Hematopoietic stem cell transplantation and cellular therapy in persons living with HIV.

PURPOSE OF REVIEW: Summarize the latest research of both stem cell transplantation and cellular therapy and present the implications with respect to persons with HIV (PWH), hematologic malignancies, and HIV-1 cure. RECENT FINDINGS: Allogeneic (alloSCT) and autologous (autoSCT) stem cell transplantation have been shown to be well tolerated and effective regardless of HIV-1 status. AlloSCT leads to a decrease in the HIV-1 latently infected reservoir orders of magnitude below that achieved with antiretroviral therapy (ART) alone. Utilization of CCR5Δ2/Δ32 donors in an alloSCT has resulted in HIV-1 cures. In the last 12 months, three cases of cure have been published, giving further insight into the conditions required for HIV-1 control. Other advances in the treatment of hematological cancers include chimeric antigen receptor T-cell (CART) therapy, which are active in PWH with lymphoma. SUMMARY: Here we discuss the advances in SCT and cellular therapy in PWH and cancer. Additionally, we discuss how these technologies are being utilized to achieve HIV-1 cure.

Richter Syndrome Presenting as Subcutaneous Nodules and a Dermal Plaque.

ABSTRACT: Richter syndrome (RS) describes a phenomenon in which a patient with chronic lymphocytic leukemia (CLL) develops an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). Reports of cutaneous RS remain exceedingly rare. We report a 61-year-old woman with relapsed/refractory CLL presenting with several subcutaneous nodules on her arms and legs and a single dermal plaque on her abdomen. Skin biopsy revealed a diagnosis of DLBCL, ABC-type, and her clinical status rapidly deteriorated following diagnosis. We review the variety of clinical presentations of cutaneous RS, its association with CLL, risk factors for RS development in CLL patients, and the distinctive histopathologic and immunophenotypic features of DLBCL. We hope to highlight the importance of prompt skin biopsy in patients with CLL presenting with progressive skin lesions and increase awareness of this aggressive clinical syndrome.

Association of p16 and Ki-67 with Risk of Recurrence in Previously Treated Cervical High-Grade Squamous Intraepithelial Lesions.

OBJECTIVE: Our main objective was to assess the association between the markers p16 and Ki-67 and recurrence of disease in patients previously treated for cervical high-grade squamous intraepithelial lesion (HSIL). DESIGN: This is a case-control study at the National Cancer Institute conducted between 2005 and 2015. Of the patients with a pathologically confirmed diagnosis of HSIL, 107 cases were selected. They were divided into 2 groups: 28 cases with recurrence after treatment and a control group of 79 patients without recurrence. We identified clinical, pathological, and treatment variables. METHODS: Two experienced pathologists performed immunohistochemical analysis of biomarkers; they agreed on their interpretation, and we calculated the odds ratios (ORs) associated with recurrence. For group comparisons, we used the Wilcoxon signed-rank, χ2, or Fisher's exact test, depending on the type of variable. We conducted logistic regression models to estimate ORs and determine the factors associated with recurrence. The recurrence-free period was defined as the time frame between conization and either recurrence of disease or the last date the patient was seen. We used Kaplan-Meier plots to visualize survival curves and log-rank tests to compare the curves. We established a p value <0.05 as statistically significant. RESULTS: After pathologists performed immunohistochemical analysis, they achieved an agreement level of 83.7% for p16 and 60% for Ki-67. We did not find an association between recurrence and either p16 expression (p = 0.69) or the percentage of Ki-67 expression (p = 0.71). The recurrence-free period analysis did not reveal a difference in p16 expression (p = 0.57) nor in the percentage of Ki-67 expression in the 3-tiered scale (p = 0.56). LIMITATIONS: Our main limitation was a reduced sample size. CONCLUSION: We found no association between p16 and Ki-67 positivity and the risk of recurrence in previously treated HSIL.

Body donation as a grateful gift for a long and active life with a Björk-Shiley valve.

An 87-year-old patient donated his body to the Institute of Anatomy and Cell Biology in gratefulness for the longevity of a Björk-Shiley convexo-concave (BSCC) prosthetic aortic valve, implanted 34 years ago. The dissection of the enlarged heart showed no major signs of thrombosis, malignant fibrosis, or any other relevant issue that could potentially lead to valve failure as in other patients. Despite the reported high mortality rate of the earlier designs, especially of the BSCC valves, some patients survived for longer than expected. In more than 34 years after the BSCC valve implantation, the patient was a very active and lively man, working both as full-time and volunteer firefighter. The lifespan of this BSCC valve is among the longest reported.

Intraoperative nerve monitoring in laryngotracheal surgery. / Neuromonitorización intraoperatoria en cirugía laringotraqueal.

Laryngotracheal surgery has an inherent risk of injury to the recurrent laryngeal nerves (RLN). These complications go from minor dysphonia to even bilateral vocal cord paralysis. The intraoperative neuromonitoring of the RLN was developed in the field of thyroid surgery, in order to preserve nerve and vocal cord function. However, tracheal surgery requires in-field intubation of the distal trachea, which limits the use of nerve monitoring using conventional endotracheal tube with surface electrodes. Given these challenges, we present an alternative method for nerve monitoring during laryngotracheal surgery through the insertion of electrodes within the endolaryngeal musculature by bilateral puncture.

Minimally invasive approach for skull base meningiomas.

INTRODUCTION: Skull base meningiomas constitute a complex group of skull base tumors. The endoscopic endonasal approaches (EEA) and endoscopic Keyhole have a minimally invasive philosophy with high effectiveness, safety, and a significant decrease in postoperative morbidity in these tumors. OBJECTIVE: To describe the results of the use of minimally invasive approaches to skull base meningiomas. METHOD: A descriptive, retrospective study was carried out in 140 patients at the "Hermanos Ameijeiras" Hospital who underwent surgery for cranial base meningiomas using minimally invasive approaches to the cranial base. The degree of tumor resection, tumor recurrence, reinterventions, and complications were evaluated. RESULTS: ESA were used in 72.8% of the study, while endoscopic Keyholes were used in 26.4% and combined approaches in 0.7%. In relation to total tumor resection, 91.9% was generally achieved. Overall tumor recurrence and reinterventions were less than 8.5% and 4%, respectively. Complications in ESA were: cerebrospinal fluid (CSF) fistula (2.1%), diabetes insipidus, hydrocephalus, cerebral infarction, surgical site hematoma, worsening of cranial nerves I-IV (1.4%) respectively. While in the Keyhole type approaches: seizures (2.9%), hydrocephalus (1.4%), CSF fistula (1.4%), worsening of Nerves IX-XII (0.7%). CONCLUSIONS: The following study reaffirms that minimally invasive approaches for skull base meningiomas constitute advanced surgical techniques for these tumors, associated with a low rate of postoperative complications.

Spatial profiling of METex14-altered NSCLC under tepotinib treatment: Shifting the immunosuppressive landscape.

MET inhibitors have demonstrated efficacy in treating patients with non-small cell lung cancer (NSCLC) harboring METex14 skipping alterations. Advancements in spatial profiling technologies have unveiled the complex dynamics of the tumor microenvironment (TME), a crucial factor in cancer progression and therapeutic response. This study uses spatial profiling to investigate the effects of the MET inhibitor tepotinib on the TME in a case of locally advanced NSCLC with a METex14 skipping alteration. A patient with resectable stage IIIB NSCLC, unresponsive to neoadjuvant platinum-based chemotherapy, received tepotinib following the detection of a METex14 skipping alteration. Paired pre- and post-treatment biopsies were subjected to GeoMx Digital Spatial Profiling using the Cancer Transcriptome Atlas and immune-related protein panels to evaluate shifts in the immune TME. Tepotinib administration allowed for a successful lobectomy and a pathological downstaging to stage IA1. The TME was transformed from an immunosuppressive to a more permissive state, with upregulation of antigen-presenting and pro-inflammatory immune cells. Moreover, a marked decrease in immune checkpoint molecules, including PD-L1, was noted. Spatial profiling identified discrete immune-enriched clusters, indicating the role of tepotinib in modulating immune cell trafficking and function. Tepotinib appears to remodel the immune TME in a patient with METex14 skipping NSCLC, possibly increasing responsiveness to immunotherapy. Our study supports the integration of genetic profiling into the management of early and locally advanced NSCLC to guide personalized, targeted interventions. These findings underscore the need to further evaluate combinations of MET inhibitors and immunotherapies.

ERASURE: early autologous blood pleurodesis for postoperative air leaks-a randomized, controlled trial comparing prophylactic autologous blood pleurodesis versus standard watch and wait treatment for postoperative air leaks following thoracoscopic anatomic lung resections.

BACKGROUND: The prolonged air leak is probably the most common complication following lung resections. Around 10-20% of the patients who undergo a lung resection will eventually develop a prolonged air leak. The definition of a prolonged air leak varies between an air leak, which is evident after the fifth, seventh or even tenth postoperative day to every air leak that prolongs the hospital stay. However, the postoperative hospital stay following a thoracoscopic lobectomy can be as short as 2 days, making the above definitions sound outdated. The treatment of these air leaks is also very versatile. One of the broadly accepted treatment options is the autologous blood pleurodesis or "blood patch". The purpose of this trial is to investigate the impact of a prophylactic autologous blood pleurodesis on reducing the duration of the postoperative air leak and therefore prevent the air leak from becoming prolonged. METHODS: Patients undergoing an elective thoracoscopic anatomic lung resection for primary lung cancer or metastatic disease will be eligible for recruitment. Patients with an air leak of > 100 ml/min within 6 h prior to the morning round on the second postoperative day will be eligible for inclusion in the study and randomization. Patients will be randomized to either blood pleurodesis or watchful waiting. The primary endpoint is the time to drain removal measured in full days. The trial ends on the seventh postoperative day. DISCUSSION: The early autologous blood pleurodesis could lead to a faster cessation of the air leak and therefore to a faster removal of the drain. A faster removal of the drain would relieve the patient from all the well-known drain-associated complications (longer hospital stay, stronger postoperative pain, risk of drain-associated infection, etc.). From the economical point of view, faster drain removal would reduce the hospital costs as well as the costs associated with the care of a patient with a chest drain in an outpatient setting. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00030810. 27 December 2022.

A phase 1-2 trial of DA-EPOCH-R plus ixazomib for MYC-aberrant lymphoid malignancies: the DACIPHOR regimen.

ABSTRACT: MYC-aberrant non-Hodgkin lymphoma (NHL) is associated with poor outcomes with conventional chemotherapy. Ixazomib is an orally bioavailable proteasome inhibitor that targets drivers of MYC expression and has demonstrated preclinical activity in aggressive MYC-aberrant NHL. We conducted a phase 1/2 study evaluating the safety and efficacy of DA-EPOCH-R with adjunctive ixazomib in aggressive MYC-aberrant NHL. For induction, patients received 6 cycles of DA-EPOCH-R with ixazomib administered twice per 21-day cycle; responders continued weekly ixazomib maintenance for up to 1 year. Primary objectives were to determine the maximum tolerated dose in phase 1 and efficacy of DA-EPOCH-R with ixazomib as measured by 12-month progression-free survival (PFS) rate in phase 2. Thirty-six patients were evaluable for response. Median age was 63 years (range, 31-77) and 44% had double-hit lymphoma (DHL)/triple-hit lymphoma (THL). In phase 1, 3 mg of ixazomib was established as recommended phase 2 dose. Twenty-nine (76.3%) patients completed 6 cycles of DA-EPOCH-R and 25 (65.8%) underwent dose escalations. The ORR after induction was 97% (95% confidence interval, 81-100) with a CR rate of 69%. At median follow-up of 18.8 months, the 12-month PFS and overall survival (OS) rates were 78% and 86%, respectively. For DHL/THL vs dual expressor lymphomas (DEL), 12-month PFS rates were 53% vs 95% and 12-month OS rates were 65% vs 100%, respectively. Grade ≥3 toxicities were predominantly hematologic. Twenty-seven (75%) of patients experienced neuropathy, nearly all low-grade. DA-EPOCH-R induction with adjunctive ixazomib is feasible and appears effective in patients with DEL. This trial was registered at www.clinicaltrials.gov as #NCT02481310.

Rapid identification of inflammatory arthritis and associated adverse events following immune checkpoint therapy: a machine learning approach.

Introduction: Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) poses a major clinical challenge to ICI therapy for cancer, with 13% of cases halting ICI therapy and ICI-IA being difficult to identify for timely referral to a rheumatologist. The objective of this study was to rapidly identify ICI-IA patients in clinical data and assess associated immune-related adverse events (irAEs) and risk factors. Methods: We conducted a retrospective study of the electronic health records (EHRs) of 89 patients who developed ICI-IA out of 2451 cancer patients who received ICI therapy at Northwestern University between March 2011 to January 2021. Logistic regression and random forest machine learning models were trained on all EHR diagnoses, labs, medications, and procedures to identify ICI-IA patients and EHR codes indicating ICI-IA. Multivariate logistic regression was then used to test associations between ICI-IA and cancer type, ICI regimen, and comorbid irAEs. Results: Logistic regression and random forest models identified ICI-IA patients with accuracies of 0.79 and 0.80, respectively. Key EHR features from the random forest model included ICI-IA relevant features (joint pain, steroid prescription, rheumatoid factor tests) and features suggesting comorbid irAEs (thyroid function tests, pruritus, triamcinolone prescription). Compared to 871 adjudicated ICI patients who did not develop arthritis, ICI-IA patients had higher odds of developing cutaneous (odds ratio [OR]=2.66; 95% Confidence Interval [CI] 1.63-4.35), endocrine (OR=2.09; 95% CI 1.15-3.80), or gastrointestinal (OR=2.88; 95% CI 1.76-4.72) irAEs adjusting for demographics, cancer type, and ICI regimen. Melanoma (OR=1.99; 95% CI 1.08-3.65) and renal cell carcinoma (OR=2.03; 95% CI 1.06-3.84) patients were more likely to develop ICI-IA compared to lung cancer patients. Patients on nivolumab+ipilimumab were more likely to develop ICI-IA compared to patients on pembrolizumab (OR=1.86; 95% CI 1.01-3.43). Discussion: Our machine learning models rapidly identified patients with ICI-IA in EHR data and elucidated clinical features indicative of comorbid irAEs. Patients with ICI-IA were significantly more likely to also develop cutaneous, endocrine, and gastrointestinal irAEs during their clinical course compared to ICI therapy patients without ICI-IA.

Uniportal VATS for Diagnosis and Staging in Non-Small Cell Lung Cancer (NSCLC).

Uniportal VATS has become an accepted approach in minimally invasive thoracic surgery since its first report for lobectomy in 2011. Since the initial restrictions in indications, it has been used in almost all procedures, from conventional lobectomies to sublobar resections, bronchial and vascular sleeve procedures and even tracheal and carinal resections. In addition to its use for treatment, it provides an excellent approach for suspicious solitary undiagnosed nodules after bronchoscopic or transthoracic image-guided biopsy. Uniportal VATS is also used as a surgical staging method in NSCLC due to its low invasiveness in terms of chest tube duration, hospital stay and postoperative pain. In this article, we review the evidence of uniportal VATS accuracy for NSCLC diagnosis and staging and provide technical details and recommendations for its safe performance for that purpose.

Isolation of Methane Enriched Bacterial Communities and Application as Wheat Biofertilizer under Drought Conditions: An Environmental Contribution.

The search for methanotrophs as plant-growth-promoting rhizobacteria (PGPR) presents an important contribution to mitigating the impact of global warming by restoring the natural soil potential for consuming methane while benefiting plants during droughts. Our in silico simulations suggest that water, produced as a byproduct of methane oxidation, can satisfy the cell growth requirement. In addition to water, methanotrophs can produce metabolites that stimulate plant growth. Considering this, we proposed that applying methanotrophs as PGPR can alleviate the effect of droughts on crops, while stimulating atmospheric methane consumption. In this work, we isolated a series of methanotrophic communities from the rhizospheres of different crops, including Italian sweet pepper and zucchini, using an atmosphere enriched with pure methane gas, to determine their potential for alleviating drought stress in wheat plants. Subsequently, 23 strains of nonmethanotrophic bacteria present in the methanotrophic communities were isolated and characterized. We then analyzed the contribution of the methane-consuming consortia to the improvement of plant growth under drought conditions, showing that some communities contributed to increases in the wheat plants' lengths and weights, with statistically significant differences according to ANOVA models. Furthermore, we found that the presence of methane gas can further stimulate the plant-microbe interactions, resulting in larger plants and higher drought tolerance.

Tepotinib in patients with non-small cell lung cancer with high-level MET amplification detected by liquid biopsy: VISION Cohort B.

High-level MET amplification (METamp) is a primary driver in ∼1%-2% of non-small cell lung cancers (NSCLCs). Cohort B of the phase 2 VISION trial evaluates tepotinib, an oral MET inhibitor, in patients with advanced NSCLC with high-level METamp who were enrolled by liquid biopsy. While the study was halted before the enrollment of the planned 60 patients, the results of 24 enrolled patients are presented here. The objective response rate (ORR) is 41.7% (95% confidence interval [CI], 22.1-63.4), and the median duration of response is 14.3 months (95% CI, 2.8-not estimable). In exploratory biomarker analyses, focal METamp, RB1 wild-type, MYC diploidy, low circulating tumor DNA (ctDNA) burden at baseline, and early molecular response are associated with better outcomes. Adverse events include edema (composite term; any grade: 58.3%; grade 3: 12.5%) and constipation (any grade: 41.7%; grade 3: 4.2%). Tepotinib provides antitumor activity in high-level METamp NSCLC (ClinicalTrials.gov: NCT02864992).

Peri-CAR-T practice patterns and survival predictors for all CAR-T patients and post-CAR-T failure in aggressive B-NHL.

Most patients receiving chimeric antigen receptor T-cell therapy (CAR-T) for aggressive B-cell non-Hodgkin lymphoma (B-NHL) do not experience a durable remission. Several novel agents are approved to treat relapsed, refractory aggressive B-NHL; however, it remains unclear how to sequence these therapies pre- and post-CAR-T. We conducted a multicenter retrospective analysis to describe peri-CAR-T practice patterns and survival predictors for patients receiving CD19-directed CAR-T. Patients (n = 514) from 13 centers treated with CAR-T for B-NHL between 2015-2021 were included in the study. Survival curves were constructed using Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the impact of the variables on survival outcomes. For all patients receiving CAR-T, a greater number of lines of therapy pre-CAR-T apheresis and bridging therapy were predictive of inferior progression-free survival (PFS) and overall survival (OS). The median PFS and OS from the time of CAR-T cell infusion were 7.6 and 25.6 months, respectively. From the time of progression post-CAR-T, the median OS was 5.5 months. The median PFS of treatments administered in the first-line post-CAR-T failure was 2.8 months. Patients with refractory disease on day 30 had inferior OS and were less likely to receive subsequent treatment(s) than other patients with CAR-T failure. Allogeneic hematopoietic cell transplantation for selected patients at any time following CAR-T failure led to durable responses in over half of patients at 1 year. These data provide a benchmark for future clinical trials in patients with post-CAR-T cell progression, which remains an unmet clinical need.

Nonintubated versus intubated thoracoscopic bullectomy for primary spontaneous pneumothorax: A multicenter propensity-matched analysis.

BACKGROUND: We aimed at comparing in a multicenter propensity-matched analysis, results of nonintubated versus intubated video-assisted thoracic surgery (VATS) bullectomy/blebectomy for primary spontaneous pneumothorax (PSP). METHODS: Eleven Institutions participated in the study. A total of 208 patients underwent VATS bullectomy by intubated (IVATS) (N = 138) or nonintubated (NIVATS) (N = 70) anesthesia during 60 months. After propensity matching, 70 pairs of patients were compared. Anesthesia in NIVATS included intercostal (N = 61), paravertebral (N = 5) or thoracic epidural (N = 4) block and sedation with (N = 24) or without (N = 46) laryngeal mask under spontaneous ventilation. In the IVATS group, all patients underwent double-lumen-intubation and mechanical ventilation. Primary outcomes were morbidity and recurrence rates. RESULTS: There was no difference in age (26.7 ± 8 vs 27.4 ± 9 years), body mass index (19.7 ± 2.6 vs 20.6 ± 2.5), and American Society of Anesthesiology score (2 vs 2). Main results show no difference both in morbidity (11.4% vs 12.8%; p = 0.79) and recurrence free rates (92.3% vs 91.4%; p = 0.49) between NIVATS and IVATS, respectively, whereas a difference favoring the NIVATS group was found in anesthesia time (p < 0.0001) and operative time (p < 0.0001), drainage time (p = 0.001), and hospital stay (p < 0.0001). There was no conversion to thoracotomy and no hospital mortality. One patient in the NIVATS group needed reoperation due to chest wall bleeding. CONCLUSION: Results of this multicenter propensity-matched study have shown no intergroup difference in morbidity and recurrence rates whereas shorter operation room time and hospital stay favored the NIVATS group, suggesting a potential increase in the role of NIVATS in surgical management of PSP. Further prospective studies are warranted.

Outcomes of Cancer Patients with COVID-19 in a Hospital System in the Chicago Metropolitan Area.

Patients with a history of malignancy have been shown to be at an increased risk of COVID-19-related morbidity and mortality. Poorer clinical outcomes in that patient population are likely due to the underlying systemic illness, comorbidities, and the cytotoxic and immunosuppressive anti-tumor treatments they are subjected to. We identified 416 cancer patients with SARS-CoV-2 infection being managed for their malignancy at Northwestern Medicine in Chicago, Illinois, between March and July of 2020. Seventy-five (18.0%) patients died due to COVID-related complications. Older age (>60), male gender, and current treatment with immunotherapy were associated with shorter overall survival. Laboratory findings showed that higher platelet counts, ALC, and hemoglobin were protective against critical illness and death from COVID-19. Conversely, elevated inflammatory markers such as ferritin, d-dimer, procalcitonin, CRP, and LDH led to worse clinical outcomes. Our findings suggest that a thorough clinical and laboratory assessment of infected patients with cancer might help identify a more vulnerable population and implement more aggressive proactive strategies.

Management of ALCL and other CD30+ peripheral T-cell lymphomas with a focus on Brentuximab vedotin.

Peripheral T-cell lymphomas (PTCL) are rare lymphoproliferative disorders with poor outcomes and high rates of relapse. Incidence varies although the most common subtypes include PTCL-not-otherwise specified, anaplastic large cell lymphoma, and angioimmunoblastic T-cell lymphoma. Anaplastic large cell lymphoma is characterized by near-universal CD30 expression and serves as a prototypic model for other CD30-expressing lymphomas. Historically, these neoplasms have been treated with regimens used in the treatment of aggressive B-cell lymphomas. Over the last decade, brentuximab vedotin, an antibody-drug conjugate, has been investigated to treat peripheral T-cell lymphomas expressing CD30. While first studied in the relapsed and refractory setting, it was later studied in the frontline setting in the ECHELON-2 trial with positive results and is now an approved treatment for CD30-expressing peripheral T-cell lymphomas. Other treatment options in the relapsed and refractory setting include histone deacetylase inhibitors, pralatrexate, and salvage multiagent chemotherapy regimens. Current research is underway regarding combination therapies and the use of other novel agents.

Novel insights into the pathogenesis and treatment of NRAS mutant melanoma.

INTRODUCTION: NRAS was the first mutated oncogene identified in melanoma and is currently the second most common driver mutation in this malignancy. For patients with NRASmutant advanced stage melanoma refractory to immunotherapy or with contraindications to immune-based regimens, there are few therapeutic options including low-efficacy chemotherapy regimens and binimetinib monotherapy. Here, we review recent advances in preclinical studies of molecular targets for NRAS mutant melanoma as well as the failures and successes of early-phase clinical trials. While there are no targeted therapies for NRAS-driven melanoma, there is great promise in approaches combining MEK inhibition with inhibitors of the focal adhesion kinase (FAK), inhibitors of autophagy pathways, and pan-RAF inhibitors. AREAS COVERED: This review surveys new developments in all aspects of disease pathogenesis and potential treatment - including those that have failed, stalled, or progressed through various phases of preclinical and clinical development. EXPERT OPINION: There are no currently approved targeted therapies for BRAF wild-type melanoma patients harboring NRAS driver mutations though an array of agents are in early phase clinical trials. The diverse strategies taken exploit combined MAP kinase signaling blockade with inhibition of cell cycle mediators, inhibition of the autophagy pathway, and alteration of kinases involved in actin cytoskeleton signaling. Future advances of developmental therapeutics into late stage trials may yield new options beyond immunotherapy for patients with advanced stage disease and NRAS mutation status.

Thrombocytosis and Thrombosis: Is There Really a Correlation?

PURPOSE OF REVIEW: Thrombocytosis is common to all myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis. Despite the traditionally held belief amongst many clinicians that thrombocytosis correlates with thrombosis risk, there is little evidence in the literature to support that claim. Herein we critically analyze the literature to better understand the relationship between thrombocytosis and risk of thrombosis in MPN. RECENT FINDINGS: Both retrospective and prospective studies argue against associations between thrombocytosis and risk of thrombosis in patients with ET and PV. Rather, most studies suggest that the presence of extreme thrombocytosis is instead associated with an increased risk of hemorrhagic events, a paradoxical phenomenon with important clinical implications. Thrombosis risk has a multifactorial set of etiologies in MPNs. While qualitative abnormalities of the platelets may contribute, associations between platelet quantity and thrombosis risk are weak in MPN patients.

Management of Intraoperative Crisis During Nonintubated Thoracic Surgery.

Nonintubated video-assisted thoracoscopic surgery programs have gradually spread all over the world. The benefits are based on less invasiveness and earlier recovery. However, complications may appear. For the correct prevention and management of all these potentially critical situations, the principles of crisis resource management (CRM) must be followed. They should also include clinical simulation as a tool to generate different scenarios to improve teamwork. The purpose of this special issue is to appraise and summarize the design, implementation, and efficacy of simulation-based CRM training programs for a specific surgery, including the management of specific surgical and medical critical scenarios.