Gut microbiota-derived metabolite trimethylamine N-oxide and biomarkers of inflammation are linked to endothelial and coronary microvascular function in patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD), which is an umbrella term used for ulcerative colitis (UC) and Crohn's disease (CD), is associated with an increased risk for atherosclerotic cardiovascular disease (CVD). We aimed to investigate the association of local and systemic biomarkers of inflammation and gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) with endothelial and coronary microvascular dysfunction in IBD. METHODS: A total of 56 patients with IBD (20 with UC and 36 with CD) and 34 age and gender matched controls were included. For all participants, samples were collected to analyze faecal calprotectin, and TMAO concentrations. Ultrasound-based examinations were done to measure flow-mediated vasodilatation (FMD) and coronary flow velocity reserve (CFVR). RESULTS: Patients with IBD had lower CFVR (2.07 (1.82-2.40)) and FMD (8.7 ± 3.7) as compared to controls (2.30 (2.07-2.74), p = 0.005 and 11.9 ± 6.8, p = 0.03). In patients with IBD, TMAO concentration (r = -0.30, p = 0.03), C-reactive protein (r = -0.29, p = 0.03) and WBC count (r = -0.37, p = 0.006) had a significant negative correlation with CFVR, and TMAO (ß = -0.27, 95 % CI: -0.23 to -0.02) and WBC count (ß = -0.31, 95 % CI: -0.56 to -0.06) were significant predictors of CFVR after multivariate adjustment. None of the biomarkers of inflammation or TMAO showed significant correlations with FMD. In patients with UC, TMAO showed a significant correlation with both CFVR (r = -0.55, p = 0.01) and FMD (r = -0.60, p = 0.005) while only WBC count had a statistically significant correlation with CFVR (r = -0.49, p = 0.004) in patients with CD. CONCLUSIONS: Gut microbiota-derived metabolite TMAO and biomarkers of systemic inflammation are associated with measures of endothelial/coronary microvascular dysfunction in patients with IBD.

Coronary microvascular dysfunction is common in patients hospitalized with COVID-19 infection.

BACKGROUND AND AIMS: Microvascular disease is considered as one of the main drivers of morbidity and mortality in severe COVID-19, and microvascular dysfunction has been demonstrated in the subcutaneous and sublingual tissues in COVID-19 patients. The presence of coronary microvascular dysfunction (CMD) has also been hypothesized, but direct evidence demonstrating CMD in COVID-19 patients is missing. In the present study, we aimed to investigate CMD in patients hospitalized with COVID-19, and to understand whether there is a relationship between biomarkers of myocardial injury, myocardial strain and inflammation and CMD. METHODS: 39 patients that were hospitalized with COVID-19 and 40 control subjects were included to the present study. Biomarkers for myocardial injury, myocardial strain, inflammation, and fibrin turnover were obtained at admission. A comprehensive echocardiographic examination, including measurement of coronary flow velocity reserve (CFVR), was done after the patient was stabilized. RESULTS: Patients with COVID-19 infection had a significantly lower hyperemic coronary flow velocity, resulting in a significantly lower CFVR (2.0 ± 0.3 vs. 2.4 ± 0.5, p < .001). Patients with severe COVID-19 had a lower CFVR compared to those with moderate COVID-19 (1.8 ± 0.2 vs. 2.2 ± 0.2, p < .001) driven by a trend toward higher basal flow velocity. CFVR correlated with troponin (p = .003, r: -.470), B-type natriuretic peptide (p < .001, r: -.580), C-reactive protein (p < .001, r: -.369), interleukin-6 (p < .001, r: -.597), and d-dimer (p < .001, r: -.561), with the three latter biomarkers having the highest areas-under-curve for predicting CMD. CONCLUSIONS: Coronary microvascular dysfunction is common in patients with COVID-19 and is related to the severity of the infection. CMD may also explain the "cryptic" myocardial injury seen in patients with severe COVID-19 infection.

A rare cause of idiopathic right outflow tract premature ventricular contraction: Type-4 renal tubular acidosis.

The premature ventricular contractions (PVCs) have usually good prognosis in patients without structural heart disease. In case of left ventricular ejection fraction depression or symptoms, antiarrhythmic drugs or cardiac ablations could be an option for management. We present a case of a patient with high burden of PVC admitted for cardiac ablation. Preoperative assessment revealed hyperkalemia and metabolic acidosis which ended up with type-4 renal tubular acidosis (RTA). Its rare cause and management may draw attention to the possibility of type -4 RTA as the cause of the PVC, and hyperkalemia.

Evaluation of COVID-19 Patients According to the Survival Time.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was first detected as a form of atypical pneumonia. COVID-19 is a highly contagious virus, and some patients may experience acute respiratory distress syndrome (ARDS) and acute respiratory failure leading to death. We aim to evaluate the clinical, imaging, and laboratory parameters according to survival time to predict mortality in fatal COVID-19 patients. METHODS: Fatal 350 and survived 150 COVID-19 patients were included in the study. Fatal patients were divided into three groups according to the median value of the survival days. Demographic characteristics and in-hospital complications were obtained from medical databases. RESULTS: Of the non-survived patients, 30% (104) died within three days, 32% (110) died within 4-10 days, and 39% (136) died within over ten days. Pneumonia on computational tomography (CT), symptom duration before hospital admission (SDBHA), intensive care unit (ICU), hypertension (HT), C-reactive protein (CRP), D-dimer, multi-organ dysfunction syndrome (MODS), cardiac and acute kidney injury, left ventricular ejection fraction (LVEF), right ventricular fractional area change (RV-FAC), and Tocilizumab/Steroid therapy were independent predictors of mortality within three days compared to between 4-10 days and over ten days mortality.  A combined diagnosis model was evaluated for the age, CT score, SDBHA, hs-TnI, and D-dimer. The combined model had a higher area under the ROC curve (0.913). CONCLUSION: This study showed that age, pneumonia on CT, SDBHA, ICU, HT, CRP, d-dimer, cardiac injury, MODS, acute kidney injury, LVEF, and RV-FAC were independently associated with short-term mortality in non-surviving COVID-19 patients in the Turkish population. Moreover, Tocilizumab/Steroid therapy was a protective and independent predictor of mortality within three days.

Combined past preeclampsia and gestational diabetes is associated with a very high frequency of coronary microvascular dysfunction.

BACKGROUND: A history of preeclampsia (pPE) and gestational diabetes (pGDM) are female-specific risk markers for atherosclerosis and future cardiovascular risk. In addition to increasing the risk of established risk factors for atherosclerosis, such as hypertension or diabetes, evidence suggests that pregnancy-related complications can also directly accelerate atherosclerosis by inducing endothelial dysfunction. A combination of both conditions is seen in a subset of patients with pregnancy, though it is not known whether this combination increases the overall risk for cardiovascular events. AIMS: Present study aimed to find the impact of combined pPE/pGDM on the prevalence of coronary microvascular dysfunction (CMD). METHODS: A total of 24 patients with combined pPE/pGDM, 19 patients with isolated pPE and 63 patients with pGDM were included to the present study and a further 36 healthy women with no previous pregnancy-related complications served as controls. Coronary flow reserve was measured using echocardiography and CMD was defined as a coronary flow reserve ≤2.5. RESULTS: Patients with combined pPE/pGDM had a high prevalence of CMD (91%), which was significantly higher than controls (5.6%, p < 0.001) and patients with pGDM (55%, p = 0.01). A history of pPE on top of pGDM was associated with an increased risk of CMD (HR:6.28, 95%CI:1.69-23.37, p = 0.006) after multivariate adjustment, but pGDM did not increase the odds for CMD in those with pPE. CONCLUSIONS: Combined pPE/pDM is associated with a very high prevalence of CMD, which may indicate an increased risk for future cardiovascular events.

HNF1A gene p.I27L is associated with co-existing preeclampsia in gestational diabetes mellitus.

The association of the FTO gene and HNF1α gene on gestational diabetes mellitus (GDM) and preeclampsia remains unclear. This is the first study to examine whether HNF1α gene and FTO gene were associated with having GDM and preeclampsia in Turkish women. Healthy pregnant women (n = 101) and women with GDM (n = 169) were included. GDM was divided into two groups as GDM-only (n = 90) and GDM-preeclampsia (n = 79). Genotyping of HNF1α gene p.I27L, p.A98V, and p.S487N, and FTO gene rs9939609 SNPs were performed using RT-PCR. The frequency of p.S487N, p.A98V, and FTO genotype were similar between the groups (p > .05). p.I27L GG-wild, GT, and TT genotype were 56.5%, 36.6%, and 6.9% in controls; 40.0%, 51.1%, and 8.9% in GDM-only; and 26.6%, 51.9%, and 21.5% in GDM-preeclampsia (p = .034). TT and GT genotype was more frequent in GDM-preeclampsia than in controls (p < .05). GT genotype was increased in GDM-only compared with controls (p < .05). TT genotype was more frequent in GDM-preeclampsia than in GDM-only (p < .05). p.I27L TT genotype was independently associated with increased blood pressure (BP) and urinary protein. p.I27L TT genotype was associated with increased preeclampsia risk in patients with GDM by increasing BP and urinary protein.

Does celiac disease impair coronary microvascular circulation: Coronary flow velocity reserve of patients with celiac disease.

BACKGROUND: Celiac disease (CD) is an enteropathy characterized with immune reaction to gliadin protein. AIM: In this study, we aimed to assess effect of CD on coronary microvascular circulation and the association between coronary flow velocity reserve (CFVR) and hs-CRP/Albumin ratio. MATERIAL AND METHODS: Study was conducted between March 2017 and November 2018 with CD at Umraniye Training and Research Hospital Gastroenterology Clinic. CFVR was defined as the ratio of hyperemic to baseline diastolic peak velocities. CFVR ≥ 2.0 was considered normal. C-reactive protein/albumin ratio (CAR) was calculated as hs-CRP/albumin. RESULTS: Serum albumin (4.27 ± 0.56 vs 4.50 ± 0.34; P value: .04) level was significantly lower in celiac group but higher Hs-CRP (2.44 ± 1.24 vs 1.82 ± 1.29; P value < .01), hs-CRP/albumin ratio (0.57 ± 0.30 vs 0.41 ± 0.31; P value: .03) were recorded in celiac group. Both hyperemic flow and CFVR substantially lower in the celiac group compared to controls. In univariate analysis; age, hs-CRP, and hs-CRP/albumin ratio were associated with low CFVR and hs-CRP/albumin level was an accurate predictor of low CFVR at the ROC curve. CONCLUSION: In this study, we found that in patients with CD, coronary flow reserve is impaired.

Relationship between malnutrition and coronary microvascular dysfunction in patients with nonischemic dilated cardiomyopathy

Background/ aim: Malnutrition is common in patients with nonischemic dilated cardiomyopathy (DCM), especially in the end stages of the disease where heart failure symptoms predominate. Malnutrition has been associated with atherosclerosis in patients with chronic kidney disease, but it is unknown whether a similar relationship exists between malnutrition and coronary microvascular dysfunction (CMD). In the present study, we aimed to analyse whether indices of malnutrition were associated with coronary flow reserve (CFR) in patients with DCM. Materials and methods: A total of 33 cases who were prospectively followed up with by institutional DCM registry were found eligible for inclusion. Coronary flow reserve was measured with transthoracic echocardiography from the left anterior descending artery. The study sample was divided into 2 groups using a CFR cut-off value of 2.0. Geriatric nutritional index (GNI), prognostic nutritional index (PNI), and C-reactive protein/albumin ratio (CAR) were calculated. Results: A total of 17 out of 33 cases (51.5%) had a low (<2.0) CFR. Both GNI and PNI were similar between the 2 groups, but the inflammatory­nutritional parameter CAR was significantly higher in those with a low CFR (1.18 ± 0.64 vs. 0.54 ± 0.28, P < 0.001). CAR remained an independent predictor of CFR on multivariate regression (ß = 0.65, P < 0.001) after adjustment for demographic (age, sex, body mass index), nutritional (GNI, PNI, albumin), and inflammatory (C-reactive protein) parameters. For a cut-off value of 0.80, CAR had a sensitivity of 85.7% and specificity of 73.6% to predict a CFR <2.0 (AUC: 0.835, 95%CI: 0.693­0.976, P = 0.001). Conclusions: Our findings indicate that not malnutrition per se but a combination of inflammation activation and malnutrition is predictive of CMD in patients with DCM.

Clinical evaluation of pituitary insufficiency in adult population

Background/aim: This retrospective study aimed to investigate the clinical profile of pituitary insufficiency (PI) in adult population. Materials and methods: One hundred and fifty patients who were diagnosed as having PI between 2012 and 2018 (53.3% female, mean age 48.13 ± 15.83 years) were retrospectively analyzed. Results: Age at diagnosis was higher in females as compared with males (51.13 ± 15.95 vs. 44.70 ± 15.08 years, P = 0.012). The most frequent presenting signs were headache (29.4%) and visual disturbance (19.6%) in general. Females frequently presented with headache (33.3%), whereas males presented with sexual dysfunction (34.4%). The most frequent cause of PI was nonfunctional pituitary adenoma (28.8%) in general population. A frequent cause of PI was Sheehan's syndrome (33.8%) among females and nonfunctional pituitary adenoma (38.6%) among males. Pituitary macroadenoma (75.8%) was frequent in pituitary tumors with PI. 55.3 % of the patients had 4 pituitary hormones deficiencies and 26.0% of patients had 3 pituitary hormones deficiencies. Gonadotropin deficiency was the leading pituitary hormone deficiency. The frequency of posttraumatic PI was 4.7% in the general population. Conclusion: Nonfunctional pituitary adenoma was the most common cause of PI among males and Sheehan's syndrome was a major etiologic factor in females. Sheehan's syndrome remains an important health problem in Turkey although obstetric care has improved. Posttraumatic PI should be considered in the differential diagnosis of idiopathic PI.

Lobectomy may not be suitable for patients with follicular neoplasm cytology

Background/aim: The most appropriate surgical management of follicular neoplasm/suspicious for follicular neoplasm (FN) lesions is still contradictory. We aimed to evaluate the data of our patients with follicular neoplasm treated with thyroidectomy. Materials and methods: We retrospectively analyzed the data of 74 patients who were diagnosed with follicular neoplasm cytology (FN cytology) by fine needle aspiration biopsy (FNAB) and had undergone total thyroidectomy or lobectomy with isthmectomy (LwI). Results: We examined a total of 74 patients, of which 64 (83.7%) were female and 10 (16.3%) were male. The malignancy rate in the pathological examinations of these patients was 31/74 (41.9%). The most common cancer among the patients with malignancy was papillary thyroid carcinomas (PTC) (20/31, 65%). Among the subtypes of PTCs, 11 were classical PTC, 5 were a follicular variant of PTC, 2 were the oncocytic variant of PTC, 1 was the diffuse sclerosing variant, and 1 was a columnar cell variant of PTC. Conclusion: Since most FN cytology has been pathologically diagnosed with papillary cancer and some papillary cancer subtypes have been unfavorable pathologically, total thyroidectomy should be the most suitable treatment option in this group. Lobectomy with LwI is not suitable for patients with FNAB-proven FN cytology.

The VDR gene FokI polymorphism is associated with gestational diabetes mellitus in Turkish women.

BACKGROUND: The association between the vitamin D receptor (VDR) gene and gestational diabetes mellitus (GDM) has not been investigated in Turkish pregnant women. We aimed to investigate associations between VDR gene BsmI (rs15444410), ApaI (rs7975232), FokI (rs19735810), and TaqI (rs731236) single nucleotide polymorphisms (SNPs) and GDM. MATERIAL-METHODS: This case-control study comprised 100 women with GDM and 135 pregnant women without GDM. The VDR polymorphism was evaluated using Sanger-based DNA sequencing. RESULT: VDR gene ApaI, BsmI, and TaqI SNPs did not differ between women with and without GDM (each, p > 0.05). ApaI, BsmI, and TaqI were not associated with GDM risk. The VDR gene FokI CT/TT genotype was associated with an increased GDM risk (CT vs. CC, OR = 1.84, 95% CI: [1.05-3.23], p = 0.031; TT vs. CC, OR = 3.95, 95% CI: [1.56-9.96], p = 0.002; CT/TT vs. CC, OR = 2.29, 95% CI: [1.35-3.89], p = 0.002; and CT/CC vs. TT, OR = 3.02, 95% CI: [1.23-7.38], p = 0.012). The FokI-TT genotype was more associated with younger age and higher glucose, HbA1c, and HOMA-IR than the CC and CT genotype. FokI-T was positively correlated with log-HOMA-IR (r = 0.326, p = 0.004). FokI SNPs were independently associated with GDM after adjusting for BMI and age (ß = 1.63, 95% CI: [1. 2-4.2], p = 0.012). There were no associations between the FokI, ApaI, BsmI and TaqI haplotypes and GDM. CONCLUSION: VDR gene FokI SNPs were independently associated with having GDM in Turkish women. VDR gene FokI SNPs might contribute to insulin resistance of developing GDM.

HNF1A gene p.I27L is associated with early-onset, maturity-onset diabetes of the young-like diabetes in Turkey.

BACKGROUND: The molecular basis of the Turkish population with suspected maturity-onset diabetes of the young (MODY) has not been identified. This is the first study to investigate the association between HNF1A-gene single-nucleotide polymorphisms (SNPs) and having early-onset, MODY-like diabetes mellitus in the Turkish population. METHODS: All diabetic patients (N = 565) who presented to our clinic between 2012 and 2015 with a clinical suspicion of MODY were included in the study. Analysis of HNF1A, HNFB, HNF4A, GCK gene mutations was performed using real-time polymerase chain reaction sequencing. After genetic analysis, diabetics (n = 46) with HNF1A, HNF1B, HNF4A, GCK gene mutations (diagnosed as MODY) and diabetics (n = 30) with HNF1B, HNF4A, GCK gene SNPs were excluded. Patients with early-onset, MODY-like diabetes (n = 486) and non-diabetic controls (n = 263) were included. Genetic analyses for the HNF1A gene p.S487 N (rs2464196), p.A98V (rs1800574) and p.I27L (rs1169288) SNPs were performed using Sanger-based DNA sequencing among the control group. RESULTS: p.S487 N and p.A98V was similar between the diabetics and controls in dominant and recessive models with no association (each, p > 0.05). p.I27L GT/TT carriers (GT/TT vs. GG, OR = 1.68, 95% CI: [1. 21-2.13]; p = 0.035) and p.I27L TT carriers had increased risk of having MODY-like diabetes (GT/GG vs. TT, OR = 1.56, 95% CI: [1. 14-2.57]; p = 0.048). Family inheritance of diabetes was significantly more common in patients with the p.I27L TT genotype. The p.I27L SNP was modestly associated with having diabetes after adjusting for body mass index and age (ß = 1.45, 95% CI: [1. 2-4.2]; p = 0.036). CONCLUSIONS: The HNF1A gene p.I27L SNP was modestly associated with having early-onset, MODY-like diabetes in the Turkish population. HNF1A gene p.I27L SNP might contribute to age at diabetes diagnosis and family inheritance.

Parathyroidectomy improves cardiovascular risk factors in normocalcemic and hypercalcemic primary hyperparathyroidism.

BACKGROUND: Parathyroidectomy has ameliorated cardiovascular risk factors in patients with hypercalcemic primary hyperparathyroidism (PHPT), but the effect of parathyroidectomy on normocalcemic PHPT is not exactly known. This case-controlled study aimed to investigate the effect of parathyroidectomy on cardiovascular risk factors in patients with normocalcemic and hypercalcemic PHPT. METHODS: Subjects with normocalcemic PHPT (n = 35), age- and sex-matched hypercalcemic PHPT (n = 60) and age- and sex-matched control (n = 60) were included. Cardiometabolic disorders were investigated with traditional cardiometabolic risk factors and the Framingham cardiovascular risk score (CRS) before and 6 months after parathyroidectomy. RESULTS: Diabetes, dyslipidemia, hypertension, obesity, insulin resistance, osteoporosis, having fractures were similarly increased in the hypercalcemic and normocalcemic PHPT groups (p > 0.05) compared with the controls (p < 0.05). Blood pressures, glucose metabolism (glucose, insulin, HOMA-IR) and lipid profiles were similarly increased in the PHPT groups (p > 0.05) compared with the controls (p < 0.05). After parathyroidectomy, blood pressures, serum total cholesterol, and HOMA-IR were decreased in both PHPT groups (p < 0.05). CRS was lower in the controls (5.74 ± 3.24, p < 0.05). After parathyroidectomy, CRS was decreased in the normocalcemic (11.98 ± 10.11 vs. 7.37 ± 4.48) and hypercalcemic (14.62 ± 11.06 vs. 8.05 ± 7.72) PHPT groups. Increased blood pressures were independent predictors of serum iPTH. CONCLUSION: The normocalcemic and hypercalcemic PHPT groups had similarly increased cardiovascular risk factors, even independently of serum calcium. Parathyroidectomy ameliorated the increased cardiovascular risk factors in both normocalcemic and hypercalcemic PHPT.

The effect of disease activity on thyroid nodules in patients with acromegaly.

Nodular thyroid disease is a very common disorder in patients with acromegaly. Insulin-like growth factor-1 (IGF-1) is a thyroid growth factor, and there is a correlation between IGF-1 levels and thyroid volume (TV) in patients with acromegaly. There is no study investigating the impact of somatostatin analog (SSA) treatment on thyroid nodule volume in patients with acromegaly. We aimed to assess thyroid nodule volume change with SSA treatment in patients with persistent acromegaly. We retrospectively analyzed data from 108 consecutive patients with acromegaly who were followed up by our clinic after undergoing surgery between 2002 and 2014. Patients who were cured after surgery were excluded. We only selected 43 patients (21 males, 22 females, mean age 52.8 ± 11.9 years) who did not meet the criteria of remission postoperatively, who were treated with SSA for at least six months and had normal thyroid function. Patients were divided into three groups (well-controlled, controlled, and active) according to their IGF-1 and growth hormone (GH) levels. All patients underwent an evaluation of TV and total thyroid nodule volume (TTNV) by ultrasound. TTNV decreased significantly in patients with well-controlled acromegaly (0.44 [0.75] to 0.23 [0.73], p < 0.001). TTNV did not change in controlled patients (0.18 [1.28] to 0.13 [1.54], p = 0.959); however TTNV increased in patients with active acromegaly (0.77 [1.46] to 1.03 [1.88], p = 0.028). Successful medical treatment of patients with active acromegaly decreases thyroid nodule volume. Sustained exposure to IGF-1 may cause an increase in thyroid nodule volume in patients with acromegaly.

Comparison of functional metacarpal splint and ulnar gutter splint in the treatment of fifth metacarpal neck fractures: a prospective comparative study.

BACKGROUND: Fifth metacarpal fractures are the most common fractures of the hand. These fractures are generally treated with conservative methods. The aim of this study was to compare the radiological and clinical outcomes of two conservative treatment methods, functional metacarpal splint(FMS) and ulnar gutter splint(UGS), for the treatment of fifth metacarpal neck fractures. METHODS: A prospective comparative study was designed to assess the conservative treatment of isolated and closed stable fractures of the fifth metacarpal neck. In total, 58 patients were included in the study and were treated with FMS or UGS after fracture reduction in a consecutive order. Angulation, shortening and functional outcome (QuickDASH scores and grip strengths) were evaluated at the 2nd and 6th months. RESULTS: Forty patients returned for follow-up. Twenty-two patients were treated with FMS, and 18 patients were treated with UGS. The average age was 28 years (SD ± 12, range;18-43) in the FMS group and 30 years (SD ± 14, range;18-58) in the UGS group. After reduction, significant correction was achieved in both groups, but the average angulation was lower in the FMS group(16 ± 7) compared with the UGS group (21 ± 8)(p = 0.043). However, this better initial reduction in FMS group(16 ± 7) could not be maintained in the 1st month follow-up (21 ± 5) (p = 0.009). In the FMS group, the improvement in QuickDASH scores between the 2nd and 6th month follow-up was significant (p = 0.003) but not in the UGS group(p = 0.075). When the expected grip strengths were calculated, the FMS group reached the expected strength values at the 2nd month follow-up, whereas the UGS group still exhibited significantly lower grip strength at the 2nd month follow-up(p = 0.008). However, at the end of the 6th month follow-up, both groups exhibited similar reduction, QuickDASH and grip strength values. CONCLUSIONS: In stable 5th metacarpal neck fractures, FMS is adequate to prevent loss of reduction and yields faster improvement in clinical scores with earlier gain of normal grip strength compared with UGS. However, in the long term, both FMS and UGS methods yield similar radiological and clinical outcomes. Patient comfort and compliance may be better with FMS due to less joint restriction, and these findings should be considered when deciding the treatment method. TRIAL REGISTRATION: ISRCTN79534571 The date of registration: 01/04/2019 Type of study/level of evidence: Therapeutic, II.

The effect of parathyroidectomy on bone mineral density in primary hyperparathyroidism

Background/aim: This study aimed to investigate the change in bone mineral density (BMD) before and 1 year after parathyroidectomy in patients with primary hyperparathyroidism (PHPT). Materials and methods: The clinical and biochemical parameters and DEXA screening of patients with symptomatic PHPT (n = 28) and asymptomatic PHPT (n = 63) were investigated before and 1 year after parathyroidectomy. Results: Patients with symptomatic PHPT had a higher prevalence of nephrolithiasis (18.2% vs. 4.6%, P = 0.032) when compared to the prevalence in patients with asymptomatic PHPT. The prevalence of osteoporosis in the lumbar spine (63.0% vs. 37.5%, P = 0.026) and femoral neck (40.7% vs. 20.6%, P = 0.048) was higher in symptomatic PHPT when compared to the prevalence in asymptomatic PHPT. After parathyroidectomy, the decreases in the prevalence of osteoporosis in the lumbar spine (25.8% vs. 9.4%, P = 0.014), femoral neck (22.1% vs. 8.2%, P =0.009), and total hip (22.4% vs. 5.3%, P = 0.007) were higher in symptomatic PHPT compared to the asymptomatic PHPT group. A higher BMD gain (g/cm2) was seen in the lumbar spine (10.83% vs. 4.65%, P=0.016) and femoral neck (12.61% vs. 4.37%, P=0.005) in symptomatic PHPT compared to the asymptomatic PHPT group. Conclusion: Parathyroidectomy provided more BMD gain in the lumbar spine and femoral neck in patients with symptomatic PHPT when compared to patients with asymptomatic PHPT 1 year after parathyroidectomy.

Effect of parathyroidectomy on epicardial fat thickness as a cardiovascular risk factor in patients with primary hyperparathyroidism

Background/aim: Several studies demonstrated that primary hyperparathyroidism is related to increased risk for cardiovascular diseases (CVDs), and risk is decreased by parathyroidectomy. Epicardial fat thickness (EFT) has been postulated as a new marker of CVD risk. We evaluated the impact of parathyroidectomy on EFT in patients with primary hyperparathyroidism (PHPT). Materials and methods: Thirty-four PHPT patients (29 female, 5 male) and 28 age- and sex-matched controls (19 female, 9 male) were included in the study. Demographic, anthropometric, and biochemical data were recorded both before parathyroidectomy and 6 months after the procedure. Epicardial fat thickness was measured by transthoracic echocardiography. Results: Mean age was 53.15 ± 8.44 years. Mean preoperative EFT was higher than mean EFT in the control group (0.49 ± 0.07 cm to 0.46 ± 0.08 cm, P: 0.0005), and EFT decreased after parathyroidectomy (0.49 ± 0.07 cm to 0.44 ± 0.08 cm, P: 0.0005). Systolic blood pressure and calcium, parathormone, and hsCRP levels decreased after parathyroidectomy (P < 0.05). Vitamin D levels increased (P < 0.05). Diastolic blood pressure, body mass index, carotid intima-media thickness, and HOMA-IR, fasting plasma glucose, and phosphorus levels were unchanged after parathyroidectomy (P > 0.05). Preoperatively, EFT was correlated with SBP (r: 0.360, P: 0.0285) and age (r: 0.466, P: 0.0036). Multiple linear regression used to identify independent predictors of change in epicardial fat did not find any predictor of change in epicardial fat (P > 0.05). Conclusion: EFT was decreased by parathyroidectomy in patients with primary hyperparathyroidism.However, the decrease in EFT was not correlated with any of the cardiovascular risk factors. More comprehensive studies evaluating the potential relation between PHPT and EFT need to be conducted.

Factors associated with glomerular filtration rate variation in primary hyperparathyroidism after parathyroidectomy

Background/aim: Prolonged hypercalcemia impairs renal function, and a reduced glomerular filtration rate (GFR) is typical in advanced primary hyperparathyroidism (PHPT). There are scarce data related to predictors of renal impairment in patients with PHPT. Hence, we aimed to evaluate changes in kidney function in PHPT patients after parathyroidectomy (PTX) and identify factors associated with GFR variation in these patients. Materials and methods: One hundred and twenty-five patients with PHPT who underwent surgery between 2012 and 2014 were enrolled in the study. Patients were divided into two groups according to GFR values: patients whose GFR was lower than 60 mL/min/1.73 m2 and higher than 60 mL/min/1.73 m2. Demographic and laboratory parameters were compared before and 6 months after parathyroidectomy. Results: Prevalence of antihypertensive drug users and patients with renal cysts and parathormone (PTH) and alkaline phosphatase levels were higher in patients with GFR of ≥60 than in GFR of <60 mL/min/1.73 m2 (P < 0.05). Systolic BP, uric acid, and magnesium were decreased in patients with GFR of ≥60, but GFR did not change in the two groups after parathyroidectomy. After parathyroidectomy, calcium and PTH decreased but 25(OH)D3 and phosphorus increased in the two groups. In multiple regression analysis, age, calcium, and baseline GFR were independent predictors of GFR variation. Parathyroid adenoma volume and urinary calcium were not independent predictors of GFR change. Conclusion: Olderage, higher preoperative calcium, and GFR were factors associated with GFR increase in PHPT patients after parathyroidectomy. Further renal impairment was prevented by parathyroidectomy in PHPT patients

VDR gene FokI polymorphism as a poor prognostic factor for papillary thyroid cancer.

This is the first study to investigate the effect of vitamin D receptor ( VDR) gene single-nucleotide polymorphisms on the clinicopathologic features of papillary thyroid cancer in Turkey. A total of 165 patients with papillary thyroid cancer and 172 controls were included in this case-control study. VDR gene single-nucleotide polymorphisms FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) were evaluated using reverse-transcription polymerase chain reaction. VDR gene polymorphisms BsmI, ApaI, and TaqI did not differ between the papillary thyroid cancer group and control group (p > 0.05, each). BsmI, ApaI, and TaqI were not associated with papillary thyroid cancer risk. The VDR gene FokI CT/TT genotype was associated with an increased papillary thyroid cancer risk (CT vs CC: odds ratio = 1.71, 95% confidence interval = 1.15-2.76, p = 0.028; TT vs CC: odds ratio = 2.44, 95% confidence interval = 1.29-4.62, p = 0.005; CT/TT vs CC: odds ratio = 1.88, 95% confidence interval = 1.20-2.96, p = 0.006; CT/CC vs TT: odds ratio = 1.80, 95% confidence interval = 1.05-3.20, p = 0.041). VDR gene polymorphisms were not in linkage disequilibrium. The FokI TT genotype was associated with having T3 and T4, stage III/IV, extra-thyroidal invasion. The FokI CT/TT or TT genotype was associated with developing N1 status, multifocality, tumor size ≥10 mm, and treatment with radioiodine therapy. Persistence/recurrence did not differ between the FokI genotypes. Carriers of the FokI T allele were at an increased risk of more advanced tumor-node-metastasis stage, greater tumor size, multifocality, and extra-thyroidal invasion of papillary thyroid cancer compared with the CC genotype. VDR gene FokI T allele and TT genotype correlated with aggressiveness of papillary thyroid cancer; thus, FokI could be useful as a poor prognostic factor to assess the high risk of papillary thyroid cancer.

Role of the oxidative stress index, myeloperoxidase, catalase activity for cardiac allograft vasculopathy in heart transplant recipients.

BACKGROUND: The aim of this study was to explore the role of oxidative stress index (OSI), myeloperoxidase (MPO), and catalase (CAT) activity in cardiac allograft vasculopathy (CAV) in heart transplant recipients (HTRs). METHODS: The study enrolled a median age of 41 ± 9 years 47 recipients. The HTx patients were divided into two groups based on the presence CAV as follows: CAV(+) and CAV(-) group. Also, CAV(+) group were divided into two groups as mild/moderate to severe CAV. The OSI, MPO, and CAT activity were analyzed in both groups. RESULTS: The mean total antioxidant capacity (0.79 ± 0.46 vs 1.03 ± 0.33 µmol H2 O2 equiv/L) P = .043 was significantly lower and OSI, MPO, CAT activity were significantly higher in CAV(+) group (63 ± 38 vs 20 ± 16 arbitrary unit, P = .001; 398 ± 242 vs 139  ± 112 µg/L, P = .001; 51 ± 42 vs 26 ± 23 pmol/mg protein, P = .013, respectively). Also, mean OSI (38 ± 41 vs 93 ± 75, P = .05) were significantly higher in severe CAV(+) group. Recipient age, male gender, and low density lipoprotein-cholesterol were significantly higher in CAV(+) group. There was a moderate correlation between the CAV grade and OSI, MPO, and CAT levels in univariate analysis (r = .560, P = .002; r = .643, P = .007; r = .681, P = .001, respectively). CONCLUSION: An increase in the serum level of OSI, MPO, and CAT was associated with CAV in HTRs.