Identification of inorganic particles resulting from degradation of ESSURE® implants: Study of 10 cases.

OBJECTIVE: Approximately 750,000 women worldwide have undergone ESSURE hysteroscopic sterilization since 2002. In 2015, an increase in adverse effects was noted, with gynaecological and systemic symptoms reported. Scanning electron microscopy (SEM) analysis of fallopian tube and uterine horn tissues and implants, after hysterectomy or salpingectomy, revealed the presence of inorganic particles resulting from implant degradation. STUDY DESIGN: Ten patients (age 42-53 years) were included in this study. Of these, eight patients had undergone hysterectomy and two patients had undergone salpingectomy. Mean exposure time was 85.5 months (standard deviation 26.8 months, range 34-105 months). Mineralogical analyses were performed on 13 tissue biopsies and four implants by SEM coupled with energy dispersive x-ray spectrometry. RESULTS: In five of the 10 patients, tin particles were observed in fallopian tube or uterine horn tissues with inflammatory cell reactions. In the other five cases, iron, chromium, nickel or platinum particles were observed. For implants, major deterioration of the weld zone was observed with either destroyed appearance or the presence of an organic coating containing numerous particles. DISCUSSION AND CONCLUSION: Analysis of the preclinical studies performed by the manufacturer suggests that degradation of the tin weld plays a major role in these adverse events, with increasing leaching and corrosion between 3 and 6 months for an intratubal insert that si designed to remain in an woman's body for her entire life. For patients with gynaecological symptoms (e.g. pain, metrorragies) needing explantation, these findings raise the question of a causal relationship between tin particles from implant degradation and the inflammatory tissue response. For patients with systemic symptoms (e.g. blurred vision, headache, asthenia, myalgia), the hypothesis that these symptoms may be related to the formation of organotin (chemical compounds based on tin with hydrocarbon substituents) in the body has yet to be proven. Tin levels in blood have to be measured before and after explantation. To the authors' knowledge, this is the first study to report significant degradation of the ESSURE implant weld, evidenced by the detection of tin particles in the uterine tissue of patients and comparison of the welding zone between unused and used implants.

Sarcoidosis, inorganic dust exposure and content of bronchoalveolar lavage fluid: the MINASARC pilot study.

Inhalation of mineral dust was suggested to contribute to sarcoidosis. We compared the mineral exposome of 20 sarcoidosis and 20 matched healthy subjects. Bronchoalveolar lavage (BAL) samples were treated by digestion-filtration and analyzed by transmission electron microscopy. The chemical composition of inorganic particles was determined by energy-dispersive X-ray (EDX) spectroscopy. Dust exposure was also assessed by a specific questionnaire. Eight sarcoidosis patients and five healthy volunteers had a high dust load in their BAL. No significant difference was observed between the overall inorganic particle load of each group while a significant higher load for steel was observed in sarcoidosis patients (p=0.029). Moreover, the building activity sub-score was significantly higher in sarcoidosis patients (p=0.018). These results suggest that building work could be a risk factor for sarcoidosis which could be considered at least in some cases as a granulomatosis caused by airborne inorganic dust. The questionnaire should be validated in larger studies. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 327-332).

Ultrastructural scoring of skin biopsies for diagnosis of vascular Ehlers-Danlos syndrome.

Vascular Ehlers-Danlos syndrome (vEDS) results from a mutation in the gene encoding alpha-1, type III pro-collagen (COL3A1) and confers fragility to skin, ligament and vascular tissue. We tested the value of skin biopsy for diagnosis of vEDS through an ultrastructure scoring procedure. Study design was a multicentric, case-control, blinded trial consisting of two phases: phase 1 was to identify an ultra-structure score providing the best discriminative value for vEDS and phase 2 was to replicate this result in a different population. We enrolled 103 patients, 66 cases defined through the revised nosology for Ehlers-Danlos syndromes and 37 control subjects selected from patients referred for other pathologies. Ultrastructure of extracellular matrix was read by three to five experienced pathologists blinded for diagnosis. We used the receiver operating curves and logistic regression analysis for ranking ultrastructure scores. We created a detailed description of lesions observed in vEDS patients with 27 items (coded 0 or 1). In the phase 1 (17 cases and 20 controls), abnormal fibroblast shape, presence of lysosomes in the fibroblast and abnormal basal lamina were found to be independent discriminative items. Addition of these three items (defining an ultrastructure score) had the best diagnosis value (area under the curve (AUC) = 0.96). In the phase 2 (49 cases, 17 controls), ultrastructure score provided odds ratio of 9.76 (95 % CI 2.91-32.78), and AUC of 0.90. The ultrastructure score of skin biopsy has predictive value for the diagnosis of vEDS. Presence of two or more signs (either abnormal fibroblast, presence of lysosomes in the fibroblast or abnormal basal lamina) is very evocative of vEDS.