The Mutual Interplay between Bone, Glucose and Lipid Metabolism: The Role of Vitamin D and PTH.

BACKGROUND: We sought to investigate the mutual interplay between bone, glucose and lipid metabolism in a wide cohort of community-based subjects. METHODS: We studied 1240 blood donors (F/M ratio 1/3.2, mean age 41.9 ± 11.7 SD). Serum ionized (Ca++), magnesium (Mg++), 25-hydroxy-vitamin D [25(OH)D], PTH-1-84, 1,25-dihydroxyvitamin D [1,25(OH)2D], total cholesterol (C), HDL-C, triglycerides and glucose were measured and LDL-C levels were calculated in all subjects. RESULTS: 25(OH)D negatively correlated with BMI (R = -0.11), PTH (R = -0.16) (p < 0.0001), total C (R = -0.06, p < 0.05) and triglycerides (R = -0.13, p < 0.0001) and positively with 1,25(OH)2D (R = 0.12) and creatinine (R = 0.17) (p < 0.0001). Serum PTH positively correlated with total C (R = 0.08, p < 0.01), LDL-C (R = 0.1, p < 0.001), triglycerides (R = 0.09, p < 0.01) and glucose (R = 0.15, p < 0.0001) and negatively with HDL-C (R = -0.09, p < 0.01). The odds of showing abnormal serum triglycerides and HDL-C increased as 25(OH)D decreased (p < 0.0001 and p < 0.03) and PTH increased (p < 0.03 and p = 0.05), while the odds of showing abnormal LDL-C levels increased in association with elevated PTH (p < 0.01). CONCLUSION: Vitamin D, PTH, glucose and lipid metabolism are mutually influenced. Hypovitaminosis D predisposes toward worsening lipid profiles through the actions of PTH, while serum PTH levels per se associate with higher glucose and LDL-C levels.

Peri-operative blood management of Jehovah's Witnesses undergoing cytoreductive surgery for advanced ovarian cancer.

BACKGROUND: The aim of this study was to evaluate the efficacy and feasibility of a peri-operative bloodless medicine and surgery (BMS) protocol in reducing severe post-operative anaemia (haemoglobin [Hb] <7 g/dL) in Jehovah's Witnesses undergoing cytoreductive surgery for advanced epithelial ovarian cancer. MATERIALS AND METHODS: This was a single-institution retrospective study enrolling Jehovah's Witnesses who underwent elective bloodless surgery for advanced epithelial ovarian cancer between October 2017 and April 2020. All patients followed a standardised bloodless medicine and surgery protocol based on ferric carboxymaltose and erythropoietin if indicated. RESULTS: Twenty-five patients with a mean age of 61.7 years (range, 35-80) were enrolled. Pre-operatively, ten patients (40%) were mildly anaemic (mean Hb of 10.2 g/dL [range, 9.2-11.4]) and received ferric carboxymaltose. Only four (16%) patients had severe anaemia after surgery (mean Hb of 6.1 g/dL [range, 4.1-6.9]) and received ferric carboxymaltose and erythropoietin. Compared to patients with a post-operative Hb ≥7 g/dL, those with Hb <7 g/dL had higher mean body mass index (25.8±1.8 vs 30.7±1.8 kg/m2; p<0.001), mean baseline CA125 (236.1±184.5 vs 783.7±273.5 IU/mL; p<0.001), median surgical complexity score (2 vs 10; p<0.001), and rate of post-operative complications (14.3 vs 100%; p<0.001). Moreover, these patients had a longer mean operating time (3.4±0.6 vs 5.5±0.4 h; p<0.001), duration of stay in hospital (5.5±0.7 vs 24.0±9.8 days; p<0.001), and time to adjuvant chemotherapy (27.2±2.6 vs 65.3±13.4 days; p<0.001). DISCUSSION: The use of a multidisciplinary bloodless medicine and surgery protocol is safe and effective in reducing the rate of severe post-operative anaemia and improving surgical and oncological outcomes of Jehovah's Witnesses with advanced epithelial ovarian cancer. Further large-scale, prospective studies are required to confirm these data.

Peri-operative blood management of Jehovah's Witnesses undergoing cytoreductive surgery for advanced ovarian cancer.

BACKGROUND: The aim of this study was to evaluate the efficacy and feasibility of a peri-operative bloodless medicine and surgery (BMS) protocol in reducing severe post-operative anaemia (haemoglobin [Hb] <7 g/dL) in Jehovah's Witnesses undergoing cytoreductive surgery for advanced epithelial ovarian cancer. MATERIALS AND METHODS: This was a single-institution retrospective study enrolling Jehovah's Witnesses who underwent elective bloodless surgery for advanced epithelial ovarian cancer between October 2017 and April 2020. All patients followed a standardised bloodless medicine and surgery protocol based on ferric carboxymaltose and erythropoietin if indicated. RESULTS: Twenty-five patients with a mean age of 61.7 years (range, 35-80) were enrolled. Pre-operatively, ten patients (40%) were mildly anaemic (mean Hb of 10.2 g/dL [range, 9.2-11.4]) and received ferric carboxymaltose. Only four (16%) patients had severe anaemia after surgery (mean Hb of 6.1 g/dL [range, 4.1-6.9]) and received ferric carboxymaltose and erythropoietin. Compared to patients with a post-operative Hb ≥7 g/dL, those with Hb <7 g/dL had higher mean body mass index (25.8±1.8 vs 30.7±1.8 kg/m2; p<0.001), mean baseline CA125 (236.1±184.5 vs 783.7±273.5 IU/mL; p<0.001), median surgical complexity score (2 vs 10; p<0.001), and rate of post-operative complications (14.3 vs 100%; p<0.001). Moreover, these patients had a longer mean operating time (3.4±0.6 vs 5.5±0.4 h; p<0.001), duration of stay in hospital (5.5±0.7 vs 24.0±9.8 days; p<0.001), and time to adjuvant chemotherapy (27.2±2.6 vs 65.3±13.4 days; p<0.001). DISCUSSION: The use of a multidisciplinary bloodless medicine and surgery protocol is safe and effective in reducing the rate of severe post-operative anaemia and improving surgical and oncological outcomes of Jehovah's Witnesses with advanced epithelial ovarian cancer. Further large-scale, prospective studies are required to confirm these data.

The relative influence of serum ionized calcium and 25-hydroxyvitamin D in regulating PTH secretion in healthy subjects.

BACKGROUND: While the inverse relationship between serum ionized calcium (Ca2+) and PTH is well-established, the relationship between 25(OH)D and PTH showed conflicting results. The study aimed to evaluate the relative contributions of age, sex, serum Ca2+, ionized magnesium (Mg2+), 25(OH)D and 1,25(OH)2D in regulating PTH secretion in healthy subjects. METHODS: This is a secondary analysis of an observational study performed from March 2014 to July 2015 carried out in 2259 blood donors (1652 men and 607 women, age range 18-68 years). Subjects with parathyroid disorders and taking drugs that affect mineral metabolism were excluded. RESULTS: Significant correlations [between Ca2+ and PTH (r = -0.223, p < 0.001), 25(OH)D and PTH (r = -0.178, p < 0.001) and between PTH and age (r = 0.322, p < 0.001)] were found. As a preliminary step to multivariate analysis, a regression tree analysis was performed using PTH as response variable and age, Ca2+, Mg2+, 25(OH)D, 1,25(OH)2D and sex as explanatory variables to determine the effect of each covariate on the response variable. For subjects <38 years, 25(OH)D was the most important parameter in regulating PTH. For subjects ≥38 both 25(OH)D and Ca2+ levels regulated PTH secretion. Subjects with 25(OH)D < 13 ng/mL had average higher PTH; in this group only, subjects with Ca2+ ≥ 1.30 mmol/L had average lower PTH compared to subjects with Ca2+ < 1.30. The multivariate analysis showed that all variables had a significant effect (p < 0.001) on PTH. Anova Type III errors c indicated that 25(OH)D accounted for 32.1% of the total variance in PTH, Ca2+ accounted for 18% of the total variance, BMI for 14.3%, and 1,25(OH)2D for 11.1%. The remaining percentage was attributable to age and sex. This was confirmed by the regression tree approach, where 25(OH)D and Ca2+ accounted for the largest variation in the average levels of PTH. DISCUSSION: Under stable conditions 25(OH)D plays a significant role in regulating PTH secretion. Under conditions of relative vitamin D sufficiency, Ca2+ also plays an important role.

Successful Management of a Chronic Refractory Leg Ulcer in an Adolescent with Sickle Cell Anemia.

Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by a wide range of clinical manifestations. Chronic leg ulcers are a disabling complication with repercussions on the quality of life. We report the case of a 14-year-old girl with a diagnosis of SCD who developed a chronic leg ulcer that was successfully treated with a multi-disciplinary approach, including local and systemic therapies. The role of different treatments, in particular low molecular weight heparin, in the refractory chronic leg ulcer healing process will be discussed.

Use of platelet-rich plasma to reinforce the staple line during laparoscopic sleeve gastrectomy: feasibility study and preliminary outcome.

AIMS: Reinforcement of the staple line is one of the most debated technical aspects concerning laparoscopic sleeve gastrectomy (LSG). Different buttressing methods have been proposed and demonstrated to be effective in reducing the incidence of staple line bleeding, although data concerning their effort on staple line leakage are not consistent. The aim of this study was to ascertain the technical feasibility and to report the preliminary outcomes of laparoscopic use of platelet-rich plasma (PRP) to reinforce the staple line during sleeve gastrectomy. PATIENTS AND METHODS: From March 2012 to May 2012, 20 patients were prospectively enrolled (10 females; mean age, 44.6 ± 11 years; mean body mass index, 42.3 ± 5.45 kg/m(2)). Type 2 diabetes mellitus was present in 4 patients, obstructive sleep apnea syndrome in 3, and hypertension in 6. LSG was performed using a 48-French bougie and gold cartridges; reinforcement of the staple lines with buttressed materials or oversewing the suture was performed excluding the last cranial cartridge. PRP was prepared by separating the platelets from autologous blood withdrawn on the same day of surgery, in order to obtain a membrane with cylindrical shape (2×5 cm) formed by fibrin and active platelets. The membrane is introduced through the 10-mm trocar and placed at the upper portion of the staple line. The overall cost for the preparation of PRP is about €15. RESULTS: No intraoperative complications and conversions have been recorded during the surgical procedures. No deaths occurred. The mean operative time was 85 ± 31 minutes, which was not significantly increased compared with the operative time of the surgeon's overall personal series (750 cases). At 12 months of follow-up the abdominal ultrasound was negative for collections, and upper contrast showed no images indicating gastric leaks. In no case did PRP induce symptoms of rejection, infection, or adverse events. CONCLUSIONS: The use of PRP during LSG is feasible, does not increase significantly the operative time, does not require any special devices, and is cost effective. A larger cohort of patients is needed to ascertain the potential effectiveness of PRP in the prevention of postoperative staple line complications.

Posterolateral arthrodesis in lumbar spine surgery using autologous platelet-rich plasma and cancellous bone substitute: an osteoinductive and osteoconductive effect.

Study Design Prospective cohort study. Objectives To analyze the effectiveness and practicality of using cancellous bone substitute with platelet-rich plasma (PRP) in posterolateral arthrodesis. Methods Twenty consecutive patients underwent posterolateral arthrodesis with implantation of cancellous bone substitute soaked with PRP obtained directly in the operating theater on the right hemifield and cancellous bone substitute soaked with saline solution on the right. Results Computed tomography scans at 6 and 12 months after surgery were performed in all patients. Bone density was investigated by comparative analysis of region of interest. The data were analyzed with repeated-measures variance analyses with value of density after 6 months and value of density after 12 months, using age, levels of arthrodesis, and platelet count as covariates. The data demonstrated increased bone density using PRP and heterologous cancellous block resulting in an enhanced fusion rate during the first 6 months after surgery. Conclusions PRP used with cancellous bone substitute increases the rate of fusion and bone density joining osteoinductive and osteoconductive effect.

Use of platelet-leukocyte membrane in arthroscopic repair of large rotator cuff tears: a prospective randomized study.

BACKGROUND: Arthroscopic rotator cuff repair generally provides satisfactory results including decreased shoulder pain and improved shoulder motion. Unfortunately, imaging studies demonstrate that the retear rate associated with the available arthroscopic techniques may be high. The purpose of this study was to evaluate the clinical and magnetic resonance imaging (MRI) results of arthroscopic rotator cuff repair with and without the use of platelet-leukocyte membrane in patients with a large posterosuperior rotator cuff tear. METHODS: Eighty consecutive patients with a large full-thickness posterosuperior rotator cuff tear were enrolled. All tears were repaired using an arthroscopic single-row technique. Patients were randomized to treatment either with or without a platelet-leukocyte membrane inserted between the rotator cuff tendon and its footprint. In patients treated with this membrane, one membrane was utilized for each suture anchor. The primary outcomes were the difference between the preoperative and postoperative Constant scores and the repair integrity assessed by MRI according to the Sugaya classification. The secondary outcome was the difference between the preoperative and postoperative Simple Shoulder Test (SST) scores. RESULTS: The only significant differences between the two groups involved the patient age and the preoperative and postoperative Constant scores; the differences in the Constant score were due to differences in the shoulder pain subscore. At a mean of thirteen months of follow-up, rotator cuff retears were observed only in the group of patients in whom the membrane had not been used, and a thin but intact tendon was observed more frequently in this group as well. The use of the membrane was associated with significantly better repair integrity (p = 0.04). CONCLUSIONS: The use of the platelet-leukocyte membrane in the treatment of rotator cuff tears improved repair integrity compared with repair without membrane. However, the improvement in repair integrity was not associated with greater improvement in the functional outcome. In fact, the Constant scores of the two groups would have been similar if the shoulder pain component (which had differed preoperatively) had been excluded.

Successful treatment of infected residual pleural space after pulmonary resection with autologous platelet-leukocyte gel.

Complications of the residual pleural space after pulmonary resection have been reported to be between 5% and 40% depending on the type of resection, and they increase morbidity, mortality, hospital stays, and costs. The therapeutic use of autologous prepared platelet leukocyte-enriched gel is a relatively new technology for the stimulation and acceleration of soft tissue and bone healing. This gel can be applied to a diversity of tissue. We describe the case of a successful application through a chest tube of platelet leukocyte gel to treat an infected residual pleural space that developed after pulmonary lobectomy for lung cancer.

Early impairment of myocardial function in young patients with beta-thalassemia major.

BACKGROUND AND OBJECTIVE: One of the chief causes of death in patients with beta-thalassemia major (TM) remains heart failure due to iron overload. We investigated possible differences in myocardial function between a population of young asymptomatic patients with TM and healthy controls all of whom underwent an echocardiographic study, including tissue Doppler (TDI) and strain imaging (SI) analysis and cardiac magnetic resonance imaging (MRI). METHODS: 30 young asymptomatic patients with TM (16 taking deferoxamine and 14 taking deferiprone) and 30 healthy subjects underwent a cardiac MRI with T2* technique and an echocardiographic evaluation including systolic myocardial velocities (Sm), early (Em) and late (Am) diastolic velocities and systolic strain (S) at the level of basal segments of the lateral left ventricle (LV), interventricular septum (Septal) and lateral right ventricle (RV) wall. The differences in T2* values and echocardiographic parameters were also compared in patients with TM subgrouped according to iron chelation therapy. RESULTS: The following TDI and SI measures were lower in patients than in controls: LV-Sm (P < 0.05), S-LV (P < 0.001), Septal-Sm (P < 0.05), Septal-Em (P < 0.001), S-Septal (P < 0.001), RV-Sm (P < 0.001), RV-Em (P < 0.001), RV-Em/Am (P < 0.05) and S-RV (P < 0.05). Myocardial function was better in the patients receiving deferiprone than those receiving deferoxamine. T2* values were higher in controls than in patients with TM and in those treated with deferiprone than those treated with deferoxamine. MRI data well correlated with SI parameters. CONCLUSIONS: Study underlines that, even in a population of young, asymptomatic and well-chelated patients with TM, there is an impairment of myocardial function and that this condition could be easily detected by more advanced ultrasound techniques such as TDI and SI. The better indices of myocardial function in patients treated with deferiprone clearly needs confirmation from larger prospective studies.

Increased QT variability in young asymptomatic patients with beta-thalassemia major.

BACKGROUND: Despite recent progress in iron chelation therapy, sudden cardiac death due to malignant ventricular arrhythmias remains a vexing, clinical problem in patients with beta-thalassemia major (TM). In this study we assessed whether the major indices of QT variability, emerging tools for risk stratification of sudden cardiac death, differ in young asymptomatic patients with TM and healthy persons. METHODS: Thirty patients with TM and 30 healthy control subjects underwent a 5-min electrocardiography recording to calculate the following variables: QT variance (QT(v)), QT(v) normalized for mean QT (QTVN) and QT variability index (QTVI). All subjects also underwent a two-dimensional and Doppler echocardiography study and magnetic resonance imaging (MRI) to determine cardiac and hepatic T2* values. RESULTS: No differences were observed in clinical and conventional echo-Doppler findings in healthy control subjects and patients with TM whereas QT(v), QTVN and QTVI values were significantly higher in patients than those in controls (QT(v), P < 0.001; QTVN, P < 0.05 and QTVI, P < 0.001) and cardiac T2* and hepatic MRI T2* values were significantly lower in patients with TM (P < 0.001). The indices of temporal QT variability correlated significantly with MRI data. CONCLUSIONS: Young asymptomatic patients with TM have increased cardiac repolarization variability as assessed by QT variability indices, probably due to cardiac iron deposition. These easily assessed, non-invasive markers could be used to identify increased myocardial repolarization lability early in asymptomatic patients with TM.