Trends in severe outcomes in SARS-CoV-2-positive hospitalized patients with rheumatic diseases: a monocentric observational and case-control study in northern Italy.

Rheumatic disease patients are at greater risk of infection due to their disease, comorbidities, and immunosuppressive therapy. COVID-19 outcomes in this patient setting appeared to be similar to those of the general population. However, data on this topic were mainly related to small studies on a limited number of patients. Consequently, to date, this field remains poorly explored, particularly in the pre-vaccine era. This monocentric study aimed to describe the intrahospital mortality in rheumatic patients with SARS-CoV-2 consecutively hospitalized from 21 February to 31 December 2020, before anti-SARS-CoV-2 vaccine administration spread, compared with non-rheumatic patients. Of 2491 included patients, 65 [3%, median (interquartile range) age 75 (64.76-82.239 years, 65% women] were suffering from rheumatic diseases. A total of 20 deaths were reported [case fatality rate 31%, 95% confidence interval (CI): 19-42] compared with 433 deaths (19%, 95% CI: 17-20) in patients without rheumatic diseases (p=0.024). However, the rheumatic disease was not associated with a significant increase in univariate mortality hazards (hazard ratio 1.374, 95% CI: 0.876-2.154), and after adjustment (hazard ratio 1.199, 95% CI: 0.759-1.894) by age, sex and Charlson comorbidity index. The incidence of intensive care unit admission, death, and discharge in the case-control study was comparable between rheumatic and non-rheumatic patients. The presence of rheumatic diseases in SARS-CoV-2-hospitalized patients did not represent an independent risk factor for severe disease or mortality.

Open versus laparoscopic gastrectomy for advanced gastric cancer: a propensity score matching analysis of survival in a western population-on behalf of the Italian Research Group for Gastric Cancer.

BACKGROUND: Oncologic outcomes after laparoscopic gastrectomy for advanced gastric cancer in the West have been poorly investigated. The aim of the present study was to compare survival outcomes in patients undergoing curative-intent laparoscopic and open gastrectomy for advanced gastric cancer in several centres belonging to the Italian Research Group for Gastric Cancer. METHODS: Data of patients operated between 2015 and 2018 were retrospectively analysed. Propensity Score Matching was performed to balance baseline characteristics of patients undergoing laparoscopic and open gastrectomy. The primary endpoint was 3-year overall survival. Secondary endpoints were 3-year disease-free survival and short-term outcomes. Multivariable regression analyses for survival were conducted. RESULTS: Data were retrieved from 20 centres. Of the 717 patients included, 438 patients were correctly matched, 219 per group. The 3-year overall survival was 73.6% and 68.7% in the laparoscopic and open group, respectively (p = 0.40). When compared with open gastrectomy, laparoscopic gastrectomy showed comparable 3-year disease-free survival (62.8%, vs 58.9%, p = 0.40), higher rate of return to intended oncologic treatment (56.9% vs 40.2%, p = 0.001), similar 30-day morbidity/mortality. Prognostic factors for survival were ASA Score ≥ 3, age-adjusted Charlson Comorbidity Index ≥ 5, lymph node ratio ≥ 0.15, p/ypTNM Stage III and return to intended oncologic treatment. CONCLUSIONS: Laparoscopic gastrectomy for advanced gastric cancer offers similar rates of survival when compared to open gastrectomy, with higher rates of return to intended oncologic treatment. ASA score, age-adjusted Charlson Comorbidity Index, lymph node ratio, return to intended oncologic treatment and p/ypTNM Stage, but not surgical approach, are prognostic factors for survival.

Futility of abdominal drain in elective laparoscopic splenectomy.

PURPOSE: Despite the implementation of minimally invasive surgery and enhanced recovery protocols, the use of drain in elective splenectomy is still controversial. The aim of this study was to assess whether the abdominal drain can impact on short-term outcome after elective laparoscopic splenectomy. METHODS: This is a retrospective analysis of a consecutively collected database including all patients who underwent elective laparoscopic splenectomy in our institution between January 2001 and June 2019. Postoperative complications were defined according to a priori criteria and graded according to Clavien-Dindo classification. All complications that occurred during hospitalization or within 30 days after discharge were considered. Primary endpoint was postoperative morbidity, and secondary endpoint was postoperative hospital length of stay. RESULTS: One hundred and sixty-one patients were analysed. Intraperitoneal drain was placed in 75 (46.6%) patients. Postoperative complications occurred in 36 (22.4%) patients, while 8 (4.9%) patients had major complications. Median postoperative length of stay was 4 days. At multivariate analysis, only malignancy was significantly associated with the onset of complications (OR 3.50; 95% CI 1.1-11.0; p = 0.032). Malignancy, ASA > 2, conversion to open surgery, presence of drain and longer operation were significantly associated with prolonged length of stay. Patients with drain showed a greater unadjusted risk of abdominal collections (RR 10.32; 95% CI 1.3-79.6; p = 0.006). CONCLUSION: Abdominal drain did not reduce morbidity and prolonged the length of stay following elective laparoscopic splenectomy. Therefore, the present study does not support the routine use of drain in such procedure.

Amplified antigen-specific immune responses in HIV-1 infected individuals in a double blind DNA immunization and therapy interruption trial.

Immunotherapy in patients with HIV-1 infection aims to restore and broaden immunological competence, reduce viral load and thereby permit longer periods without combined antiretroviral treatment (cART). Twelve HIV-1-infected patients on cART were immunized on the skin with DNA plasmids containing genes of several HIV-1 subtypes with or without the addition of hydroxyurea (HU), or with placebo. The mean net gain of HIV-specific CD8+ T cell responses were higher and broader in the HIV DNA vaccine groups compared to non-vaccinated individuals (p<0.05). The vaccine-induced immune responses per se had no direct effect on viral replication. In all patients combined, including placebo, the viral set point after a final structured therapy interruption (STI) was lower than prior to initiation of cART (p=0.003). Nadir CD4 levels appeared to strongly influence the post-STI viral titers. After the sixth immunization or placebo, patients could stay off cART for a median time of 15 months. The study shows that HIV DNA immunization induces broader and higher magnitudes of HIV-specific immune responses compared to structured therapy interruptions alone. Although compromised by small numbers of patients, the study also demonstrates that well-monitored STI may safely function as an immunological read out of HIV vaccine efficacy.

Cross-clade immune responses to Gag p24 in patients infected with different HIV-1 subtypes and correlation with HLA class I and II alleles.

Individuals infected with different subtypes of HIV-1 (A, B, C, D, CRF01_AE and CRF02_AG) were analyzed for their antigen-specific immune response with respect to their HLA genetics. The p24 Gag protein was selected for analysis, since previous studies of the same cohort of patients had shown that almost 80% of these individuals responded to Gag peptides of subtypes A, B and/or C. A large number of Gag antigen-specific responses were recorded. Both previously recognized as well as new epitopes were identified, assumed to bind HLA classes I and/or II. Fifteen individuals showed class I cellular responses to T cell epitopes irrespective of the infecting virus subtype. For five individuals infected with subtypes A, B, D and CRF02_AG, new T cell epitopes are described. Responses related to the patient's class I alleles are frequent, and several new putative class II responses were found.

TSH-secreting adenomas: rare pituitary tumors with multifaceted clinical and biological features.

TSH-secreting pituitary adenomas (TSH-omas) are a rare cause of hyperthyroidism in clinical practice. As their diagnosis is often delayed, these tumors are mostly diagnosed as macroadenomas, preventing an effective and radical cure and leading to serious local and systemic comorbidities. In addition to neurosurgery, medical therapy with the effective and tolerable SS analogs is a fundamental tool for the treatment of TSHomas. We report 3 cases of TSH-macroadenomas which displayed different clinical presentations. All patients showed increased free-thyroid hormone levels with inappropriately normal (2 patients) or high (1 patient) TSH levels. Magnetic resonance imaging (MRI)/computed tomography (CT) evidenced a pituitary macroadenoma and octreoscan was positive in all patients. In the 2 patients who underwent neurosurgery, hormonal hypersecretion by the tumor normalized. Histology showed nuclear pleomorphism and fibrosis, whereas immunohistochemistry showed positivity for TSH and, in a lesser amount, for FSH. In one of these patient (case 1), however, the presence of a tumor remnant inside the left cavernous sinus prompted us, in accordance with the patient, to start therapy with octreotide- long-acting release. As the third patient had a cardiac comorbidity which contraindicated neurosurgery, he underwent satisfactory treatment with long-acting SS analogs alone which normalized thyroid hormone levels. In this case, previous treatment with amiodarone confused and delayed the correct diagnosis of TSH-oma. As a result of improved laboratory and morphological techniques, TSH-omas should currently be diagnosed in early stages, thus enabling most patients to be managed satisfactorily through a combined approach.

Primary "empty sella" in adults: endocrine findings.

Increasing evidence of impaired pituitary function in many subjects with primary empty sella (PES) has been reported. We conducted a retrospective analysis of our patients with PES, in order to ascertain presenting symptoms and endocrine status on diagnosis and during follow-up. Magnetic resonance imaging (MRI) of the pituitary leading to the diagnosis of PES was performed in 8 patients (5 F and 3 M, age: 60.1 +/- 3.3 years, M +/- SE; group 1) after the diagnosis of global anterior hypopituitarism (H), and in 20 patients (F, age 56.9 +/- 2.2 years, group 2) for other clinical reasons. Baseline determinations of pituitary and target gland hormones and of IGF-I were performed. GH response to GHRH plus arginine stimulation was also evaluated. Ten age- and BMI-matched subjects (7 F, 3 M, age: 53.0 +/- 4.0 years) with normal pituitary function served as controls (C). In group 1, the presenting symptoms leading to the diagnosis of H were consciousness disturbances, hyponatremia and chronic fatigue. The GH response to stimulation was absent (peak:1.0 +/- 0.3 ng/ml) and IGF-I levels (60.1 +/- 9.3 ng/ml) were significantly lower (p<0.001) than in C and group 2 PES patients. Among group 2 PES patients, the main presenting symptoms were headache and visual alterations. Baseline hormone levels proved normal in 17 subjects, while slight hyperprolactinemia was observed in 2 and hypogonadotropic hypogonadism in one. The GH response to stimulation (12.9 +/- 3.4 ng/ml) and IGF-I levels (141.7 +/- 12.0 ng/ml) were lower (p<0.05) than in C (GH: 33.4 +/- 8.8 ng/ml, IGF-I: 193.1 +/- 20.3 ng/ml). PES is a heterogeneous condition that ranges from hypopituitarism to various degrees of isolated GH deficiency, and which needs careful endocrine assessment, treatment and follow-up.

[Effect of long-term treatment with octreotide-lar in a TSH-secreting pituitary macroadenoma and secondary hyperthyroidism]. / Effetto del trattamento a lungo termine con octreotide-Lar in un caso di macroadenoma ipofisario TSH-secernente.

A 74 year-old man was admitted to the hospital for heart failure and atrial fibrillation episodes. He had been irregularly treated for hyperthyroidism during the previous 3 years, with poor control. Thyroid function evaluation showed secondary hyperthyroidism, with high free thyroid hormone levels and TSH inappropriately in the high-normal range (4.2 mU/ml), only slightly responsive to TRH-stimulation (6 microU/ml). Alpha-subunits were hyper-responsive to TRH stimulation (+123%). Thyroid autoimmunity tests were negative and ultrasonography evidenced a diffusely enlarged gland. Magnetic resonance (MR) imaging of the pituitary showed a macroadenoma. The patient underwent transphenoidal adenomectomy, and immunohistochemistry confirmed the diagnosis of a TSH-secreting pituitary macroadenoma. A moderate secondary hyperthyroidism was still present and a new MR evidenced residual disease, involving the right cavernous sinus. A (111)In-octreoscan revealed an increased captation in this area. The patient was treated with octreotide-Lar (20 mg/monthly), which normalized FT3, FT4 and TSH levels already after 3 months of therapy. This effect is still maintained at 42 months of treatment. MR imaging showed a reduction in the residual lesion after 18 months (>50% in comparison with postsurgical MR) and a further decrease after 36 months of treatment). This suggests that the antiproliferative effect on the adenomatous cells is progressive and continues over time. This patients did not receive radiotherapy, so this action is entirely due to the medical treatment. No significant side effects developed and the patient's compliance was good. He has not had further arrhythmic episodes.

Leydig cell tumour-induced bilateral gynaecomastia in a young man: endocrine abnormalities.

Among the various causes of gynaecomastia, testicular malignancies are an uncommon, life-threatening condition, which require prompt treatment. The case of a 26-year-old healthy man is described, who reported a 6-month painful bilateral gynaecomastia associated with secondary hypogonadism. Normal circulating 17beta-oestradiol (E2) levels showed an enhanced response to human chorionic gonadotrophin (hCG) testing, which led to a reduced testosterone (T)/E2 ratio. Both clinical and hormonal findings normalized following surgical exeresis of a left testicular mass, which proved to be a Leydig cell tumour (LCT) at histology. This report underlines the importance of ultrasonographic evaluation of the testes, whenever breast enlargement occurs in a healthy man, despite unremarkable findings on testicular examination. In addition, our case demonstrates that normal unstimulated circulating E2 levels do not allow the presence of a stromal testicular tumour to be ruled out and that the response of restored T levels to hCG testing can remain blunted up to 1 year after surgery. Finally, we claim that T/E2 ratio may be a useful tool in evaluating derangement of the endocrine milieu secondary to LCT.

[Severe postmenopausal hyperandrogenism due to an ovarian lipoid cell tumor: a case report]. / Descrizione di un caso clinico di severo iper-androgenismo postmenopausale dovuto a un tumore ovarico a cellule lipidiche.

The case of a 62-year-old woman with severe post-menopausal hirsutism is described. Her clinical history revealed regular menstrual periods until menopause at the age of 50, hysterectomy for fibromatosis at 58 years, non-insulin dependent diabetes mellitus, hypertension, obesity, severe hirsutism, which had developed in the previous 3 years, with a deeping of the voice. Examination showed android obesity, hypertension and severe hirsutism involving the face and the trunk. Endocrine evaluation pointed out regular adrenal function, serum total and free-testosterone in the adult male range, with normal androstenedione, DHEAS and 17OHP levels. Estradiol was slightly increased and LH and FSH were inappropriately low for her post-menopausal age. Computed tomography of the abdomen showed regular adrenal glands, and a radio-labeled cholesterol scan was negative. A further pelvic transvaginal ultrasonography revealed a small cystic formation near the right ovary and a slight increase in the size of the left ovary. The patient underwent bilateral ovariectomy. Histological examination showed a lipoid cell tumor within the left ovary. Immunohistochemical studies were positive for inhibin and cytokeratin. After surgery, serum testosterone fell to normal levels, gonadotropins increased to menopausal levels, confirming that the tumor was able to produce both LH, and FSH-inhibiting factors, and hirsutism greatly improved. Periodic hormonal tests remained normal and CT of the abdomen and pelvic ultrasonography did not show alterations at a 3 years follow-up.

Use of an artificial neural network to predict Graves' disease outcome within 2 years of drug withdrawal.

BACKGROUND: Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism, which can relapse in many patients after antithyroid drug treatment withdrawal. Several studies have been performed to predict the clinical course of GD in patients treated with antithyroid drugs, without conclusive results. The aim of this study was to define a set of easily achievable variables able to predict, as early as possible, the clinical outcome of GD after antithyroid therapy. METHODS: We studied 71 patients with GD treated with methimazole for 18 months: 27 of them achieved stable remission for at least 2 years after methimazole therapy withdrawal, whereas 44 patients relapsed. We used for the first time a perceptron-like artificial neural network (ANN) approach to predict remission or relapse after methimazole withdrawal. Twenty-seven variables obtained at diagnosis or during treatment were considered. RESULTS: Among different combinations, we identified an optimal set of seven variables available at the time of diagnosis, whose combination was useful to efficiently predict the outcome of the disease following therapy withdrawal in approximately 80% of cases. This set consists of the following variables: heart rate, presence of thyroid bruits, psycological symptoms requiring psychotropic drugs, serum TGAb and fT4 levels at presentation, thyroid-ultrasonography findings and cigarette smoking. CONCLUSIONS: This study reveals that perceptron-like ANN is potentially a useful approach for GD-management in choosing the most appropriate therapy schedule at the time of diagnosis.

[Genotypic sex and phenotypic sex: clinical, biochemical and molecular aspects in a patient with male hypogonadism and 46XX-45XO karyotype]. / Sesso genotipico e sesso fenotipico: aspetti clinici, biochimici e molecolari in un paziente con ipogonadismo maschile e cariotipo 46XX-45X0.

We report here the case of a patient with primary male ipogonadism, with small testes and deficient virilization of the external genitalia, but with 46XX, 45X0 karyotype. Hormonal determinations showed high LH and FSH and low testosterone levels. Ultrasonography confirmed the presence of small testes within the scrotum. Cytogenetic analysis demonstrated a female karyotype, with 90% 46XX, 10% 45X0 mosaicism. Using DNA probes for genes located on the Y chromosome, the presence of the "Sex-Determining Region" of the Y chromosome (SRY) was evidenced in the genomic DNA of this patient. By Fluorescence in Situ Hybridization (FISH), SRY locus was localized in the p terminal region of an X chromosome. SRY is the primary inducer of testis development; it acts as a transcription factor leading to a sequence of gene activations critical in the process of testicular differentiation and morphogenesis. A condition characterized by testicular development in subjects who lack a normal Y chromosome has been described; most of these patients are carriers of the short arm of the Y chromosome transferred to one of the two X chromosome, suggesting a form of X-Y paternal interchange. In our patient, the development of male gonade in the absence of an Y chromosome was explained by the demonstration of the SRY gene in an X chromosome.

[Pituitary pathology in elderly patients admitted in a division of internal medicine. Description of 3 cases]. / Patologia ipofisaria in anziani ricoverati presso una Divisione di Medicina Interna. Descrizione di tre casi.

Pituitary diseases are often unrecognized in the elderly, although if they can be at the basis of several pathological conditions. We report three clinical cases. Patient n. 1: 87 years old woman, in poor general condition. Thyroid function evaluation showed secondary hypothyroidism. Subsequent pituitary function evaluation demonstrated hypopituitarism with empty sella. The diagnosis was "hypopituitarism with secondary hypothyroidism and adrenocortical insufficiency, in empty sella" starting substitutive treatment with glucocorticoids and L-thyroxine, with improvement in her clinical conditions. Patient n. 2: 74 years old woman, with severe congestive heart failure. Her clinical history revealed hypothyroidism. An endocrine evaluation (in absence of therapy) demonstrated panhypopituitarism with secondary hypothyroidism and adrenocortical insufficiency in presence of empty sella. The patients was started on substitutive treatment and her conditions improved. Patient n. 3: 74 years old man with several atrial fibrillation episodes and hyperthyroidism. Thyroid function evaluation suggested secondary hyperthyroidism confirmed by the presence of a pituitary macroadenoma. The patient underwent surgical adenomectomy by trans-sphenoidal route. The clinical conditions of the patient improved, but a slight secondary hyperthyroidism was still present caused by the persistence of residual pathological tissue in the right cavernous sinus region confirmed by octreoscan suggesting the presence of a lesion endowed with somatostatin receptors. The patient was started on long acting octreotide treatment, which is still in progress. In conclusion, pituitary diseases pass often unrecognized in the elderly. Their prompt recognition and treatment can resolve dangerous situations for the patients.

Lymphocytic hypophysitis. Case report.

Lymphocytic hypophysitis is a very unusual disease typically observed in the peripartum period but found also in non-pregnant women or in men. We report the case of a 50-year-old woman with a five-year history of erithema nodosus for which was treated with variable doses of steroids. One year before admission the patient began to complain of headache, amenorrhea and rapidly progressive hypopituitarism. Magnetic resonance imaging showed an expanding sellar mass with homogeneous contrast enhancement while lacking the hyperintense signal of posterior lobe. The MRI findings and the history of autoimmune disease raised the suspicion of hypophysitis. The growth of the lesion and its unresponsiveness to the prolonged steroid therapy made surgery, which is both diagnostic and therapeutic, mandatory. The pathogenesis, diagnosis and management of this unusual clinical condition are discussed.

[Control measures in an influenza pandemic in Switzerland]. / Massnahmen bei einer Influenza-Pandemie in der Schweiz.

As an influenza pandemic is to be expected, contingency plans are being developed in industrialized nations. During the interpandemic phase the responsibilities are clearly defined and no shortage occurs with respect to vaccines and drugs. In contrast, a lack of material and of infrastructure must be expected in a pandemic which will stress public health and disrupt social and business life. This plan illustrates how with the available means we should attempt to the best possible primarily to reduce premature mortality, secondarily to diminish morbidity and to maintain essential public services and security. Options are described, for instance how an increased production of vaccine already during the interpandemic phase would probably reduce the impact of a pandemic.

Sobre un caso de lupus eritematoso sistémico en una mujer de 86 años / About a case of systemic lupus erythematosus in an 86 year-old woman

El LES afecta predominantemente a mujeres entre la segunda y quinta década de la vida.El comienzo de esta patología luego de los 80 años de edad es excepcional.Comunicamos el caso de un paciente que inicia el LES a los 86 años con el cuadro clínico de neumositis aguda grave, posterior desarrollo de glomerulonefritis y púrpura trombocitopénica y evolución rápidamente fatal.Se analiza la forma de presentación y evolución del LES en personas de edad avanzada en contraposición con los más jóvenes.Se llama la atención sobre la posibilidad del diagnóstico de LES en pacientes añosos, en los cuales el mismo no es habitualmente considerado

[Carpal tunnel syndrome as initial manifestation of polymyalgia rheumatica]. / Síndrome del túnel carpiano como manifestación inicial de polimalgia reumática.

A case of polymyalgia rheumatica with atypical manifestations, including carpal tunnel syndrome, distal myalgias and a low eritro sedimentation is reported. The association of polymyalgia rheumatica and carpal tunnel syndrome is controversial. Although it has been reported previously in a recent and large review of carpal tunnel syndrome in Rochester, USA, there was not any more cases of polymyalgia rheumatica associated with carpal tunnel syndrome than in the general population. In our patient, the symptoms of polymyalgia rheumatica and of carpal tunnel syndrome were present at the beginning, and both responded satisfactorally to the treatment with methylprednisone. This form of presentation and its response to treatment suggest that the symptoms of carpal tunnel syndrome are caused by the inflammation of the carpal synovial, which is an unfrequent manifestation of polymyalgia rheumatica. We report this case for the purpose of altering to an unusual form of presentation of polymyalgia rheumatica in order to avoid unnecessary surgery for the carpal tunnel syndrome.