Levelling the playing field through the London Network of the UK clinical trials accelerator platform.

Cystic fibrosis (CF) is a multisystem, genetic disease with a significantly reduced life expectancy. Despite substantial progress in therapies in the last 10-15 years, there is still no cure. There are dozens of drugs in the development pipeline and multiple clinical trials are being conducted across the globe. The UK Cystic Fibrosis Trust's (CFT) Clinical Trials Accelerator Platform (CTAP) is a national initiative bringing together 25 UK based CF centres to support the CF community in accessing and participating in CF clinical trials. CTAP enables more CF centres to run a broader portfolio of trials and increases the range of CF studies available for UK patients. There are four large specialist CF centres based in London, all within a small geographical region as well as two smaller centres which deliver CF care. At the launch of CTAP, these centres formed a sub-network in a consortium-style collaboration. The purpose of the network was to ensure equity of access to trials for patients across the UK's capital, and to share experience and knowledge. Four years into the programme we have reviewed our practices through working group meetings and an online survey. We sought to identify strengths and areas for improvement. We share our findings here, as we believe they are relevant to others delivering research in regions outside of London and in other chronic diseases.

The influence of primary language on postoperative stroke outcomes.

BACKGROUND: Language barriers have the potential to influence acute stroke outcomes. Thus, we examined postoperative stroke outcomes among non-English primary language speakers. METHODS: Utilizing the Healthcare Cost and Utilization Project State Inpatient Database (2016-2019), we conducted a retrospective cohort study of adults diagnosed with a postoperative stroke in Michigan, Maryland, and New Jersey. Patients were classified by primary language spoken: English (EPL) or non-English (n-EPL). The primary outcome was hospital length-of-stay. Secondary outcomes included stroke intervention, feeding tube, tracheostomy, mortality, cost, disposition, and readmission. Propensity-score matching and post-match regression were used to quantify outcomes. RESULTS: Among 3078 postoperative stroke patients, 6.2 â€‹% were n-EPL. There were no differences in length-of-stay or secondary outcomes, except for higher odds of feeding tube placement (OR 1.95, 95 â€‹% CI 1.10-3.47, p â€‹= â€‹0.0227) in n-EPL. CONCLUSIONS: Postoperative stroke outcomes were comparable by primary language spoken. However, higher odds of feeding tube placement in n-EPL may suggest differences in patient-provider communication.

Post-discharge Mental Healthcare and Emergency General Surgery Readmission for Patients with Serious Mental Illness.

OBJECTIVE: To determine the association between post-discharge mental healthcare and odds of readmission after emergency general surgery (EGS) hospitalization for patients with serious mental illness (SMI). BACKGROUND DATA: A mental health visit (MHV) after medical hospitalization is associated with decreased readmissions for patients with SMI. The impact of a MHV after surgical hospitalization is unknown. METHODS: Using Medicare claims, we performed a retrospective cohort study of hospitalized EGS patients with SMI aged >65.5 (2016-2018). EGS included colorectal, general abdominal, hepatopancreatobiliary, hernia, intestinal obstruction, resuscitation, and upper gastrointestinal conditions. SMI was defined as schizophrenia spectrum, mood, or anxiety disorders. The exposure was MHV within 30 days of discharge. The primary outcome was 30-day readmission. Secondary outcomes included emergency department presentation and psychiatric admission. Inverse probability weighting was used to evaluated outcomes. RESULTS: Of 88,092 analyzed patients, 11,755 (13.3%) had a MHV within 30 days of discharge. 23,696 (26.9%) of patients were managed operatively, 64,395 (73.1%) non-operatively. After adjustment for potential confounders, patients with a post-discharge MHV had lower odds of acute care readmission than patients without a MHV in both operative (OR 0.60; 95% CI: [0.40-0.90]) and non-operative (OR 0.67; 95% CI [0.53-0.84]) cohorts. There was no association between post-discharge MHV and ED presentation or psychiatric admission in the operative or non-operative groups. CONCLUSIONS: Post-discharge MHV after EGS hospitalization was associated with decreased odds of readmission for patients with SMI managed operatively and nonoperatively. In older EGS patients with SMI, coordination of MHVs may be a mechanism to reduce readmission disparities.

Barriers and Facilitators to Clinical Practice Development in Men and Women Surgeons.

Importance: Many early-career surgeons struggle to develop their clinical practices, leading to high rates of burnout and attrition. Furthermore, women in surgery receive fewer, less complex, and less remunerative referrals compared with men. An enhanced understanding of the social and structural barriers to optimal growth and equity in clinical practice development is fundamental to guiding interventions to support academic surgeons. Objective: To identify the barriers and facilitators to clinical practice development with attention to differences related to surgeon gender. Design, Setting, and Participants: A multi-institutional qualitative descriptive study was performed using semistructured interviews analyzed with a grounded theory approach. Interviews were conducted at 5 academic medical centers in the US between July 12, 2022, and January 31, 2023. Surgeons with at least 1 year of independent practice experience were selected using purposeful sampling to obtain a representative sample by gender, specialty, academic rank, and years of experience. Main Outcomes and Measures: Surgeon perspectives on external barriers and facilitators of clinical practice development and strategies to support practice development for new academic surgeons. Results: A total of 45 surgeons were interviewed (23 women [51%], 18 with ≤5 years of experience [40%], and 20 with ≥10 years of experience [44%]). Surgeons reported barriers and facilitators related to their colleagues, department, institution, and environment. Dominant themes for both genders were related to competition, case distribution among partners, resource allocation, and geographic market saturation. Women surgeons reported additional challenges related to gender-based discrimination (exclusion, questioning of expertise, role misidentification, salary disparities, and unequal resource allocation) and additional demands (related to appearance, self-advocacy, and nonoperative patient care). Gender concordance with patients and referring physicians was a facilitator of practice development for women. Surgeons suggested several strategies for their colleagues, department, and institution to improve practice development by amplifying facilitators and promoting objectivity and transparency in resource allocation and referrals. Conclusions and Relevance: The findings of this qualitative study suggest that a surgeon's external context has a substantial influence on their practice development. Academic institutions and departments of surgery may consider the influence of their structures and policies on early career surgeons to accelerate practice development and workplace equity.

Ambulatory surgical management of most displaced tibial tubercle fractures in children is safe and efficient.

Purpose: The purpose of this study is to compare the outcome of patients with displaced tibial tubercle fractures treated surgically who spent one or more nights in the hospital after surgery with that of patients treated in an ambulatory setting with no perioperative hospitalization. We hypothesized that tibial tubercle fractures have a low rate of complications and that most patients do well without an overnight hospital stay for observation. Methods: We retrospectively reviewed all pediatric tibial tubercle fractures treated operatively by a single surgeon over a 13.5-year period. Fractures treated in an inpatient setting, defined as at least one night of overnight hospitalization postoperatively, were compared with fractures treated in an ambulatory setting with no perioperative hospitalization. Results: Seventy-one fractures in 70 patients were analyzed. All fractures were treated with open reduction and internal fixation with unicortical screws. Thirty-five fractures (49.3%) were fixed in an ambulatory setting, while 36 (50.7%) were inpatient. There were no significant differences between inpatient demographics (age, gender, body mass index, fracture type). Average operative time was significantly longer in the inpatient group compared with the ambulatory group (97.8 min versus 58.8 min, p < 0.001). There was no significant difference in the incidence of complications between inpatient and ambulatory groups (25.0% versus 11.4%, p = 0.22). No cases of compartment syndrome were noted. Conclusion: Ambulatory surgical treatment of select tibial tubercle fractures with same-day discharge is safe and efficient. Not all patients with surgically treated tibial tubercle fractures need to stay overnight in the hospital.

Technical considerations for replantation: from bony fixation to soft tissue coverage.

Digital replantation is a challenging and at-time tedious operation, but if approached thoughtfully and with reasonable expectations can be a reliable and rewarding undertaking. This article summarizes technical considerations for digital replantations involving flexor tendon zone II. The article has been ordered according to the recommended sequence of a structure-by-structure repair in a non-thumb digit. Special considerations are described for thumb, multiple digits, and heterotopic replantation.

Barriers and facilitators to surgical access in underinsured and immigrant populations.

BACKGROUND: Marginalized communities are at risk of receiving inequitable access to surgical care. We aimed to examine the barriers and facilitators to access to surgery in underinsured and immigrant populations. METHODS: A systematic review of disparities in access to surgical care was performed between January 1, 2000-March 2, 2022. Methodological quality was assessed with the Mixed Methods Appraisal Tool. A convergent integrated approach was used to code common themes between studies. RESULTS: Of 1315 publications, a total of 66 studies were included for systematic review. Eight studies specifically discussed immigrant patient populations. Barriers and facilitators to surgical access were categorized by patient and health systems related factors. CONCLUSIONS: Established facilitators to improve surgical access are centered on patient-level factors while interventions to address systems-related barriers are limited and may be an area for further investigation. Research focused on access to surgery in immigrant populations remains sparse.

Effect of Serious Mental Illness on Surgical Consultation and Operative Management of Older Adults with Acute Biliary Disease: A Nationwide Study.

BACKGROUND: Mental illness is associated with worse outcomes after emergency general surgery. To understand how preoperative processes of care may influence disparate outcomes, we examined rates of surgical consultation, treatment, and operative approach between older adults with and without serious mental illness (SMI). STUDY DESIGN: We performed a nationwide, retrospective cohort study of Medicare beneficiaries aged 65.5 years or more hospitalized via the emergency department for acute cholecystitis or biliary colic. SMI was defined as schizophrenia spectrum, mood, and/or anxiety disorders. The primary outcome was surgical consultation. Secondary outcomes included operative treatment and surgical approach (laparoscopic vs open). Multivariable logistic regression was used to examine outcomes with adjustment for potential confounders related to patient demographics, comorbidities, and rates of imaging. RESULTS: Of 85,943 included older adults, 19,549 (22.7%) had SMI. Before adjustment, patients with SMI had lower rates of surgical consultation (78.6% vs 80.2%, p < 0.001) and operative treatment (68.2% vs 71.7%, p < 0.001), but no significant difference regarding laparoscopic approach (92.0% vs 92.1%, p = 0.805). In multivariable regression models with adjustment for confounders, there was no difference in odds of receiving a surgical consultation (odds ratio 0.98 [95% CI 0.93 to 1.03]) or undergoing operative treatment (odds ratio 0.98 [95% CI 0.93 to 1.03]) for patients with SMI compared with those without SMI. CONCLUSIONS: Older adults with SMI had similar odds of receiving surgical consultation and operative treatment as those without SMI. As such, differences in processes of care that result in SMI-related disparities likely occur before or after the point of surgical consultation in this universally insured patient population.

Antibiotic Prophylaxis and Infectious Complications in Isolated Gunshot Wounds to the Upper Extremity.

BACKGROUND: Prophylactic antibiotics are variably prescribed after isolated upper extremity gunshot wounds (UE GSWs). The risk of infection and factors influencing prescribing practice remain poorly understood, and clinical practice guidelines are lacking. METHODS: Adults with isolated UE GSWs over a 10-year period were included. Medical records were reviewed for demographic and injury variables, comorbidities, surgical treatments, antibiotic administration, infectious complications, and follow-up duration. Infection rate was calculated. Bivariate and multivariable linear regression analyses were used to identify patient-related and injury-related factors predictive of prophylactic antibiotic prescription. RESULTS: A total of 281 patients were eligible for inclusion. Prophylactic antibiotics were prescribed at discharge for 111 patients (40%). Multivariable analysis revealed that patients with more distal injuries and ballistic fractures were significantly more likely to receive prophylactic antibiotics. Of patients with at least 30-day postinjury follow-up, 6% developed infections. CONCLUSION: Prophylactic antibiotic administration after UE GSWs was inconsistent but more common in patients with ballistic fractures and injuries in the hand. The overall incidence of infection was found to lie between 3% and 6%. The rate of infection in the antibiotic prophylaxis (2%-6%) group was similar to that in the no-antibiotic (5%-7%) group, suggesting that antibiotic prophylaxis may not have a large impact on infectious risk. However, because this study is nonrandomized, and because this study is underpowered for multivariable modeling of infectious risk, it remains possible that subgroups of this population may still benefit from antibiotic prophylaxis.

Intracranial hemangioma-associated cranial nerve VII palsy treated with propranolol in an infant with possible PHACE syndrome.

A 2-week-old infant with a large vascular birthmark involving her right face presented with right-sided facial paralysis. MRI of the brain revealed multiple intracranial hemangiomas, and the hemangioma within the right temporal bone impinged on the facial nerve, which resulted in paralysis. Cranial nerve palsies are a rare neurological manifestation of PHACE syndrome. We report successful treatment of the facial nerve palsy with oral propranolol.

Childhood lymphomatoid papulosis Type D, a rare and challenging diagnosis.

A 10-year-old female with a several-year history of pityriasis lichenoides (PL) presented with a new, asymptomatic, large, and necrotic ulcer of her right upper arm. Skin biopsy was consistent with lymphomatoid papulosis (LyP) Type D, a recently recognized subtype of LyP that is distinguished histologically by marked epidermotropism and a perivascular infiltrate of medium-sized pleomorphic lymphocytes with a cytotoxic phenotype (CD3+, CD8+). This is only the sixth reported case of LyP Type D in a child, and while the prognosis in children appears favorable, with no reports of progression to lymphoma to date, more experience in children with longer-term follow-up is needed. Our case highlights both the challenging clinical diagnosis, since in our patient the longstanding clinical presentation was indistinguishable from PL, as well as histopathologic diagnosis, which required expert opinion and consensus.

Weight status and meeting the physical activity, sleep, and screen-time guidelines among Texas children: results from a population based, cross-sectional analysis.

BACKGROUND: Evidence suggests that the interactive effects of physical activity, screen-time and sleep are stronger than independent effects of these behaviors on pediatric obesity. However, this hypothesis has not been fully examined among samples of young school-aged children. The aim of this study is to determine the association of weight status with meeting the physical activity, screen-time, and sleep guidelines, independently and concurrently, among 2nd grade children. METHODS: The Texas School Physical Activity and Nutrition Project collected parent-reported physical activity, screen-time, and sleep, and measured body height and weight on a statewide representative weighted sample (n = 320,005) of children. Weighted multivariable logistic regressions were used to assess associations of weight status (classified using age- and sex-specific body weight [kg]/height [m]2, based on International Obesity Task Force cutoffs) with meeting the physical activity, screen-time, and sleep guidelines, while controlling for relevant covariates (age, sex, race/ethnicity, comorbidities etc.). RESULTS: A greater proportion of healthy weight children (9.9%) met the physical activity, screen-time, and sleep guidelines concurrently compared to children who are thin (3.3%), or children with overweight (5.7%), obese (3.5%), and morbid obesity (1.0%). Children who were thin (adjusted odds ratio [aOR]:0.40, 95% confidence interval [CI]: 0.10, 1.50), overweight (aOR = 0.75, CI: 0.33, 1.70), obese (aOR = 0.53, CI: 0.15, 1.81), and morbidly obese (aOR = 0.10, CI: 0.02, 0.28) had lower odds of concurrently meeting the guidelines compared to children with healthy weight. CONCLUSIONS: Among this representative sample of Texas children, weight status was associated with meeting physical activity, screen-time, and sleep guidelines. Future studies should aim to evaluate causal relations between these behaviors and weight status.

Neurotoxicity studies with a tropomyosin-related kinase A inhibitor, ASP7962, on the sympathetic and sensory nervous systems in rats.

ASP7962 is a small molecule inhibitor for the nerve growth factor (NGF) receptor, tropomyosin-related kinase A (TrkA). NGF contributes to the survival of sensory and sympathetic neurons through TrkA receptor activation. Gross, microscopic, and quantitative effects to the nervous system were evaluated following oral ASP7962 administration to Sprague Dawley rats for 4 weeks and 13 weeks and after a recovery period. Histopathological findings included reversible neuronal atrophy but no neuronal death in the sympathetic ganglia (cervicothoracic ganglion, cranial mesenteric ganglion or superior [cranial] cervical ganglion). Stereological analysis showed reversible decreased ganglion volume and/or decreased neuron size in the superior (cranial) cervical ganglion in both the 4-week and the 13-week repeated dose studies. There were no test article related changes in the brain, dorsal root ganglia with spinal nerve roots or trigeminal ganglia and no functional deficits. ASP7962 did not cause any detectable dysfunction of the sympathetic and sensory nervous system in either study.

The effects of N-acetyl cysteine on acute viral respiratory infections in humans: A rapid review.

Current evidence suggests that N-Acetyl Cysteine (NAC) administration may help improve outcomes in people with acute respiratory distress syndrome and acute lung injury - conditions that closely resemble the signs and symptoms of COVID-19. Few mild and transient adverse events were reported in published randomised-controlled trials, indicating that NAC may be reasonably safe. These findings suggest that NAC may complement the management of COVID-19 infection, particularly when administered intravenously within an intensive care unit (ICU) environment. Verdict Current evidence suggests that N-Acetyl Cysteine (NAC) administration may help improve outcomes in people with acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) - conditions that closely resemble the signs and symptoms of COVID-19. In this rapid review, NAC was predominately administered intravenously to patients with ARDS or ALI, who were at risk of or requiring mechanical ventilation, and were admitted to a hospital intensive care unit. Findings indicated that NAC administration may assist in improving markers of inflammation or oxidation, systemic oxygenation, the need for / duration of ventilation, rate of patient recovery and clinical improvement score. The effects of NAC on patient length of stay, CT/x-ray images, mortality rate and pulmonary complications were inconclusive. Few mild and transient adverse events were noted, indicating that NAC may be safe for use in acute respiratory distress syndrome or acute lung injury. Based on the evidence identified, and the similar symptomatic profiles of ARDS/ALI and COVID-19, the findings suggest that NAC may be used to complement the management of COVID-19 infection within an acute care setting. The safety and efficacy of orally administered NAC for the management of milder forms of COVID-19 infection within the community setting, remains uncertain. The current research evidence suggests NAC warrants further research for acute respiratory viral infections, including COVID-19.

Leptin-induced Notch and IL-1 signaling crosstalk in endometrial adenocarcinoma is associated with invasiveness and chemoresistance.

BACKGROUND: Obesity is a recognized risk factor for endometrial cancer (EmCa) and other cancer types. Leptin levels are significantly increased in obese individuals. Leptin-induced signaling crosstalk [Notch, Interleukin-1 (IL-1) and leptin outcome, NILCO] has been associated with breast cancer progression. This complex signaling crosstalk affects cancer cell proliferation, migration, invasion, angiogenesis, apoptosis and chemoresistance. NILCO expression was previously detected in human EmCa. However, it is unknown whether leptin regulates NILCO and alters EmCa's response to chemotherapeutics. It is hypothesized that leptin induces NILCO and increases aggressiveness and chemoresistance in EmCa cells. AIM: To determine whether leptin induces NILCO molecules in EmCa affecting cell proliferation, aggressiveness and chemoresistance. METHODS: Leptin's effects on the expression of NILCO molecules [mRNAs and proteins for Notch receptors (Notch1-4), ligands (JAG1 and DLL4) and downstream effectors (survivin, Hey2), and leptin (OB-R) and IL-1 (IL-1R tI) receptors] was examined in EmCa cells (type I: Ishikawa, and HEC-1A, and type II: An3Ca and KLE) using Real-time PCR and Western blot analysis, respectively. In addition, the effects of leptin on cell cycle, proliferation and cell invasion were determined using cytometric analysis (Cellometer Vision CBA system), MTT cell proliferation and Matrigel-based invasion assays, respectively. Inhibitors of leptin (nanoparticle-bound leptin peptide receptor antagonist-2, IONP-LPrA2), IL-1 (anti-IL-1R tI antibody) and Notch (siRNA interference RNA) were used to investigate NILCO's effects on cell proliferation and invasion. Leptin's effects on Paclitaxel cytotoxicity in EmCa cells was determined by the CCK8 and Cellometer-based Annexin V assays. RESULTS: For the first time it was shown that leptin is an inducer of Notch in EmCa. Experimental data suggest that leptin induced the expression of NILCO molecules, promoted proliferation and S- phase progression, and reduced Paclitaxel cytotoxicity on EmCa cells. Leptin's effects were higher in type II EmCa cells. The progression of this more aggressive form of the disease is associated with obesity. Remarkably, the use of the leptin signaling antagonist, IONP-LPrA2, re-sensitized EmCa cells to Paclitaxel. CONCLUSION: Present data suggest the notion that leptin-induced NILCO could be a link between obesity and EmCa progression and chemoresistance. Most aggressive type II EmCa cells were higher sensitive to leptin, which appears to increase proliferation, cell cycle progression, aggressiveness, and chemoresistance to Paclitaxel. Therefore, leptin and NILCO could be novel therapeutic targets for type II EmCa, which does not have targeted therapy. Overall, IONP-LPrA2 has a potential as a novel adjuvant drug to enhance the effectiveness of type II EmCa chemotherapy.

Pharmacological evidence of medicinal cannabis in oncology: a systematic review.

PURPOSE: This systematic literature review examines research into the use of medicinal cannabis in cancer management. The aim was to identify the gaps in knowledge on the dose, dosing schedule and absorption of the administration routes of medicinal cannabis use in oncology. METHODS: A comprehensive search of the literature was conducted across six databases to identify original data reporting the pharmacology of medicinal cannabis in oncology. RESULTS: Eighteen articles were selected for review. Of the selected articles, ten were identified as randomised control trials, two experimental studies, two retrospective cohort studies and four case studies. Four articles reported absorption data and one drug interaction study was identified. CONCLUSIONS: There is little evidence reported in the literature on the absorption of medicinal cannabis in cancer populations. Various reasons are explored for the lack of pharmacokinetic studies for medicinal cannabis in cancer populations, including the availability of assays to accurately assess cannabinoid levels, lack of clinical biomarkers and patient enrolment for pharmacokinetic studies.

Decreased osteoprogenitor proliferation precedes attenuation of cancellous bone formation in ovariectomized rats treated with sclerostin antibody.

Sclerostin antibody (Scl-Ab) stimulates bone formation, which with long-term treatment, attenuates over time. The cellular and molecular mechanisms responsible for the attenuation of bone formation are not well understood, but in aged ovariectomized (OVX) rats, the reduction in vertebral cancellous bone formation is preceded by a reduction in osteoprogenitor (OP) number and significant induction of signaling pathways known to suppress mitogenesis and cell cycle progression in the osteocyte (OCy) (Taylor et al., 2016). To determine if the reduction in OP number is associated with a decrease in proliferation, aged OVX rats were administered vehicle or Scl-Ab for 9 or 29 days and implanted with continuous-delivery 5-bromo-2'-deoxyuridine (BrdU) mini-osmotic pumps 5 days prior to necropsy. The total number of BrdU-labeled osteoblasts (OB) was quantified in vertebral cancellous bone to indirectly assess the effects of Scl-Ab treatment on OP proliferation at the time of activation of modeling-based bone formation at day 9 and at the time of maximal mineralizing surface, initial decrease in OP number, and transcriptional changes in the OCy at day 29. Compared with vehicle, Scl-Ab resulted in an increase in the total number of BrdU-positive OB (+260%) at day 9 that decreased with continued treatment (+50%) at day 29. These differences in proliferation occurred at time points when the increase in total OB number was significant and similar in magnitude. These findings suggest that reduced OP proliferation contributes to the decrease in OP numbers, an effect that would limit the OB pool and contribute to the attenuation of bone formation that occurs with long-term Scl-Ab treatment.

The chemotherapeutic agent paclitaxel selectively impairs reversal learning while sparing prior learning, new learning and episodic memory.

Chemotherapy is widely used to treat patients with systemic cancer. The efficacy of cancer therapies is frequently undermined by adverse side effects that have a negative impact on the quality of life of cancer survivors. Cancer patients who receive chemotherapy often experience chemotherapy-induced cognitive impairment across a variety of domains including memory, learning, and attention. In the current study, the impact of paclitaxel, a taxane derived chemotherapeutic agent, on episodic memory, prior learning, new learning, and reversal learning were evaluated in rats. Neurogenesis was quantified post-treatment in the dentate gyrus of the same rats using immunostaining for 5-Bromo-2'-deoxyuridine (BrdU) and Ki67. Paclitaxel treatment selectively impaired reversal learning while sparing episodic memory, prior learning, and new learning. Furthermore, paclitaxel-treated rats showed decreases in markers of hippocampal cell proliferation, as measured by markers of cell proliferation assessed using immunostaining for Ki67 and BrdU. This work highlights the importance of using multiple measures of learning and memory to identify the pattern of impaired and spared aspects of chemotherapy-induced cognitive impairment.

Type II Endometrial Cancer Overexpresses NILCO: A Preliminary Evaluation.

OBJECTIVE: The expression of NILCO molecules (Notch, IL-1, and leptin crosstalk outcome) and the association with obesity were investigated in types I and II endometrial cancer (EmCa). Additionally, the involvement of NILCO in leptin-induced invasiveness of EmCa cells was investigated. METHODS: The expression of NILCO mRNAs and proteins were analyzed in EmCa from African-American (n = 29) and Chinese patients (tissue array, n = 120 cases). The role of NILCO in leptin-induced invasion of Ishikawa and An3ca EmCa cells was investigated using Notch, IL-1, and leptin signaling inhibitors. RESULTS: NILCO molecules were expressed higher in type II EmCa, regardless of ethnic background or obesity status of patients. NILCO proteins were mainly localized in the cellular membrane and cytoplasm of type II EmCa. Additionally, EmCa from obese African-American patients showed higher levels of NILCO molecules than EmCa from lean patients. Notably, leptin-induced EmCa cell invasion was abrogated by NILCO inhibitors. CONCLUSION: Type II EmCa expressed higher NILCO molecules, which may suggest it is involved in the progression of the more aggressive EmCa phenotype. Obesity was associated with higher expression of NILCO molecules in EmCa. Leptin-induced cell invasion was dependent on NILCO. Hence, NILCO might be involved in tumor progression and could represent a new target/biomarker for type II EmCa.