, 15 MB events occurred, corresponding to an incidence rate of 1.24 (95% confidence interval [CI], 0.75-2.06) per 100 patient-years. Gastrointestinal bleeding represented 40% of all MB events. At multivariate analysis, the presence of esophageal varices emerged as independent predictor of MB (hazard ratio 5.4; 95% CI, 1.4-21.1). The incidence rate of vascular events on treatment was 1.37 (95% CI, 0.84-2.23) per 100 patient-years and the mortality rate was 0.83 (95% CI, 0.44-1.54) per 100 patient-years. CONCLUSIONS: Selected SVT patients followed by anticoagulation clinics for the management of VKA treatment show a low rate of major bleeding and vascular events.

The use of non-invasive ventilation in very old patients with hypercapnic acute respiratory failure because of COPD exacerbation.

AIMS: We prospectively enrolled 207 patients (121 were 75 or older and 86 younger than 75) who were admitted to three Respiratory Monitoring Units. The primary outcomes were intubation and mortality rates; the secondary outcomes were changes in arterial blood gases analysis, non-invasive ventilation (NIV) duration and length of hospital stay. RESULTS: Hospital mortality was similar in the two groups, as were intubation rates. The proportion who died in the very old patient group was 19.8% (24/121) vs. 10.4% (9/86) in the younger group. Intubation rate was 10.7% (13/121) in the very old patient group and 11.6% (10/86) in the younger group. The presence of comorbidities, the severity of illness (SAPS II), the level of consciousness, NIV failure (intubation), absolute value of pH prior to NIV, as well as the changes in pH and paCO2 and PaO2 /FiO2 after 2 h of NIV, were the variables associated with higher mortality. Very old patients had significantly higher NIV duration than younger patients (69.0 ± 47.0 vs. 57.0 ± 27.0 h) (p ≤ 0.03) and hospital stays (11.6 ± 3.8 vs. 8.4 ± 1.4) (p ≤ 0.02). CONCLUSIONS: The use of NIV in very old patients was effective in many cases. Endotracheal intubation after NIV failure was not efficacious in either group.

Non-invasive ventilation in the treatment of sleep-related breathing disorders: A review and update.

Non-invasive mechanical ventilation (NIV) was originally used in patients with acute respiratory compromises or exacerbations of chronic respiratory diseases as an alternative to intubation. Over the last thirty years NIV has been used during the night in patients with stable chronic lung diseases such as obstructive sleep apnea, the overlap syndrome (COPD and obstructive sleep apnea), neuromuscular disorders, obesity-hypoventilation syndrome and in other conditions such as sleep disorders associated with congestive heart failure. In this review we discuss the different types of NIV, the specific conditions in which they can be used as well as the indications, recommendations, and evidence supporting the efficacy of NIV.

A validated cadaveric model of trochlear dysplasia.

PURPOSE: Despite the high prevalence of trochlear dysplasia among patients with patellar instability, it is not well studied and is infrequently addressed surgically. The lack of a validated cadaveric model of trochlear dysplasia may be a contributing factor. The goal of this study was to develop a simple, reproducible, and realistic cadaveric model of trochlear dysplasia by surgically modifying cadaveric femora with normal anatomy and then to validate this model through the use of mechanical and fluoroscopic measurements. METHODS: The floor of the trochlear groove was surgically elevated using an inflatable bone tamp in eight cadaveric femora. The trochlear depth (TD) was measured with a custom-designed measuring device, and radiographic markers of dysplasia (sulcus angle, crossing sign, and prominence) were assessed before and after surgical modification. RESULTS: The average TD was 3.6±1.4, 4.6±1.1, and 5.1±1.0 mm prior to reverse trochleoplasty (RT) and 1.0±1.8, 2.3±1.3, and 3.3±2.5 mm following RT at 0°, 20°, and 40° of flexion, respectively. These direct measurements of TD were confirmed with fluoroscopy. The sulcus angle averaged 141° prior to RT and 157° after RT. The average prominence across all specimens was 3.3±0.7 mm before RT, and 5.5±1.5 mm after RT. Finally, the crossing sign was found to be absent in all knees prior to RT and present in 7 of the 8 after RT. CONCLUSIONS: The results of this study show that elevation of the trochlear floor with an inflatable bone tamp can reproducibly create a simulated dysplastic trochlea. This model may be useful in biomechanical studies of treatments for patellofemoral instability.

Open circuit mouthpiece ventilation: Concise clinical review.

In 2013 new "mouthpiece ventilation" modes are being introduced to commercially available portable ventilators. Despite this, there is little knowledge of how to use noninvasive intermittent positive pressure ventilation (NIV) as opposed to bi-level positive airway pressure (PAP) and both have almost exclusively been reported to have been used via nasal or oro-nasal interfaces rather than via a simple mouthpiece. Non-invasive ventilation is often reported as failing because of airway secretion encumbrance, because of hypercapnia due to inadequate bi-level PAP settings, or poor interface tolerance. The latter can be caused by factors such as excessive pressure on the face from poor fit, excessive oral air leak, anxiety, claustrophobia, and patient-ventilator dys-synchrony. Thus, the interface plays a crucial role in tolerance and effectiveness. Interfaces that cover the nose and/or nose and mouth (oro-nasal) are the most commonly used but are more likely to cause skin breakdown and claustrophobia. Most associated drawbacks can be avoided by using mouthpiece NIV. Open-circuit mouthpiece NIV is being used by large populations in some centers for daytime ventilatory support and complements nocturnal NIV via "mask" interfaces for nocturnal ventilatory support. Mouthpiece NIV is also being used for sleep with the mouthpiece fixed in place by a lip-covering flange. Small 15 and 22mm angled mouthpieces and straw-type mouthpieces are the most commonly used. NIV via mouthpiece is being used as an effective alternative to ventilatory support via tracheostomy tube (TMV) and is associated with a reduced risk of pneumonias and other respiratory complications. Its use facilitates "air-stacking" to improve cough, speech, and pulmonary compliance, all of which better maintain quality of life for patients with neuromuscular diseases (NMDs) than the invasive alternatives. Considering these benefits and the new availability of mouthpiece ventilator modes, wider knowledge of this technique is now warranted. This review highlights the indications, techniques, advantages and disadvantages of mouthpiece NIV.

Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update.

Biomarkers currently play an important role in the detection and management of patients with several different types of gastrointestinal cancer, especially colorectal, gastric, gastro-oesophageal junction (GOJ) adenocarcinomas and gastrointestinal stromal tumors (GISTs). The aim of this article is to provide updated and evidence-based guidelines for the use of biomarkers in the different gastrointestinal malignancies. Recommended biomarkers for colorectal cancer include an immunochemical-based fecal occult blood test in screening asymptomatic subjects ≥50 years of age for neoplasia, serial CEA levels in postoperative surveillance of stage II and III patients who may be candidates for surgical resection or systemic therapy in the event of distant metastasis occurring, K-RAS mutation status for identifying patients with advanced disease likely to benefit from anti-EGFR therapeutic antibodies and microsatellite instability testing as a first-line screen for subjects with Lynch syndrome. In advanced gastric or GOJ cancers, measurement of HER2 is recommended in selecting patients for treatment with trastuzumab. For patients with suspected GIST, determination of KIT protein should be used as a diagnostic aid, while KIT mutational analysis may be used for treatment planning in patients with diagnosed GISTs.

A systemic approach to cancer treatment: tumor cell reprogramming focused on endocrine-related cancers.

The term "cancer cell reprogramming" is used to define any kind of intervention aimed at transforming cancer cells into terminally differentiated cells. Using this approach, new technologies have been applied with different methods for a more systemic approach to cancer treatment. This review reports on advances of these technologies, including our personal contributions, mainly carried out on endocrine-related cancers. Some of the interventions, aimed at reverting cancer cells into a normal phenotype, are based on the evidence that tumor development is suppressed by the embryonic microenvironment. On the basis of this rationale, experiments have been conducted using stem cell differentiation stage factors (SCDSFs) taken at different stages of development of Zebrafish embryos, oocyte extracts, or naïve human umbilical cord matrix derived stem cells (UMDSCs). SCDSFs induce significant growth inhibition on different tumor cell lines in vitro, likely because of increases in cell cycle regulatory molecules, such as p53 and pRb. Treatment with these factors activates apoptosis and differentiation related to caspase-3. This is achieved via p73 apoptotic-dependent pathway activation with a concurrent normalization of the E-cadherin and beta-catenin ratio. Extracts from prophase amphibian oocytes could reprogram relevant epigenetic alterations in MCF-7 and HCC1954 breast cancer cell lines, while un-engineered (naïve) human UMDSCs attenuated growth of MDA-231 human breast carcinoma cells. A product prepared for human treatments, containing SCDSFs at very low doses, yielded favorable results in breast cancer and in intermediate-advanced hepatocellular carcinoma. Other reprogramming interventions used in the models of breast, prostate and ovarian cancer cell lines are described. Finally, current and future perspectives of this novel technology are discussed and a new hallmark of cancer is suggested: the loss of differentiation of cancer cells.

Interlinking of hypoxia and estrogen in thyroid cancer progression.

Estrogen aids in neo-vascularization of various tumors during hypoxic conditions, however the role of estrogen within the hypoxic environment of thyroid cancer is not known. In a series of experimentations, using human thyroid cancer cells, we observed that estrogen and hypoxia modulate the hypoxia inducible factor-1 (HIF-1) signaling which is abrogated by the anti-estrogen fulvestrant and the HIF-1 inhibitor YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole). Furthermore, we found that the conditioned medium from estrogen treated thyroid cancer cells lead to enhanced migration and tubulogenesis of human umbilical vein endothelial cells (HUVECs) which is abrogated by HIF-1 inhibitor. These findings, in addition to our previous and other scientific literature data, lead us to conclude that estrogen and hypoxia are interlinked in thyroid cancer and can equally modulate epithelial-endothelial cell interactions by mediating key cellular, metabolic and molecular processes of thyroid cancer progression. We believe that the hormonal component and cellular adaptation to oxygen tension of cancer cells are functionally equivalent with a cellular transition that can be exploited clinically for a combinational approach for thyroid cancer treatment involving antiestrogens as well as anti-hypoxic agents.

Changing the endocrine dependence of breast cancer: data and hypotheses.

Among the most common human cancers, often only breast and prostate cancers have advantage of hormone dependence. For a long time, this advantage permitted breast cancer to be efficaciously managed in the adjuvant and metastatic settings with low side effects by endocrine therapy. Unfortunately, soon or afterward hormone dependence is lost in most patients. In breast cancer, de novo or acquired hormone resistance is an hot issue and the focus of endless debate. Although a lack of oestrogen receptors (ERs) is considered to be the main reason for de novo hormone resistance, many studies have been conducted and many different mechanisms have been hypothesised to account for acquired hormone resistance. Thus far, hormone resistance appears to be occasionally delayed or avoided in "in vivo" experiments. However, this finding did not have a significant benefit in current clinical practice. The principal aim of this review article is to sum up and update the issue of changing the endocrine dependence of breast cancer. Recent molecular insights extensively elucidating and shedding new light on this very controversial issue are considered. Moreover, based on our recent reports, a new mechanistic interpretation of and a therapeutic approach for overcome hormone resistance are proposed.

Neuroendocrine tumors of the lung: hystological classification, diagnosis, traditional and new therapeutic approaches.

Lung neuroendocrine tumors are neoplasms originating from bronchopulmonary neuroendocrine cells, usually Kulchitsky cells, loaded with argentaffin granules. They account for 20-25% of all primitive lung tumors, the most common being the small-cell undifferentiated carcinoma. They include different tumors, from tumors of low-grade malignancy, especially the typical carcinoids, with high survival rates after surgical therapy, to the high-grade malignancy tumors, especially small-cell undifferentiated carcinomas. The latter have very few indications for surgical treatment with a low survival rate, even after multimodal therapy. The aim of this review is to describe the present knowledge and discuss possible new developments in the management of pulmonary neuroendocrine tumors. The authors examine and discuss in particular the role that surgical techniques should have in the treatment of small-cell lung cancer in opposition to a nihilism position that has limited therapies to non-surgical approaches. The critical review of this attitude opens the door to a more aggressive approach. In the meantime the review shows that it might be possible to include the new minimally invasive percutaneous ablative techniques as cryosurgery, thermotherapy and irreversible electroporation within a modern and flexible framework. The authors also present the hypothesis that cancer stem cells (CSC) are at the basis of recurrences of small-cell lung cancer (SCLC) and therefore that the issue is of difficult solution with the conventional oncologic approach considering the chemo-resistance of CSC to drugs. For these reasons an epigenetic therapy based on differentiation factors is proposed alongside the usual surgical and chemo-radiation protocols.

Effectiveness and predictors of success of noninvasive ventilation during H1N1 pandemics: a multicenter study.

BACKGROUND: The use of non-invasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF) due to H1N1 virus infection is controversial. In this multicenter study we aimed to assess the efficacy of NIV in avoiding endotracheal intubation (ETI) and to identify predictors of success or failure. METHODS: In this prospective multicenter study, 98 patients with new pulmonary infiltrate(s) sustained by H1N1 virus and a PaO(2)/FiO2<300 were eligible for study; 38/98 required immediate ETI, while the others received NIV as a first line therapy; 13/60 patients failed NIV and were intubated after 5.8+5.5 hours from enrolment. The remaining 47/60 patients were successfully ventilated with NIV. RESULTS: Hospital mortality was significantly higher in those patients who failed NIV vs. those who succeeded (53.8% vs. 2.1%; OR=0.52, P<0.001). ETI was associated with higher number of infectious complications, mainly sepsis and septic shock. The OR of having one of these events in the NIV failure group vs. NIV success was 16.7, P<0.001. According to logistic regression model, a SAPS II>29 and a PaO(2)/FIO(2)≤127 at admission and PaO2/FIO(2)≤149 after 1 hr of NIV were independently associated with the need for ETI. CONCLUSION: The early application of NIV, with the aim to avoid invasive ventilation, during the H1N1 pandemics was associated with an overall success rate of 47/98 (48%). Patients presenting at admission with an high SAPS II score and a low PaO(2)/FiO(2) ratio and/or unable to promptly correct gas exchange are at high risk of intubation and mortality.

Chest radiological findings of influenza A H1N1 pneumonia.

OBJECTIVE: The objective of this study was to review chest radiographs (CXR) and chest computer tomography (CT) findings in patients with influenza A H1N1 virus pneumonia. MATERIALS AND METHODS: Of ninety-eight patients with influenza A H1N1 infections seen in the General Hospitals of Villa Scassi, Genoa, and Sestri Levante from September 2009 to December 2009, twenty-eight developed pneumonia. The initial CXR were evaluated for radiological patterns: (ground-glass, consolidation, nodules, reticulation), distribution, and extent of the disease. Chest CT scans were reviewed for the same findings. A new radiographic score (CXR score) was used to evaluate the severity of the illness. RESULTS: The predominant radiological findings on chest CT in the patients at presentation were unilateral or bilateral multifocal ground glass opacities (84.5% of the patients). Consolidation areas had a peribronchovascular and subpleural predominance and were found mainly in the middle and upper zones of the lung. Reticular opacities were found in about 20% of the cases. The most outstanding CXR and chest CT features of the disease were basal and axial alveolar consolidation and ground-glass opacities. The severity of disease as determinate by need for mechanical ventilation was greater in patients with a greater number of lobes involved and a higher CXR score. CONCLUSION: Bilateral ground-glass opacities and areas of consolidation were the predominant radiological findings of influenza A (H1N1) virus pneumonia. Multifocal bilateral opacities and CXR score are strictly correlated with the severity of the illness.

Peritoneal sarcoidosis: an unusual presentation and a brief review of the literature.

Peritoneal involvement continues to be a rare manifestation of sarcoidosis: its involvement is not always isolated and sarcoid granulomas are also found elsewhere. Peritoneal diseases tend to have an increased incidence in women. Peritoneal involvement presents as ascites, as peritoneal thickening and multiple soft tissue nodules, and can often simulate peritoneal carcinomatosis. We describe a case of a man presenting abdominal pain, nausea, vomiting and a clinical picture of intestinal obstruction, with peritoneal sarcoidosis and abdominal findings suggesting peritoneal carcinomatosis. The diagnosis of sarcoidosis was confirmed by biopsy of the peritoneum during surgical laparotomy. Peritoneal involvement is a rare manifestation of sarcoidosis (less than 30 cases described in English medical literature): to our knowledge this is the first reported case of the disease presenting with an acute abdominal obstruction treated with surgery.

Cancer stem cells: perspectives of new therapeutical approaches for breast cancer.

Currently stem cells are hypothesized to play a central role in the origin, spread and resistance to treatment of breast cancer. Common anticancer therapy is effective but transient, with tumor relapse and metastatic disease often occurring. For therapy to be more effective, debulking of differentiated tumors must occur followed by targeting of the remaining surviving often quiescent tumor stem cells. New therapeutics aimed at cancer stem cells are achieved through non immunological and immunological methods. The former include elective ABC drug transporters or the heat shock protein 90 inhibition, targeting the self-renewal signalling pathways or the EMT program, differentiation therapy, or other interventions to eliminate BrCSCs. The latter include targeting specific antigens expressed on BrCSCs, dendritic cells (DCs) based vaccination and blockers of the extrinsic signals at CSC niche. Here all these novel approaches related to breast cancer stem cells are described.