Characterization of 554 Mexican Patients With Nonsyndromic Cleft Lip and Palate: Descriptive Study.

Orofacial clefts are one of the most common birth defects and the most common craniofacial malformation worldwide. The most common orofacial clefts (OFCs) are congenital cleft lip with or without cleft palate (CL ± P) and isolated cleft palate (CP). The incidence of OFCs varies depending on region and ethnicity; however, it affects approximately 1 in 600 newborns worldwide. In most cases, CL ± P and CP are multifactorial congenital malformations, where both exogenous and genetic factors play an important role. The objective of this study was to describe the frequency of potential risk factors associated with the development of CL ± P and CP in Mexican population. Patients were referred for multisystemic treatment, from private and public institutions in different regions of the country (center, north, and south). Sociodemographic information, prenatal and parental history were obtained through direct interviews with the patients or the patients' mothers in the case of underaged patients. Referred patients were invited to participate in the study. No interventions were applied for this study. The relationship between these factors and the prevalence of CL ± P and CP was studied. A total of 554 patients were included, the majority with CLP (30% to 7%), statistically significant differences were found for folic acid ( P = 0.02) consumption. Familial aggregation did not reach statistical significance for first-degree family members ( P = 0.34) but was significant for second-degree family members ( P = 0.007). More risk factors associated with CL ± P and CP may still be unknown, prompting more epidemiological research and research in other little-studied areas, such as; specific genetic factors in Mexican population.

Patient-reported symptoms at discharge and risk of complications after gynecologic surgery.

OBJECTIVE: Current gaps in knowledge limit clinicians from fully implementing patient-reported outcomes in routine post-operative care. METHODS: This prospective study assessed symptoms via the gynecologic module of the MD Anderson Symptom Inventory (MDASI-PeriOp-GYN) in patients who underwent open laparotomy. RESULTS: At discharge, patient-reported moderate to severe (≥4 on a 0-10 scale) abdominal bloating or abdominal cramping, combined with length of stay of ≥4 days, were found to be associated with a higher risk of 30-day post-operative grade II-IV complications by the Clavien-Dindo system (all p values <0.01). Also, length of stay of ≥4 days and moderate to severe urinary urgency at discharge were found to be associated with the need for re-admission (all p values <0.01). CONCLUSION: This study defined the clinically meaningful symptoms that related to the risk of developing important complications after discharge from major open gynecological surgery.These findings support the integration of assessment of patient-reported outcomes into patient-centered post-operative care.

Use of failure-to-rescue after emergency surgery as a dynamic indicator of hospital resilience during the COVID-19 pandemic. A multicenter retrospective propensity score-matched cohort study.

BACKGROUND: Surgical failure-to-rescue (FTR, death rate following complications) is a reliable cross-sectional quality of care marker, but has not been evaluated dynamically. We aimed to study changes in FTR following emergency surgery during the COVID-19 pandemic. MATERIAL AND METHODS: Matched cohort study including all COVID-19-non-infected adult patients undergoing emergency general surgery in 25 Spanish hospitals during COVID-19 pandemic peak (March-April 2020), non-peak (May-June 2020), and 2019 control periods. A propensity score-matched comparative analysis was conducted using a logistic regression model, in which period was regressed on observed baseline characteristics. Subsequently, a mixed effects logistic regression model was constructed for each variable of interest. Main variable was FTR. Secondary variables were post-operative complications, readmissions, reinterventions, and length of stay. RESULTS: 5003 patients were included (948, 1108, and 2947 in the pandemic peak, non-peak, and control periods), with comparable clinical characteristics, prognostic scores, complications, reintervention, rehospitalization rates, and length of stay across periods. FTR was greater during the pandemic peak than during non-peak and pre-pandemic periods (22.5% vs. 17.2% and 12.7%), being this difference confirmed in adjusted analysis (odds ratio [OR] 2.13, 95% confidence interval [95% CI] 1.27-3.66). There was sensible inter-hospital variability in FTR changes during the pandemic peak (median FTR change +8.77%, IQR 0-29.17%) not observed during the pandemic non-peak period (median FTR change 0%, IQR -6.01-6.72%). Greater FTR increase was associated with higher COVID-19 incidence (OR 2.31, 95% CI 1.31-4.16) and some hospital characteristics, including tertiary level (OR 3.07, 95% CI 1.27-8.00), medium-volume (OR 2.79, 95% CI 1.14-7.34), and high basal-adjusted complication risk (OR 2.21, 95% CI 1.07-4.72). CONCLUSION: FTR following emergency surgery experienced a heterogeneous increase during different periods of the COVID-19 pandemic, suggesting it to behave as an indicator of hospital resilience. FTR monitoring could facilitate identification of centres in special needs during ongoing health care challenges.

Erratum: Physiological lentiviral vectors for the generation of improved CAR-T cells.

[This corrects the article DOI: 10.1016/j.omto.2022.05.003.].

Physiological lentiviral vectors for the generation of improved CAR-T cells.

Anti-CD19 chimeric antigen receptor (CAR)-T cells have achieved impressive outcomes for the treatment of relapsed and refractory B-lineage neoplasms. However, important limitations still remain due to severe adverse events (i.e., cytokine release syndrome and neuroinflammation) and relapse of 40%-50% of the treated patients. Most CAR-T cells are generated using retroviral vectors with strong promoters that lead to high CAR expression levels, tonic signaling, premature exhaustion, and overstimulation, reducing efficacy and increasing side effects. Here, we show that lentiviral vectors (LVs) expressing the transgene through a WAS gene promoter (AW-LVs) closely mimic the T cell receptor (TCR)/CD3 expression kinetic upon stimulation. These AW-LVs can generate improved CAR-T cells as a consequence of their moderate and TCR-like expression profile. Compared with CAR-T cells generated with human elongation factor α (EF1α)-driven-LVs, AW-CAR-T cells exhibited lower tonic signaling, higher proportion of naive and stem cell memory T cells, less exhausted phenotype, and milder secretion of tumor necrosis factor alpha (TNF-α) and interferon (IFN)-É£ after efficient destruction of CD19+ lymphoma cells, both in vitro and in vivo. Moreover, we also showed their improved efficiency using an in vitro CD19+ pancreatic tumor model. We finally demonstrated the feasibility of large-scale manufacturing of AW-CAR-T cells in guanosine monophosphate (GMP)-like conditions. Based on these data, we propose the use of AW-LVs for the generation of improved CAR-T products.

Isogenic GAA-KO Murine Muscle Cell Lines Mimicking Severe Pompe Mutations as Preclinical Models for the Screening of Potential Gene Therapy Strategies.

Pompe disease (PD) is a rare disorder caused by mutations in the acid alpha-glucosidase (GAA) gene. Most gene therapies (GT) partially rely on the cross-correction of unmodified cells through the uptake of the GAA enzyme secreted by corrected cells. In the present study, we generated isogenic murine GAA-KO cell lines resembling severe mutations from Pompe patients. All of the generated GAA-KO cells lacked GAA activity and presented an increased autophagy and increased glycogen content by means of myotube differentiation as well as the downregulation of mannose 6-phosphate receptors (CI-MPRs), validating them as models for PD. Additionally, different chimeric murine GAA proteins (IFG, IFLG and 2G) were designed with the aim to improve their therapeutic activity. Phenotypic rescue analyses using lentiviral vectors point to IFG chimera as the best candidate in restoring GAA activity, normalising the autophagic marker p62 and surface levels of CI-MPRs. Interestingly, in vivo administration of liver-directed AAVs expressing the chimeras further confirmed the good behaviour of IFG, achieving cross-correction in heart tissue. In summary, we generated different isogenic murine muscle cell lines mimicking the severe PD phenotype, as well as validating their applicability as preclinical models in order to reduce animal experimentation.

Upfront surgery versus self-expanding metallic stent as bridge to surgery in left-sided colonic cancer obstruction: A multicenter observational study.

BACKGROUND: Oncological outcomes of self-expanding metallic stent used as a bridge to surgery in potential curative patients with left-sided colonic cancer obstruction remain unclear. The aim of this study was to investigate perioperative and mid-term oncological outcomes of 2 of the currently most commonly performed treatments in left-sided colonic cancer obstruction. METHODS: This is a retrospective multicenter study including patients with left-sided colonic cancer obstruction treated with curative intent between 2013 and 2017. The presence of metastasis at diagnosis was an exclusion criterion. The primary outcome was to evaluate the noninferiority, in terms of overall survival, of bridge to surgery strategy compared with emergency colonic resection. The secondary outcomes were perioperative morbimortality, disease free survival, local recurrence, and distant recurrence. RESULTS: A total of 564 patients were included, 320 in the emergency colonic resection group and 244 in the bridge to surgery group. Twenty-seven patients of the bridge-to-surgery group needed urgent operation. Postoperative morbidity rates were statistically higher in the emergency colonic resection group (odds ratio [95% confidence interval] 0.37 [0.24-0.55], P < .001). There was no difference in 90-day mortality between groups (odds ratio [95% confidence interval] 0.85 [0.36-1.99], P = .702). The median follow-up was 3.80 years (2.29-4.92). The results show the noninferiority of bridge to surgery versus emergency colonic resection in terms of overall survival (hazard ratio [95% confidence interval) 0.78 [0.56-1.07], P = .127). There were no differences in disease free survival, distant recurrence, and local recurrence rates between bridge to surgery and emergency colonic resection groups. CONCLUSION: Self-expanding metallic stent as bridge to surgery might not lead to a negative impact on the long-term prognosis of the tumor compared with emergency colonic resection in expert hands and selected patients.

P-POSSUM as mortality predictor in COVID-19-infected patients submitted to emergency digestive surgery. A retrospective cohort study.

BACKGROUND: COVID-19 infection is associated with a higher mortality rate in surgical patients, but surgical risk scores have not been validated in the emergency setting. We aimed to study the capacity for postoperative mortality prediction of the P-POSSUM score in COVID-19-positive patients submitted to emergency general and digestive surgery. MATERIAL AND METHODS: Consecutive patients undergoing emergency general and digestive surgery from March to June 2020, and from March to June 2019 in 25 Spanish hospitals were included in a retrospective cohort study. MAIN OUTCOME: 30-day mortality. P-POSSUM discrimination was quantified by the area under the curve (AUC) of ROC curves; calibration was assessed by linear regression slope (ß estimator); and sensitivity and specificity were expressed as percentage and 95% confidence interval (CI). RESULTS: 4988 patients were included: 177 COVID-19-positive; 2011 intra-pandemic COVID-19-negative; and 2800 pre-pandemic. COVID-19-positive patients were older, with higher surgical risk, more advanced pathologies, and higher P-POSSUM values (1.79% vs. 1.09%, p < 0.001, in both the COVID-19-negative and control cohort). 30-day mortality in the COVID-19-positive, intra-pandemic COVID-19-negative and pre-pandemic cohorts were: 12.9%, 4.6%, and 3.2%. The P-POSSUM predictive values in the three cohorts were, respectively: AUC 0.88 (95% CI 0.81-0.95), 0.89 (95% CI 0.87-0.92), and 0.91 (95% CI 0.88-0.93); ß value 0.97 (95% CI 0.74-1.2), 0.99 (95% CI 0.82-1.16), and 0.78 (95% CI 0.74-0.82); sensitivity 83% (95% CI 61-95), 91% (95% CI 84-96), and 89% (95% CI 80-94); and specificity 81% (95% CI 74-87), 76% (95% CI 74-78), and 80% (95% CI 79-82). CONCLUSION: The P-POSSUM score showed a good predictive capacity for postoperative mortality in COVID-19-positive patients submitted to emergency general and digestive surgery.

Patient-Reported Symptom and Functioning Status during the First 12 Months after Chimeric Antigen Receptor T Cell Therapy for Hematologic Malignancies.

Chimeric antigen receptor (CAR) T cell therapy is being increasingly used to treat patients with advanced hematologic malignancies; however, the symptoms related to standard of care CAR T cell therapy during the first year after treatment have not been assessed using patient-reported outcome (PRO) measurements. This study aimed to quantify patients' perspectives of symptom burden and functional status using PROs during the first year after CAR T cell therapy for hematologic malignancies, especially in patients who experienced grade 2-4 toxicities. Sixty patients were enrolled in this observational cross-sectional study at any time during their first 12 months post-treatment. All 60 had received CAR T cell therapy as standard of care at MD Anderson Cancer Center in 2019. PROs were measured using the MD Anderson Symptom Inventory (MDASI), the PROs Measurement Information System 29 (PROMIS-29), the global health tool EQ5D-5L, and the single-item health-related quality of life scale (HRQoL). Twenty-two additional symptoms related to CAR T cell therapy, as identified by an expert panel, were also evaluated. CAR T cell therapy-related toxicities were rated according to the ASTCT consensus grading criteria. The majority of patients (52 of 60; 87%) received axicabtagene ciloleucel (Yescarta). One-third of the patients developed grade 2-4 cytokine release syndrome or neurotoxicity. The first 90 days after infusion represented the most symptomatic period, in which >10% of patients rated 18 symptoms as severe (ie, MDASI symptom score of 7 to 10 on scale of 0 to 10), strongly indicating the need for effective symptom management. Physical functioning, measured by interference on the "general activity" item on the MDASI and this domain on the PROMIS-29, were significantly worse in patients who underwent therapy during the first 30 days compared with those who underwent therapy over 90 days (all P < .05 with the Hochberg step-up procedure), whereas the EQ5D-5L and single-item HRQoL did not detect such differences. Compared with patients who had mild cytokine release syndrome or neurotoxicity (grade 0-1), patients who developed grade 2-4 toxicities persistently reported multiple severe symptoms after 30 days following therapy (all P < .05). Furthermore, although using a different recall period, patient-reported scores on several PROMIS-29 domains were significantly correlated with the scores of corresponding MDASI symptom items. This real-world quantitative PRO symptoms study provides evidence of unique profiles of the physical, psychological, and cognitive symptom burden in patients undergoing CAR T cell therapy that varies within the first year after infusion and demonstrates differences among PRO measurement scales. These results support the need for validation of fit-for-purpose PRO measurements for routinely monitoring symptom and toxicity burdens in CAR T cell therapy care settings.

Development of a patient-reported outcome tool for assessing symptom burden during perioperative care in liver surgery: The MDASI-PeriOp-Hep.

PURPOSE: Based on the MD Anderson Symptom Inventory (MDASI), we developed a Patient-reported outcomes tool for hepatectomy perioperative care (MDASI-PeriOp-Hep). METHODS: To establish the content validity, we generated PeriOp-Hep-specific candidate items from qualitative interviews of patients (n = 30), and removed items that lacked clinical relevance on the basis of input from panels of patients, caregivers, and clinicians. The psychometric properties of the MDASI-PeriOp-Hep were validated (n = 150). The cognitive debriefing and clinical interpretability were assessed to confirm the ease of comprehension, relevance, and acceptability of the tool. RESULTS: Five symptoms specific to hepatectomy (abdominal bloating, tightness, or fullness; abdominal cramping; muscle weakness, instability, or vertigo; constipation; and incisional tightness) were identified as module items to form the MDASI-PeriOp-Hep. The Cronbach αs for symptoms and for interference were 0.898 and 0.861, respectively. The test-retest reliability was 0.887 for all 18 symptom severity items. Compared to other commonly used tools, correlation of MDASI-PeriOp-Hep scores to performance status (all, P < 0.001) and to the phase of perioperative care confirmed known-group validity. Convergent validity was excellent against other standard Patient-reported outcomes tools. Cognitive debriefing demonstrated that the MDASI-PeriOp-Hep was an easy to use and understandable tool. CONCLUSIONS: For integrating patient-reported outcomes in perioperative patient care, a procedure-specific tool is desirable. The MDASI-PeriOp-Hep is a valid, reliable, concise tool for measuring symptom severity and functional interference in patients undergoing liver surgery.

Minocycline for symptom reduction in patients with multiple myeloma during maintenance therapy: a phase II placebo-controlled randomized trial.

BACKGROUND: Patients with multiple myeloma (MM) experience substantial cancer/treatment-related symptom burden during maintenance therapy. This is a phase II randomized, double-blinded, placebo-controlled clinical trial to examine the effect of minocycline for symptom reduction by its potential anti-inflammatory effect. METHODS: Eligible MM patients for maintenance therapy were randomized to receive minocycline (100 mg twice daily) or placebo. The MD Anderson Symptom Inventory for MM (MDASI-MM) was used to assess multiple symptoms weekly during the trial. Clinician-rated toxicities and blood samples were prospectively collected. The effect size, area under the curve (AUC), and t tests were used to determine the symptom burden between treatment groups and identify the 5 most-severe MDASI-MM symptoms. The longitudinal analysis compared the changes in symptom severity and associated inflammatory markers between groups over time. RESULTS: Sixty-nine evaluable MM patients (33 from the intervention group and 36 from the placebo group) were included. No grade 3+ adverse events related to study medication were noted. The AUCs for the 5 worst MDASI-MM symptoms (fatigue, pain, disturbed sleep numbness/tingling, and drowsiness) were not significantly different between two arms. Regardless of group assignment, pain reduction was positively associated with decreased serum levels of soluble tumor necrosis factor-α receptors 1 and 2 during therapy (all P < 0.05). CONCLUSIONS: This pPhase II randomized study observed no statistically significant positive signal impact from minocycline on symptom reduction or inflammatory markers during maintenance therapy for MM, although using minocycline was feasible and had a low toxicity profile.

Assessment of physical function by subjective and objective methods in patients undergoing open gynecologic surgery.

OBJECTIVE: To evaluate the utility of patient-reported outcomes (PROs) to measure physical functioning in perioperative care for patients with gynecological (GYN) tumors. METHODS: 180 patients with GYN tumors undergoing open surgery participated in this longitudinal study. The physical functioning was measured by a subjective PRO tool, the Interference subscales of the MD Anderson Symptom Inventory (MDASI-I); as well as by an objective tool, the Timed Up & Go test (TUGT), perioperatively. Longer time (>20 s) needed to complete the TUGT was defined as "Prolonged". Patients completed EuroQoL-5D as well. The association between the scores of MDASI-I items and TUGT was assessed via the Spearman correlation coefficient. The known-group validity was assessed using the t-test and Cohen's D effect size. RESULTS: Compliance rates at preoperative, discharge and postoperative time points of MDASI-I were 98%, 95%, 96%; while TUGT completion rates were 92%, 75%, and 80%, respectively. Patients who had refused TUGT at discharge reported a significantly worse "MDASI-general activity" score compared to patients who completed TUGT (mean score of 7.00 vs. 5.38, P = 0.020). Patient-reported "Walking" on MDASI-I significantly differentiated patients with prolonged vs. those with frail/normal TUGT at discharge (mean score of 4.89 vs. 2.79, Cohen's d effect size = 0.82, P < 0.001). MDASI-I demonstrated excellent known-group validity per performance status and for the EuroQoL-5D subscales. CONCLUSION: Patient-reported physical functioning impairment after GYN surgery correspond with observed worse scores of the objective functioning measure test (TUGT). MDASI-I assessment represents a feasible and valid tool to evaluate functional status and warrants further implementation in the perioperative setting.

Symptom burden and its functional impact in patients with "symptomatic" relapsed or refractory multiple myeloma.

PURPOSE: Relapsed or refractory multiple myeloma (RRMM) is labeled "symptomatic" based on laboratory values, but not relevant to quantitative measure of patient's perspectives. This study aimed to describe symptom burden, health status, and quality of life in RRMM patients. METHODS: The cross-sectional study included 184 MM patients (141 RRMM cases and 43 MM patients on follow-up without diagnosis/treatment of RRMM disease as controls), while 64 RRMM patients also provided longitudinal patient-reported outcomes (PROs) data. Symptomatic status was based on clinical measures of disease activity. PROs included the MD Anderson Symptom Inventory multiple myeloma module (MDASI-MM), single-item quality of life (SIQOL), and EuroQol-5D (EQ-5D). Wilcoxon rank test and effect size were used for comparisons. Regression models were used to describe symptom trajectory and to identify predictors of high symptom burden during 3 months of RRMM therapy. RESULTS: Most patients were clinically identified as symptomatic (93%). RRMM patients tended to report more severe symptoms, with significantly lower QOL scores and more severe fatigue, poor appetite, and lower enjoyment of life compared with controls (all p < 0.05). In RRMM patients, lower hemoglobin and higher B-2 microglobulin levels significantly correlated with higher burdens of fatigue, pain, and muscle weakness and also with lower QOL and EQ-5D scores (all p < 0.05). During RRMM therapy, being female, with any comorbidity, ≥ 65 years old, and ≥ 5 years MM history, contributed to high symptoms burden and poor QOL status (each p < 0.05). CONCLUSIONS: MDASI-MM modules were sensitive to detect the RRMM-related symptoms burden, which correlated with objective clinical measures. RRMM patients reported a more compromised QOL.

Prueba diagnóstica entre la citología, biopsia por congelación e histopatología en el diagnóstico del Nódulo Tiroideo en pacientes atendidos en Solca desde el año 2009 ­2017 / Diagnostic Test between cytology, frozen biopsy and histopathology in the diagnosisof the thyroid nodule in patients treated at Solca from 2009 -2017

Introducción: La citología de nódulos tiroideos es una técnica que, evita procedimientos quirúrgicos innecesarios por lo que se lo ha determinado como primera línea dentro del algoritmo de diagnóstico, el objetivo del estudio fue determinar la sensibilidad y la especificidad de la citología y biopsia por congelación frente al estudio histopatológico en el diagnóstico de nódulos tiroideos en pacientes atendidos en Solca desde el año 2009 -2017. Métodos: Es un estudio de tipo observacional, retrospectivo y de correlación diagnóstica; los datos fueron obtenidos de las historias clínicas de pacientes intervenidos quirúrgicamente por nódulos tiroideos con biopsia por congelación, a quienes se les realizó previamente un estudio citológico en el Departamento de patología de SOLCA de la ciudad de Cuenca, Ecuador. El cálculo del tamaño de la muestra fue de 324 casos. Resultados:324 casos fueron incluidos. El 8.3% correspondió a hombres y el 91.7% a mujeres. La media de la edad fue 51.8 años; la gran mayoría provenían de la provincia Azuay con el 64.8%. En los estudios citológicos el 34.6% (112 casos)corresponden a lesiones inflamatorias benignas; el 11.1% [36 casos]a patologías malignas y 14.2% (46 casos)fueron insatisfactorios. En la biopsia por congelación el mayor porcentaje estuvo concentrado en enfermedades benignas con un 62.6% y 35.5% a lesiones malignas. Hubo 6 casos con el 1.9% en donde fue diferido el criterio diagnóstico. En el histopatológico definitivo el 60.2% (195 casos)fueron patologías benignas y el 39.8% (129 casos)fueron lesiones malignas. La sensibilidad de la PAAF frente a histopatológico es alta con un 91.79%, pero la especificidad es baja con un 51.94%. La sensibilidad y la especificidad de la biopsia por congelación frente a histopatológico es alta con un 98.97% y 90.70% respectivamente lo que le confiere una metodología óptima. Conclusiones: La PAAF de tiroides demuestra ser una metodología útil en el diagnóstico de nódulos, siempre y cuando sea realizada y observada por personal capacitado. La biopsia por congelación constituye una técnica con alta sensibilidad y especificidad que nos permite discriminar lesiones benignas de las malignas. Palabras claves: Nódulo tiroideo, Biopsia con Aguja, Servicio de Patología en Hospital, Oncología Médica, Agencias Voluntarias de Salud, Biología Celular, Biopsia con Aguja Fina

Introduction:Cytology of thyroid nodules is a technique that avoids unnecessary surgical procedures and has therefore been determined as the first line within the diagnostic algorithm.General Objective:To determine the sensitivity and specificity of cytology and freezing biopsy versus histopathological study in the diagnosis of thyroid nodules in patients treated in Solca since 2009 -2017. Methods:This is an observational, retrospective and diagnostic correlation study; the data were obtained from the clinical histories of patients surgically treated by thyroid nodules with freeze biopsy, who underwent a cytological study in the Department of pathology of the city of Cuenca, Ecuador. The calculation of the sample size was 324 cases. Results:8.3% corresponded to men and 91.7% to women. The mean age was 51.8 years; The vast majority came from the province of Azuay with 64.8%. In cytological studies, 34.6% [112 cases]correspond to benign inflammatory lesions; 11.1% [36 cases]to malignant pathologies and 14.2% [46 cases]were unsatisfactory. In the freeze biopsy the greater percentage was concentrated in benign diseases with 62.6% and 35.5% to malignant lesions. There were 6 cases with 1.9% where the diagnostic criterion was deferred. In the definitive histopathological, 60.2% [195 cases]were benign pathologies and 39.8% [129 cases]were malignant lesions. The sensitivity of FNAB to histopathological is high with 91.79%, but the specificity is low with 51.94%. The sensitivity and specificity of freezing versus histopathological biopsy is high with 98.97% and 90.70% respectively, which gives it an optimal methodology. Conclusions: Thyroid PAAF proves to be a useful methodology in the diagnosis of nodules, as long as it is performed and observed by trained personnel. Freezing biopsy is a technique with high sensitivity and specificity that allows us to discriminate benign from malignant lesions. Key words:Thyroid Nodule; Biopsy, Needle;Pathology Department, Hospital; Medical Oncology; Voluntary Health Agencies; Cell Biology; Biopsy, Fine-Needle

Neoplasia Pseudopapilar sólida del Páncreas. A Propósito de un Caso / Solid Pseudopapillary Neoplasia of the Pancreas. Case Report

Introducción: La neoplasia pseudopapilarsólida del páncreas es una patología poco frecuente, que se presenta en mujeres jóvenes y es de comportamiento incierto. La prevalencia es del 1-2% y el tratamiento es quirúrgico. En el presente caso se describe a una paciente de sexo femenino de 10 años de edad que muestra esta patología y su correspondiente manejo. Caso clínico:Paciente de sexo femenino, de 10 años de edad, con antecedentes de una nefrectomía hace 6 años por hidronefrosis, refiere dolor abdominal localizado en egigastrio tipo cólico y pérdida de peso. En los estudio de imagen a nivel peritoneal se observa lesión de aspecto ocupativo de tipo sólido neoplásico con área central de probable necrosis y que desplaza en sentido posterior al páncreas así como al estómago y se asocia con adenomegalias peritoneales y retroperitoneales. Evolución:Lapaciente fue sometido a una espleno-pancreatectomía distal.El estudio anatomo-patológico concluyó en neuplasia pseudopapilar sólida del páncreas.Continúa en valoración por consulta externa. Conclusión:Neoplasia Pseudopapilar sólida del Páncreasdebe ser sospechada en pacientes con una masa sólida o quística pancreática con un estudio de imágenes compatibles. Palabras clave:Neoplasia pseudopapilar sólida del páncreas, prevalencia, inmunohistoquímica, receptores progestágenos,Informe de caso

Introduction:Solid pseudopapillary neoplasia of the pancreas is a rare pathology that occurs in young women and has an uncertain behavior. The prevalence is 1-2% and the treatment is surgical. In the present case, a 10-year-old female patient with this pathology and its corresponding management is described. Clinical case: A 10-year-old femalepatient with a history of nephrectomy 6 years ago due to hydronephrosis, complains of colicky localized abdominal pain in the egigastrium and weight loss. In peritoneal imaging studies, a neoplastic solid type occupational lesion with a central area of probable necrosis is observed, which displaces the pancreas as well as the stomach posteriorly and is associated with peritoneal and retroperitoneal adenomegaly. Evolution: The patient underwent a distal spleno-pancreatectomy. The anatomopathological studyconcluded in solid pseudopapillary neuplasia of the pancreas. He continues to be evaluated by external consultation. Conclusion: Solid Pseudopapillary Neoplasia of the Pancreas should be suspected in patients with a solid or cystic pancreatic mass with a compatible imaging study. Key words:Solid pseudopapillary neoplasm of the pancreas, prevalence, immunohistochemistry, progestin receptors, Case Report.

Radical Cystectomy and Perioperative Sexual Function: A Cross-Sectional Analysis.

BACKGROUND: Cancer-related changes in sexual function (SF) negatively impact quality of life and intimate partner relationships. There is a lack of data regarding SF among patients who underwent radical cystectomy (RC). AIM: To comparatively evaluate perioperative SF among patients who underwent RC. METHODS: A prospective cohort of 150 patients undergoing RC for bladder cancer and participating in an internal validation study at a single institution from 2016 to 2019 were eligible for analysis. The European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire-Bladder Cancer Muscle Invasive (EORTC QLQ-BLM 30) and Functional Assessment of Cancer Therapy-Bladder were administered; those completing the SF subscale of the EORTC QLQ-BLM 30 were included in final analysis. Analysis was performed using descriptive statistics and generalized linear modeling. OUTCOMES: The primary outcome was interest or engagement in sexual activity within 4 weeks of survey completion, whereas the secondary outcome was a mean score on the EORTC QLQ-BLM 30 SF subscale. RESULTS: Overall, 132 of 150 (88%) of patients were eligible, of whom 82% were male, and the median age was 68.5 years. 53% reported at least a little interest in sexual activity, and 40% endorsed sexual activity within the last 4 weeks. The mean SF subscale score was 61.5 ± 25.2. Women had significantly worse mean scores of 72.9 ± 27.1 versus 59.1 ± 24.2 for men (P = .02). On multivariate analysis, both age and female gender were independently associated with higher SF domain scores. CLINICAL IMPLICATIONS: A substantial portion of patients who underwent RC endorse being sexually active or express interest in sexually activity in the perioperative period. Given the recent increase in attention given to SF outcomes and quality of life, this work supports further efforts to explore this area and develop novel interventions to improve outcomes. STRENGTHS AND LIMITATIONS: Strengths include rigorously collected, cross-sectional data using standardized methodology. Limitations include a relatively small sample size of female patients and unknown meaningful clinical difference. CONCLUSIONS: A substantial portion of patients report sexual interest and activity in the perioperative period; however, female gender is associated with worse SF domain scores. These findings support further inquiry into this topic. Westerman ME, Kokorovic A, Wang XS, et al. Radical Cystectomy and Perioperative Sexual Function: A Cross-Sectional Analysis. J Sex Med 2020;17:1995-2004.

What Do Patients With Non-Small-Cell Lung Cancer Experience? Content Domain for the MD Anderson Symptom Inventory for Lung Cancer.

PURPOSE: Symptom monitoring has demonstrated improved outcomes in patients with cancer, including quality of life, resource utilization, ability to continue treatment, and survival. The use of disease-specific patient-reported outcome (PRO) measures facilitates symptom monitoring. While the MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC), a PRO measure of symptom burden in lung cancer, is psychometrically validated for use in patients with NSCLC, its content validity has not been verified through direct patient input. Our purpose is to describe the symptom experience of patients with NSCLC and to confirm that the MDASI-LC contains the key symptoms specific to NSCLC from the patient perspective. METHODS: Patients with NSCLC described their symptom experience in single qualitative interviews. Content analysis was used to define the content domain for a PRO measure of NSCLC symptom burden. RESULTS: Participants (N = 40) had a mean age of 66.1 years (standard deviation, 10.9 years); 60.0% were male, 77.5% were White, and 56.4% had stage IV disease. Thirty-two symptoms were described, with 6 reported by ≥ 20% of participants. Symptom variations were noted by treatment modality but not by stage of disease. Patients with NSCLC commonly reported shortness of breath, cough, distress, fatigue, pain, and constipation. In patients receiving chemotherapy, treatment-related symptoms, including neuropathy and sore mouth, were commonly noted. The presence of these symptoms resulted in interference with daily activities, relationships, life plans, treatment adherence, and mood. CONCLUSION: The symptoms included in the MDASI-LC are important components of the content domain of an NSCLC symptom burden measure. The presence of these symptoms affect daily life and, therefore, is of clinical consequence.

Genome-edited adult stem cells: Next-generation advanced therapy medicinal products.

Over recent decades, gene therapy, which has enabled the treatment of several incurable diseases, has undergone a veritable revolution. Cell therapy has also seen major advances in the treatment of various diseases, particularly through the use of adult stem cells (ASCs). The combination of gene and cell therapy (GCT) has opened up new opportunities to improve advanced therapy medicinal products for the treatment of several diseases. Despite the considerable potential of GCT, the use of retroviral vectors has major limitations with regard to oncogene transactivation and the lack of physiological expression. Recently, gene therapists have focused on genome editing (GE) technologies as an alternative strategy. In this review, we discuss the potential benefits of using GE technologies to improve GCT approaches based on ASCs. We will begin with a brief summary of different GE platforms and techniques and will then focus on key therapeutic approaches that have been successfully used to treat diseases in animal models. Finally, we discuss whether ASC GE could become a real alternative to retroviral vectors in a GCT setting.

A Randomized, Placebo-Controlled, Double-Blind Study of Minocycline for Reducing the Symptom Burden Experienced by Patients With Advanced Pancreatic Cancer.

CONTEXT: Although it is well known that patients with advanced pancreatic cancer (PC) experience significant symptom burden, few strategies for effective symptom intervention are available for them. OBJECTIVES: To investigate the efficacy of minocycline, an anti-inflammatory agent, for symptom reduction in patients with advanced PC. METHODS: We conducted Phase II, randomized, and placebo-controlled trial to obtain preliminary estimates of the effects on symptom reduction with 100 mg of minocycline or placebo given twice a day. Eligible patients had diagnosed advanced PC and were scheduled for standard chemotherapy. Patient-reported symptoms were measured weekly during the eight-week trial using the MD Anderson Symptom Inventory (MDASI) module in patients with gastrointestinal cancer. The primary outcome measure was the area under the curve values of the five most severe symptoms in the two arms. RESULTS: Of the 44 patients recruited, 31 (71%) were evaluable for the primary efficacy analysis, with 18 received minocycline and 13 placebo. Fatigue, pain, disturbed sleep, lack of appetite, and drowsiness were the most severe symptoms reported by both groups. No significant differences in area under the curve values over time between the study arms were found for the composite MDASI score or single-item scores of the five most severe MDASI items. No treatment-related deaths were reported, and no Grade 3-4 toxicities were observed. CONCLUSION: Minocycline is safe for use in patients receiving treatment for PC. There is no observed symptom reduction with minocycline on the major symptom burden associated with advanced PC compared with placebo. Attrition because of rapid disease progression impacted the study significantly.