Polyvictimization and Psychiatric Sequelae Associated with Female Genital Mutilation/Cutting (FGM/C)

Female Genital mutilation/cutting (FGM/C) is associated with enduring psychiatric complications. In this study, we investigate the rates of co-morbid abuses and polyvictimization experienced by survivors of FGM/C. This is a sub-analysis of a cohort study examining the patient population at the EMPOWER Center for Survivors of Sex Trafficking and Sexual Violence in New York City. A retrospective chart-review of electronic medical records was conducted for all consenting adult patients who had FGM/C and had an intake visit between January 16, 2014 and March 6, 2020. Of the 80 participants, ages ranged from 20 to 62 years with a mean of 37.4 (SD?=?9.1) years. In addition to FGM/C, participants were victims of physical abuse (43; 53.8%), emotional abuse (35; 43.8%), sexual abuse (35; 43.8%), forced marriage (20; 25%), child marriage (13; 16.3%), and sex trafficking (1; 1.4%). There was a high degree of polyvictimization, with 41 (51.2%) experiencing 3 or more of the aforementioned abuses. Having FGM/C on or after age 13 or having a higher total abuse score was also found to be strong predictors of depression and PTSD. The high rates of polyvictimization among survivors of FGM/C are associated with development of depression and PTSD. Despite co-morbid abuses, patients still attribute substantial psychiatric symptoms to their FGM/C. Health care providers should understand the high risk of polyvictimization when caring for this patient population.

     

Clinical presentation of young people (10–24 years old) with brain tumors: results from the international MOBI-Kids study

Journal of Neuro-Oncology - We used data from MOBI-Kids, a 14-country international collaborative case–control study of brain tumors (BTs), to study clinical characteristics of the tumors in...     

Management of immune-related adverse events resulting from immune checkpoint blockade

Introduction: Immune checkpoint inhibitors (ICI) are now a standard of care in the treatment of many cancers leading to durable responses in patients with metastatic disease. These agents are generally well tolerated but may lead to the occurrence of immune-related adverse events (irAEs). As any organ may be affected, clinicians should be aware of the broad range of clinical manifestations and symptoms and keep in mind that toxicities may occur late, at any point along a patient’s treatment course. Although the most common irAEs are rarely severe, some of them may be associated with great morbidity and even become life-threatening. The rate of occurrence, type and severity of irAEs may vary with the type of ICI; thus, grade 3 and 4 irAEs are reported in more than 55% of patients treated with the combination of ipilimumab 3 mg/kg and nivolumab 1 mg/kg.

Area covered: This review presents the management of irAEs resulting from checkpoint blockade, with a focus on rare irAEs.

Expert commentary: With the development of immuno-oncology and the expanding role of ICI, physicians have learnt to diagnose and treat most of the irAEs that can occur. This review provides an overview of current guidelines, previously published studies and our multidisciplinary team based practices.     

Effects of Cling Film Draping Material on Body Temperature of Mice During Surgery

General anesthesia induces many systemic effects, including thermoregulatory impairment and subsequent perioperative hypothermia. Due to the animals’ small size, monitoring and maintaining body temperatures in laboratory rodents during anesthesia is important for successful surgical outcomes and prompt anesthetic recovery. Draping materials have the potential to aid in thermal support during surgical anesthesia. In this study, rectal and surface (infrared) temperatures were measured in C57BL/6 mice under isoflurane anesthesia every 5 min for the duration of a 35-min sham surgery. In addition to placement on a circulating water bath, mice (n = 6/group) were draped with commercial cling film (CF; Press''n Seal, Glad, Oakland, CA), a conventional paper drape (PD), or no drape (ND) during surgery. Results demonstrated that CF-draped animals had significantly higher rectal temperatures than nondraped animals. Furthermore, surface temperatures of CF-draped mice were considerably higher than those of both paper-draped and undraped animals. The data indicate that cling film is an effective material to help minimize hypothermia in mice and potentially in other laboratory rodents requiring general anesthesia.

Surgery and anesthesia introduce many challenges, especially in veterinary medicine, due to the diversity of species. One major challenge during general anesthesia involves changes in an animal''s thermoregulatory ability.^1,14 Body temperatures in mice and rats fall significantly during anesthesia if no thermal support is provided.^29,30 Hypothermia occurs due to drug-induced alterations to the thermoregulatory center, inadequate circulation, and a loss of body heat to the environment from evaporation, radiation, conduction, and convection.⁷ Mice are particularly susceptible to hypothermia, due to their large surface area per gram of body weight, which permits significant physiologic changes in response to fluctuations in the ambient temperature.³¹ Covering the animal''s body with towels, drapes, or blankets to reduce the area exposed to the environment can minimize heat loss.^6,7,13 Placing the animal on an insulated surface can limit conductive heat loss. In larger animals, warmed fluids can be given perioperatively, heated anesthetic gasses can be administered, and heated blankets and heat packs can be applied to body surfaces to provide exogenous heat.^1,7 Safer and more practical methods for rodents are circulating water heating blankets, thermal gel packs, and warming lamps, which are commonly used for thermal support during anesthesia.^5,14 Addressing all of these factors can contribute to maintaining normothermia during anesthesia.Risk of mortality is elevated during anesthesia and in the postoperative period, including in rodents.^1,13 Hypothermia induced by anesthesia can negatively affect rodents by altering vital parameters such as heart rate and blood pressure and delaying anesthetic recovery.^3,5,12,19 These risks require careful selection of an appropriate anesthetic protocol and careful monitoring of the patient throughout anesthesia until full recovery occurs. Strict anesthetic monitoring and the use of supplemental heat devices have been shown to reduce the likelihood of complications, improve overall postoperative recovery, and reduce mortality associated with surgical procedures.^1,7,15,16 However, due to these species’ small size, monitoring equipment must be specialized and is often costly. Cost-effective and practical alternative equipment and materials would facilitate monitoring and care of rodents.Various draping options are available for rodent surgery, and their use is vital for both sterile technique and heat retention. Traditionally, paper draping material has been a popular option, because it is relatively inexpensive and can be autoclaved together with surgical instruments.^15,16 Some institutions have adopted varying methods and types of draping, including no drape and paper draping. Commercial cling film (CF) has been used as draping due to its low cost, ease of use, and sterility straight out of the box.⁹ Our study team sought to evaluate the effects of draping material on intraoperative thermoregulation in mice by measuring rectal temperature (modified rectal probe) and surface temperature (infrared device) during a 35-min laparotomy procedure, with both temperature devices chosen for affordability and availability. We hypothesized that mice draped with CF would maintain a higher intraoperative body temperature under general anesthesia than would mice with traditional paper drapes or no drape.     

Effects of Oxygen Supplementation on Injectable and Inhalant Anesthesia in C57BL/6 Mice

Oxygen supplementation is rarely considered when anesthetizing laboratory mice, despite reports that mice become profoundly hypoxic under anesthesia. Little is known about the effects of hypoxia on anesthetic performance. This article focuses on the effects of oxygen supplementation on physiologic parameters and depth of anesthesia in male and female C57BL/6 mice. Anesthesia was performed via common injectable anesthetic protocols and with isoflurane. Mice anesthetized with injectable anesthesia received one of 3 drug protocols. Low-dose ketamine/xylazine (100/8 mg/kg) was chosen to provide immobilization of mice, suitable for imaging procedures. Medium-dose ketamine/xylazine/acepromazine (100/10/1 mg/kg) was chosen as a dose that has been recommended for surgical procedures. High-dose ketamine/xylazine/acepromazine (150/12/3 mg/kg) was chosen after pilot studies to provide a long duration of a deep plane of anesthesia. We also tested the effects of oxygen supplementation on the minimum alveolar concentration (MAC) of isoflurane in mice. Mice breathed supplemental 100% oxygen, room air, or medical air with 21% oxygen. Anesthetized mice that did not receive supplemental oxygen all became hypoxic, while hypoxia was prevented in mice that received oxygen. Oxygen supplementation did not affect the MAC of isoflurane. At the high injectable dose, all mice not receiving oxygen supplementation died while all mice receiving oxygen supplementation survived. At low and medium doses, supplemental oxygen reduced the duration of the surgical plane of anesthesia (low dose with oxygen: 22 ± 14 min; low dose without supplementation: 29 ± 18 min; medium dose with oxygen: 43 ± 18 min; medium dose without supplementation: 61 ± 27 min). These results suggest that mice anesthetized with injectable and inhalant anesthesia without supplemental oxygen are routinely hypoxic. This hypoxia prolongs the duration of anesthesia with injectable drug protocols and affects survival at high doses of injectable anesthetics. Because of variable responses to injectable anesthetics in mice, oxygen supplementation is recommended for all anesthetized mice.

Anesthesia is frequently required for mice used in biomedical research, but anecdotal communications suggest that mice receive significantly less anesthetic monitoring and supportive care than do other research species. Monitoring of anesthetized mice is often minimal due to lack of specialized monitoring equipment, and the fact that many rodent surgeries are performed by a single person who acts as both surgeon and anesthetist. Supportive care during anesthesia is limited by a lack of supporting experimental evidence. The lack of monitoring and supportive care may increase the mortality rate in anesthetized mice.Previous studies have shown that mice anesthetized with both inhalant and injectable anesthetics without supplemental oxygen become profoundly hypoxic.^{1,6,8,9,19,26,39,41} While mice in these studies appear to recover normally from anesthesia, little is known about the effects of hypoxia on physiologic parameters, anesthetic depth, and perioperative mortality. Respiratory complications, including hypoxia and hypoventilation, are second only to cardiovascular complications as a cause of perioperative mortality in veterinary species, and in humans, hypoxemia accounts for over 50% of deaths under anesthesia.⁴ To mitigate the risk of hypoxia under anesthesia, oxygen supplementation is commonly provided to anesthetized humans and animals, but is rarely provided to mice in research settings.^6,19All anesthetics affect respiratory function; ketamine and isoflurane are particularly known to cause respiratory depression in mice and rats by impairing the normal physiologic responses to hypoxemia and hypercapnia.^{9,12,20,23,28} The peripheral chemoreceptors, primarily in the carotid body, normally sense dropping arterial partial pressure of oxygen (PaO₂) while central chemoreceptors located in the medulla sense changes in pH and rising partial pressure of carbon dioxide (PaCO₂).^22,23,29,40 Both sets of chemoreceptors compensate by initiating increases in respiratory rate and tidal volume.^{23,28,31,34,40} Injectable and inhalant anesthetic agents depress the function of these chemoreceptors, preventing the increases in respiration that compensate for hypoxia and hypoventilation.^22,29Pulse oximetry is commonly used to monitor peripheral oxygen saturation and detect the presence of hypoxia. Pulse oximeters use the difference in light absorption of oxygenated hemoglobin and deoxygenated hemoglobin in arterial blood to provide an estimate of arterial oxygen content, abbreviated as SpO₂.¹⁷ An SpO₂ of less than 90% to 95% generally corresponds to a PaO₂ of less than 60 to 80 mm Hg, which is considered hypoxic in most species of mammals.^7,17 Because of the small size of mice, species-specific pulse oximetry equipment is necessary to obtain this measurement. Therefore, measurement of SpO₂ in anesthetized mice is not routinely performed, meaning that hypoxia under anesthesia generally goes unrecognized, and is likely more common than is appreciated by our field.The purpose of this study was to confirm that mice become hypoxic after receiving a ketamine/xylazine based anesthetic admixture or isoflurane, which are commonly used anesthetics in mice and to investigate the effects of oxygen supplementation on anesthetic depth, physiologic values, and anesthetic requirements in these mice.^9,35 We hypothesized that mice not receiving supplemental oxygen would be hypoxic, as indicated by lower SpO₂ while anesthetized, and that supplemental oxygen would correct this hypoxia. We also hypothesized that oxygen supplementation would increase the doses of injectable and inhalant anesthesia necessary to maintain mice at a surgical plane of anesthesia.     

Microglial responses after phagocytosis: Escherichia coli bioparticles,but not cell debris or amyloid beta,induce matrix metalloproteinase-9 secretion in cultured rat primary microglial cells

Upon infection or brain damage, microglia are activated to play roles in immune responses, including phagocytosis and soluble factor release. However, little is known whether the event of phagocytosis could be a trigger for releasing soluble factors from microglia. In this study, we tested if microglia secrete a neurovascular mediator matrix metalloproteinase-9 (MMP-9) after phagocytosis in vitro. Primary microglial cultures were prepared from neonatal rat brains. Cultured microglia phagocytosed Escherichia coli bioparticles within 2 hr after incubation and started to secrete MMP-9 at around 12 hr after the phagocytosis. A TLR4 inhibitor TAK242 suppressed the E. coli-bioparticle-induced MMP-9 secretion. However, TAK242 did not change the engulfment of E. coli bioparticles in microglial cultures. Because lipopolysaccharides (LPS), the major component of the outer membrane of E. coli, also induced MMP-9 secretion in a dose–response manner and because the response was inhibited by TAK242 treatment, we assumed that the LPS-TLR4 pathway, which was activated by adhering to the substance, but not through the engulfing process of phagocytosis, would play a role in releasing MMP-9 from microglia after E. coli bioparticle treatment. To support the finding that the engulfing step would not be a critical trigger for MMP-9 secretion after the event of phagocytosis in microglia, we confirmed that cell debris and amyloid beta were both captured into microglia via phagocytosis, but neither of them induced MMP-9 secretion from microglia. Taken together, these data demonstrate that microglial response in MMP-9 secretion after phagocytosis differs depending on the types of particles/substances that microglia encountered.