COVID-19: a trigger for severe thrombotic microangiopathy in a patient with complement gene variant

The evidence regarding thrombotic microangiopathy (TMA) related to Coronavirus Infectious Disease 2019 (COVID-19) in patients with complement gene mutations as a cause of acute kidney injury (AKI) are limited. We presented a case of a 23-year-old male patient admitted with an asymptomatic form of COVID-19, but with uncontrolled hypertension and AKI. Kidney biopsy showed severe lesions of TMA. In evolution patient had persistent microangiopathic hemolytic anemia, decreased level of haptoglobin and increased LDH level. Decreased complement C3 level and the presence of schistocytes were found for the first time after biopsy. Kidney function progressively decreased and the patient remained hemodialysis dependent. Complement work-up showed a heterozygous variant with unknown significance in complement factor I (CFI) c.-13G>A, affecting the 5' UTR region of the gene. In addition, the patient was found to be heterozygous for the complement factor H (CFH) H3 haplotype (involving the rare alleles of c.-331C>T, Q672Q and E936D polymorphisms) reported as a risk factor of atypical hemolytic uremic syndrome. This case of AKI associated with severe TMA and secondary hemolytic uremic syndrome highlights the importance of genetic risk modifiers in the alternative pathway dysregulation of the complement in the setting of COVID-19, even in asymptomatic forms.

Serum Uric Acid as a Predictor of cardio-and cerebro-vascular diseases in Maintenance Hemodialysis Patients

Background: Hyperuricemia is associated with an increased risk of cardio-and cerebrovascular disease (CVD) in general population. However, in the hemodialysis (HD) patients, low serum uric acid (SUA) increases the risk of mortality. Considering that CVD is the principal cause of death among maintenance HD patients, the present study aimed to determine the predictive value of SUA for CVD outcome in this population. Methods: In this two-year follow-up prospective study, 205 outpatients under maintenance HD were enrolled from March 2017 to 2020. Patients’ demographic data, underlying diseases, and the results of serum tests, as well as two-year follow-up results of CVD events and mortality were recorded. Results: A total of 130 (63%) patients were eligible for analysis; 62.9% were male; mean age of participants was 59±13years. At follow-up, coronary artery disease was observed in 43.2%, peripheral artery disease in 26.5%, and cerebrovascular disease in 20.5%; angiography was required in 52.3% and 4.5% died of CVD. SUA was ≤5.4 mg/dL in 52 patients, 5.5-6.1 mg/dL in 19, and ≥6.2 mg/dL in 59 patients with significant difference based on mean age, sex distribution, occurrence of cerebrovascular disease and cardiovascular mortality (P<0.05). Patients with cerebrovascular disease had a significantly lower SUA levels (P=0.006). Logistic regression showed the significant effect of SUA on the occurrence of cerebrovascular disease (P=0.008). Conclusion: Low SUA can predict two-year incidence of cerebrovascular disease in HD patients. However, SUA levels did not show significant predictive effect on two-year coronary events, peripheral artery disease and cardiovascular mortality.

Autoimmune Polyglandular Syndrome Type II presenting as Subacute Combined Degeneration of Spinal Cord: A Neuroendocrinology Crossroad

Introduction - Autoimmune polyglandular syndrome (APS) is a condition having multiple endocrine abnormalities. It is divided into three types depending on the involvement of various endocrinopathies. It is also associated with other systemic involvement. The basic pathophysiology of this syndrome revolves around autoimmunity. Case Presentation - We present a 50 year old gentleman who presented to us in emergency with subacute onset progressive weakness of both lower limbs followed by upper limbs. On examination, patient was confused and disoriented. General examination findings include hypotension, pallor, facial puffiness and vitiligo. Neurological examination revealed spasticity and motor weakness in all four limbs with extensor planter response. Sensory examination during hospital course revealed posterior column involvement. Laboratory and radiological investigations confirmed subacute combined degeneration of spinal cord secondary to pernicious anaemia, Addison’s disease and autoimmune thyroid disease. The final diagnosis of autoimmune polyglandular syndrome type II was made after fulfilment of the required criteria. Conclusion – Autoimmune polyglandular syndrome type II can rarely present to neurologist as subacute combined degeneration of spinal cord. This syndrome and its systemic association should be kept in mind in order to reach the final diagnosis.

Cardiac biomarkers alterations in patients with SARS-CoV-2 infection

Reliable biomarkers are necessary for the risk stratification of patients infected with SARS-CoV-2. This novel coronavirus is now established to affect several organs in addition to the lungs, most prominently the heart. This is achieved through direct damage to the myocardium and indirect immune-associated effects during the cytokine storm. We performed a literature review aiming to identify the prognostic value of alterations of cardiac biomarkers in SARS-CoV-2 infection. Cardiac biomarkers are significantly elevated in patients with severe COVID-19 and are independent predictors of mortality. High-sensitivity troponin I and T are correlated with multiple inflammatory indexes and poor outcomes. Although cut-off values have been established for most of cardiac biomarkers, lower limits for troponins may have better prognostic values and longitudinal monitoring of cardiac biomarkers can help the clinician assess the patient’s course. Additional measurements of NT-proBNP, can detect the subgroup of patients with poor prognosis.

Non secretory myeloma in young man mimicking the Gorham disease: case report and the literature review

Multiple myeloma is a neoplasm of plasma cells affecting mostly the elderly with incidence peaks between 60 and 70 years. This disease is exceedingly rare in younger people, especially in adults under 30-year-old. Non-secretory multiple myeloma accounts for 1–5% of all cases of multiple myeloma. It is also a rare condition in young adult patients, and only six cases have been reported [1]. We herein describe a rare case of non-secretory myeloma in a 22- year-old male, explaining from chest wall pain, without general manifestation. Plain radiography and CT scans revealed diffuse osteolytic lesion mimicking the Gorham disease. A bone marrow biopsy was conducted, revealing the diagnosis of myeloma.

Discontinuation of Eculizumab treatment after hematological remission in patients with atypical and drug-induced hemolytic uremic syndrome

Introduction: To evaluate the effect of therapeutic plasma exchange(TPE) and eculizumab on hematological and renal survival in atypical hemolytic uremic syndrome(aHUS). Additionally, to examine the reliability of discontinuation of eculizumab treatment. Methods: This was an observational and retrospective study of 18 patients diagnosed with aHUS. Results: The median age of the study population was 30(22-66) years. Four of 18 patients achieved hematological remission with the TPE alone. However, one patient in the died after three sessions of TPE. Eculizumab was used in 13 patients and no death was observed. One year after treatment, improved kidney function was observed in 2 of 3(66%) patients for TPE and 5 of 9(56%) patients for Eculizumab. We discontinued eculizumab treatment in 9 patients. One of the patients who had a C3 gene mutation experienced disease relapse after Eculizumab discontinuation. None of the patients who had drug associated aHUS, developed disease relapse after Eculizumab discontinuation. Conclusion: Eculizumab treatment is a life-saving therapy in aHUS. Treatment discontinuation may be considered at least six months after hematologic remission in patients who had stable renal function or no expectancy for renal survival. Moreover, drug-associated cases seem to tend not to develop disease relapse in the long term.

Association between admission blood glucose and prognosis in non-diabetic patients with first-ever acute myocardial infarction

Background: Admission hyperglycemia has been associated with major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with acute coronary syndrome. Methods: In this study we sought to determine the association between admission blood sugar (ABS) and the outcomes of non-diabetic patients with first-ever acute myocardial infarction (MI). Non-diabetic patients with MI were evaluated from March 2016 to March 2019. Baseline characteristics, laboratories, electrocardiogram, and baseline left ventricular ejection fraction (LVEF) were recorded. All patients were followed up and outcomes were obtained. Follow-up data comprised of repeating electrocardiogram and echocardiography at 1 year, and MACCE, including re-MI, stroke, and mortality. Results: A total of 312 patients with a mean age of 54.2 ± 11.9 years were evaluated. All patients were followed up for a median of 38 months. The frequencies of in-hospital mortality and MACCE at late follow-up were higher in third tertile of ABS compared with those in first and second tertiles (both p <0.05). Based on the Cox regression analysis, the independent predictors of MACCE included age (hazard ratio [HR] 1.068, 95% confidence interval [CI] 1.033 – 1.105, p <0.001), third tertile of ABS >172 mg/dL (HR 21.257, 95% CI 2.832 – 159.577, p=0.003), and baseline LVEF (HR 0.947, 95% CI 0.901 – 0.995, p=0.031). Conclusion: Admission stress hyperglycemia is associated with increased rates of in-hospital mortality and MACCE at late follow-up in non-diabetic patients with MI. Moreover, elevated ABS, older ages, and a decreased value of baseline LVEF predicted MACCE during follow-up.

The Frailty Phenotype in Hemodialysis Patients and its Association with Biochemical Markers of Mineral Bone Disorder, Inflammation and Nutrition

Introduction: Frailty is a state of increased vulnerability to physical stressors. It is common in patients with end-stage renal disease (ESRD) who are on hemodialysis (HD). The aim of this study was to analyze the presence of frailty phenotype among HD patients and to evaluate their interrelationship with different biochemical markers. Methods: For the frailty assessment the Frailty Phenotype by Fried et al. was used, where frailty was reported if three of the following criteria were met: unintentional weight loss, self-reported exhaustion, weakness, slow walking speed and low physical activity. From 281 HD patients, 126 patients were frail, 58 were pre-frail (two criteria were met) and the rest of the study population were robust (97 patients). BMI was calculated for all patients and venous blood samples were taken to determine laboratory parameters for bone alkaline phosphatase (BAP), phosphate (P), potassium (K), C-reactive protein (CRP) and albumin. Results: Patients who were on HD longer than 60 months have more characters of frailty. (p=0.019). A statistically significant positive correlations between frailty score and BAP (rho = 0.189; p = 0.001), and CRP (rho = 0.233; p < 0.001) were observed, and significant negative correlations between frailty score and albumin (rho = - 0.218; p < 0.001) and K (rho = - 0.198; p = 0.001). Conclusions: The associations of frailty with markers of mineral bone disorder, inflammation and nutrition indicate the importance of these parameters in the indirect assessment of the frailty phenotype in HD patients.

A Practical Review of Diabetes Mellitus Type 2 Treatment in Primary Care

The treatment of diabetes mellitus type 2 (DM2) is becoming more complex as new medications are approved. Primary care providers must maintain their medical knowledge on emerging medications for best patient care. This review simplifies the non-insulin treatments of diabetes with an emphasis on the cardio-renal protectants, sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1).