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1.
J Bone Miner Res ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622481

RESUMO

Fractures and vascular calcifications (VCs) are common in patients with chronic kidney disease (CKD). They are related to abnormalities in vitamin D metabolism, calcium, phosphorus, parathyroid hormone, and fibroblast growth factor 23 (FGF23)/Klotho that occur with CKD. Impaired vitamin D metabolism and abnormal levels of calcium, phosphate, parathyroid hormone (PTH), and FGF23/Klotho drive bone and vascular changes in CKD. It is unclear if oral calcitriol safely mitigates fracture risk without increasing the burden of calcifications. Therefore, we investigated whether treatment with calcitriol affected the prevalence of fractures and VC progression in hemodialysis (HD) patients. This report is a secondary analysis of the Vitamin K Italian (VIKI) study, a cross-sectional study involving 387 HD patients. We assessed vitamin 25(OH)D, alkaline phosphatase, PTH, calcium, phosphate, osteocalcin or bone Gla protein, matrix Gla protein, and vitamin K levels. Vertebral fractures (VFs) and VCs were determined by spine radiograph. A reduction of >20% of vertebral body height was considered a VF. VCs were quantified by the length of calcific lesions along the arteries. The patients treated with oral calcitriol were 177 of 387 patients (45.7%). The prevalence of VF was lower in patients receiving oral calcitriol than in those untreated (48.6% versus 61.0%, p = 0.015), whereas the presence of aortic and iliac calcifications was similar (aortic: 81.9% versus 79.5%, respectively, p = 0.552; iliac: 52.0% and 59.5%, respectively, p = 0.167). In multivariable logistic regression analysis, oral calcitriol was associated with a 40.2% reduced odds of fracture (OR 0.598; 95% confidence interval [CI], 0.363-0.985; p = 0.043). In conclusion, we found a significant association between oral calcitriol and lower VF in HD patients without an increase in the burden of VC. Further prospective and interventional studies are needed to confirm these findings. © 2021 American Society for Bone and Mineral Research (ASBMR).

2.
Artigo em Inglês | MEDLINE | ID: mdl-34625375

RESUMO

We describe adipose stromal/stem cells (ASCs) in the structural/functional context of the adipose tissue (AT) stem niche (adiponiche), including cell-cell interactions and the microenvironment, and emphasize findings obtained in humans and in lineage-tracing models. ASCs have distinctive markers, 'colors', and anatomical 'locations' which influence their functions. Each adiponiche component can become impaired, thereby contributing to the pathological AT alterations seen in obesity and metabolic diseases. We discuss adiposopathy with a focus on adiponiche dysfunction, and underline the mechanisms that control AT expansion and energy balance. Better understanding of adiponiche regulation and ASC features could help to identify therapeutic targets that favor weight loss and counteract weight regain, and also contribute to innovative strategies for regenerative medicine.

3.
Sleep Breath ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34487305

RESUMO

PURPOSE: Obstructive sleep apnea (OSA) is a widespread comorbidity of obesity. Nasal continuous positive airway pressure (CPAP) has been demonstrated very effective in treating patients with OSA. The aims of this study were to investigate whether or not cardiopulmonary exercise testing (CPET) can characterize patients with OSA and to evaluate the effect of nasal CPAP therapy. METHODS: An observational study was conducted on patients with moderate to severe obesity and suspected OSA. All patients underwent cardiorespiratory sleep study, spirometry, and functional evaluation with ECG-monitored, incremental, maximal CPET. RESULTS: Of the 147 patients, 94 presented with an apnea-hypopnea index (AHI) ≥ 15 events/h and were thus considered to have OSA (52 receiving nasal CPAP treatment; 42 untreated) while 53 formed a control group (AHI < 15 events/h). Patients with untreated OSA showed significantly lower oxygen uptake (VO2), heart rate, minute ventilation (VE), and end tidal carbon dioxide (PETCO2) at peak exercise compared to controls. Patients receiving nasal CPAP showed higher VE and VO2 at peak exercise compared to untreated patients. A difference in PETCO2 between the maximum value reached during test and peak exercise (ΔPETCO2 max-peak) of 1.71 mmHg was identified as a predictor of OSA. CONCLUSION: Patients with moderate to severe obesity and untreated OSA presented a distinctive CPET-pattern characterized by lower aerobic and exercise capacity, higher PETCO2 at peak exercise associated with a lower ventilatory response. Nasal CPAP treatment was shown to positively affect these cardiorespiratory adaptations during exercise. ΔPETCO2 max-peak may be used to suggest OSA in patients with obesity.

4.
Pituitary ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518997

RESUMO

PURPOSE: Oro-facial manifestations of acromegaly are among the earliest signs of the disease and are reported by a significant number of patients at diagnosis. Despite this high prevalence of acromegaly oral manifestation, dentists do not play a pivotal role in acromegaly identification and diagnosis. The aim of our study was to evaluate the ability of dentists and orthodontists in the early recognition of the oro-facial manifestations of acromegaly. METHODS: A telematic questionnaire was administered to dentists and orthodontists. The questionnaire included photos with facial and oral-dental details and lateral teleradiography of acromegaly patients (ACRO). RESULTS: The study included 426 participants: 220 dentists and 206 orthodontists. Upon reviewing the photos, dentists most often observed mandibular prognathism and lips projection, while orthodontists also reported the impairment of relative soft tissue. Orthodontists, who usually use photos to document patients' oral-facial characteristics, paid more attention to oral-facial impairment than dentists. During dental assessment, 90% of the participants usually evaluated tongue size and appearance, diastemas presence, and signs of sleep impairment (mainly orthodontists). Orthodontists were also more able to identify sella turcica enlargement at teleradiography. A total of 10.8% of the participants had ACRO as patients and 11.3% referred at least one patient for acromegaly suspicion. CONCLUSION: The study highlighted dentists' strategic role in identifying ACRO. Increasing dentists' awareness about acromegaly clinical issues may improve early diagnosis, potentially resulting in an increased quality of life and decreased mortality among ACRO.

5.
Obes Facts ; 14(5): 543-549, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34482305

RESUMO

INTRODUCTION: Overweight and obesity are associated with a more severe COronaVirus Disease 19 (COVID-19). Adipose tissue-related chronic inflammation could be a promoter for the occurrence of the cytokine storm that predicts aggravation of COVID-19. The primary aim was to investigate if this increased risk for more severe COVID-19 was associated with a higher inflammatory response. METHODS: We enrolled patients <75 years old hospitalized in a medical COVID-19 ward with SARS-CoV-2-related pneumonia. Patients were classified according to BMI as normal weight, overweight, and obesity. Laboratory parameters were measured at admission and every second day during the hospital stay. RESULTS: Ninety patients (64.4% males; median age 61 years) were enrolled. Invasive mechanical ventilation (IMV) was needed in 9% of the patients with normal weight, in 32.4% of the patients with overweight, and in 12.9% of the patients with obesity (p = 0.045). Maximal C-reactive protein (CRP) level during hospital stay was 92 (48-122) mg/L in patients with normal weight, 140 (82-265) mg/L in patients with overweight, and 117 (67-160) mg/L in patients with obesity (p = 0.037). Maximal ferritin values were 564 (403-1,379) µg/L in patients with a normal weight, 1,253 (754-2,532) µg/L in patients with overweight, and 828 (279-1,582) µg/L in patients with obesity (p = 0.015). CONCLUSION: Patients with overweight and obesity required more IMV and had higher peaks of CRP and ferritin than patients with normal weight during COVID-19.

6.
Nutrients ; 13(8)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34444930

RESUMO

Fewer studies compared the improvement of plasma lipid levels after different types of surgery, in particular compared to one-anastomosis gastric bypass (OAGB). The aim of our study was to investigate how laparoscopic sleeve gastrectomy (LSG) and OAGB impact on weight loss and lipid profile 18 months after surgery, in patients with severe obesity. Forty-six patients treated with OAGB were matched to eighty-eight patients submitted to LSG. Weight loss after OAGB (33.2%) was more evident than after LSG (29.6%) (p = 0.024). The difference in the prevalence of dyslipidemia showed a statistically significant reduction only after OAGB (61% versus 22%, p < 0.001). After adjustment for delta body mass index (BMI), age and sex, we demonstrated a statistically significant decrease of the differences between the changes before and after (delta Δ) the two surgery procedures: Δ total cholesterol values (p < 0.001), Δ low density lipoprotein-cholesterol values (p < 0.001) and Δ triglycerides values (p = 0.007). Patients with severe obesity undergoing to OAGB presented a better improvement of lipid plasma values than LSG patients. The reduction of lipid plasma levels was independent of the significant decrease of BMI after surgery, of age and of sex.


Assuntos
Gastrectomia/métodos , Derivação Gástrica/métodos , Lipídeos/sangue , Obesidade Mórbida/sangue , Adolescente , Adulto , Idoso , Antropometria , Índice de Massa Corporal , Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Período Pós-Operatório , Resultado do Tratamento , Triglicerídeos/sangue , Perda de Peso , Adulto Jovem
7.
Obes Facts ; 14(4): 415-424, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34344002

RESUMO

INTRODUCTION: Metabolic adaptations to maximal physical exercise in people with obesity (PwO) are scarcely described. This cross-sectional study evaluates the metabolic response to exercise via the respiratory exchange ratio (RER) in PwO and different degrees of glycemic control. METHODS: Eighty-five PwO (body mass index 46.0 [39.0-54.0] kg/m2), that is, 32 normoglycemic (Ob-N), 25 prediabetic (Ob-preDM), and 28 diabetic (Ob-T2DM) subjects and 18 healthy subjects performed an incremental, maximal cardiopulmonary exercise test. The RER was measured at rest (RERrest) and at peak exercise (RERpeak). RESULTS: RERpeak was significantly higher in healthy subjects than that in PwO. Among those, RERpeak was significantly higher in Ob-N than that in Ob-preDM and Ob-T2DM (1.20 [1.15-1.27] vs. 1.18 [1.10-1.22] p = 0.04 and vs. 1.14 [1.10-1.18] p < 0.001, respectively). Accordingly, ΔRER (RERpeak-RERrest) was lower in Ob-preDM and Ob-T2DM than that in Ob-N (0.32 [0.26-0.39] p = 0.04 and 0.29 [0.24-0.36] p < 0.001 vs. 0.38 [0.32-0.43], respectively), while no significant difference was found in ΔRER between Ob-preDM and Ob-T2DM and not even between Ob-N and healthy subjects. Moreover, ΔRER in PwO correlated with glucose area under curve (p = 0.002). CONCLUSIONS: PwO demonstrate restricted metabolic response during maximal exercise. Particularly, those with prediabetes already show metabolic inflexibility during exercise, similarly to those with type 2 diabetes. These findings also suggest a potential role of cardiopulmonary exercise testing in detecting early metabolic alterations in PwO.

8.
PLoS One ; 16(6): e0253433, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34138945

RESUMO

PURPOSE: To evaluate if reduced muscle mass, assessed with Computed Tomography (CT), is a predictor of intensive care unit (ICU) hospitalization in COVID-19 patients. METHODS: In this Institution Review Board approved study, we retrospectively evaluated COVID-19 patients treated in our tertiary center from March to November 2020 who underwent an unenhanced chest CT scan within three weeks from hospitalization.We recorded the mean Hounsfield Unit (Hu) value of the right paravertebral muscle at the level of the 12th thoracic vertebra, the hospitalization unit (ICU and COVID-19 wards), clinical symptoms, Barthel Index, and laboratory findings.Logistic regression analysis was applied to assess if muscle loss (Hu<30) is a predictor of ICU admission and outcome.Fisher's exact and Student's tests were applied to evaluate if differences between patients with and without muscle loss occurred (p<0.05). RESULTS: One-hundred-fifty patients matched the inclusion criteria (46 females; mean age±SD 61.3±15 years-old), 36 treated in ICU. Patients in ICU showed significantly lower Hu values (29±24 vs 39.4±12, p = 0.001). Muscle loss was a predictor of ICU admission (p = 0.004).Patients with muscle loss were significantly older (73.4±10 vs 56.4±14 years), had lower Barthel Index scores (54.4±33 vs 85.1±26), red blood-cell count (3.9±1 vs 4.6±1×1012L-1), and Hb levels (11.5±2 vs 13.2±2g/l) as well as higher white blood-cell count (9.4±7 vs 7.2±4×109L-1), C-reactive protein (71.5±71 vs 44±48U/L), and lactate dehydrogenase levels (335±163 vs 265.8±116U/L) (p<0.05, each). CONCLUSIONS: Muscle loss seems to be a predictor of ICU hospitalization in COVID-19 patients and radiologists reporting chest CT at admission should note this finding in their reports.


Assuntos
COVID-19/terapia , Hospitalização/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Músculos/metabolismo , SARS-CoV-2/isolamento & purificação , Idoso , COVID-19/diagnóstico , COVID-19/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculos/diagnóstico por imagem , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/fisiologia , Tomografia Computadorizada por Raios X/métodos
9.
Mycoses ; 64(10): 1223-1229, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34157166

RESUMO

BACKGROUND: An increasing number of reports have described the COVID-19-associated pulmonary aspergillosis (CAPA) as being a further contributing factor to mortality. Based on a recent consensus statement supported by international medical mycology societies, it has been proposed to define CAPA as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Considering current challenges associated with proven diagnoses, there is pressing need to study the epidemiology of proven CAPA. METHODS: We report the incidence of histologically diagnosed CAPA in a series of 45 consecutive COVID-19 laboratory-confirmed autopsies, performed at Padova University Hospital during the first and second wave of the pandemic. Clinical data, laboratory data and radiological features were also collected for each case. RESULTS: Proven CAPA was detected in 9 (20%) cases, mainly in the second wave of the pandemic (7/17 vs. 2/28 of the first wave). The population of CAPA patients consisted of seven males and two females, with a median age of 74 years. Seven patients were admitted to the intensive care unit. All patients had at least two comorbidities, and concomitant lung diseases were detected in three cases. CONCLUSION: We found a high frequency of proven CAPA among patients with severe COVID-19 thus confirming at least in part the alarming epidemiological data of this important complication recently reported as probable CAPA.


Assuntos
COVID-19/epidemiologia , Aspergilose Pulmonar Invasiva/epidemiologia , Insuficiência Respiratória/mortalidade , Idoso , Idoso de 80 Anos ou mais , Aspergillus , COVID-19/mortalidade , COVID-19/patologia , Comorbidade , Feminino , Humanos , Unidades de Terapia Intensiva , Aspergilose Pulmonar Invasiva/mortalidade , Aspergilose Pulmonar Invasiva/patologia , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/microbiologia , Insuficiência Respiratória/patologia , SARS-CoV-2
10.
Biomolecules ; 11(6)2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073591

RESUMO

Angiotensin-converting enzyme 2 (ACE-2) is the main cell entry receptor for severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2), thus playing a critical role in causing Coronavirus disease 2019 (COVID-19). The role of smoking habit in the susceptibility to infection is still controversial. In this study we correlated lung ACE-2 gene expression with several clinical/pathological data to explore susceptibility to infection. This is a retrospective observational study on 29 consecutive COVID-19 autopsies. SARS-CoV-2 genome and ACE-2 mRNA expression were evaluated by real-time polymerase chain reaction in lung tissue samples and correlated with several data with focus on smoking habit. Smoking was less frequent in high than low ACE-2 expressors (p = 0.014). A Bayesian regression also including age, gender, hypertension, and virus quantity confirmed that smoking was the most probable risk factor associated with low ACE-2 expression in the model. A direct relation was found between viral quantity and ACE-2 expression (p = 0.028). Finally, high ACE-2 expressors more frequently showed a prevalent pattern of vascular injury than low expressors (p = 0.049). In conclusion, ACE-2 levels were decreased in the lung tissue of smokers with severe COVID-19 pneumonia. These results point out complex biological interactions between SARS-CoV-2 and ACE-2 particularly concerning the aspect of smoking habit and need larger prospective case series and translational studies.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/patologia , Pulmão/metabolismo , Idoso , Idoso de 80 Anos ou mais , Enzima de Conversão de Angiotensina 2/genética , Teorema de Bayes , COVID-19/virologia , Feminino , Humanos , Pulmão/patologia , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Fumantes
11.
Int J Obes (Lond) ; 45(9): 1949-1957, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33990701

RESUMO

BACKGROUND/OBJECTIVES: Different approaches are used to classify obesity severity. Beyond classical anthropometric measurements, the Edmonton Obesity Staging System (EOSS) considers medical, physical and psychological parameters. However, this method has some limitations, principally due to the absence of an objective measure for physical impairment. The aim of our study is thus to overcome this limitation suggesting a new functional parameter obtained by cardiopulmonary exercise testing (CPET), i.e., cardiorespiratory fitness (CRF), expressed as weight-adjusted peak oxygen consumption (VO2peak/kg). SUBJECTS/METHODS: This observational cross-sectional study conducted on a population of 843 patients affected by obesity finally enrolled 500 subjects. Every patient underwent clinical, anthropometric, biochemical assessment and CPET. First, participants have been classified according to standard EOSS in five stages. Second, patients were reclassified according to the new modified EOSS (EOSS-CRF) based on their age- and gender-appropriate VO2peak/kg percentiles as reported in the healthy normal-weight population of the FRIEND registry. RESULTS: VO2peak/kg was significantly different between standard EOSS classes 1 and 2 and classes 1 and 3 (ANCOVA p model = 0.004), whereas patients in classes 2 and 3 showed similar CRF. The EOSS-CRF classification varied in number of patients in each class compared to EOSS, particularly with a shift from class 2 to class 3. Moreover, CRF showed that physical impairment is less addressed by EOSS when compared to EOSS-CRF. CONCLUSIONS: The integration of EOSS with CRF allowed us to assign to each patient a severity index that considers not only clinical parameters, but also their functional impairment through a quantitative and prognostically important parameter (VO2peak/kg). This improvement of the staging system may also provide a better approach to identify individuals at increased risk of mortality leading to targeted therapeutic management and prognostic risk stratification for patients with obesity.

12.
Sleep Med Rev ; 59: 101497, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34044356

RESUMO

Hypertension and blunted blood pressure (BP) dipping during nighttime sleep are associated with increased cardiovascular risk. Chronic insomnia and restless legs syndrome (RLS) may affect the 24-h BP profile. We systematically reviewed the association of insomnia and RLS with BP values during nighttime sleep and the relative BP dipping pattern. We searched relevant articles in any language with selection criteria including enrolment of subjects with insomnia or RLS and with obstructive sleep apnea comorbidity assessment. Of the 872 studies originally retrieved, seven were selected. Four studies enrolled subjects with insomnia. One study relied on sleep diaries to classify nighttime sleep BP, whereas three relied only on clock time. At meta-analysis, subjects with insomnia displayed an attenuated dipping of systolic BP (-2.00%; 95% confidence interval (CI): -3.61 - -0.39%) and diastolic BP (-1.58%; 95% CI: -2.66 ̶ -0.49%) during nighttime sleep compared to controls. Three studies enrolled subjects with RLS. One study relied on polysomnography to classify nighttime sleep BP, whereas two relied only on clock time. Subjects with RLS showed increases in nighttime sleep systolic BP (5.61 mm Hg, 95% CI 0.13̶-11.09 mm Hg) compared to controls. In conclusion, the limited available data suggest that insomnia and RLS are both associated with altered BP control during nighttime sleep. There is need for more clinical studies to confirm these findings, specifically focusing on measurements of BP during objectively defined sleep, on causal roles of leg movements during sleep and alterations in sleep architecture, and on implications for cardiovascular risk. PROSPERO ACKNOWLEDGEMENT OF NUMBER: CRD42020217947.

13.
Pharmacol Res ; 169: 105649, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962014

RESUMO

Several pharmacological approaches to controlling body weight have been developed over the last decades, albeit with limited success. Currently available agents include centrally acting appetite suppressants and peripherally acting compounds. Efficacy and safety of these agents in the clinical setting require a difficult balance. Further strategies including multiagonists able to simultaneously target multiple actors involved in obesity initiation and expansion such as the glucagon receptor family are under investigation. The results of recent clinical trials are encouraging and highlight emerging compounds as potential game changers. In view of the rising prevalence of obesity and the associated burden of comorbidities worldwide, and compared with other areas of pharmacological intervention, we feel that the field of obesity has been affected by therapeutic inertia. Of note, obesity may also affect the response to concomitant medications such as low-dose aspirin. Lessons from withdrawn agents such as the cannabinoid receptor antagonist rimonabant include developing compounds with a more targeted action profile (i.e., central vs peripheral, or antagonist versus inverse agonist) as well as careful selection of patients based on individual risk factors. We anticipate that the expanding knowledge base and clinical testing will result in improved outcomes for patients with obesity in the near future.

15.
Eat Weight Disord ; 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34052990

RESUMO

Obesity is a complex chronic relapsing disease, resulting from the interaction between multiple environmental, genetic and epigenetic causes, and supported by changes in the neuroendocrine mechanisms regulating energy balance and body weight. Adipose tissue dysfunction contributes to obesity-related complications. However, the prevalent narrative about the causes and mechanisms of obesity remains a much more simplistic one, based on the false assumption that individuals can fully control their body weight through appropriate behavioural choices. According to this narrative, obesity is simply reversible "persuading" the patient to follow healthier and more virtuous individual behaviours (moral judgement). This persistent narrative forms the deep root of the stigmatisation of people with obesity at the individual level and creates a clear discrepancy on how obesity prevention and cure are designed in comparison with the case of other non-communicable chronic diseases (clinical stigma). The promotion of systemic preventive measures against obesity is not supported at a political and social level by the persistence of a narrative of obesity as the simple consequence of individual failures and lack of willpower. The simplistic narrative of obesity as a self-imposed condition with an easy way-out ("eat less and move more") creates a clear discrepancy on how obesity is managed by health care systems in comparison with other NCDs. The over-estimation of the efficacy of therapeutic intervention solely based on patients education and lifestyle modification is responsible of therapeutic inertia in health care professionals and in clinical guidelines, limiting or delaying the adoption of more effective therapeutic strategies, like anti-obesity medications and bariatric surgery. In conclusion, the persistence of a narrative describing obesity as a self-induced easily reversible condition has profound consequences on how obesity prevention and management are build, including the design and implementation of obesity management guidelines and a tendency to therapeutic inertia.Level of evidence: No level of evidence.

16.
Endocr Relat Cancer ; 28(7): 449-456, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-33974555

RESUMO

The knowledge of the molecular landscape of ileal neuroendocrine tumors (NETs) is affected by the lack of systematic studies investigating intra-tumoral heterogeneity. In this study, intra-tumoral heterogeneity was investigated in 27 primary ileal G1-NETs and their matched nodal and liver metastases in order to assess the tumor grading, the expression status of two somatostatin receptor isoforms (i.e. SSTR2A and SSTR5) and mTOR signaling dysregulation (ph-mTOR, ph-p70S6K, ph-4EBP1, PTEN and miR-21). Among the 27 G1 primary tumors, 4 shifted to G2 in the matched liver metastasis. Although mTOR activation was pretty consistent between primary and secondary malignancies, mTOR effectors (ph-p70S6K and ph-4EBP1) were overexpressed in matched liver metastases, whereas PTEN expression profile changed in only two cases. MiR-21 was significantly up-regulated in the metastatic setting. Although SSTRs expression was present in most of the primary tumors and matched metastasis, we found SSTR5 expression to be significantly increased in liver metastases. Notably, SSTRs expression was heterogeneous within the same lesions in most of the lesions. Overall, despite primary and metastatic ileal NETs show a similar molecular landscape, tumor grading and mTOR signaling pathway may diverge in the metastatic setting, thus affecting prognosis and treatment.

17.
Pathol Res Pract ; 221: 153451, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33932720

RESUMO

Few studies have focused on COVID-19 patients' hepatic histopathological features. Many of the described morphological landscapes are non-specific and possibly due to other comorbidities or to Sars-CoV-2-related therapies. We describe the hepatic histopathological findings of 3 liver biopsies obtained from living COVID-19 patients in which active SARS-CoV-2 infection was molecularly confirmed and biopsied because of significant alterations of liver function tests and 25 livers analyzed during COVID-19-related autopsies. Main histopathological findings were (i) the absence of significant biliary tree or vascular damages, (ii) mild/absent lymphocytic hepatitis; (iii) activation of (pigmented) Kupffer cells, (iv) hepatocellular regenerative changes, (v) the presence of steatosis, (vi) sinusoidal ectasia, micro-thrombosis and acinar atrophy in autopsy specimens No viral particle actively infecting the hepatic or endothelial cells was detected at in situ hybridization. The morphological features observed within the hepatic parenchyma are not specific and should be considered as the result of an indirect insult resulting from the viral infection or the adopted therapeutic protocols.


Assuntos
COVID-19/complicações , Hepatopatias/patologia , Hepatopatias/virologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2
18.
Intern Emerg Med ; 16(4): 1005-1015, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33893976

RESUMO

During the COVID-19 2020 outbreak, a large body of data has been provided on general management and outcomes of hospitalized COVID-19 patients. Yet, relatively little is known on characteristics and outcome of patients managed in Internal Medicine Units (IMU). To address this gap, the Italian Society of Internal Medicine has conducted a nationwide cohort multicentre study on death outcome in adult COVID-19 patients admitted and managed in IMU. This study assessed 3044 COVID-19 patients at 41 referral hospitals across Italy from February 3rd to May 8th 2020. Demographics, comorbidities, organ dysfunction, treatment, and outcomes including death were assessed. During the study period, 697 patients (22.9%) were transferred to intensive care units, and 351 died in IMU (death rate 14.9%). At admission, factors independently associated with in-hospital mortality were age (OR 2.46, p = 0.000), productive cough (OR 2.04, p = 0.000), pre-existing chronic heart failure (OR 1.58, p = 0.017) and chronic obstructive pulmonary disease (OR 1.17, p = 0.048), the number of comorbidities (OR 1.34, p = 0.000) and polypharmacy (OR 1.20, p = 0.000). Of note, up to 40% of elderly patients did not report fever at admission. Decreasing PaO2/FiO2 ratio at admission was strongly inversely associated with survival. The use of conventional oxygen supplementation increased with the number of pre-existing comorbidities, but it did not associate with better survival in patients with PaO2/FiO2 ratio < 100. The latter, significantly benefited by the early use of non-invasive mechanical ventilation. Our study identified PaO2/FiO2 ratio at admission and comorbidity as the main alert signs to inform clinical decisions and resource allocation in non-critically ill COVID-19 patients admitted to IMU.


Assuntos
COVID-19/mortalidade , COVID-19/terapia , Hospitalização , Medicina Interna , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , Estudos de Coortes , Cuidados Críticos , Mortalidade Hospitalar , Humanos , Itália , Pessoa de Meia-Idade , Respiração Artificial , Taxa de Sobrevida
19.
Artigo em Inglês | MEDLINE | ID: mdl-33870099

RESUMO

Objective: To conduct a comprehensive evaluation of coagulation profiles - via traditional and whole blood thromboelastometry tests - in COVID-19 positive vs. COVID-19 negative patients admitted to medical wards for acute pneumonia. Patients and Methods: We enrolled all consecutive patients admitted to Internal Medicine wards of Padova University Hospital between 7 March and 30 April 2020 for COVID-19-related pneumonia (cases) vs. non-COVID-19 pneumonia (controls). A group of healthy subjects acted as baseline for thromboelastometry parameters. Results: Fifty-six cases (mean age 64±15 yrs, M/F 37/19) and 56 controls (mean age 76±11 yrs, M/F 35/21) were enrolled. Cases and controls showed markedly hypercoagulable thromboelastometry profiles vs. healthy subjects, mainly characterized by a significantly shorter propagation phase of coagulation (Clot Formation Time, CFT) and significantly increased maximum clot firmness (MCF) (p <0.001 in all comparisons). COVID-19 patients with pneumonia had significantly shorter CFT and higher MCF (p <0.01 and <0.05, respectively in all comparisons) vs. controls. Conclusion: Patients admitted to internal medicine wards for COVID-19 pneumonia presented a markedly prothrombotic state, which seems peculiar to COVID-19 rather than pneumonia itself.

20.
Eur J Intern Med ; 88: 73-80, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33888393

RESUMO

BACKGROUND: Fixed dose unfractionated or low molecular weight heparin is the recommended treatment for venous thromboembolism (VTE) prevention in hospitalized patients. However, its efficacy has been questioned in obese population. Results of previous studies on weight-adjusted doses of heparin for VTE prevention are contradictory. Different anticoagulant regimens are used in clinical practice, but their role remains to be elucidated. AIMS: To clarify the efficacy and safety of weight-adjusted dose heparin for VTE prevention in obese subjects hospitalized for medical and surgical conditions. METHODS: Twelve studies were identified as reporting VTE occurrence, major or minor bleeding and anti-Xa levels. A random-effect meta-analysis was conducted to derive odds ratios (OR) comparing fixed vs weight adjusted-doses heparins on VTE occurrence, bleeding, anti-Xa levels. Medical and surgical patients, prospective vs retrospective and quality of studies were extracted for moderators and meta-regression analysis. RESULTS: Weight-adjusted dose heparin administration was not associated with reduced VTE occurrence (6320/13317 patients, OR 1.03, 95% C.I. 0.79 to 1.35), nor increased bleeding (5840/10906 patients, OR 0.84, 95% C.I. 0.65 to 1.08), but it was associated with higher anti-Xa levels (284/294 patients, ES 2.04, 95% C.I. 1.16 to 2.92, p<0.0001). A significant heterogeneity was present for comparison of anti-Xa levels (I2=94%, p=0.0001) but not for VTE occurrence or bleeding (I2=7.6% and 12.8% respectivel). None of the moderators explained the heterogeneity of the results among primary studies. CONCLUSION: Weight-adjusted dose as compared to fixed-dose of heparins in the prevention of VTE in obese patients was not associated with a lower risk of VTE nor a higher risk of bleeding.


Assuntos
Heparina , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular , Humanos , Obesidade/complicações , Estudos Prospectivos , Estudos Retrospectivos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle
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