Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.

Sjögren's syndrome with anticentromere antibodies.

Clinical and laboratory findings in 10 women with Sjogren's syndrome and positive anticentromere antibodies were compared to those in 50 patients with Sjögren's syndrome and typical serologic features. The anticentromere antibody-positive patients were more likely to have Raynaud's phenomenon and less likely to have leukopenia polyclonal hypergammaglobulinemia, rheumatoid factor, and anti-SSA/Ro antibody. Four anticentromere antibody-positive patients developed limited cutaneous scleroderma during follow-up, but none had lymphoma; some of the other patients in this group exhibited stable symptoms typical for Sjögren's syndrome. Among our overall population of Sjogren's syndrome patients who met diagnostic criteria for primary Sjogren's syndrome at the first evaluation, 16.6% tested positive for anticentromere antibodies.

A case of parvovirus-B19 adult acute arthritis with some allergic disease clinical features.

A 31-year old woman suddenly presented arthralgias at wrists, knees and feet, swelling of eyelids and the upper lip, itching behind the ears, fever and macular rash on the extensory surface of legs, face and back. Signs and symptoms were strongly suggestive of an allergic reaction but human Parvovirus-B19 serology was positive, IgE serum levels were normal, skin prick tests and RAST for aliments were negative. Joint symptoms and swelling diminished in about four weeks. The relationship between the clinical manifestation of Parvovirus-B19 infection and features of allergic diseases is discussed.

Finger skin temperature in patients affected by Raynaud's phenomenon with or without anticentromere antibody positivity.

We evaluated finger skin temperature in 36 patients affected by Raynaud's phenomenon with or without anticentromere antibody positivity. The temperature measured under basal conditions and after dipping the finger in water at 10 degrees C for 5 min was similar in both groups; the temperature at the end of an 18-min recovery period was significantly lower in anticentromere antibody positive patients. This observation suggests a persistent digital vasospasm after the cold test in patients suffering from Raynaud's phenomenon with anticentromere antibody positivity. This autoantibody seems to identify a subgroup of patients affected by Raynaud's phenomenon with a severe involvement of the microcirculation.

Anticentromere antibody--clinical associations. A study of 44 patients.

The objective of this study was to determine the clinical features of 44 patients with anticentromere antibody (ACA) positivity. We undertook a retrospective review of 44 ACA-positive patients (1 male and 43 females with a mean +/- SD age of 53.6 +/- 12.2 years). There were 25 patients with limited systemic sclerosis, 12 with Raynaud's disease, 2 with Sjögren's syndrome, 2 with systemic lupus erythematosus and 3 with polyarthritis. ACA was more frequently found in patients affected by limited systemic sclerosis with mild visceral involvement and in patients with Raynaud's disease. Moreover, ACA was detected in other connective tissue diseases that were characterized by an atypical autoantibody profile.

[Liver involvement in systemic lupus erythematosus]. / Interessamento epatico nel lupus eritematoso sistemico.

From the revision of the literature it emerges that liver disease in systemic lupus erythematosus (SLE) has been reported in 8 to 23% of the patients and usually is of modest clinical relevance. The incidence of liver abnormalities in 86 patients affected by SLE (9 men and 77 women, mean age 42.1 +/- 13.1 years) was therefore analysed. In our study, liver involvement was defined when at least two abnormal liver function tests in two different occasions were detected. Evidence of liver disease was found in 20 of our patients (23.2%); in 6 cases liver abnormalities were not directly caused by SLE: in 3 subjects the abnormalities found were induced by drugs, in 2 patients by infection and in the last one by fatty liver. In the remaining 14 cases (16.2%), whose hepatic involvement was really due to SLE, a higher frequency of positivity for anti-ds-DNA antibodies than in the other patients was observed (92.8% and 51.3% respectively in the two groups, p < 0.05). As not reported previously, these data suggest that liver disease is a prerogative feature of severe SLE. From our casistic in only 1 case the hepatic injury was the onset clinical manifestation of the disease and was clinically relevant as it was diagnosed as chronic active hepatitis. These observations therefore offer the opportunity to discuss the relationship between SLE and autoimmune hepatitis.

Immunological and clinical effects of intramuscular rIFN alpha-2a and low dose subcutaneous rIL-2 in patients with advanced malignant melanoma.

Fifteen patients with tumour recurrence following radical surgical excision of malignant melanoma were treated with a combination of interferon alpha-2a (rIFN alpha-2a) and interleukin-2 (rIL-2). Immunological monitoring (performed prior to therapy and on days 7, 21, and 28, of each course of treatment) showed significant changes of several parameters after rIFN alpha-2a and rIL-2 administration. A significant increase in cells expressing CD16 (cells bearing Fc receptor), CD25 (cells bearing IL-2 receptor), and CD56 (NK cells, activated lymphocytes), as well in levels of soluble IL-2 receptor, beta 2-microglobulin and neopterin was observed. Immunological changes were closely related to the injection of the biological agent and were more relevant during the first than the second cycle of treatment. rIFN alpha-2a and rIL-2 exerted a clear synergistic activity on the same immunological parameters. No major response was seen with the present approach: four subjects showed rapid progression of decrease during the first month of therapy, while of 11 patients who completed two courses of treatment, only five were considered in stable disease. In conclusion, our results suggest that a combination of rIFN alpha-2a and rIL-2, at dosages and schedules, used in this trial, was well-tolerated and immunologically active, but was clinically ineffective in the management of advanced melanoma.

[Myasthenia gravis, palindromic rheumatism and systemic lupus erythematosus. A clinical case report]. / Miastenia gravis, reumatismo palindromico, lupus eritematoso sistemico. Descrizione di un caso clinico.

We describe a case of a 59-year-old white woman, that first developed a myasthenia gravis picture, then palindromic rheumatism and, in the end, systemic lupus erythematosus. We have searched in the literature the common features and the differences between myasthenia gravis and systemic lupus erythematosus. In this report we emphasize the possible connection between palindromic rheumatism and autoimmune diseases.

Plasma and urinary growth hormone and insulin-like growth factor I in children with chronic renal insufficiency.

We investigated the plasma and urinary growth hormone (GH) levels, and plasma insulin-like growth factor (IGF-I) in 15 (8 prepubertal and 7 pubertal) subjects with chronic renal insufficiency. Four of our 7 pubertal patients had a short stature (standard deviation score from -2.7 to -4.0). Significantly increased plasma GH and IGF-I levels were found in pubertal subjects alone (p less than 0.05). The urinary GH levels was significantly increased in prepubertal and pubertal subjects (p less than 0.001 and 0.05, respectively). A significantly inverse correlation between urinary GH excretion and creatinine clearance was found (r = -0.55; p less than 0.05). Increased plasma GH, IGF-I and urinary GH levels seem to suggest a complex alteration of GH and somatomedin metabolism in central and peripheral (receptor) cells.

Male pseudohermaphroditism due to 3 beta-hydroxysteroid dehydrogenase-isomerase deficiency associated with atrial septal defect.

Male pseudohermaphroditism in a 6 month old boy, due to congenital 3 beta-hydroxysteroid dehydrogenase deficiency, associated with atrial septal defect, is reported. At 2 weeks he required therapy for severe dehydration and projectile vomiting. The parents were first cousins and one female sibling had died suddenly at 2 months. The patient presented with melanoderma, perineal hypospadias with testicles in a bifid scrotum and atrial septal defect (ostium secundum). Complete cytogenetic studies showed a 46,XY karyotype. Serum sodium ranged from 129 to 140 mEq/l and serum potassium from 5.1 to 4.6 mEq/l. Basal plasma hormonal studies showed normal androstenedione (delta 4A), decreased cortisol (F), slightly elevated ACTH, 17-hydroxy-progesterone (17-OH-P) and testosterone (T), and highly increased dehydroepiandrosterone-sulphate (DHEA-S) levels. ACTH stimulation increased and DXM suppression decreased the plasma levels of DHEA-S, 17-OH-P and T but not that of F; hCG stimulation during cortisone therapy did not change the levels of DHEA-S and T. Corticosteroid therapy normalized electrolyte levels and reduced melanoderma and hormonal hypersecretion. Moderately elevated plasma levels of 17-OH-P and T suggest a partial testicular 3 beta-HSD deficiency. The multifactorial inheritance and the relatively high prevalence of atrial septal defect vs the rarity of adrenal enzymatic defect suggest a causal association even if a common genetic factor cannot be excluded.