Chemosensory dysfunction in primary Sjögren's syndrome: a topical review.

Primary Sjögren's syndrome is an autoimmune exocrinopathy related to lymphocytic infiltration of the exocrine glandular epithelia (such as salivary, lacrimal, nasal, and sebaceous glands or vaginal mucosa) with systemic manifestations of an immuno-inflammatory nature, and not associated with any other systemic disease. It is characterized by severe dryness (Sicca syndrome), particularly in mouth and eyes, with potential strong impact on quality of life and could increase the risk of depression in Sjögren's patient. To date, the impairment of taste and olfactory functions related to Sjögren syndrome remains poorly assessed; so is the trigeminal functions which remain sparsely studied in patients with Sjögren disease. However, other factors can also modify chemosensory functions (olfactory or gustatory sensations and trigeminal nerves), in particular the reduction of the masticatory coefficient or halitosis, due to oral saliva flow decrease, and poor dental condition, which are often present in Sjögren patients. Of the 12 articles evaluated after a 22-year literature search of this review, chemosensory disorders (including taste, smell, and trigeminal impairments) are described and evaluated in pSS patients, with mainly poorer performance compared to healthy controls. Diagnostic and therapeutic (including rehabilitation) approaches of chemosensory disorders in pSS are discussed in this review. Clinician should be more attentive to taste as well as olfacto-trigeminal disorders in primary Sjögren's disease, if possible at the earlier stage, in order to take the best care of Sjögren's patients. This review also highlights some lack in knowledge on pSS chemosensory disorders that should provide new research perspectives. Key Points •Chemosensory functions (including taste, smell, and trigeminal functions) are altered in patients with primary Sjögren's syndrome (pSS) due to dryness of the mouth and the nose. •The trigeminal nerve which interacts with olfactory and gustatory nerves contributes to olfactory and taste perception but remains little studied to date. •Chemosensory function should be considered in the daily clinical assessment of patients with pSS. •Chemosensory function treatment is not standardized yet, however symptomatic treatment of Sjögren syndrome-associated dryness transiently would improve taste and smell, and olfactory or gustatory rehabilitation in pSS patients would be useful.

Analysis of the dental care queries in the "Mouth-Nose" discussion forum of the French association of patients with Gougerot-Sjögren's syndromes and dryness.

BACKGROUND: Primary Sjögren Syndrome is a rare autoimmune systemic disease characterized by impaired secretory functions of the exocrine gland. One of the main clinical features is dry mouth and subsequent oral diseases, which are also found in patients with Sicca. This leads to a marked deterioration in the quality of life and the patient's search for information and solutions. Many patients turn to patients' associations that offer moments of sharing to their members, especially through online discussion forums. Today, these forums represent quality material for a sociological or biomedical analysis of patients' concerns, as close as possible to their daily lives. Our objective is to analyze the concerns of patients with SS or Sicca regarding their dry mouth especially dental care. METHODS: In this cross-sectional observation study, a quantitative analysis of the Mouth-Nose online forum discussion of the French Association of Patients with Gougerot-Sjögren's Syndromes and Dryness have been performed. After reading and re-reading, initial request themes, topics, and subtopics were established and coding was performed. Then, the 885 threads were classified depending the initial request, pragma-linguistic indices and the main topic discussed in the thread. After identifying the threads dealing with dental care, we looked at which types of care were most discussed and classified the discussions according to whether or not the patient was satisfied with their care at the dentist. RESULTS: The majority of the initial requests are posts for experiences sharing and/or advice. The topic of "dental care" is one of the main concerns of the forum users. Among the threads that concern dental care, requests to share experience with implants are in the majority. Finally, the majority of the posts on dental care relate to care in private dental practice, deals with dental implants and prevention and resulted mainly in patient satisfaction. CONCLUSIONS: Analysis of the forum reveals importance of patient concerns about prevention, and care costs due to implant treatment, which add to disease burden. Most of messages relate favorable experiences with their dentists, which is in line with the approach of sharing experiences and support characteristic of a forum.

NLRP3 is involved in long bone edification and the maturation of osteogenic cells.

Overexpression of the nucleotide-binding leucine-rich repeat protein 3 (NLRP3) inflammasome in chronic auto-immune diseases leads to skeletal anomalies, with severe osteopenia due to the activation of osteoclasts. Reproducing this phenotype in Nlrp3 knock-in mice has provided insights into the role of NLRP3 in bone metabolism. We studied the role of NLRP3 in physiological bone development using a complete Nlrp3 knock-out mouse model. We found impaired skeletal development in Nlrp3-/- mice, resulting in a shorter stature than that of Nlrp3+/+  mice. These growth defects were associated with altered femur bone growth, characterized by a deficient growth plate and an osteopenic profile of the trabeculae. No differences in osteoclast recruitment or activity were observed. Instead, Nlrp3-/- femurs showed a less mineralized matrix in the trabeculae than those of Nlrp3+/+  mice, as well as less bone sialoprotein (BSP) expressing hypertrophic chondrocytes. In vitro, primary osteoblasts lacking NLRP3 expression showed defective mineralization, together with the downregulation of BSP expression. Finally, follow-up by micro-CT highlighted the role of NLPR3 in bone growth, occurring early in living mice, as the osteopenic phenotype diminishes over time. Overall, our data suggest that NLRP3 is involved in bone edification via the regulation of hypertrophic chondrocyte maturation and osteoblast activity. Furthermore, the defect appeared to be transitory, as the skeleton recovered with aging.

[Prophylactic hysterectomy in Lynch syndrome: Feasibility and outcomes]. / Faisabilité et résultats de l'hystérectomie prophylactique dans le syndrome de Lynch.

OBJECTIVES: Lynch syndrome (LS) is a hereditary predisposition to cancers, first of all, colo-rectal and endometrial cancers in women. Although recommended, gynecologic screening has never proven its benefit. Prophylactic surgery can be considered once the parental project is completed. There are few data regarding the assessment of prophylactic surgery. The objectives of our study were to evaluate the feasibility and morbidity of prophylactic hysterectomy in patients with Lynch syndrome. METHODS: This is a descriptive retrospective study of consecutive patients with LS undergoing prophylactic hysterectomy at the Georges-Pompidou European Hospital from 2002 to 2016. We collected demographic characteristics, results of preoperative assessment, intra- and postoperative data, final pathologic result as well as postoperative follow-up data. RESULTS: Forty patients were included in the study, and seventeen women had a history of colon cancer surgery. All hysterectomies were performed by laparoscopy, with two cases of laparoconversion. Two intraoperative complications occurred: serosal small bowel injuries and superficial bladder injury. Two early postoperative complications occurred (a peritonitis on small bowel perforation and a peritonitis on left ureteral injury) and two late complications (vesico-vaginal fistula and adhesive small bowel obstruction). All operative specimens were benign. With a median follow-up of 28 months [5-52], no patient had peritoneal cancer. CONCLUSIONS: Our study shows that prophylactic hysterectomy in Lynch syndrome should be done with caution. Per and postoperative complication rates appear to be higher than in general population, probably related to a more frequent history of colorectal cancer. However, total hysterectomy with bilateral salpingo-oophorectomy appears to be an effective strategy for preventing gynecological cancers in women with the Lynch syndrome.

Precaval positive sentinel lymph node with bilateral negative pelvic sentinel lymph node in low-risk endometrial cancer patient.

We here describe a case report of a positive precaval sentinel lymph node with negative pelvic sentinel lymph node in a patient with endometrial cancer. A 45-years-old woman was diagnosed with a grade 2 endometrioid carcinoma of the endometrium. She was treated with a hysterectomy and bilateral salpingo-oophorectomy, associated with dissection of sentinel lymph nodes (SLNs). We detected bilateral external and common bilateral iliac nodes and one precaval node. At pathological examination the pelvic nodes were non-metastatic, but the precaval node was positive. In this patient, sentinel node biopsy improved risk-assessment and adjuvant treatment.

What about sentinel lymph node biopsy for early breast cancer during pregnancy?

Pregnancy-associated breast cancer is rare, but this clinical situation arises in 1/10,000-1/3000 pregnancies. In patients presenting an early-stage breast tumor devoid of clinically pathological lymph node, sentinel lymph node (SLN) biopsy has not yet been validated as a routine procedure for pregnant women due to the lack of data in the literature. The blue dye injection is not recommended because of 2% theoretical risk of anaphylactic shock. Several studies have shown that Tc99m injection at conventional dose between 12.1 and 18.5MBq exposed the fetus to an irradiation between 0.011 and 0.0245mSv much below the 50mSv recommended threshold. As evidenced by lymphoscintigraphy scans, the dose of injected Tc99m is localized at the injection site and in the SLN. According to the literature, the SLN technique does not seem to impact the fetal or obstetrical prognosis. Studies involving larger cohorts are required to confirm these data and to indicate this technique in pregnant women. Considering the benefit for the patient and the low risk incurred on both fetal and obstetrical levels, it appears reasonable to discuss the indication of SLN on a case-by-case basis in multidisciplinary oncologic meetings.

Differences between inflammatory and catabolic mediators of peri-implantitis and periodontitis lesions following initial mechanical therapy: An exploratory study.

BACKGROUND AND OBJECTIVE: The aim of this study was to analyze the differences in inflammatory and catabolic mediators expressed in peri-implantitis compared to periodontitis lesions after non-surgical therapy. Peri-implantitis is associated with a faster rate of bone loss when compared with periodontitis, and peri-implant non-surgical therapy is ineffective to cure peri-implantitis. This may be due to persistent inflammation in peri-implantitis tissues after initial mechanical treatment. MATERIAL AND METHODS: Eleven patients with peri-implantitis and 10 with severe chronic periodontitis received non-surgical therapy. They were included at re-evaluation (8 weeks) if they presented pocket depth ≥6 mm with bleeding on probing, and the indication for open flap debridement surgery. Connective tissues were harvested during surgery from diseased sites. Healthy gingiva were harvested during third molar extraction in a third group of healthy patients (n=10). Explants were incubated for 24 hours in media culture and the release of cytokines, chemokines, growth factors, osteoprotegerin, receptor activator of nuclear factor kappa-B ligand (RANKL), matrix metalloproteinase and tissue inhibitors of matrix metalloproteinase (TIMP) in the conditioned media was analyzed by an exploratory multiplex immunoassay. When difference was found in the conditioned media, an immunohistochemistry was performed to compare expression in the tissues. RESULTS: Connective tissues from non-stabilized peri-implantitis exhibited a distinct cytokine profile compared to periodontitis lesions that did not respond to initial therapy. Indeed, TIMP-2 was significantly increased in media from peri-implantitis (P≤.05). In addition, the in situ expression of TIMP-2, interleukin-10 and RANKL was also significantly increased in peri-implantitis tissues (P≤.05). However, the ratio of RANKL/osteoprotegerin-positive cells did not vary (P≥.05). CONCLUSION: This study suggests that peri-implantitis and periodontitis connective tissues exhibit differences in response to non-surgical treatment, which may contribute to a different pattern of disease evolution.

A potential role of chondroitin sulfate on bone in osteoarthritis: inhibition of prostaglandin E2 and matrix metalloproteinases synthesis in interleukin-1ß-stimulated osteoblasts.

OBJECTIVES: To determine the effect of chondroitin sulfate (CS) on inflammatory mediators and proteolytic enzymes induced by interleukin-1ß (IL-1ß) and related to cartilage catabolism in murine osteoblasts. DESIGN: Osteoblasts were obtained by enzymatic digestion of calvaria from Swiss mice and cultured for 3 weeks as a primary culture. Cells were then stimulated with IL-1ß (1 or 10 ng/ml). CS-treated osteoblasts were incubated with 100 µg/ml of CS during the last week of culture w/o IL-1ß for the last 24 h. Expressions of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), 15-PG dehydrogenase (15-PGDH), matrix metalloproteinases-3 and -13 (MMP-3 and -13), osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) were determined by real-time polymerase chain reaction (PCR). PGE2, MMP-3 and MMP-13 release were assessed in the medium by enzyme-linked immunosorbent assay or western-blotting. RESULTS: IL-1ß increased COX-2, mPGES-1, MMP-3, MMP-13, RANKL expressions, decreased 15-PGDH expression, and increased PGE2, MMP-3 and MMP-13 release. Interestingly, 7 days of CS treatment significantly counteracted IL-1ß-induced expression of COX-2 (-62%, P<0.001), mPGES-1 (-63%, P<0.001), MMP-3 (-39%, P=0.08), MMP-13 (-60%, P<0.001) and RANKL (-84%, P<0.001). Accordingly, IL-1ß-induced PGE2, MMP-3 and MMP-13 releases were inhibited by 86% (P<0.001), 58%(P<0.001) and 38% (P<0.01) respectively. CONCLUSIONS: In conclusion, our data demonstrate that, in an inflammatory context, CS inhibits the production of PGE2 and MMPs. Since CS has previously been shown to counteract the production of these mediators in chondrocytes, we speculate that the beneficial effect of CS in Osteoarthritis (OA) could not only be due to its action on cartilage but also on subchondral bone.

[Severe haemoptysis revealing a Rasmüssen aneurysm]. / Hémoptysie massive sur anévrisme de Rasmüssen.

INTRODUCTION: The incidence of pulmonary tuberculosis is actually increasing. In active tuberculosis, an aneurysm of the pulmonary artery represents a frequent cause of haemoptysis. In cases of tuberculosis sequelae, the origin of the haemoptysis is often a bronchial artery. CASE REPORT: We describe the case of a man from Morocco who presented with severe haemoptysis. He was cachectic, had a fever and his chest X-ray showed a cavity in the left lower lobe. CT angiography (MDCTA) showed a Rasmüssen aneurysm of the pulmonary artery. This was occluded with coils, and multi-drug therapy against Mycobacterium tuberculosis was initiated as soon as tuberculosis was diagnosed. Two months later, there was no recurrence of the haemoptysis and repeat the MDCTA showed no opacification of the aneurysm. CONCLUSIONS: In patients with severe haemoptysis and evidence of active pulmonary tuberculosis, MDCTA may allow correct identification of the bleeding origin. In our case, the management of the pulmonary aneurysm relied upon pulmonary artery vasoocclusion. This treatment allowed us to wait for the antituberculosis treatment to be effective and reduces the need for a thoracic surgery.

[An unusual complication of thoracostomy]. / Une complication inhabituelle d'une thoracostomie.

INTRODUCTION: Post pneumonectomy infection is a well-described surgical complication. Treatment usually involves thoracostomy and requires local treatments. We report here an unusual complication of this situation. CASE REPORT: A 62 year old man had a pneumonectomy for non-small cell lung cancer. Following this he required a thoracostomy to treat a thoracic empyema and this was treated with local anti-septic agents. Subsequently he developed asthenia and a diagnosis of hyperthyroidism was made secondary to local disinfectant treatment with iodine agents. CONCLUSIONS: We describe an original case of thyroxicosis occurring in a patient following treatment for post-pneumonectomy empyema. We would recommend monitoring thyroid function in this context.

Stress-induced signaling pathways in hyalin chondrocytes: inhibition by Avocado-Soybean Unsaponifiables (ASU).

OBJECTIVE: Avocado-Soybean Unsaponifiables (ASU) represent one of the most commonly used drugs for symptomatic osteoarthritis (OA). The mechanisms of its activities are still poorly understood. We investigate here the effects of ASU on signaling pathways in mouse or human chondrocytes. METHODS: Mouse or human chondrocytes stimulated with interleukin-1beta (IL1beta, 10 ng/ml) and cartilage submitted to a compressive mechanical stress (MS) were studied in the presence or absence of ASU (10 microg/ml). Nuclear factor kappaB (NF-kappaB) activation was assessed by immunoblot, using an I-kappa B alpha antibody, nuclear translocation of NF-kappaB using p65 antibody, and extra-cellular signal-regulated kinase (ERK)1/2 activation using phospho and ERK1/2 antibodies. The binding of the p50/p65 complex on DNA was studied by electrophoretic mobility shift assay. RESULTS: ASU decrease matrix metalloproteinases-3 and -13 expressions and Prostaglandin E(2) (PGE(2)) release in our model. The degradation of I-kappa B alpha is prevented in the presence of ASU as shown by the persistent expression of I-kappa B alpha protein in the cytosol when chondrocytes are stimulated by IL1beta or MS. Nuclear translocation of the NF-kappaB complex is shown by the decrease of the p65 protein from the cytosol, whereas p65 appears in the nucleus under IL1beta stimulation. This translocation is abolished in the presence of ASU. Moreover, bandshift experiments show an inhibition of the IL1beta-induced binding of p50/p65 complexes to NF-kappaB responsive elements in response to ASU. Finally, among the different mitogen-activated protein kinases known to be induced by IL1beta, ERK1/2 was the sole kinase inhibited by ASU. CONCLUSION: These results demonstrate that ASU express a unique range of activities, which could counteract deleterious processes involved in OA, such as inflammation.

Two hundred intrauterine exchange transfusions in severe blood incompatibilities.

Two hundred intrauterine exchange transfusions were performed under local anesthesia in 107 cases of blood incompatibilities (60 fetuses with severe anemia and 47 with hydrops). Under sonographic guidance, depending on fetal and placental position, an optimal puncturing site was selected along the umbilical vein: placental insertion, fetal insertion, or fetal intraabdominal segment. Tests were immediately performed to confirm fetal origin of blood obtained and estimate hemoglobin level. Blood used for exchange transfusion was compatible with maternal blood and had a hematocrit value of 75%. Exchange transfusion was continued until a hemoglobin level of 16 gm/dl was reached. This procedure was first associated with intraperitoneal transfusions and was subsequently used independently once a month to maintain an adequate hemoglobin level. In 4 fetuses with hydrops, antenatal regression of this sign was observed in 33 cases (70.2%). Overall outcome of 107 fetuses after exchanges was 84 living neonates (78.5%), 15 deaths in utero, and eight neonatal deaths. The survival rate was 91.6% for fetuses without hydrops and 61.7% for those with hydrops. The advantage of exchange transfusion appears to be rapid and efficient correction of anemia with elimination of incompatible fetal red blood cells.