PTEN deficiency exposes a requirement for an ARF GTPase module for integrin-dependent invasion in ovarian cancer.

Dysregulation of the PI3K/AKT pathway is a common occurrence in high-grade serous ovarian carcinoma (HGSOC), with the loss of the tumour suppressor PTEN in HGSOC being associated with poor prognosis. The cellular mechanisms of how PTEN loss contributes to HGSOC are largely unknown. We here utilise time-lapse imaging of HGSOC spheroids coupled to a machine learning approach to classify the phenotype of PTEN loss. PTEN deficiency induces PI(3,4,5)P3 -rich and -dependent membrane protrusions into the extracellular matrix (ECM), resulting in a collective invasion phenotype. We identify the small GTPase ARF6 as a crucial vulnerability of HGSOC cells upon PTEN loss. Through a functional proteomic CRISPR screen of ARF6 interactors, we identify the ARF GTPase-activating protein (GAP) AGAP1 and the ECM receptor ß1-integrin (ITGB1) as key ARF6 interactors in HGSOC regulating PTEN loss-associated invasion. ARF6 functions to promote invasion by controlling the recycling of internalised, active ß1-integrin to maintain invasive activity into the ECM. The expression of the CYTH2-ARF6-AGAP1 complex in HGSOC patients is inversely associated with outcome, allowing the identification of patient groups with improved versus poor outcome. ARF6 may represent a therapeutic vulnerability in PTEN-depleted HGSOC.

A Model of Stakeholder Engagement with American Indians and Alaska Natives from the Native-CHART Study.

American Indian (AI) and Alaska Native (AN) community stakeholder engagement has the power to transform health research. However, the engagement and dissemination process is challenging in AIAN communities due to the historical and current negative experiences of AIAN populations in health research (Dillard et al., 2018). Whereas there is a paucity of recommendations about how to engage stakeholders in health research, from agenda-setting to proposal development, study design, recruitment, data collection, analysis, results, and dissemination (Concannon et al., 2014), there is limited information about how these recommendations are operationalized within the context of AIAN health research and practice (Concannon et al., 2014; Forsythe et al., 2016). For the purposes of this article, stakeholders are individuals, organizations, or communities who have a direct interest in the process and outcomes of a project, research, or policy effort (Boaz et al., 2018). Stakeholder engagement is a systematic process involving stakeholders, which provides opportunities for consultation, input, reviews, reactions, support, and assistance with dissemination. Dissemination focuses on how, when, by whom, and under what circumstances evidence spreads throughout agencies, organizations, states, counties, communities, tribes, researchers, policy makers, and service organizations.

Key regulator PNPLA8 drives phospholipid reprogramming induced proliferation and migration in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and leads to the poorest patient outcomes despite surgery and chemotherapy treatment. Exploring new molecular mechanisms of TNBC that could lead to the development of novel molecular targets are critically important for improving therapeutic options for treating TNBC. METHODS: We sought to identify novel therapeutic targets in TNBC by combining genomic and functional studies with lipidomic analysis, which included mechanistic studies to elucidate the pathways that tie lipid profile to critical cancer cell properties. Our studies were performed in a large panel of human breast cancer cell lines and patient samples. RESULTS: Comprehensive lipid profiling revealed that phospholipid metabolism is reprogrammed in TNBC cells. We discovered that patatin-like phospholipase domain-containing lipase 8 (PNPLA8) is overexpressed in TNBC cell lines and tissues from breast cancer patients. Silencing of PNPLA8 disrupted phospholipid metabolic reprogramming in TNBC, particularly affecting the levels of phosphatidylglycerol (PG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and glycerophosphocholine (GPC). We showed that PNPLA8 is essential in regulating cell viability, migration and antioxidation in TNBC cells and promoted arachidonic acid and eicosanoid production, which in turn activated PI3K/Akt/Gsk3ß and MAPK signaling. CONCLUSIONS: Our study highlights PNPLA8 as key regulator of phospholipid metabolic reprogramming and malignant phenotypes in TNBC, which could be further developed as a novel molecular treatment target.

Engineered type 1 regulatory T cells designed for clinical use kill primary pediatric acute myeloid leukemia cells.

Type 1 regulatory (Tr1) T cells induced by enforced expression of IL-10 (LV-10) are being developed as a novel treatment for chemotherapy-resistant myeloid leukemias. In vivo, LV-10 cells do not cause graft vs host disease while mediating graft vs leukemia (GvL) effect against adult acute myeloid leukemia (AML). Since pediatric AML (pAML) and adult AML are different on a genetic and epigenetic level, we investigate herein whether LV-10 cells also efficiently kill pAML cells. We show that the majority of primary pAML are killed by LV-10 cells, with different levels of sensitivity to killing. Transcriptionally, pAML sensitive to LV-10 killing expressed a myeloid maturation signature. Overlaying the signatures of sensitive and resistant pAML onto the public NCI TARGET pAML dataset revealed that sensitive pAML clustered with M5 monocytic pAML and pAML with MLL rearrangement. Resistant pAML clustered with myelomonocytic leukemias and those bearing the core binding factor translocations inv(16) or t(8;21)(RUNX1-RUNX1T1). Furthermore, resistant pAML upregulated the membrane glycoprotein CD200, which binds to the inhibitory receptor CD200R1 on LV-10 cells. To examine if CD200 expression on target cells can impair LV-10 cell function, we overexpressed CD200 in myeloid leukemia cell lines ordinarily sensitive to LV-10 killing. Indeed, LV-10 cells degranulated less and killed fewer CD200-overexpressing cells compared to controls, indicating that pAML can utilize CD200 expression for immune evasion. Altogether, the majority of pAML are killed by LV-10 cells in vitro, supporting further LV-10 cell development as an innovative cell therapy for pAML.

Surgical cure of primary hyperparathyroidism ameliorates gastroesophageal reflux symptoms.

OBJECTIVE: Gastroesophageal reflux disease (GERD) symptoms are commonly reported in primary hyperparathyroidism (pHPT). Although a calcium-mediated cause-and-effect relationship has been suggested, it remains unknown if parathyroidectomy improves GERD symptoms. METHODS: Over a 22-month period, 1,175 (39%) of 3,000 consecutive adult patients with pHPT and symptomatic GERD (on prescription reflux medications daily for ≥2 years) undergoing parathyroidectomy were entered into a prospective study. Standardized Frequency Scale for Symptoms of GERD (FSSG) questionnaire was used to assess symptoms before, 1 and 2 years after parathyroidectomy. RESULTS: Daily prescription medication was used by 81%, while 19% used daily non-prescription drugs, both for a mean of 2.9 ± 0.7 years. GERD symptoms improved (26%) or resolved completely (36%) in 62% of patients (p < 0.0001 vs. preoperative baseline) 1 year after parathyroidectomy. Prescription medications for GERD decreased from 81% of enrolled patients to 26% (p < 0.0001) 12 months postoperatively, with 39% having complete symptom relief and taking no medications (p < 0.0001). Daily use of prescription GERD medications decreased to occasional over-the-counter drug use in 35% after parathyroidectomy (p < 0.0001). Mean FSSG scores decreased significantly postoperatively (pre-op: 18.0 ± 8.0 vs. post-op: 10.0 ± 5.0; p < 0.0001), with significant improvements in all 12 FSSG categories, including motility (pre-op: 7.3 ± 3.0 vs. post-op: 4.4 ± 3.0; p < 0.0001) and acid reflux symptoms (pre-op: 10.8 ± 5.0 vs. post-op: 5.9 ± 4.0; p < 0.0001). Symptomatic improvements were durable 2 years after parathyroidectomy. CONCLUSION: Symptomatic GERD is common in pHPT. Parathyroidectomy provides significant, durable relief of both motility and acid reflux symptoms allowing discontinuation of prescription drug use for GERD in most (74%) patients providing yet another indication for parathyroidectomy in pHPT.

Problems Facing the Visiting Anesthesia Team in an Underdeveloped Nation and Possible Solutions.

More than 50% of the population in most developing countries is younger than 18 years, and it has been estimated that 85% of these children may require some sort of surgery before their 15th birthday. Common congenital surgical requirements are for cleft lip and palate, inguinal hernia, meningomyelocele, as well as hydrocephalus. In addition, there is a greater incidence of trauma experienced by pediatric patients. Burn and scald injuries are also common because of the proximity of domestic open fires and boiling pots of water. Infectious conditions such as osteomyelitis and skin abscesses are more frequent in developing countries than in the developed world.Given this backdrop, the visiting anesthesiology team is faced with significant logistic issues related to a large and varied set of surgeries. This requires careful planning to ensure there will be enough personnel, equipment, and drugs available for the trip. Anesthesia teams very often have to rely on their own supplies on these excursions. Careful questioning of previous visiting groups is vital in preparation. For example, it is pointless to bring cases of sevoflurane to an operating room where the anesthesia machine only has a halothane vaporizer.

Association of COVID 19 pneumonitis and acute mesenteric ischemia.

Key Clinical Message: D. dimer could be useful as an indicator in diagnosis of mesenteric ischemia in COVID patients. A two staged damage control emergency laparotomy is of good benefits in such patients. Abstract: Bowel ischemia in COVID 19 patients is extremely rare condition results from migrating thrombus formed by a hypercoagulable inflammatory state that is frequently associated COVID 19 infection. A two staged damage control emergency laparotomy is of good benefits in general especially in those with active COVID 19 infection.

Notochord segmentation in zebrafish controlled by iterative mechanical signaling.

In bony fishes, patterning of the vertebral column, or spine, is guided by a metameric blueprint established in the notochord sheath. Notochord segmentation begins days after somitogenesis concludes and can occur in its absence. However, somite patterning defects lead to imprecise notochord segmentation, suggesting that these processes are linked. Here, we identify that interactions between the notochord and the axial musculature ensure precise spatiotemporal segmentation of the zebrafish spine. We demonstrate that myoseptum-notochord linkages drive notochord segment initiation by locally deforming the notochord extracellular matrix and recruiting focal adhesion machinery at these contact points. Irregular somite patterning alters this mechanical signaling, causing non-sequential and dysmorphic notochord segmentation, leading to altered spine development. Using a model that captures myoseptum-notochord interactions, we find that a fixed spatial interval is critical for driving sequential segment initiation. Thus, mechanical coupling of axial tissues facilitates spatiotemporal spine patterning.

Interaction between LIS1 and PDE4, and its role in cytoplasmic dynein function.

LIS1, a WD40 repeat scaffold protein, interacts with components of the cytoplasmic dynein motor complex to regulate dynein-dependent cell motility. Here, we reveal that cAMP-specific phosphodiesterases (PDE4s) directly bind PAFAH1B1 (also known as LIS1). Dissociation of LIS1-dynein complexes is coupled with loss of dynein function, as determined in assays of both microtubule transport and directed cell migration in wounded monolayers. Such loss in dynein functioning can be achieved by upregulation of PDE4, which sequesters LIS1 away from dynein, thereby uncovering PDE4 as a regulator of dynein functioning. This process is facilitated by increased intracellular cAMP levels, which selectively augment the interaction of long PDE4 isoforms with LIS1 when they become phosphorylated within their regulatory UCR1 domain by protein kinase A (PKA). We propose that PDE4 and dynein have overlapping interaction sites for LIS1, which allows PDE4 to compete with dynein for LIS1 association in a process enhanced by the PKA phosphorylation of PDE4 long isoforms. This provides a further example to the growing notion that PDE4 itself may provide a signalling role independent of its catalytic activity, exemplified here by its modulation of dynein motor function.

Hollow microneedles for intradermal injection fabricated by sacrificial micromolding and selective electrodeposition.

Limitations with standard intradermal injections have created a clinical need for an alternative, low-cost injection device. In this study, we designed a hollow metal microneedle for reliable intradermal injection and developed a high-throughput micromolding process to produce metal microneedles with complex geometries. To fabricate the microneedles, we laser-ablated a 70 µm × 70 µm square cavity near the tip of poly(lactic acid) (PLA) microneedles. The master structure was a template for multiple micromolded poly(lactic acid-co-glycolic acid) (PLGA) replicas. Each replica was sputtered with a gold seed layer with minimal gold deposited in the cavity due to masking effects. In this way, nickel was electrodeposited selectively outside of the cavity, after which the polymer replica was dissolved to produce a hollow metal microneedle. Force-displacement tests showed the microneedles, with 12 µm thick electrodeposition, could penetrate skin with an insertion force 9 times less than their axial failure force. We injected fluid with the microneedles into pig skin in vitro and hairless guinea pig skin in vivo. The injections targeted 90 % of the material within the skin with minimal leakage onto the skin surface. We conclude that hollow microneedles made by this simple microfabrication method can achieve targeted intradermal injection.

Faster pharmacokinetics and increased patient acceptance of intradermal insulin delivery using a single hollow microneedle in children and adolescents with type 1 diabetes.

OBJECTIVE: In an effort to improve compliance with insulin therapy and to accelerate insulin pharmacokinetics, we tested the hypothesis that intradermal insulin delivery using a hollow microneedle causes less pain and leads to faster onset and offset of insulin pharmacokinetics in children and adolescents with type 1 diabetes (T1DM) compared with a subcutaneous, insulin pump catheter. RESEARCH DESIGN AND METHODS: In this repeated measures study, 16 children and adolescents with T1DM received Lispro insulin by microneedle and subcutaneous administration on separate days. Subjects rated the pain of insertion and infusion using a visual analog scale. Blood specimens were collected over 4 h to determine insulin and glucose concentrations. RESULTS: Microneedle insertion pain was significantly lower compared with insertion of the subcutaneous catheter (p = 0.005). Insulin onset time was 22 min faster (p = 0.0004) and offset time was 34 min faster (p = 0.017) after hollow microneedle delivery compared with subcutaneous delivery. CONCLUSIONS: In this study, intradermal insulin delivery using a single, hollow microneedle device resulted in less insertion pain and faster insulin onset and offset in children and adolescents with T1DM. A reduction in pain might improve compliance with insulin delivery. The faster onset and offset times of insulin action may enable closed-loop insulin therapy.

Dublin Anti-Bullying Self-Efficacy Scales: Bifactor and Item Response Theory Models.

Dublin Anti-Bullying Self-Efficacy Scales aim to measure the effectiveness of school anti-bullying programs in promoting five steps that victims and bystanders take against online and offline bullying behaviors. These steps are anti-bullying self-efficacy beliefs to recognize bullying behaviors, comprehend emergency, take responsibility, know what to do, and intervene. However, when an anti-bullying program is very effective for the majority of participants who give high scores, a considerable number of participants who give low scores are very likely to be detected as outliers. This raises two measurement issues. First, high scores create highly negatively skewed data and lead to measuring a unidimensional rather than multidimensional construct. This could be one reason why recent research has been unclear about the extent to which the scales measure a unidimensional, multidimensional, or bifactor construct. Second, should outliers be removed or be considered as participants for whom the program was ineffective? If the scales had measurement invariance across the group of outliers and non-outliers or low and high self-efficacy, it could be concluded that the anti-bullying program was ineffective for some participants. The current research aims to address these issues by testing both measurement invariance as well as unidimensional and bifactor models of anti-bullying self-efficacy. Results of Pure Exploratory Bifactor (PEBI) Analyses and Item Response Theory (IRT) with Two-Parameter-Logistic (2PL) Models of data from a convenience sample of 14-year-old students in Ireland (N = 1,222) indicated sufficient psychometric properties of both unidimensional and multidimensional scales for victim offline, victim online, bystander offline, and bystander online. Further research can use these scales for measuring the bifactor model of anti-bullying self-efficacy as well as the cut-off score for distinguishing between low and high anti-bullying self-efficacy.

Nonconsensual Dissemination of Sexual Images Among Adolescents: Associations With Depression and Self-Esteem.

The nonconsensual dissemination of sexual images is a form of image-based sexual abuse that is relatively common among adolescents. However, literature on this issue with adolescent samples is relatively scarce. Therefore, this study is aimed at investigating how this phenomenon varies based on gender and sexual orientation, along with its association with depression and self-esteem. Participants were 728 secondary school students in Sweden (50.4% girls and 46.4% boys; 14.4% lesbian, gay, bisexual [LGB+]) aged from 12 to 19 years (M = 14.35, SD = 1.29). A survey was administered during school hours, including a measure assessing the nonconsensual dissemination of sexual images, the short version of the Moods and Feelings Questionnaire, and the Rosenberg's Self-Esteem Scale. Results showed that LGB+ participants were more likely to indicate that they were victimized compared to their heterosexual peers, while no differences were observed for gender. Being the target of nonconsensual dissemination of sexual images was positively associated with depression, whereas no significant associations were yielded for self-esteem. Based on the findings from this study, we suggest raising adolescent awareness in relation to the nonconsensual dissemination of sexual images as a form of sexual abuse that can have detrimental effects on those who are targeted. Such educational programs should be inclusive of sexual minority adolescents, as they are at a particular risk of being the target of nonconsensual dissemination of sexual images. Psychological support should be provided to the targets of this form of abuse, through both school and online counseling. Future research should adopt longitudinal designs while recruiting diverse samples.

Dynamic BMP signaling mediates notochord segmentation in zebrafish.

The vertebrate spine is a metameric structure composed of alternating vertebral bodies (centra) and intervertebral discs.1 Recent studies in zebrafish have shown that the epithelial sheath surrounding the notochord differentiates into alternating cartilage-like (col2a1/col9a2+) and mineralizing (entpd5a+) segments which serve as a blueprint for centra formation.2,3,4,5 This process also defines the trajectories of migrating sclerotomal cells that form the mature vertebral bodies.4 Previous work demonstrated that notochord segmentation is typically sequential and involves the segmented activation of Notch signaling.2 However, it is unclear how Notch is activated in an alternating and sequential fashion. Furthermore, the molecular components that define segment size, regulate segment growth, and produce sharp segment boundaries have not been identified. In this study, we uncover that a BMP signaling wave acts upstream of Notch during zebrafish notochord segmentation. Using genetically encoded reporters of BMP activity and signaling pathway components, we show that BMP signaling is dynamic as axial patterning progresses, leading to the sequential formation of mineralizing domains in the notochord sheath. Genetic manipulations reveal that type I BMP receptor activation is sufficient to ectopically trigger Notch signaling. Moreover, loss of Bmpr1ba and Bmpr1aa or Bmp3 function disrupts ordered segment formation and growth, which is recapitulated by notochord-specific overexpression of the BMP antagonist, Noggin3. Our data suggest that BMP signaling in the notochord sheath precedes Notch activation and instructs segment growth, facilitating proper spine morphogenesis.

Dublin Anti-Bullying Self-Efficacy Models and Scales: Development and Validation.

Literature on anti-bullying programs shows a growing consensus about promoting victims and bystanders' self-efficacy against bullying, but provides no theoretical model nor measurement scale to assess the extent of achieving this aim. The current research aims to address these theoretical and empirical gaps by proposing the Dublin Anti-Bullying Self-Efficacy Models and Scales, using a convenience sample of 14-year-old students in Ireland (N = 1,100). After establishing both content and face validity, four separate scales were tested to measure anti-bullying self-efficacy beliefs among offline victims (20-item), online victims (20-item), offline bystanders (20-item), and online bystanders (20-item). Thereafter, four separate exploratory factor analyses of the scale items were followed by reflective measurement analyses of their internal consistency and construct (convergent and discriminant) validity. Results indicated sufficient psychometric properties of each scale measuring five dimensions of anti-bullying self-efficacy: recognition, emergency comprehension, responsibility, knowledge, and intervention. Further research is needed to test the proposed model and scale for assessing effectiveness of an anti-bullying program in promoting self-efficacy beliefs.

The forgotten people: Hepatitis B virus (HBV) infection as a priority for the inclusion health agenda.

Hepatitis B virus (HBV) infection represents a significant global health threat, accounting for 300 million chronic infections and up to 1 million deaths each year. HBV disproportionately affects people who are under-served by health systems due to social exclusion, and can further amplify inequities through its impact on physical and mental health, relationship with stigma and discrimination, and economic costs. The 'inclusion health' agenda focuses on excluded and vulnerable populations, who often experience barriers to accessing healthcare, and are under-represented by research, resources, interventions, advocacy, and policy. In this article, we assimilate evidence to establish HBV on the inclusion health agenda, and consider how this view can inform provision of better approaches to diagnosis, treatment, and prevention. We suggest approaches to redress the unmet need for HBV interventions among excluded populations as an imperative to progress the global goal for the elimination of viral hepatitis as a public health threat.

Axial segmentation by iterative mechanical signaling.

In bony fishes, formation of the vertebral column, or spine, is guided by a metameric blueprint established in the epithelial sheath of the notochord. Generation of the notochord template begins days after somitogenesis and even occurs in the absence of somite segmentation. However, patterning defects in the somites lead to imprecise notochord segmentation, suggesting these processes are linked. Here, we reveal that spatial coordination between the notochord and the axial musculature is necessary to ensure segmentation of the zebrafish spine both in time and space. We find that the connective tissues that anchor the axial skeletal musculature, known as the myosepta in zebrafish, transmit spatial patterning cues necessary to initiate notochord segment formation, a critical pre-patterning step in spine morphogenesis. When an irregular pattern of muscle segments and myosepta interact with the notochord sheath, segments form non-sequentially, initiate at atypical locations, and eventually display altered morphology later in development. We determine that locations of myoseptum-notochord connections are hubs for mechanical signal transmission, which are characterized by localized sites of deformation of the extracellular matrix (ECM) layer encasing the notochord. The notochord sheath responds to the external mechanical changes by locally augmenting focal adhesion machinery to define the initiation site for segmentation. Using a coarse-grained mathematical model that captures the spatial patterns of myoseptum-notochord interactions, we find that a fixed-length scale of external cues is critical for driving sequential segment patterning in the notochord. Together, this work identifies a robust segmentation mechanism that hinges upon mechanical coupling of adjacent tissues to control patterning dynamics.

Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function.

The glycocalyx component and sialomucin podocalyxin (PODXL) is required for normal tissue development by promoting apical membranes to form between cells, triggering lumen formation. Elevated PODXL expression is also associated with metastasis and poor clinical outcome in multiple tumor types. How PODXL presents this duality in effect remains unknown. We identify an unexpected function of PODXL as a decoy receptor for galectin-3 (GAL3), whereby the PODXL-GAL3 interaction releases GAL3 repression of integrin-based invasion. Differential cortical targeting of PODXL, regulated by ubiquitination, is the molecular mechanism controlling alternate fates. Both PODXL high and low surface levels occur in parallel subpopulations within cancer cells. Orthotopic intraprostatic xenograft of PODXL-manipulated cells or those with different surface levels of PODXL define that this axis controls metastasis in vivo. Clinically, interplay between PODXL-GAL3 stratifies prostate cancer patients with poor outcome. Our studies define the molecular mechanisms and context in which PODXL promotes invasion and metastasis.

Cinacalcet (Sensipar) provides no measurable clinical benefits for patients with primary hyperparathyroidism and may accelerate bone loss with prolonged use.

BACKGROUND: Cinacalcet (Sensipar) has been shown to decrease calcium levels in patients with primary hyperparathyroidism (PHPT); however, few other endpoints have been studied and long-term effects are not known. METHODS: At the discretion of a referring doctor, 70 patients began Cinacalcet as an alternative to surgery for PHPT. Patients were followed as long as the drug was tolerated at which time all underwent parathyroidectomy. RESULTS: Before treatment, serum calcium levels averaged 11.7 ± 0.5 (range, 11.0-15.1) and PTH averaged 156 ± 42 (range, 88-815); 93% had two or more classic parathyroid symptoms (average, 5.3; range, 0-9). Cinacalcet was discontinued in 19 patients (26%) within 4 months because of nausea/vomiting. The remainder (n = 51) were treated from 8 to 28 months. Calcium levels decreased in all patients but remained variable. PTH levels decreased in 80% of patients but always remained elevated. Only 3 (6%) had symptom relief (p = 0.8), whereas 11 (21.6%) felt worse (p < 0.05). Twenty-three patients took Cinacalcet for >1.5 years, 14 of which showed significant (>1 SD) decreases in bone density (p < 0.05), and none had increases in bone density. All had curative outpatient parathyroid surgery followed by partial or complete resolution of symptoms within 3 months in 88% (p < 0.001). CONCLUSIONS: Cinacalcet reduces serum calcium but is not tolerated by many patients. Cinacalcet does not provide symptom relief of PHPT and more commonly increases subjective symptoms. Prolonged use is associated with continued bone loss in some patients, possibly due to persistent elevated PTH levels. With very few exceptions, pHPT can be cured via a quick outpatient operation, which remains the treatment of choice.

Human Amnion/Chorion Membrane May Reduce Transient Recurrent Laryngeal Nerve Injury During Thyroid Surgery.

Recurrent laryngeal nerve (RLN) damage is a significant and prevalent complication of thyroid surgery. Based on the beneficial role of a human amnion/chorion membrane (HACM) allograft in wound management and nerve regeneration, we investigated whether placement of a commercially available HACM allograft on dissected RLN could reduce the occurrence and/or duration of RLN injury during thyroidectomy. Among 67 patients undergoing thyroidectomy, 100 at-risk nerves (exposure of at least 3 cm of RLN) received intraoperative placement of HACM; 205 at-risk RLNs without HACM in 134 matched patients served as controls. Patient-reported vocal analysis, physician-assessed vocal analysis, and laryngoscopic assessment of vocal-fold dysfunction were performed before and after surgery. At 24 h after surgery, 17 patients in the control group (12.5%) had documented voice changes; these changes persisted for at least 3 weeks in seven patients (5%). Only one patient (1.5%) in the HACM group had vocal changes at 24 h after surgery, which resolved within 1 week (P < 0.01). Intraoperative placement of the HACM allograft over at-risk RLNs during thyroidectomy may reduce the incidence, severity, and/or duration of intraoperative RLN injury, which could address a significant complication of head and neck surgery. A larger prospectively designed clinical study is warranted to further investigate a possible benefit of the HACM allograft in thyroid surgery and to begin to understand the mechanisms through which a clinical benefit might be mediated.