Changes in bone mineral density, lean body mass and fat content as measured by dual energy x-ray absorptiometry in patients with prostate cancer without apparent bone metastases given androgen deprivation therapy

PURPOSE: We characterize the consequences of androgen deprivation therapy on body composition in elderly men. MATERIALS AND METHODS: Using a dual energy x-ray absorptiometry instrument, we determined the changes in bone mineral density, bone mineral content, fat body mass and lean body mass in 35 patients with prostate cancer without bone metastases who received luteinizing hormone releasing hormone analogue for 12 months. RESULTS: At baseline conditions 46% of cases were classified as osteopenic and 14% as osteoporotic at the lumbar spine and 40% were osteopenic and 4% osteoporotic at the hip. Androgen deprivation significantly decreased bone mineral density either at the lumbar spine (mean gm./cm.2 [SD] 1.00 [0.194], 0.986 [0.172] and 0.977 [0.182] at baseline, and 6 and 12 months, respectively, p <0.002) or the hip (0.929 [0.136], 0.926 [0.144] and 0.923 [0.138], p <0.03). A more than 2% decrease in bone mineral density was found at the lumbar spine in 19 men (54.3%) and at the hip in 15 (42.9%). Bone mineral content paralleled the bone mineral density pattern. Lean body mass decreased (mean gm. [SD] 50,287 [6,656], 49,296 [6,554] and 49,327 [6,345], p <0.003), whereas fat body mass consistently increased (18,115 [6,209], 20,724 [6,029] and 21,604 [5,923] p <0.001). CONCLUSIONS: Serial bone densitometry evaluation during androgen deprivation therapy may allow the detection of patients with prostate cancer at risk for osteoporotic fractures, that is those with osteopenia or osteoporosis at baseline and fast bone loss. The change in body composition may predispose patients to accidental falls, thus increasing the risk of bone fracture.     

Evaluation of bone height and bone density after tooth extraction: an experimental study in minipigs.

OBJECTIVE: The objective of this study was to radiographically quantify bone density and bone height preservation in tooth extraction alveolus filled with xenograft. STUDY DESIGN: The maxillary and mandibular fourth deciduous molars and fourth premolars of 6 minipigs were removed. Randomly, in 3 animals the right side was used as the test side and in the other 3 animals the left side was the test side. Intraoral radiographs were performed to compare the condition at the initial time and 3 months later. Measurements of bone height and bone density were performed using KS300 (Zeiss) software. RESULTS: After 3 months, there was a statistically significant smaller bone height loss for the test group. The test group presented a statistically greater bone density immediately after tooth extraction. However, after 3 months there was no statistically significant difference between the groups. CONCLUSIONS: The results suggest that treatment of postextraction alveolus with xenograft can preserve bone height initially but differences in bone density compared to when no xenograft is used are not sustained.     

Preliminary results of Anaconda aortic endografts: a single center study.

OBJECTIVE: To evaluate the peri-operative results of Anaconda endograft in the first 49 cases treated in a single centre. METHODS: The study was carried out prospectively on cases of infrarenal abdominal aortic aneurysm (AAA) treated with Anaconda endograft. The characteristics of the proximal aortic neck and of the iliac access vessels were considered. The following operative results were assessed: the main body oversizing, the need to correct the positioning of the main body, the use of iliac extensions, the use of ballooning, the covering of patent hypogastric arteries, the presence of endoleaks and the need for conversion. Peri-operative (30 days) mortality and morbidity were also considered. RESULTS: Of the 49 cases treated, 44 were males with a mean age of 73 years (range: 55-89 yrs; SD+/-7 yrs). The mean diameter of the AAA was 56 mm (range 45-91 mm; SD+/-11); 4 cases had common iliac aneurysms with a diameter >3 cm. The mean neck diameter and length were 23 mm (range 19-28 mm; SD+/-3) and 25 mm (range 15-50 mm; SD+/-10) respectively. An aortic neck angle between 40 degrees and 70 degrees was present in 10 cases (20%) (mean 58 degrees; SD+/-15 degrees), and 20 cases (41%) had iliac tortuosity with an angle greater than 60 degrees (mean 85 degrees; SD+/-25 degrees). There were no cases of conversion or intra-operative death. One (2%) peri-operative death occurred, for reasons not related to the endograft. There were two cases of iliac limb thrombosis. CT at one month showed 12 cases (25%) of type II endoleak. There were no cases of type I or type III endoleaks. CONCLUSIONS: The preliminary data of this series demonstrates that the Anaconda endograft has good peri-operative results in the treatment of infrarenal AAAs with a neck length not less than 15 mm.     

Induction of neural-like differentiation in human mesenchymal stem cells derived from bone marrow, fat, spleen and thymus

Mesenchymal stem cells (MSCs) from bone marrow (BM) and sub-cutaneous fat are known to differentiate into neural cells under appropriate stimuli. We describe here the neural-like differentiation of human MSCs obtained from spleen and thymus, induced either with chemical factors or with co-culture with human Schwann cells (Sc). Under the effect of neural differentiation medium, most MSCs from BM, fat, spleen and thymus acquired morphological changes suggestive of cells of astrocytic/neuronal and oligodendroglial lineages with general up-regulation of neural molecules not correlated with morphological changes. The process was transient and reversible, as MSCs recovered basal morphology and phenotype, as well as their multilineage differentiation potential. Thus, we hypothesized that chemical factors may prime MSCs for neural differentiation, by inducing initial and poorly specific changes. By contrast, co-cultures of MSCs of different origin with Sc induced long-lasting and Sc differentiation, i.e., the expression of Sc myelin proteins for up to 12 days. Our results show that a MSC reservoir is present in tissues other than BM and fat, and that MSCs of different origin have similar neural differentiation potential. This evidence provides new insights into BM-like tissue plasticity and may have important implications for future therapeutic interventions in chronic neuropathies.     

hMLH1 and hMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer

Background The aim of this study was to search for mutations in the humanmutS homolog 2 (hMSH2) and humanmutL homolog 1 (hMLH1) genes in 25 unrelated Brazilian kindreds with suspected hereditary nonpolyposis colorectal cancer (HNPCC). Methods The families were grouped according to the following clinical criteria: Amsterdam I or II; familial colorectal cancer (CRC); an early age of onset of CRC in the proband only; or with at least one or two relatives who had HNPCC-related cancers; CRC in the proband only. All patients were studied with direct sequencing. Results Ten mutations were detected (10 of 25 [40%]); of nine different mutations, seven were novel. ThehMLH1 gene had a higher mutation detection rate thanhMSH2 (8 of 25 [32%] vs. 2 of 25 [8%]). Only 3 of these 10 families fulfilled the Amsterdam criteria. Two different polymorphisms were detected in thehMLH1 gene and four in thehMSH2 gene. Conclusions ThehMLH1 gene had a higher mutation detection rate thanhMSH2. The physician who deals with CRC must take into consideration the heredity issue with patients who present with an early age of onset or a familial history of CRC- or HNPCC-related cancers, including gastric cancer, even if they do not fulfill the former Amsterdam criteria.     

Total thyroidectomy for management of benign thyroid disease: review of 526 cases

Total thyroidectomy is not frequently performed in cases of benign disease because of the associated risk of postoperative hypoparathyroidism and recurrent laryngeal nerve (RLN) damage. We chose a series of patients who had undergone total thyroidectomy (TT) for benign thyroid tumors to evaluate the safety of this approach and its role in the treatment of nonmalignant lesions of the thyroid. We considered only patients with a minimum follow-up of 24 months. Records of 526 patients who underwent TT were carefully reviewed, assessing for perioperative complications and late sequelae. The mean age was 44 +/- 15.7 years; 109 patients (20.7%) were male and 417 (79.3%) were female. Altogether, 65 patients (12.3%) were operated on for toxic goiter, 429 (81.6%) for bilateral nodular goiter, and 32 (6.1%) for thyroiditis. Postoperative hemorrhage requiring reoperation occurred in 8 cases (1.5%). The incidences of permanent RLN palsy (considered as a percentage of the nerves at risk) and permanent hypocalcemia were 0.4% and 3.4%, respectively. A trend toward a decrease in the complication rate was observed during the last 5 years. There were no disease recurrences during a mean follow-up of 44 months. The results of our series show that TT can be performed safely in patients, with a low incidence of lifetime disabilities. TT has the advantage of reducing/avoiding the risk of disease recurrence and reoperation and should therefore be considered a valuable option for treating benign thyroid diseases.     

The secret life of the mitral valve

In secondary mitral regurgitation, the concept that the mitral valve (MV) is an innocent bystander, has been challenged by many studies in the last decades. The MV is a living structure with intrinsic plasticity that reacts to changes in stretch or in mechanical stress activating biohumoral mechanisms that have, as purpose, the adaptation of the valve to the new environment. If the adaptation is balanced, the leaflets increase both surface and length and the chordae tendineae lengthen: the result is a valve with different characteristics, but able to avoid or to limit the regurgitation. However, if the adaptation is unbalanced, the leaflets and the chords do not change their size, but become stiffer and rigid, with moderate or severe regurgitation. These changes are mediated mainly by a cytokine, the transforming growth factor‐β (TGF‐β), which is able to promote the changes that the MV needs to adapt to a new hemodynamic environment. In general, mild TGF‐β activation facilitates leaflet growth, excessive TGF‐β activation, as after myocardial infarction, results in profibrotic changes in the leaflets, with increased thickness and stiffness. The MV is then a plastic organism, that reacts to the external stimuli, trying to maintain its physiologic integrity. This review has the goal to unveil the secret life of the MV, to understand which stimuli can trigger its plasticity, and to explain why the equation “large heart = moderate/severe mitral regurgitation” and “small heart = no/mild mitral regurgitation” does not work into the clinical practice.     

Timing of cranial reconstruction after cranioplasty infections: are we ready for a re-thinking? A comparative analysis of delayed versus immediate cranioplasty after debridement in a series of 48 patients

Neurosurgical Review - The optimal management of cranioplasty infections remains a matter of debate. Most authors have suggested that the infected bone/implant removal is mandatory, combined with...     

Management of Chemotherapy-Induced Nausea and Vomiting with Trastuzumab Deruxtecan: A Case Series

IntroductionTrastuzumab deruxtecan is a monoclonal antibody linked to a chemotherapy moiety that was recently approved by the Food and Drug Administration (FDA) for the treatment of metastatic human epidermal growth factor receptor 2 (HER2) positive breast cancers. There are labeled black box warnings for interstitial lung disease (ILD)/pneumonitis and embryo-fetal toxicity. Additionally, chemotherapy-induced nausea and vomiting (CINV) was reported to be as high as 78% (∼8% grade 3 or higher) in phase I and II clinical trials. Clinical trial and package insert recommendations for the management of CINV are not available, making real-world management difficult.Case PresentationWe reviewed the first 10 patients who received trastuzumab deruxtecan at our hospital-based community cancer center to determine if CINV management was adequate. We found a rate of 28.9% CINV (all grade 1 and 2) despite treatment as a moderate emetic potential regimen. Interventions by the treatment team to manage trastuzumab deruxtecan as a high-risk emetic regimen resulted in reduced CINV and ongoing treatment for all patients.Discussion and ConclusionThis review indicates that management of CINV for patients receiving trastuzumab deruxtecan should follow recommendations for regimens with a high-risk emetic potential.