Emergency Resection for Colonic Cancer Has an Independent and Unfavorable Effect on Long-Term Oncologic Outcome

Background Long-term outcomes in patients undergoing emergency versus elective resection for colorectal cancer (CRC) remain controversial. This study aims to assess short- and long-term outcomes of emergency versus elective CRC surgery. Methods In this single-center retrospective cohort study, patients undergoing emergency or elective colonic resections for CRC from January 2013 to December 2017 were included. Primary outcome was long-term survival. As secondary outcomes, we sought to analyze potential differences on postoperative morbidity and concerning the oncological standard of surgical resection. The Kaplan-Meier curves and Cox proportional hazard model were used to compare survival between the groups. Results Overall, 225 CRC patients were included. Of these 192 (85.3%) had an elective and 33 (14.7%) an emergency operation. Emergency indications were due to obstruction, perforation, or bleeding. Patients in the emergency group had higher ASA score (p = 0.023), higher Charlsson comorbidity index (CCI, p = 0.012), and were older than those in the elective group, with median age 70 (IQR 63-79) years and 78 (IQR 68-83) years, for elective and emergency, respectively (p = 0.020). No other preoperative differences were observed. Patients in the emergency group experienced significantly more major complications (12.1% vs. 3.6%, p = 0.037), more anastomotic leakage (12.1% vs. 1.6%, p = 0.001), need for reoperation (12.1% vs. 3.1%, p = 0.021), and postoperative mortality (2 patients vs. 0, p < 0.001). No differences in terms of final pathological stage, nor in accuracy of lymphadenectomy were observed. Overall survival was significantly worse in case of emergency operation, with estimated median 41 months vs. not reached in elective cases (p < 0.001). At the multivariate analysis, emergency operation was confirmed as independent unfavorable determinant of survival (with hazard rate HR = 1.97, p = 0.028), together with age (HR = 1.05, p < 0.001), postoperative major morbidity (HR = 3.18, p = 0.012), advanced stage (HR = 5.85, p < 0.001), and need for transfusion (HR = 2.10, p = 0.049). Conclusion Postoperative morbidity and mortality were increased in emergency versus elective CRC resections. Despite no significant differences in terms of accuracy of resection and pathological stages, overall survival was significantly worse in patients who underwent emergency procedure, and independent of other determinants of survival

In Vitro Megakaryocyte Differentiation and Proplatelet Formation in Ph-Negative Classical Myeloproliferative Neoplasms: Distinct Patterns in the Different Clinical Phenotypes

Background: Ph-negative myeloproliferative neoplasms (MPNs) are clonal disorders that include primary myelofibrosis (PMF), polycythemia vera (PV) and essential thrombocythemia (ET). Although the pathogenesis of MPNs is still incompletely understood, an involvement of the megakaryocyte lineage is a distinctive feature. Methodology/Principal Findings: We analyzed the in vitro megakaryocyte differentiation and proplatelet formation in 30 PMF, 8 ET, 8 PV patients, and 17 healthy controls (CTRL). Megakaryocytes were differentiated from peripheral blood CD34+ or CD45+ cells in the presence of thrombopoietin. Megakaryocyte output was higher in MPN patients than in CTRL with no correlation with the JAK2 V617F mutation. PMF-derived megakaryocytes displayed nuclei with a bulbous appearance, were smaller than ET- or PV-derived megakaryocytes and formed proplatelets that presented several structural alterations. In contrast, ET- and PV-derived megakaryocytes produced more proplatelets with a striking increase in bifurcations and tips compared to both control and PMF. Proplatelets formation was correlated with platelet counts in patient peripheral blood. Patients with pre-fibrotic PMF had a pattern of megakaryocyte proliferation and proplatelet formation that was similar to that of fibrotic PMF and different from that of ET. Conclusions/Significance: In conclusion, MPNs are associated with high megakaryocyte proliferative potential. Profound differences in megakaryocyte morphology and proplatelet formation distinguish PMF, both fibrotic and prefibrotic, from ET and PV

High Frequency of Endothelial Colony Forming Cells Marks a Non-Active Myeloproliferative Neoplasm with High Risk of Splanchnic Vein Thrombosis

Increased mobilization of circulating endothelial progenitor cells may represent a new biological hallmark of myeloproliferative neoplasms. We measured circulating endothelial colony forming cells (ECFCs) in 106 patients with primary myelofibrosis, fibrotic stage, 49 with prefibrotic myelofibrosis, 59 with essential thrombocythemia or polycythemia vera, and 43 normal controls. Levels of ECFC frequency for patient's characteristics were estimated by using logistic regression in univariate and multivariate setting. The sensitivity, specificity, likelihood ratios, and positive predictive value of increased ECFC frequency were calculated for the significantly associated characteristics. Increased frequency of ECFCs resulted independently associated with history of splanchnic vein thrombosis (adjusted odds ratio = 6.61, 95% CI = 2.54–17.16), and a summary measure of non-active disease, i.e. hemoglobin of 13.8 g/dL or lower, white blood cells count of 7.8×109/L or lower, and platelet count of 400×109/L or lower (adjusted odds ratio = 4.43, 95% CI = 1.45–13.49) Thirteen patients with splanchnic vein thrombosis non associated with myeloproliferative neoplasms were recruited as controls. We excluded a causal role of splanchnic vein thrombosis in ECFCs increase, since no control had elevated ECFCs. We concluded that increased frequency of ECFCs represents the biological hallmark of a non-active myeloproliferative neoplasm with high risk of splanchnic vein thrombosis. The recognition of this disease category copes with the phenotypic mimicry of myeloproliferative neoplasms. Due to inherent performance limitations of ECFCs assay, there is an urgent need to arrive to an acceptable standardization of ECFC assessment

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections