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INTRODUCTION Rib fracture fixation is becoming more popular and widely accepted among trauma surgeons worldwide as the recommended treatment method for flail chest injury. Recent data demonstrate improved results when compared with non-operative treatment. Improved outcomes were reported regarding ICU stay, need for tracheostomy, length of hospital stay, ventilator-associated pneumonia (VAP), and even death. The objective of this study was to ascertain whether clinical respiratory para-meters are improved after rib fracture fixation procedure. MATERIAL AND METHODS This is a prospective study using a retrospective cohort for control, which took place at the Soroka University Medical Centre, Israel. Inclusion criteria included all patients over 18 years of age with flail chest injury or multiple ribs fractures, who were admitted to the General Intensive Care Unit (GICU). Between October 2015 and December 2018, we identified 24 patients who had their rib fractures operatively fixed and compared them to 61 patients with flail chest and multiple rib fractures, who were admitted to our GICU between the years 2010 and 2015 and were treated non-opera-tively. In all the surgical cases operations were performed within 72 hours of arrival in accordance with our treatment algorithm. All fractures were fixed using specialised anatomic locking plates/nails. Demographic data were collected, and respiratory parameters before and after the surgery were recorded and analysed. RESULTS We compared patients who had had their rib fractures fixed with a cohort group of patients who had been treated non-operatively in the past. No demographic differences were found between the 2 groups, nor were there any differences in their clinical trauma scoring, mechanical ventilation days, length of ICU stay, VAP, and death rates. The respiratory parameters (paO2/FiO2 ratio and chest wall compliance) were significantly higher during the 3 ensuing days after surgery and continued to improve in Group 1 (rib fixation group), in comparison to group 2 (non-operative) patients (P = 0.007 and P < 0.0001, respectively). The peak inspiratory pressure and PEEP para-meters were significantly lower in group 1 in comparison to group 2 during the 3 days, in favour of the operated group, with significant improvement noted over the 3 days post-surgery (P = 0.007 and P = 0.02, respectively). CONCLUSIONS We suggest that surgical treatment of flail chest and multiple rib fractures has clinical benefit and improves respiratory parameters even in the presence of multiple trauma injuries.

Since 1998, over 120 upper extremity transplants have been successfully performed around the world; however, the field of vascularized composite allotransplantation (VCA) continues to face various medical challenges and ethical controversies. This article summarizes the worldwide experience with transplantation of vascularized composite upper extremities in children and discusses the unique considerations facing potential pediatric VCA recipients. Three children have successfully received composite upper or lower extremity transplants, of which two involved isografts and one involved allografts. Numerous research and clinical advances relevant to VCA have been made, including patient screening, perioperative rehabilitation, allograft preservation and transportation, enhancement of nerve regeneration, understanding of cortical plasticity, and immunomodulatory strategies. Ethical and psychosocial issues remain at the forefront when evaluating potential pediatric VCA recipients. For ethically and rigorously screened pediatric patients with debilitating upper extremity absence, VCA is a compelling option to restore form and function and has a promising future.

The accumulation of circulating low-density neutrophils (LDN) has been described in cancer patients and associated with tumor-supportive properties, as opposed to the high-density neutrophils (HDN). Here we aimed to evaluate the clinical significance of circulating LDN in lung cancer patients, and further assessed its diagnostic vs prognostic value. Using mass cytometry (CyTOF), we identified major subpopulations within the circulating LDN/HDN subsets and determined phenotypic modulations of these subsets along tumor progression. LDN were highly enriched in the low-density (LD) fraction of advanced lung cancer patients (median 7.0%; range 0.2%-80%, n = 64), but not in early stage patients (0.7%; 0.05%-6%; n = 35), healthy individuals (0.8%; 0%-3.5%; n = 15), or stable chronic obstructive pulmonary disease (COPD) patients (1.2%; 0.3%-7.4%, n = 13). Elevated LDN (>10%) remarkably related with poorer prognosis in late stage patients. We identified three main neutrophil subsets which proportions are markedly modified in cancer patients, with CD66b+ /CD10low /CXCR4+ /PDL1inter subset almost exclusively found in advanced lung cancer patients. We found substantial variability in subsets between patients, and demonstrated that HDN and LDN retain a degree of inherent spontaneous plasticity. Deep phenotypic characterization of cancer-related circulating neutrophils and their modulation along tumor progression is an important advancement in understanding the role of myeloid cells in lung cancer.

Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure 30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation

Post-stroke depression (PSD) is a common and serious complication following stroke. Both stroke and depression have independently been associated with pathologically elevated glutamate levels in the brain's extra-cerebral fluid (ECF). Here we evaluate an alternative therapeutic approach to PSD with pyruvate. Rats were randomly assigned into one of 3 groups: Middle Cerebral Artery Occlusion (MCAO) plus pyruvate treatment, MCAO plus placebo treatment, and sham operated rats. Post-MCAO depressive and anxiety-like behavior was assessed, along with neurological status, brain infarct zone, brain edema, blood brain barrier (BBB) breakdown, cerebrospinal fluid and blood glutamate levels. Anxiety-like behavior and levels of blood alanine and α-ketoglutarate were measured in naive rats treated with pyruvate, as a control. Post-stroke neurological deficit with concurrent elevation in glutamate levels were demonstrated, with peak glutamate levels 24 h after MCAO. Treatment with pyruvate led to reduced glutamate levels 24 h after MCAO and improved neurologic recovery. Pyruvate treatment reduced lesion volume, brain edema and the extent of BBB permeability 24 h post-MCAO. Naive rats treated with pyruvate showed increased levels of α-ketoglutarate. Rats demonstrated post-stroke depressive behavior that was improved by the administration of pyruvate. There was less anxiety-like behavior in post-stroke rats treated with placebo in comparison to the post-stroke rats treated with pyruvate or sham operated rats. Glutamate scavenging with pyruvate appears to be an effective as a method in providing neuroprotection following stroke and as a therapeutic option for the treatment of PSD by reducing the consequent elevations in CNS glutamate levels.

Here we evaluate an alternative protocol to histologically examine blood-brain barrier (BBB) breakdown, brain edema, and lesion volume following traumatic brain injury (TBI) in the same set of rodent brain samples. We further compare this novel histological technique to measurements determined by magnetic resonance imaging (MRI) and a neurological severity score (NSS). Sixty-six rats were randomly assigned to a sham-operated, mild TBI, moderate TBI, or severe TBI group. 48 h after TBI, NSS, MRI and histological techniques were performed to measure TBI severity outcome. Both the histological and MRI techniques were able to detect measurements of severity outcome, but histologically determined outcomes were more sensitive. The two most sensitive techniques for determining the degree of injury following TBI were NSS and histologically determined BBB breakdown. Our results demonstrate that BBB breakdown, brain edema, and lesion volume following TBI can be accurately measured by histological evaluation of the same set of brain samples.

Introduction: A pressure gradient of over 8 mm Hg across the stenosis (usually located in the transverse-sigmoid junction) is one of the criteria for cerebral venous stenting in idiopathic intracranial hypertension (IIH) patients. The possible inaccuracy of the traditional microcatheter-based pressure measurements has been discussed in previous studies. In the cardiology field, a dual-sensor pressure wire is routinely used for the evaluation of stenotic lesions. Using a pressure wire for cerebral vasculature was previously discussed in a small case series and case reports. In this study, we compared venous pressure measurements obtained using both a microcatheter and a pressure wire in patients who were candidates for stenting.Methods: A retrospective study was conducted, comparing the two methods of pressure measurements in 26 patients with venous stenosis. Altogether, 120 measurements were performed using both methods. Demographic characteristics, medical history, procedural details, medications, indications for the procedure, and complications were collected from the patient charts.Results: Based on an 8-mm Hg pressure gradient cutoff indication, 19 patients were found eligible to go through unilateral venous stenting based on catheter measurements alone. The wire results corroborated the catheter results in detecting all cases indicated for a stent. This finding implies a sensitivity equal to 100% for the wire measurements. There were no wire-related complications, demonstrating its safety.Conclusions: We conclude that the pressure wire is as safe as the microcatheter and can identify cases requiring intervention. A larger-scale study is needed to assess the measurement accuracy of the pressure wire in brain vasculature.

BACKGROUND: There is little information regarding diaphragmatic dysfunction (DD) following thoracic surgery. Ultrasound allows for non-invasive repeated assessments of diaphragmatic excursion (DE) and thickening fraction (DTF) at the bedside, reflecting DD. We aimed at determining the prevalence of DD and the time-course of DE and DTF following elective thoracic surgery. Secondary endpoints included the association between DD and postoperative complications. METHODS: We led a prospective, single center, observational study in consecutive patients undergoing thoracic surgery. DE and DTF were measured by two observers blinded to each other at 3 different time-points: prior to surgery (D-1), immediately after extubation (D0) and on postoperative day 3 (D3). The changes in excursion and thickening fraction of both hemi-diaphragms over time were compared according to the side (operated or non-operated) using a two-way ANOVA. The association with postoperative complications was assessed using logistic regression.RESULTS: Fifty patients, 60% males, aged 60±15 years were included. Surgical procedures included lobectomy (n=30), wedge-resection (n=17) or pneumonectomy (n=3). DD was highly prevalent after thoracic surgery and was observed on the operated side (or both sides) in, at least, 68% of patients immediately after surgery (D0). Among those patients, 46% still had this DD on the operated side on D3. On the operated side, we observed a decrease in DE and DTF at D0 (-0.71±0.12mm, PPPPP=0.001), ICU-admission (P=0.04) according to univariate analysis and a prolonged length in hospital (OR:1.3, 95% CI [1.1-1.7], P=0.016) according to multivariate analysis.CONCLUSIONS: Diaphragmatic Dysfunction (DD) was very common after thoracic surgery, mainly concerned the operated side and was associated with an increase in the diaphragmatic excursion on the non-operated side. When this dysfunction failed to regress within 72 hours, it was associated with a significant increase in the length of hospital stay.

Retroperitoneal sarcoma is a rare malignancy arising from mesenchymal cells.[1][1] Surgical resection with wide negative margins remains the cornerstone of treatment as it decreases the risk of recurrence.[2][2] The proximity to critical abdominal structures makes a total resection with nerve and

Achievement of initial remission remains the most important clinical factor predicting long term survival in acute myeloid leukemia (AML) patients treated with intensive chemotherapy. Yet, whether the patient subset in need of a second cycle of intensive induction chemotherapy to reach remission experiences inferior outcomes compared to patients reaching remission after a single cycle of therapy, remains uncertain.Retrospective analysis of 302 consecutive AML patients treated with intensive induction chemotherapy in our institution in 2007-2020.Median patient age was 55 years with a median follow-up duration of 23 months. In terms of European LeukemiaNet (ELN) 2017 classification, 122 patients (40%) were designated as favorable risk disease, 108 patients (36%) were intermediate risk, and 71 patients (24%) were adverse risk. A hundred and seventy-seven patients (60%) attained remission following initial chemotherapy while 58 patients (20%) required an additional cycle of intensive chemotherapy for remission. Patients requiring 2 cycles to reach remission were less likely to be NPM1 mutated (33% versus 51%; P=.025) or be in the ELN 2017 favorable risk category (25% versus 57%; P.001). In multivariate analysis achievement of remission following 2 cycles of intensive compared with a single cycle resulted in significantly inferior survival [hazard ratio (HR)=1.67, 95% CI, 1.07-2.59; P=.025] whereas leukemia-free survival was not significantly impacted (HR=1.26, 95% CI, 0.85-1.85) (P=.23). Relapse rates also did not differ to a significant degree between groups (45% versus 47%, P=.8).Attainment of an early remission significantly impacts long term survival in AML patients.

Critically ill patients with severe hypoxemia are often treated in the intensive care unit (ICU) with inhaled nitric oxide (iNO). These patients are at higher risk when they require intrahospital transportation. In this study, we collected clinical and laboratory data from 221 patients who were hospitalized in the general ICU and treated with iNO at Soroka Medical Center, Israel, between January 2010 and December 2019. We retrospectively compared the 65 patients who received iNO during intrahospital transportation to the 156 patients who received iNO without transportation. Among critically ill patients who were transported while being administered iNO, only one patient had an adverse event (atrial fibrillation) on transport. We found that maximal iNO dosage during ICU stay, duration of mechanical ventilation, and percent of vasopressor support were the only independent risk factors for ICU mortality in both study groups. No difference in primary outcome of ICU mortality rate was found between the critically ill patients treated with iNO during intrahospital transportation and those who were treated with iNO but not transported during the ICU stay. We anticipate that this study will advise clinical decision-making in the ICU, especially when treating patients who are administered iNO.

BACKGROUND Esophageal cancer represents a global challenge. Despite significant evolution of treatment protocols in the past decade, recurrence rates are still high and survival rates are poor. Current treatment paradigm for localized gastroesophageal junction (GEJ) carcinoma remains to be further elucidated as for the role of neoadjuvant chemoradiation versus perioperative chemotherapy. AIM To identify biomarkers for response to chemoradiation in esophageal and gastroesophageal cancer, we performed an in-depth proteomic analysis of esophageal and gastroesophageal tumors, to describe differences in pathway activation between patients with favorable and poor prognosis following neoadjuvant chemoradiation. METHODS Patients with locally advanced esophageal and gastroesophageal cancer following neoadjuvant chemoradiation were included in the cohort. The study cohort was dichotomized into two groups of patients, named "favorable prognosis" and "poor prognosis" according to the postoperative disease-free interval. We performed a mass spectrometry analysis of proteins extracted from the malignant regions of surgical specimens and analyzed data from electronic medical records. Clinical data was correlated with differences in protein expression between patient with a favorable and poor prognosis using validated gene expression pathways. RESULTS The study included 35 patients with adenocarcinoma. All patients in this cohort had esophageal adenocarcinoma. Patients median age was 62 years. Twenty-five (71.3%) patients underwent neoadjuvant chemoradiation, and 28.7% underwent neoadjuvant chemotherapy only. A proteomic analysis of our cohort identified 2885 proteins. Enrichment levels of 98 of these proteins differed significantly between favorable and poor prognosis cohorts in patients who underwent neoadjuvant chemoradiation (p

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a global health threat with the potential to cause severe disease manifestations in the lungs. Although COVID-19 has been extensively characterized clinically, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown. Here, we compared the clinical, histopathological, and immunological characteristics of patients with COVID-19 and pandemic influenza A(H1N1). We observed a higher frequency of respiratory symptoms, increased tissue injury markers, and a histological pattern of alveolar pneumonia in pandemic influenza A(H1N1) patients. Conversely, dry cough, gastrointestinal symptoms and interstitial lung pathology were observed in COVID-19 cases. Pandemic influenza A(H1N1) was characterized by higher levels of IL-1RA, TNF-α, CCL3, G-CSF, APRIL, sTNF-R1, sTNF-R2, sCD30, and sCD163. Meanwhile, COVID-19 displayed an immune profile distinguished by increased Th1 (IL-12, IFN-γ) and Th2 (IL-4, IL-5, IL-10, IL-13) cytokine levels, along with IL-1β, IL-6, CCL11, VEGF, TWEAK, TSLP, MMP-1, and MMP-3. Our data suggest that SARS-CoV-2 induces a dysbalanced polyfunctional inflammatory response that is different from the immune response against pandemic influenza A(H1N1). Furthermore, we demonstrated the diagnostic potential of some clinical and immune factors to differentiate both diseases. These findings might be relevant for the ongoing and future influenza seasons in the Northern Hemisphere, which are historically unique due to their convergence with the COVID-19 pandemic.

Background Patients with GBS may develop hypoalbuminemia following treatment with Intravenous Immunoglobulin (IVIG), which is related to a poorer outcome. This report presents a patient with GBS and his clinical response to two courses of IVIG treatments in association with his albumin level. Case report: A previously healthy 21-year-old male was admitted to the GICU due to GBS with severity grade 5 (required assisted ventilation). IVIG treatment was initiated. Over the next two weeks there was no clinical improvement and Albumin level dropped from 4.5 gr/dL to a nadir of 2.3 gr/dL. A second course of IVIG was initiated. After initiation of the second course the patient’s albumin began rising to 3.0 gr/dL and a clinical improvement followed this rise. Subsequently, he was weaned from mechanical ventilation within a few days. Conclusions When considering a second course of IVIG treatment, serum albumin levels may be considered a biomarker as part of the decision algorithm.

Background Patients who undergo surgical procedures that impair the integrity of the chest wall frequently experience extremely severe postoperative pain. Opiates and weaker analgesics, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are not sufficiently effective in achieving control of severe pain and might cause respiratory and gastrointestinal complications. In the past decade, there has been an increased interest in the use of regional nerve blocks for post-thoracoscopy and post-thoracotomy analgesia. Methods This is a prospective, randomized, double-blind and single-center study. We recruited 104 patients who underwent elective thoracoscopy. Prior to surgery, the participating patients were randomized into one of two study groups: Group 1- the "standard control group" that received standard postoperative pain control with intravenous opioids, NSAIDs and acetaminophen (paracetamol) and Group 2- the "block group" that was treated by ultrasound-guided serratus anterior plane (SAP) block (a single injection of 0.25% bupivacaine hydrochloride 2 mg/kg plus dexamethasone 8 mg) with standard postoperative pain control regimen. We compared the clinical, laboratory, and postoperative pain assessment data of both groups. Results Patients in the SAP block Group 2 reported significantly lower levels of pain after thoracic surgery as assessed by their visual analog scale scores, as compared to the patients in the standard pain control Group 1 (P

Background Sentinel lymph node biopsy (SLNB) is routinely performed during surgery for malignant melanoma, using double mapping. Still, in some cases, a sentinel lymph node identified pre-operatively by lymphoscintigraphy is not identified during surgery. We hypothesized that disease specific survival would not be significantly impacted by intra-operative lymph node mapping (IOLM) failure. Methods The patient population study included 1300 malignant melanomas operated on by a single surgical oncologist (H.G.) after sentinel lymph node scintigraphy. Patients were included in the analysis if intra-operative lymph node (IOLM) mapping failed. Results Among 1300 patients who underwent surgery for malignant melanoma during the study period and after median follow up of >10 years, 33/36 lymphatic drainage basins with failed sentinel node identification were free of disease. Disease specific survival for the entire group of 33 patients with IOLM failure was 91.0%, which is comparable to previously published disease specific survival for all melanoma patients. Conclusion We conclude that failure to identify a pre-operatively marked sentinel lymph node by an experienced melanoma surgeon has, generally, no impact on disease specific survival, as demonstrated in this review of a series of surgical melanoma patients.

On March 3, 2021, we lost an honored member of the virology community, Mavis Agbandje-McKenna, to amyotrophic lateral sclerosis (ALS). Mavis was a leading light in the fields of viral structure, functions, and gene therapy. She was also a treasured friend and collaborator to scientists around the world and an impactful mentor to a multitude of trainees.

Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality. SMA is a spectral disorder and is categorised based on symptom onset and severity. The median life expectancy for infants with SMA presenting before 6 months of age is less than 2 years without respiratory support. To date, there is no cure for SMA. In June 2017, nusinersen was approved in Canada as the first disease-modifying drug for SMA because of its demonstrated benefits on motor function and survival in clinical trials. However, with a price tag of almost 1 million dollars for the first year of therapy, careful clinical, treatment-based and ethical consideration of the principles of (i) best interests; (ii) universality; (iii) portability; (iv) public administration; (v) accessibility; and (vi) comprehensiveness are important guideposts to ensure transparent and equitable allocation of health-care resources for nusinersen and all other future orphan drugs.

SummaryBackgroundSepsis has no proven specific pharmacologic treatment. Reported mortality in sepsis ranges from 30%–45%. This study was designed to determine the safety preliminary efficacy of allogenic apoptotic cells administered for immunomodulation in septic patients.MethodsThe primary aim of this phase IB study was to determine the safety profile of apoptotic cell infusion in subjects presenting to the emergency room with sepsis. Sepsis was determined by clinical infections and Sequential Organ Failure Assessment (SOFA) scores >2. The secondary aims were to measure organ dysfunction, intensive care unit (ICU) and hospital stays, and mortality, that were compared to historical controls. Exploratory endpoints included measuring immune modulator agents to elucidate the mechanism of action using Luminex® analysis.FindingsTen patients were treated with apoptotic cells, administered as a single dose or two sequential doses. All 10 patients had mild-to-moderate sepsis with a SOFA score range of 2–6 upon entering the study. No serious adverse events (SAEs) and no related AEs were reported. All 10 study subjects survived while matched historical controls had a mortality rate of 27%. The study subjects exhibited rapid resolution of organ dysfunction and had significantly shorter ICU lengths of stay compared to matched historical controls (pInterpretationAdministration of apoptotic cells to patients with mild-to-moderate sepsis was safe and had a significant immuno-modulating effect, leading to early resolution of the cytokine storm.Trial registrationClinicalTrials.gov Identifier: NCT03925857FundingThe study was sponsored by Enlivex Therapeutics Ltd.

BackgroundCXCL17 is chemotactic for myeloid cells, exhibits broad-spectrum bactericidal activity, and is expressed in mucosal tissues. This chemokine is constitutively expressed in the respiratory tract, suggesting a role for CXCL17 in lung defenses. However, little is known about the possible participation of CXCL17 during respiratory infections in humans. Here, we evaluated the role of CXCL17 as a biomarker in patients with severe pandemic influenza A(H1N1) and coronavirus disease 2019 (COVID-19). MethodsWe conducted a prospective cohort study in hospitalized patients with severe influenza A(H1N1) and COVID-19 admitted to two national reference centers in Mexico City. Peripheral blood samples were obtained on admission for determinations of the serum levels of CXCL17 by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 in lung autopsy specimens from patients that succumbed to both diseases was assessed by immunohistochemistry (IHQ). Serum CXCL17 levels were compared between patients grouped according to their disease and clinical outcome. The diagnostic and predictive value of serum CXCL17 levels was evaluated using machine-learning algorithms and regression analyses. ResultsA total of 92 patients were enrolled in the study, from which 68 were infected with influenza and 24 had COVID-19. Their clinical characteristics were similar, although dyspnea, rhinorrhea, and sputum production were more common during influenza, whereas dry cough and vomit were more frequent among COVID-19 patients. Both diseases induced the local expression of CXCL17 in the lung. However, serum levels of CXCL17 were increased only in patients with influenza but not COVID-19. CXCL17 not only differentiates influenza from COVID-19 but serves as a prognostic biomarker associated with mortality and renal failure in influenza patients. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages produce CXCL17 after influenza A(H1N1) pdm09 virus infection. ConclusionsOur results suggest a possible role for CXCL17 in the pathogenesis of influenza A(H1N1), supporting the use of this molecule as a prognostic biomarker. Future studies on the role of CXCL17 in COVID-19 are warranted.

Background Symptomatic carotid stenosis is responsible for 10% of all strokes. Currently, CT angiography (CTA) is the main diagnostic tool for carotid stenosis. It is frequently the only diagnostic test preceding recommendations for carotid angioplasty and stenting (CAS) or carotid endarterectomy (CEA). However, the specificity of CTA, especially in patients with 50–70% stenosis, was previously reported to be relatively low. Most studies testing the diagnostic accuracy of CTA were published more than a decade ago. Therefore, we aimed to test the diagnostic accuracy of CTA, performed with current available technology, compared with digital subtraction angiography (DSA) in patients with carotid stenosis. This study aims to characterize patients who were candidates for CAS/CEA based on CTA, but may not require it based on DSA. Methods Consecutive candidates for carotid interventions (CAS or CEA) following CTA were identified from prospectively maintained stroke center registries at two large academic centers. As part of our institutional practice all patients had a routine pre-procedural diagnostic DSA. In each patient, degree of carotid stenosis was compared between CTA and DSA. Patients with concordant degree of stenosis on DSA and CTA (true positive group) were compared to patients with a discordant degree of stenosis with less than 50% on DSA (false positive group). Results Out of 90 patients with significant stenosis on CTA, only 70 (78%) were found to have a significant stenosis on DSA. Severe plaque calcification was significantly more common in the false-positive group. In those patients whose CTA reported stenosis of ≥90%, we found a strong agreement between CTA and DSA (positive predictive value [PPV] – 0.9) for a significant stenosis (≥50%). Conversely, the correlation between CTA and DSA in patients with CTA reported 50–70% stenosis was poor (PPV – 0.29) (p Conclusions Our results suggest that despite ongoing radiological progress, the specificity of CTA in accurately assessing carotid stenosis remains relatively low in patients with both moderate stenosis and heavily calcified plaques. Consequently, patients could possibly be referred for unnecessary CEA surgery and may become exposed to associated potential complications.

Objective To analyze the applicability and efficiency of amulti-approach laparoscopic training in improving basic laparoscopic skills of obstetrics and gynecology (OBGYN) residents. Methods Cross-sectional, observational and descriptive study, developed at the Experimentation and Surgery Training Center (CETEC, in the Portuguese acronym) of the Hospital Israelita Albert Einstein with OBGYN residents. Theoretical and practical tests were applied to 24 OBGYN residents to assess their laparoscopic skills before and after their participation in an 8-week course. The course involved theoretical lectures and practical laparoscopic surgery exercises developed using rubber models, black boxes, virtual simulators and animal models (pigs). Results There was an overall improvement in the ability of the residents, with an increase in the number of correct answers in the theoretical evaluation and decrease in the time needed to perform practical tests (needle holder assembly and laparoscopic node). The course was evaluated by the students as highly relevant for both improving their surgical skills and motivating them to continue practicing. Conclusion Laparoscopic training using multiple approaches resulted in significant improvement of surgical skills with a high satisfaction level of the participants. Further studies are still needed to measure the long-term retention of these acquired skills. Resumo Objetivo Analisar a aplicabilidade e eficiência de um treinamento em laparoscopia com múltiplas abordagens, em melhorar as habilidades laparoscópicas básicas de residentes de ginecologia e obstetrícia (GO). Métodos Estudo transversal, observacional e descritivo, desenvolvido no Centro de Treinamento em Experimentação e Cirurgia (CETEC) do Instituto de Pesquisa do Hospital Albert Einstein com residentes de GO. Foram aplicadas avaliações teóricas e práticas a 24 residentes de GO com o objetivo de avaliar suas habilidades laparoscópicas antes e após sua participação em um curso de 8 semanas. O curso envolveu palestras teóricas e exercícios práticos de cirurgia laparoscópica através de modelos de borracha, caixas pretas, simuladores virtuais e modelos animais (porcos). Resultados Houve uma melhora geral na habilidade dos residentes, comaumento do número de respostas corretas na avaliação teórica e diminuição do tempo na execução dos testes práticos (montagem do porta-agulha e realização de nó laparoscópico). O curso foi avaliado pelos alunos como altamente relevante por melhorar suas habilidades cirúrgicas e motivá-los a continuar praticando. Conclusão O treinamento laparoscópico utilizando múltiplas abordagens resultou em melhora significativa das habilidades cirúrgicas atrelado a alto nível de satisfação dos participantes. Novos estudos ainda são necessários para mensurar a retenção destas habilidades adquiridas a longo prazo.

Background Ischemic stroke is one of the leading causes of mortality and morbidity. The currently available non-invasive therapeutic options are not sufficiently efficacious. Post-ischemic brain is characterized by a prominent inflammatory response. Little is known about the involvement of cyclooxygenase (COX)-1 in the pathophysiology of ischemic stroke. Objective This study was undertaken to examine the effects of a highly selective COX-1 inhibitor – mofezolac – on clinical outcomes and brain inflammatory markers in post-stroke rats. Methods Stroke was induced by subjecting rats to permanent middle cerebral artery occlusion (MCAO). Control rats underwent a sham surgery. Rats were treated with mofezolac (50 mg/kg, intraperitoneally [ip]) once daily for 14 days. Control animals were treated with vehicle. Body temperature (BT), neurological score (NS) and cumulative mortality were monitored at different time points. At the end of the experiment, rats were euthanized and three brain regions (hypothalamus, hippocampus and frontal cortex) were extracted. Levels of interleukin (IL)-6, prostaglandin (PG)E2 and tumor necrosis factor (TNF)-α in these brain regions were determined by ELISA kits. Results BT, NS and cumulative mortality were all significantly higher in post-MCAO rats than in sham-operated rats, irrespective of the treatment given. BT, NS and mortality rate did not differ significantly between mofezolac-treated and vehicle-treated sham-operated animals. BT was significantly lower in mofezolac-treated as compared to vehicle-treated post-MCAO rats. Mofezolac did not significantly alter NS in post-MCAO rats at any time-point. Cumulative 14-day mortality was non-significantly higher in mofezolac-treated as compared to vehicle-treated post-MCAO rats (48 % vs. 21 %, respectively; P = 0.184). Mostly, IL-6 and TNF-α levels did not differ between post-MCAO and sham-operated rats and were not affected by mofezolac treatment. In contrast, mofezolac significantly decreased PGE2 levels in post-MCAO rats’ brains. Conclusion Overall, these results suggest that chronic treatment with the selective COX-1 inhibitor mofezolac did not reduce morbidity or mortality in post-stroke rats.

Background: Glucocorticoids (GCS) are commonly administered to critically ill patients. Due to their mineralocorticoid effect, GCS might have a substantial influence on a positive fluid balance. We assessed the association between glucocorticoids (GCS) therapy and fluid balance in critically ill patients with sepsis.Methods: This is a retrospective study of patients with sepsis hospitalized during 2006-2018 in a general intensive care unit (ICU) at a 1100-bed tertiary medical center.Results – We considered two definitions of exposure: daily exposure to GCS and GCS treatment at any time in the ICU. Of 945 patients with a diagnosis of sepsis, 375 were treated with GCS at any time and 570 were not. We applied four regression models to assess the association between GCS treatment and fluid balance; in our first model, fluid balance did not differ during days with GCS treatment, between patients who were and were not treated with GCS in the ICU (coefficient estimate 79.5 (-55.4 to 214.4), p=0.25). In our second model, daily fluid balance was increased by 139.8 ml (10.8 to 268.9; p=0.03) in patients who were ever treated with GCS during their ICU stay compared to untreated patients. In the third model, which included only patients treated with GCS during their ICU stay, GCS treatment days were not associated with daily fluid balance (coefficient estimate -190.6 (-485.1 to 103.9), p-value=0.21). In the last model, on "steroid free days", patients who received GCS treatment during their ICU stay had a positive fluid balance compared to those who were never treated with steroids (coefficient estimate 157.7 (-24.6 to 340.1), p-value=0.09).Conclusions – Despite their known mineralocorticoid activity, GCS themselves appear not to contribute substantially to fluid retention. The findings highlight the importance of a clear definition of exposure.

Post-stroke depression (PSD) is a major complication of stroke that significantly impacts functional recovery and quality of life. While the exact mechanism of PSD is unknown, recent attention has focused on the association of the glutamatergic system in its etiology and treatment. Minimizing secondary brain damage and neuropsychiatric consequences associated with excess glutamate concentrations is a vital part of stroke management. The blood glutamate scavengers, oxaloacetate and pyruvate, degrade glutamate in the blood to its inactive metabolite, 2-ketoglutarate, by the coenzymes glutamate–oxaloacetate transaminase (GOT) and glutamate–pyruvate transaminase (GPT), respectively. This reduction in blood glutamate concentrations leads to a subsequent shift of glutamate down its concentration gradient from the blood to the brain, thereby decreasing brain glutamate levels. Although there are not yet any human trials that support blood glutamate scavengers for clinical use, there is increasing evidence from animal research of their efficacy as a promising new therapeutic approach for PSD. In this review, we present recent evidence in the literature of the potential therapeutic benefits of blood glutamate scavengers for reducing PSD and other related neuropsychiatric conditions. The evidence reviewed here should be useful in guiding future clinical trials.

The brain undergoes significant physiologic changes during pregnancy. Pregnant women who are critically ill with obstetric disorders, such as eclampsia, preeclampsia, intracranial hemorrhage (ICH), and benign intracranial hypertension, and those with severe TBI or other disorders that need prolonged sedation in the ICU may require appropriate neuromonitoring during their ICU stay. Despite the variety of invasive and noninvasive neuromonitoring tools, daily clinical neurological examination (including Glasgow coma scoring, assessment of pupil size, and daily focal neurologic deficit evaluation) remains the cornerstone component of neuromonitoring during the ICU stay of such patients.

Juvenile idiopathic arthritis (JIA) is the most common chronic arthropathy in the pediatric population. Although the diagnosis is essentially clinical for many affected joints, MR imaging has become an important tool for the assessment of joints that are difficult to evaluate clinically, such as temporomandibular and sacroiliac joints, and for screening of inflammatory changes in the entire body by whole body MRI (WBMRI) assessment. The utilization of MR imaging is challenging in the pediatric population given the need for discrimination between pathological and physiological changes in the growing skeleton. Several multicentric multidisciplinary organizations have made major efforts over the past decades to standardize, quantify, and validate scoring systems to measure joint changes both cross-sectionally and longitudinally according to rigorous methodological standards. In this paper, we (1) discuss current trends for the diagnosis and management of JIA, (2) review challenges for detecting real pathological changes in growing joints, (3) summarize the current status of standardization of MRI protocols for data acquisition and the quantification of joint pathology in JIA by means of scoring systems, and (4) outline novel MR imaging techniques for the evaluation of anatomy and function of joints in JIA. Optimizing the role of MRI as a robust biomarker and outcome measure remains a priority of future research in this field.

People with Parkinson's disease have been shown to have difficulty switching between movement plans. In the great majority of studies, the need to switch between tasks was made explicitly. Here, we tested whether people with Parkinson's disease, taking their normal medication, have difficulty switching between implicitly specified tasks. We further examined whether this switch is performed predictively or reactively. Twenty five people with Parkinson's disease continuously increased or decreased the frequency of their arm movements, inducing an abrupt-but unaware-switch between rhythmic movements (at high frequencies) and discrete movements (at low frequencies). We tested whether that precipitous change was performed reactively or predictively. We found that 56% of participants predictively switched between the two movement types. The ability of people with Parkinson's disease, taking their regular medication, to predictively control their movements on implicit tasks is thus preserved.

ObjectivesTo evaluate the association between postconcussive symptomatology and heading in professional soccer players, overcoming the bias of self-reported exposure, we evaluated several clinical neuropsychiatric symptoms using questionnaires after a thorough objective follow-up of players’ heading exposure throughout an entire season.MethodsWe collected heading data for all Israeli Premier League players for an entire season using a web-based platform for performance analysis, which enabled us to quantify the exact number of headers per player. Players filled out questionnaires regarding postconcussion symptoms, depression, anxiety, and sleep disorders. We tested the association between the number of headers and each outcome using a negative binomial regression corrected for the hours played.ResultsA total of 159 players were included, of whom 79 were considered in the high heading exposure group (49%), defined as more than median number of headings (1.34 per game hour). Among players without any past head injury, those with higher heading exposure were less likely to have postconcussion symptoms compared with players with low heading exposure (relative risk [RR] per heading per hour 0.94, 95% confidence interval [CI] 0.912–0.963). Players with high heading exposure had fewer depression symptoms (RR 0.98, 95% CI 0.961–0.997), anxiety (RR 0.98, 95% CI 0.958–0.997), and sleep disorders (RR 0.98, 95% CI 0.961–0.996).ConclusionProfessional soccer players with high heading rate do not display higher postconcussive symptomatology severity. Symptoms among players with low heading exposure might be explained by low resilience, possibly associated with an inferior heading technique. Alternatively, it can reflect heading-avoidant behavior.

Background: The symptoms of patients with Parkinson’s disease (PD) have been shown to improve when they perform fast-paced rhythmic cycling movements with their lower limbs. Objective: Our goal in this pilot experiment was to test the feasibility and the benefits of a short exercise program involving fast-paced rhythmic movements of the upper limb for patients with PD. Methods: We used an experimental procedure that elicits large, fast-paced movements by the participants without the direct instructions to do so by the experimenter. Ten participants with PD (71.0±6.5 years old) performed a 50-min fast-paced rhythmic exercise of the upper limb after withdrawal from PD medication for at least 12 hours. Results: Participants improved their kinematic performance, in terms of accuracy and combined speed and amplitude (p

Objectives To assess the economic impact of introducing the soluble FMS-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test into clinical practice in two Brazilian hospitals. Methods An economic model estimating the incremental value of the information from a Brazilian public and private healthcare payer perspective generated by the sFlt-1/PlGF ratio test, compared with current diagnostic procedures, in guiding the management of women with suspected pre-eclampsia. A cohort of 1000 pregnant women between 24 weeks and 36 + 6 weeks of gestation were managed in either a ‘test’ scenario in which the sFlt-1/PlGF test is used in addition to current diagnostic procedures, or a ‘no-test’ scenario. Information on the costs associated with diagnosis, prediction and management were derived from the cost database of Hospital M'Boi Mirim (public) and Hospital Einstein (private). The probabilities used in the decision tree were derived from PROGNOSIS. The main outcome measure from the model was the cost per patient per episode of care (from first suspicion of pre-eclampsia to birth). Results Introduction of the sFlt-1/PlGF ratio test resulted in cost savings in both settings (M’Boi Mirim: R$185.06 and Einstein: R$635.84 per patient) compared with a ‘no-test’ scenario. Savings are generated primarily through an improvement in diagnostic accuracy and a reduction in unnecessary hospitalization. Conclusions The sFlt-1/PlGF ratio test has the potential to improve clinical decision-making and allocation of scarce resources by reducing unnecessary hospitalization of women at low risk of developing pre-eclampsia, and ensuring that women at higher risk are identified and managed appropriately.

Objective To analyze the pregestational body mass index and weight gain during pregnancy, and to associate data to perinatal outcomes of pregnant women from a Prenatal Care Program. Methods A retrospective study was carried out with 151 patients seen at the Healthy Gestation Program of Hospital Israelita Albert Einstein . Data were collected from a medical chart review of the patients seen between March 2015 and March 2016. Results The chance of developing gestational diabetes for obese patients in early gestation was estimated at 7.5-fold as compared to patients with low or normal body mass index. Conclusion There was a significant association between obesity in early pregnancy and the occurrence of gestational diabetes mellitus in this population.

Stroke is a major cause of global morbidity and mortality. Middle cerebral artery occlusion (MCAO) has historically been the most common animal model of simulating ischemic stroke. The extent of neurological injury after MCAO is typically measured by cerebral edema, infarct zone, and blood-brain barrier (BBB) permeability. A significant limitation of these methods is that separate sets of brains must be used for each measurement. Here we examine an alternative method of measuring cerebral edema, infarct zone and BBB permeability following MCAO in the same set of brain samples. Ninety-six rats were randomly divided into three experimental groups. Group 1 (n = 27) was used for the evaluation of infarct zone and brain edema in rats post-MCAO (n = 17) vs. sham-operated controls (n = 10). Group 2 (n = 27) was used for the evaluation of BBB breakdown in rats post-MCAO (n = 15) vs. sham-operated controls (n = 10). In Group 3 (n = 42), all three parameters were measured in the same set of brain slices in rats post-MCAO (n = 26) vs. sham-operated controls (n = 16). The effect of Evans blue on the accuracy of measuring infarct zone by 2,3,5-triphenyltetrazolium chloride (TTC) staining was determined by measuring infarct zone with and without an applied blue filter. The effects of various concentrations of TTC (0, 0.05, 0.35, 0.5, 1, and 2%) on the accuracy of measuring BBB permeability was also assessed. There was an increase in infarct volume (p < 0.01), brain edema (p < 0.01) and BBB breakdown (p < 0.01) in rats following MCAO compared to sham-operated controls, whether measured separately or together in the same set of brain samples. Evans blue had an effect on measuring infarct volume that was minimized by the application of a blue filter on scanned brain slices. There was no difference in the Evans blue extravasation index for the brain tissue samples without TTC compared to brain tissue samples incubated in TTC. Our results demonstrate that measuring cerebral edema, infarct zone and BBB permeability following MCAO can accurately be measured in the same set of brain samples.

Enzyme replacement therapy (ERT) is a newly approved disease-modifying treatment for hypophosphatasia (HPP), a rare metabolic bone disorder. With an orphan drug and ultra-rare disease, sharing information about responders and non-responders is particularly important, as any one centre's familiarity with its use will be limited. Nearly all published data in infants and very young children with life-threatening HPP are from three small clinical trials that have reported generally positive outcomes. We describe in detail a patient with perinatal HPP for whom treatment with ERT was not successful. Lessons learned from this case can inform clinical decision-making and provide topics for the research agenda. We also discuss practical and ethical challenges related to treatment of an ultra-rare disease with an expensive new medication in a publicly funded healthcare system.

Background: This study aimed to compare the neurophysiological responses to sound in adults with hypersensitivity compared to adults without hypersensitivity, and correlate the daily-life experiences to the neurophysiological manifestations. Material and Methods: The Adolescent/Adult Sensory Profile (AASP) was administered to 27 adults, separated by their cut-off scores. Differences in neurophysiological responses were measured by N1-P2 Event-Related Potentials (ERP) in response to auditory changes in frequency and intensity. Reactions to daily sounds were measured by the hyperacusis questionnaire. Correlations between AASP, hyperacusis questionnaire, and ERP were measured. Results: The basic ability to detect a change in stimuli manifested in N1 waveform was not significantly different. However, participants with hypersensitivity presented a stronger P2 response and a higher hyperacusis score. Daily expressions of auditory hypersensitivity correlated (p = 0.05 - p = 0.01) with larger ERP responses. Conclusions: Auditory hypersensitivity as reflected in daily scenarios is evident in neurophysiological manifestations measured by ERPs. Understanding the relationship between the neural mechanisms of auditory hyper-ensitivity and its daily expressions, may optimize participation and wellbeing for people with hypersensitivity.

OBJECTIVE: To evaluate the effects of early treatment with CPAP on nutritional intake and in-hospital growth rates of extremely preterm (EPT) infants. STUDY DESIGN: EPT infants (24–0/7 to 27–6/7 weeks of gestation) enrolled in the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) were included. EPT infants who died before 36 weeks’ postmenstrual age (PMA) were excluded. The growth rates from birth to 36 weeks’ PMA and follow-up outcomes at 18–22 months’ corrected age of EPT infants randomized at birth to either early CPAP (intervention group) or early intubation for surfactant administration (control group) were analyzed. RESULTS: 810 of 1316 infants enrolled in SUPPORT (414 in intervention group, 396 in control group) had growth data analyzed. Median gestational age was 26 weeks and mean birthweight was 839 grams. Baseline characteristics, total nutritional intake, and in-hospital comorbidities were not significantly different between groups. In a regression model, growth rates between birth and 36 weeks’ PMA as well as growth rates during multiple intervals from birth to day 7, day 7 to14, day 14 to 21, day 21 to 28, day 28 to 32 weeks’ PMA, and 32 weeks’ PMA to 36 weeks’ PMA did not differ between treatment groups. Independent of treatment group, higher growth rates from day 21 to day 28 were associated with a lower risk of Bayley III cognitive score

Objective We aimed to determine whether fecal microbiota transplant (FMT) is safe and possibly efficacious in treating constipation, motor, and non-motor symptoms in Parkinson's disease (PD) patients. Methods Patients with PD, constipation and an indication for screening colonoscopy were treated with FMT. The study was conducted from December 2017 to November 2019, and clinical outcomes assessing motor, non-motor and constipation symptoms were compared at baseline (week 0) and at 2, 4, 8, 12, 16, 20, and 24 weeks after the FMT. Results Six patients (3 men, age range 47–73, median age 52) were treated with FMT. Four weeks following the FMT, motor, non-motor and constipation scores were improved in 5 of 6 patients. At week 24, compared to before the FMT, the changes in motor scores ranged from − 13–7 points, in non-motor scores from − 2 to − 45 points, and in constipation scores from − 12–1 point. One patient had a serious adverse event requiring admission for observation only, and no adverse events were observed in all other patients. Conclusions In this preliminary uncontrolled case series of 6 PD patients, a treatment with donor FMT infused via colonoscopy, was safe and resulted in improvement of PD motor and non-motor symptoms, including constipation, at 6 months. Further research is needed to assess longer-term maintenance of efficacy and safety, including in large scale randomized controlled trials. Trial registration ClinicalTrials.gov – NCT03876327

Background:Inadvertent hyperthermia during anaesthesia is a rare but life-threatening complication. We have encountered several cases of severe hyperthermia in paediatric patients undergoing anaesthesia for cochlear implantation.Methods:This study aimed to describe the clinical characteristics of children who developed hyperthermia while undergoing cochlear implantation, and to explore possible mechanisms and predisposing factors. The anaesthetic charts of all patients aged under 18 years who underwent cochlear implantation, or mastoid or ophthalmic surgery, between 1 January 2006 and 31 December 2009, at Soroka Medical Center in Beer Sheva, Israel, were reviewed. Patients undergoing mastoid and ophthalmic surgical procedures were used as controls.Results:A larger percentage of patients who underwent cochlear implant surgery (10 per cent) developed hyperthermia compared to controls (0.7 per cent, p < 0.05). In five of the seven cases, hyperthermia appeared in combination with tachycardia and hypercapnia, adhering to the clinical triad of malignant hyperthermia.Conclusion:Patients undergoing cochlear implantation are susceptible to developing intra-operative hyperthermia. This article describes the hyperthermic events that occur during paediatric cochlear implantation, and attempts to identify potential triggers of hyperthermia.

Serious complications in obstetric anesthesia are a rare occurrence. High neuraxial block, respiratory arrest in labor and delivery, and an unrecognized spinal catheter are among the most frequently reported serious complications. A serious complication occurs in approximately 1:3000 obstetric patients. Neuraxial hematoma after obstetric epidural analgesia or anesthesia is extremely rare. We present a case of a puerperal spinal epidural hematoma following epidural labor analgesia. The patient presented with foot drop, which resolved after conservative treatment. We reviewed the epidemiology, clinical manifestations and treatment options for this rare complication.

Like all antithrombotic drugs, antiplatelet agents expose to a risk of bleeding complications. Clinical research has extensively focused on the efficacy of these drugs to reduce ischemic events. The bleeding risk associated with them was solely considered as an inevitable and acceptable complication. When two new potent P2Y12-receptor inhibitors, prasugrel and ticagrelor, were marketed, the risk of major bleeding increased. These new agents have modified the balance between the absolute risk reduction in ischemic events and the absolute risk increase in bleeding events. This paper is an update on the bleeding risk assessment associated with antiplatelet agents. It discusses the place of platelet function monitoring, and the optimal management of bleeding complications. It addresses the challenging issue of reversal of antiplatelet therapy, focusing especially on ticagrelor, which pharmacodynamics complicate bleeding management.

Acute lymphoblastic leukemia (ALL) affects the quality of life of many children in the world and particularly in Mexico, where a high incidence has been reported. With a proper financial investment and with well-organized institutions caring for those patients, together with solid platforms to perform high-throughput analyses, we propose the creation of a Mexican repository system of serum and cells from bone marrow and blood samples derived from tissues of pediatric patients with ALL diagnosis. This resource, in combination with omics technologies, particularly proteomics and metabolomics, would allow longitudinal studies, offering an opportunity to design and apply personalized ALL treatments. Importantly, it would accelerate the development of translational science and will lead us to further discoveries, including the identification of new biomarkers for the early detection of leukemia.

Parkinson&rsquo, s disease (PD) and fibromyalgia (FM) are two relatively common disorders that are considered distinct diagnoses. The aim of this study was to investigate the epidemiological characteristics of patients with both PD and FM, as well as their comorbidities and medication use. We performed a population-based retrospective cohort study in Israel from 2000 to 2015. We identified patients with PD according to a refined medication tracer algorithm and patients with FM according to their medical records. Using the algorithm, we identified 2606 patients diagnosed with PD, 60 of them (2.3%) were also diagnosed with FM. Most of the patients were females (88.3%) and the mean age of FM diagnosis was 63.95 &plusmn, 12.27 years. These patients had a higher prevalence of depression, anxiety, and dementia. Of the patients diagnosed with PD + FM, 46 (76.7%) were diagnosed with FM after the diagnosis of PD. Patients with PD + FM used analgesics of distinct kinds in higher rates, as well as more anti-PD medications. We suggest that patients with PD + FM represent a distinct subgroup with a fibromyalgia-like syndrome associated with Parkinson&rsquo, s disease (FLISPAD). Their PD is more treatment resistant, and they take more medications, both analgesics and anti-PD.

Background To compare covert closed-circuit television (CCTV) monitoring to standard overt observation in assessing the hand hygiene (HH) conduct of health care workers (HCWs) caring for patients infected with multidrug-resistant organisms (MDROs). This was a cross-sectional study in a general intensive care unit of a 1,000-bed university hospital. Methods Forty-six general intensive care unit HCWs (staff physicians, registered nurses, and auxiliary workers) caring for contact isolation MDRO-infected patients. The study incorporated the following 3 phases: phase 1, establishment of interrater reliability between 2 simultaneous observers using the overt observation method; phase 2, establishment of interrater reliability between 2 simultaneous observers using the CCTV method; and phase 3, simultaneous monitoring of HH by both methods to evaluate the suitability of CCTV as an alternative to direct observation of the HH conduct of HCWs caring for MDRO-infected patients. Results Overall, 1,104 opportunities to perform HH were documented during 49 observation sessions. The compliance rate observed by the overt method (37.3%) was significantly higher than that observed when only the covert method was used (26.5%). However, simultaneous overt-covert observations were found to have intraclass correlation coefficients of >0.85. Conclusions Covert CCTV observation of HCW HH compliance appears to provide a truer and more realistic picture than overt observation, probably because of its ability to neutralize the Hawthorne effect of overt observation. The high intraclass correlation coefficients between covert observation and overt observation supports this conclusion.

Clinical decisions in allogeneic hematopoietic stem cell transplantation (allo-HSCT) are supported by the use of prognostic scores for outcome prediction. Scores vary in their features and in the composition of development cohorts. We sought to externally validate and compare the performance of 8 commonly applied scoring systems on a cohort of allo-HSCT recipients. Among 528 patients studied, acute myeloid leukemia was the leading transplant indication (44%) and 46% of patients had a matched sibling donor. Most models successfully grouped patients into higher and lower risk strata, supporting their use for risk classification. However, discrimination varied (2-year overall survival area under the receiver operating characteristic curve [AUC]: revised Pretransplantation Assessment of Mortality [rPAM], 0.64; PAM, 0.63; revised Disease Risk Index [rDRI], 0.62; Endothelial Activation and Stress Index [EASIx], 0.60; combined European Society for Blood and Marrow Transplantation [EBMT]/Hematopoietic Cell Transplantation-specific Comorbidity Index [HCT-CI], 0.58; EBMT, 0.58; Comorbidity-Age, 0.58; HCT-CI, 0.55); AUC ranges from 0.5 (random) to 1.0 (perfect prediction). rPAM and PAM, which had the greatest predictive capacity across all outcomes, are comprehensive models including patient, disease, and transplantation information. Interestingly, EASIx, a biomarker-driven model, had comparable performance for nonrelapse mortality (NRM; 2-year AUC, 0.65) but no predictive value for relapse (2-year AUC, 0.53). Overall, allo-HSCT prognostic systems may be useful for risk stratification, but individual prediction remains a challenge, as reflected by the scores’ limited discriminative capacity.

Post-stroke depression (PSD) is the most recurrent of all psychiatric complications resulting from an ischemic stroke. A greater majority (about 60%) of all ischemic stroke patients suffer from PSD, a disorder considered to be an ischemic stroke-related precursor for increased death and degradation in health. The pathophysiology of PSD is still obscure. To study the mechanism of development and occurrence of PSD further, and to find out a therapy, we attempted to develop a new protocol that requires occluding the middle cerebral artery (MCA) via the internal carotid artery (ICA) in rats. This protocol describes a model of PSD induced in rats through the middle cerebral artery occlusion (MCAO). Also used in the experiment are the Porsolt forced swim test and the sucrose preference test to confirm and evaluate the depressive mood of the rats under investigation. Rather than inserting the catheter through the external carotid artery (ECA), as stipulated for the original procedure, this MCAO technique has the monofilament passing directly through the ICA. This MCAO technique was developed a few years ago and leads to a reduction in mortality and variability. It is generally accepted that the criteria used are preferred in the selection of biological models. The data obtained with this protocol show that this model of MCAO could be a way of inducing PSD in rats and could potentially lead to the understanding of the pathophysiology and the future development of new drugs and other neuroprotective agents.

Background A common experimental rodent model for stroke includes induction by a technique in which middle cerebral artery is transiently (MCAO-t) or permanently (MCAO-p) occluded by catheterization. However, this model has prominent disadvantages which consist of the high variability of localization and size of the ischemic area, cases of intracranial hemorrhage and high mortality. Furthermore, the duration of a single MCAO operation takes about thirty minutes and requires highly trained staff. In this article, we propose an alternative method, which is based on laser-induced stroke in the motor cortex. In our research, we compared the original MCAO-p and MCAO-t models and a novel laser model. Results Compared with the impact of original MCAO-p and MCAO-t technique on brain tissue, the minimally invasive laser model demonstrated a decrease in: variability in body temperature, percent of infarcted volume, blood brain barrier breakdown and brain edema, as well as a prominent decrease of mortality and intracranial hemorrhage. Among other findings of this article, it can be noted that damage to the brain tissue in laser groups occurred only in the region of the motor cortex, without involving the striatal area. Conclusions The data presented in this paper show that the model of laser irradiation can serve as an effective method of inducible brain cortical infarction and may lead to a better understanding of the pathophysiology of ischemic stroke and the future development of new drugs and other neuro-protective agents.