US-guided high-intensity focused ultrasound as a promising non-invasive method for treatment of primary hyperparathyroidism.

OBJECTIVES: To investigate the long-term efficacy and safety of ultrasound (US)-guided high-intensity focused ultrasound (HIFU) treatment in patients with primary hyperparathyroidism (PHPT). METHODS: In our prospective study, 13 of 72 screened patients with PHPT were eligible for HIFU treatment, which was performed in one or two sessions. Parathyroid adenoma size and function were evaluated at baseline, 1, 3, 6, 9, and 12 months after the final HIFU session. RESULTS: In 11 females and 2 males, mean age 55.2 ± 12.41 years, the mean applied energy was 15.2 ± 7.7 kJ. Parathyroid size and parathyroid hormone decreased significantly one month after HIFU therapy (p < 0.002 and p < 0.02, respectively). Calcium concentration decreased slowly to reach significant reduction nine months later (p < 0.05). Complete remission was noted in three patients (23%) after one year, good disease control was achieved in nine (69%), and procedure was unsuccessful in one patient (8%). Number of sessions was significantly related to treatment success (p < 0.05). Transitory side effects were impaired vocal cord mobility in three patients (23.1%), subcutaneous oedema in three patients (23.1%), and a combination of both in two patients (15.4%). CONCLUSIONS: HIFU is a promising non-invasive technique for PHPT treatment, which could serve as therapeutic alternative for selected patients. KEY POINTS: US-guided HIFU is a new non-invasive ablative technique for parathyroid adenomas. The method is efficient and ensures good disease control in most patients. HIFU is a good alternative for patients not meeting surgery criteria. Treatment is well-tolerated with only transient side effects.

The sensing of poorly deformable red blood cells by the human spleen can be mimicked in vitro.

Retention of poorly deformable red blood cells (RBCs) by the human spleen has been recognized as a critical determinant of pathogenesis in hereditary spherocytosis, malaria, and other RBC disorders. Using an ex vivo perfusion system, we had previously shown that retention of Plasmodium falciparum-infected RBCs (Pf-RBCs) occur in the splenic red pulp, upstream from the sinus wall. To experimentally replicate the mechanical sensing of RBCs by the splenic microcirculation, we designed a sorting device where a mixture of 5- to 25-µm-diameter microbeads mimics the geometry of narrow and short interendothelial splenic slits. Heated RBCs, Pf-RBCs, and RBCs from patients with hereditary spherocytosis were retained in the microbead layer, without hemolysis. The retention rates of Pf-RBCs were similar in microbeads and in isolated perfused human spleens. These in vitro results directly confirm the importance of the mechanical sensing of RBCs by the human spleen. In addition, rigid and deformable RBC subpopulations could be separated and characterized at the molecular level, and the device was used to deplete a stored RBC population from its subpopulation of rigid RBCs. This experimental approach may contribute to a better understanding of the role of the spleen in the pathogenesis of inherited and acquired RBC disorders.

Bifurcations, sustained oscillations and torus bursting involving ionic concentrations dynamics in a canine atrial cell model.

Atrial fibrillation is a disorganization of the electrical propagation in the atria often initiated by ectopic beats. This spontaneous activity might be associated with the appearance of sustained oscillations in some portion of the tissue. Adrenergic stress and specific gene polymorphisms known to promote atrial fibrillation are notably related to calcium and potassium channel conductances. We performed codimension-one and two bifurcation analysis along these conductances in an ionic canine atrial myocyte model. Two Hopf bifurcations were found, related to two distinct mechanisms: (1) a fast calcium gating-driven oscillator, and (2) a slow concentration-driven oscillator. These two mechanisms interact through a double Hopf bifurcation (HH) in a neighborhood of which a torus (Neimark-Sacker) bifurcation leads to bursting. A complex codimension-two theoretical scenario was identified around HH, through systematic comparison with the attractors found numerically. The concentration oscillator was further decomposed to reveal the minimal oscillating subnetwork, in which the Na(+)/Ca(2+) exchanger plays a prominent role.

High-intensity focused ultrasound ablation of thyroid nodules: first human feasibility study.

BACKGROUND: Thyroid surgery is common, but complications may occur. High-intensity focused ultrasound (HIFU) is a minimally invasive alternative to surgery. We hypothesized that an optimized HIFU device could be safe and effective for ablating benign thyroid nodules without affecting neighboring structures. METHODS: In this open, single-center feasibility study, 25 patients were treated with HIFU with real-time ultrasound imaging 2 weeks before a scheduled thyroidectomy for multinodular goiter. Thyroid ultrasonography imaging, thyroid function, were evaluated before and after treatment. Adverse events were carefully recorded. Each patient received HIFU for one thyroid nodule, solid or mixed, with mean diameter ≥8 mm, and no suspicion of malignancy. The HIFU device was progressively adjusted with stepwise testing. The energy level for ablation ranged from 35 to 94 J/pulse for different groups of patients. One pathologist examined all removed thyroids. RESULTS: Three patients discontinued treatment due to pain or skin microblister. Among the remaining 22 patients, 16 showed significant changes by ultrasound. Macroscopic and histological examinations showed that all lesions were confined to the targeted nodule without affecting neighboring structures. At pathological analysis, the extent of nodule destruction ranged from 2% to 80%. Five out of 22 patients had over 20% pathological lesions unmistakably attributed to HIFU. Seventeen cases had putative lesions including nonspecific necrosis, hemorrhage, nodule detachment, cavitations, and cysts. Among these 17 cases, 12 had both ultrasound changes and cavitation at histology that may be expected for an HIFU effect. In the last three patients ablated at the highest energy level, significant ultrasound changes and complete coagulative necrosis were observed in 80%, 78%, and 58% of the targeted area, respectively. There were no major complications of ablation. CONCLUSION: This study showed the potential efficacy of HIFU for human thyroid nodule ablation. Lesions were clearly visible by histology and ultrasound after high energy treatments, and safety and tolerability were good. We identified a power threshold for optimal necrosis of the target thyroid tissue. Further studies are ongoing to assess nodule changes at longer follow-up times.