Acquired Hemophilia in an Elderly Patient with Non-Small Cell Lung Cancer: a Case Report.

Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies against coagulation factor VIII and characterized by spontaneous hemorrhage in patients with no previous family or personal history of bleeding. We report here a case of AHA that occurred in the Department of Medicina D'Urgenza in Sant'Andrea Hospital in a patient with previous diagnosis of NSLC. The aim of this article is to allow a more comprehensive knowledge of AHA that both for the rarity and the poor literature is underdiagnosed; for all these reasons, it is important that different specialists, like emergency specialists, experts in internal medicine, hematologists, and oncologists, acquire a more complete knowledge of the clinical and laboratory features of this disease, allowing an early diagnosis crucial for the evolution of the coagulopathy.

The evaluation of the intracavitary effusions by a bedside ultrasound examination.

OBJECTIVE: This study aims to evaluate the bedside use of the pocket-sized ultrasound (US) device for the detection of the intracavitary effusions. METHODS: We randomly enrolled 40 patients admitted to S. Andrea Hospital of Rome. Every patient received a clinical and biochemical evaluation and a bedside US examination to detect and estimate the intracavitary (pleural, pericardial and intra-abdominal) effusions; the US measurements have been compared to the computed tomography (CT) scans (as gold standard). RESULTS: The patients presented a high prevalence of effusions: right pleural 16/40 = 40% (esteemed volume 236.3±500.7 ml, mean±standard deviation m±SD), left pleural 8/40 = 20% (127.0±377.4 ml), pericardial 12/40 = 30% (47.5±72.8 ml) and intra-abdominal effusions 5/40 = 12.5% of cases (110.9±600.6 ml). Linear regression analysis showed a significant correlation between US and CT measurements: pleural r = 0.973 p <  1×10-38, pericardial r = 0.927 p <  1×10-39, intra-abdominal space r = 0.921 p <  1×10-59. The accuracy of the bedside US at the pleural, pericardial and abdominal level was respectively 98%, 93% and 96% (Cohen's kappa coefficient 0.966, 0.841 and 0.833). CONCLUSIONS: The present study showed a high prevalence of the intracavitary effusions and a high accuracy of the bedside US. The bedside US by a pocket-sized device is promising tool for its advantages of reproducibility and non-invasiveness of the device.

The cortisol burden in elderly subjects with metabolic syndrome and its association with low-grade inflammation.

BACKGROUND: Elderly people are exposed to an increased load of stressful events and neuro-hormonal stimulation is a key finding in metabolic syndrome and its related disorders. AIMS: To determine the role of cortisol in elderly subjects, with or without metabolic syndrome (MetS), by means of a national multicentre observational study, AGICO (AGIng and Cortisol). METHODS: From 2012 to 2017, the AGICO study enrolled n.339 subjects (aged > 65), after obtaining their informed consent. The investigators assessed a cardio-metabolic panel (including electrocardiogram, carotid ultrasonography and echocardiography), the presence of MetS (on Adult Treatment Panel III criteria), a neurological examination (including brain imaging), and cortisol activity (using a consecutive collection of diurnal and nocturnal urine). RESULTS: In the patients presenting with MetS, the standardized diurnal and nocturnal cortisol excretion rates were 210.7 ± 145.5 and 173.7 ± 118.1 (mean ± standard deviation) µg/g creatinine/12 h; in those without MetS, the standardized diurnal and nocturnal cortisol excretion rates were 188.7 ± 92.7 and 144.1 ± 82.3 µg/g creatinine/12 h, respectively (nocturnal urinary cortisol in patients with MetS versus those without MetS p = 0.05, female patients with MetS vs female patients without MetS, p < 0.025). A significant positive correlation was found between the CRP levels and both the diurnal and nocturnal urinary cortisol levels with r = 0.187 (p < 0.025) and r = 0.411 (p < 0.00000001), respectively. DISCUSSION: The elderly patients with MetS showed a trend towards increased standardized nocturnal cortisol excretions, with particular regard to the female subjects. CONCLUSION: The positive correlation between cortisol excretion and low-grade inflammation suggests a common mechanism driving both hormonal and inflammatory changes.

Hypovitaminosis D: comparison between patients with hip fracture and patients with vertebral fractures.

This study analyses the difference in 25OH-vitamin D values between two groups of patients both affected by severe osteoporosis with fragility fractures, but one group has vertebral fractures and the other one has hip fractures. Patients with hip fractures have vitamin D values lower than patients with vertebral fractures. INTRODUCTION: The purpose of this study was to evaluate 25OHD levels in patients with fragility vertebral fractures (VF) and hip fractures (HF) and make a comparison between the groups. METHODS: In the first group were enrolled ambulatory patients with 3 or more moderate to severe VF; in the second group were enrolled patients hospitalized in the Department of Orthogeriatrics undergoing surgery for HF. For all patients, we collected values of 25OHD and PTH. The group of patients with VF was further subdivided into pre-existing VF or recent VF treated within 30 days with vertebroplasty. RESULTS: The sample consists of 180 subjects divided into two groups: 90 with VF and 90 with HF. The average value of 25OHD in the total sample was 13.2 ± 9.6 ng/ml, Vitamin D was significantly lower in the HF group than the VF group (p < 0.001)(VF 18.6 ± 9.7 ng/ml, HF 7.9 ± 5.7 ng/ml). The mean PTH value in the total sample was 67.5 ± 54.9 pg/ml and PTH was significantly higher in the HF group compared to the group with VF (p < 0.001) (VF 55.6 ± 27.2 pg/ml, HF 78.7 ± 70.2 pg/ml). The mean 25OHD value in the recent VF group is 16.0 ± 6.6 ng/ml while in the pre-existing VF group is 19.5 ± 10.4 ng/ml with a statistically significant difference (p < 0.001). CONCLUSIONS: Patients of the same age with severe osteoporosis have a lower 25OHD value when the fracture occur at the hip and is recent, probably this is due to the inflammation caused by fracture and/or surgical intervention.

Screening of frailty in elderly patients with disability by the means of Marigliano-Cacciafesta polypathology scale (MCPS) and Canadian Study of Health and Aging (CSHA) scales.

Frailty is an age-related condition, characterized by a decreased homeostatic reserve and increased vulnerability to stressful events, with high risk of adverse outcomes. The aim of this study was to compare the evaluation of the frailty by the means of the MCPS and the Rockwood criteria. We enrolled 98 patients (mean age ± standard deviation, m ± SD, 80.7 ± 7.0 years) and 20 controls (82.7 ± 3.4 ys), who attended our outpatient clinic for the evaluation of disability and the renewal of driving license, respectively. The multidisciplinary geriatric assessment (MGA) was performed including the administration of the following scales for frailty: MCPS scale (range 0-245), CSHA-Rules-Based Definition of Frailty (CSHA-RBDF) (range 0-3) and CSHA-Clinical Frailty Scale (CSHA-CFS) (range 0-7). The patients and controls showed MCPS=52.39 ± 11.36 and 4.6 ± 3.28, CSHA-RBDF=2.27 ± 0.62 and 0.10 ± 0.44, CSHA-CFS=6.22 ± 0.75 and 2.95 ± 0.51, respectively (p<0.000001). Frailty scores were higher in female than in male (p=0.065 for CSHA-RDBF and p<0.05 for CSHA-CFS). The MCPS scores were significantly related to both CSHA-RDBF (r=0.753, p<0.001) and CSHA-CFS scores (r=0.793, p<0.001). The frailty scales were significantly related to disability, cognitive impairment and polypathology. In conclusion, the frail patient may be a carrier of multiple chronic pathologies and/or of physical/cognitive decline. The frail patient has to be considered the elective geriatric patient, characterized by a continuous multidimensional care requirement. MCPS is an useful tool for the frailty screening and to set up a tailored program of geriatric rehabilitation, in order to prevent or reduce the development of frailty-related complications.

Sex steroids in autoimmune diseases.

A sexual dysmorphism in the immune response has been described and females display an increased incidence of autoimmune diseases. Experimental data show that sex steroids influence immune cell development and have immunomodulatory effects. The distribution, the action (genomic and nongenomic), the sex and tissue-depending expression pattern of estrogen, progesterone and androgen receptors and their functional disruptions in corresponding receptor knockout animals will be discussed, pointing out the difference among sex steroid hormones. Recent advances indicate an immunomodulatory role of sex steroids in the pathogenesis of systemic lupus erythematosus, multiple sclerosis and rheumatoid arthritis. The outcomes of the clinical trials will help to find the best use of sex steroids in combination with current therapeutic drugs in autoimmune diseases. Sex steroid receptor modulating drugs will provide new therapeutic approaches in these pathologies.

The evaluation of the presence of comorbidity by the Marigliano-Cacciafesta polypathology scale (MCPS) and the cumulative illness rating scale (CIRS) in elderly subjects with disability.

Multiple factors associated with the frailty syndrome may be involved in the appearance of disability, including the presence of comorbidity. The CIRS is commonly used for the evaluation of comorbidity, consisting of two parts: the comorbidity index (CI) and the severity index (SI). A multidimensional scale, the MCPS, has been recently developed, predicting the risk to develop disability. Fifty-nine subjects were examined by a structured multidimensional geriatric assessment. The MCPS and CIRS was significantly correlated (r=0.410; p<0.01 with the CI; and r=0.443, p<0.001 with the SI). The patients were divided in two groups, according to the MCPS score. The mean activities of daily living (ADL) and instrumental activities of daily living (IADL), as well as the corrected mini-mental state examination (MMSE) score (+/-S.E.M.) were: 3.19+/-0.26; 0.28+/-0.04 and 24.00+/-1.14 in moderate-severe polypathology (n=21); 2.16+/-0.22; 0.13+/-0.02 and 21.23+/-0.72 in severe polypathology (n=38) (p<0.001, p<0.01 and p<0.05), respectively. The MCPS score was correlated with the main indices of disability. In conclusion, we found that the MCPS is a useful tool in order to quantify and classify the presence of comorbidity, with results significantly related to that obtained with the CIRS. The MCPS offers an important stratification of the patients on the base of a well-established classification, not supplied by the CIRS.

Sex-related variations in serum nerve growth factor concentration in humans.

A role of nerve growth factor (NGF) in the neuro-endocrine-immune interactions has been recently suggested by the presence of NGF and its receptors in cells of the immune and endocrine systems. The improvement in the comprehension of the role played by NGF in humans is linked to the availability of a sensitive and reliable method to quantify NGF concentrations in body fluids and tissues. As a consequence of different methods used, normal levels of human serum NGF reported in the literature show wide differences. The present results indicate that ELISA appears very sensitive (detection limit 1.4pg/ml) and allows the discrimination of subtle variations of serum NGF concentrations. ELISA performed in serum obtained from men indicated that NGF concentration was 40.8+/-10.8pg/ml, whereas women showed significantly lower levels that were influenced by the menstrual cycle. In particular, the mean value of this neurotrophin during the follicular phase was 8.2+/-1.4pg/ml; the luteal phase, in turn, showed levels up to 14.4+/-2.9pg/ml. The difference of serum NGF concentrations between the follicular and luteal phase in each woman was statistically significant. Differences in NGF concentrations between men and women (in both phases of the menstrual cycles) were also statistically significant. In conclusion, a possible role of sex steroids as modulators of NGF secretion in humans is strongly supported by the present paper. However, mechanisms underlying this phenomenon are still unknown. The evidence indicating physiological sex hormone-related variations in NGF levels would be of interest in view of the possible use of circulating NGF modifications as a laboratory biomarker in different diseases.

High incidence of hyperandrogenism-related clinical signs in patients with multiple sclerosis.

A mild prevalence of multiple sclerosis (MS) is present in females (2:1). To elucidate the pathogenetic role of sex steroids on the disease, we studied 76 women affected by MS, compared to 50 healthy women (mean age +/- SD, 34.9 +/- 0.9 vs. 33.4 +/- 1.7 years). The menarche was at mean age of 12.3 +/- 0.2 vs. 12.4 +/- 0.2. Interval between menses was 28.0 +/- 0.3 vs 27.8 +/- 0.3 days, with duration of menstrual flow of 5.0 +/- 0.2 vs. 5.0 +/- 0.2 days. Oligo- or amenorrhea was present in 20% of patients and in 16% of controls. Oral contraceptives were assumed by 21% of patients and 34% of controls (n.s.). Premenstrual symptoms were found in 43% of patients and in 46% of controls (n.s.). The incidence of hyperandrogenism (greasy skin, acne and hirsutism), evaluated by a specific questionnaire, was higher and statistically significant in MS patients than in controls (28% vs. 10%, p<0.05). Further studies, including a complete clinical and laboratory evaluation of gonadal function, are necessary in order to clarify whether hyperandrogenism may influence MS disease activity.

Hashimoto's disease during interferon-alpha therapy in a patient with pre-treatment negative anti-thyroid autoantibodies and with the specific genetic susceptibility to the thyroid disease.

OBJECTIVES: The authors described a case of Hashimoto's disease during interferon-alpha (IFN-alpha) treatment for chronic viral C hepatitis in a patient with the specific genetic susceptibility associated with the thyroid disease. RESULTS: A 60-year-old woman with chronic active viral C hepatitis (HCV genotype = 3a) started IFN-alpha therapy in November '96. Before treatment thyroid function tests were normal and anti-thyroid (anti-thyroglobulin and anti-thyroid peroxidase) Abs were negative. During IFN therapy, serum aminotransferases fell within the normal range and viremia (serum HCV-RNA) became negative after one year. After 20 months, the patient presented clinical features of primary hypothyroidism. Anti-thyroid Abs were found positive. Hormonal, ultrasonographic, radioiodine scanning and fine needle aspiration findings were consistent with the diagnosis of Hashimoto's thyroiditis. The tissutal typing of the patient showed the presence of Human Leukocyte Antigen (HLA) DRB1*11 gene (corresponding to DR5 antigen). IFN-alpha therapy was suspended and a treatment with l-T4 started. Chronic viral infection relapsed after the suspension of the IFN-alpha therapy. CONCLUSIONS: This case report showed that the clinical appearance of Hashimoto's disease after IFN-alpha therapy for chronic C hepatitis in our patient was associated with a specific genetic predisposition (DR5) for this pathology. Further studies are necessary to evaluate whether the study of HLA antigens may be a very useful tool to detect the patients with a predisposition to develop autoimmune thyroiditis, in order to make a early diagnosis of thyroid disorders during the IFN-alpha treatment.

Thyrotoxicosis, unstable angina and normal coronary angiogram.

It is well known that thyrotoxicosis may elicit acute myocardial ischemia even in patients with angiographically normal coronary vessels. The involved mechanisms are not clearly defined although some hypothesis have been suggested. We report a case of a 54-year-old woman affected by Graves' disease with thyrotoxicosis which was referred to our Institute because of unstable angina. During hospitalization a two dimensional echocardiogram, performed during chest discomfort, showed left ventricular apical akinesis and impaired global systolic function. A subsequent coronary angiography revealed normal epicardial vessels. She was successfully treated with high-dose methimazole and propranolol and a repeat echocardiogram evaluation showed normalization of left ventricular systolic function. Six months later, because of the appearance of paroxysmal atrial fibrillation, the patient underwent total thyroidectomy and a substitutive therapy with L-T4 (100 micrograms/die) was started. The authors review the possible mechanisms involved in the pathogenesis of myocardial ischemia during thyrotoxicosis.

MRI in multiple sclerosis during the menstrual cycle: relationship with sex hormone patterns.

We investigated MRI activity in MS during the menstrual cycle in relation to physiologic sex hormone fluctuations. Eight women with relapsing-remitting MS were submitted to serial brain gadolinium-enhanced MRI examinations over a 3-month period in two alternate follicular and luteal phases of the menstrual cycle. The ratio of progesterone/17-beta-estradiol during the luteal phase was significantly associated with both number (r = 0.6, p = 0.03) and volume (r = 0.7, p = 0.009) of enhancing lesions, providing support for a role of these hormones as immunomodulatory factors in MS.

Effect of r-interferon alpha administration on hypothalamus-pituitary-thyroid axis in chronic hepatitis.

Recent studies pointed out the development of autoimmune thyroid diseases during interferon (IFN) therapy, mainly in patients with positive thyroid autoantibodies (MsAb and TgAb) before treatment. The effects of recombinant human IFN alpha (rhIFNalpha) on thyroid function and thyroid autoantibodies were studied in 12 patients with chronic active hepatitis associated with virus B or C, selected on the basis of negative results for MsAb and TgAb. No significant variation in T3, T4 and TSH levels was observed either after the first administration of rhIFN alpha (3 million IU i.m.) or after three months of therapy (3 million IU i.m. 3 times a week). TSH response to TRH was in the normal range either before or after the therapy. The absence of MsAb and TgAb was confirmed in all the patients at the end of the treatment. These results indicate that no patient developed thyroid disorder during IFN therapy. Nevertheless, since positive MsAb and TgAb have been considered as a risk factor for thyroid diseases, in patients selected for IFN therapy they should be carefully assessed for autoantibodies before undergoing IFN treatment.

Subacute thyroiditis during interferon-alpha therapy for chronic hepatitis C.

A 34-year-old woman with chronic hepatitis C received interferon-alpha (IFN-alpha) therapy. Her thyroid function was normal and thyroid autoantibodies were negative before treatment. Four months after the beginning of the therapy she presented a clinical course of thyroiditis with a transient thyrotoxicosis. The diagnosis of subacute thyroiditis was confirmed by laboratory, ultrasonography, radioiodine scanning and fine needle aspiration findings. Thyroid autoantibodies were persisting negative. She suspended IFN-alpha therapy and she started non steroidal anti-inflammatory agents and beta-blockers. Latent hypothyroidism subsequently developed, but L-thyroxine therapy resulted in a rapid normalization of thyroid function tests.

Hormonal and metabolic effects of transdermal estradiol/progestagen administration in postmenopausal women.

OBJECTIVE: To evaluate the effects on hormonal and metabolic variables and bone density of a transdermal system delivering estrogen and progestagen. DESIGN: Twenty-one patients were included in the study and randomly assigned to the following treatments: group A was treated with transdermal 17 beta-estradiol, 50 micrograms/day (Estraderm TTS 50), from the first to the fourteenth day of the cycle and with a transdermal combination of 17 beta-estradiol (50 micrograms/day) and norethisterone acetate (NETA) 250 micrograms/day during the following 14 days; group B was treated with Estraderm TTS 50 from the first to the twenty-eighth day, adding oral medroxyprogesterone acetate (MPA), 10 mg/day, during the final 14 days. DHEAS, testosterone, SHBG, prolactin, gonadotropins, and estrogens were measured in basal conditions and after 6 months' therapy. In the same schedule, lipid patterns (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides), phosphocalcium variables (osteocalcin, calcitonin, parathormone), and bone mineral density were also studied. RESULTS: Both treatments were efficient in reducing menopausal symptoms. An increase of DHEAS (P < .05) and a decrease of FSH and LH (P < .02, < .01, respectively) were observed in group B. No significant modifications in lipid and lipoprotein metabolism were shown in either group after 6 months. The calcium-regulating hormone osteocalcin (BCG) decreased significantly (P < .05) only in group A; calcitonin, parathormone, and bone density were unchanged after treatment. CONCLUSION: Transdermal administration of estrogen plus progestagen reduces menopausal symptoms, but does not induce changes in metabolic variables and hormonal levels (androgens and prolactin).

Neuroendocrinoimmunology.

Interest in neuroendocrinoimmunology has increased greatly in the last decade. The most important evidence of neuroendocrine-immune system interactions is that spleen, thymus, bone marrow and lymph nodes are innervated by neurons of the autonomic nervous system; changes in brain functions can affect different immune responses; immune and neuroendocrine cells share receptors (e.g., lymphocytes and macrophages have receptors for a vast number of hormones and neuropeptides); hormones and neuropeptides can alter the functional activity of immune system cells; several hormones and neuropeptides can be synthesized by leukocytes; cytokines produced by leukocytes are able to modulate neuroendocrine system activity, behaviour, sleep and thermoregulation. The recent literature on neuroendocrinoimmunology has laid the physiopathological groundwork for a new clinical approach which perceives and treats the patient as a psychic and somatic whole.