new morphologic variants of the hand motor cortex as seen with mr imaging in a large study population

BACKGROUND AND PURPOSE: The hand motor cortex (HMC) has been classically described as having an omega or epsilon shape in axial-plane images obtained with CT and MR imaging. The aim of this study was to use MR imaging and Talairach normalization in a large sample population that was homogeneous for age and handedness to evaluate in a sex model a new classification with 5 morphologic variants of the HMC in the axial plane (omega, medially asymmetric epsilon, epsilon, laterally asymmetric epsilon, and null). MATERIALS AND METHODS: Structural brain MR images were obtained from 257 right-handed healthy subjects (143 men and 114 women; mean age, 23.1 ± 1.1 years) via a Talairach space transformed 3D magnetization-prepared rapid acquisition of gradient echo sequence. The frequencies of the different HMC variants were reported for hemisphere and sex. RESULTS: The new variants of the HMC (medially asymmetric epsilon, laterally asymmetric epsilon, and null) were observed in 2.9%, 7.0%, and 1.8% of the hemispheres, respectively. Statistically significant sex differences were observed: The epsilon variant was twice as frequent in men, and an interhemispheric concordance for morphologic variants was observed only for women. CONCLUSION: The large study population permitted the description of a new morphologic classification that included 3 new variants of the HMC. This new morphologic classification should facilitate the identification of the precentral gyrus in subsequent studies and in everyday practice

Free testosterone (FT) is inversely related to frailty in human immunodeficiency virus (HIV)-infected men.

BACKGROUND HIV-infection is associated to several age-related comorbidities, such as a premature decline of serum testosterone (T). There is evidence about the relationship between health status, represented by frailty and comorbidities, and serum T levels in general population, while only one previous retrospective study investigated it in HIV-infected men. AIM To investigate the association between frailty and gonadal status by assessing serum total T (TT) with Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS) in a cohort of HIV-infected men. METHODS Prospective, cross-sectional, observational study on HIV-infected men (age years) with ongoing Highly Active Antiretroviral Therapy (HAART). Serum TT was assessed by the gold standard ID- LC-MS/MS. Sex hormone-binding globulin (SHBG) was measured by chemiluminescent immunoassay. Free T (FT) was calculated by Vermeulen equation. Frailty was calculated through -items multimorbidity frailty index. Saca aa Parameters were not normally distributed and Mann- Whitney U test was used to compare continuous variables. Correlations were performed using linear regression models. RESULTS consecutive HIV-infected men were enrolled (mean age .. years; average duration of HIV-infection .. years). patients (.) had TT below ng/dL and patients (.) had calculated FT below pg/mL. Overall, patients (.) had T deficiency defined by low TT levels and/or low FT. patients (.) showed SHBG above the normal range (. nmol/L). Frailty score (p.), age (p.), duration of HIV-infection and of HAART (p.) significantly differed between eugonadic and hypogonadic patients, while no difference was found for BMI (p.). FT inversely correlated with frailty score (p., R.), while TT did not (p.). At stepwise multivariate regression analysis, FT showed an inverse relation with age (p.,R.), years of infection (-.,p.,R.) and years of HAART (-.,p.,R.), but not with frailty score and BMI of patients. CONCLUSIONS To the best of our knowledge, this is the first properly-designed prospective study aiming to investigate the relationship between general health status and gonadal function in a cohort of HIV-infected men. FT is inversely related to frailty score, suggesting an impairment of gonadal function in those patients affected by more multimorbidities in this setting as well as in general population. At the same time, the age of patient and the duration of HIV-infection seem to be more potent predictive factors for serum FT levels than frailty score. In clinical practice it is important to check for testosterone in these patients due to frequent alterations of SHBG

Redistribution of CD8+ T cell subsets in metastatic renal cell carcinoma patients treated with anti-PD-1 therapy

Renal-cell carcinoma (RCC) is responsible for the majority of tumors arising from the kidney parenchyma. Although a progressive improvement in median overall survival has been observed after the introduction of anti-PD-1 therapy, many patients do not benefit from this treatment. Therefore, we have investigated T cell dynamics to find immune modification induced by anti-PD-1 therapy. Here, we show that, after therapy, RCC patients (5 responders and 14 nonresponders) are characterized by a redistribution of different subsets across the memory T cell compartment

Low Serum Testosterone (T) Is Associated with Poor Health Status in Young to Middle-Aged Human Immunodeficiency Virus (HIV)-Infected Men.

BACKGROUND: The relationship between health status, defined by frailty and comorbidities, and serum T levels has been widely demonstrated in general population, while only one previous retrospective study has explored it in HIV-infected men1. AIM: To investigate the association between frailty and go- nadal status by assessing serum total T (TT) with Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS) in a cohort of HIV-infected men. METHODS: Prospective, cross-sectional, observational study on HIV-infected men (age <50 years) with on- going Highly Active Antiretroviral Therapy. Serum TT was assessed by the gold standard ID-LC-MS/MS. Sex hormone-binding globulin (SHBG) was measured by chem- iluminescent immunoassay. Calculated free T (cFT) was obtained by Vermeulen equation. Multimorbidity was de- fined as at least 3 comorbid conditions, including: hyperten- sion, diabetes, cardiovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, osteoporosis, chronic viral hepatitis and cancers. Frailty was calculated through the validated 37-item frailty index (FI)2. Patients with FI>0.21 were considered frail. Statistical ana- lysis: Mann-Whitney U test was used to compare contin- uous variables. Correlations were performed using linear regression models. RESULTS: 315 consecutive HIV-infected men were enrolled (mean age 45.3\ub15.3 years; average duration of HIV-infection 16.3\ub18.8 years). 128 patients (40.5%) were co- morbid and 207 (64.9%) were frail. Either cFT (p=0.001) or TT (p<0.001) were lower in comorbid patients than others. FT was inversely related to the number of comorbidities (p<0.001, R2=0.045). Accordingly, cFT (p=0.003) and TT (p<0.001) were significantly lower in frail patients.Frailty score was inversely correlated with cFT (p<0.001, R2=0.058), TT (p=0.041, R2=0.014) and SHBG (p=0.003, R2=0.029). However, after adjustment for age and duration of HIV-infection, cFT, TT and SHBG were excluded from the regression model. CONCLUSIONS: Low cFT and TT levels are associated with multimorbidity and poor health status in HIV infected men. The bidirectional nature of this relationship leads to the figuration of an intriguing vicious circle where T de- ficiency triggers the onset of comorbidities or, vice versa, poor health status induces hypogonadism. At the same time, notwithstanding the inverse relation between FT and frailty, it seems that other stronger predictive factors, and in particular the duration of infection, are involved in de- termining the health outcome in this clinical setting

The morphology and clinical importance of the axillary arch

The axillary arch is the main variation of the axillary muscle. It was first described by Ramsay in 1795. In its classical form, it arises from the latissimus dorsi muscle and extends from this towards the pectoralis major, crossing the base of the axilla and creating a close relationship with the elements of the axillary neurovascular bundle. We describe the finding of 9 axillary arches, including one case of a bilateral arrangement. We develop a searching and finding technique for the axillary arch, essential for the safe and successful development of surgical procedures in the axillary region. Knowledge of this muscle variation and the possibility of finding it during axillary procedures is crucial for lymph node staging and lymphadenectomy and is also important for differential diagnosis in compressive pathologies of the axillary vessels and brachial plexus

Circulating mucosal-associated invariant T cells identify patients responding to anti-PD-1 therapy

Immune checkpoint inhibitors are used for treating patients with metastatic melanoma. Since the response to treatment is variable, biomarkers are urgently needed to identify patients who may benefit from such therapy. Here, we combine single-cell RNA-sequencing and multiparameter flow cytometry to assess changes in circulating CD8+ T cells in 28 patients with metastatic melanoma starting anti-PD-1 therapy, followed for 6 months: 17 responded to therapy, whilst 11 did not. Proportions of activated and proliferating CD8+ T cells and of mucosal-associated invariant T (MAIT) cells are significantly higher in responders, prior to and throughout therapy duration. MAIT cells from responders express higher level of CXCR4 and produce more granzyme B. In silico analysis support MAIT presence in the tumor microenvironment. Finally, patients with >1.7% of MAIT among peripheral CD8+ population show a better response to treatment. Our results thus suggest that MAIT cells may be considered a biomarker for patients responding to anti-PD-1 therapy

Expansion of plasmablasts and loss of memory B cells in peripheral blood from COVID-19 patients with pneumonia

Studies on the interactions between SARS-CoV-2 and humoral immunity are fundamental to elaborate effective therapies including vaccines. We used polychromatic flow cytometry, coupled with unsupervised data analysis and principal component analysis (PCA), to interrogate B cells in untreated patients with COVID-19 pneumonia. COVID-19 patients displayed normal plasma levels of the main immunoglobulin classes, of antibodies against common antigens or against antigens present in common vaccines. However, we found a decreased number of total and na\uefve B cells, along with decreased percentages and numbers of memory switched and unswitched B cells. On the contrary, IgM+ and IgM 12 plasmablasts were significantly increased. In vitro cell activation revealed that B lymphocytes showed a normal proliferation index and number of dividing cells per cycle. PCA indicated that B-cell number, naive and memory B cells but not plasmablasts clustered with patients who were discharged, while plasma IgM level, C-reactive protein, D-dimer, and SOFA score with those who died. In patients with pneumonia, the derangement of the B-cell compartment could be one of the causes of the immunological failure to control SARS-Cov2, have a relevant influence on several pathways, organs and systems, and must be considered to develop vaccine strategies

Plasma Cytokine Atlas Reveals the Importance of TH2 Polarization and Interferons in Predicting COVID-19 Severity and Survival

Although it is now widely accepted that host inflammatory response contributes to COVID-19 immunopathogenesis, the pathways and mechanisms driving disease severity and clinical outcome remain poorly understood. In the effort to identify key soluble mediators that characterize life-threatening COVID-19, we quantified 62 cytokines, chemokines and other factors involved in inflammation and immunity in plasma samples, collected at hospital admission, from 80 hospitalized patients with severe COVID-19 disease who were stratified on the basis of clinical outcome (mechanical ventilation or death by day 28). Our data confirm that age, as well as neutrophilia, lymphocytopenia, procalcitonin, D-dimer and lactate dehydrogenase are strongly associated with the risk of fatal COVID-19. In addition, we found that cytokines related to TH2 regulations (IL-4, IL-13, IL-33), cell metabolism (lep, lep-R) and interferons (IFNα, IFNβ, IFNγ) were also predictive of life-threatening COVID-19

Plasma Cytokine Atlas Reveals the Importance of TH2 Polarization and Interferons in Predicting COVID-19 Severity and Survival

Although it is now widely accepted that host inflammatory response contributes to COVID-19 immunopathogenesis, the pathways and mechanisms driving disease severity and clinical outcome remain poorly understood. In the effort to identify key soluble mediators that characterize life-threatening COVID-19, we quantified 62 cytokines, chemokines and other factors involved in inflammation and immunity in plasma samples, collected at hospital admission, from 80 hospitalized patients with severe COVID-19 disease who were stratified on the basis of clinical outcome (mechanical ventilation or death by day 28). Our data confirm that age, as well as neutrophilia, lymphocytopenia, procalcitonin, D-dimer and lactate dehydrogenase are strongly associated with the risk of fatal COVID-19. In addition, we found that cytokines related to TH2 regulations (IL-4, IL-13, IL-33), cell metabolism (lep, lep-R) and interferons (IFNα, IFNβ, IFNγ) were also predictive of life-threatening COVID-19

Rapamycin treatment for amyotrophic lateral sclerosis protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial)

Introduction: Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions. Rapamycin also expands regulatory T lymphocytes (Treg) and increased Treg levels are associated with slow progression in ALS patients. Therefore, we planned a randomized clinical trial testing Rapamycin treatment in ALS patients. Methods: RAP-ALS is a phase II randomized, double-blind, placebo-controlled, multicenter (8 ALS centers in Italy), clinical trial. The primary aim is to assess whether Rapamycin administration increases Tregs number in treated patients compared with control arm. Secondary aims include the assessment of safety and tolerability of Rapamycin in patients with ALS; the minimum dosage to have Rapamycin in cerebrospinal fluid; changes in immunological (activation and homing of T, B, NK cell subpopulations) and inflammatory markers, and on mTOR downstream pathway (S6RP phosphorylation); clinical activity (ALS Functional Rating Scale-Revised, survival, forced vital capacity); and quality of life (ALSAQ40 scale). Discussion: Rapamycin potentially targets mechanisms at play in ALS (i.e., autophagy and neuroinflammation), with promising preclinical studies. It is an already approved drug, with known pharmacokinetics, already available and therefore with significant possibility of rapid translation to daily clinics. Findings will provide reliable data for further potential trials. Ethics and dissemination: The study protocol was approved by the Ethics Committee of Azienda Ospedaliero Universitaria of Modena and by the Ethics Committees of participating centers (Eudract n. 2016-002399-28) based on the Helsinki declaration