An unusual neurological presentation in a patient with primary hypereosinophilic syndrome.

Hypereosinophilic syndromes are characterized by an increased number of blood eosinophils (usually more than 1.5 × 109) infiltrating tissues and causing organ damage through over-production of pro-inflammatory cytokines with heterogeneous clinical presentation. Here we present a case of a 47 years old male, with an unremarkable previous medical history, with a sudden onset of subungual hemorrhage and low back pain. Admitted for right arm weakness and vomiting, was raised the suspicion of acute cerebrovascular syndrome, but a brain CT scan with angiogram and perfusion sequences did not show any signs of early ischaemic lesions; conversely, lab tests revealed an increased peripheral eosinophil blood count. Clinical conditions rapidly worsened and a brain MRI showed multiple sub-acute ischaemic lesions compatible with vasculitis while EEG was in favor of widespread cortical distress. Diagnosis of the hypereosinophilic syndrome was made through peripheral blood smear and osteo-medullar biopsy, which showed a rich prevalence of eosinophils. The molecular biology testing showed FIP1L1-PDGRA gene mutation. Despite the prompt therapy beginning with intravenous corticosteroids and tyrosine-kinase inhibitors with normalization of cell blood count in a few days, the patient remained in minimal consciousness. When facing unusual symptoms onset (low back pain with weakness in one limb) and a highly impaired WBC not consistent with other courses (such as infections, vasculitis, allergies, and other diseases involving the immune system) clinicians should take into account the possibility of a hematological disorder and treat it as soon as possible to avoid a poor prognosis.

Haloperidol for preventing delirium in ICU patients: a systematic review and meta-analysis.

OBJECTIVE: Delirium, a common behavioral manifestation of acute brain dysfunction in Intensive Care Unit (ICU), is a significant contributor to mortality and worse long-term outcome. Antipsychotics, especially haloperidol, are commonly administered for the treatment and prevention of delirium in critically ill patients while the evidence for the safety and efficacy of these drugs is still lacking. Therefore, we conducted a systematic review of the benefits of haloperidol for the prevention of delirium in ICU patients. MATERIALS AND METHODS: We made a systematic review and meta-analysis. RESULTS: Eight RCTs with 2806 patients were included. The prophylactic use of haloperidol did not reduce the delirium incidence (RR: 0.90, 95% CI: 0.69-1.71), the duration of delirium (MD: -0.33, 95% CI: -1.25-0.588) and the delirium/coma free days (MD: 0.08, 95% CI: -0.06-0.23). We did not find an increase of extrapyramidal effects (RR: 1.86, 95% CI: 0.30-11.39), QTc prolongation (RR: 1.11, 95% CI: 0.79-1.55) and arrhythmias (RR: 1.26, 95% CI: 0.72-2.19). The use of haloperidol did not increase the ICU (MD: 0.77, 95% CI: -0.28-1.83) and hospital length of stay (MD: -0.57, 95% CI: -1.32-0.18). Haloperidol did not increase the sedation level (RR: 1.88, 95% CI: 0.76-4.63) and mortality (RR: 0.97, 95% CI: 0.83-1.18). CONCLUSIONS: Haloperidol did not reduce the delirium incidence, the delirium duration, the delirium/coma free-days and did not increase the incidence of extrapyramidal effects, arrhythmias, the ICU and hospital length of stays and sedation.

Video vs. direct laryngoscopy for adult surgical and intensive care unit patients requiring tracheal intubation: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis aimed to determine whether a specific videolaryngoscopy technique is superior to standard direct laryngoscopy using a Macintosh blade to reduce the risk of difficult intubation in surgical and intensive care unit patients. MATERIALS AND METHODS: We identified all randomized controlled trials comparing videolaryngoscopes (VLSs) to direct laryngoscopy in the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE (from inception to April 2020). The primary outcome was difficult intubation in adult surgical and intensive care unit patients. Secondary outcomes were successful intubation at the first attempt, airway trauma, sore throat, hoarseness, hypoxia, and mortality. RESULTS: We included 97 randomized controlled trials to evaluate 12775 patients. A high risk of bias was found in at least 50% of the included studies for each outcome. VLSs reduced the risk of difficult intubation compared to direct Macintosh laryngoscopy (RR 0.48, 95% CI from 0.35 to 0.65). VLSs increased the rate of successful intubation at the first attempt when compared to direct Macintosh laryngoscopy (RR 1.03, 95% CI from 1.00 to 1.07). Lower risks of airway trauma were found with VLSs (RR 0.69, 95% CI from 0.55 to 0.86). A decreased risk of hoarseness was associated with the use of VLSs (RR 0.67, 95% CI from 0.54 to 0.83). In addition, VLSs did not significantly reduce the risk of hypoxia compared with direct laryngoscopy (RR 0.83, 95% CI from 0.60 to 1.16). CONCLUSIONS: In this systematic review and meta-analysis, we found that the use of VLSs reduced the risk of difficult intubation and slightly increased the ratio of successful intubation at the first attempt among adult patients.

Lopinavir/ritonavir for the treatment of SARS, MERS and COVID-19: a systematic review.

OBJECTIVE: Lopinavir/ritonavir has been used for the treatment of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) coronavirus infections. It has been suggested that, based on this experience, this drug should also be studied in SARS-CoV2 infection. MATERIALS AND METHODS: We performed a systematic review of the literature regarding the use of lopinavir/ritonavir for the treatment of these three infections. We systematically searched the PubMed database from inception to April 30th, 2020, to identify in-vitro and animal studies and any reports of human use of lopinavir/ritonavir for the treatment of SARS, MERS and COVID-19. We also searched the Clinicatrial.gov to identify ongoing trials. RESULTS: Five in-vitro studies evaluated the effect of lopinavir/ritonavir in SARS. Three additional in-vitro studies reported the EC50 of the antiviral activity of lopinavir/ritonavir in MERS. We identified no in vitro studies evaluating the effect of lopinavir/ritonavir on the novel coronavirus. Two retrospective matched-cohort studies reported the use of lopinavir/ritonavir in combination with ribavirin for SARS patients. Three case reports and one retrospective study described the use of lopinavir/ritonavir in MERS. Twenty-two papers describe the use of lopinavir/ritonavir in adult patients with COVID-19. CONCLUSIONS: The existing literature does not suffice for assessing whether Lopinavir/ritonavir has any benefit in SARS, MERS or COVID-19.

Retinal vascular density in multiple sclerosis: a 1-year follow-up.

BACKGROUND AND PURPOSE: Vascular pathology is increasingly acknowledged as a risk factor for multiple sclerosis (MS). Vascular density (VD) is reduced in the eyes of patients with MS on optical coherence tomography (OCT) angiography. We performed a 1-year prospective study to estimate VD variations over time and possible clinical correlates. METHODS: A total of 50 patients with MS underwent spectral domain-OCT and OCT angiography at baseline and after 1-year follow-up. Mixed-effect linear regression models were used to assess variations of each OCT measure and its relation to treatment and clinical outcomes. RESULTS: We observed an increase in parafovea VD (coefficient, 1.147; 95% confidence interval, 0.081-2.214; P = 0.035). Reduction in parafovea VD was associated with increase in Expanded Disability Status Scale score (coefficient, -0.969; 95% confidence interval, -1.732/-0.207; P = 0.013). CONCLUSIONS: Retinal VD can improve over time in MS, particularly in patients experiencing disease stability. Longer follow-up, inclusion of early MS cases and combination with conventional markers of MS severity (i.e. brain atrophy) are needed to better define VD as a potential new biomarker.

Early neutropenia with thrombocytopenia following alemtuzumab treatment for multiple sclerosis: case report and review of literature.

Alemtuzumab is a monoclonal antibody targeting the CD52 antigen used in the treatment of relapsing-remitting multiple sclerosis (RRMS). CD52 is expressed by lymphocytes and monocytes but less by neutrophils and not by platelets. We present a case of a 38-year-old woman with RRMS who developed early neutropenia with thrombocytopenia after alemtuzumab infusion. She had no fever or symptoms of infection or purpura. After two weeks her haematological disorders spontaneously resolved. We reported the first case of neutropenia and thrombocytopenia as a possible event occurring after alemtuzumab infusion in MS patients, even if in a mild grade. So, we recommend to not underestimate these two conditions.

Navigator® and SmartPilot® View are helpful in guiding anesthesia and reducing anesthetic drug dosing.

BACKGROUND: The recently introduced Navigator® (GE Healthcare, Helsinki, Finland) and SmartPilot® View (Dräger Medical, Lübeck, Germany) show the concentrations and predicted effects of combined anesthetic drugs, and should facilitate more precisely their titration. Our aim was to evaluate if Navigator® or SmartPilot® View guided anesthesia was associated with a good quality of analgesia, depth of hypnosis and may reduce anesthetic requirements. METHODS: We performed a prospective non-randomized study. Sixty ASA I-II patients undergoing balanced general anesthesia for abdominal and plastic surgery were enrolled. Patients were divided in 4 groups. Group 1 (N. 15) and group 3 (N. 15) were cases in whom anesthesia was performed with standard monitoring plus the aid of Navigator® (Nav) or SmartPilot® View (SPV) display. Group 2 (N. 15) and group 4 (N. 15) were controls in whom anesthesia was performed with standard monitoring (heart rate, NIBP, SpO2, end-tidal CO2, end-expired sevoflurane concentration, train of four, Bispectral Index [Aspect Medical Systems, Natick, MA, USA] or Entropy [GE Healthcare]). Patients' vital parameters and end-expired sevoflurane concentration were recorded during anesthesia. RESULTS: All patients recovered uneventfully and showed hemodynamic stability. End-tidal sevoflurane concentrations values [median (min-max)], during maintenance of anesthesia, were significantly (P<0.05) lower in SPV [1.1% (0.8-1.5)] and Nav [1%(0.8-1.8)] groups compared to SPV-control group [1.5%(1-2.5)] and Nav-control group [1.5%(0.8-2)]. BIS and entropy values were respectively higher in the SPV group [53 (46-57)] compared to the control group [43 (37-51)] (P<0.05) and Nav group [53 (43-60)] compared to the control group [41 (35-51)] (P<0.05). No significant differences in Remifentanil dosing were observed in the four groups. CONCLUSION: Navigator® and SmartPilot® View may be of clinical use in monitoring adequacy of anesthesia. Both displays can optimize the administration and monitoring of anesthetic drugs during general anesthesia and may reduce the consumption of volatile anesthetic agents.

Bedside tested ocular motor disorders in multiple sclerosis patients.

Background/Aims. Ocular motor disorders (OMDs) are a common feature of multiple sclerosis (MS). In clinical practice, if not reported by patients, OMDs are often underdiagnosed and their prevalence is underestimated. Methods. We studied 163 patients (125 women, 76.7%, 38 men, 23.3%; median age 45.0 years; median disease duration 10 years; median EDSS 3.5) with definite MS (n = 150, 92%) or clinically isolated syndrome (n = 13, 8%) who underwent a thorough clinical examination of eye movements. Data on localization of previous relapses, MS subtype, and MRI findings were collected and analyzed. Results. Overall, 111/163 (68.1%) patients showed at least one abnormality of eye movement. Most frequent OMDs were impaired smooth pursuit (42.3%), saccadic dysmetria (41.7%), unilateral internuclear ophthalmoplegia (14.7%), slowing of saccades (14.7%), skew deviation (13.5%), and gaze evoked nystagmus (13.5%). Patients with OMDs had more severe disability (P = 0.0005) and showed more frequently infratentorial MRI lesions (P = 0.004). Localization of previous relapses was not associated with presence of OMDs. Conclusion. OMDs are frequent in patients with stable (no relapses) MS. A precise bedside examination of eye motility can disclose abnormalities that imply the presence of subclinical MS lesions and may have a substantial impact on definition of the diagnosis and on management of MS patients.

Posterior reversible encephalopathy syndrome: the endothelial hypotheses.

Posterior reversible encephalopathy syndrome (PRES) is characterised by headache, visual disorders, seizures, altered mentation, consciousness disturbances and focal neurological signs. Initially described in patients with pre and eclampsia, severe hypertension, posterior reversible encephalopathy syndrome can occur in other clinical conditions such as infection, sepsis, shock, cancer chemotherapy, autoimmune diseases and hypercalcemia. Pathogenesis of brain lesions in PRES is not full understood and two opposite theories have been proposed. Both models are based on the central role of hypertension. According to the first theory, hypertension could cause a breakdown of the autoregulatory system in cerebral circulation, leading to brain edema. The second theory suggests that hypertension causes activation of autoregulatory system, which finally results in a vasoconstriction of brain vessels with hypoperfusion, ischemia and subsequent fluid leakage. However a large number of patients, with PRES, doesn't show hypertension. We here describe the hypothesis of the crucial role of endothelial dysfunction and activation in PRES pathogenesis. Our hypothesis offers a common pathogenetic mechanism in which every PRES-related condition can be set. In our model, the activation of immune system and the consequent endothelial activation start a molecular cascade which finally causes the production of molecules which alter the normal homeostasis of blood-brain barrier. This alteration consists in a weakening of brain vessel tight junctions, which allows fluid leakage and edema. In this scenario, hypertension would be an epiphenomenon of the underlying mechanism and not the cause and, for this reason, it can be present or not in PRES.

Informed consent for tracheostomy procedures in Intensive Care Unit: an Italian national survey.

BACKGROUND: Critically ill patients in Intensive Care Unit (ICU), due to their temporary or permanent incompetence, are often not capable to provide informed consent (IC), although required, for not emergency invasive procedures, like elective tracheostomy. By Italian law, a person with partially/temporarily physical/mental impairment needs a legal tutorship appointed by the court (Support Administrator, SA). We performed a national survey in Italy to investigate IC practice for elective tracheostomy procedure in critically ill conscious and unconscious patients in ICU. METHODS: Questions about IC were included in a survey concerning the clinical practice of tracheostomy in ICU. The survey was approved by the Italian Society of Anesthesia, Analgesia and Intensive Care (SIAARTI, n° 434 - 28 March 2012) and sent by e-mail to all members included in its mailing list. The duration of the survey was three months from April to June 2012. All required information was referred to the year 2011. RESULTS: The mailed questionnaire correctly fulfilled was sent back by 131/427 (30%) national ICUs. Our data showed 1) in conscious patients, IC was obtained by 82.4% of ICUs; 2) in unconscious patients, IC was obtained in only 61.8% with different procedures not following the current Italian law, 3) for surgical tracheostomy performed in operating room, IC was obtained in conscious and unconscious patients in only 69.8% and 47.2% of ICUs, respectively, 4) risk/benefit informative document was provided in 61.1% ICUs, but available only in 47.2% of ICUs performing tracheostomy in operating room. CONCLUSION: In Italian ICUs, participating to this study, the procedures related to IC for conscious and unconscious critically ill patients requiring surgical or percutaneous tracheostomy are not in line with current legal rules and procedures.

Hepatocyte odd protein shuttling (HOPS) is a bridging protein in the nucleophosmin-p19 Arf network.

Nucleophosmin (NPM), a ubiquitously and abundantly expressed protein, occurs in the nucleolus, shuttling between the nucleoplasm and cytoplasm. The NPM gene is mutated in almost 30% of human acute myeloid leukemia cells. NPM interacts with p53 and p19(Arf), directs localization of p19(Arf) in the nucleolus and protects the latter from degradation. Hepatocyte odd protein shuttling (HOPS) is also a ubiquitously expressed protein that moves between the nucleus and cytoplasm. Within the nucleus of resting cells, HOPS overexpression causes cell cycle arrest in G0/G1. HOPS knockdown causes centrosome hyperamplification leading to multinucleated cells and the formation of micronuclei. We demonstrate a direct interaction of HOPS with NPM and p19(Arf), resulting in a functionally active trimeric complex. NPM appeared to regulate HOPS half-life, which, in turn, stabilized p19(Arf) and controlled its localization in the nucleolus. These findings suggest that HOPS acts as a functional bridge in the interaction between NPM and p19(Arf), providing new mechanistic insight into how NPM and p19(Arf) will oppose tumor cell proliferation.

Tracheostomy in Intensive Care Unit: a national survey in Italy.

BACKGROUND: The aim of the present study was to evaluate the frequency of different techniques, indications, timing, as well as procedural features, sedation and ventilation protocols, early and late complications of tracheostomy in Intensive Care Unit (ICU). METHODS: This was a retrospective survey on data collected in 2011. A questionnaire was mailed to all members of the Italian Society of Anesthesia, Analgesia and Intensive Care (SIAARTI). RESULTS: We included in the analysis 131 questionnaires. We found that: 1) Ciaglia Blue-Rhino® (CBR) was the most commonly used tracheostomy (32.8%; N.=1953) and the main indication was prolonged mechanical ventilation (58.8%; N.=77); 2) tracheostomy was performed between 7-15 days (71.8%; N.=94) from ICU admission by a dedicated team (62.6%; N.=82) involving more than one intensive care physician and a nurse; 3) tracheostomy was frequently guided by fiberoptic bronchoscope (93.1%, N.=122) while neck ultrasounds were used as a screening procedure to assess at-risk structure often in presence of pathological anatomical structures (68.7%; N.=90); 4) ventilation protocol and sedation-analgesia-neuromuscular blocking protocol were available in 83.2% and 58.8% of ICUs, respectively; 5) minor bleeding controlled by compression was the most common early and late complication. CONCLUSION: Percutaneous tracheostomy is well established in Italian ICUs and CBR is the most popular technique performed in patients requiring prolonged mechanical ventilation. Tracheostomy is usually performed by a dedicated team using a specific sedation-analgesia-neuromuscular blocking and ventilation protocol, guided by fiberoptic bronchoscope and/or neck ultrasounds. Bleeding controlled by compression was the most common early and late complication.

BDNF Val66Met polymorphism and brain volumes in multiple sclerosis.

Brain derived neurotrophic factor (BDNF) regulates several CNS physiological and pathological processes. To investigate in multiple sclerosis (MS) patients, the relationship between the Val66Met polymorphism of BDNF and clinical markers of disease activity and MRI markers of focal and diffuse brain pathologies. 45 MS patients and 34 healthy controls (HCs) were genotyped and subjected to clinical-MRI examination. Global white matter fraction (gWM-f), gray matter-f (GM-f), cerebrospinal fluid-f (CSF-f), and abnormal WM-f were measured. We studied 26 Val/Val and 19 Val/Met patients and 23 Val/Val and 11 Val/Met HCs. We found that Val/Val patients had lower GM-f and higher CSF-f than Val/Val HCs; such differences were not statistically significant comparing Val/Met patients to HCs. The regression analysis showed that both Val/Met genotype and relapse number were associated with lower CSF-f. Our data suggest that Met allele might be a protective factor against MS as it is associated to a lower brain atrophy.

Different patterns of lung recruitment maneuvers in primary acute respiratory distress syndrome: effects on oxygenation and central hemodynamics.

BACKGROUND: The aim of this study was to test if different recruitment maneuver (RM) patterns, that achieve the same maximum pressure for the same length of time in humans, have a similar efficacy on alveolar recruitment, intrathoracic vascular pressures and flows, and on cardiac function and ventricular filling. METHODS: Forty patients were randomly allocated to undergo different RM patterns: sustained inflation (SI) or pressure controlled ventilation (PCV). The RM methods tested are as follows: SI was achieved by raising peak inspiratory pressure to 45 cmH(2)O and sustaining it for 40 seconds. The PCV was set to obtain a 45 cmH(2)O peak inspiratory pressure for 2 minutes, I:E 1:2, PEEP 16 RR 8/min. During the study period, patients were mechanically ventilated to obtain a volume of 6 mL/kg, FiO(2) 0.7, PEEP 14, RR 14, Pplateau < or =30 cmH(2)O according to the ARDSnet trial. All patients were sedated and paralyzed during the study period. All patients were given i.v. norepinephrine. Heart rate, pulse oxymetry, blood pressure, pulmonary artery catheter data (C.I., PVRI, MPAP, PAOP, SvO(2), CVP), and arterial and right heart side venous blood gas analysis data (ph, PaO(2), PaCO(2), SatO(2), HCO(3)(-), SvO(2)) were recorded before and immediately after the lung recruitment maneuver. The static compliance of the respiratory system (CRS) was recorded. Echocardiographic spot evaluations before and after RM were obtained in all cases. RESULTS: Central venous pressure increased during RM. Mean pulmonary artery pressure, pulmonary capillary wedge pressure and pulmonary vascular resistance index were reduced during PCV RM compared to SI RM (P<0.05). The right ventricle stroke work index decreased to a major extent during PCV RM (P<0.05). The P/F ratio was significantly increased after PCV RM compared to SI RM (P<0.05). PaCO(2) levels were similar in the two groups. Compared to baseline, the Qs/Qt decreased significantly after the PCV recruitment maneuver. Ventricular end-diastolic and end-systolic areas decreased during both RM protocols, but they were decreased to a greater extent after SI RM than after PCV RM (P<0.05). The eccentricity index increased from baseline after the SI RM (P<0.05). CONCLUSION: Given its comparable, or even superior, performance over the SI RM, we favor the PCV technique over the time-honored SI maneuver.

Do simple ventilation and gas exchange measurements predict early successful weaning from respiratory support in unselected general intensive care patients?

BACKGROUND: The value of respiratory variables as weaning predictors in the intensive care unit (ICU) is controversial. We evaluated the ability of tidal volume (Vt(exp)), respiratory rate (f), minute volume (MV(exp)), rapid shallow breathing index (f/Vt), inspired-expired oxygen concentration difference [(I-E)O(2)], and end-tidal carbon dioxide concentration (Pe'(co(2))) at the end of a weaning trial to predict early weaning outcomes. METHODS: Seventy-three patients who required >24 h of mechanical ventilation were studied. A controlled pressure support weaning trial was undertaken until 5 cm H(2)O continuous positive airway pressure or predefined criteria were reached. The ability of data from the last 5 min of the trial to predict whether a predefined endpoint indicating discontinuation of ventilator support within the next 24 h was evaluated. RESULTS: Pre-test probability for achieving the outcome was 44% in the cohort (n=32). Non-achievers were older, had higher APACHE II and organ failure scores before the trial, and higher baseline arterial H(+) concentrations. The Vt, MV, f, and f/Vt had no predictive power using a range of cut-off values or from receiver operating characteristic (ROC) analysis. The [I-E]O(2) and Pe'(co(2)) had weak discriminatory power [area under the ROC curve: [I-E]O(2) 0.64 (P=0.03); Pe'(co(2)) 0.63 (P=0.05)]. Using best cut-off values for [I-E]O(2) of 5.6% and Pe'(co(2)) of 5.1 kPa, positive and negative likelihood ratios were 2 and 0.5, respectively, which only changed the pre- to post-test probability by about 20%. CONCLUSIONS: In unselected ICU patients, respiratory variables predict early weaning from mechanical ventilation poorly.