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Silva-Nunes, José António

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  • Metformin in SARS-CoV-2 infection: a hidden path - from altered inflammation to reduced mortality (a review from the literature)
    Publication . Pedrosa, Ana Realista; Martins, Diana Cruz; Rizzo, Manfredi; Silva-Nunes, José
    SARS-CoV-2 infection has been a major threat to human health and a huge challenge to Medicine. In only two years, COVID-19 affected >350 million people, causing >5.6 million deaths. Chronic inflammatory states, such as diabetes or obesity, are known risk factors for COVID-19 poorest outcomes, with a higher risk for disease severity and greater mortality. Metformin remains on the first line of the management of hyperglycemia in type 2 diabetes. Through its anti-inflammatory and immunomodulatory mechanisms, metformin appears as an opportunity to control the dysregulated cytokine storm secondary to SARS-CoV-2 infection. Recent studies point towards a potential protective role of metformin in the course of COVID-19, showing that current or previous treatment with metformin associates with better outcomes.
  • Absolute hyperglycemia versus stress hyperglycemia ratio for the prognosis of hospitalized patients with COVID-19 in the first months of the pandemic: a retrospective study
    Publication . Matias, Alexandra A.; Manique, Inês; Sabino, Teresa; Rego, Teresa; Mihon, Claudia; Panarra, António; Rizzo, Manfredi; Silva-Nunes, José
    Diabetes is a risk factor for the greater severity of coronavirus disease 2019 (COVID-19). The stress hyperglycemia ratio (SHR) is an independent predictor of critical illness, and it is reported to have a stronger association than absolute hyperglycemia. The aim of this study was to assess the relationship between absolute hyperglycemia and SHR with the severity of COVID-19 since there are no studies investigating SHR in patients with COVID-19. We conducted a retrospective observational study on hospitalized patients with COVID-19 in the first months of the pandemic, regarding absolute hyperglycemia, SHR, and severity outcomes. Of the 374 patients, 28.1% had a previous diagnosis of type 2 diabetes. Absolute hyperglycemia (64.8% versus 22.7%; p < 0.01) and SHR [1.1 (IQR 0.9-1.3) versus 1.0 (IQR 0.9-1.2); p < 0.001] showed a statistically significant association with previous diabetes. Absolute hyperglycemia showed a significant association with the clinical severity of COVID-19 (79.0% versus 62.7%; p < 0.001), need for oxygen therapy (74.8% versus 54.4%; p < 0.001), invasive mechanical ventilation (28.6% versus 11.6%; p < 0.001), and intensive care unit (30.3% versus 14.9%; p = 0.002), but not with mortality; by contrast, there was no statistically significant association between SHR and all these parameters. Our results are in agreement with the literature regarding the impact of absolute hyperglycemia on COVID-19 severity outcomes, while SHR was not a significant marker. We, therefore, suggest that SHR should not be evaluated in all patients admitted to the hospital for COVID-19, and we encourage the standard measures at the admission of blood glucose and HbA1c levels.
  • Does the hyperglycemia impact on COVID-19 outcomes depend upon the presence of diabetes? An observational study
    Publication . Manique, Inês; Matias, Alexandra Abegão; Bouça, Bruno; Rego, Teresa; Cortez, Luísa; Sabino, Teresa; Panarra, António; Rizzo, Manfredi; Silva-Nunes, José
    Diabetes mellitus (DM) has emerged as a major risk factor for COVID-19 severity and SARS-CoV-2 infection can worsen glycemic control and may precipitate new-onset diabetes. At-admission hyperglycemia (AH) is a known predictor for worse outcomes in many diseases and seems to have a similar effect in COVID-19 patients. In this study, we aimed to assess the impact of AH regardless of pre-existing diabetes mellitus and new-onset diabetes diagnosis in the clinical severity of COVID-19 inpatients in the first months of the pandemic. A retrospective monocentric study on 374 COVID-19 inpatients (209 males) was developed to assess associations between AH (blood glucose levels in the Emergency Department or the first 24 h of hospitalization greater than 140 mg/dL) and severity outcomes (disease severity, respiratory support, admission to Intensive Care Unit (ICU) and mortality) in patients with and without diabetes. Considering diabetic patients with AH (N = 68;18.1%) there was a correlation with COVID-19 severity (p = 0.03), invasive mechanical ventilation (p = 0.008), and ICU admission (p = 0.026). No correlation was present with any severity outcomes in diabetic patients without AH (N = 33; 8.8%). All of the New-onset Diabetes patients (N = 15; 4%) had AH, and 12 had severe COVID-19; additionally, five patients were admitted to the ICU and three patients died. However, severity outcomes did not reach statistical correlation significance in this group. In nondiabetic patients with AH (N = 51; 13.6%), there was a statistically significant association with the need for oxygen therapy (p = 0.001), invasive mechanical ventilation (p = 0.01), and ICU admission (p = 0.03). Our results support data regarding the impact of AH on severity outcomes. It also suggests an effect of AH on the prognosis of COVID-19 inpatients, regardless of the presence of pre-existing diabetes or new-onset diabetes. We reinforce the importance to assess at admission glycemia in all patients admitted with COVID-19.
  • Central diabetes insipidus following immunization with BNT162b2 mRNA COVID-19 vaccine: a case report
    Publication . Bouça, Bruno; Roldão, Marisa; Bogalho, Paula; Cerqueira, Luís; Silva-Nunes, José
    Introduction: Cases of central diabetes insipidus (CDI) have been reported after COVID-19 infection, with hypophysitis being the most likely cause. COVID-19 vaccines' potential adverse effects may mimetize some of these complications. Case report: Woman 37 years old, with rheumatoid arthritis under adalimumab (40 mg twice a month) since December 2018. She was in her usual state of health when she received the second dose of the BNT162b2 mRNA COVID-19 vaccine (June 2021). Seven days later, she started reporting intense thirst and polyuria and consulted her family physician. Blood analysis: creatinine 0.7 mg/dL, glucose 95mg/dL, Na+ 141mEq/L, K+ 3.9 mEq/L, TSH 3.8 mcUI/L (0.38-5.33), FT4 0.9 ng/dL (0.6-1.1), cortisol 215.4 nmol/L (185-624), ACTH 21.9 pg/mL (6- 48), FSH 4.76 UI/L, LH5.62 UI/L, estradiol 323 pmol/L, IGF1 74.8 ng/mL (88-209), PRL 24.7mcg/L (3.3-26.7) osmolality 298.2 mOs/Kg (250- 325); Urine analysis: volume 10200 mL/24h, osmolality 75 mOs/Kg (300-900), density 1.002. On water restriction test: 0' - Serum osmolality 308.8mOsm/Kg vs. urine osmolality 61.0 mOsm/Kg; 60' - urine osmolality 102 mOsm/Kg; urine osmolality 1 h after desmopressine was 511mOsm/kg. MRI revealed no abnormal signs consistent with hypophysitis except for the loss of the posterior pituitary bright spot on T1 weighted imaging. Diagnosis of CDI was assumed and started therapy with desmopressine. A report of potential adverse effects was addressed to national health authorities. Conclusion: In hypophysitis, MRI often shows loss of posterior pituitary bright spot on T1 weighted imaging, pituitary enlargement, or stalk thickening but those findings were not present in this patient. To the best of our knowledge, CDI has never been reported following the administration of a COVID-19 vaccine.