How to implement of patient blood management pillar 1: An Italian expert opinion based on a "bundles" approach.

Worldwide iron anemia is a common disorder with a significant economic burden on health-care systems. Red blood cell transfusion is the mainstay to correct anemia in surgical settings, but it is also an overused procedure and recent data support its possible role in worsening patient outcomes. Patient Blood Management (PBM) is a multidisciplinary approach to optimize hemostasis, manage anemia, minimize iatrogenic blood loss, and improve tolerance to anemia. The present paper aims to provide a "bundles" approach, based on several preoperative anemia management measures, to implement PBM Pillar 1 in clinical practice

Tumour infiltrating lymphocytes and immune-related genes as predictors of outcome in pancreatic adenocarcinoma

Background: We investigated the correlation between pancreatic ductal adenocarcinoma patient progno- sis and the presence of tumour infiltrating lymphocytes and expression of 521 immune sys- tem genes. Methods: Intratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochem- istry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenect- omy. The results were correlated with gene expression profile using the digital multiplexed NanoString nCounter analysis system (NanoString Technologies, Seattle, WA, USA). Results: Twenty immune system genes were significantly differentially expressed in patients with a good prognosis relative to patients with a worse prognosis: TLR2 and TLR7 (Toll-like recep- tor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell develop- ment); TNF, TNFRF1A (TNF superfamily); HCK (leukocyte function); C1QA (complement system); BAX, PNMA1 (apoptosis); IKBKE (NF\u3baB pathway). Differential expression was more than twice log 2 for TLR7, TNF, C1QA, FOXP3, and CD37. Discussion: Tumour infiltrating lymphocytes were present at higher levels in samples from patients with better prognosis. Our findings indicate that tumour infiltrating lymphocyte levels and expres- sion level of the immune system genes listed above influence pancreatic ductal adenocarcinoma prognosis. This information could be used to improve selection of best responders to immune inhibitors

Hypoxia Modifies the Transcriptome of Human NK Cells, Modulates Their Immunoregulatory Profile, and Influences NK Cell Subset Migration

Hypoxia, which characterizes most tumor tissues, can alter the function of different immune cell types, favoring tumor escape mechanisms. In this study, we show that hypoxia profoundly acts on NK cells by influencing their transcriptome, affecting their immunoregulatory functions, and changing the chemotactic responses of different NK cell subsets. Exposure of human peripheral blood NK cells to hypoxia for 16 or 96 h caused significant changes in the expression of 729 or 1,100 genes, respectively. Gene Set Enrichment Analysis demonstrated that these changes followed a consensus hypoxia transcriptional profile. As assessed by Gene Ontology annotation, hypoxia-targeted genes were implicated in several biological processes: metabolism, cell cycle, differentiation, apoptosis, cell stress, and cytoskeleton organization. The hypoxic transcriptome also showed changes in genes with immunological relevance including those coding for proinflammatory cytokines, chemokines, and chemokine-receptors. Quantitative RT-PCR analysis confirmed the modulation of several immune-related genes, prompting further immunophenotypic and functional studies. Multiplex ELISA demonstrated that hypoxia could variably reduce NK cell ability to release IFNγ, TNFα, GM-CSF, CCL3, and CCL5 following PMA+Ionomycin or IL15+IL18 stimulation, while it poorly affected the response to IL12+IL18. Cytofluorimetric analysis showed that hypoxia could influence NK chemokine receptor pattern by sustaining the expression of CCR7 and CXCR4. Remarkably, this effect occurred selectively (CCR7) or preferentially (CXCR4) on CD56bright NK cells, which indeed showed higher chemotaxis to CCL19, CCL21, or CXCL12. Collectively, our data suggest that the hypoxic environment may profoundly influence the nature of the NK cell infiltrate and its effects on immune-mediated responses within tumor tissues

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Dinamiche di transizione in ecovillaggi del Senegal

La ricerca di dottorato è stata un viaggio alla ricerca di intuizioni trasformative multiverso che emergono dal movimento degli eco-villaggi senegalese e da esperienze alternative anti-egemoniche. La domanda da cui sono partita si interroga su cosa possiamo apprendere dalle esperienze di transizione socio-ecologica di successo degli ecovillaggi del Senegal. La prima questione ha generato riflessioni su quali metodi di emersione delle forme di transizione impiegare per includere una pluralità di voci e prospettive. I metodi attivati sono in linea con principi etico-filosofici inspirati al pensiero decoloniale. Tali metodi si propongono di restituire la complessità dei diversi sistemi insediativi e le differenze esistenti in significati, traiettorie, visioni, cosmologie, valori e pratiche delle diverse forme di transizione. Si è optato pertanto per la costruzione di un disegno valutativo multidimensionale comparativo in grado di comprendere spunti trasformativi e aspetti etico-filosofici appresi dalle scuole africane, ed effettuare un’analisi di sensitività relativa all’incidenza delle pratiche antropiche e delle condizioni climatiche sulle dinamiche di transizione. La ricerca di correlazione tra forme di transizione e spinte sociali ha portato ad evidenziare tra i casi studio le esperienze anti-egemoniche di resistenza, quelle di adattamento proattivo e all’estremo opposto di resa. Questi ultimi rinviano a casi di migrazione dovuti a crisi ambientali irreversibili. La ricerca ha applicato una metodologia variegata, utilizzando spettacoli di teatro-forum come pratica decoloniale per discutere i problemi della transizione ecologica con gli abitanti dei luoghi e un itinerario metodologico diversificato, che ha seguito un disegno valutativo ricorsivo per aggiornare le ipotesi in itinere. I risultati mostrano la co-presenza di molteplici prospettive africane endogene, che tendono ad arricchire il messaggio "Africa-Mondo". Il messaggio è veicolato dal linguaggio con cui le nicchie (eco-villaggi) traducono il termine transizione ecologica, dalle forme di vita che riproducono nella loro spazialità, dalla resistenza delle connessioni di legame e dalla condivisione degli ecosistemi sociali nelle prassi e nelle cosmo-visioni, nonostante le perturbazioni del colonialismo, capitalismo e la poli-esposizione alla globalizzazione. Le cosmo-visioni si relazionano con gli immaginari e le spiegazioni fornite dalle comunità sull'origine del mondo e sul loro rapporto con la terra. Le auto-narrazioni dei luoghi presentano modi alternativi di abitare la terra e di relazionarsi con i non umani, più che con gli umani. I risultati della ricerca consentono di riflettere sul senso delle sfide ecologiche contemporanee in prospettiva africana. Si tratta di risultati parziali ottenuti mettendo in tensione esplorazioni sul campo con ‘paradigmi africani’ emergenti. La tensione non si è dimostrata indolore su entrambi i versanti. Se da un lato esperienze di connessione e cosmologie sembrano produrre forme di vita in parziale equilibrio con la natura, connotate da cooperazione sociale e legami che ne arricchiscono la qualità, dall’altro i nuovi ‘paradigmi africani’ sembrano difettare in autonomia, ma soprattutto incontrano difficoltà di legittimazione continentale. Non è un caso che i tentativi di traduzione delle cosmologie nelle pratiche di vita generino ecologie ibride che, oltre a mettere in discussione genealogie ‘scientifiche’ coloniali, sollevano il più generale quesito di cosa siano oggi le Afriche. La scoperta di quali risorse rappresentino leve di una transizione ecologica endogena su cui scommettere per rafforzare l’autonomia locale e la meta-stabilità di sistemi socio-ecologiche potrebbe aprire significative piste di ricerca per l’Africa e i suoi luoghi.The PhD research was a journey in search of multiverse transformative insights emerging from the Senegalese eco-village movement and alternative anti-hegemonic experiences. The question I started from asks what can we learn from the successful socio-ecological transition experiences of Senegal's eco-villages. The first question generated reflections on which methods of emerging forms of transition to employ in order to include a plurality of voices and perspectives. The methods applied are in line with ethical-philosophical principles inspired by de-colonial thinking. These methods aim to reveal the complexity of different settlement systems and the existing differences in meanings, trajectories, visions, cosmologies, values and practices of different forms of transition. We therefore opted for the construction of a comparative multidimensional evaluative design capable of encompassing transformative cues and ethical-philosophical aspects learnt from African schools, and carry out a sensitivity analysis on the impact of anthropic practices and climatic conditions on transition dynamics. The search for correlations between forms of transition and social drives led to the identification among the case studies of anti-hegemonic experiences of resistance, those of proactive adaptation and at the opposite extreme of surrender. The latter refer to cases of migration due to irreversible environmental crises. The research applied a hybrid methodology, using theatre-forum performances as a decolonial practice to discuss issues of ecological transition with local inhabitants, and a diverse methodological itinerary, which followed a recursive evaluative design to update hypotheses in progress. The results show the co-presence of multiple endogenous African perspectives, which tend to enrich the "Africa-World" message. The message is conveyed by the language with which the niches (eco-villages) translate the term ecological transition, the forms of life they reproduce in their spatiality, the resilience of bonding connections and the sharing of social ecosystems in practices and cosmo-visions, despite the disruptions of colonialism, capitalism and poly-exposure to globalisation. Cosmo-visions relate to the imaginaries and explanations provided by communities about the origin of the world and their relationship to the earth. The self-narratives of places present alternative ways of inhabiting the earth and relating to non-humans, rather than humans. The research findings allow us to reflect on the meaning of contemporary ecological challenges from an African perspective. They are partial results obtained by tensioning field explorations with emerging 'African paradigms'. The tension has not proved painless on both sides. While experiences of connectedness and cosmologies seem to produce forms of life in partial balance with nature, connoted by social cooperation and ties that enrich their quality, the new 'African paradigms' seem to lack autonomy, but above all they encounter difficulties with continental legitimacy. It is no coincidence that attempts to translate cosmologies into life practices generate hybrid ecologies that, in addition to questioning colonial 'scientific' genealogies, raise the more general question of what Africa is today. The discovery of which resources represent levers of an endogenous ecological transition on which to focus in order to strengthen local autonomy and the meta-stability of socio-ecological systems could open up significant avenues of research for Africa and its places

Laparoscopic reversal of Hartmann procedure: is it safe and feasible?

Abstract The Hartmann procedure (HP) consists of a sigmoidectomy followed by a terminal colostomy in the left iliac fossa and closure of the rectal stump. Although done as a temporary procedure, up to 74 % of patients will not have stoma reversal with subsequent negative impact on the quality of life. A literature search was performed using MEDLINE (PubMed), The Cochrane Library, and Google Scholar, and the articles from January 2000 until December 2015, edited in English, Italian and French, prospective or retrospective, were analyzed. Outcome variables included number of patients, mean age, sex, etiology of Hartmann's procedure, time interval between initial procedure and reversal procedure (in days), mean operative time (in minutes), number of patients converted to open surgery, causes of conversion, length of hospital stay, mortality, and complication rates. For the purpose of this review, only 21 studies were considered for the final analysis and a total of 681 patients were evaluated. The mean time interval between the initial procedure and the reversal (reported in 18 articles) was 181.6 days (range 95-330 days), while the mean operative time (reported in 20 articles) was 163.2 min (range 62-285). Overall, 80 patients (11.7 %) were converted to open technique. The length of hospitalization was between 3 and 12 days. The mortality rate was reported in 19 articles and was 0.7 % (5 patients). 113 patients (16.6 %) underwent post-operative complications. The HP reversal is a challenging procedure, but it can be safely performed laparoscopically providing various advantages when compared to the open technique and it should be proposed only to a selected group of patients, young and without a severe peritonitis at the first operation

Between process and form: Hybridisation of knowledge in the coworking project

The article reflects on the contamination of professionalisms and disciplines in the architectural project. It proposes a first exploration of the concept of hybridisation of knowledge in the design of coworking spaces. The experiences of designers and managers of coworking spaces, collected through interviews, bring out multiple facets of hybridisation: (a) hybridisation of different professions and disciplines in the complex process of management and design; (b) hybridisation of the formal, morphological and typological outcome, in a space that is flexible in form, function and process. The areas of design first and then management overlap towards a transdisciplinary approach