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.

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.

[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.

The interferon-induced Mx protein of chickens lacks antiviral activity.

cDNA sequencing revealed that chick Mx protein consists of 705 amino acids. Its 84 N-terminal amino acids show no significant sequence homology to other Mx proteins. They are followed by 514 residues that include a tripartite GTP binding consensus motif. This region shows 50-70% sequence identity to mammalian and duck Mx proteins. Sequences near the C terminus, including a leucine zipper motif, are also conserved, whereas the intervening 19 amino acids lack sequence similarity. This unique sequence corresponds to a highly variable region in mammalian Mx proteins, suggesting that it serves as a spacer between functional domains. Chick and mouse cells transiently transfected with cDNA expression constructs synthesized chick Mx protein at a level that could easily be detected with specific antibodies. Chick Mx protein in such cells was mainly cytoplasmic and had a granular appearance. Permanently transfected cell lines expressing high levels of chick Mx protein could not be established, suggesting low metabolic stability of chick Mx protein or incompatibility with cell proliferation. The antiviral activity of chick Mx protein was tested at the single-cell level using immunofluorescence techniques. Transfected cells expressing chick Mx protein showed no enhanced resistance to influenza A virus, vesicular stomatitis virus, Thogoto virus, or Sendai virus. Thus, chick Mx joins the list of Mx proteins without recognized antiviral activity, supporting the concept that Mx proteins serve unrelated functions.

Effects of dihydrotestosterone and hydroxyflutamide on androgen receptors in cultured human breast cancer cells (EVSA-T).

The purpose of our study was to evaluate the effects of 5 alpha-dihydrotestosterone (DHT) and hydroxyflutamide (HF), alone or in combination, on androgen receptor (AR) dynamics and on cellular growth in cultured breast cancer cells (EVSA-T). The incubation of cells with DHT increased the concentration of nuclear AR after 24 and 48 h. HF was also able to promote the nuclear accumulation of AR after 24 and 48 h of treatment. When HF-treated cells are incubated with DHT, the nuclear AR concentration is lower than that found in cells treated with DHT alone. We conclude that HF acts by increasing nuclear accumulation of receptor-antiandrogen complexes. Moreover, DHT stimulates cell growth while HF has an inhibitory effect. Thymidine incorporation in cells also increased after DHT treatment and decreased after HF incubation. The HF-induced inhibition of cell growth persisted both after renewal of the medium and after the addition of DHT to cultures. It may be hypothesized that either DHT is converted to inactive metabolites or that HF exerts a persistent inhibitory effect. In the latter case, the antiandrogen action of HF could be exerted by retention of high levels of antiandrogen in cells or by such a depressed protein synthesis that the renewal of growth is slower than the 48 h period studied.

The impact of obesity on hormonal parameters in hirsute and nonhirsute women.

The influence of obesity on sex hormone-binding globulin (SHBG) and androgen concentrations in hirsute and nonhirsute women has been evaluated. The study was performed in 226 hirsute women (88 obese and 138 non-obese) classified as being affected by polycystic ovarian syndrome (PCOS) or by idiopathic hirsutism (IH) and in 100 nonhirsute control women ([C] 60 lean and 40 obese). SHBG, free testosterone (fT), androstenedione (A), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), and gonadotropin levels were measured during the first week of the menstrual cycle by radioimmunoassay (RIA). A significant negative correlation between SHBG and body mass index (BMI) was observed in PCOS, IH, and C women. In obese women--whether PCOS, IH, or C-fT levels were significantly higher and, conversely, SHBG levels were lower than in non-obese women. A negative correlation between SHBG and fT was evidenced in each group. Upper-body obesity was associated with lower SHBG and higher fT levels than lower-body obesity. In conclusion, obesity, particularly upper-body obesity, is associated with a reduction in SHBG and an increase in fT in both nonhirsute and hirsute women.

Relationship between PRL levels and steroid receptors in breast cancer.

The role of PRL in human breast cancer is still debated. We examined 259 women undergoing surgery for breast cancer (K = 183) and for other diseases (n = 76). In all subjects blood samples were taken for the RIA assay of PRL, during the preanaesthesia. In the breast cancer specimens, estrogen (ER) and progesterone (PGR) receptors were assayed and T.N.M. was evaluated. PRL mean values were assayed and T.N.M. was evaluated. PRL mean values were found to be above the normal range in both groups. PRL values in ER+ and PGR+ were lower than in ER- and PGR-. We also divided the patients into two groups (PRL values greater than 50 or less than 50 ng/ml). The difference between the two groups was significant for ER (p less than 0.005) and PGR (p less than 0.05), using Student's unpaired t-test. Besides this, we observed a significant negative linear correlation between PRL values and receptor values. The finding of this correlation suggests that high PRL values could be associated with unfavourable prognosis in breast cancer.

Cytosolic and nuclear androgen receptors in colorectal adenomas.

The aim of this study was to verify the presence of androgen receptors (AR) in human colorectal adenomas and in normal adjacent mucosa, and to determine whether there is any difference in AR tissue content between females and males. Our data show higher levels of nuclear AR in normal mucosa than in adenomas (p less than 0.001). A significant difference was also present in males between normal and pathological tissue both in cytosolic (p less than 0.05) and nuclear receptors (p less than 0.01). In female subjects this difference was also evident, but not significant. Our results seem to support the hypothesis of protective effects of androgens in colonic mucosa.

[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.

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.

[Validity of contact thermography in breast diagnosis]. / Indicazioni sulla validità della termografia a contatto nella diagnostica mammaria.

Study has been carried out with "an plaque" thermographic method on 42 patients affected by carcinoma of the breast. From the data it's possible to distinguish two typical vascular findings: the greater anomalies and the smaller anomalies. With the above method we have had 92,85% positive test and 7,14% false negative tests for cancer. The value of these findings are discussed, first of all about their importance for diagnosis and prognosis of breast cancer.

[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.

Effects of fenfluramine and cyproheptadine on growth hormone secretion.

The behaviour of GH, its biological behaviour and response to insulin-induced hypoglycemia in obese and underweight patients, of ages varying from 10 to 39 years, was studied before and after treatment wie circadian course of the hormone following adminstration of either drug. Neither did pre-treatment with fenfluramine and cyproheptadine, No modification was noted in the circadian course of the hormaone following administration of either drug. Neither did pre-treatment with cyproheptadine modify the hormonal level in the stimulated test. It was, however, noted that pre-treatment with fenfluramine appears to influence the somatotropinic response to insulin-induced hypoglycemia, yet of different significance in children and adults.

[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.

[Non-neoplastic pathology of the last ileal ansa (anatomo-surgical problems)]. / La patologia non neoplastica dell'ultima ansa ileale (problemi anatomo-chirurgici).

The surgery of the last ileal ansa in case of non-neoplastic pathology bears some problems of technical nature, bound to the remarkable anatomic variabilities in the arterial blood supply to terminal ileum. The authors report the observation of three cases of non-neoplastic pathology of the last ileal ansa, treated with different technique in relation to the type of arterial blood supply remarked. In a case an ileum resection with termino-terminal anastomosis was performed, and in the other two cases a resection of the last ileal ansa, followed by an ileo-caecal reimplantation, was effected.

[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.

[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.

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.