RESUMO
OBJECTIVE: To report cross-sectionally serum levels of 25-hydroxyvitamin D [25(OH)D] in women living in Italy within 12 months from breast cancer (BC) diagnosis. METHODS: Baseline data were obtained from 394 women diagnosed with primary BC, enrolled from 2016 to 2019 in a lifestyle trial conducted in Italy. Subjects' characteristics were compared between two 25(OH)D concentrations (hypovitaminosis D<20 and ≥20 ng/mL) with the Chi-squared test or Fisher's exact test for small-expected counts. Using multiple logistic regression-adjusted models, we estimated odds ratios (ORs) of hypovitaminosis D with 95% confidence intervals (CIs) in the total sample and in the unsupplemented subgroup. RESULTS: Hypovitaminosis D was found in 39% of all subjects, 60% in unsupplemented subjects, and 10% in supplemented subjects. Increasing ORs of hypovitaminosis D were found with increasing body mass index, 25-30, >30, and ≥35 versus <25 kg/m2 (ORs: 2.50, 4.64, and 5.81, respectively, in the total cohort and ORs: 2.68, 5.38, and 7.08 in the unsupplemented); living in the most southern Italian region (OR 2.50, 95%CI 1.22-5.13); and with hypertriglyceridemia (OR 2.46; 95%CI 1.16-5.22), chemotherapy history (OR 1.86, 95%CI 1.03-3.38), and inversely with anti-estrogenic therapy (OR 0.43, 95%CI 0.24-0.75) in the total sample. CONCLUSIONS: Hypovitaminosis D in women recently diagnosed with BC and participating in a lifestyle trial in Italy was widespread and highest with obesity, hypertriglyceridemia, and chemotherapy use. Considering that hypovitaminosis D is a risk factor for lower efficacy of bone density treatments and possibly BC mortality, our results suggest the need to promptly address and treat vitamin D deficiency.
Assuntos
Neoplasias da Mama , Hipertrigliceridemia , Deficiência de Vitamina D , Vitamina D , Feminino , Humanos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/complicações , Hipertrigliceridemia/complicações , Itália/epidemiologia , Estilo de Vida , Fatores de Risco , Vitamina D/análogos & derivados , Deficiência de Vitamina D/epidemiologiaRESUMO
PURPOSE: Bariatric surgery, as Roux-en-Y gastric bypass (RYGB), laparoscopic gastric banding (LGB), and laparoscopic sleeve gastrectomy (LSG), is considered the gold standard treatment to achieve long-term weight loss in severe obesity. In patients who fail to maintain the achieved weight, pharmacological treatment may be required. Here, we reported our real-life experience on the efficacy of liraglutide therapy in 62 patients who regained weight after bariatric surgery. METHODS: We retrospectively evaluated 62 (60 F-2 M; mean age: 43.6 ± 9.9 years) patients received liraglutide for weight loss after bariatric surgery (17 RYGB, 22 LGB, and 23 LSG). Body mass index (BMI) before and after surgery was, respectively, of 45.4 ± 5.5 kg/m2 and 29.5 ± 4.9 kg/m2. Patients were followed up from 2016 until 2021. Liraglutide was administered after weight regain once-daily subcutaneously at starting dose of 0.6 mg and with weekly increases up to 3.0 mg. Treatments were administered when a weight regain of 10-15% occurred after reaching a minimum weight loss from bariatric surgery or if weight loss after bariatric surgery was unsatisfactory. RESULTS: After a mean of 70.7 ± 43.7 months from any bariatric surgery, all patients started liraglutide therapy. At this time, mean BMI was 34.2 ± 4.8 kg/m2 (mean increased BMI: 4.7 ± 2.8 kg/m2). After a mean of 10.5 ± 4.4 months from the beginning of liraglutide, 9 patients achieved normal weight (BMI 24.1 ± 0.9 kg/m2), and 28 were overweight (BMI 26.9 ± 1.6 kg/m2). Twenty patients achieved grade I (BMI 32.1 ± 1.5 kg/m2), 5 grade II (BMI 37.3 ± 2.0 kg/m2) obesity, and none had grade III obesity (mean BMI change: - 5.1 ± 2.5 kg/m2). The treatment was well tolerated, and no serious adverse events were recorded. CONCLUSION: These data confirm the efficacy and safety of liraglutide in patients who experienced weight regain after bariatric surgery. Considering the long-term follow-up, patients should be followed up regularly and the pharmacological treatment should be adapted to the weight fluctuations observed during the clinical history. LEVEL OF EVIDENCE: V. Opinions of authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.
Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Adulto , Gastrectomia/efeitos adversos , Derivação Gástrica/efeitos adversos , Humanos , Liraglutida/uso terapêutico , Pessoa de Meia-Idade , Obesidade/etiologia , Obesidade Mórbida/tratamento farmacológico , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Aumento de Peso , Redução de PesoRESUMO
Belimumab, a specific inhibitor of the soluble B lymphocyte stimulator (BlyS), is the first biological drug approved by the United States Food and Drug Administration for the treatment of patients with active systemic lupus erythematosus (SLE) refractory to standard therapy. Given that an imbalance between regulatory T cells (Treg) and interleukin (IL)-17A-secreting T cells (Th17) has been reported in various autoimmune disorders, we assessed the frequency of both Treg and Th17 peripheral blood populations before and after belimumab administration in 20 patients with active SLE refractory to standard therapy. After six months of treatment, the mean SELENA-SLEDAI score as well as the mean anti-double-stranded DNA antibody titers were significantly decreased. In addition, we observed a significant increase in Treg percentages and a parallel, significant decrease in Th17 percentages, accompanied by significantly reduced serum levels of IL-21. In vitro studies showed that Treg purified from belimumab-treated patients were fully functional and displayed a suppressor function similar to that of Treg purified from healthy donors. Belimumab can restore Treg/Th17 balance in SLE patients with uncontrolled disease activity, and this results in decreased flare rate and reduced glucocorticoid dosage.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Fator Ativador de Células B/antagonistas & inibidores , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Adulto , Anticorpos Antinucleares/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Resultado do TratamentoRESUMO
PURPOSE: The incidence of neuroendocrine tumors (NETs) is progressively increasing. Most cases arise from the digestive system, where ileum, rectum and pancreas represent the commonest site of origin. Liver metastases are frequently detected at diagnosis or during the follow-up. Contrast-enhanced ultrasound (CEUS) is used in patients with pancreatic NETs (P-NETs) and liver metastases from P-NET but its role has not been standardized. The aim of this retrospective study was to investigate CEUS in patients with P-NETs and liver metastases from P-NET both as prognostic factor and predictor of response to therapy with somatostatin analogues (SSAs). METHODS: CEUS was performed at the diagnosis of NET and 3, 6 and 12 months after the beginning of SSAs. CEUS pattern was compared with contrast-enhanced computed tomography (CT) pattern. RESULTS: There was a significant association between CEUS and CT pattern (X 2 = 79.0; p < 0.0001). A significant association was found between CEUS pattern and Ki-67 index (X 2 = 24.6; p < 0.0001). The hypervascular homogeneous CEUS typical pattern was associated with low tumor grading (G1 or G2) (X 2 = 24.0; p < 0.0001). CEUS pattern changed from hypervascular homogeneous in baseline to hypovascular/hypervascular inhomogeneous after SSA therapy, with a significant association between tumor response at CT scan and appearance of hypervascular inhomogeneous pattern at CEUS evaluation (6 months: X 2 = 57.0; p < 0.0001; 12 months: X 2 = 49.8; p < 0.0001). CONCLUSIONS: In patients with P-NET, CEUS pattern correlates with tumor grading, being homogeneous in G1-G2 but not in G3 tumors. After therapy with SSAs, CEUS is predictive of response to SSAs. These findings seem to support a role of CEUS as prognostic and predictive factor of response.
Assuntos
Terapia Biológica , Meios de Contraste , Hormônio do Crescimento Humano/uso terapêutico , Neoplasias Hepáticas/secundário , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Ultrassonografia/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Prognóstico , Estudos RetrospectivosRESUMO
Acne is a common and complex skin disease, with a very complex pathogenesis. Although in women the relationship between acne and insulin resistance is well known, in particular in women with PCOS, in males this relationship has been poorly investigated. In total, 20 subjects with an altered metabolic profile were considered for this study and randomized as follows: 10 patients were treated with metformin plus a hypocaloric diet for 6 months (group A), while 10 patients did not receive any treatment with metformin and were only followed up (group B). All patients of group A, after 6 months of metformin therapy, had a statistically significant improvement compared with patients in group B. Our study reveals the importance of diet and insulin resistance in acne pathogenesis, and underlines the possible use of metformin and diet as possible adjuvant therapy for male patients with acne.
Assuntos
Acne Vulgar/terapia , Dieta Redutora , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Acne Vulgar/patologia , Adolescente , Adulto , Terapia Combinada , Glucose/metabolismo , Índice Glicêmico , Humanos , Insulina/metabolismo , Resistência à Insulina/fisiologia , Masculino , Adulto JovemRESUMO
Human leucocyte antigen (HLA)-G has a tolerogenic function and could play a role in the pathogenesis of immune-mediated diseases, including systemic sclerosis (SSc). The aim of this study was to evaluate HLA-G serum expression (sHLA-G) and the HLA-G gene 14 base pairs (bp) insertion/deletion (del(-)/del(+)) polymorphism in patients with Ssc, to search for possible associations with clinical and laboratory variables. sHLA-G was measured by enzyme-linked immunosorbent assay (ELISA) in sera from 77 patients with SSc and 32 healthy donors (HD); the 14 bp del(-)/del(+) polymorphism was evaluated by polymerase chain reaction (PCR) amplification of peripheral blood mononuclear cells (PBMC) genomic DNA. Receiver operating characteristics (ROC) analysis identified the HLA-G cut-off that best discriminated dichotomized clinical and serological variables, that was subsequently employed to subdivide SSc patients into HLA-G high (HLA-G(+)) and low (HLA-G(-)) profile groups. sHLA-G were not statistically different between SSc patients and HD, nor between distinct SSc autoantibody subsets. Subdividing SSc patients by HLA-G positivity or negativity yielded significant differences for the modified Rodnan skin score (mRss) (P = 0.032), 'general' (P = 0.031) and 'kidney' (P = 0.028) Medsger severity scores (MSS) and disease activity index, and especially Δ heart/lung (P = 0.005). A worse 'general' MSS (P = 0.002) and Δ heart/lung (P = 0.011) were more frequent in the low sHLA-G group. These two variables and mRss were associated with sHLA-G levels at logistic regression analysis. Treatment had no influence on sHLA-G. Moreover, a higher frequency of scleredema was detected in the del(+)/del(+) than the del(-)/del(+) group (P = 0.04). These data suggest modulatory effects of sHLA-G on SSc. Prospective studies are needed to investigate a role in predicting the disease course.
Assuntos
Antígenos HLA-G/sangue , Antígenos HLA-G/genética , Leucócitos Mononucleares/imunologia , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/imunologia , Feminino , Frequência do Gene , Antígenos HLA-G/imunologia , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Estudos RetrospectivosRESUMO
BACKGROUND: Somatostatin analogues (SSA) represent one of the main therapeutic option in patients affected with functioning well-differentiated neuroendocrine tumours (NETs). There are no studies specifically focusing on NETs associated with Multiple Endocrine Neoplasia type 1 (MEN1). AIM: To evaluate the efficacy of the long-acting SSA octreotide in MEN1 patients with early-stage duodeno-pancreatic NETs. PATIENTS AND METHODS: Forty patients with MEN1 were retrospectively evaluated. Twenty patients with evidence of one or more MEN1-related duodeno-pancreatic NETs < 20 mm in size (age range 26-61 years) were treated with octreotide long-acting octreotide (LAR) as first-line therapy. Treatment duration ranged 12-75 months. At the baseline radiological evaluation, multiple duodeno-pancreatic NETs (range 1-8, size 3-18 mm) were detected. RESULTS: An objective tumour response was observed in 10%, stable disease in 80% and progression of disease in 10% of cases. In six patients with abnormally increased CgA, gastrin and/or insulin serum concentrations, a significant clinical and hormonal response occurred in 100% of cases and was stable along the time. CONCLUSIONS: Therapy with SSA is highly safe and effective in patients with early-stage MEN1 duodeno-pancreatic NETs, resulting in long-time suppression of tumour and hormonal activity and 10% objective response. This suggests to early start therapy with SSA in patients with MEN1-related NETs.
Assuntos
Neoplasia Endócrina Múltipla Tipo 1/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Octreotida/uso terapêutico , Adulto , Diferenciação Celular , Progressão da Doença , Sistema Endócrino/fisiologia , Feminino , Gastrinas/sangue , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 1/complicações , Tumores Neuroendócrinos/complicações , Estudos Retrospectivos , Somatostatina/química , Fatores de Tempo , Resultado do TratamentoRESUMO
Severe pulmonary arterial hypertension (PAH) is rarely observed as the initial manifestation of systemic lupus erythematosus (SLE), and the diagnosis is often delayed. Here we present the case of a 32-year-old woman with severe PAH as the initial manifestation of SLE, who was successfully treated with mycophenolate mofetil and cyclosporine. This case offered the opportunity to critically review the epidemiology data, predictive markers, and pathogenic pathways of SLE-associated PAH (SLE-PAH) in relation to the currently available therapeutic options and to the main clinical trials of the last 10 years focused on the treatment of SLE-PAH. Mycophenolate mofetil and cyclosporine - currently used in the maintenance phase of the disease in certain clinical settings - should be considered, as an alternative to cyclophosphamide, in future clinical trials aimed at evaluating the most effective treatment of SLE-PAH at presentation.
Assuntos
Anticorpos Antifosfolipídeos/sangue , Ciclosporina/administração & dosagem , Endotelina-1/sangue , Hipertensão Pulmonar , Lúpus Eritematoso Sistêmico , Ácido Micofenólico/análogos & derivados , Fator Reumatoide/sangue , Adulto , Autoimunidade/efeitos dos fármacos , Biomarcadores/sangue , Ensaios Clínicos como Assunto , Diagnóstico Tardio/prevenção & controle , Gerenciamento Clínico , Hipertensão Pulmonar Primária Familiar , Feminino , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/imunologia , Hipertensão Pulmonar/fisiopatologia , Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Ácido Micofenólico/administração & dosagem , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Currently, sunitinib represents one of the therapeutic strongholds for renal cell carcinoma, but the criteria for treatment selection are lacking. We assessed the role of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) polymorphisms in the prediction of the clinical outcome in metastatic renal cell carcinoma (mRCC) patients. METHODS: A total of 84 tumour samples from mRCC patients receiving first-line sunitinib were tested for VEGF and VEGFR single-nucleotide polymorphisms (SNPs). The SNP results were correlated with progression-free survival (PFS) and overall survival (OS). RESULTS: Median PFS was 8.22 months, although whereas median OS was 32.13 months. The VEGF A rs833061 resulted significant in PFS (17 vs 4 months; P<0.0001) and OS (38 vs 10 months; P<0.0001). The VEGF A rs699947 was significant for PFS (18 vs 4 months; P=0.0001) and OS (37 vs 16 months; P<0.0001). The VEGF A rs2010963 was significant in PFS (18 vs 8 vs 2 months; P=0.0001) and OS (31 vs 36 vs 9 months; P=0.0045). The VEGR3 rs6877011 was significant in PFS (12 vs 4 months; P=0.0075) and OS (36 vs 17 months; P=0.0001). At multivariate analysis, rs833061, rs2010963 and rs68877011 were significant in PFS, and rs833061 and rs68877011 were independent factors in OS. CONCLUSIONS: In our analysis, patients with TT polymorphism of rs833061, CC polymorphism of rs699947, CC polymorphism of rs2010963 and CG polymorphism of rs6877011 seem to have a worse PFS and OS when receiving first-line sunitinib.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/genética , Indóis/uso terapêutico , Neoplasias Renais/genética , Polimorfismo de Nucleotídeo Único , Pirróis/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Sunitinibe , Resultado do TratamentoRESUMO
AIM: Primary hyperparathyroidism (PHPT) is one of main cause of morbidity in patients with multiple endocrine neoplasia type 1 (MEN1). Medical therapy with cinacalcet-hydrochloride may modify the therapeutic strategy of MEN1 related PHPT. We present an experience with cinacalcet-hydrochloride in two patients with MEN1 PHPT. METHODS: The study included two MEN1 patients belonging to the same family (a 50-year-old woman and her daughter aged 20 years) with PHPT secondary to multiple involvement of parathyroid glands and other MEN1 related tumors. As both patients refused to undergo parathyroid surgery, we decided to start medical treatment with cinacalcet at the dose of 30 mg/day, which was the first treatment for the youngest patient, while the oldest had already been treated with partial parathyroidectomy. Serum concentrations of PTH, calcium and phosphorus, 24-h urine calcium-to-creatinine ratio and renal-threshold-phosphate concentration were evaluated before and after therapy. RESULTS: Serum calcium and PTH levels were normalized after 1 and 6 months of therapy, respectively, and 60 and 54 months after the beginning of cinacalcet remained normal. Hypercalciuria, hypophosphoremia and renal-threshold-phosphate normalized during therapy with cinacalcet. At ultrasonography, parathyroid nodular lesion remained unchanged. Cinacalcet was well tolerated without occurrence of side effects. CONCLUSION: Cinacalcet seems to be highly effective in controlling PHPT in patients with MEN1 either in naïve patients or in those with postsurgical recurrence. If cinacalcet will be confirmed to ensure a long-time control of PHPT or even to prevent the development and progression of PHPT, this may led to modify the therapeutic strategy of MEN1 PHPT.
Assuntos
Calcimiméticos/uso terapêutico , Hiperparatireoidismo Primário/tratamento farmacológico , Hiperparatireoidismo Primário/genética , Neoplasia Endócrina Múltipla Tipo 1/complicações , Naftalenos/uso terapêutico , Adulto , Biomarcadores/sangue , Cálcio/sangue , Cinacalcete , Feminino , Seguimentos , Humanos , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/cirurgia , Pessoa de Meia-Idade , Mães , Núcleo Familiar , Hormônio Paratireóideo/sangue , Linhagem , Fósforo/sangue , Resultado do TratamentoRESUMO
The authors hypothesize a concept, Consumer Hypnotic-Like Suggestibility (CHLS), defined as an altered state of consciousness, as a state causing a tendency to respond positively to messages aimed at inducing consumers to make unplanned purchases. This study aims to investigate the associations of CHLS with interpersonal variables and compulsive purchasing--a frequent and uncontrollable preoccupation with buying or impulses to buy. A study was conducted on a sample of 232 subjects (n = 111 men; M age = 41 yr.), through the administration of a questionnaire, which measured: CHLS, compulsive purchasing, consumer susceptibility to interpersonal influence (the necessity to enhance one's image in the opinion of others through the consumption of products), and consumer atmospherics, i.e., environmental stimuli known to influence purchasing decisions. Modeling and mediation analyses suggested that internal and external drivers--Consumer Susceptibility to Interpersonal Influence and atmospherics--are positively related to CHLS which affects compulsive purchasing.
Assuntos
Comportamento de Escolha/fisiologia , Comércio/métodos , Comportamento Compulsivo/psicologia , Sugestão , Adolescente , Adulto , Meio Ambiente , Feminino , Humanos , Hipnose/métodos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
This research investigates the effects of mixed emotions on the positioning and on the intention to purchase different categories of branded products (i.e., Attractiveness-products, Expertise-products, and Trustworthiness-products), in relation to their main component of credibility (Ohanian, 1990). On the basis of a focus group (n = 12) aimed to identify the three branded products used as stimuli and a pre-test (n = 240) directed to discover emotions elicited by them, two studies (n = 630; n = 240) were carried out. Positioning and multiple regression analyses showed that positive and negative emotions are positively related with the positioning and the purchase intention of Attractiveness-products, and, respectively, positively and negatively related with those of Trustworthiness-products; whereas negative emotions are negatively associated with those of Expertise-products. Brand Emotional Credibility--i.e., the emotional believability of the brand positioning signals--may help to identify unconscious elements and the simultaneous importance of mixed emotions associated with different products to match consumers' desires and expectations.
Assuntos
Comportamento do Consumidor , Emoções/fisiologia , Marketing/normas , Adulto , Feminino , Humanos , Masculino , Projetos Piloto , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Lactate dehydrogenase (LDH) represents a predictive factor in colorectal cancer patients treated with the angiogenesis inhibitor PTK/ZK. We explored the role of pre-treatment LDH serum levels in colorectal cancer patients receiving first-line bevacizumab. METHODS: Metastatic colorectal cancer treated with first-line bevacizumab was eligible. A control group including all consecutive patients treated with chemotherapy alone was also considered. Pre-treatment LDH serum levels were collected for all cases. RESULTS: Median progression-free survival (PFS) in the control group for patients with high and low LDH levels was 4.2 and 8 months, respectively (P=0.0003). Median overall survival (OS) was 19.6 and 34.9 months for patients with high and low LDH levels, respectively (P=0.0014). In the bevacizumab group, partial responses were seen in 14 (58%) high-LDH and 8 (14%) low-LDH patients (P=0.0243), respectively, median PFS was 7.3 and 8.5 months, respectively (P=0.2), and median OS was 22 and 26.6 months, respectively (P=0.7). CONCLUSION: High LDH levels correlated with worse prognosis. Bevacizumab seemed capable of improving clinical outcome in this specific group of patients who usually present with an adverse natural history. The improved response rate also suggests a role for LDH as a predictive marker.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , L-Lactato Desidrogenase/sangue , Adulto , Idoso , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Bevacizumab , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/imunologiaRESUMO
Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.
Assuntos
Linfócitos B , Aprendizado de Máquina , Análise de Sequência de RNA , Análise de Célula Única , Linfócitos T , Transcriptoma , Células Cultivadas , Humanos , Especificidade de ÓrgãosRESUMO
Thyroid diseases are the commonest endocrine disorders in the general population. In most of the cases, they are consistent with benign conditions which may be asymptomatic or affect people at a variable extent. Since they often represent chronic conditions their prevalence increases by age and reaches in elderly the highest rates. Thyroid nodules are a common clinical finding. Most subjects with thyroid nodules have few or no symptoms. Thyroid nodules are more commonly non-functioning. However, in elderly, toxic multinodular goiter is the most frequent cause of spontaneous hyperthyroidism and often, it emerges insidiously from nontoxic multinodular goiter. Although autoimmune thyroiditis is the most common cause of hypothyroidism in elderly subjects, other causes, such as drugs, neck radiotherapy, thyroidectomy or radioiodine therapy, are frequently observed among these subjects. A small subset of medications including dopamine agonists, glucocorticoids and somatostatin analogs affect thyroid function through suppression of TSH. Other medications that may affect TSH levels are metformin, antiepileptic medications, lithium carbonate and iodine-containing medications. Other drugs can alter T4 absorption, T4 and T3 transport in serum and metabolism of T4 and T3, such as proton-pump inhibitors and antacids, estrogens, mitotane and fluorouracil, phenobarbital and rifampin. Amiodarone administration is associated with thyrotoxicosis or hypothyroidism. Thyroid cancer has similar characteristics in elderly as in general population, however the rate of aggressive forms such as the anaplastic histotype, is higher in older than younger subjects. Diagnosis of thyroid diseases includes a comprehensive medical history and physical examination and appropriate laboratory tests. A correct diagnosis of thyroid diseases in the elderly is crucial for proper treatment, which consists in the removal of medications that may alter thyroid function, in the use of levo-thyroxine in case of hypothyroidism, anti-thyroid drugs in case of hyperthyroidism and use of surgery, radioiodine therapy and percutaneous ablative procedures in selected cases. In conclusion, thyroid diseases in patients older than 60 years deserve attention from different points of view: the prevalence is different from the young adult; symptoms are more nuanced and makes difficult the diagnosis; age and comorbidity often force therapeutic choices and may limit safety and efficacy of therapy. Finally, in elderly patients for whom specific therapy is necessary, more gradual and careful therapeutic approach and close follow-up are recommended in order to minimize the alterations of thyroid function which are induced by many drugs commonly used in clinical practice.
Assuntos
Envelhecimento , Doenças da Glândula Tireoide , Idoso , Idoso de 80 Anos ou mais , Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/tratamento farmacológico , Hipertireoidismo/epidemiologia , Hipertireoidismo/etiologia , Hipotireoidismo/diagnóstico , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/epidemiologia , Hipotireoidismo/etiologia , Itália/epidemiologia , Prevalência , Fatores de Risco , Doenças da Glândula Tireoide/diagnóstico , Doenças da Glândula Tireoide/tratamento farmacológico , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/etiologia , Testes de Função Tireóidea , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/etiologia , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/tratamento farmacológico , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/etiologiaRESUMO
UNLABELLED: AM: Patients with Fabry disease (FD), a genetic disorder caused by lysosomal a-galactosidase-A enzyme deficiency and characterized by a systemic accumulation of globotriaosylceramides, present high prevalence of subclinical hypothyroidism. The pathogenic mechanism is thought not to be related to anti-thyroid autoimmunity and may be dependent by intra-thyroid lipid accumulation. In this study, it was investigated whether thyroid function recovers in FD after long-term enzyme replacement therapy (ERT). METHODS: Study population included 14 FD patients (7 females, 7 males, aged 21-62 years) and 14 sex- and age-matched normal subjects. Thyroid function was evaluated in each patient at baseline and after the beginning of ERT with rh-a-galactosidase-A (1 mg/kg/BW every 2 weeks) for three years. RESULTS: TSH levels were higher in FD patients than in controls (P<0.05). In FD patients, TSH levels were higher before than after ERT (1.9±0.2 vs 1.2±0.2 mU/L, P<0.01) while fT3 and fT4 levels were normal at baseline and unchanged after ERT. At baseline, TSH levels were >3 mU/L in three patients and normalize after ERT. Anti-Tg and/or anti-TPO titres were positive in 14% of patients and 21% of controls. After ERT, the rate of autoimmunity was unchanged. At the thyroid ultrasonography, a slight hypoechoic pattern was found in 71% of patients at baseline and decreased to 43% after ERT. CONCLUSION: Primary hypothyroidism in FD patients is reverted after long-term ERT. A screening of thyroid function and periodical re-evaluation during ERT is mandatory in all FD patients.
Assuntos
Terapia de Reposição de Enzimas , Doença de Fabry/sangue , Hipotireoidismo/sangue , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto , Algoritmos , Biomarcadores/sangue , Estudos de Casos e Controles , Terapia de Reposição de Enzimas/métodos , Doença de Fabry/complicações , Doença de Fabry/diagnóstico , Doença de Fabry/tratamento farmacológico , Doença de Fabry/enzimologia , Feminino , Humanos , Hipotireoidismo/diagnóstico , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/etiologia , Masculino , Pessoa de Meia-Idade , Testes de Função Tireóidea/métodos , Fatores de Tempo , alfa-Galactosidase/uso terapêuticoRESUMO
The B lymphocyte-associated antigen CD20 is becoming an important immunotherapy target for autoimmune diseases, although its biological function has not been defined. Besides rheumatoid arthritis, growing experience with B cell-depleting therapy indicates that it may be effective in Sjögren's syndrome, dermatomyositis-polymyositis, systemic lupus erythematosus and some types of vasculitides. However, controlled clinical trials are still lacking for some of these indications. Infection has not been seen as a major limitation to this therapy, but reports of progressive multifocal leukoencephalopathy in an extremely small number of patients are of concern. Here, we review the therapeutic actions of anti-CD20 antibodies, and the recent and ongoing clinical trials with CD20-depleting therapy in autoimmune diseases.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígenos CD20/imunologia , Doenças Autoimunes/tratamento farmacológico , Linfócitos B/imunologia , Fatores Imunológicos/uso terapêutico , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais Murinos , Doenças Autoimunes/imunologia , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/imunologia , Camundongos , Ensaios Clínicos Controlados Aleatórios como Assunto , RituximabRESUMO
OBJECTIVE: Crohn's Disease (CD) has been associated with non-Hodgkin lymphoma. Follicular Lymphoma (FL) limited to the liver is extremely rare, accounting for 1% to 4.4% of all Primary Hepatic Lymphoma (PHL). CASE PRESENTATION: In 2018, an 85-years old male patient with post-operative recurrence of ileal CD referred rare episodes of fever and mild diffuse abdominal pain. Since cholecystectomy in 2001, clinical history was characterized by recurrent episodes of cholangitis and common bile duct stones. In 2018, ultrasonography and MRI showed a solid focal hepatic lesion (FHL)(4.5 cm x 2.5 cm) in the IV hepatic segment. The radiographic aspect of the lesion was unusual. Initially, focal nodular hyperplasia was suspected. Clinical history of cholangitis and radiological findings subsequently suggested a diagnosis of Hepatic Abscess (HA). A progressive enlargement of the FHL (7.3 cm x 5.8 cm) despite antibiotic treatments, led to perform a liver biopsy. Histological and immunophenotypical analysis of the FHL (7.5 cm x 5.4 cm) enabled a final diagnosis of FL. The "in situ" hybridization for Epstein-Barr virus (EBER) was negative. No additional lesions related to FL were initially detected, thus suggesting a very rare case of PHL in an old patient with CD never treated with thiopurines. CONCLUSIONS: This case report highlights the need to consider a rare diagnosis of FL of the liver in patients showing a challenging focal hepatic lesion of unknown origin.
Assuntos
Doença de Crohn/diagnóstico , Neoplasias Hepáticas/diagnóstico , Linfoma Folicular/diagnóstico , Idoso de 80 Anos ou mais , Humanos , MasculinoRESUMO
Raynaud's phenomenon (RP) is a clinical disorder characterized by recurrent, reversible episodes of digital vasospasm. RP can be classified as primary (pRP) or secondary, depending on whether it occurs as a benign condition (not disease-associated) or is associated with other diseases, mainly of the connective tissues. In both cases, it can be triggered by environmental factors, as indicated by the increased incidence of pRP episodes following exposure to cold, vibration injury or chemicals. The purpose of this prospective case-control study was to assess, in an Italian cohort of 132 pRP patients, the association of the phenomenon with demographic, lifestyle habits, environmental and work-related factors. Compared to healthy controls, pRP was found to be inversely associated with the use of contact lenses (OR = 0.4; p = 0.004) and of chlorous-based disinfectants (OR = 0.3; p < 0.001) and directly associated with the presence of prosthesis implants (OR = 5.3; p = 0.001) and the use of hydrogen peroxide-based compounds (OR = 2.6; p = 0.002), suggesting that the latter should be avoided in RP affected patients. Multivariate and multivariable analysis confirmed the associations. Further investigations are needed to understand the mechanism(s) underlying these findings.
Assuntos
Lentes de Contato/estatística & dados numéricos , Peróxido de Hidrogênio/efeitos adversos , Próteses e Implantes/efeitos adversos , Doença de Raynaud/epidemiologia , Adulto , Estudos de Casos e Controles , Desinfetantes/química , Feminino , Humanos , Incidência , Itália/epidemiologia , Estilo de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Próteses e Implantes/estatística & dados numéricos , Doença de Raynaud/etiologiaRESUMO
We describe a model evaluating changes in the optical isolation of a Faraday isolator when passing from air to vacuum in terms of different thermal effects in the crystal. The changes are particularly significant in the crystal thermal lensing (refraction index and thermal expansion) and in its Verdet constant and can be ascribed to the less efficient convection cooling of the magneto-optic crystal of the Faraday isolator. An isolation decrease by a factor of 10 is experimentally observed in a Faraday isolator that is used in a gravitational wave experiment (Virgo) with a 10 W input laser when going from air to vacuum. A finite element model simulation reproduces with a great accuracy the experimental data measured on Virgo and on a test bench. A first set of measurements of the thermal lensing has been used to characterize the losses of the crystal, which depend on the sample. The isolation factor measured on Virgo confirms the simulation model and the absorption losses of 0.0016 +/- 0.0002/cm for the TGG magneto-optic crystal used in the Faraday isolator.