Virological and immunological features of SARS-CoV-2-infected children who develop neutralizing antibodies.

As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.

How to dissect the plasticity of antigen-specific immune response: a tissue perspective.

Generation of antigen-specific humoral responses following vaccination or infection requires the maturation and function of highly specialized immune cells in secondary lymphoid organs (SLO), such as lymph nodes or tonsils. Factors that orchestrate the dynamics of these cells are still poorly understood. Currently, experimental approaches that enable a detailed description of the function of the immune system in SLO have been mainly developed and optimized in animal models. Conversely, methodological approaches in humans are mainly based on the use of blood-associated material because of the challenging access to tissues. Indeed, only few studies in humans were able to provide a discrete description of the complex network of cytokines, chemokines and lymphocytes acting in tissues after antigenic challenge. Furthermore, even fewer data are currently available on the interaction occurring within the complex micro-architecture of the SLO. This information is crucial in order to design particular vaccination strategies, especially for patients affected by chronic and immune compromising medical conditions who are under-vaccinated or who respond poorly to immunizations. Analysis of immune cells in different human tissues by high-throughput technologies, able to obtain data ranging from gene signature to protein expression and cell phenotypes, is needed to dissect the peculiarity of each immune cell in a definite human tissue. The main aim of this review is to provide an in-depth description of the current available methodologies, proven evidence and future perspectives in the analysis of immune mechanisms following immunization or infections in SLO.

Malignant cerebral edema related to Systemic Lupus Erythematosus.

BACKGROUND: The neurological manifestations of Systemic Lupus Erythematosus (SLE) are varied and incompletely described. A few case series report a benign idiopathic intracranial hypertension (IIH) related to SLE, which is responsive to immunotherapy. There are limited reports of patients with malignant cerebral edema, and diffuse white matter changes in the absence of central nervous system (CNS) vasculitis. METHODS: Case series from our tertiary care center and review of the relevant literature. RESULTS: Case one was a 32year-old woman admitted with nausea, vomiting and cranial nerve palsies. Serology was significant for a diagnosis of probable SLE. MRI was performed and showed bilateral symmetric diffuse T2/FLAIR hyperintensities throughout the white matter and cerebral angiography was unremarkable. The patient developed recalcitrant cerebral edema with intracranial hypertension despite immunosuppressive therapies and subsequently expired. Post mortem evaluation showed a white matter inflammatory process, but no vascular changes consistent with CNS vasculitis. Case two was a 29year-old woman with known SLE that presented with a loss of consciousness. Imaging included a CT that showed diffuse cerebral edema with white matter involvement and a normal cerebral angiogram. Again, despite maximal medical management the patient herniated resulting in death by neurologic criteria. CONCLUSIONS: These two cases represent a syndrome of white matter changes and diffuse cerebral edema associated with SLE that have yet to be reported in the literature. It is unclear if this process has a similar pathology to SLE related IIH. Because this syndrome causes a fulminant cerebral edema, further research is needed to better understand the underlying pathology and identify potential treatment options.

The EPIICAL project: an emerging global collaboration to investigate immunotherapeutic strategies in HIV-infected children.

The EPIICAL (Early-treated Perinatally HIV-infected Individuals: Improving Children's Actual Life with Novel Immunotherapeutic Strategies) project arises from the firm belief that perinatally infected children treated with suppressive antiretroviral therapy (ART) from early infancy represent the optimal population model in which to study novel immunotherapeutic strategies aimed at achieving ART-free remission. This is because HIV-infected infants treated within 2-3 months of life have a much reduced viral reservoir size, and rarely show HIV-specific immunity but preserve normal immune development. The goal of EPIICAL is the establishment of an international collaboration to develop a predictive platform using this model to select promising HIV therapeutic vaccine candidates, leading to prioritisation or deprioritisation of novel immunotherapeutic strategies. To establish this platform, the EPIICAL Consortium aims to: develop predictive models of virological and immunological dynamics associated with response to early ART and to treatment interruption using available data from existing cohorts/studies of early-treated perinatally HIV-infected children; optimise methodologies to better characterise immunological, virological and genomic correlates/profiles associated with viral control; test novel immunotherapeutic strategies using in vivo proof-of-concept (PoC) studies with the aim of inducing virological, immunological and transcriptomic correlates/profiles equivalent to those defined by the predictive model. This approach will strengthen the capacity for discovery, development and initial testing of new therapeutic vaccine strategies through the integrated efforts of leading international scientific groups, with the aim of improving the health of HIV-infected individuals.

The laparoscopic mini-gastric bypass: the Italian experience: outcomes from 974 consecutive cases in a multicenter review.

BACKGROUND: Due to the failure of the "old Mason loop," the mini-gastric bypass (MGB) has been viewed with skepticism. During the past 12 years, a growing number of authors from around the world have continued to report excellent short- and long-term results with MGB. METHODS: One university center, three regional hospitals, and two private hospitals participated in this study. From July 2006 to December 2012, 475 men (48.8 %) and 499 women (51.2 %) underwent 974 laparoscopic MGBs. The mean age of these patients was 39.4, and their preoperative body mass index was 48 ± 4.58 kg/m(2). Type 2 diabetes mellitus (T2DM) affected 224 (22.9 %) of the 974 patients, whereas 291 of the 974 patients (29.8 %) presented with hypertension. The preoperative gastrointestinal status was explored in all the patients through esophagogastroduodenoscopia. The major end points of the study were definitions of both MGB safety and efficacy in the long term as well as the endoscopic changes in symptomatic patients eventually produced by surgery. RESULTS: The rate of conversion to open surgery was 1.2 % (12/974), and the mortality rate was 0.2 % (2/974). The perioperative morbidity rate was 5.5 % (54/974), with 20 (2 %) of the 974 patients requiring an early surgical revision. The mean hospital length of stay was 4.0 ± 1.7 days. At this writing, 818 patients are being followed up. Late complications have affected 74 (9 %) of the 818 patients. The majority of these complications (66/74, 89.1 %) have occurred within 1 year after surgery. Bile reflux gastritis was symptomatic, with endoscopic findings reported for 8 (0.9 %) and acid peptic ulcers for 14 (1.7 %) of the 818 patients. A late revision surgery was required for 7 (0.8 %) of the 818 patients. No patient required revision surgery due to biliary gastritis. At 60 months, the percentage of excess weight loss was 77 ± 5.1 %, the T2DM remission was 84.4 %, and the resolution of hypertension was 87.5 %. CONCLUSIONS: Despite initial skepticism, this study, together with many other large-scale, long-term similar studies from around the world (e.g., Taiwan, United States, France, Spain, India, Lebanon) demonstrated the MGB to be a short, simple, low-risk, effective, and durable bariatric procedure.

Premature ageing of the immune system relates to increased anti-lymphocyte antibodies (ALA) after an immunization in HIV-1-infected and kidney-transplanted patients.

Low-affinity immunoglobulin (Ig)G with potential autoreactivity to lymphocytes and hypergammaglobulinaemia have been described previously in HIV-1-infected patients. Whether such antibodies increase after challenging the immune system, for example with an immunization, is not known. In the present study, the modulation of antibodies with low affinity and potential autoreactivity was evaluated after 2012-13 seasonal flu vaccination with a simple empirical laboratory test measuring the titres of anti-lymphocyte antibodies (ALA) in two different models of secondary immunodeficiency: HIV-1 vertically infected patients (HIV) and patients treated with immunosuppressive therapies after kidney transplantation (KT) compared to healthy individuals (HC). In parallel, the activation status of B cells and their degree of immune senescence was evaluated by measuring the B cell interleukin (IL)-21R expression/plasma IL-21 levels and the frequencies of mature-activated (MA) and double-negative (DN) B cells. A significant increase of ALA titres was observed after vaccination in HIV and KT but not in HC, and this correlated directly with the frequencies of both MA and DN and inversely with the B cell IL-21R expression. This suggests that the quality of an immune response triggered by flu vaccination in HIV and KT may depend upon the activation status of B cells and on their degree of immune senescence. Further investigations are needed to verify whether high frequencies of MA and DN may also relate to increase autoimmunity after immunization in high-risk populations.

Neurocritical care education during neurology residency: AAN survey of US program directors.

OBJECTIVE: Limited information is available regarding the current state of neurocritical care education for neurology residents. The goal of our survey was to assess the need and current state of neurocritical care training for neurology residents. METHODS: A survey instrument was developed and, with the support of the American Academy of Neurology, distributed to residency program directors of 132 accredited neurology programs in the United States in 2011. RESULTS: A response rate of 74% (98 of 132) was achieved. A dedicated neuroscience intensive care unit (neuro-ICU) existed in 64%. Fifty-six percent of residency programs offer a dedicated rotation in the neuro-ICU, lasting 4 weeks on average. Where available, the neuro-ICU rotation was required in the vast majority (91%) of programs. Neurology residents' exposure to the fundamental principles of neurocritical care was obtained through a variety of mechanisms. Of program directors, 37% indicated that residents would be interested in performing away rotations in a neuro-ICU. From 2005 to 2010, the number of programs sending at least one resident into a neuro-ICU fellowship increased from 14% to 35%. CONCLUSIONS: Despite the expansion of neurocritical care, large proportions of US neurology residents have limited exposure to a neuro-ICU and neurointensivists. Formal training in the principles of neurocritical care may be highly variable. The results of this survey suggest a charge to address the variability of resident education and to develop standardized curricula in neurocritical care for neurology residents.

Use of hypothermia for traumatic brain injury: point of view.

Traumatic brain injury (TBI) is one of the major causes of disability in modern society. The World Health Organization has predicted that, by 2020, traffic accidents will represent the greatest burden of global disease and injury. Brain injury after trauma occurs in two stages. Primary injury is directly associated with the biomechanical effects of the trauma, whereas secondary injury occurs later and can be attributed to processes that develop within the brain. Currently, there is no consensus for the use of hypothermia in the treatment of secondary injury after TBI. Until the results of ongoing studies are published, maintaining normothermia and avoiding hyperthermia should be used in managing patient with TBI.

Ventilator-associated pneumonia in trauma patients is associated with lower mortality: results from EU-VAP study.

BACKGROUND: Differences in trauma patients developing ventilator-associated pneumonia (VAP) are described regarding etiology and risk factors associated. We aim to describe the differences in outcomes in trauma and nontrauma patients with VAP. METHODS: A prospective, observational study conducted in 27 intensive care units from nine European countries. We included patients requiring invasive mechanical ventilation for >48 hours who developed VAP. Logistic regression model was used to assess the factors independently associated with mortality in trauma patients with VAP. RESULTS: A total of 2,436 patients were evaluated; 465 developed VAP and of these 128 (27.5%) were trauma patients. Trauma patients were younger than nontrauma (45.3 ± 19.4 vs. 61.1 ± 16.7, p < 0.0001). Nontrauma had higher simplified acute physiology score II compared with trauma patients (45.5 ± 16.3 vs. 41.1 ± 15.2, p = 0.009). Most prevalent pathogens in trauma patients with early VAP were Enterobacteriaceae spp. (46.9% vs. 27.8%, p = 0.06) followed by methicillin-susceptible Staphylococcus aureus (30.6% vs. 13%, p = 0.03) and then Haemophilus influenzae (14.3% vs. 1.9%, p = 0.02), and the most prevalent pathogen in late VAP was Acinetobacter baumannii (12.2% vs. 44.4%, p < 0.0001). Mortality was higher in nontrauma patients than in trauma patients (42.6% vs. 17.2%, p < 0.001, odds ratio [OR] = 3.55, 95%CI = 2.14-5.88). A logistic regression model adjusted for sex, age, severity of illness at intensive care unit admission, and sepsis-related organ failure assessment score at the day of VAP diagnosis confirmed that trauma was associated with a lower mortality compared with nontrauma patients (odds ratio [OR] = 0.37, 95%CI = 0.21-0.65). CONCLUSIONS: Trauma patients developing VAP had different demographic characteristics and episodes of etiology. After adjustment for potential confounders, VAP episodes in trauma patients are associated with lower mortality when compared with nontrauma patients.

Status epilepticus as initial manifestation of posterior reversible encephalopathy syndrome.

We report 10 cases of status epilepticus (SE) in patients with posterior reversible encephalopathy syndrome (PRES). In all cases, SE brought PRES to medical attention. The majority of the cases had focal-onset complex partial SE. Complete resolution of SE was achieved after combined treatment of PRES and SE in all cases. SE in the setting of PRES carries a favorable prognosis but requires timely recognition and treatment of the course of PRES.

Malignant pleural effusions: review of treatment and our experience.

More than half of patients with malignancy present with a pleural effusion at some time in their course. Recurrent malignant pleural effusions (MPE) impair functions and worsen the quality of life. Once a patient develops MPE, only mechanical drainage relieves pulmonary compression and dyspnea. Optimal treatment is however, still controversial. During January 2001 to January 2006, our group treated 48 patients with outpatient insertion of chronic indwelling pleural catheter (IPC), Pleurx (Pleurx, Surgimedics, Denver Biomaterials, Denver, CO, USA). Primary malignancy of 48 patients included: 27 lung cancers, 11 mesotheliomas, 5 breast cancers, 3 colon cancers, 2 pancreas cancers and 1 ovarian cancer. Eligibility for IPC required prior thoracentesis with histological confirmation of malignancy and chest roentgenogram evidence of effusion. All patients treated were made aware of their prior malignancy and positive cytology for MPE. Major complications, as systemic or pleural infections, were not registered. Permanence mean time of IPC was estimated as 88 days. Median time of draining interval was 7.0 days with maximum amount of effusion drained off being 1000 ml. Pleurodesis occurred in 23 of 48 (47.92%) patients with a mean time of pleurodesis being 43 days. IPC allows ambulatory treatment with a safe and effective drainage of MPE and is an alternative treatment to procedures in use.

Mannitol bolus preferentially shrinks non-infarcted brain in patients with ischemic stroke.

Changes in brain tissue volume in six patients who had acute complete middle cerebral artery (MCA) infarctions and CT evidence of midline shift were measured using the brain boundary shift integral (BBSI) on sequential T1-weighted MR images acquired before and after a 1.5-g/kg bolus infusion of mannitol. At 50 to 55 minutes after the baseline scan, total brain volume decreased by 8.1 +/- 2.8 mL (0.6%, p < 0.005). Brain in the noninfarcted hemisphere shrank more (0.8 +/- 0.4%) than in the infarcted hemisphere (0.0 +/- 0.5%, p < 0.05).

The hemostatic balance after plasma-exchange transfusion in myasthenia Gravis.

BACKGROUND: To study the effects of plasma-exchange on removal and recovery of haemostatic factors and inhibitors using albumin or PPS as replacement fluid. DESIGN: Prospective, noninterventional study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: The study included 11 consecutive patients with Myasthenia Gravis, whose haemostatic parameters were normal before plasma-exchange. INTERVENTIONS: Plasma coagulative factors and inhibitors were studied before at the end of and 24 hours after each exchange. RESULTS: Immediately after exchange plasma coagulation factors and inhibitors evaluated were reduced, except for factor VIII; 24 hours later only fibrinogen was significantly decreased; D-Dimer was not found increased; the platelets, after exchange, were at normal levels. CONCLUSIONS: Our data show a parallel lowering of haemostatic factors and inhibitors after plasmapheresis using material devoid of coagulation factors as replacement, this explains the absence of hemorrhagic or thrombotic complications. So we think that careful monitoring of coagulation during plasma-exchange is not useful.

[NMR in the diagnosis and treatment of neurologic lesions in decompression sickness]. / Contributo della RMN alla conoscenza ed al trattamento delle lesioni neurologiche da MDD.

The case of a decompression sickness in woman, diving to 26 meter depth is reported. The patient was helped by instructor's computer (error!) and she presented risk factors for embolic disease (obesity, smoke, estroprogestinic therapy). She presented with many symptoms of decompression sickness during immersion and during re-ascent (headache, vertigoes and paresthesias). She was not treated on the place of incident, but only 36 hours later at our center of hyperbaric medicine. Her Magnetic Resonance imaging showed hyperintensity lesions of white matter.

The effects of mannitol on cerebral edema after large hemispheric cerebral infarct.

OBJECTIVE: To evaluate the effect of a single large dose of mannitol on midline tissue shifts after a large cerebral infarction. BACKGROUND: Theoretically, mannitol use in the largest cerebral infarctions may preferentially shrink noninfarcted cerebral tissue, thereby aggravating midline tissue shifts and worsening neurologic status. To test this theory, we studied patients with hemispheric infarctions using continuous and sequential MRI during administration of a single dose of mannitol. METHODS: Patients with neurologic deterioration from complete middle cerebral artery (MCA) infarctions and CT evidence of at least 3 mm of midline shift were studied using T1-weighted three-dimensional multiplanar rapid acquisition gradient echo image data sets acquired at 5- to 10-minute intervals before, during, and after a 1.5 gm/kg bolus infusion of mannitol. Horizontal and vertical displacements were calculated by previously described methods. Glasgow Coma Scale (GCS) and MCA Stroke Scale (MCASS) were measured before and after mannitol administration. Mean changes in tissue shifts were compared using repeated measures analysis of variance. Clinical variables were compared using paired t-tests. RESULTS: Seven patients were enrolled. The final average change in midline shift compared with the initial displacement was 0.0 +/- 1 mm for horizontal (F = 0.06, p = 0.99) and 0.25 +/- 1.3 mm for vertical displacement (F = 0.06, p = 0.99). Whereas average scores for the group did not change, MCASS improved in two, GCS improved in three, and pupillary light reactivity returned in two patients. No patient worsened. CONCLUSIONS: Acute mannitol used in patients with cerebral edema after a large hemispheric infarction does not alter midline tissue shifts or worsen neurologic status.

[Hyponatremia in neurosurgical patients]. / Iposodiemia nel paziente neurochirurgico.

Hyponatremia played an essential role in this case, determining the rapid transition from consciousness to a state of coma in female patient who had just come through the critical phase of intensive care. This circumstance underlines the importance of a correct water balance in patients undergoing neurosurgery, as well as a knowledge of the inappropriate antidiuretic hormone secretion (SIADH) syndrome responsible, either alone or in association, for the genesis of severe hyponatremia. In the differential diagnosis of hyponatremia, it is important to recall the role of an often mistaken syndrome (cerebral salt wasting syndrome) characterized by the secretion of a natriuretic factor that has still not been clearly identified.

[Giromitra syndrome caused by false morel]. / Sindrome gyromitriana da spugnola falsa.

Three cases of mushrooms poisoning (by false morel) with associated gyromitra syndrome, due to a thermolabil toxin are reported. They showed a syndrome like to Amanita phalloides poisoning (gastroenteric symptomatology, diarrhoea) some hours after eating and then neurologic signs; they were hospitalized (without haemolytic signs) and were discharged from hospital a few days later in a good health.

Mechanical ventilation for ischemic stroke and intracerebral hemorrhage: indications, timing, and outcome.

OBJECTIVE: To compare the incidence, indication, and timing of intubation and outcome in patients with cerebral infarction (ISCH) and intracerebral hemorrhage (HEM) requiring mechanical ventilation (MV). BACKGROUND: Poor outcomes have been reported for ISCH patients requiring MV. Because the target population, pathophysiology, and management of ISCH and HEM patients differ considerably, we compared the characteristics of patients with ISCH and HEM who required MV. METHODS: A retrospective review of ISCH and HEM stroke patients who underwent MV at a tertiary care academic center from 1994 to 1997 was performed to determine age, sex, type, and location of stroke (anterior or posterior circulation); brainstem dysfunction at intubation (pupillary, corneal, and oculocephalic reflexes); indication for intubation (neurologic deterioration, cardiopulmonary deterioration, or elective intubation for surgery); timing of intubation (on presentation or later); comorbidities; and outcome (hospital disposition). RESULTS: A total of 230 patients, 74 with ISCH and 156 with HEM (mean age, 61 +/- 16 years; male-to-female ratio, 1.15:1), underwent MV. Intubation rates were 6% for ISCH patients and 30% for HEM patients. Two-thirds of the patients required intubation on presentation (84% were intubated for neurologic deterioration) and 131 patients (57%) died (ISCH, 55%; HEM, 58%). Signs of brainstem dysfunction predicted a higher mortality for both groups. Additionally, early intubation and older age predicted mortality for HEM, and male gender predicted mortality in ISCH. Stroke location and comorbidities did not influence outcome. CONCLUSIONS: MV in acute stroke is associated with high mortality. Mortality and outcome were similar for ISCH and HEM; however, the factors predictive of outcome may differ and influence decisions about the use of MV in such patients.