Cemented vs cementless stems for revision arthroplasties due to Vancouver B2 periprosthetic hip fracture.

PURPOSE: According to Vancouver classification, B2 type fractures are most often treated with removal of the loose stem and implantation of a long stem that bypasses the fracture site. However, there is a controversy about the stem fixation that should be used: cemented or cementless. Hence, this study aims to compare cemented and cementless stems in prosthetic revision due to Vancouver B2 (VB2) periprosthetic hip fracture. METHODS: A retrospective study was done including all the patients treated with stem exchange due to VB2 periprosthetic hip fracture in a tertiary hospital between 2015 and 2022. Patients were divided into two groups according to the stem fixation used: cemented or cementless. Functional outcomes, hospital stay, surgical time, complication rate, and mortality were compared between the two groups of patients. RESULTS: Of the 30 included patients, 13 (43.4%) were treated with cementless stems and 17 (56.7%) with cemented stems. There were no statistically significant differences in age, gender, anesthesia risk scale (ASA) or functional capacity prior to the intervention. Patients treated with cementless stems had a higher complication and reintervention rate than those treated with cemented stems: 62 and 45% versus 34 and 6% (p = 0.035; p = 0.010), respectively. Furthermore, in the group of cementless stems a higher proportion of non-union was found (53.8% vs. 17.6%; p = 0.037). Also, the hospital stay (33 vs. 24 days; p = 0.037) and the time to full weight-bearing (21 days vs. 9 days; p < 0.001) were longer in the cementless stem group. CONCLUSION: Cemented fixation in stem revision due to Vancouver B2 periprosthetic hip fracture could be an optimal option with faster recovery which could decrease the rate of complications and reintervention, without compromising the fracture healing and patient mortality. Thus, this option can be considered when an anatomical reduction can be obtained, especially in elderly patients with multiple comorbidities in which a less aggressive surgical option should be considered.

Vena cava replacement and major hepatectomy for liver tumors: international multicenter retrospective cohort study.

INTRODUCTION: Involvement of the inferior vena cava (IVC) and hepatic veins (HV) has been considered a relative contraindication to hepatic resection for primary and metastatic liver tumors. However, patients affected by tumors extending to the IVC have limited therapeutic options and suffer worsening of quality of life due to IVC compression. METHODS: Cases of primary and metastatic liver tumors with vena cava infiltration from 10 international centers were collected (7 European, 1 US, 2 Brazilian, 1 Indian) were collected. Inclusion criteria for the study were major liver resection with concomitant vena cava replacement. Clinical data and short-term outcomes were analyzed. RESULTS: 36 cases were finally included in the study. Median tumor max size was 98 mm (range: 25-250). A biliary reconstruction was necessary in 28% of cases, while a vascular reconstruction other than vena cava in 34% of cases. Median operative time was 462 min (range: 230-750), with 750 median ml of estimated blood loss and a median of one pRBC transfused intraoperatively (range: 0-27). Median ICU stay was 4 days (range: 1-30) with overall in-hospital stay of 15 days (range: 3-46), post-operative CCI score of 20.9 (range: 0-100), 12% incidence of PHLF grade B-C. Five patients died in a 90-days interval from surgery, 1 due to heart failure, 1 due to septic shock and 3 due to multiorgan failure. With a median follow-up of 17 months (interquartile range: 11-37), the estimated five-years overall survival was 48% (95% CI: 27%-66%), and five-year cumulative incidence of tumor recurrence was 55% (95% CI: 33%-73%). CONCLUSIONS: Major liver resections with vena cava replacement can be performed with satisfactory results in expert HPB centers. This surgical strategy represents a feasible alternative for otherwise unresectable lesions and is associated with favorable prognosis compared to non-operative management, especially in patients affected by intrahepatic cholangiocarcinoma.

Fused hip conversion to total hip arthroplasty with the direct anterior approach: surgical technique on a regular surgical table under fluoroscopic guidance.

PURPOSE: Conversion of a fused hip to a total hip arthroplasty (THA) is technically challenging due to the loss of anatomical references. Here, a reproducible technique using the direct anterior approach (DAA) with a regular surgical table under fluoroscopic guidance is described, which has several advantages over traditional such as lateral or posterior approaches. METHODS: There were reported 11 cases of ankylosis hip that were converted to THA using the same surgical technique protocol. Clinical and radiographic outcomes were recorded at 3.2 years of follow-up. A detailed preoperative evaluation was performed, including a pelvis radiological evaluation and magnetic resonance image (MRI) to assess the integrity of the periarticular soft tissue and flexor muscles. RESULTS: The DAA has considerable advantages, such as allowing more precise targeting during surgery, avoiding the risk of pseudoarthrosis due to the absence of a trochanteric osteotomy, preserving the abductors, and allowing an easier-to-use of intraoperative fluoroscopy due to the supine position. Besides, the use of a standard table reduces surgical time and allows assessment of limb length, hip stability, and impingement in all planes in an intraoperative dynamic range, which decreases postoperative complications. CONCLUSION: Conversion from hip fusion to THA is a rare and complex procedure. The use of DAA with a standard table and fluoroscopy helps to avoid high complications since it allows a dynamic intra-operative examination of the range of motion to rule out impingements, reduces the risk of dislocation, and allows leg lengthening verification.

Vancouver B2 periprosthetic hip fractures treatment: fix or replace? A retrospective study comparing both techniques.

INTRODUCTION: Vancouver B2 periprosthetic hip fractures involve stem stability and they have been classically treated with revision surgery. Crucial factors such as age, clinical comorbidities and functional status are often neglected. The current study aims to compare clinical outcomes between patients treated with open reduction and internal fixation (ORIF) or femoral stem exchange. METHODS: This is a retrospective study that includes all Vancouver B2 periprosthetic hip fractures in a tertiary referral hospital from 2016 to 2020. Patients were divided into two groups: Group 1. Patients treated with an ORIF and Group 2. Patients treated with stem replacement. The outcomes that were compared between groups included demographic data, functional capacity, complications and mortality. RESULTS: 29 periprosthetic Vancouver B2 fractures were finally analyzed. 11 (37.9%) were treated with ORIF (Group 1) and 18 (62.1%) by stem replacement (Group 2). Surgery time (143 vs. 160 min), hemoglobin drop (1.8 vs. 2.5 g/dL) and hospital stance (25.5 vs. 29.6 days) were shorter in Group 1. According to complications, 18.2% of patients in the ORIF group had orthopedic complications compared with 44.4% in the revision group. In the revision group, 3 cases needed a two-stage revision and one of these revisions ended up with a resection arthroplasty (Girdlestone). The first-year mortality rate was 27% in Group 1 and 11% in Group 2. DISCUSSION: ORIF treatment seems to be a less aggressive and complex procedure which can lead to a faster general recovery. Revision surgery can imply a higher risk of orthopedic complications which can be severe and may require further aggressive solutions. The ORIF group mortality was similar to the proximal femur fracture rate (20-30%). In conclusion, ORIF treatment seems to be a good option especially in fragile patients with low functional demand when anatomical reduction is possible.

Differentially Expressed Genes Involved in Primary Resistance to Immunotherapy in Patients with Advanced-Stage Pulmonary Cancer.

In the last few years, nivolumab has become the standard of care for advanced-stage lung cancer patients. Unfortunately, up to 60% of patients do not respond to this treatment. In our study, we identified variations in gene expression related to primary resistance to immunotherapy. Bronchoscopy biopsies were obtained from advanced non-small cell lung cancer (NSCLC) patients previously characterized as responders or non-responders after nivolumab treatment. Ten tumor biopsies (from three responders and seven non-responders) were analyzed by the differential expression of 760 genes using the NanoString nCounter platform. These genes are known to be involved in the response to anti-PD1/PD-L1 therapy. All the patients were treated with nivolumab. Examining the dysregulated expression of 24 genes made it possible to predict the response to nivolumab treatment. Supervised analysis of the gene expression profile (GEP) revealed that responder patients had significantly higher levels of expression of CXCL11, NT5E, KLRK1, CD3G, GZMA, IDO1, LCK, CXCL9, GNLY, ITGAL, HLA-DRB1, CXCR6, IFNG, CD8A, ITK, B2M, HLA-B, and HLA-A than did non-responder patients. In contrast, PNOC, CD19, TP73, ARG1, FCRL2, and PTGER1 genes had significantly lower expression levels than non-responder patients. These findings were validated as predictive biomarkers in an independent series of 201 patients treated with nivolumab (22 hepatocellular carcinomas, 14 non-squamous cell lung carcinomas, 5 head and neck squamous cell carcinomas, 1 ureter/renal pelvis carcinoma, 120 melanomas, 4 bladder carcinomas, 31 renal cell carcinomas, and 4 squamous cell lung carcinomas). ROC curve analysis showed that the expression levels of ITK, NT5E, ITGAL, and CD8A were the best predictors of response to nivolumab. Further, 13/24 genes showed an adverse impact on overall survival (OS) in an independent, large series of patients with NSCLC (2166 cases). In summary, we found a strong association between the global GEP of advanced NSCLC and the response to nivolumab. The classification of NSCLC patients based on GEP enabled us to identify those patients who genuinely benefited from treatment with immune checkpoint inhibitors (ICIs). We also demonstrated that abnormal expression of most of the markers comprising the genomic signature has an adverse influence on OS, making them significant markers for therapeutic decision-making. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these biomarkers.

Liver Histology Predicts Liver Regeneration and Outcome in ALPPS: Novel Findings From A Multicenter Study.

BACKGROUND AND AIMS: Alterations in liver histology influence the liver's capacity to regenerate, but the relevance of each of the different changes in rapid liver growth induction is unknown. This study aimed to analyze the influence of the degree of histological alterations during the first and second stages on the ability of the liver to regenerate. METHODS: This cohort study included data obtained from the International ALPPS Registry between November 2011 and October 2020. Only patients with colorectal liver metastases were included in the study. We developed a histological risk score based on histological changes (stages 1 and 2) and a tumor pathology score based on the histological factors associated with poor tumor prognosis. RESULTS: In total, 395 patients were included. The time to reach stage 2 was shorter in patients with a low histological risk stage 1 (13 vs 17 days, P ˂0.01), low histological risk stage 2 (13 vs 15 days, P <0.01), and low pathological tumor risk (13 vs 15 days, P <0.01). Regarding interval stage, there was a higher inverse correlation in high histological risk stage 1 group compared to low histological risk 1 group in relation with future liver remnant body weight ( r =-0.1 and r =-0.08, respectively), and future liver remnant ( r =-0.15 and r =-0.06, respectively). CONCLUSIONS: ALPPS is associated with increased histological alterations in the liver parenchyma. It seems that the more histological alterations present and the higher the number of poor prognostic factors in the tumor histology, the longer the time to reach the second stage.

Living Donor Liver Transplantation for Hepatocellular Carcinoma Within and Outside Traditional Selection Criteria: A Multicentric North American Experience.

OBJECTIVE: To evaluate long-term oncologic outcomes of patients post-living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score. BACKGROUND: LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC). METHODS: Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method. RESULTS: Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% ( P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% ( P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival of 65.3%. CONCLUSIONS: Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-year rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.

Update to 'A Contemporary Systematic Review on Liver Transplantation for Unresectable Liver Metastasis of Colorectal Cancer'.

Colorectal cancer is the second most common cause of cancer-related death worldwide, and half of patients present with colorectal liver metastasis (CRLM). Liver transplant (LT) has emerged as a treatment modality for otherwise unresectable CRLM. Since the publication of the Lebeck-Lee systematic review in 2022, additional evidence has come to light supporting LT for CRLM in highly selected patients. This includes reports of >10-year follow-up with over 80% survival rates in low-risk patients. As these updated reports have significantly changed our collective knowledge, this article is intended to serve as an update to the 2022 systematic review to include the most up-to-date evidence on the subject.

Identification of BRCC3 and BRCA1 as Regulators of TAZ Stability and Activity.

TAZ (WWTR1) is a transcriptional co-activator regulated by Hippo signaling, mechano-transduction, and G-protein couple receptors. Once activated, TAZ and its paralogue, YAP1, regulate gene expression programs promoting cell proliferation, survival, and differentiation, thus controlling embryonic development, tissue regeneration, and aging. YAP and TAZ are also frequently activated in tumors, particularly in poorly differentiated and highly aggressive malignancies. Yet, mutations of YAP/TAZ or of their upstream regulators do not fully account for their activation in cancer, raising the possibility that other upstream regulatory pathways, still to be defined, are altered in tumors. In this work, we set out to identify novel regulators of TAZ by means of a siRNA-based screen. We identified 200 genes able to modulate the transcriptional activity of TAZ, with prominence for genes implicated in cell-cell contact, cytoskeletal tension, cell migration, WNT signaling, chromatin remodeling, and interleukins and NF-kappaB signaling. Among these genes we identified was BRCC3, a component of the BRCA1 complex that guards genome integrity and exerts tumor suppressive activity during cancer development. The loss of BRCC3 or BRCA1 leads to an increased level and activity of TAZ. Follow-up studies indicated that the cytoplasmic BRCA1 complex controls the ubiquitination and stability of TAZ. This may suggest that, in tumors, inactivating mutations of BRCA1 may unleash cell transformation by activating the TAZ oncogene.

Immune checkpoint inhibitors in non-small cell lung cancer: from current perspectives to future treatments-a systematic review.

Background: The introduction of immunotherapy in the treatment of non-small cell lung cancer (NSCLC) has resulted in a radical change in patients' treatment responses and survival rates. The increased percentage of long survivors, improved toxicity profiles compared to chemotherapy, and the possible applications for different NSCLC scenarios, have led to immune checkpoint inhibitors (ICIs) becoming the cornerstone of NSCLC treatment. Therefore, the objective of this review is to describe the current and future perspectives of NSCLC treatment. Methods: A systematic review according to the PRISMA criteria has been performed based on clinical trials with immunotherapy in NSCLC from the start of these treatments until June 2022. Results: The use of ICIs is widespread across both first- and second-line treatments with anti-PD-1, anti-PD-L1, and anti-CTLA-4 drugs. New indications for immunotherapy in NSCLC have focused on adjuvant (atezolizumab) and neoadjuvant (nivolumab), with ICIs now present in all stages of NSCLC treatment. Given the promising results seen in clinical trials, new ICIs [anti- lymphocyte activation gene-3 (LAG-3) or IDO1] currently under development, will soon be used as standard treatment for NSCLC. Conclusions: Immunotherapy is the mainstay of NSCLC treatment in all stages, including adjuvant, neoadjuvant and advanced tumors. The development of new molecules will revolutionize the treatment of NSCLC in the coming years.

Cardiotoxicity Secondary to Immune Checkpoint Inhibitors in the Elderly: Safety in Real-World Data.

INTRODUCTION: Immunotherapy represents a key pillar of cancer treatments, with high response rates and long survival. Its use is increasing, mainly at the expense of the geriatric population due to the ageing of this population. However, despite its benefit, its safety in certain areas such as cardiotoxicity is largely unknown. The aim of this study is to assess the safety of immunotherapy in elderly patients using real-world data. METHODS: This is an ambispective study of patients ≥ 70 years old with solid tumours who were treated with immunotherapy at the University Hospital of Salamanca. Cardiotoxicity was assessed using the CTCAEv5.0 criteria. RESULTS: In total, 195 patients were included (76.9% male and 23.1% female), with a mean age of 75 years [70-93]. The percentage of patients with cardiotoxicity was 1.54%; 1.35% of patients with previous heart disease were diagnosed with cardiotoxicity, and 1.65% of those without previous heart disease were diagnosed with cardiotoxicity. The median time from the initiation of treatment until the cardiac event was 45 days [14-96]. The most frequent toxicity was myocarditis in 66.7% of patients, followed by arrhythmias in 33.3% of patients. CONCLUSIONS: Immunotherapy is shown to be a safe treatment in elderly cancer patients in terms of cardiotoxicity. The event rate shows no difference between patients with or without cardiac comorbidity.

Comparable and Complimentary Modalities for Treatment of Small-Sized HCC: Surgical Resection, Radiofrequency Ablation, and Microwave Ablation.

BACKGROUND: Over the past decade, there has been continual improvement in both ablative and surgical technologies for the treatment of hepatocellular carcinoma (HCC). The efficacy of ablative therapy compared to surgical resection for HCC has not been thoroughly evaluated using multiple large-scale randomized controlled trials. By international consensus, if a patient is eligible, surgery is the primary curative treatment option, as it is believed to confer superior oncologic control. OBJECTIVE: to determine the efficacies of percutaneous ablative therapies and surgical resection (SR) in the treatment of HCC. Data sources, study appraisal, and synthesis methods: A meta-analysis using 5 online databases dating back to 1989 with more than 31,000 patients analyzing patient and tumor characteristics, median follow-up, overall survival, and complication rate was performed. RESULTS: Ablative therapies are suitable alternatives to surgical resection in terms of survival and complication rates for comparable patient populations. For the entire length of the study from 1989-2019, radiofrequency ablation (RFA) produced the highest 5-year survival rates (59.6%), followed by microwave ablation (MWA) (50.7%) and surgical resection (SR) (49.9%). In the most recent era from 2006 to 2019, surgical resection has produced the highest 5-year survival rate of 72.8%, followed by RFA at 61.7% and MWA at 50.6%. Conclusions and key findings: Depending on the disease state and comorbidities of the patient, one modality may offer superior overall survival rates over the other available techniques. Interventional ablative methods and surgical resection should be used in conjunction for the successful treatment of small-sized HCC.

Habilidades prácticas en estudiantes de Enfermería Técnica de tercer año, Facultad Finlay-Albarrán, 2021 / Practical skills in third-year Technical Nursing students, Finlay-Albarrán Faculty, 2021 / Competências práticas em estudantes de enfermagem técnica do terceiro ano, Finlay-Albarrán Faculty, 2021

Introducción: El proceso de formación de habilidades es superior a la simple asimilación del contenido, ya que las habilidades resultan indispensables en el aprendizaje, requiriéndose que la enseñanza sea activa a través de diferentes etapas interrelacionadas, pero con cierta flexibilidad en su aplicación, según su complejidad. Objetivo: Diagnosticar el estado de desarrollo de las habilidades prácticas en estudiantes de 3° año (9° grado) de la carrera de Enfermería Técnica Facultad Finlay-Albarrán marzo-mayo 2021. Metodología: El estudio corresponde a un diseño descriptivo de corte transversal en la Facultad Finlay-Albarrán con estudiantes de 3° año de la carrera de Enfermería Técnica durante el período marzo-mayo 2021.El universo estuvo representado por los estudiantes que iniciaron en la rotación de Enfermería Ginecobstétrica (N=28). Para el estudio se combinaron métodos teóricos, empíricos y estadísticos. Resultados: Los alumnos del 3° año de Enfermería, reconocen como habilidades a desarrollar la medición de signos vitales para un 57.14%, el examen físico general, para un 67.85%, la cura de herida quirúrgica para un 53.57% y la evolución de Enfermería para un 82.1%, no consideran el Proceso de Atención de Enfermería, o sea la aplicación de este que es el método científico de la profesión, como un saber esencial en la práctica de Enfermería. Conclusiones: Se diagnosticó el estado de las habilidades prácticas en estudiantes de 3° año de Enfermería.

Introduction: The skills training process is superior to the simple assimilation of the content, since the skills are essential in learning, requiring that the teaching be active through different interrelated stages, but with some flexibility in its application, according to its complexity. Objective: To diagnose the state of development of practical skills in third year students (ninth grade) of the Finlay-Albarrán Faculty of Technical Nursing career, March-May 2021. Methodology: The study corresponds to a descriptive cross-sectional design in the Finlay-Albarrán Faculty with third year students of the Technical Nursing career during the period March-May 2021.The universe was represented by the students who started in the Gyneco-Obstetric Nursing rotation (N = 28) .For the study, theoretical, empirical, and statistical methods were combined. Results: The 3rd year Nursing students recognize as skills to develop the measurement of vital signs for 57.14%, the general physical examination, for a 67.85%, surgical wound healing for 53.57% and Nursing evolution for 82.1%, do not consider the Nursing Care Process, that is, the application of this, which is the scientific method of the profession, as essential knowledge in Nursing practice. Conclusions: The state of practical skills in third year Nursing students was diagnosed.

Introdução: O processo de formação de competências é superior à simples assimilação do conteúdo, uma vez que as competências são essenciais na aprendizagem, exigindo que o ensino seja ativo em diferentes etapas inter-relacionadas, mas com alguma flexibilidade na sua aplicação, de acordo com a sua complexidade. Objetivo: Diagnosticar o estado de desenvolvimento de habilidades práticas em alunos do 3º ano (9º ano) da carreira da Faculdade de Enfermagem Técnica Finlay-Albarrán, março-maio de 2021. Metodologia: O estudo corresponde a um desenho transversal descritivo no Finlay-Albarrán Docente com alunos do 3º ano da carreira de Técnico de Enfermagem durante o período março-maio de 2021. O universo foi representado pelos alunos que iniciaram no rodízio de Enfermagem Gineco-Obstétrica (N = 28). Para o estudo foram combinados métodos teóricos, empíricos e estatísticos. Resultados: Os alunos do 3º ano de Enfermagem reconhecem como habilidades para desenvolver a mensuração dos sinais vitais para 57,14%, o exame físico geral, para 67,85%, a cicatrização de feridas cirúrgicas para 53,57% e a evolução da Enfermagem para 82,1%, não consideram o Processo de Assistência de Enfermagem, ou seja, a aplicação deste, que é o método científico da profissão, como conhecimento essencial na prática da Enfermagem. Conclusões: Foi diagnosticado o estado das habilidades práticas em alunos do 3º ano de Enfermagem.

Liver transplantation for unresectable colorectal liver metastasis.

PURPOSE OF REVIEW: To summarize the current state of liver transplantation (LT) for unresectable colorectal liver metastases (uCRLM), and to address future directions. RECENT FINDINGS: The Norwegian secondary cancer (SECA) I and SECA II studies demonstrated that after LT the 5-year survival of a highly selected group of patients with uCRLM could be as high as 60% and 83%, respectively. After long-term follow-up, the 5- and 10-year survival was shown to be 43% and 26%, respectively. Furthermore, data has accumulated in other countries and a North American study reported a 1.5-year survival of 100%. In addition, steady growth has been demonstrated in the US, with 46 patients transplanted to date and 19 centers enrolling patients for this indication. Lastly, although recurrence is almost universal in patients with a high tumor burden, it has not been an accurate surrogate for survival, reflecting the relatively indolent nature of recurrence after LT. SUMMARY: Growing evidence has shown that excellent survival and even cure can be achieved in highly selected patients with uCRLM, with survival rates far superior than in patients treated with chemotherapy. The next step is to create national registries to standardize selection criteria and establish the optimal approach and best practices for incorporating LT for uCRLM into the treatment armamentarium.

The relationship between PARP inhibitors with the relapse and leukemisation of lymphomas: a case report.

Background: Nowadays the poly-ADP ribose polymerase inhibitors (iPARPs) are the mainly treatment for the ovarian cancer and other solid tumours. However, given its recent use, long-term toxicity is still under study. The occurrence of acute leukaemias and myelodysplastic syndromes (MDS) secondarily to iPARPs is known (0.5-1%). Case Description: We present the case of a 78-year-old patient with a serous carcinoma of ovary in maintenance treatment with Niraparib after response to platinum. Along with the ovarian carcinoma the patient developed a diffuse large cell B lymphoma (DLBCL) five years ago, treated with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone) with complete response. The patient was evaluated in the emergency due to constitutional syndrome, objectifying a bicytopenia (platelets 28,000/mcL, haemoglobin 9.6 g/dL). In the study of bicytopenia, a bone marrow infiltration by high-grade B lymphoma was diagnosed. Conclusions: The action of iPARPs on the selection of acquired mutations in clonal haematopoiesis maybe have been able to accelerate the process of relapse and leukemisation of the previous lymphoma. The association of treatment with iPARPs and the development of lymphomas is key for increasing knowledge of the safety profiles these drugs.

Rosuvastatin Synergistically Enhances the Antinociceptive Efficacy of Duloxetine in Paclitaxel-Induced Neuropathic Pain in Mice.

Paclitaxel, a widely used cancer chemotherapeutic agent, has high incidence of neurotoxicity associated with the production of neuropathic pain, for which only duloxetine has shown significant but moderate analgesic effect. Since statins, classically used to reduce hypercholesterolemia, have shown antinociceptive effect in preclinical studies on neuropathic pain, we studied whether the antinociceptive efficacy of duloxetine could be synergistically potentiated by rosuvastatin in a model of paclitaxel-induced neuropathy in mice. The astrocytic and microglial responses in the spinal cord of paclitaxel-treated mice were also assessed by measuring GFAP and CD11b proteins, respectively. Paclitaxel treatment did not impair motor coordination and balance in rotarod testing. Rosuvastatin, duloxetine, and the rosuvastatin/duloxetine combination (combined at equieffective doses) dose-dependently decreased mechanical allodynia (ED30, von Frey testing) and thermal hyperalgesia (ED50, hot plate testing) in paclitaxel-treated mice. Isobolographic analysis showed a superadditive interaction for rosuvastatin and duloxetine, as both the ED30 and ED50 for the rosuvastatin/duloxetine combination contained only a quarter of each drug compared to the individual drugs. The rosuvastatin/duloxetine combination reversed paclitaxel-induced GFAP overexpression, indicating that such effects might depend in part on astrocyte inactivation. Results suggest that statins could be useful in synergistically enhancing the efficacy of duloxetine in some chemotherapy-induced neuropathic conditions.