Prognostic bioindicators in severe COVID-19 patients.

BACKGROUND: Severe acute respiratory syndrome caused by novel coronavirus 2 (SARS-CoV-2) emerged in Wuhan (China) in December 2019. Here we evaluated a panel of biomarkers to phenotype patients and to define the role of immuno-inflammatory mediators as biomarkers of severity. MATERIALS AND METHODS: Serum samples were obtained from 24 COVID-19 patients on admission to hospital, before any treatment or infusion of intravenous steroids or invasive ventilation. KL-6 IL-6 and C-peptide were measured by chemiluminescent enzyme immunoassay. IL-6 assay was validated for accuracy and precision. The validity of variables used to distinguish severe from mild-to-moderate patients was assessed by areas under curves (AUC) of the receiver operating characteristic (ROC) and logistic regression was performed to combine parameters of the two groups. RESULTS: In the severe group, IL-6, CRP and KL-6 concentrations were significantly higher than in mild-to-moderate patients. KL-6, IL-6 and CRP concentrations were directly correlated with each other. ROC curve analysis of the logistic regression model including IL-6, KL-6 and CRP showed the best performance with an AUC of 0.95. CONCLUSIONS: Besides corroborating previous reports of over-expression of IL-6 in severe COVID-19 patients requiring mechanical ventilation, analytical determination of other mediators showed that IL-6 concentrations were correlated with those of KL-6 and CRP. The combination of these three prognostic bioindicators made it possible to distinguish severe COVID-19 patients with poor prognosis from mild-to-moderate patients.

Rest-activity rhythm in breast cancer survivors: an update based on non-parametric indices.

Recently we evaluated by actigraphy the rest-activity circadian rhythm (RAR) in breast cancer (BC) survivors at 5 years from primary diagnosis, as well as in a control group with similar age and body mass index (BMI). RAR, analyzed by Cosinor method, resulted significantly different in BC survivors compared to healthy subjects: BC survivors showed lower values of MESOR and Amplitude (A), while acrophase (φ) was similar in the two groups. Now, using non-parametric methods we have detected Interdaily Stability (IS), Intradaily Variability (IV), nocturnal activity (L5), and daily activity (M10) on the same sample of previous study: 15 BC survivors at 5 years from the primary diagnosis (mean age = 56.7 ± 6.6 yrs; mean BMI = 24.5 ± 3.8 Kg/m2) and 13 healthy controls (mean age = 54.4 ± 7.2 yrs; mean BMI = 25.2 ± 2.8 Kg/m2). The non-parametric indices showed that in BC-group IV was significantly higher than in Ctrl-group (0.86 vs. 0.65 a.u. in BC and Ctrl, respectively; p <.01), while L5 (11.27 vs. 34.41 a.c. in BC and Ctrl, respectively; p <.0001) and M10 (326.82 vs. 428.07 a.c. in BC and Ctrl, respectively; p <.01) were significantly lower compared to Ctrl-group. The data suggest that BC patients need constant clinical assessment of RAR characteristics along the years following the primary diagnosis. The analysis of RAR in all its components, parametric and non-parametric, is important to detect alterations in the sleep-wake cycle and can be useful for developing new strategies for health protection, such as structured and tailored physical activity programs, to improve circadian activity level in order to raise the quality of life in BC survivors.

Effect of chronotype on motor skills specific to soccer in adolescent players.

Circadian rhythms influence daily behavior, psychological and physiological functions, as well as physical performance. Three chronotypes are distinguished according to the preferences people typically display for activity at certain times of day: Morning, Neither, and Evening types (M-, N- and E-types). The chronotype changes with age: eveningness tends to be stronger in youth and morningness in older age. The progressive shift toward eveningness during adolescence creates misalignment with morning society schedules and can lead to a deterioration in intellectual and physical performance. Soccer is one of the world's most popular sports practiced by adolescents and soccer workouts are usually held after school in the afternoon or evening. Performance in soccer is related to a host of factors, including physiological variables and motor skills that have a circadian variation. The aim of this study was to determine the effect of chronotype on motor skills specific to soccer, specifically whether agility, aerobic endurance, and explosive power differ among the three chronotypes in relation to the time of day. For this study 141 adolescent soccer players filled in the Morningness-Eveningness Questionnaire (MEQ) for the assessment of chronotype. A subsample of 75 subjects, subdivided in M-types (n= 25), E-types (n= 25), and N-types (n= 25), performed three tests (Sargent Jump Test - SJT, Illinois Agility Test - IAT, and 6-Minutes Run Test - 6MRT) at a morning and an evening training session (9:00 am and 6:00 pm). Mixed ANOVA was used to test the interactions between chronotypes, physical performance, and time. On all tests, better performance during the morning than the evening session was observed for the M-types (p< .05), whereas the E-types performed better in the evening than in the morning session (p< .05), and no differences in test performance were detected for the N-types. These findings underline the importance of a correct chronobiological approach to sports training. Scheduling training sessions according to an athlete's circadian preferences could be a valid strategy to enhance performance.

Effect of chronotype on academic achievement in a sample of Italian University students.

Circadian rhythms play an important role in biological function; their expression differs across individuals; three chronotypes are distinguished: Morning- [MT], Evening- [ET], and Neither- [NT] type. MT achieve peak activation in the first part of the day and are generally more conscientious and achievement-oriented than ET, which reach their best during the second half of the day and express a higher intelligence. University class schedules can sometimes conflict with ET circadian preferences, compromising their academic performance compared with their MT classmates. Conversely, MT students, being more aligned with their daily schedule, might be more advantaged in their mental performance. The attitudes and performance of NT students are little considered. No studies to date have investigated academic achievement in relation to chronotype in an Italian student population. To fill this gap, this study examined the relationship between chronotype and academic performance in a population of Motor Science Faculty in Milan, differentiating achievement in theoretical and practical subjects by chronotype. The study population was 423 university students (290 males and 133 females) and categorized by chronotype according to Morningness-Eveningness Questionnaire (MEQ) scores. Student transcripts were reviewed to obtain exam grades on three practical and three theoretical subjects. The interaction between MEQ score or chronotypes and mean exam grade was evaluated using one-way ANOVA. The mean grades on the theoretical and practical exams were higher for the MT than for either the ET or the NT students. The NT students (24.8 ± 0.1) had lower mean grades for the theoretical subjects than either the MT (26.3 ± 0.4) or the ET (25.3 ± 0.2) students, while the ET (26.6 ± 0.2) performed worse than either the MT (27.8 ± 0.2) or the NT students (26.9 ± 0.1) on the practical exams. The same trend was observed for the total sample and when subdivided by sex. In the total sample, significant differences in theoretical and practical exam grades were noted between chronotypes: MT vs ET (p < .002, p < .0006) and MT vs NT (p < .04, p < .003). The differences between the males were significant for the theoretical (p < .006, MT vs NT, p < .002) and the practical subjects (MT vs ET p < .004, MT vs NT, p < .01), but no significant differences were noted between the females. Our findings indicate overall better academic achievement by the MT students, whereas the NT had lower exam grades for the theoretical subjects and the ET performed worse on the practical exams. We speculate that the higher intelligence expressed by the ET students might have helped them compensate the disadvantage on the theoretical but not on practical exams, in which the effect of misalignment between circadian preferences and university class schedule was more evident.

Effect of aerobic exercise intervention on markers of insulin resistance in breast cancer women.

Insulin may affect breast cancer (BC) risk and prognosis. Exercise reduces insulin in obese BC survivors. We designed a randomised controlled trial to test the effect of an aerobic exercise intervention (AEI) on insulin parameters and body composition in non-obese BC women without insulin resistance. Thirty-eight BC women were randomised into an intervention group (IG = 18) or control group (CG = 20). IG participated in a structured AEI for 3 months, while CG received only the Word Cancer Research Fund/American Institute Cancer Research (WCRF/AICR) recommendation to be physically active. Fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) index, metabolic parameters and body composition were collected at baseline and after the AEI. IG reduced insulin and HOMA-IR index by 15% and 14%, while CG increased these parameters (+12% and +16%). Insulin changed differently over time in the two randomised groups (pinteraction  = .04). The between-group differences in the change of insulin (IG = -1.2 µU/ml versus CG = +0.8 µU/ml) and HOMA-IR index (IG = -0.26 versus CG = +0.25) were respectively significant (p = .04) and non-significant (p = .06). IG significantly improved lower limb muscle mass in comparison with CG (p = .03). A structured AEI may improve insulin, HOMA-IR index and body composition in non-obese BC survivors without insulin resistance.

Rest-activity circadian rhythm and sleep quality in patients with binge eating disorder.

Recent findings suggest that altered rest-activity circadian rhythms (RARs) are associated with a compromised health status. RARs abnormalities have been observed also in several pathological conditions, such as cardiovascular, neurological, and cancer diseases. Binge eating disorder (BED) is the most common eating disorder, with a prevalence of 3.5% in women and 2% in men. BED and its associate obesity and motor inactivity could induce RARs disruption and have negative consequences on health-related quality of life. However, the circadian RARs and sleep behavior in patients with BED has been so far assessed only by questionnaires. Therefore, the purpose of this study was to determine RARs and sleep parameters by actigraphy in patients with BED compared to a body mass index-matched control group (Ctrl). Sixteen participants (eight obese women with and eight obese women without BED diagnosis) were recruited to undergo 5-day monitoring period by actigraphy (MotionWatch 8®, CamNtech, Cambridge, UK) to evaluate RARs and sleep parameters. In order to determine the RARs, the actigraphic data were analyzed using the single cosinor method. The rhythmometric parameters of activity levels (MESOR, amplitude and acrophase) were then processed with the population mean cosinor. The Actiwatch Sleep Analysis Software (Cambridge Neurotecnology, Cambridge, UK) evaluated the sleep patterns. In each participant, we considered seven sleep parameters (sleep onset: S-on; sleep offset: S-off; sleep duration: SD; sleep latency: SL; movement and fragmentation index: MFI; immobility time: IT; sleep efficiency: SE) calculated over a period of five nights. The population mean cosinor applied to BED and Ctrl revealed the presence of a significant circadian rhythm in both groups (p < 0.001). The MESOR (170.0 vs 301.6 a.c., in BED and Ctrl, respectively; p < 0.01) and amplitude (157.66 vs 238.19 a.c., in BED and Ctrl, respectively p < 0.05) differed significantly between the two groups. Acrophase was not different between BED and Ctrl, as well as all sleep parameters. Both groups displayed a low level of sleep quality (SE 80.7% and 75.7% in BED and Ctrl, respectively). These data provided the first actigraphy-based evidence of RARs disruption and sleep behavior disorder in patients with BED. However, while sleep disorders could be reasonably ascribed to overweight/obesity and the related lower daily physical activity, RARs disruption in this pathology should be ascribed to factors other than reduced physical activity. The circadian timing approach can represent a novel potential tool in the treatment of patients with eating disorders. These data provide exploratory evidence of behavioral association in a small population of patients that, if confirmed in a wider number of subjects and across different populations, may lead to a revision and enhancement of interventions in BED patients.

Acute renal failure and nephrotic syndrome due to membranoproliferative nephritis during the second trimester of pregnancy.

We report the case of a patient with acute renal failure and nephrotic syndrome during the second trimester of an otherwise uncomplicated pregnancy. Despite pregnancy, percutaneous renal biopsy was performed to evaluate the etiology, showing Type I membranoproliferative glomerulonephritis. Two therapeutic options were considered: pregnancy termination, suggested by the gynecologists, and our proposal of starting steroid therapy, in order to reduce proteinuria and improve renal function. The patient refused pregnancy termination. She received i.v. methylprednisolone boluses, followed by maintenance oral prednisone and aspirin, with prompt acute renal failure resolution and reduced proteinuria. At Week 34 + 5 days of gestation, cesarean section was performed, without intra- and postoperative complications both for mother and newborn. Clinical maternal and fetal outcomes were excellent. One-year follow-up showed normal renal function and absence of proteinuria. Lacking guidelines concerning treatment of acute renal failure due to primary nephropathy in pregnancy, we consider this case of interest for our decision-making process and for the favorable outcome.

Migraine and coronary artery disease: an open study on the genetic polymorphism of the 5, 10 methylenetetrahydrofolate (MTHFR) and angiotensin I-converting enzyme (ACE) genes.

Genetic factors that increase susceptibility to oxidative stress, endothelial disfunction and, possibly, stroke include angiotensin-converting enzyme gene deletion polymorphism (ACE-DD) and the methylentetrahydropholate reductase (MTHFR) C677-TT polymorphism. The relationship of ACE-DD genotype to ischemic stroke and cardiovascular disease is controversial, but it has been independently linked to lacunar infarction, in the absence of carotid atheroma. Lea et al. (2005) reported that the ACE DD genotype acts in combination with the MTHFR T/T genotype to increase migraine susceptibility, with the greatest effect in those with aura. The "TT" polymorphism is also associated with an increased risk of migraine with aura, independent of other cardiovascular risk factors. The aim of our study was to evaluate the incidence of ACE and MTHFR genes polymorphisms in a consecutive series of migrainous patients and of patients affected by myocardial infarction. We studied a series of 103 migrainous patients (1), whose age was between 13 and 75 years (81 suffering from migraine without aura, MwA, 9 from migraine with aura, MWA, 13 from mixed forms MwA-MWA, according to ICHD-II 2004 criteria) and of 336 patients (2) suffering from ischaemic cardiopathy (myocardial infarction, MI). The analysis, based on Polymerase Chain Reaction (PCR) and on reverse-hybridization, showed as follows: MTHFR (C677T): 60 patients (58%) (1) and 186 (56%) (2) were heterozygous; 9 patients (9%) (1) and 54 (16%) (2) were mutated. The result of 1 patient (2) was unknown. MTHFR (A1298C): 54 patients (52%) (1) and 146 (44%) (2) were heterozygous, 7 patients (7%) (1) and 33 (10%) (2) were mutated. The result of 1 patient (2) was unknown. ACE (evaluated on 101 patients (1) and 245 (2)): 45 patients (43%) (1) and 133 (54%) (2) had an ID genotype; 42 (41%) (1) and 87 (36%) (2) had a DD genotype. The results of our study confirm the high incidence in the genetic polymorphisms ACE and MTHFR in migraineuse. These data are confirmed in the sample of patients affected by myocardial infarction. This gives evidence of a strong relationship between migraine and major vascular diseases and let us hypothesize an important role of ACE and MTHFR system in the pathogenetic model of migraine for its capability to interfere with the endothelial regulation tone. Once an effective role in the genesis of migraine and in the increased risk of migrainous patients to evolve into an ischemic pathology has been obviously assigned to this genetic mutation, future researches must aim through wider and more controlled casistics also to clarify the role that drugs acting on these systems may have on the resolution of these diseases.

Urine chemokines: biomarkers of human lupus nephritis?

Lupus nephritis is characterized by intrarenal inflammation. Leukocytes trafficking from peripheral blood into affected tissues spaces represent an important factor in the development of many renal diseases. During the past few years has been attributed the crucial role of a family of chemotactic cytokines--the chemokines--in this process. In the course of renal diseases, the infiltration of monocytes/macrophages and T cells into kidneys represent an important role in progressive interstitial fibrosis and the progression of chronic renal failure. In this review, we summarize the in vitro and in vivo data on chemokines and chemokine receptors in kidney diseases, with a special focus on urine chemokine measurement as possible biomarker of human lupus nephritis.

[A 52 year-old woman with fever, cough and dyspnoea]. / Donna di 52 anni con febbre, tosse e dispnea.

A 52 year-old woman with gastric cancer treated with surgery and chemotherapy, is admitted in our Internal Medicine Department because of the presence of fever (max 41.2 degrees C), dyspnoea, non-productive cough and mental confusion. The anamnesis and the physical examination address to the diagnosis of CAP (Community-Acquired Pneumonia); in particular the alteration of consciousness and the onset of symptoms after the insertion of a nose-gastric tube let us to consider the diagnosis of aspiration pneumonia. The clinical presentation and radiological imaging (Rx and CT of thorax) suggest the pattern of bronchiolitis obliterans with organizing pneumonia (BOOP). BOOP is not a disease, but a non specific pattern of answer to a lung injury. It can be either idiopathic or associated with a variety of causes, such as infections, drugs, radiations and connective tissue diseases. Besides the clinical course is complicated by the onset of an ARDS (Adult Respiratory Distress Syndrome). The gold standard for the diagnosis is represented by lung biopsy with hystopathologic confirmation but, if it cannot be done, it's necessary to start immediately steroid therapy because BOOP may be fatal. The patient received antibiotic and steroid therapy with success.

[Multiple cerebral tuberculomas resistant to conventional therapy in an immunocompromised subject]. / Tubercolomi cerebrali multipli resistenti alla terapia convenzionale in un soggetto immunosoppresso.

A 33 years old immunocompromised woman was admitted for a fever of unknown origin during the last five months. She referred a body temperature up to 38.3 degrees C, headache, weakness. The physical examination revealed right homonymous hemianopia, hyperreflexia and Babinski on her right side. A TC scan and a following bioptic specimen showed multiple cerebral tuberculomas. A conventional therapy was started but no significative improvement was observed. She was finally treated with interferon gamma and GM-CSF in addition to the therapy with an important regression of the lesions and significative improvement of the fever and neurological findings.

[A 74-year-old woman with macrocytic anemia]. / Donna di 74 anni con anemia macrocitica.

A seventy-four years old woman is assessed for asthenia, fatigue, non ulcerous dyspepsia with macrocytic anemia. The patient's medical history taking in Binswanger disease--diagnosed 5 aa before-, epilepsy-2 aa before- and a previous episode of TVP of the left leg, suggested the hypothesis that a B12 deficiency, by a chronic gastritis, would involve an increase of homocysteine cause of the clinical manifestations of megaloblastic anemia, Binswanger disease, tardive epilepsy and previous TVP. The fisic and blood and instrumental exams confirmed the clinical diagnosis. The patient is having vitamin B12.