Lymphocyte recovery after bendamustine therapy in patients with mantle cell lymphoma. Results of a retrospective analysis and prognostic impact in the CAR-T era.

Bendamustine in combination with rituximab (BR) or with rituximab and cytarabine (R-BAC) is the standard first-line immunochemotherapy in mantle cell lymphoma (MCL) for elderly patients and patients ineligible for intensive regimens or autologous transplantation. As bendamustine causes prolonged lymphopenia and the literature lacks evidence of its persistence in patients with MCL, this retrospective analysis aims to estimate the lymphocyte recovery time, also in view of potential immunotherapy with CAR-T cells. Data were collected from 44 consecutive MCL patients who received bendamustine (BR or R-BAC) as first-line therapy at the Hematology Unit of Sapienza University Hospital between May 2011 and April 2022. Twenty patients (45%) were treated with R-BAC and 24 (55%) with BR. At baseline, the median lymphocyte count was 1795/µl (range: 370-11730/µL). One month after the end of therapy, it was 450/µl (range: 50-3300/µl) and 3 months after 768/µl (range: 260-1650/µl). After 6 and 9 months, we observed a gradual increase in median lymphocyte count of 900/µl (range: 370-2560/µl and 130-2770/µl, respectively). After 12 months median lymphocyte count was 1256/µl (range: 240-4140/µl). Median lymphocyte count at 1, 3, 6, and 9 months post-treatment was significantly lower than baseline but showed recovery by the 12 months. This finding is crucial for MCL patients considering CAR-T cell therapy, suggesting a minimum 9-month interval between bendamustine administration and leukapheresis.

Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS).

BACKGROUND: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. METHODS: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. RESULTS: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). CONCLUSIONS: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients.

Culprit plaque morphology determines inflammatory risk and clinical outcomes in acute coronary syndrome.

AIMS: Rupture of the fibrous cap (RFC) and erosion of an intact fibrous cap (IFC) are the two predominant mechanisms causing acute coronary syndromes (ACS). It is uncertain whether clinical outcomes are different following RFC-ACS vs. IFC-ACS and whether this is affected by a specific inflammatory response. The prospective, translational OPTIcal-COherence Tomography in Acute Coronary Syndrome study programme investigates the impact of the culprit lesion phenotype on inflammatory profiles and prognosis in ACS patients. METHODS AND RESULTS: This analysis included 398 consecutive ACS patients, of which 62% had RFC-ACS and 25% had IFC-ACS. The primary endpoint was a composite of cardiac death, recurrent ACS, hospitalization for unstable angina, and target vessel revascularization at 2 years [major adverse cardiovascular events (MACE+)]. Inflammatory profiling was performed at baseline and after 90 days. Patients with IFC-ACS had lower rates of MACE+ than those with RFC-ACS (14.3% vs. 26.7%, P = 0.02). In 368-plex proteomic analyses, patients with IFC-ACS showed lower inflammatory proteome expression compared with those with RFC-ACS, including interleukin-6 and proteins associated with the response to interleukin-1ß. Circulating plasma levels of interleukin-1ß decreased from baseline to 3 months following IFC-ACS (P < 0.001) but remained stable following RFC-ACS (P = 0.25). Interleukin-6 levels decreased in patients with RFC-ACS free of MACE+ (P = 0.01) but persisted high in those with MACE+. CONCLUSION: This study demonstrates a distinct inflammatory response and a lower risk of MACE+ following IFC-ACS. These findings advance our understanding of inflammatory cascades associated with different mechanisms of plaque disruption and provide hypothesis generating data for personalized anti-inflammatory therapeutic allocation to ACS patients, a strategy that merits evaluation in future clinical trials.

De-escalation strategies in patients with acute coronary syndrome: a step towards precision medicine.

INTRODUCTION: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is a cornerstone in the treatment of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Current international guidelines recommend the use of 12 months of DAPT with newer P2Y12 inhibitors (i.e. ticagrelor or prasugrel) as first-line therapy in this setting. However, intense and prolonged DAPT regimens are associated with an increased risk of bleeding, with relevant prognostic implications. Recently, a strategy of de-escalation of P2Y12 inhibitors has been proposed as an alternative to conventional DAPT to mitigate the risk of bleeding while preserving ischemic protection after ACS. AREAS COVERED: In this review, we summarize the available evidence on guided and unguided strategies for P2Y12 inhibitor de-escalation in patients with ACS undergoing PCI. EXPERT OPINION: Among patients with ACS, guided and unguided de-escalation strategies are safe and effective for secondary cardiovascular prevention. Although the implementation of genetic and platelet function tests is of interest for treatment personalization, the routine use of guided de-escalation strategies seems impractical. In this context, unguided de-escalation approaches appear more attractive, convenient, and suitable for contemporary practice.

Early management of isolated severe traumatic brain injury patients in a hospital without neurosurgical capabilities: a consensus and clinical recommendations of the World Society of Emergency Surgery (WSES).

BACKGROUND: Severe traumatic brain-injured (TBI) patients should be primarily admitted to a hub trauma center (hospital with neurosurgical capabilities) to allow immediate delivery of appropriate care in a specialized environment. Sometimes, severe TBI patients are admitted to a spoke hospital (hospital without neurosurgical capabilities), and scarce data are available regarding the optimal management of severe isolated TBI patients who do not have immediate access to neurosurgical care. METHODS: A multidisciplinary consensus panel composed of 41 physicians selected for their established clinical and scientific expertise in the acute management of TBI patients with different specializations (anesthesia/intensive care, neurocritical care, acute care surgery, neurosurgery and neuroradiology) was established. The consensus was endorsed by the World Society of Emergency Surgery, and a modified Delphi approach was adopted. RESULTS: A total of 28 statements were proposed and discussed. Consensus was reached on 22 strong recommendations and 3 weak recommendations. In three cases, where consensus was not reached, no recommendation was provided. CONCLUSIONS: This consensus provides practical recommendations to support clinician's decision making in the management of isolated severe TBI patients in centers without neurosurgical capabilities and during transfer to a hub center.

Posterior communicating artery infundibulum with oculomotor nerve palsy treated with microvascular decompression: a case report and 2-dimensional technical operative video.

Oculomotor nerve palsies are typically associated with posterior communicating artery (PcommA) aneurysms. We report a rare case of an oculomotor nerve palsy caused by a PcommA infundibular dilatation. Although there are cases of infundibular dilatations causing cranial nerve palsies, only reports of three involving the PcommA exists. We review these reported cases in the literature and discuss their treatments as well as other non-aneurysmal compressive etiologies that may cause oculomotor nerve palsies. We present the case of a 53-year-old female with transient oculomotor nerve palsy that was initially diagnosed with a PcommA aneurysm. She underwent a craniotomy with plans of microsurgical clipping; however, the dilatation was identified correctly as an infundibulum intraoperatively. The operation was completed as a microvascular decompression and her oculomotor nerve palsy has not returned at the 1-year follow-up. We provide a detailed microsurgical report and video detailing the operative technique and relevant anatomy for this operation. Although rare and not as life-threatening as aneurysms, infundibular dilatations as a cause of oculomotor nerve palsy should remain as a differential diagnosis. Given the difference in natural history and treatment of these two entities, it is important to diagnose and treat them appropriately. Multimodal imaging such as thin-sliced computed tomography angiogram (CTA) and 3-dimensional (3D) rotational angiography can aid in diagnosis.

The Era of Onyx Embolization: A Systematic and Literature Review of Preoperative Embolization Before Stereotactic Radiosurgery for the Management of Cerebral Arteriovenous Malformations.

INTRODUCTION: The current treatment paradigm for intracranial arteriovenous malformations (AVMs) focuses on reducing the risk of intracranial hemorrhage using various therapeutic means including embolization, stereotactic radiosurgery (SRS), and microsurgical resection. To improve AVM obliteration rates with SRS, pre-radiosurgical embolization has been trialed in a number of studies to reduce the volume of the AVM nidus prior to radiosurgery. This study aimed to review the efficacy of pre-radiosurgical embolization in the pre-Onyx era compared to the current Onyx era. METHODS: A systematic review was performed using PubMed to identify studies with 20 or more AVM patients, embolization material, and obliteration rates for both embolization + stereotactic radiosurgery (E+SRS) and SRS-only groups. RESULTS: Seventeen articles consisting of 1133 eligible patients were included in this study. A total of 914 (80.7%) patients underwent embolization prior to SRS. Onyx was used as the embolysate in 340 (37.2%) patients in the E+SRS cohorts. Mean obliteration rate for the embolized cohort was 46.9% versus 46.5% in the SRS-only cohort. When comparing obliteration rates based on embolysate material, obliteration rate was 42.1% with Onyx+SRS and 50.0% in the non-Onyx embolysate + SRS cohort. CONCLUSIONS: Onyx (ethylene vinyl-alcohol copolymer dissolved in dimethyl sulfoxide and suspended in micronized tantalum powder) has been increasingly used for the embolization of intracranial AVMs with increased success regarding its ease of use from a technical standpoint and performs similarly to other embolysate materials.

Decompressive hemicraniectomy and cranioplasty using subcutaneously preserved autologous bone flaps versus synthetic implants: perioperative outcomes and cost analysis.

OBJECTIVE: It has not been well-elucidated whether there are advantages to preserving bone flaps in abdominal subcutaneous (SQ) tissue after decompressive hemicraniectomy (DHC), compared to discarding bone flaps. The authors aimed to compare perioperative outcomes and costs for patients undergoing autologous cranioplasty (AC) after DHC with the bone flap preserved in abdominal SQ tissue, and for patients undergoing synthetic cranioplasty (SC). METHODS: A retrospective review was performed of all patients undergoing DHC procedures between January 2017 and July 2021 at two tertiary care institutions. Patients were divided into two groups: those with flaps preserved in SQ tissue (SQ group), and those with the flap discarded (discarded group). Additional analysis was performed between patients undergoing AC versus SC. Primary end points included postoperative and surgical site complications. Secondary endpoints included operative costs, length of stay, and blood loss. RESULTS: A total of 248 patients who underwent DHC were included in the study, with 155 patients (62.5%) in the SQ group and 93 (37.5%) in the discarded group. Patients in the discarded group were more likely to have a diagnosis of severe TBI (57.0%), while the most prevalent diagnosis in the SQ group was malignant stroke (35.5%, p < 0.05). There were 8 (5.2%) abdominal surgical site infections and 9 (5.8%) abdominal hematomas. The AC group had a significantly higher reoperation rate (23.2% vs 12.9%, p = 0.046), with 11% attributable to abdominal reoperations. The average cost of a reoperation for an abdominal complication was $40,408.75 ± $2273. When comparing the AC group to the SC group after cranioplasty, there were no significant differences in complications or surgical site infections. There were 6 cases of significant bone resorption requiring cement supplementation or discarding of the bone flap. Increased mean operative charges were found for the SC group compared to the AC group ($72,362 vs $59,726, p < 0.001). CONCLUSIONS: Autologous bone flaps may offer a cost-effective option compared to synthetic flaps. However, when preserved in abdominal SQ tissue, they pose the risk of resorption over time as well as abdominal surgical site complications with increased reoperation rates. Further studies and methodologies such as cryopreservation of the bone flap may be beneficial to reduce costs and eliminate complications associated with abdominal SQ storage.

Bleeding Complications in Patients With Perioperative COVID-19 Infection Undergoing Cardiac Surgery: A Single-Center Matched Case-Control Study.

OBJECTIVE: Previous studies reported a poor outcome in patients with coronavirus 2019 (COVID-19) undergoing cardiac surgery. Complications most frequently described were respiratory failure, renal failure, and thromboembolic events. In their recent experience, the authors observed a very high incidence of bleeding complications. The purpose of the study was to investigate a possible significant correlation between perioperative COVID-19 infection and hemorrhagic complications compared to non-COVID-19 patients. DESIGN: Single-center, observational, retrospective, matched case-control (1:2) study involving patients who underwent open-heart cardiac surgery from February 2020 and March 2021 with positive perioperative diagnosis of COVID-19 infection, matched with patients without COVID-19 infection. SETTING: Cardiac surgery unit and intensive care unit of a university tertiary center in a metropolitan area. PARTICIPANTS: In the study period, 773 patients underwent cardiac surgery on cardiopulmonary bypass (CPB). Among them, 23 consecutive patients had perioperative diagnosis of COVID-19 infection (study group). These patients were compared with 46 corresponding controls (control group) that matched for age, sex, body mass index, and Society of Thoracic Surgeons score. INTERVENTIONS: Open-heart cardiac surgery on CPB. MEASUREMENTS AND MAIN RESULTS: In the study group, 2 patients (9%) died in the intensive care unit from severe respiratory failure, shock, and multiple organ failure. In the study group, patients showed a significantly higher incidence of bleeding complications (48% v 2%, p = 0.0001) and cases of surgical reexploration for bleeding (35% v 2%, p = 0.0001), a higher incidence of severe postoperative thrombocytopenia (39% v 6%, p = 0.0007), and a higher need of blood components transfusions (74% v 30%, p = 0.0006). Chest tubes blood loss and surgical hemostasis time were markedly prolonged (p = 0.02 and p = 0.003, respectively). CONCLUSIONS: A worrisome increased risk of early and late bleeding complications in COVID-19 patients was observed, and it should be considered when assessing the operative risk. CPB-related inflammatory reaction could exacerbate the deleterious effect of COVID-19 on the coagulation system and likely deviate it toward a hemorrhagic pattern.

Middle meningeal artery embolization with subdural evacuating port system for primary management of chronic subdural hematomas.

Optimal treatment for chronic subdural hematomas remains controversial and perioperative risks and comorbidities may affect management strategies. Minimally invasive procedures are emerging as alternatives to the standard operative treatments. We evaluate our experience with middle meningeal artery (MMA) embolization combined with Subdural Evacuating Port System (SEPS) placement as a first-line treatment for patients with cSDH. A single institution retrospective review was performed of all patients undergoing intervention. Patients were stratified by treatment with MMA embolization and SEPS placement, MMA embolization and surgery, SEPS placement only, and surgery only for cSDH from 2017 to 2020, and cohorts were compared against each other. Patients treated with MMA/SEPS were more likely to be older, be on anticoagulation, have significant comorbidities, have shorter length of stay, and less likely to have symptomatic recurrence compared to SEPS only cohort. Thus, MMA/SEPS appears to be a safe and equally effective minimally invasive treatment for cSDH patients with significant comorbidities who are poor surgical candidates.

Abnormal neurological pupil index is associated with malignant cerebral edema after mechanical thrombectomy in large vessel occlusion patients.

BACKGROUND AND OBJECTIVES: Malignant cerebral edema (MCE) is a feared complication in patients suffering from large vessel occlusion. Variables associated with the development of MCE have not been clearly elucidated. Use of pupillometry and the neurological pupil index (NPi) as an objective measure in patients undergoing mechanical thrombectomy (MT) has not been explored. We aim to evaluate variables significantly associated with MCE in patients that undergo MT and hypothesize that abnormal NPi is associated with MCE in this population. METHODS: A retrospective analysis of patients with acute ischemic stroke who had undergone MT at our institution between 2017 and 2020 was performed. Baseline and outcome variables were collected, including NPi values from pupillometry readings of patients within 72 h after the MT. Patients were divided into two groups: MCE versus non-MCE group. A univariate and multivariate analysis was performed. RESULTS: Of 284 acute ischemic stroke patients, 64 (22.5%) developed MCE. Mean admission glucose (137 vs. 173; p < 0.0001), NIHSS on admission (17 vs. 24; p < 0.01), infarct core volume (27.9 vs. 17.9 mL; p = 0.0036), TICI score (p = 0.001), and number of passes (2.9 vs. 1.8; p < 0.0001) were significantly different between the groups. Pupillometry data was present for 64 patients (22.5%). Upon multivariate analysis, abnormal ipsilateral NPi (OR 21.80 95% CI 3.32-286.4; p = 0.007) and hemorrhagic conversion were independently associated with MCE. CONCLUSION: Abnormal NPi and hemorrhagic conversion are significantly associated with MCE in patients following MT. Further investigation is warranted to better define an association between NPi and patient outcomes in this patient population.

JET 7 XTRA Flex reperfusion catheter related complications during endovascular thrombectomy.

Endovascular thrombectomy has revolutionized the management of acute ischemic stroke from emergent large vessel occlusion. Continued technological advancement in the field, as evidenced by successive introduction of large bore aspiration catheters with enhanced trackability and large inner diameter, has played a major role in achieving fast and robust recanalization and improved clinical outcome. Here, we present three patients with intraprocedural device malfunction related to the JET 7 XTRA Flex reperfusion catheter.

Macrophage infiltrates in coronary plaque erosion and cardiovascular outcome in patients with acute coronary syndrome.

BACKGROUND AND AIMS: Plaque erosion (PE) is responsible for at least one-third of acute coronary syndrome (ACS), and inflammation plays a key role in plaque instability. We assessed the presence of optical coherence tomography (OCT)-defined macrophage infiltrates (MØI) at the culprit site in ACS patients with PE, evaluating their clinical and OCT correlates, along with their prognostic value. METHODS: ACS patients undergoing OCT imaging and presenting PE as culprit lesion were retrospectively selected. Presence of MØI at culprit site was assessed. The incidence of major adverse cardiac events (MACEs), defined as the composite of cardiac death, recurrent myocardial infarction and target-vessel revascularization (TVR), was assessed [follow-up median (interquartile range, IQR) time 2.5 (2.03-2.58) years]. RESULTS: We included 153 patients [median age (IQR) 64 (53-75) years, 99 (64.7%) males]. Fifty-one (33.3%) patients presented PE with MØI and 102 (66.7%) PE without MØI. Patients having PE with MØI compared with PE patients without MØI had more vulnerable plaque features both at culprit site and at non-culprit segments. MACEs were significantly more frequent in PE with MØI patients compared with PE without MØI [11 (21.6%) vs. 6 (5.9%), p = 0.008], mainly driven by a higher risk of cardiac death and TVR. At multivariable Cox regression, PE with MØI was an independent predictor of MACEs [HR = 2.95, 95% CI (1.09-8.02), p = 0.034]. CONCLUSIONS: Our study demonstrates that among ACS patients with PE the presence of MØI at culprit lesion is associated with more vulnerable plaque features, along with a worse prognosis at a long-term follow-up.

Efficacy and safety of novel oral anticoagulants versus low molecular weight heparin in cancer patients with venous thromboembolism: A systematic review and meta-analysis.

Novel Oral Anticoagulants (NOACs) have been considered for treating cancer-related venous thromboembolism (VTE), but safety issues have been raised. We performed a systematic review and pairwise meta-analysis of the efficacy and safety of NOACs versus low molecular weight heparin (LMWH) in this setting. Four randomized controlled trials were included, providing data on 2894 patients. Compared to LMWH, NOACs were associated with a significantly lower risk of VTE recurrence and were not associated with an increased risk of major bleedings (MB). NOACs were non inferior to LMWH for a composite outcome of VTE recurrence and MB, pulmonary embolism recurrence and all-cause mortality; however, NOACs were associated with an increased risk of clinically relevant nonmajor bleedings (CRNMB) and gastrointestinal MB. In conclusion, in patients with cancer-related VTE, NOACs are effective and safe in reducing VTE recurrence compared to LMWH. An increased risk of CNRMB and GI MB should nonetheless be considered.

Spontaneous Occlusion of a Complex Brain Arteriovenous Malformation Following Partial Embolization.

BACKGROUND: Curative embolization for cerebral arteriovenous malformation (AVM) cannot always be achieved. Rather, embolization plays a role in AVM treatment as an adjuvant therapy before radiosurgery and microsurgery. Curative embolization for large, complex AVMs is not commonly seen. CASE DESCRIPTION: A man in his 30s with an unruptured left cerebral AVM underwent radiosurgery in 2014 and was lost to follow-up. He presented with intracerebral hemorrhage in 2019, and diagnostic cerebral angiography demonstrated a large, complex AVM. The patient was scheduled for 2-stage embolization in preparation for microsurgical resection. Initial embolization targeted and occluded 20% of the AVM nidus involving primarily the anteroinferior portion. A cerebral angiogram obtained 5 weeks following initial embolization revealed spontaneous occlusion of the remaining AVM. CONCLUSIONS: There are few reported cases of spontaneous occlusion of a large, complex AVM following embolization with previous radiation therapy. The spontaneous occlusion in this case suggests that at least some AVMs that receive embolization after radiation, rather than before, may have a potential for spontaneous, curative thrombosis.

Emergency department utilization of case-managed patients following benign gynecologic surgery.

BACKGROUND: Case management has been shown to reduce the amount of unnecessary emergency department visits among Medicaid or uninsured patients. This study aims to determine whether case management is associated with decreased unnecessary emergency department visits among benign gynecology surgical patients in the first 30 days following surgery. RESULTS: Out of 875 patients, there were a total of 58 return visits to the emergency department within 30 days and only 6 readmissions. Twenty-four emergency department visits occurred in the case-managed group, and thirty-eight emergency department visits occurred in the non-case-managed group. The two factors that were statistically significant for increase odds of return to the emergency department were the type of surgery (inpatient versus outpatient) and case management. The odds for returning to the emergency department for those not receiving case management was found to be 4.53 to that of the case-managed group when controlling for BMI, age, marital status, and type of surgery. CONCLUSION: In an effort to reduce healthcare costs, case management is a promising intervention to help postoperative patients manage their care while minimizing emergency department visits.

Survival after traumatic brain injury improves with deployment of neurosurgeons: a comparison of US and UK military treatment facilities during the Iraq and Afghanistan conflicts.

INTRODUCTION: Traumatic brain injury (TBI) is the most common cause of death on the modern battlefield. In recent conflicts in Iraq and Afghanistan, the US typically deployed neurosurgeons to medical treatment facilities (MTFs), while the UK did not. Our aim was to compare the incidence, TBI and treatment in US and UK-led military MTF to ascertain if differences in deployed trauma systems affected outcomes. METHODS: The US and UK Combat Trauma Registries were scrutinised for patients with HI at deployed MTFs between March 2003 and October 2011. Registry datasets were adapted to stratify TBI using the Mayo Classification System for Traumatic Brain Injury Severity. An adjusted multiple logistic regression model was performed using fatality as the binomial dependent variable and treatment in a US-MTF or UK-MTF, surgical decompression, US military casualty and surgery performed by a neurosurgeon as independent variables. RESULTS: 15 031 patients arrived alive at military MTF after TBI. Presence of a neurosurgeon was associated with increased odds of survival in casualties with moderate or severe TBI (p<0.0001, OR 2.71, 95% CI 2.34 to 4.73). High injury severity (Injury Severity Scores 25-75) was significantly associated with a lower survival (OR 4×104, 95% CI 1.61×104 to 110.6×104, p<0.001); however, having a neurosurgeon present still remained significantly positively associated with survival (OR 3.25, 95% CI 2.71 to 3.91, p<0.001). CONCLUSIONS: Presence of neurosurgeons increased the likelihood of survival after TBI. We therefore recommend that the UK should deploy neurosurgeons to forward military MTF whenever possible in line with their US counterparts.