Monitoring of Isothermal Crystallization and Time-Temperature Transformation of Amorphous Felodipine: The Time-Domain Nuclear Magnetic Resonance Method.

The isothermal crystallization process of felodipine has been investigated using the time-domain Nuclear Magnetic Resonance (NMR) method for amorphous bulk and ground samples. The obtained induction and crystallization times were then used to construct the time-temperature-transformation (TTT) diagram, both above and below the glass transition temperature (Tg). The Nose temperature was found equal to 363 K. Furthermore, the dynamics of crystalline and amorphous felodipine were compared across varying temperatures. Molecular dynamics simulations were also employed to explore the hydrogen-bond interactions and dynamic properties of both systems.

Effects on growth, weight and body composition after CFTR modulators in children with cystic fibrosis.

BACKGROUND: Cystic Fibrosis (CF) is associated with compromised nutrition status, which is responsible for morbidity and mortality along with lung function decline. This study was designed to examine changes in anthropometric markers and body composition parameters by bioelectrical impedance analysis after CFTR modulator (CFTRm) treatment. METHODS: We compared anthropometric parameters and body composition before and after 6 and 12 months of CFTRm treatment. Results are stratified into subgroups according to the modulator used with dual therapy with lumacaftor + ivacaftor or tezacaftor + ivacaftor (LUMA/TEZ + IVA) or triple therapy with elexacaftor + tezacaftor + ivacaftor (ELE + TEZ + IVA). Body composition data are available in patients treated with ELE + TEZ + IVA. RESULTS: Two hundred and thirty-four children (55.1% male) were recruited. The median age was 13.6 years (inter-quartile range [IQR] 10.7-16.1). We can observe a statistically significant increase in the weight Z score and BMI Z score after CFTRm. In terms of changes in body composition, we observe a significant increase in fat mass (FM) expressed both in kilograms and as a percentage at 6 months (p < .05; Wilcoxon-test), with no such differences found at 12 months. We also observe a statistically significant increase in fat-free-mass (FFM), expressed in kilograms at 6 and 12 months (p < .05; Wilcoxon-test). CONCLUSION: Weight status improved and changes in body composition occurred in children after CFTRm therapy, including an increase of fat mass. Further studies are needed to confirm these changes in body composition and their impact on disease progression.

A framework for translating tauopathy therapeutics: Drug discovery to clinical trials.

The tauopathies are defined by pathological tau protein aggregates within a spectrum of clinically heterogeneous neurodegenerative diseases. The primary tauopathies meet the definition of rare diseases in the United States. There is no approved treatment for primary tauopathies. In this context, designing the most efficient development programs to translate promising targets and treatments from preclinical studies to early-phase clinical trials is vital. In September 2022, the Rainwater Charitable Foundation convened an international expert workshop focused on the translation of tauopathy therapeutics through early-phase trials. Our report on the workshop recommends a framework for principled drug development and a companion lexicon to facilitate communication focusing on reproducibility and achieving common elements. Topics include the selection of targets, drugs, biomarkers, participants, and study designs. The maturation of pharmacodynamic biomarkers to demonstrate target engagement and surrogate disease biomarkers is a crucial unmet need. HIGHLIGHTS: Experts provided a framework to translate therapeutics (discovery to clinical trials). Experts focused on the "5 Rights" (target, drug, biomarker, participants, trial). Current research on frontotemporal degeneration, progressive supranuclear palsy, and corticobasal syndrome therapeutics includes 32 trials (37% on biologics) Tau therapeutics are being tested in Alzheimer's disease; primary tauopathies have a large unmet need.

[Short-term and long-term mortality comparison between myocardial infarction with and without ST segment elevation undergoing myocardial revascularization by percutaneous coronary angioplasty]. / Comparación de mortalidad a corto y largo plazo entre el infarto del miocardio con y sin supradesnivel del segmento ST sometido a revascularización miocárdica por angioplastia coronaria percutánea.

OBJECTIVES: To compare the early and late mortality of patients that have suffered an ST segment elevation myocardial infarction (STEMI) and a non-ST segment elevated myocardialinfarction (NSTEMI). METHODS: Retrospective study of patients treated at the Regional Clinical Hospital of Concepción from January the 1rst 2013 to December 31 rst 2015, with diagnostic of STEMI and NSTEMI that required coronary angioplasty during their hospitalization. Descriptive and multivariate analysis was performed to compare mortality rates between both populations before 30 days and in follow-up at 4 years. RESULTS: 1838 patients were included with an average follow-up of 82 months. The population with STEMI was 921 and was younger, with a higher prevalence of arterial hypertension and smoking. The population with NSTEMI had a higher prevalence of diabetes mellitus, a lower glomerular filtration rate, and a higher incidence of left main coronary artery disease and chronic occlusions. At the end of follow-up, the overall survival rate was 76%, with no significant difference between the two groups. Patients with STEMI had twice the risk of dying in the first 30 days (Long Rank: 0.012). After 30 days, mortality was higher in the NSTEMI group (80.8% vs 75.6%). CONCLUSIONS: This study did not show significant differences in overall mortality during prolonged follow-up of patients with STEMI and NSTEMI. The STEMI group had a higher risk of early death, while the NSTEMI group had higher long-term mortality.

Thermoelectric bismuth telluride nanostructures fabricated by electrodeposition within flexible templates.

Bismuth telluride, a highly efficient thermoelectric material, stands out for applications around room temperature in wearable devices. By harnessing the thermal gradient established between the human body and ambient temperature, we can generate useable electricity. Notably, bismuth telluride nanostructures exhibit significantly lower thermal conductivities compared to their bulk counterparts. As a result, the thermoelectric efficiency achieved is notably higher. Our research focuses on developing efficient nanostructured materials based on bismuth telluride inside a flexible substrate made of polyester. We employ scalable methods, such as template-assisted electrochemical deposition, to fabricate these nanostructures. In this study, we present an approach to the development of flexible nanostructured thermoelectric materials. Despite using a reduced quantity of active material, our electrochemically deposited nanostructures inside a flexible template demonstrate a remarkable performance. They exhibit 24 % of the Power Factor reported for conventional electrochemically fabricated Bi2Te3 thin films, and notably, they even surpass the Power Factor reported for flexible Bi2Te3-based inks used in the creation of flexible generators. This achievement underscores the potential of our method in the advancement of efficient, flexible thermoelectric devices.

Follicular Lymphoma in Chile in the Adult Public Cancer Program: The Impact of Chemoimmunotherapy.

BACKGROUND: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma (NHL) in the United States and Europe. However, data on FL from Latin America are scant. AIMS: This study aims at better understand the clinical features, treatment patterns and outcomes of patients with FL in Chile. Of special interest was to evaluate POD24 as an adverse marker. METHODS AND RESULTS: We collected retrospective data from 722 patients 15 years or older diagnosed with FL and treated in 17 cancer centers in Chile between 2000 and 2019. Time to first treatment (TTFT), progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional-hazard regression models were fitted to investigate prognostic factor. The median age at diagnosis was 62 with a female predominance (63%); 73% of patients had advance stage disease and 68% had bone marrow involvement; 63% had intermediate or high FLIPI scores. The 1-year TTFT rate was 96%, and 30% of patients received chemoimmunotherapy. Adding rituximab to chemotherapy was associated with a higher complete response (69% vs. 60%; p < 0.001) and superior median OS (16 vs. 8 years; p < 0.001). Patients who experience POD24 had an inferior median OS (2.4 vs. 15 years). CONCLUSION: Our study shows a female predominance in patients with FL in Chile and confirms superior response and survival outcomes with adding rituximab to chemotherapy. Our study also confirms a poor OS in patients who experience POD24.

Killer-cell immunoglobulin-like receptor polymorphism is associated with COVID-19 outcome: Results of a pilot observational study.

The pathogenesis of COVID-19 warrants unravelling. Genetic polymorphism analysis may help answer the variability in disease outcome. To determine the role of KIR and HLA polymorphisms in susceptibility, progression, and severity of SARS-CoV-2 infection, 458 patients and 667 controls enrolled in this retrospective observational study from April to December 2020. Mild/moderate and severe/death study groups were established. HLA-A, -B, -C, and KIR genotyping were performed using the Lifecodes® HLA-SSO and KIR-SSO kits on the Luminex® 200™ xMAP fluoroanalyser. A probability score using multivariate binary logistic regression analysis was calculated to estimate the likelihood of severe COVID-19. ROC analysis was used to calculate the best cut-off point for predicting a worse clinical outcome with high sensitivity and specificity. A p ≤ 0.05 was considered statistically significant. KIR AA genotype protected positively against severity/death from COVID-19. Furthermore, KIR3DL1, KIR2DL3 and KIR2DS4 genes protected patients from severe forms of COVID-19. KIR Bx genotype, as well as KIR2DL2, KIR2DS2, KIR2DS3 and KIR3DS1 were identified as biomarkers of severe COVID-19. Our logistic regression model, which included clinical and KIR/HLA variables, categorised our cohort of patients as high/low risk for severe COVID-19 disease with high sensitivity and specificity (Se = 94.29%, 95% CI [80.84-99.30]; Sp = 84.55%, 95% CI [79.26-88.94]; OR = 47.58, 95%CI [11.73-193.12], p < 0.0001). These results illustrate an association between KIR/HLA ligand polymorphism and different COVID-19 outcomes and remarks the possibility of use them as a surrogate biomarkers to detect severe patients in possible future infectious outbreaks.

Genotypic spectrum of ABCA4-associated retinal degenerations in 211 unrelated Mexican patients: identification of 22 novel disease-causing variants.

The purpose of this study was to analyze and molecularly describe the largest group of patients with ABCA4-associated retinal degeneration in Latin America. Pathogenic variants in ABCA4, a member of the ATP Binding Cassette (ABC) transporters superfamily, is one of the most common causes of inherited visual deficiency in humans. Retinal phenotypes associated with genetic defects in ABCA4 are collectively known as ABCA4-associated retinal degenerations (ABCA4R), a group of recessively inherited disorders associated with a high allelic heterogeneity. While large groups of Caucasian and Asiatic individuals suffering from ABCA4R have been well characterized, molecular information from certain ethnic groups is limited or unavailable, precluding a more realistic knowledge of ABCA4-related mutational profile worldwide. In this study, we describe the molecular findings of a large group of 211 ABCA4R index cases from Mexico. Genotyping was performed using either next generation sequencing (NGS) of a retinal dystrophy genes panel or exome. ABCA4 targeted mutation testing was applied to a subgroup of subjects in whom founder mutations were suspected. A total of 128 different ABCA4 pathogenic variants were identified, including 22 previously unpublished variants. The most common type of genetic variation was single nucleotide substitutions which occurred in 92.7% (408/440 alleles). According to the predicted protein effect, the most frequent variant type was missense, occurring in 83.5% of disease-causing alleles (368/440). Mutations such as p.Ala1773Val are fully demonstrated as a founder effect in native inhabitants of certain regions of Mexico. This study also gives us certain indications of other founder effects that need to be further studied in the near future. This is the largest molecularly characterized ABCA4R Latin American cohort, and our results supports the value of conducting genetic screening in underrepresented populations for a better knowledge of the mutational profile leading to monogenic diseases.

[Translated article] Truths and myths about augmentation techniques in the treatment of fragility fractures.

The main event of osteoporosis is fragility fractures. Vertebral compression fractures are the most commonly fragility fracture related to osteoporosis. Our goal is to review the available literature to confirm or deny concepts learned about spinal cementation and adapt our clinical practice according to scientific evidence. In the complex world of spine surgery, constant innovations seek to improve the quality of life of patients. Among these, vertebral augmentation has emerged as an increasingly popular technique, but often shrouded in myths and misunderstandings. In this systematic review, we will thoroughly explore the truths behind vertebral augmentation, unravelling common myths and providing a clear insight into this technique. As specialists in the field, it is crucial to understand the reality surrounding these interventions to offer our patients the best possible information and make informed decisions.

NKG2C/KLRC2 tumor cell expression enhances immunotherapeutic efficacy against glioblastoma.

BACKGROUND: Activating and inhibitory receptors of natural killer (NK) cells such as NKp, NKG2, or CLEC are highly relevant to cold tumors including glioblastoma (GBM). Here, we aimed to characterize the expression of these receptors in GBM to gain insight into their potential role as modulators of the intratumoral microenvironment. METHODS: We performed a transcriptomic analysis of several NK receptors with a focus on the activating receptor encoded by KLRC2, NKG2C, among bulk and single-cell RNA sequencing GBM data sets. We also evaluated the effects of KLRC2-overexpressing GL261 cells in mice treated with or without programmed cell death protein-1 (PD-1) monoclonal antibody (mAb). Finally, we analyzed samples from two clinical trials evaluating PD-1 mAb effects in patients with GBM to determine the potential of NKG2C to serve as a biomarker of response. RESULTS: We observed significant expression of several inhibitory NK receptors on GBM-infiltrating NK and T cells, which contrasts with the strong expression of KLRC2 on tumor cells, mainly at the infiltrative margin. Neoplastic KLRC2 expression was associated with a reduction in the number of myeloid-derived suppressor cells and with a higher level of tumor-resident lymphocytes. A stronger antitumor activity after PD-1 mAb treatment was observed in NKG2Chigh-expressing tumors both in mouse models and patients with GBM whereas the expression of inhibitory NK receptors showed an inverse association. CONCLUSIONS: This study explored the role of neoplastic NKG2C/KLRC2 expression in shaping the immune profile of GBM and suggests that it is a predictive biomarker for positive responses to immune checkpoint inhibitor treatment in patients with GBM. Future studies could further validate this finding in prospective trials.

Relationship of litterfall anomalies with climatic anomalies in a mangrove swamp of the Yucatan Peninsula, Mexico.

Among the set of phenological traits featuring mangrove ecosystems, litterfall production stands out with marked intra-annual and longer-term variation. Furthermore, mangrove forests resilience is one of the most important ecological attribute, reconciling the juxtaposed terrestrial and marine environment such transitional systems occupy. However, world's mangroves are nowadays facing recurrent climatic events, reflected in anomalies depicted by major drivers, including temperature and precipitation. This physical-environmental setting may either constrain or favor overall forest productivity. A combination of time series analysis (spectral density and cross-correlation techniques) and statistical model fitting (General additive model) was implemented to explore trends in total litterfall of a well-developed mangrove forest in southeastern Gulf of Mexico (Celestun Lagoon, SE Mexico) and potential association with the varying behavior of temperature (°C) and precipitation (mm month-1), highlighting their anomalies. The results are consistent with a synchronous response between litterfall production and climatic variables (mean monthly temperature and total monthly precipitation). Concurrent peak litterfall production in Celestun lagoon with high temperatures and precipitation occurred during June and October, featuring a two-month time lag for the response time. More than half of the litterfall anomalies (53.5%) could be reflecting either multiple sources of climatic anomalies (maximum, minimum, and monthly average temperature and monthly total precipitation) or single point events (cyclone landfall). This relationship dynamics showed an interannual persistence (1999-2010). The structure portrayed by the litterfall time-series was not unequivocally related to climatic anomalies. Arguably, climatic anomalies behave with different intensities and even may exhibit complex interactions among them. The study of anomalies provides a baseline for a better grasp of: i) mangrove anomalies responses and ii) their vulnerability to these extremes.

Age-adjusted Charlson comorbidity index and its association with body composition and overall survival in patients with colorectal cancer.

OBJECTIVE: To examine the relationship between the age-adjusted Charlson comorbidity index (A-CCI) with body composition and overall survival in patients newly diagnosed with colorectal cancer (CRC). RESEARCH METHODS AND PROCEDURES: In this cohort study, patients (≥ 18 years old) with CRC were followed for 36 months. Computed tomography images of the third lumbar were analyzed to determine body composition, including skeletal muscle area (SMA), skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Phenotypes based on comorbidity burden assessed by A-CCI and body composition parameters were established. RESULTS: A total of 436 participants were included, 50% male, with a mean age of 61 ± 13.2 years. Approximately half of the patients (50.4%) had no comorbidity, and the A-CCI median score was 4 (interquartile range: 3-6). A higher A-CCI score was a risk factor for 36-month mortality (HR = 3.59, 95% CI = 2.17-5.95). Low SMA and low SMD were associated with a higher A-CCI. All abnormal phenotypes (high A-CCI and low SMA; high A-CCI and low SMD; high A-CCI and high VAT) were independently associated with higher 36-month mortality hazard (adjusted HR 5.12, 95% CI 2.73-9.57; adjusted HR 4.58, 95% CI 2.37-8.85; and adjusted HR 2.36, 95% CI 1.07-5.22, respectively). CONCLUSION: The coexistence of comorbidity burden and abnormal body composition phenotypes, such as alterations in muscle or fat compartments, may pose an additional risk of mortality in patients newly diagnosed with CRC. Early assessment and management of these phenotypes could be crucial in optimizing outcomes in such patients.

Thigh muscle by CT images as a predictor of mortality in patients with newly diagnosed colorectal cancer.

This study aimed to evaluate the prognostic value of thigh muscle assessed by CT images to predict overall mortality in patients with colorectal cancer (CRC). This was a multicenter cohort study including adults (≥ 18 years old) newly diagnosed with CRC, who performed a diagnostic computed tomography (CT) exam including thigh regions. CT images were analyzed to evaluate skeletal muscle (SM in cm2), skeletal muscle index (SMI in cm2/m2), and skeletal muscle density (SMD in HU). Muscle abnormalities (low SM, SMI, and SMD) were defined as the values below the median by sex. Kaplan-Meyer curves and hazard ratios (HRs) for low SM, SMI and SMD were evaluated for overall mortality, stratified by sex. A total of 257 patients were included in the final analysis. Patients' mean age was 62.6 ± 12.1 years, and 50.2% (n = 129) were females. In males, low thigh SMI was associated with shorter survival (log-rank P = .02). Furthermore, this low thigh SMI (cm2/m2) was independently associated with higher mortality rates (HR adjusted 2.08, 95% CI 1.03-4.18). Our additional findings demonstrated that low SMD was independently associated with overall mortality among early-stage patients (I-III) (HR adjusted 2.78, 95% CI 1.26-6.15).

Limited ilioinguinal approach for unstable pelvic fractures in children aged <3 years.

Background: Pelvic fractures in pediatric trauma account for 0.5-1 % of total hospital admissions, whereas acetabular fracture occurs at a rate of one case per 100,000 children; the low presentation rate is due to its unique characteristics. Standardized management for this age group is impossible. Conservative treatment has been commonly used but surgical correction has gained popularity. The purpose of this study was to report the authors' experience using a limited ilioinguinal approach for unstable pelvic fracture in two toddlers. Methods: Description of case studies. Results: Herein, we describe the treatment of two patients: a male patient struck by a vehicle (aged 1 year and 7 months) and a female patient ejected from a motor vehicle (aged 2 years and 1 month). They sustained an unstable type IV fracture in the modified Torode and Zieg classification. Surgical treatment was performed using a limited ilioinguinal approach, and stabilization was achieved using 3.5-mm reconstruction plate. There were no iatrogenic nerve injuries or infection. The female patient had left hip dislocation 2 months post-surgery and was unfortunately lost to follow-up. The male patient achieved radiological bone union without discrepancy, with no loss of reduction or evidence of pain during the mean follow-up period of 18 months. Conclusion: Pelvic fracture in children is rare. Based on fracture patterns, surgical stabilization may be necessary to prevent major complications in the short, medium, or long term. The limited ilioinguinal approach was proven to be a viable alternative for managing unstable pelvic fracture in children aged <3 years with minimal blood lo and shorter operative time, allowing more anatomical and stable reduction.

[Idiopathic intracranial hypertension. Review of our experience in the last eight years (2016-2023)]. / Hipertensión intracraneal idiopática. Revisión de nuestra experiencia en los últimos ocho años (2016-2023).

INTRODUCTION: Idiopathic intracranial hypertension (IIH) or benign intracranial hypertension is a rare disease in childhood. The clinical presentation in pediatric patients can be very variable, being more unespecific in younger patients. PATIENTS AND METHODS: A retrospective descriptive study was carried out on patients diagnosed of IIH in the last eight years (2016-2023) in the neuropediatrics unit of a tertiary hospital. In the present study, the clinical-epidemiological characteristics and the diagnostic-therapeutic procedure carried out in each case were analyzed. RESULTS: We studied 14 patients, 57% were women. The average age at diagnosis was 9 years, headache was the most common reason for consultation. In all patients, papilledema was found in the fundus and neuroimaging didn´t find alterations. Optical coherence tomography has been carried out in 78.5% of the sample, > 80% of patients showed thickening of the retinal nerve fiber layer. All patients had a high cerebrospinal fluid opening pressure (>25 cmH2O). 57% of patients required treatment with acetazolamide, a carbonic anhydrase inhibito. In all patients the resolution was complete, however almost 30% of them have presented recurrences during follow-up. CONCLUSIONS: In recent years there has been an increase in the incidence of this entity, making early diagnosis and treatment essential to avoid possible irreversible damage.

TITLE: Hipertensión intracraneal idiopática. Revisión de nuestra experiencia en los últimos ocho años (2016-2023).Introducción. La hipertensión intracraneal idiopática (HII), o hipertensión intracraneal benigna, es una enfermedad poco frecuente en la infancia. La presentación clínica en pacientes pediátricos puede ser muy variable, y es más inespecífica a menor edad. Pacientes y métodos. Se ha realizado un estudio descriptivo retrospectivo de los pacientes diagnosticados de HII en los últimos ocho años (2016-2023) en la consulta de neuropediatría de un hospital de tercer nivel. En el presente estudio se analizaron las características clinicoepidemiológicas y el procedimiento diagnosticoterapéutico llevado a cabo en cada caso. Resultados. Se estudió a 14 pacientes, de los cuales el 57% eran mujeres. La edad media en el momento del diagnóstico fue de 9 años, y la cefalea fue el motivo de consulta más habitual. En todos los pacientes se constató papiledema en el fondo de ojo y una prueba de neuroimagen sin alteraciones. Se llevó a cabo una tomografía de coherencia óptica en el 78,5% de la muestra, y >80% de los pacientes presentaba engrosamiento de la capa de fibras nerviosas retiniana. La totalidad de los pacientes presentaba una presión de apertura de líquido cefalorraquídeo elevada (> 25 cmH2O). El 57% de los pacientes precisó como tratamiento acetazolamida, un inhibidor de la anhidrasa carbónica. En todos los pacientes la resolución fue completa; sin embargo, casi el 30% de ellos presentó recurrencias durante el seguimiento. Conclusiones. En los últimos años se ha mostrado un aumento en la incidencia de esta entidad, y es fundamental un diagnóstico y un tratamiento precoces para evitar posibles secuelas irreversibles.

Dicrocoeliidae Family: Major Species Causing Veterinary Diseases.

This chapter analyses the taxonomic position of the Dicrocoeliidae family and several of its genera and species. The chapter reviews the biology of major veterinary disease-causing species, including Dicrocoelium dendriticum, Dicrocoelium hospes, Dicrocoelium chinensis, Eurytrema pancreaticum and Platynosomum fastosum. All these species have indirect life cycles with two intermediate hosts: molluscs as the first host and ants, grasshoppers and lizards as the second host. Dicrocoelium dendriticum is a widespread liver fluke found in ruminants across Europe, Asia, North Africa and North America. It can also infect humans. Dicrocoelium hospes is widely distributed in the savanna areas of Africa south of the Sahara, while D. chinensis is mainly found in ruminants in East Asia and some European countries (probably imported from Asia). Eurytrema pancreaticum is a common parasite that lives in the bile ducts, gall bladder, pancreatic ducts and intestines of ruminants. It is found in Europe, Madagascar, Asia and South America. Adults of P. fastosum live in the liver, gall bladder and pancreas of birds and mammals in Europe, Africa, Asia, North, Central and South America. Information on the epidemiology, pathology, clinical aspects, diagnosis, treatment, control, prevention and economic impact of Dicrocoeliosis caused by D. dendriticum, Eurytrematodosis and Platynosomiosis have been included.

Reactive Infiltration: Effects of Different Parameters.

Currently, the production of complex SiC and SiC/SiC parts through reactive infiltration is one of the most widely used technologies, due to its versatility and cost-effectiveness compared to more conventional technologies such as Hot Isostatic Pressing (HIP). This technology, while widely adopted, still faces some debate regarding the mechanisms of infiltration. Questions persist about what determines how infiltration occurs and whether the process is governed by physics (flow dynamics) or chemistry (reactions at the triple line (LT: (contact line between the solid, liquid and gas phases)). The present work provides new strong/consistent proof that reactive infiltration is mainly controlled by chemical reaction.

Different mutational profiles of subcutaneous panniculitis-like T-cell lymphoma and lupus panniculitis: an additional case series.

BACKGROUND AND OBJECTIVE: subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed. OBJECTIVES: the aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP. MATERIALS AND METHODS: we studied a total of 10 SPTCL and 10 LEP patients using targeted Next Generation Sequencing and pyrosequencing. Differences in gene expression between molecular subgroups were investigated using NanoString technology. Clinical data were collected, and correlations sought with the molecular data obtained. RESULTS: the mutational profile of SPTCL and LEP is different. We identified fewer pathogenic mutations than previously reported in SPTCL, noting a single HAVCR2-mutated SPTCL case. Interestingly, 40% of our SPTCL cases showed the pathogenic TP53 (p.Pro72Arg) (P72R) variant. Although cases showing HAVCR2 mutations or the TP53 (P72R) variant had more severe symptomatic disease, none developed hemophagocytic syndrome (HPS). Furthermore, TP53 (P72R)-positive cases were characterized by a lower metabolic signaling pathway and higher levels of CD28 expression and Treg signaling genes. In addition, 30% of our cases featured the same mutation (T735C) of the epigenetic modificatory gene DNMT3A. None of the LEP cases showed mutations in any of the studied genes. CONCLUSIONS: the mutational landscape of SPTCL is broader than previously anticipated. We describe, for the first time, the involvement of the TP53 (P72R) pathogenic variant in this subgroup of tumors, consider the possible role of different genetic backgrounds in the development of SPTCL, and conclude that LEP does not follow the same pathogenic pathway as SPTCL.