Inhibition of Mertk Signaling Enhances Bone Healing after Tooth Extraction.

Regeneration of alveolar bone is an essential step in restoring healthy function following tooth extraction. Growth of new bone in the healing extraction socket can be variable and often unpredictable when systemic comorbidities are present, leading to the need for additional therapeutic targets to accelerate the regenerative process. One such target is the TAM family (Tyro3, Axl, Mertk) of receptor tyrosine kinases. These proteins have been shown to help resolve inflammation and maintain bone homeostasis and thus may have therapeutic benefits in bone regeneration following extraction. Treatment of mice with a pan-TAM inhibitor (RXDX-106) led to accelerated alveolar bone fill following first molar extraction in a mouse model without changing immune infiltrate. Treatment of human alveolar bone mesenchymal stem cells with RXDX-106 upregulated Wnt signaling and primed the cells for osteogenic differentiation. Differentiation of human alveolar bone mesenchymal stem cells with osteogenic media and TAM-targeted inhibitor RXDX-106 (pan-TAM), ASP-2215 (Axl specific), or MRX-2843 (Mertk specific) showed enhanced mineralization with pan-TAM or Mertk-specific inhibitors and no change with Axl-specific inhibitor. First molar extractions in Mertk-/- mice had increased alveolar bone regeneration in the extraction socket relative to wild type controls 7 d postextraction. Flow cytometry of 7-d extraction sockets showed no difference in immune cell numbers between Mertk-/- and wild type mice. RNAseq of day 7 extraction sockets showed increased innate immune-related pathways and genes associated with bone differentiation in Mertk-/- mice. Together, these results indicate that TAM receptor signaling, specifically through Mertk, can be targeted to enhance bone regeneration after injury.

Single-Incision vs. Multiport Robotic Sacrocolpopexy: 126 Consecutive Cases at a Single Institution.

Robot-assisted laparoscopic sacrocolpopexy (RSC) has gained popularity as a method for easier intracorporeal suturing than conventional laparoscopic sacrocolpopexy. However, few studies have compared multiport RSC (MP-RSC) and single-incision RSC (SI-RSC). We aimed to compare perioperative outcomes between these techniques for advanced pelvic organ prolapse (POP). We analyzed 126 patients who underwent RSC for POP quantification (all stage III to IV) between March 2019 and May 2021 at Seoul Asan Medical Center. We prospectively collected operation-related data, including total operation time (OT; from skin incision to closure) and perioperative outcomes. A total of 106 and 20 patients underwent MP-RSC and SI-RSC, respectively. The mean ages were 57.49 ± 10.89 and 56.20 ± 10.30 years in the MP-RSC and SI-RSC groups, respectively. The mean total OT was significantly shorter for MP-RSC than for SI-RSC (105.43 ± 24.03 vs. 121.10 ± 26.28 min). The OT difference was 15.67 min (95% confidence interval, 3.90-25.85, p = 0.009). No statistically significant differences were observed in terms of perioperative variables (estimated blood loss, hospital stay) and postoperative adverse events (POP recurrence, mesh erosion). SI-RSC had comparable intraoperative and postoperative outcomes to MP-RSC, with additional cosmetic benefits. MP-RSC had significantly shorter OT than SI-RSC.

First report comparing the two types of single-incision robotic sacrocolpopexy: Single site using the da Vinci Xi or Si system and single port using the da Vinci SP system.

OBJECTIVE: The gold standard procedure for treating patients with apical pelvic organ prolapse (POP) is sacrocolpopexy. However, no report comparing the two types of single-incision robotic sacrocolpopexy, namely, single-site robotic sacrocolpopexy (SS-RSC) and single-port robotic sacrocolpopexy (SP-RSC) exists. Therefore, we compared the safety and effectiveness of SS-RSC and SP-RSC. MATERIALS AND METHODS: In this study, 48 patients who underwent single-incision RSC, 40 non-consecutive patients who underwent SS-RSC, and 8 consecutive patients who underwent SP-RSC for symptomatic POP quantification stage III-IV and were eligible for the 1-year follow-up (FU) were included. We compared the surgical time and operative outcomes of SS-RSC and SP-RSC. We also compared the data of the initial 8 cases in each group. RESULTS: The mean patient age was 59.2 ± 11.0 years and 66.1 ± 8.0 years in the SS-RSC (n = 40) and SP-RSC (n = 8) groups, respectively. The mean operative time (OT) and console time were comparable between the SS-RSC and SP-RSC groups (135.3 ± 31.6 min vs 141.8 ± 23.5 min; 94.6 ± 32.2 min vs 89 ± 9.5 min, respectively). The docking time and cervix suturing time were short in the SP-RSC group (P < 0.05). However, in the analysis of the initial 8 cases in each group, all surgical times except the cervix suturing time were shorter in the SP-RSC group (P < 0.05). Three cases had intraoperative bladder injury (two [5.0%] in the SS-RSC and one [12.5%] in the SP-RSC group). Two cases (5.0%) had umbilical incisional hernia in the SS-RSC group. Two cases had vaginal mesh erosion on the posterior vaginal wall, with 1 case in each group. One case (2.5%) experienced a recurrence of POP; an anterior compartment POP-Q stage 2 following SS-RSC at the 4-week FU. CONCLUSION: Single-incision RSC, both SS-RSC and SP-RSC, is a feasible and effective surgical option for treating symptomatic apical POP with an aesthetic finish.

Resistance training in patients with schizophrenia: Concept and proof of principle trial.

Resistance training has been shown to contribute to the prevention and management of cardiovascular diseases, which is why it can help reducing morbidity and mortality in schizophrenia patients. Moreover, positive effects on different schizophrenia symptom domains have been proposed. However, a specific resistance training tailored to the needs of schizophrenia patients and its evaluation is still lacking. The objective in this proof of principle trial was to evaluate the feasibility and efficacy of a newly developed 12-week resistance program according to current recommendations of the WHO and the American College of Sports Medicine. We employed a single blind, parallel assignment clinical trial design with participants randomized to attend either a resistance training including three 50min units per week or a balance and tone program as control condition. The primary outcome was the impact on health-related difficulties assessed with the World Health Organization Disability Assessment Schedule (WHO-DAS). Secondary outcome parameters included the level of functioning, schizophrenia symptoms, selected cognitive parameters as well as risk factors for cardiovascular diseases. In our proof of principle trial, we could not find significant time or group effects of resistance training on the WHO-DAS. However, we could observe significant positive effects on the level of functioning assessed with the Global Assessment of Functioning Scale (GAF) over the course of time, which were more pronounced in the intervention group. Our findings indicated that patients with schizophrenia could safely participate in resistance training with relevant improvements in their level of functioning. Well-powered replication trials are needed to provide more efficacy data.

Anaphylactic shock to vaginal misoprostol: a rare adverse reaction to a frequently used drug.

Misoprostol is widely used in daily practice for induction of labor and cervical dilatation prior to intrauterine procedures, including dilatation and curettage or hysteroscopy. Anaphylactic shock to intravaginal misoprostol can occur not only in pregnant women, as reported in 2 previous cases, but also in a non-pregnant, perimenopausal woman, as in the case described herein. A 49-year-old woman received vaginal misoprostol for cervical ripening prior to hysteroscopic myomectomy and experienced anaphylactic shock. Two 400 µg doses of misoprostol 6 hours apart caused uncontrolled shaking and high fever followed by shock. In conclusion, the possibility of anaphylactic shock should be considered in patients with sudden hypotension following misoprostol administration. Prompt identification and management are crucial to prevent morbidity and mortality following an anaphylactic shock to misoprostol.

[Psychosis - clinical differential diagnosis]. / Differenzialdiagnose psychotischer Symptome.

BACKGROUND: Many patients with psychiatric and organic disorders may present primary or secondary psychotic symptoms. Based on the ICD 10 classification, this article describes the possible underlying diseases and their subdivision. The main focus will be differential-diagnostic evaluations of psychotic syndromes. RESULTS: In the clinical setting, the differential diagnosis of the paranoid schizophrenia and other psychotic disorders into three main disease groups is important: 1. other psychiatric diseases, 2. primary and secondary organic diseases and 3. autoimmune diseases. The first group contains, for example, drug-induced psychoses, affective disorders, personality disorders. The second group includes forms of dementia, forms of deliria or metabolic diseases. Recently, another focus is set on autoimmune diseases, especially encephalitides. SUMMARY: A detailed medical history, a physical examination and organic diagnostic can lead to the correct diagnosis and therapy. The differential-diagnostic classification and the detection of organic causes is an important part of psychiatric care, but often a good cooperation with organic specialties is needed.