Mosaic Deletions of Known Genes Explain Skeletal Dysplasias With High and Low Bone Mass.

Mosaicism, a state in which an individual has two or more genetically distinct populations of cells in the body, can be difficult to detect because of either mild or atypical clinical presentation and limitations in the commonly used detection methods. Knowledge of the role of mosaicism is limited in many skeletal disorders, including osteopathia striata with cranial sclerosis (OSCS) and cleidocranial dysplasia (CCD). We used whole-genome sequencing (WGS) with coverage >40× to identify the genetic causes of disease in two clinically diagnosed patients. In a female patient with OSCS, we identified a mosaic 7-nucleotide frameshift deletion in exon 2 of AMER1, NM_152424.4:c.855_861del:p.(His285Glnfs*7), affecting 8.3% of the WGS reads. In a male patient with CCD, approximately 34% of the WGS reads harbored a 3710-basepair mosaic deletion, NC_000006.11:g.45514471_45518181del, starting in intron 8 of RUNX2 and terminating in the 3' untranslated region. Droplet digital polymerase chain reaction was used to validate these deletions and quantify the absolute level of mosaicism in each patient. Although constitutional variants in AMER1 and RUNX2 are a known cause of OSCS and CCD, respectively, the mosaic changes here reported have not been described previously. Our study indicates that mosaicism should be considered in unsolved cases of skeletal dysplasia and should be investigated with comprehensive and sensitive detection methods. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Atypical femoral fracture in a metastatic bone disease patient six months after discontinuation of denosumab received sequentially to previous bisphosphonate therapy - A case report.

Although, both bisphosphonates and denosumab are effective in reducing the risk of skeletal-related events in patients with metastatic bone disease, many concerns were being raised about the possible association between their use and atypical femoral fractures. A case of an atypical femoral fracture in a metastatic bone disease patient, six months after discontinuation of long-term zoledronic acid therapy and sequential treatment with denosumab is reported. After extensive laboratory and imaging examination, the fracture was classified as atypical and it was finally treated with discontinuation of denosumab, long cephalomedullary interlocking nailing and vitamin D administration. Sequential treatment with bisphosphonates and denosumab in patients with metastatic bone disease, may lead to an overlapping treatment effect, increasing bone suppression and the risk of atypical femoral fracture. In addition, discontinuation of denosumab may activate bone remodeling units in an area with microdamage accumulation in cortical bone caused by the previous bone suppression from the antiresorptive treatment. The activation of bone remodeling units may accelerate the occurrence of the atypical femoral fractures.

Atypical Femoral Fracture in a Patient without Bisphosphonate or Denosumab Exposure-A Case Report.

Introduction: Atypical femoral fractures (AFF) are associated with the use of bisphosphonates (BPs) or denosumab. However, few cases that meet the characteristics of these fractures, as established by the American Society of Bone and Mineral Research, have occurred in patients who have never used antiresorptive drugs. Case Report: We report a case of AFF in a 67-year-old woman who had never used antiresorptive medications. The history and comorbidities of the patient, the characteristics of the fracture, and the subsequent treatment are presented. Conclusion: AFFs may occur even in patients who have never been exposed to BPs or denosumab. The absence of antiresorptive osteoporosis therapy and the lack of radiographic focal periosteal reaction in the lateral femoral cortex, as in our case, can make it difficult to detect and prevent the disorder. Prolonged use of proton pump inhibitors and Vitamin D deficiency-related osteomalacia may contribute to the occurrence of these fractures. Further studies are required to accurately understand all inciting factors contributing to the development of AFFs.

Primary Myxoid Liposarcoma of the Upper Thoracic Spine in an Elderly Patient.

Liposarcoma, one of the most common soft-tissue sarcomas, originates from primitive mesenchymal cells, and its diagnostic criteria have been well established. Myxoid liposarcoma is the second most common histological subtype, occurring more frequently during the fourth and fifth decades of life. There are only a few sporadic published cases of spinal liposarcomas, whatever primary or metastatic. We describe an unusual case of primary myxoid liposarcoma of the thoracic spine in a 79-year-old male, presented with a 2-month history of intractable dorsal pain and progressive weakness of lower limbs. Surgical treatment was performed with wide tumor resection, spinal cord decompression, and posterior instrumentation complemented by radiotherapy. Only one other case has been reported with this spinal localization in the literature. Despite its rarity, myxoid liposarcoma should be considered in the differential diagnosis of primary tumors of the thoracic spine.

Secondary aneurysmal bone cyst in McCune-Albright syndrome.

Polyostotic fibrous dysplasia in combination with caféau-lait macules and hyperfunctioning endocrinopathies consists of a rare clinical condition termed as McCune-Albright syndrome. Aneurysmal bone cysts are tumor-like cystic lesions, composed of blood-filled compartments. They may occur as primary lesions or secondary to other pathologies; most commonly giant cell tumors of bone. However, secondary aneurysmal bone cysts in McCune-Albright syndrome are exceptional. We present a 28-year-old female with McCune-Albright syndrome. She experienced precocious puberty at age 3 months. In childhood, she experienced multiple long bone fractures, facial deformity and progressive visual and hearing impairment. One year ago, she experienced a painful, gradually enlarging bone lesion involving the right ilium, pubic and ischial bone with groundglass appearance, septa, marginal sclerosis, endosteal scalloping and blow-out expansion resulting in localized thinning of the cortex. CT-guided needle biopsy of the pelvic lesion showed aneurysmal bone cyst. Selective arterial embolization was recommended, however, the patient and her relatives did not consent to proceed to treatment, and she remained in close surveillance thereafter.

Extensive colonic necrosis following cardiac arrest and successful cardiopulmonary resuscitation: report of a case and literature review.

Non-occlusive colonic ischaemia is a recognized albeit rare entity related to low blood flow within the visceral circulation and in most reported cases the right colon was affected. This is the second case report in the literature of extensive colonic necrosis following cardiac arrest and cardiopulmonary resuscitation (CPR). A 83-year-old Caucasian woman was admitted to our hospital due to a low energy hip fracture. On her way to the radiology department she sustained a cardiac arrest. CPR started immediately and was successful. A few hours later, the patient developed increasing abdominal distension and severe metabolic acidocis. An abdominal multidetector computed tomography (MDCT) scan was suggestive of intestinal ischaemia. At laparotomy, the terminal ileum was ischaemic and extensive colonic necrosis was found, sparing only the proximal third of the transverse colon. The rectum was also spared. The terminal ileum and the entire colon were resected and an end ileostomy was fashioned. Although the patient exhibited a transient improvement during the immediate postoperative period, she eventually died 24h later from multiple organ failure. Histology showed transmural colonic necrosis with no evidence of a thromboembolic process or vasculitis. Therefore, this entity was attributed to a low flow state within the intestinal circulation secondary to the cardiac arrest.

Use of fat suppression in R2 relaxometry with MRI for the quantification of tissue iron overload in beta-thalassemic patients.

PURPOSE: To assess the performance and results of R(2) relaxometry using a fat-suppressed (FS) multiecho sequence and compare these to conventional R(2) relaxometry in estimating tissue iron overload. MATERIALS AND METHODS: Relaxation rate values (R(2)=1/T2) of the liver, spleen, pancreas and vertebral bone marrow (VBM) were estimated in 21 patients with ß-thalassemia major, using a respiratory-triggered 16-echo Carr-Purcell-Meiboom-Gill (CPMG) spin-echo sequence before (R(2)) and after (R(2) FS) the application of chemically selective fat suppression. RESULTS: Hepatic and splenic R(2) FS values correlated with respective R(2) values (r=0.98 and r=0.96, P<.001), whereas correlations between R(2) FS and R(2) values for pancreas and VBM were not statistically significant. Bland-Altman plots show disagreement between R(2) and R(2) FS values, particularly for pancreas and VBM. Hepatic, pancreatic and VBM R(2) FS values correlated with serum ferritin (r=0.88, P<.001; r=0.51, P<.003; and r=0.75, P<.002, respectively). Hepatic R(2) FS values correlated with splenic R(2) FS (r=0.77, P<.03), pancreatic R(2) FS (r=0.61, P<.006) and VBM R(2) FS values (r=0.70, P<.001), whereas pancreatic R(2) FS values correlated also with VMB R(2) FS values. On the contrary, among the R(2) values of the above tissues, obtained without fat suppression, only hepatic R(2) values correlated with serum ferritin, whereas no correlation was documented between hepatic and pancreatic or VBM R(2) values. The application of fat suppression did not improve breathing or flow artifacts. CONCLUSION: Application of fat suppression in the standard CPMG sequence improved the capability of MRI in noninvasive quantification of iron, particularly in lipid-rich tissues, such as vertebral bone marrow (VBM) and pancreas.

Focal, asymptomatic epididymal masses--B-mode and color Doppler sonographic evaluation. Case report.

We reported the case of an adult male with an extratesticular mass prove to be postoperative a chronic inflammatory process. The importance of B-mode and color Doppler sonography in the differential diagnosis and literature regarding epididymal nodules and tumors of the paratesticular structures (epididymis) is reviewed and discussed.

Focal hepatic lesion ultrasound-guided biopsies.

PURPOSE: To compare the results of pathologic and cytologic reports of specimens acquired from focal liver lesions using ultrasound-guided biopsy and to evaluate the necessity of performing both techniques in the same patient. MATERIALS AND METHODS: 21 patients were eligible for enrollment in the study. Specimens for both pathologic and cytologic examination were obtained from 16 lesions using a 17G needle guide in a single puncture attempt. In 2 cases the diagnosis was based on cytologic smears. In 3 cases only histologic sections were acquired. The needle was introduced under continuous ultrasonographic control using a freehand technique. A cytologist was present at all times. RESULTS: The diagnostic sensitivity of cytologic examination was 83.33% and that of histologic examination was 94.74%. Histology diagnosed all cases of benign lesions and was proved inconclusive in 1 patient. The diagnostic sensitivity and accuracy of both methods combined reached 100%. In 94.4% malignancy was immediately diagnosed by cytology. CONCLUSIONS: Combination of both methods should increase the sensitivity and accuracy in diagnosing focal liver lesions performing a safe minimally invasive technique.

Can low doses of simvastatin enhance fracture healing? An experimental study in rabbits.

Several observational and experimental studies have investigated the potential anabolic effects of statins on undisturbed bone but only a few recent studies have examined the effect of statins on skeletal repair. The goal of the study is to investigate any potential early anabolic effect of the systemic administration of simvastatin in low doses (based on earlier safety and efficacy studies on undisturbed bone) on fracture healing. Fifty-four skeletally mature male New Zealand White rabbits were used for the study. The rabbits were assigned to one of three experimental groups: a control group, and two groups that were orally administrated a diet with 10 and 30 mg/kg/day of simvastatin, respectively. A complete biochemical blood count was performed to exclude drug-induced complications. Half of the animals of each group were sacrificed at 15 days and the other half at 30 days after surgery at which time intervals healing quality was assessed. The bones were subjected to biomechanical testing, histomorphometric analysis and peripheral quantitative computed tomography. In animals received simvastatin of 30 mg/kg/day a significant reduction of BMD, stiffness, and energy absorbed to failure were observed. At 15 days, the amount of cartilaginous callus formation was reduced, and the void space was significantly increased, in the animals of both groups that received simvastatin when compared to the control group (p<.05). Our results suggest that simvastatin doses of 30 mg/kg/day may have a negative anabolic effect on callus formation in rabbits, whereas doses of 10 mg/kg/day seem not to produce a significant positive or a negative effect, especially at the early stages of fracture remodeling.