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Osteonecrosis of the Jaws in Patients Receiving Anti-Angiogenic Drugs and Chemotherapeutics: Literature Review and Case Reports

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is a relatively rare but serious pathology associated with the use of bisphosphonates (BPs) and antiresorptive drugs in patients with bone metastases, multiple myeloma and osteoporosis. Various cases of patients with jaw bone necrosis due to BPs have recently been reported in the literature. Anti-angiogenic drugs are novel anticancer agents prescribed to patients with renal carcinoma, lung carcinoma, soft tissue metastases, etc. Anti-angiogenic drugs target the vascular endothelial growth factor’s (VEGF) signaling pathways via different mechanisms and thus inhibit tumor cell proliferation, neoangiogenesis and tumor growth. Several reports have suggested a higher incidence of MRONJ in patients treated with BPs in combination with anti-angiogenic drugs. However, there is currently no sufficient data in the literature about the risk of ONJ in patients taking anti-angiogenic drugs or cancer chemotherapy alone. We present two clinical cases of osteonecrosis of the jaw in patients treated with chemotherapy, but no history of BPs. In the first case the necrosis is related to the anti-angiogenic agent sunitinib in a patient with lung metastases and in the second case- to complex chemotherapy in a patient with acute myeloid leukemia. We recommend conservative treatment with antibiotics in both cases, together with antiseptics and surgical removal of the necrotic bone following total demarcation of the sequesters.

Open access
Renal Changes in Cocaine Abuse and Addiction

Abstract

Cocaine is a natural alkaloid extracted from the leaves of the South American plant Erythroxylum coca or synthesized chemically. After cannabis, it is the second most frequently abused recreational substance worldwide. Cocaine can affect every tissue and organ within the human body, including the kidneys, causing tissue ischemia due to vasoconstriction, endothelial dysfunction and damage, procoagulant activity and oxidative stress with subsequent ischemic infarctions and fibrosis. The renal changes in cocaine abuse and addiction are due to rhabdomyolysis, ischemic, hypertensive, and inflammatory changes with the development of cell proliferation and fibrosis. The authors present three patients with cocaine-associated renal damage and discuss the underlying mechanisms of cocaine-induces tissue changes.

Open access
Shoulder Instability – Results of Different Methods of Treatment

Abstract

The aim of this study is to present results after different procedures of surgical treatment of the unstable shoulder joint: arthroscopic stabilization; arthroscopic stabilization followed by the operative technique by Matev; the Latarjet procedure in cases with the presence of bone defects. From 2004 to 2017 291 patients aged between 15 and 35 years were operated at the University Hospital “Prof. B. Boychev”, Medical University − Sofia. 247 patients had anterior and 44 − combined shoulder instability. 173 of the patients were active athletes practicing different disciplines. The average age at the time of the first dislocation was 17 years. In 172 patients, the first dislocation occurred without significant trauma, 124 of them had anterior shoulder instability and 48 – combined shoulder instability. In 120 patients with anterior dislocations, there was history of a serious injury during the first accident. The number of dislocations varied between ten and fifteen in all patients. For the same period, 45 patients with significant bone defects requiring open surgery (Latarjet procedure) were operated. Among the patients with bone defects, the dislocations were between 8 and 30 before the first examination. There were 11 patients, who had undergone previous surgery in different hospitals and different number of relaxations after surgery were found. The data were evaluated radiographically and clinically. Functionally, the patients recovered according to a well-established protocol of physiotherapy and the external rotation regained the full range of motion. The patients were able to return to their sports activity. The successful results in all patients show that these combined operative techniques can be the method of choice in the treatment of a greater number of dislocations of the shoulder, especially in people who seek to quickly return to active sport activities.

Open access
Antiretroviral Therapy and Bone Health

Abstract

Objective: To determine the incidence of osteopenia and osteoporosis in Bulgarian human immunodeficiency virus (HIV)-infected patients.

Methods: Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry in 41 Bulgarian HIV-infected patients.

Results: Overall, 27% of patients had reduced BMD (7% osteoporosis and 20% osteopenia). There was a significant correlation between low BMD and increasing age and between low BMD and duration of antiretroviral therapy (ART) but no correlation with gender, therapy regimen or serum calcium or phosphate levels. Seventy-one percent had elevated serum cystatin C levels but there was no correlation between BMD and cystatin C levels. Serum calcium, phosphate, cystatin C and creatinine levels and the T- and Z-scores were tested for dependence on duration of therapy. Dependence was found for T- and Z-scores, (p = 0.048 and p = 0.038) but not for calcium, phosphate, cystatin C or creatinine levels. These variables were subsequently tested by means of cross-tabulation tables for correlations between pairs of parameters; no significant correlation was found between any pairs (R > 0.5 for all comparisons).

Conclusions: Significant correlations were observed between low BMD and increasing age and longer duration of ART but no relationship was observed with gender or therapy regimen.

Open access
Application of Positive End-Expiratory Pressure (PEEP) in Patients During Prolonged Gynecological Surgery

Abstract

Introduction: A lot of clinical studies have shown that during prolonged surgery protective ventilation strategy, including low tidal volume, PEEP and recruitment maneuvers (RM) can reduce the rate of postoperative pulmonary complications, which are the second most common cause for postoperative mortality. Therefore, it is important to investigate clinical methods for preventing them. The strategy of protective ventilation is easy and safe for the patients and inexpensive for application during prolonged surgery.

Aims: The objective of this trial was to study whether application of PEEP in patients during prolonged gynecological surgery could decrease the postoperative complications.

Material and Methods: We compared the rates of postoperative complications in patients after prolonged open gynecological surgery, who were divided into 2 groups – group A, which was the control group on non-protective ventilation (35 patients) and group B on protective ventilation (35 patients). The patients in the control group were ventilated with tidal volume (VT) of 8-10 ml/kg without PEEP and RM; the patients in group B were ventilated with VT = 6-8 ml/kg according to their Predicted Body Weight, with a PEEP of 6 cm H2O and RM, which consisted of applying continuous positive airway pressure of 30 cm H2O for 30 seconds. RM was performed after intubation, after every disconnection from ventilator and before extubation. The study was successfully performed without a need for a change in the type of ventilation strategy because of hypoxia or hemodynamic instability. Statistical nonparametric test (e.g. chi-square) was applied.

Results: Total rate of all postoperative complications observed in both groups was 27,1%. We found a significant relationship between application of PEEP and lower rates of postoperative pulmonary complications in group A (39,4%) compared to group B (12,1%), lower rate of respiratory failure (33,3% in group A vs. 9,1% in group B -) and atelectasis (21,2% in group A vs. 0% in group B).

Conclusion: The protective ventilation strategy (low VT, PEEP and RM) in patients during prolonged gynecological surgery can reduce the rate of postoperative pulmonary complications such as respiratory failure and atelectasis.

Open access
Assessment of Chaenomeles Maulei Fruit Juice Effects in Tests for Depression and Anxiety

Abstract

Depression and anxiety are prevalent chronic psychiatric disorders affecting many people worldwide. Over the past decades, much attention has been drawn to herbal psychopharmacology, offering fewer adverse reactions. The main bioactive compounds in Chaenomeles maulei fruits are polyphenols known for their behavioral effects. The objective of the present study was to assess Chaenomeles maulei fruit juice (CMFJ) effects in tests for anxiety and depression. The animals used were 32 male healthy Wistar rats treated orally with CMFJ for 16 days. They were divided in four groups of 8 animals. The control group received distilled water and the rest of the groups were treated with CMFJ at 2.5, 5 and 10 ml/kg doses. We assessed the social interaction time as a measure of anxiety and the immobility time in the forced swim test as a measure of behavioral despair. In the social interaction test, the 14 days administration of CMFJ did not produce any significant changes in the time spent in social interaction. After 16 days of administration all doses of CMFJ significantly decreased the immobility time of the rats (p < 0.05) in comparison to the control group. These results allow making the conclusion that CMFJ lacked anxiolytic activity, but showed an antidepressant-like effect.

Open access
Calcium-Phosphate Metabolism Disorders in Patients with Renal Failure Clinical Significance, Diagnosis and Treatment

Abstract

Chronic kidney diseases (CKD) are commonly associated with calcium and phosphorus metabolism disorders. The general term of “renal osteodystrophy” (ROD) encompasses a complex spectrum of abnormalities in bone and mineral metabolism in CKD. This is one of the most serious and debilitating complications of CKD. It is related to disproportionately high direct and indirect costs of healthcare, thus posing a major burden on society. The development of ROD begins too early in the course of CKD. Some mechanisms involved in the pathogenesis of ROD are reduced calciferol production, calcium deficiency and hyperphosphatemia. Clinically, ROD occurs with varied manifestations – osteomalacia, osteoporosis, adynamic bone disease. The diagnosis and the treatment are a challenge for the physician and effort should be made to prolong the duration and quality of life of the affected patients.

Open access
Cost-Minimization Analysis of Non-Invasive and Invasive Mechanical Ventilation for De Novo Acute Hypoxemic Respiratory Failure in an Eastern European Setting

Abstract

Introduction: In the light of constant pressure for minimizing healthcare costs we made a cost-minimization analysis comparing invasive mechanical ventilation (IMV) and non-invasive ventilation (NIV) as treatment for hypoxemic acute respiratory failure (ARF).

Aim: The primary objective was to estimate the direct medical costs generated by a patient on IMV and NIV. A secondary objective was to identify which aspect of the treatment was most expensive.

Material and Methods: This is a single center retrospective study including 36 patients on mechanical ventilation due to hypoxemic ARF, separated in two groups – NIV (n = 18) and IMV (n = 18). We calculated all direct medical costs in Euro and compared them statistically.

Results: On admission the PaO2/FiO2 and SAPS II score were comparable in both groups. We observed a significant difference in the costs per patient for drug treatment (NIV: 616.07; IQR: 236.68, IMV:1456.18; IQR:1741.95, p = 0.005), consumables (NIV: 16.47; IQR: 21.44, IMV: 98.79; IQR: 81.52, p < 0.001) and diagnostic tests (NIV: 351; IQR: 183.88, IMV: 765.69; IQR: 851.43, p < 0.001). We also computed the costs per patient per day and there was a significant difference in the costs in all above listed categories. In both groups the highest costs were for drug treatment – around 61%.

Conclusions: In the setting of hypoxemic ARF NIV reduces significantly the direct medical costs of treatment in comparison to IMV. The decreased costs in NIV are not associated with severity of disease according to the respiratory quotient and SAPS II score.

Open access
HLA DRB1 and HLA DQB1 Alleles in Bulgarian Patients with Primary and Secondary Antiphospholipid Syndrome

Abstract

Antiphospholipid syndrome (APS) is an autoimmune disease with multifactorial and polygenic pathogenesis. Recently, the genetic predisposition in APS has been subjected to wide discussion. The aim of this study is to determine the prevalence of DRB1 and DQB1 loci in Bulgarian population of healthy persons and patients with primary (PAPS) and secondary (SAPS) APS. Patients are divided in 5 groups: I-29 patents with systemic lupus erythematosus (SLE) with SAPS, II-35 patients with PAPS, III-32 women with spontaneous abortions without aPL, IV-15 patients with different thrombosis (deep venous thromboses, pulmonary embolism, mesenterial thrombosis, myocardial infarction, stroke) without laboratory data for APS, and V-16 SLE patients without clinical and laboratory data for APS. SAPS patients have more frequently DRB1*03 and DQB1*02 and more rarely DRB1*11 and DQB1*03 in comparison with healthy subjects and patients with PAPS. Patents with PAPS, those with spontaneous abortions and patients with thrombotic events but without antiphospholipid antibodies (aPL) have DRB1*03, DRB1*11, DQB1*02 and DQB1*03 alleles similar to the general population. There are no differences between group I (SLE+APS) and group V (SLE) in DRB1* and DQB1*alleles.

Open access
Lipid Indices, Elastin Turnover and the Development of Microvascular Complications – A Study in Diabetic Patients with Arterial Hypertension

Abstract

Background and Aims: An important factor in the development of vascular wall lesions is the degradation of the elastic fiber major protein – elastin. Elastin peptides (EDP) derived from this degradation are present in the circulation and are a stimulus for the production of anti-elastin antibodies (AEAbs) IgM, IgG and IgA. The aim of this study was to investigate the possible association between AEAbs, lipid indices and the development of microvascular complications.

Material and Methods: Sera of 93 patients with type 2 diabetes mellitus (T2DM) and arterial hypertension (AH) were investigated (mean age 61,4 ± 11,3 years, diabetes duration 9,88 ± 3,12 years; hypertension duration 9,28 ± 4,98). ELISA was used for determination of anti-elastin antibodies. These levels were compared to serum AEAbs in 42 age- and sex-matched controls. Diabetic patients were divided in two groups according to the presence – Group 1 (n = 67) or absence – Group 2 (n = 26) of microangiopathy. The lipid profile and lipid indices (log TG/HDL, LDL/HDL, TC/HDL and TG/HDL) were also studied.

Results: Patients with T2DM and AH showed statistically significant higher levels of serum AEAbs IgA than healthy controls – 0,338 (0,133÷0,452) vs. 0,006 (0,052÷0,068) (KW = 19,54; P < 0.0001). Group 1 showed statistically significant higher levels of AEAbs IgA than patients without microangiopathy – 0,353 (0,173÷0,471) vs. 0,235 (0,098÷0,377) (KW = 3,36; p = 0.05) and healthy controls – 0,353 (0,173÷0,471) vs. 0,006 (0,052÷0,068) (KW = 20,37; p < 0,0001) (0.37 ± 0,03 vs. 0.06÷0.01) (p = 0.0001). Patients from Group 2 showed significantly higher levels of AEAbs IgA than controls 0,235 (0,098÷0,377) vs. 0,006 (0,052÷0,068) (KW = 8,54; P = 0.003). AEAbs IgA showed correlation with insulin dose (r = −0.35); (p = 0.01), SBP (r = 0.31); (p = 0.001), HbA1c (r = 0.21); (p = 0.04), BMI (r = 0.22); (p = 0.01). AEAbs IgA correlated with log TG/HDL (r = 0.28); (p = 0.001), LDL/HDL (r = 0.22); (p = 0.01) TC/HDL (r = 0.22); (p = 0.01) and with TG/HDL (r = 0.15); (p = 0.05).

Conclusion: Our study proved a relationship between elevation of AEAb IgA, high lipid indices and the development of microvascular complications in patients with type 2 diabetes mellitus and arterial hypertension.

Open access