Primary Cutaneous Acral CD8-Positive Lymphoproliferative Disorder: A Case Report With Nonacral Presentation.

In this study, we describe a patient of primary cutaneous acral CD8-positive lymphoproliferative disorder located in a nonacral region. A 65-year-old male presented with an ill-defined lesion of rubbery consistency and a maximum diameter of 2.5 cm localized in the right thigh. Histologically, it was composed of a diffuse dermal infiltration of medium-sized atypical lymphocytes that expressed CD3, CD8, and TIA-1. In addition, a characteristic paranuclear positivity with CD68 was observed. During the follow-up, the patient had a recurrence of the disease in the abdomen with a lesion showing similar morphology and phenotype. To our knowledge, < 20 patients of primary cutaneous acral CD8-positive lymphoproliferative disorder with a nonacral presentation have been described in English literature. Although rare, its identification is essential to differentiate it from other T-cell lymphoma that express CD8 and cytotoxic markers, and whose clinical courses are very aggressive.

CD61 identifies a superior population of aged murine HSCs and is required to preserve quiescence and self-renewal.

ABSTRACT: Aging leads to a decline in function of hematopoietic stem cells (HSCs) and increases susceptibility to hematological disease. We found CD61 to be highly expressed in aged murine HSCs. Here, we investigate the role of CD61 in identifying distinct subpopulations of aged HSCs and assess how expression of CD61 affects stem cell function. We show that HSCs with high expression of CD61 are functionality superior and retain self-renewal capacity in serial transplantations. In primary transplantations, aged CD61High HSCs function similarly to young HSCs. CD61High HSCs are more quiescent than their CD61Low counterparts. We also show that in aged bone marrow, CD61High and CD61Low HSCs are transcriptomically distinct populations. Collectively, our research identifies CD61 as a key player in maintaining stem cell quiescence, ensuring the preservation of their functional integrity and potential during aging. Moreover, CD61 emerges as a marker to prospectively isolate a superior, highly dormant population of young and aged HSCs, making it a valuable tool both in fundamental and clinical research.

Evolución del riesgo y protección en la infancia y la adolescencia / Evolution of risk and vulnerability in childhood and adolescence

(analítico) Los factores de riesgo y protección pueden ser utilizados para evaluar, prevenir e intervenir en el maltrato infantil. El objetivo de este estudio es analizar longitudinalmente el riesgo en la infancia y la adolescencia, para determinar qué factores pueden ser empleados como indicadores de evolución. Se empleó una muestra de 102 niños, niñas y adolescentes que participaban en el sistema de bienestar infantil español, en tres momentos temporales. Los resultados indicaron que existe una evolución del riesgo, con una tendencia general de disminución de riesgos e incremento de elementos protectores. Nuestros hallazgos identificaron la existencia de factores dinámicos y estáticos. Este estudio pone de manifiesto la relevancia de la atención e intervención continuada y a largo plazo para fortalecer los factores de protección y disminuir los de riesgo en niños, niñas y adolescentes.

(analytical) Risk and protective factors can be used for risk and needs assessments, prevention, and intervention in cases involving mistreatment of children. The aim of this study is to provide a longitudinal analysis of risks and vulnerabilities in childhood and adolescence, with the goal of determining which factors can be used as indicators for progress with cases. A sample of 102 children and adolescents supported by the child welfare system in Spain was used along with measurements based on three different points in time. The study's results indicated that there is a change in risk levels, with a general trend of decreasing risk and increasing protective elements. The study's findings identified the existence of a group of dynamic factors and another group of static factors. This study highlighted the relevance of continuous and long-term care and intervention in order to strengthen protection and decrease risks for children.

(analítico) Os factores de risco e protecção podem ser utilizados para avaliar, prevenir e intervir em casos de maustratos a crianças. O objectivo deste estudo é analisar o risco na infância e adolescência longitudinalmente, a fim de determinar que factores podem ser utilizados como indicadores de evolução. Uma amostra de 102 crianças e adolescentes participantes no sistema espanhol de bem-estar infantil foi utilizada em três pontos no tempo. Os resultados indicaram que existe uma evolução do risco, com uma tendência geral de diminuição do risco e aumento dos elementos protectores. Os nossos resultados identificaram a existência de factores dinâmicos e estáticos. Este estudo destaca a relevância dos cuidados e intervenções contínuos e a longo prazo para reforçar os factores de protecção e diminuir os factores de risco nas crianças.

A deficient immune response to SARS-CoV-2 in the nasopharynx is associated with severe COVID-19 pneumonia.

OBJECTIVES: We analyzed the expression of inflammatory and antiviral genes in the nasopharynx of SARS-CoV-2 infected patients and their association with the severity of COVID-19 pneumonia. METHODS: We conducted a cross-sectional study on 223 SARS-CoV-2 infected patients. Clinical data were collected from medical records, and nasopharyngeal samples were collected in the first 24 hours after admission to the emergency room. The gene expression of eight proinflammatory/antiviral genes (plasminogen activator urokinase receptor [PLAUR], interleukin [IL]-6, IL-8, interferon [IFN]-ß, IFN-stimulated gene 15 [ISG15], retinoic acid-inducible gene I [RIG-I], C-C motif ligand 5 [CCL5], and chemokine C-X-C motif ligand 10 [CXCL10]) were quantified by real-time polymerase chain reaction. Outcome variables were: (i) pneumonia; (ii) severe pneumonia or acute respiratory distress syndrome. Statistical analysis was performed using multivariate logistic regression analyses. RESULTS: We enrolled 84 mild, 88 moderate, and 51 severe/critical cases. High expression of PLAUR (adjusted odds ratio [aOR] = 1.25; P = 0.032, risk factor) and low expression of CXCL10 (aOR = 0.89; P = 0.048, protective factor) were associated with pneumonia. Furthermore, lower values of ISG15 (aOR = 0.88, P = 0.021), RIG-I (aOR = 0.87, P = 0.034), CCL5 (aOR = 0.73, P <0.001), and CXCL10 (aOR = 0.84, P = 0.002) were risk factors for severe pneumonia/acute respiratory distress syndrome. CONCLUSION: An unbalanced early innate immune response to SARS-CoV-2 in the nasopharynx, characterized by high expression of PLAUR and low expression of antiviral genes (ISG15 and RIG-I), and chemokines (CCL5 and CXCL10), was associated with COVID-19 severity.

Implementation of an ERAS protocol on elderly patients in liver resection.

BACKGROUND: The increase of quality of life, the improvement in the perioperative care programs, the use of the frailty index, and the surgical innovation has allowed to access of complex abdominal surgery for elderly patients like liver resection. Despite of this, in patients aged 70 or older there is a limitation for the implementation ERAS protocolos. The aim of this study is to evaluate the implementation ERAS protocol on elderly patients (≥70 years) undergoing liver resection. METHODS: A prospective cohort study of patients who underwent liver resection from December 2017 to December 2019 with an ERAS program. We compare the outcomes in patients ≥70 years (G ≥ 70) versus <70 years (G < 70). The frailty was measured with the Physical Frailty Phenotype score. RESULTS: A total of 101 patients were included. 32 of these (31.6%) were patients ≥70 years. 90% of the both groups had performed >70% of the ERAS. Oral diet tolerance and mobilization on the first postoperative day were quicker in <70 years group. The hospital stay was similar in both groups (3.07days/2.7days). Morbidity and mortality were similar; Clavien I-II(G ≥ 70:41% vs G < 70:30,5%) and Clavien ≥ III (G ≥ 70:6% vs G < 70:8.5%), like hospital readmissions. Mortality was <1%. ERAS protocol compliance was associated with a decrease in complications (ERAS < 70%:80% vs ERAS > 90%:20%; p = 0.02) and decrease in severity of complications in both study groups. Frailty was found in 6% of the elderly group; the only patient who died had a frailty index of 4. CONCLUSION: Implementation of ERAS protocol for elderly patients is possible, with major improvements in perioperative outcomes, without an increase in morbidity, mortality neither readmissions.

El impacto de la soledad y la fragilidad en el bienestar de los mayores europeos / The impact of loneliness and frailty on the well-being of older Europeans

Resumen Introducción: El bienestar es un constructo importante cuyos determinantes asociados deben ser identificados para comprender con mayor profundidad los procesos para envejecer de forma saludable. El estudio del impacto de la fragilidad en el bienestar de las personas mayores requiere incorporar los dominios físico, psicológico y social. Así, el adulto mayor frágil puede definirse a partir de la fragilidad física, junto con la soledad como fragilidad social. Este estudio propone un modelo para estudiar el impacto de la fragilidad física y la soledad sobre el bienestar de las personas mayores, diferenciando entre control, autonomía, placer y autorrealización. Método: Se realizó un estudio de carácter transversal con una muestra de 13569 personas mayores provenientes de la encuesta SHARE, para estimar un modelo de ecuaciones estructurales en el que se contemplaban los efectos de la fragilidad y la soledad en el bienestar (cuestionario CASP), controlado por el género, la edad y la salud percibida. Resultados: El modelo final contemplaba el efecto del género sobre el indicador de fuerza de prensión de fragilidad. Los resultados mostraron un ajuste adecuado del modelo a los datos y consiguieron explicar un 80.1% de la varianza de control, un 48.6% de la de autonomía, un 43.6% de la de placer y un 61.3% de la varianza de autorrealización. Conclusiones: La soledad y la fragilidad presentaron efectos diferenciales en función del componente de bienestar. Se discuten las implicaciones de dichos efectos en el desarrollo de intervenciones.

Abstract Introduction: Well-being is an important construct whose associated determinants must be identified in order to further understand the processes for healthy aging. The study of the impact of frailty on older people's wellbeing requires the incorporation of physical, psychological and social domains. Hence, frail older adults can be defined from physical frailty, together with loneliness as social frailty. This study proposes a model to study the impact of frailty and loneliness on well-being of older adults, differentiating among control, autonomy, pleasure and self-realization. Method: A cross-sectional study was carried out with a sample of 13569 older adults from the SHARE project was employed in order to estimate a structural equation model in which frailty and loneliness affected well-being (CASP questionnaire), while controlling for gender, age and perceived health. Results: The final model additionally contemplated the effect of gender on the grip strength frailty indicator. Results showed a good fit of the model to the data and could explain 80.1% of the variance of control, 48.6% of autonomy's, 43.6% of pleasure's and 61.3% of the variance of self-realization. Conclusions: Loneliness and frailty showed differential effects on the different components of well-being. Implications of these effects on intervention development are discussed

Safety of tongue base procedures for sleep apnoea in adults: A systematic review and metanalysis from the YO-IFOS study group.

OBJECTIVE: Tongue base and hypopharynx are the major sites of obstruction in OSA patients with failed palatal surgery. In recent years, several minimally invasive procedures have been developed to address tongue base obstruction. However, the research focus has consistently been on the effectiveness of surgery in reducing obstructive sleep apnoea rather than on postoperative complications. In this systematic review and metanalysis we aim to review the complication rate of minimally invasive base of tongue procedures for OSAS in adults. DATA SOURCES: PubMed (Medline), the Cochrane Library, EMBASE, Scopus, SciELO and Trip Database. REVIEW METHODS: Data sources were checked by three authors of the YO-IFOS sleep apnoea study group. Three authors extracted the data. Main outcome was expressed as the complication rate and 95% confidence interval for each surgical technique. RESULTS: 20 studies (542 patients) met the inclusion criteria. The mean complication rate is 12.79%; 4.65% for minor complications, 6.42% if they are moderate, and 1.77% if severe. The most reported complication overall is infection, in 1.95% of cases, followed by transient swallowing disorder, occurring in 1.30% of the total sample. CONCLUSION: The heterogeneity amongst the included studies prevents us from obtaining solid conclusions. The available evidence suggests that minimally invasive base of tongue procedures may present a wide spectrum of complication rates, ranging from 4.4% in tongue base radiofrequency to up to 42.42% in tongue base ablation.

Treatment of acute intraoperative Budd-Chiari syndrome by placement of silicone prosthesis.

Complete liver mobilization for major resections sometimes causes liver tilting due to the release of the suspensory elements of the liver. Rarely this may take to a liver abnormal position with acute obstruction to venous flow at the suprahepatic level (Budd-Chiari syndrome). To avoid this complication, techniques such as post-operative stent implantation have been described. The case of a patient who underwent a complete mobilization of the liver for resection of the inferior venous cava and a right renal tumor, was reported. After that, an acute Budd-Chiari Syndrome was observed caused of the liver malposition, which was solved with the placement of two silicone prostheses in the liver cell.

Assessing the effect of adenoidectomy on nasal resistance and airflow. A systematic review and meta-analysis.

OBJECTIVE: Clinical guidelines suggest adenoidectomy when enlarged adenoids are associated with nasal obstruction and other symptoms. Given that nasal obstruction is the leading symptom of adenoid hypertrophy, it should be thoroughly explored. However, there is no consensus regarding what could be the best approach. This systematic review is designed with the objective of exploring the extent to which adenoidectomy can decrease nasal resistance through rhinomanometry. REVIEW METHODS: 3 authors members of the YO-IFOS rhinology study group independently analyzed the data sources (Pubmed, the Cochrane Library, EMBASE, SciELO) for papers assessing the change in nasal resistance and/or nasal airflow in rhinomanometry after adenoidectomy in pediatric patients. RESULTS: A total of 9 studies with a total population of 423 participants (323 patients excluding healthy controls) met the inclusion criteria. All of them found decreased nasal resistance after adenoidectomy. 5 studies could be combined in a metanalysis, which revealed a statistically significant difference of 0.52 Pa in basal conditions, and 0.64 Pa in rhinomanometry under nasal decongestion. 4 authors explored changes in nasal airflow. All of them found a statistically significant increase in nasal airflow after adenoidectomy. However, their results could not be merged in a meta-analysis. CONCLUSION: This systematic review and meta-analysis demonstrated the existence of a systematic decrease in nasal resistance and increase in nasal airflow with and without nasal decongestant after adenoidectomy. The available evidence suggests that rhinomanometry with nasal decongestant could help in intermediate cases of adenoid hypertrophy, in order to identify the presence of nasal obstruction and, when present, the possibility of other causes for it rather than enlarged adenoids, mainly turbinate hypertrophy.

Right and Left Colorectal Cancer: Differences in Post-Surgical-Care Outcomes and Survival in Elderly Patients.

(1) There is evidence of the embryological, anatomical, histological, genetic and immunological differences between right colon cancer (RCC) and left colon cancer (LCC). This research has the general objective of studying the differences in outcome between RCC and LCC. (2) A longitudinal analytical study with prospective follow-up of the case-control type was conducted from 1 January 2010 to 31 December 2017 including 398 patients with 1:1 matching, depending on the location of the tumor. Inclusion criteria: programmed colectomies, 15 cm above the anal margin, adults and R0 surgery. (3) Precisely 6.8% of the exitus occurred in the first 6 months of the intervention. At 6 months, patients with LCC presented a mean survival of 7 months higher than RCC (p = 0.028). In the first stages, it can be observed that most of the exitus are for patients with RCC (stage I p = 0.021, stage II p = 0.014). In the last stages, the distribution of the deaths does not show differences between locations (stage III p = 0.683, stage IV p = 0.898). (4) The results show that RCC and LCC are significantly different in terms of evolution, progression, complications and survival. Patients with RCC have a worse prognosis, even in the early stages of the disease, due to more advanced N stages, larger tumor size, more frequently poorly differentiated tumors and a greater positivity of lymphovascular invasion than LCC.

Head and neck squamous cell carcinoma in solid organ transplant recipients.

PURPOSE: Characterize head and neck squamous cell carcinomas in solid transplant recipients and compare outcomes with non-transplanted population. METHODS: We carried a retrospective cohort analysis in a tertiary care center in Madrid, Spain. The study reviews 26 cases of non-cutaneous HNSCC diagnosed in solid organ transplant recipients between 2000 and 2017. We select a cohort of 130 (1:5) non-transplanted patients among all non-transplanted patients diagnosed during the same period for comparison purposes, through hierarchical clustering analysis. Univariate, overall and specific survival analysis and multivariate Cox proportional hazards regression were used to evaluate our objectives. RESULTS: The overall risk of non-cutaneous HNSCC in solid transplant recipients was 7.2 cases per 1000. Alcohol abuse (p = 0.021) and upfront surgery (p = 0.019) were more likely to occur in transplanted patients. Age > 60 was an independent predictor of worse outcomes both for overall (HR = 2.4, p < 0.001) and specific (HR = 2.1, p = 0.012) survival. Transplant significantly worse overall survival (HR = 2.1, p = 0.012) but no statistical significant differences were observed on specific survival (p = 0.392). CONCLUSIONS: Solid organ transplant recipients have a higher risk of suffering non-cutaneous HNSCC. The higher mortality rate of these patients does not appear to be directly related to suffering from head and neck cancer, although it seems to contribute to developing other fatal complications in these fragile patients.

Ethyl alcohol threshold test: a fast, reliable and affordable olfactory Assessment tool for COVID-19 patients.

OBJECTIVE: COVID-19 patients may present mild symptoms. The identification of paucisymptomatic patients is paramount in order to interrupt the transmission chain of the virus. Olfactory loss could be one of those early symptoms which might help in the diagnosis of COVID-19 patients. In this study, we aim to develop and validate a fast, inexpensive, reliable and easy-to-perform olfactory test for the screening of suspected COVID-19 patients. STUDY DESIGN: Phase I was a case-control study and Phase II a transversal descriptive study. SUBJECTS AND METHODS: Olfaction was assessed with the ethyl alcohol threshold test and symptoms with visual analogue scales. The study was designed in two phases: In Phase I, we compared confirmed COVID-19 patients and healthy controls. In Phase II, patients with suspected COVID-19 infection referred for testing were studied. RESULTS: 275 participants were included in Phase I, 135 in Phase II. The ROC curve showed an AUC of 0.749 in Phase I, 0.737 in Phase II. The cutoff value which offered the highest amount of correctly classified patients was ≥ 2 (10% alcohol) for all age intervals. The odds ratio was 8.19 in Phase I, 6.56 in Phase II with a 75% sensitivity. When cases report normal sense of smell (VAS < 4), it misdiagnoses 57.89% of patients detected by the alcohol threshold test. CONCLUSION: The olfactory loss assessed with the alcohol threshold test has shown high sensitivity and odds ratio in both patients with confirmed COVID-19 illness and participants with suspected SARS-CoV-2 infection.

A Classifier to Predict Viral Control After Antiretroviral Treatment Interruption in Chronic HIV-1-Infected Patients.

OBJECTIVES: To construct a classifier that predicts the probability of viral control after analytical treatment interruptions (ATI) in HIV research trials. METHODS: Participants of a dendritic cell-based therapeutic vaccine trial (DCV2) constituted the derivation cohort. One of the primary endpoints of DCV2 was the drop of viral load (VL) set point after 12 weeks of ATI (delta VL12). We classified cases as "controllers" (delta VL12 > 1 log10 copies/mL, n = 12) or "noncontrollers" (delta VL12 < 0.5 log10 copies/mL, n = 10) and compared 190 variables (clinical data, lymphocyte subsets, inflammatory markers, viral reservoir, ELISPOT, and lymphoproliferative responses) between the 2 groups. Naive Bayes classifiers were built from combinations of significant variables. The best model was subsequently validated on an independent cohort. RESULTS: Controllers had significantly higher pre-antiretroviral treatment VL [110,250 (IQR 71,968-275,750) vs. 28,600 (IQR 18737-39365) copies/mL, P = 0.003] and significantly lower proportion of some T-lymphocyte subsets than noncontrollers: prevaccination CD4CD45RA+RO+ (1.72% vs. 7.47%, P = 0.036), CD8CD45RA+RO+ (7.92% vs. 15.69%, P = 0.017), CD4+CCR5+ (4.25% vs. 7.40%, P = 0.011), and CD8+CCR5+ (14.53% vs. 27.30%, P = 0.043), and postvaccination CD4+CXCR4+ (12.44% vs. 22.80%, P = 0.021). The classifier based on pre-antiretroviral treatment VL and prevaccine CD8CD45RA+RO+ T cells was the best predictive model (overall accuracy: 91%). In an independent validation cohort of 107 ATI episodes, the model correctly identified nonresponders (negative predictive value = 94%), while it failed to identify responders (positive predictive value = 20%). CONCLUSIONS: Our simple classifier could correctly classify those patients with low probability of control of VL after ATI. These data could be helpful for HIV research trial design.

Satisfacción Laboral en el Docente Dominicano: Antecedentes Laborales / Job Satisfaction of the Dominican Teacher: Labor Background / Satisfação Profissional no Docente Dominicano: Antecedentes Profissionais

Resumen La satisfacción laboral del colectivo docente ha sido estudiada desde diversas perspectivas, debido a los importantes efectos que esta puede tener tanto a nivel económico como a nivel organizacional. La muestra empleada en este trabajo se compone de 978 docentes dominicanos, y fue obtenida mediante un muestreo estratificado, y, por tanto, representativo de la población. En este estudio se examina un modelo de ecuaciones estructurales en el cual el contexto de trabajo y las condiciones laborales afectan el burnout y el engagement de los profesores. A su vez, se plantea que burnout y engagement afectan la satisfacción laboral docente. El modelo ajustó a los datos: x2(223)= 1089.9, p<.001; CFI=.93; RMSEA=.066; SRMR=.107. Los resultados arrojan luz sobre los factores contextuales del plano educativo que pudieran replantearse en el desarrollo de futuras políticas educativas.

Abstract The job satisfaction of the teachers' collective has been studied from various perspectives due to the significant effect it can have at both the economic and organizational levels. The sample used for this study was made up of 978 Dominican teachers, obtained through stratified sampling so that it would be representative of the population. An analysis of a structural equations model shows that work context and labor conditions affect the burnout and engagement of teachers. The study suggests that both burnout and engagement affect the job satisfaction of teachers. The model fits the data: x2(223)=1089.9, p<.001; CFI=.93; RMSEA=.066; SRMR=.107. The results shed light on the contextual factors of the educational field that could be reformulated in the development of future education policies.

Resumo A satisfação profissional do coletivo docente vem sendo estudada de diversas perspectivas, devido aos importantes efeitos que ela pode ter tanto no âmbito econômico quanto no organizacional. A amostra deste trabalho está composta por 978 docentes dominicanos e foi obtida mediante uma amostragem estratificada, e, portanto, representativa da população. Neste estudo, foi examinado um modelo de equações estruturais em que o contexto de trabalho e as condições de trabalho afetam o burnout e o engagement dos professores. Por sua vez, argumenta-se que burnout e engagement afetam a satisfação profissional docente. O modelo ajusta-se aos dados: x2(223)=1089.9, p<.001; CFI=.93; RMSEA=.066; SRMR=.107. Os resultados esclarecem os fatores contextuais do plano educativo que podem ser repensados no desenvolvimento de futuras políticas educativas.

Bulky Bartholin's gland cyst: Case report of an incidental finding.

INTRODUCTION: Distal blockage of the Bartholin's gland duct can result in the retention of secretions, with consequent formation of a cyst or abscess. CASE REPORT: A 57-year-old woman, in whom a bulky vulvar mass in the left labia majora was detected during cystoscopy for urinary symptoms, was referred to the gynaecology clinic. We performed complete removal of the mass as well as ipsilateral vulvar reconstruction. Histological analysis confirmed a large benign Bartholin's duct cyst without acute infection. DISCUSSION: Epidermoid cysts take a long time to develop and so large cysts are rare. The differential diagnosis of a Bartholin's cystic mass should be considered among many other pathologies in the vulvovaginal area. Treatment with complete surgical excision should be carefully performed, under prophylactic antibiotic coverage if required. CONCLUSION: Urogynaecological complaints require a careful consideration of the symptoms and an adequate physical examination before additional tests are requested. Although a differential diagnosis can be made preoperatively, confirmation is necessarily histological.

Ultrasound Elastography Images in Vascular Anomalies.

Ultrasound elastography is an emerging imaging technique that provides an objective method to assess the relative or absolute stiffness of soft tissues. The authors have not found any description in the use of ultrasound elastography in vascular anomalies, and we want to share our experience in different cases with ultrasound elastography and its applications in these pathologies.

Nuclear Pores Promote Lethal Prostate Cancer by Increasing POM121-Driven E2F1, MYC, and AR Nuclear Import.

Nuclear pore complexes (NPCs) regulate nuclear-cytoplasmic transport, transcription, and genome integrity in eukaryotic cells. However, their functional roles in cancer remain poorly understood. We interrogated the evolutionary transcriptomic landscape of NPC components, nucleoporins (Nups), from primary to advanced metastatic human prostate cancer (PC). Focused loss-of-function genetic screen of top-upregulated Nups in aggressive PC models identified POM121 as a key contributor to PC aggressiveness. Mechanistically, POM121 promoted PC progression by enhancing importin-dependent nuclear transport of key oncogenic (E2F1, MYC) and PC-specific (AR-GATA2) transcription factors, uncovering a pharmacologically targetable axis that, when inhibited, decreased tumor growth, restored standard therapy efficacy, and improved survival in patient-derived pre-clinical models. Our studies molecularly establish a role of NPCs in PC progression and give a rationale for NPC-regulated nuclear import targeting as a therapeutic strategy for lethal PC. These findings may have implications for understanding how NPC deregulation contributes to the pathogenesis of other tumor types.