Long peripheral catheters for intravenous infusions of iloprost or alprostadil therapy in rheumatologic outpatients.

BACKGROUND: Long peripheral catheters (LPCs) role in Difficult IntraVenous Access (DIVA) patients admitted to the emergency department has already been studied, resulting in a rapid, safe, and cost-effective procedure. Although their use in outpatient settings is established, there is a lack of studies assessing their benefits. In particular, rheumatologic outpatients affected by scleroderma, especially those affected by digital ulcers, are often treated with intravenous infusions of prostaglandin I2 (PGI2) analog (IV-PGI2A). OBJECTIVE AND METHODS: From 1 October 2021 to 31 March 2024, we conducted a prospective study enrolling DIVA outpatients affected by systemic sclerosis or undifferentiated connective tissue disease who needed IV-PGI2A therapy at L. Sacco Hospital in Milan (Italy). Each treatment cycle consisted of four consecutive days of infusion of iloprost or alprostadil. The primary aim was to assess the efficacy and potential complications associated with LPCs for IV-PGI2A. RESULTS: Twenty-six patients were enrolled 23 were females (88.5%), and the median age was 72 years (IQR 56-78.7). In total, 97 LPCs were inserted, with a mean number of insertions per patient/year of 2.3. An increase in LPCs insertion during the 30 months of the enrollment period was observed. Eighteen patients required more than one LPC placement, and in 61% of them, the second venipuncture was executed at a different site. No procedural complications were registered (accidental puncture of the brachial artery, accidental median nerve puncture, bleeding) nor late complications (Catheter-Related Thrombosis, Catheter-Related Bloodstream Infections, Accidental Removal). CONCLUSIONS: Our experience shows that LPCs could be valuable and safe for rheumatologic outpatients. The increased number of insertions and new and total patients enrolled each year defines the satisfaction of patients and health care professionals.

Analysis of prognostic factors and the role of epilepsy in neurosurgical patients with brain metastases.

Background: Brain metastases (BMs) represent the most frequent brain tumors in adults. The identification of key prognostic factors is essential for choosing the therapeutic strategy tailored to each patient. Epilepsy can precede several months of other clinical presentations of BMs. This work aimed to study the impact of epilepsy and other prognostic factors on BMs patients' survival. Methods: This retrospective study included 51 patients diagnosed with BMs and who underwent neurosurgery between 2010 and 2021. The impact of BM features and patient's clinical characteristics on the overall survival (OS) was analyzed through uni- and multivariate analysis. Results: The average OS was 25.98 months and differed according to the histology of the primary tumor. The primary tumor localization and the presence of extracranial metastases had a statistically significant impact on the OS, and patients with single BM showed a superior OS to those with multifocal lesions. The localization of BMs in the temporal lobe correlated with the highest OS. The OS was significantly higher in patients who presented seizures in their clinical onset and in those who had better post-surgical Karnofsky performance status, no post-surgical complications, and who underwent post-surgical treatment. Conclusion: Our study has highlighted prognostically favorable patient and tumor factors. Among those, a clinical onset with epileptic seizures can help identify brain metastasis hitherto silent. This could lead to immediate diagnostic-therapeutic interventions with more aggressive therapies after appropriate multidisciplinary evaluation.

Management of Trastuzumab Deruxtecan-related nausea and vomiting in real-world practice.

Background: Nausea and vomiting are common side effects of Trastuzumab Deruxtecan (T-DXd), but guidelines for optimal management were not initially available. This retrospective single-center study aimed at evaluating the efficacy of two antiemetic regimens in patients receiving T-DXd. Methods: Data from metastatic breast cancer patients receiving T-DXd were collected. Two groups were defined: patients treated with 5-HT3 receptor antagonists (RA) ± dexamethasone (5-HT3-group) and patients treated with a fixed oral combination of netupitant (NK1RA) and palonosetron ± dexamethasone (NK1 group). Physicians preferentially offered the NK1 regimen to patients at higher risk of nausea and vomiting based on internal recommendations. Only nausea and vomiting during cycles 1 and 2 were considered. Comparisons of nausea and vomiting by the antiemetic prophylaxis group were assessed using chi-square. Results: A total of 53 patients were included in the analysis. At cycle 1, 72% and 28% of patients received the 5-HT3 and NK1 prophylaxis, respectively. Overall, 58% reported nausea, with no differences between groups (58% vs. 60%; p = 0.832), but with a trend for lower grade in the NK1 group (33.3% G1; 26.7% G2) compared to the 5-HT3 group (23.7% G1; 31.6% G2; 2.6% G3). Vomiting was reported by 21% and 0% of patients in the 5-HT3 and the NK1 group, respectively (p = 0.054). Among the 15 patients in the 5-HT3 group with nausea at cycle 1 who escalated to NK1 at cycle 2, nausea decreased from 100% to 53% (p = 0.022) and vomiting decreased from 47% to 13% (p = 0.046). Conclusions: The NK1 regimen improved vomiting control at cycle 1 and, when introduced at cycle 2, significantly improved both nausea and vomiting. The biased NK1 selection for higher-risk patients may have dampened the differences between groups at cycle 1. These findings support enhanced control of T-DXd-related nausea and vomiting with NK1RA.

Success Predictors of Endoscopic Sleeve Gastroplasty.

OBJECTIVE: Endoscopic sleeve gastroplasty (ESG) is a minimally invasive procedure that proved to be safe and effective in obesity treatment. However, not all subjects respond to treatment in the same way, and, with a view to personalized care, it is essential to identify predictors of success or failure. METHODS: A retrospective 2-year followed-up cohort of ESG subjects was analyzed to investigate the presence of any baseline or early indicators of long-term optimal or suboptimal ESG outcomes. RESULTS: A total of 315 subjects (73% women) were included, with 73% of patients exhibiting an Excess weight loss percentage (%EWL) >25% at the 24 months. Neither demographic parameters (age and sex), smoking habits, and menopause in women nor the presence of comorbidities proved potential predictive value. Interestingly, the %EWL at 1 month after ESG was the strongest predictor of 24-month therapeutic success. Subsequently, we estimated an "early threshold for success" for 1 month-%EWL by employing Youden's index method. CONCLUSIONS: ESG is a safe and effective bariatric treatment that can be offered to a wide range of subjects. Early weight loss seems to impact long-term ESG results significantly and may allow proper early post-operative care optimization.

Circulating hematopoietic stem/progenitor cell subsets contribute to human hematopoietic homeostasis.

ABSTRACT: In physiological conditions, few circulating hematopoietic stem/progenitor cells (cHSPCs) are present in the peripheral blood, but their contribution to human hematopoiesis remain unsolved. By integrating advanced immunophenotyping, single-cell transcriptional and functional profiling, and integration site (IS) clonal tracking, we unveiled the biological properties and the transcriptional features of human cHSPC subpopulations in relationship to their bone marrow (BM) counterpart. We found that cHSPCs reduced in cell count over aging and are enriched for primitive, lymphoid, and erythroid subpopulations, showing preactivated transcriptional and functional state. Moreover, cHSPCs have low expression of multiple BM-retention molecules but maintain their homing potential after xenotransplantation. By generating a comprehensive human organ-resident HSPC data set based on single-cell RNA sequencing data, we detected organ-specific seeding properties of the distinct trafficking HSPC subpopulations. Notably, circulating multi-lymphoid progenitors are primed for seeding the thymus and actively contribute to T-cell production. Human clonal tracking data from patients receiving gene therapy (GT) also showed that cHSPCs connect distant BM niches and participate in steady-state hematopoietic production, with primitive cHSPCs having the highest recirculation capability to travel in and out of the BM. Finally, in case of hematopoietic impairment, cHSPCs composition reflects the BM-HSPC content and might represent a biomarker of the BM state for clinical and research purposes. Overall, our comprehensive work unveiled fundamental insights into the in vivo dynamics of human HSPC trafficking and its role in sustaining hematopoietic homeostasis. GT patients' clinical trials were registered at ClinicalTrials.gov (NCT01515462 and NCT03837483) and EudraCT (2009-017346-32 and 2018-003842-18).

Pilot study on cultural and metagenomic analysis of bile and biliary stentslead to unveiling the key players in stent occlusion.

Endoscopic Retrograde Cholangio-Pancreatography (ERCP) with biliary stenting is a minimally invasive medical procedure employed to address both malignant and benign obstructions within the biliary tract. Benign biliary strictures (BBSs), typically arising from surgical interventions such as liver transplants and cholecystectomy, as well as chronic inflammatory conditions, present a common clinical challenge. The current gold standard for treating BBSs involves the periodic insertion of plastic stents at intervals of 3-4 months, spanning a course of approximately one year. Unfortunately, stent occlusion emerges as a prevalent issue within this treatment paradigm, leading to the recurrence of symptoms and necessitating repeated ERCPs. In response to this clinical concern, we initiated a pilot study, delving into the microbial composition present in bile and on the inner surfaces of plastic stents. This investigation encompassed 22 patients afflicted by BBSs who had previously undergone ERCP with plastic stent placement. Our preliminary findings offered promising insights into the microbial culprits behind stent occlusion, with Enterobacter and Lactobacillus spp. standing out as prominent bacterial species known for their biofilm-forming tendencies on stent surfaces. These revelations hold promise for potential interventions, including targeted antimicrobial therapies aimed at curtailing bacterial growth on stents and the development of advanced stent materials boasting anti-biofilm properties.

Cerebral autoregulation in traumatic brain injury: ultra-low-frequency pressure reactivity index and intracranial pressure across age groups.

BACKGROUND: The ultra-low-frequency pressure reactivity index (UL-PRx) has been established as a surrogate method for bedside estimation of cerebral autoregulation (CA). Although this index has been shown to be a predictor of outcome in adult and pediatric patients with traumatic brain injury (TBI), a comprehensive evaluation of low sampling rate data collection (0.0033 Hz averaged over 5 min) on cerebrovascular reactivity has never been performed. OBJECTIVE: To evaluate the performance and predictive power of the UL-PRx for 12-month outcome measures, alongside all International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) models and in different age groups. To investigate the potential for optimal cerebral perfusion pressure (CPPopt). METHODS: Demographic data, IMPACT variables, in-hospital mortality, and Glasgow Outcome Scale Extended (GOSE) at 12 months were extracted. Filtering and processing of the time series and creation of the indices (cerebral intracranial pressure (ICP), cerebral perfusion pressure (CPP), UL-PRx, and deltaCPPopt (ΔCPPopt and CPPopt-CPP)) were performed using an in-house algorithm. Physiological parameters were assessed as follows: mean index value, % time above threshold, and mean hourly dose above threshold. RESULTS: A total of 263 TBI patients were included: pediatric (17.5% aged ≤ 16 y) and adult (60.5% aged > 16 and < 70 y and 22.0% ≥ 70 y, respectively) patients. In-hospital and 12-month mortality were 25.9% and 32.7%, respectively, and 60.0% of patients had an unfavorable outcome at 12 months (GOSE). On univariate analysis, ICP, CPP, UL-PRx, and ΔCPPopt were associated with 12-month outcomes. The cutoff of ~ 20-22 for mean ICP and of ~ 0.30 for mean UL-PRx were confirmed in all age groups, except in patients older than 70 years. Mean UL-PRx remained significantly associated with 12-month outcomes even after adjustment for IMPACT models. This association was confirmed in all age groups. UL-PRx resulted associate with CPPopt. CONCLUSIONS: The study highlights UL-PRx as a tool for assessing CA and valuable outcome predictor for TBI patients. The results emphasize the potential clinical utility of the UL-PRx and its adaptability across different age groups, even after adjustment for IMPACT models. Furthermore, the correlation between UL-PRx and CPPopt suggests the potential for more targeted treatment strategies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05043545, principal investigator Paolo Gritti, date of registration 2021.08.21.

Unusual anterior and posterior segment features of coats disease.

PURPOSE: To report the clinical course and management of unusual anterior and posterior segment features of Coats disease and their relation to the age of the patients to increase the awareness towards these rare clinical features rarely described in the current literature. METHODS: A retrospective descriptive review of 45 eyes of 45 patients affected by Coats disease was conducted at the Retinoblastoma Referral Center and Ophthalmology Unit of the University of Siena in Italy analyzing data from 2000 to 2022. Medical records and images were revised to find some cases presenting unusual anterior and posterior segment features in patients affected by Coats disease.We identified therefore 4 unusual clinical conditions: retinal macrocysts, anterior chamber cholesterolosis, fovea-sparing Coats disease and secondary vasoproliferative tumor. RESULTS: Two patients presented with retinal macrocyst (2/45 = 4.4%), one with anterior chamber cholesterolosis (1/45 = 2.2%), two with fovea sparing Coats disease (2/45 = 4.4%) and one with vasoproliferative tumor associated (1/45 = 2.2%) for a total of six (6/45 = 13.3%) patients manifesting unusual anterior or posterior segment features in Coats disease. CONCLUSION: Unusual anterior and posterior segment features of Coats disease such as retinal macrocyst and anterior chamber cholesterolosis have been more frequently reported in younger children while fovea-sparing and vasoproliferative tumors have been more commonly described in older patients. Age is then a strong prognostic marker which allows to distinguish two different phenotypes of Coats disease: patients younger and older than 3 years old with more aggressive and milder phenotype respectively.

Sex dimorphism and cancer immunotherapy: May pregnancy solve the puzzle?

In the immunoncology era, growing evidence has shown a clear sex dimorphism in antitumor immune response with a potential impact on outcomes upon immunecheckpoint blockade (ICI) in patients with cancer. Sex dimorphism could affect tumor microenvironment composition and systemic anticancer immunity; however, the modifications induced by sex are heterogeneous. From a clinical perspective, six metanalyses have explored the role of sex in cancer patients receiving ICI with conflicting results. Environmental and reproductive factors may further jeopardize the sex-related heterogeneity in anticancer immune response. In particular, pregnancy is characterized by orchestrated changes in the immune system, some of which could be long lasting. A persistence of memory T-cells with a potential fetal-antigen specificity has been reported both in human and mice, suggesting that a previous pregnancy may positively impact cancer development or response to ICI, in case of fetal-antigen sharing from tumor cells. On the other hand, a previous pregnancy may also be associated with a regulatory memory characterized by increased tolerance and anergy towards cancer-fetal common antigens. Finally, fetal-maternal microchimerism could represent an additional source of chronic exposure to fetal antigens and may have important immunological implications on cancer development and ICI activity. So far, the role of pregnancy dimorphism (nulliparous vs parous) in women and the impact of pregnancy-related variables remain largely underexplored in cancer patients. In this review, we summarize the evidence regarding sex and pregnancy dimorphism in the context of immune response and anticancer immunotherapy and advocate the importance of analyzing pregnancy variables on ICIs clinical trials.

Effects of CPAP and FiO2 on respiratory effort and lung stress in early COVID-19 pneumonia: a randomized, crossover study.

BACKGROUND: in COVID-19 acute respiratory failure, the effects of CPAP and FiO2 on respiratory effort and lung stress are unclear. We hypothesize that, in the compliant lungs of early Sars-CoV-2 pneumonia, the application of positive pressure through Helmet-CPAP may not decrease respiratory effort, and rather worsen lung stress and oxygenation when compared to higher FiO2 delivered via oxygen masks. METHODS: In this single-center (S.Luigi Gonzaga University-Hospital, Turin, Italy), randomized, crossover study, we included patients receiving Helmet-CPAP for early (< 48 h) COVID-19 pneumonia without additional cardiac or respiratory disease. Healthy subjects were included as controls. Participants were equipped with an esophageal catheter, a non-invasive cardiac output monitor, and an arterial catheter. The protocol consisted of a random sequence of non-rebreather mask (NRB), Helmet-CPAP (with variable positive pressure and FiO2) and Venturi mask (FiO2 0.5), each delivered for 20 min. Study outcomes were changes in respiratory effort (esophageal swing), total lung stress (dynamic + static transpulmonary pressure), gas-exchange and hemodynamics. RESULTS: We enrolled 28 COVID-19 patients and 7 healthy controls. In all patients, respiratory effort increased from NRB to Helmet-CPAP (5.0 ± 3.7 vs 8.3 ± 3.9 cmH2O, p < 0.01). However, Helmet's pressure decreased by a comparable amount during inspiration (- 3.1 ± 1.0 cmH2O, p = 0.16), therefore dynamic stress remained stable (p = 0.97). Changes in static and total lung stress from NRB to Helmet-CPAP were overall not significant (p = 0.07 and p = 0.09, respectively), but showed high interpatient variability, ranging from - 4.5 to + 6.1 cmH2O, and from - 5.8 to + 5.7 cmH2O, respectively. All findings were confirmed in healthy subjects, except for an increase in dynamic stress (p < 0.01). PaO2 decreased from NRB to Helmet-CPAP with FiO2 0.5 (107 ± 55 vs 86 ± 30 mmHg, p < 0.01), irrespective of positive pressure levels (p = 0.64). Conversely, with Helmet's FiO2 0.9, PaO2 increased (p < 0.01), but oxygen delivery remained stable (p = 0.48) as cardiac output decreased (p = 0.02). When PaO2 fell below 60 mmHg with VM, respiratory effort increased proportionally (p < 0.01, r = 0.81). CONCLUSIONS: In early COVID-19 pneumonia, Helmet-CPAP increases respiratory effort without altering dynamic stress, while the effects upon static and total stress are variable, requiring individual assessment. Oxygen masks with higher FiO2 provide better oxygenation with lower respiratory effort. Trial registration Retrospectively registered (13-May-2021): clinicaltrials.gov (NCT04885517), https://clinicaltrials.gov/ct2/show/NCT04885517 .

Genotoxic effects of base and prime editing in human hematopoietic stem cells.

Base and prime editors (BEs and PEs) may provide more precise genetic engineering than nuclease-based approaches because they bypass the dependence on DNA double-strand breaks. However, little is known about their cellular responses and genotoxicity. Here, we compared state-of-the-art BEs and PEs and Cas9 in human hematopoietic stem and progenitor cells with respect to editing efficiency, cytotoxicity, transcriptomic changes and on-target and genome-wide genotoxicity. BEs and PEs induced detrimental transcriptional responses that reduced editing efficiency and hematopoietic repopulation in xenotransplants and also generated DNA double-strand breaks and genotoxic byproducts, including deletions and translocations, at a lower frequency than Cas9. These effects were strongest for cytidine BEs due to suboptimal inhibition of base excision repair and were mitigated by tailoring delivery timing and editor expression through optimized mRNA design. However, BEs altered the mutational landscape of hematopoietic stem and progenitor cells across the genome by increasing the load and relative proportions of nucleotide variants. These findings raise concerns about the genotoxicity of BEs and PEs and warrant further investigation in view of their clinical application.

miR-126 identifies a quiescent and chemo-resistant human B-ALL cell subset that correlates with minimal residual disease.

Complete elimination of B-cell acute lymphoblastic leukemia (B-ALL) by a risk-adapted primary treatment approach remains a clinical key objective, which fails in up to a third of patients. Recent evidence has implicated subpopulations of B-ALL cells with stem-like features in disease persistence. We hypothesized that microRNA-126, a core regulator of hematopoietic and leukemic stem cells, may resolve intratumor heterogeneity in B-ALL and uncover therapy-resistant subpopulations. We exploited patient-derived xenograft (PDX) models with B-ALL cells transduced with a miR-126 reporter allowing the prospective isolation of miR-126(high) cells for their functional and transcriptional characterization. Discrete miR-126(high) populations, often characterized by MIR126 locus demethylation, were identified in 8/9 PDX models and showed increased repopulation potential, in vivo chemotherapy resistance and hallmarks of quiescence, inflammation and stress-response pathway activation. Cells with a miR-126(high) transcriptional profile were identified as distinct disease subpopulations by single-cell RNA sequencing in diagnosis samples from adult and pediatric B-ALL. Expression of miR-126 and locus methylation were tested in several pediatric and adult B-ALL cohorts, which received standardized treatment. High microRNA-126 levels and locus demethylation at diagnosis associate with suboptimal response to induction chemotherapy (MRD > 0.05% at day +33 or MRD+ at day +78).

Impact of Pregnancy on Weight Loss After Endoscopic Sleeve Gastroplasty.

PURPOSE: Obesity and pregnancy are strictly related: on the one hand, obesity-one of the most common comorbidities in women of reproductive age-contributes to infertility and obesity-related pregnancy complications, whereas pregnancy is a condition in which, physiologically, the pregnant woman undergoes weight gain. Endoscopic sleeve gastroplasty (ESG) may be used for the treatment of obesity in women of childbearing age. MATERIALS AND METHODS: A retrospective analysis was conducted to evaluate weight trajectories, the evolution of obesity-related comorbidities, and lifestyle modification in women who became pregnant after ESG. A comparison was made between childbearing-age women who became pregnant after ESG and non-pregnant women. RESULTS: A total of 150 childbearing-age women underwent ESG at a large tertiary medical center. Of these, 11 patients (33.4 ± 6.2 years) became pregnant after the procedure, following a mean time interval of 5.5 ± 3.9 months. Three women (two affected by polycystic ovary syndrome) reported difficulty getting pregnant before undergoing ESG. The mean preconception BMI was 31.9±4.0 kg/m2 (-7.24 ± 4.0 kg/m2 after ESG). Total body weight loss (TBWL, %) was 18.08 ± 8.00, 11.00 ± 11.08, and 12.08 ± 8.49, at the beginning of pregnancy, at the delivery, and at the first follow-up (19.6 ± 7.8 months after ESG). TBWL of at least 5% was achieved before pregnancy in all patients (73% reached a TBWL ≥ 10%). No significant differences in weight loss and QoL were found between the pregnancy and non-pregnancy groups up to 24 months after ESG. CONCLUSIONS: Endoscopic sleeve gastroplasty allows for adequate weight loss before and after pregnancy in patients with obesity.

Four-point functions of gravitons and conserved currents of CFT in momentum space: testing the nonlocal action with the TTJJ.

We present an analysis of the perturbative realization of the TTJJ correlator, with two stress energy tensors and two conserved currents, using free field theory, integrating out conformal sectors in the quantum corrections. This allows to define, around flat space, an exact perturbative expansion of the complete anomaly effective action - up to 4-point functions - whose predictions can be compared against those of the anomaly induced action. The latter is a variational solution of the conformal anomaly constraint at d=4 in the form of a nonlocal Wess-Zumino action. The renormalization procedure and the degeneracies of the tensor structures of this correlator are discussed, valid for a generic conformal field theory, deriving its anomalous trace Ward identities (WIs). In this application, we also illustrate a general procedure that identifies the minimal number of tensorial structures and corresponding form factors for the TTJJ and any 4-point function. The approach is implemented for three, four and five dimensions, addressing the tensor degeneracies of the expansion in momentum space. We show that the renormalized TTJJ can be split into two contributions, a non anomalous and an anomalous part, each separately conserved. The first satisfies ordinary trace WIs, while the second satisfies anomalous trace WIs. The result of the direct computation is compared against the expression of the same 4-point function derived from the nonlocal anomaly induced action. We show that the prediction for the anomalous part of the TTJJ derived from such action, evaluated in two different conformal decompositions, the Riegert and Fradkin-Vilkovisky (FV) choices, differ from the anomaly part identified in the perturbative TTJJ, in the flat spacetime limit. The anomaly part of the correlator computed with the Riegert choice is affected by double poles, while the one computed with the FV choice does not satisfy the conservation WIs. We present the correct form of the expansion of the anomaly induced action at the second order in the metric perturbations around flat space that reproduces the perturbative result.

Tissue- and liquid biopsy-based biomarkers for immunotherapy in breast cancer.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and now represent the mainstay of treatment for many tumor types, including triple-negative breast cancer and two agnostic registrations. However, despite impressive durable responses suggestive of an even curative potential in some cases, most patients receiving ICIs do not derive a substantial benefit, highlighting the need for more precise patient selection and stratification. The identification of predictive biomarkers of response to ICIs may play a pivotal role in optimizing the therapeutic use of such compounds. In this Review, we describe the current landscape of tissue and blood biomarkers that could serve as predictive factors for ICI treatment in breast cancer. The integration of these biomarkers in a "holistic" perspective aimed at developing comprehensive panels of multiple predictive factors will be a major step forward towards precision immune-oncology.

Glioblastoma: A Retrospective Analysis of the Role of the Maximal Surgical Resection on Overall Survival and Progression Free Survival.

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults; despite advances in the understanding of GBM pathogenesis, significant achievements in treating this disease are still lacking. The aim of this study was to evaluate the prognostic significance of the extent of surgical resection (EOR), beyond the neoplastic mass, on the overall survival (OS). METHODS: A retrospective review of a single-institution glioblastoma patient database (January 2012-September 2021) was undertaken. The series is composed of 64 patients who underwent surgery at the University Department of Neurosurgery of Ancona; the series was divided into four groups based on the amount of tumor mass excision with the fluid-attenuated inversion recovery (FLAIR) abnormalities (SUPr-supratotal resection, GTR-gross total resection, STR-subtotal resection, BIOPSY). The hypothesis was that the maximal resection of FLAIR abnormalities may improve the overall survival compared to the resection of the visible T1 contrast-enhanced neoplastic area only. RESULTS: In the univariate analysis, SUPr and GTR are correlated with the overall survival (p = 0.001); the percentage of total neoplastic removal threshold conditioning outcome was 90% (p = 0.027). These results were confirmed by the multivariate analysis. CONCLUSIONS: Maximal surgical resection, when feasible, involving areas of FLAIR abnormalities represents an advantageous approach for the OS in GBM patients.

Acute cholecystitis: Which flow-chart for the most appropriate management?

Acute cholecystitis (AC) is a very common disease in clinical practice. Laparoscopic cholecystectomy remains the gold standard treatment for AC, however due to aging population, the increased prevalence of multiple comorbidities and the extensive use of anticoagulants, surgical procedures may be too risky when dealing with patients in emergency settings. In these subsets of patients, a mini-invasive management may be an effective option, both as a definitive treatment or as bridge-to-surgery. In this paper, several non-operative treatments are described and their benefits and drawbacks are highlighted. Percutaneous gallbladder drainage (PT-GBD) is one of the most common and widespread techniques. It is easy to perform and has a good cost/benefit ratio. Endoscopic transpapillary gallbladder drainage (ETGBD) is a challenging procedure that is usually performed in high volume centers by expert endoscopists, and it has a specific indication for selected cases. EUS-guided drainage (EUS-GBD) is still not widely available, but it is an effective procedure that could have several advantages, especially in rate of reinterventions. All these treatment options should be considered together in a stepwise approach and addressed to patients after an accurate case-by-case evaluation in a multidisciplinary discussion. In this review, we provide a possible flowchart in order to optimize treatments, resource and provide to patients a tailored approach.