The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.

NUT carcinoma of the mandible in a child: case report and systematic review.

Nuclear protein of the testis (NUT) carcinoma is a rare, undifferentiated carcinoma that is characterized by NUTM1 gene rearrangements. Patients with NUT carcinoma have an overall survival of approximately 5% at 5 years despite a multimodal treatment approach. This report illustrates the management of mandibular NUT carcinoma in a pediatric patient, complemented by a systematic review of head and neck NUT carcinoma. A 5-year-old female presented with an enlarging jaw mass that was diagnosed as BRD4-NUTM1 carcinoma and was treated with hemimandibulectomy and chemoradiation. She remains disease-free 21 months after completion of therapy. A total of 63 patient cases reported in 34 articles were identified in the review. Only 26.9% (14/52) of tumors were correctly diagnosed initially as NUT carcinoma, whereas 73.1% (38/52) were incorrectly diagnosed as another malignancy; the initial diagnosis was not reported for 11 patients. The mandibular tumor subtype was among the rarest reported (n = 1; 1.6%). Combination therapy, including surgery and chemoradiation, was the most common treatment (55.2%). The patient case presented here is a novel case of pediatric mandibular NUT carcinoma. Due to the poor overall survival of patients with NUT carcinoma, aggressive upfront resection with 2-cm margins followed by adjuvant chemoradiation is advocated.

Mycobacterium avium infection associated with sterile polyarthritis in a dog.

A 1-year-old male neutered Portuguese Podengo dog was presented for lameness, inappetence, pyrexia, diarrhoea and abdominal moderate to severe lymphadenomegaly. Cytology of synovial fluid revealed neutrophilic inflammation in multiple joints suggestive of immune-mediated polyarthritis. Cytology of fine-needle-aspiration material obtained from lymph nodes revealed macrophages with intracytoplasmic, rod-like Ziehl-Neelsen positive staining structures, indicative of mycobacteria. Four-month treatment with enrofloxacin, rifampicin and clarithromycin resulted in clinical improvement and resolution of polyarthritis as evidenced on repeat synoviocentesis, but diarrhoea recurred, Ziehl-Neelsen positive organisms were again found on lymph node cytology and analysis of the 16S rRNA-gene using the Basic Local Alignment Search Tool facility resulted in a match to Mycobacterium avium with 100% sequence identity. Treatment was adjusted to include pradofloxacin, doxycycline, rifampicin and ethambutol and 3 months later the dog is clinically normal. Based on the literature search, this is the first time canine Mycobacterium avium infection associated with immune-mediated polyarthritis is reported. Based on scoping searches, this is the first report of canine Mycobacterium avium infection associated with immune-mediated polyarthritis.

Imaging of therapeutic airway interventions in thoracic oncology.

Tracheobronchial obstruction, haemoptysis, and airway fistulas caused by airway involvement by primary or metastatic malignancies may result in dyspnoea, wheezing, stridor, hypoxaemia, and obstructive atelectasis or pneumonia, and can lead to life-threatening respiratory failure if untreated. Complex minimally invasive endobronchial interventions are being used increasingly to treat cancer patients with tracheobronchial conditions with curative or, most often, palliative intent, to improve symptoms and quality of life. The selection of the appropriate treatment strategy depends on multiple factors, including tumour characteristics, whether the lesion is predominately endobronchial, shows extrinsic compression, or a combination of both, the patient's clinical status, the urgency of the clinical scenario, physician expertise, and availability of tools. Pre-procedure multidetector computed tomography (MDCT) imaging can aid in the most appropriate selection of bronchoscopic treatment. Follow-up imaging is invaluable for the early recognition and management of any potential complication. This article reviews the most commonly used endobronchial procedures in the oncological setting and illustrates the role of MDCT in planning, assisting, and follow-up of endobronchial therapeutic procedures.

Use of computed tomography sinography for evaluation of draining tracts in 27 dogs and one cat.

OBJECTIVES: To describe the clinical findings, imaging findings and outcome in patients in which CT sinography was performed, and assess to what degree this technique adds information about the extent of a tract or increases the accuracy of diagnosis of foreign bodies on CT. MATERIALS AND METHODS: Retrospective review of medical records of 27 dogs and one cat with draining tracts that had CT sinography. Pre- and post-intravenous (IV) contrast CT series were compared with CT sinography in each patient. RESULTS: Median duration of clinical signs before referral was 85 days (range 2 to 1478 days). The most common reported clinical signs were swelling (14/28, 50%) and regional pain (5/28, 18%). CT sinography revealed a more extensive tract than post-IV contrast CT in 21% cases. On post-IV contrast CT, 31% of foreign bodies were detected compared to 23% on CT sinography. All four foreign bodies detected by CT were observed in the non-contrast images. Surgery was performed after CT in 22 (79%) cases. Thirteen (46%) draining tracts resolved after surgery, three (11%) resolved without surgery, six (21%) persisted or recurred after surgery, and six (21%) were lost to follow-up. CLINICAL SIGNIFICANCE: CT sinography provides limited additional information about the extent of draining tracts compared to pre- and post-IV contrast CT images and did not increase the number of foreign bodies identified.

Liver transplant with controlled donors after circulatory death with normothermic regional perfusion and brain dead donors: A multicenter cohort study of transfusion, one-year graft survival and mortality.

BACKGROUND: Controlled donation after circulatory death (cDCD) has expanded the donor pool for liver transplantation (LT). However, transfusion requirements and perioperative outcomes should be elucidated. The aim of this multicenter study was to assess red blood cell (RBC) transfusions, one-year graft and patient survival after LT after cDCD with normothermic regional perfusion (NRP) compared with donors after brain death (DBD). METHODS: 591 LT carried out in ten centers during 2019 were reviewed. Thromboelastometry was used to manage coagulation and blood product transfusion in all centers. Normothermic regional perfusion was the standard technique for organ recovery. RESULTS: 447 patients received DBD and 144 cDCD with NRP. Baseline MCF Extem was lower in the cDCD group There were no differences in the percentage of patients (63% vs. 61% p = 0.69), nor in the number of RBC units transfused (4.7 (0.2) vs 5.5 (0.4) in DBD vs cDCD, p = 0.11. Twenty-six patients (6%) died during admission for LT in the DBD group compared with 3 patients (2%) in the cDCD group (p = 0.15). To overcome the bias due to a worse coagulation profile in cDCD recipients, matched samples were compared. No differences in baseline laboratory data, or in intraoperative use of RBC or one-year outcome data were observed between DBD and cDCD recipients. CONCLUSIONS: cDCD with NRP is not associated with increased RBC transfusion. No differences in graft and patient survival between cDCD and DBD were found. Donors after controlled circulatory death with NRP can increasingly be utilized with safety, improving the imbalance between organ donors and the ever-growing demand.

Primer consenso cubano sobre el uso de terapia convencional y biológica en pacientes con artritis reumatoide / First Cuban consensus on the use of conventional and biological therapy in patients with rheumatoid arthritis

resumen está disponible en el texto completo

Introduction: The development of recommendations for the treatment of rheumatoid arthritis (RA) in the Cuban context may be one of the ways to achieve better control of this disease. Objective: To reach a consensus and update relevant aspects of conventional and biological RA modifier therapy in Cuba. Methods: 18 specialists from 8 Cuban provinces, experts in RA care, were summoned, according to the years of dedication to the specialty, the conferences on this topic and their publications. The first meeting took place in March 2016 in the provincial hospital of Villa Clara, Cuba, with the participation of all the experts. A review of the literature on conventional and biological therapy previously collected by the participants was developed, and two teams were formed: the first would address everything related to conventional therapy in RA (HRCT) and the other, biological therapy in RA (TBAR). Three questionnaires related to the use of corticosteroids, HRCT and TBAR, were prepared, answered by the participants via email. In a second meeting, held in October 2016 in Havana, the analysis of all the responses provided was carried out. Questions with a response of 90% or more votes were considered as recommendations. Results: The questionnaires were answered by 95% of the participants. 9 recommendations and 1 algorithm were established. The recommendations are as follows: methotrexate is the drug of choice in the treatment of RA after diagnosis; The administration of another conventional drug (DMARDc) (azathioprine, salazosulfapyridine, antimalarials and leflunomide) is recommended in patients with a diagnosis of active RA in whom methotrexate is contraindicated or there is a failure in response - consider the administration of low doses of prednisone or equivalent (<7.5 mg/d) associated with DMARDc in patients with active moderate to severe RA, for the shortest possible time; perform serological control including tests for hepatitis B and C viruses and screening for HIV in all patients diagnosed with RA before starting treatment with DMARDc and biologics; in patients in remission or, at least, with a DAS-28 below 3.2, consideration should be given to withdrawing one of the DMARDs or reducing, to the minimum possible expression, the dose of both disease modifiers; if methotrexate fails, tocilizumab in combination with methotrexate or as monotherapy will be indicated. Conclusions: Aspects related to conventional therapy with methotrexate, azathioprine, salazosulfapyridine, antimalarials and leflunomide were agreed. The value of early diagnosis and immediate initiation of DMARDc therapy and the use of glucocorticoids was analyzed. Treatment with tocilizumab, the only biological available in Cuba against RA, will be administered when there is a failure in the response to conventional therapy and combinations between these drugs. It is recommended to hold educational conferences through the mass media aimed at patientshttp(AU)

Focal adhesion kinase inhibition synergizes with nab-paclitaxel to target pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a very lethal disease, with minimal therapeutic options. Aberrant tyrosine kinase activity influences tumor growth and is regulated by phosphorylation. We investigated phosphorylated kinases as target in PDAC. METHODS: Mass spectrometry-based phosphotyrosine proteomic analysis on PDAC cell lines was used to evaluate active kinases. Pathway analysis and inferred kinase activity analysis was performed to identify novel targets. Subsequently, we investigated targeting of focal adhesion kinase (FAK) in vitro with drug perturbations in combination with chemotherapeutics used against PDAC. Tyrosine phosphoproteomics upon treatment was performed to evaluate signaling. An orthotopic model of PDAC was used to evaluate the combination of defactinib with nab-paclitaxel. RESULTS: PDAC cell lines portrayed high activity of multiple receptor tyrosine kinases to various degree. The non-receptor kinase, FAK, was identified in all cell lines by our phosphotyrosine proteomic screen and pathway analysis. Targeting of this kinase with defactinib validated reduced phosphorylation profiles. Additionally, FAK inhibition had anti-proliferative and anti-migratory effects. Combination with (nab-)paclitaxel had a synergistic effect on cell proliferation in vitro and reduced tumor growth in vivo. CONCLUSIONS: Our study shows high phosphorylation of several oncogenic receptor tyrosine kinases in PDAC cells and validated FAK inhibition as potential synergistic target with Nab-paclitaxel against this devastating disease.

Co-expression analysis of pancreatic cancer proteome reveals biology and prognostic biomarkers.

PURPOSE: Despite extensive biological and clinical studies, including comprehensive genomic and transcriptomic profiling efforts, pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease, with a poor survival and limited therapeutic options. The goal of this study was to assess co-expressed PDAC proteins and their associations with biological pathways and clinical parameters. METHODS: Correlation network analysis is emerging as a powerful approach to infer tumor biology from omics data and to prioritize candidate genes as biomarkers or drug targets. In this study, we applied a weighted gene co-expression network analysis (WGCNA) to the proteome of 20 surgically resected PDAC specimens (PXD015744) and confirmed its clinical value in 82 independent primary cases. RESULTS: Using WGCNA, we obtained twelve co-expressed clusters with a distinct biology. Notably, we found that one module enriched for metabolic processes and epithelial-mesenchymal-transition (EMT) was significantly associated with overall survival (p = 0.01) and disease-free survival (p = 0.03). The prognostic value of three proteins (SPTBN1, KHSRP and PYGL) belonging to this module was confirmed using immunohistochemistry in a cohort of 82 independent resected patients. Risk score evaluation of the prognostic signature confirmed its association with overall survival in multivariate analyses. Finally, immunofluorescence analysis confirmed co-expression of SPTBN1 and KHSRP in Hs766t PDAC cells. CONCLUSIONS: Our WGCNA analysis revealed a PDAC module enriched for metabolic and EMT-associated processes. In addition, we found that three of the proteins involved were associated with PDAC survival.

Improving clinical management of colon cancer through CONNECTION, a nation-wide colon cancer registry and stratification effort (CONNECTION II trial): rationale and protocol of a single arm intervention study.

BACKGROUND: It is estimated that around 15-30% of patients with early stage colon cancer benefit from adjuvant chemotherapy. We are currently not capable of upfront selection of patients who benefit from chemotherapy, which indicates the need for additional predictive markers for response to chemotherapy. It has been shown that the consensus molecular subtypes (CMSs), defined by RNA-profiling, have prognostic and/or predictive value. Due to postoperative timing of chemotherapy in current guidelines, tumor response to chemotherapy per CMS is not known, which makes the differentiation between the prognostic and predictive value impossible. Therefore, we propose to assess the tumor response per CMS in the neoadjuvant chemotherapy setting. This will provide us with clear data on the predictive value for chemotherapy response of the CMSs. METHODS: In this prospective, single arm, multicenter intervention study, 262 patients with resectable microsatellite stable cT3-4NxM0 colon cancer will be treated with two courses of neoadjuvant and two courses of adjuvant capecitabine and oxaliplatin. The primary endpoint is the pathological tumor response to neoadjuvant chemotherapy per CMS. Secondary endpoints are radiological tumor response, the prognostic value of these responses for recurrence free survival and overall survival and the differences in CMS classification of the same tumor before and after neoadjuvant chemotherapy. The study is scheduled to be performed in 8-10 Dutch hospitals. The first patient was included in February 2020. DISCUSSION: Patient selection for adjuvant chemotherapy in early stage colon cancer is far from optimal. The CMS classification is a promising new biomarker, but a solid chemotherapy response assessment per subtype is lacking. In this study we will investigate whether CMS classification can be of added value in clinical decision making by analyzing the predictive value for chemotherapy response. This study can provide the results necessary to proceed to future studies in which (neo) adjuvant chemotherapy may be withhold in patients with a specific CMS subtype, who show no benefit from chemotherapy and for whom possible new treatments can be investigated. TRIAL REGISTRATION: This study has been registered in the Netherlands Trial Register (NL8177) at 11-26-2019, https://www.trialregister.nl/trial/8177 . The study has been approved by the medical ethics committee Utrecht (MEC18/712).

Terapia vestibular en vestibulopatía bilateral por gentamicina: reporte de un caso y revisión de la literatura / Vestibular therapy in a case of gentamicin-induced vestibulopathy: case report and literature revision

La vestibulopatía bilateral es poco frecuente, se caracteriza principalmente por inestabilidad al caminar o al estar de pie, visión borrosa inducida por el movimiento u oscilopsia al caminar o al realizar movimientos rápidos de la cabeza o del cuerpo, empeoramiento de la estabilidad en la oscuridad o terrenos irregulares, reducción de los síntomas al estar en condiciones estáticas, ganancia del reflejo vestíbulo-ocular angular reducida de forma bilateral, entre otros. Existen múltiples causas. Dentro de las causas identificables, se describen principalmente medicamentos ototóxicos, meningitis y enfermedad de Ménière. Se presenta el caso de una paciente de 64 años diagnosticada con vestibulopatía bilateral posterior a tratamiento intramuscular con gentamicina por sobreinfección bacteriana cutánea de las manos. La evaluación vestibular complementada con videonistagmografía y prueba de impulso cefálico asistida por video confirman el diagnóstico y se inicia tratamiento con rehabilitación vestibular enfocada en promover la compensación central a través de estrategias de sustitución principalmente; además de habituación y adaptación vestibular, favoreciendo la estabilización de la mirada, mantención del equilibrio, control postural, marcha y reducción de los síntomas.

Bilateral vestibulopathy is infrequent, and it is characterized mostly by unstable walking or when standing, blurred vision induced by movement, or oscillopsia when walking or performing fast movements; worsening of the stability in darkness or uneven ground, but with lack of symptoms in static conditions. Other symptoms may include bilateral reduction of the oculo-vestibular reflex. Among the identifiable causes, there is the use of ototoxic medication, meningitis, Ménière's disease, although it can be idiopathic or have a neurological cause. We hereby describe the case of a 64-year-old woman, diagnosed with bilateral vestibulopathy secondary to intramuscular treatment with gentamicin due to a bacterial hand infection. Vestibular assessment was complemented with video-nystagmography and video head impulse test which confirmed the diagnosis, and therapy was started with vestibular rehabilitation focused on promoting central compensation mainly, through substitution strategies. Also, habituation exercise and vestibular adaptation strategies were used, thus promoting sight stabilization, balance maintenance, postural control, walking, and reduction of the symptoms.

[Adverse obstetric and perinatal outcome with in vitro fertilization technology: A French nationwide population-based study]. / Risques de morbidité maternelle et périnatale en fécondation in vitro : une étude nationale de cohorte française.

OBJECTIVES: The objective of this study was to quantify the risk of maternal and perinatal morbidity with in vitro fertilization (IVF) technology compared to non-IVF pregnancies in a recent French national cohort. METHOD: The data was extracted from the hospital information data system, including all pregnancies with a delivery from 2013 to 2016. The risks of preterm birth, maternal morbidity (venous and arterial thrombosis, gestational diabetes, vascular disorders, placenta previa, placenta abruption), hypotrophy and congenital malformation were compared in both groups in univariate and multivariate analysis after adjustment on the characteristics of women (age, parity, obesity, tobacco dependence, history of diabetes or high blood pressure), multiple deliveries and sex of children. RESULTS: In all, 2,875,662 pregnancies and 2,922,712 births were analyzed, of which 49,224 were derived from IVF (1.7%). In multivariate analysis, all risks were significantly higher in IVF: premature deliveries (ORajusted=1.28; CI95%=1.24-1.32), maternal morbidity (ORajusted=1.24; CI95%=1.21-2.28), (mainly for thrombosis venous, placenta previa and placenta abruption). The risks of hypotrophy (ORajusted=1.13; CI95%=1.10-1.16) and congenital malformations (ORajusted=1.11; CI95%=1.05-1.17) were slightly increased. CONCLUSION: The results of this study on a large cohort of recent births in France confirm that there was an increased risk of maternal and perinatal morbidities in IVF. These risks were similar to those published in the international literature. This study is the starting point for a forthcoming surveillance.

Role of boost radiotherapy for local control of pure ductal carcinoma in situ after breast-conserving surgery: a multicenter, retrospective study of 622 patients.

PURPOSE: To evaluate the effect of boost radiotherapy on ipsilateral breast tumor recurrence (IBTR) for ductal carcinoma in situ (DCIS) after breast-conserving surgery and whole breast radiotherapy (WBRT) with or without boost. METHODS AND MATERIALS: Retrospective, multicentre study of 622 patients (624 tumors) diagnosed with pure DCIS from 1993-2011. RESULTS: Most tumors (377/624; 60.4%) received a boost. At a median follow-up of 8.8 years, IBTR occurred in 64 cases (10.3%). A higher percentage of patients with risk factors for IBTR received a boost (p < 0.05). Boost was not associated with lower rates of IBTR than WBRT alone (HR 0.75, 95% CI 0.42-1.35). On the univariate analyses, IBTR was significantly associated with tumor size (11-20 mm, HR 2.32, 95% CI 1.27-4.24; and > 20 mm, HR 2.10, 95% CI 1.14-3.88), re-excision (HR 1.76, 95% CI 1.04-2.96), and tamoxifen (HR 2.03, 95% CI 1.12-3.70). Boost dose > 16 Gy had a protective effect (HR 0.39, 95% CI 0.187-0.824). Multivariate analyses confirmed the independent associations between IBTR and 11-20 mm (p = 0.02) and > 20 mm (p = 0.009) tumours, and re-excision (p = 0.006). On the margin-stratified multivariate analysis, tamoxifen was a poor prognostic factor in the close/positive margin subgroup (HR 4.28 95% CI 1.23-14.88), while the highest boost dose ( > 16 Gy) had a significant positive effect (HR 0.34, 95% CI 0.13-0.86) in the negative margin subgroup. CONCLUSIONS: Radiotherapy boost did not improve the risk of IBTR. Boost radiotherapy was more common in patients with high-risk disease. Tumor size and re-excision were significant independent prognostic factors.

[Reversible cerebral vasoconstriction syndrome associated with anastrozole: an unusual cause of high impact]. / Sindrome de vasoconstriccion cerebral reversible asociado a anastrozol: una causa inusual de alto impacto.

INTRODUCTION: Reversible cerebral vasoconstriction syndrome (RCVS) is a low incidence disability with a multifactorial etiology and a wide array of symptoms. The main symptom is a thunderclap headache, accompanied sometimes with various neurological deficits that can lead to death. RCVS is usually diagnosed through radiological imaging technology. The treatment includes adopting general measures of monitoring, symptomatic management, identifying the etiology and acting on it to avoid recurrence. CASE REPORT: A 71-year-old woman with a history of breast cancer originally treated with tamoxifen. Due to urticaria, the anastrozole management was staggered. She was admitted for aphasia, drowsiness and a thunderclap headache. The patient reported a similar event two weeks prior admission. In brain resonance, there was evidence of small sub-arachnoidal haemorrhage (SAH) of the left parietal temporal convexity and cerebral angiography. As well as documented vasospasm in the posterior parietal region confirming the diagnosis of RCVS plus SAH. During the stay, she presented three events with the same characteristics, requiring intensive monitoring and two therapeutic panangiographies with intra-arterial nimodipine with subsequent resolution of the vessel spasm. The patient remains asymptomatic six months later. CONCLUSION: RCVS is difficult to diagnose given its wide array of symptoms and multifactorial etiology. In this case, RCVS plus SAH is associated with the use of anastrozole. So far there are no reported cases of aromatase inhibitors associated with this pathology and should be reported in the literature for pharmacovigilance.

TITLE: Sindrome de vasoconstriccion cerebral reversible asociado a anastrozol: una causa inusual de alto impacto.Introduccion. El sindrome de vasoconstriccion cerebral reversible (SVCR) es una entidad de baja incidencia, de etiologia multifactorial y amplio espectro de presentacion. El principal sintoma es la cefalea de tipo trueno. Puede estar acompañado de focalizacion neurologica y cursar con desenlaces clinicos variable que incluso pueden llevar a la muerte. El diagnostico es clinico e imaginologico, y el tratamiento incluye adoptar medidas generales de monitorizacion, manejo sintomatico, identificar la etiologia y actuar sobre ella para evitar recurrencia. Caso clinico. Mujer de 71 años con antecedente de cancer de seno, tratada inicialmente con tamoxifeno; por presentar urticaria, se escalono tratamiento con anastrozol. Ingreso por cefalea de tipo trueno, afasia anterior y somnolencia. La paciente refirio un evento similar una semana antes del ingreso. En la resonancia magnetica cerebral evidencio una hemorragia subaracnoidea (HSA) pequeña de la convexidad temporoparietal izquierda, y la panangiografia documento vasoespasmo en la region parietal posterior, lo que confirmo el diagnostico de SVCR mas HSA. Durante el ingreso presento tres eventos de iguales caracteristicas, que requirieron monitorizacion intensiva y dos panangiografias terapeuticas con nimodipino intraarterial, con posterior resolucion del vasoespasmo. Permanece asintomatica seis meses despues. Conclusion. El SVCR constituye un reto diagnostico dada su presentacion variable y su etiologia multifactorial. En este caso, el SVCR mas HSA esta asociado al uso de anastrozol. Hasta el momento no hay casos descritos de inhibidores de la aromatasa asociados a esta patologia, que debe comunicarse para su farmacovigilancia.

Morbidly Obese Patients Awaiting Liver Transplantation-Sleeve Gastrectomy: Safety and Efficacy From a Liver Transplant Unit Experience.

BACKGROUND: The prevalence of obesity has increased dramatically, even in the population awaiting a liver transplantation. Despite their associated complications, we cannot consider morbid obesity any longer as an absolute contraindication to liver transplantation. Dietary approaches alone are usually completely ineffective. Bariatric surgery is the gold-standard treatment for morbid obesity and can be performed before, during, or after transplantation. MATERIALS AND METHODS: At our Liver Transplantation Unit, a single surgeon performed a sleeve gastrectomy in 8 patients with liver cirrhosis due to nonalcoholic steatohepatitis, alcohol, or HCV. The Child score was A in 6 patients and B in the remaining 2 patients. Two of our patients had portal hypertension with mild esophageal varices. The procedure was performed laparoscopically in 7 cases (87.5%); in the other case, it was performed by open approach due to portal hypertension and according to patient preferences. RESULTS: Patients showed no postoperative morbidity or mortality. The mean postoperative body mass index of our patients was 37.4, 33.3, and 30.3 kg/m2 at 3, 6, and 12 months after surgery, respectively. The mean percentage excess weight loss of our patients was 42.9%, 62.2%, and 76.3% at 3, 6, and 12 months. Two of the patients have already undergone a successful liver transplant. CONCLUSION: Bariatric surgery in selected patients with compensated cirrhosis and without significative portal hypertension is reasonable. There are not clear guidelines on the use of bariatric surgery in patients with cirrhosis. In our experience, the sleeve gastrectomy is safe and effective in the treatment of patients with compensated cirrhosis; in a short time, the sleeve gastrectomy can improve candidacy in morbidly obese patients awaiting transplantation.

Long-term outcomes after prophylactic use of onlay mesh in midline laparotomy.

BACKGROUND: The prevalence of incisional hernias (IHs) is still high after midline laparotomy (ML). There is an increasing body of evidence that prophylactic mesh placement (PMP) can be safe and efficient in the short-term outcomes, but there still are some concerns about the potential long-term complications of these meshes. This study describes our long-term PMP experience. METHODS: Observational and prospective study including all patients undergoing the use of prophylactic onlay large-pore polypropylene meshes for the closure of ML since 2008 to 2014. Outcome measures included demographics, perioperative details, wound complications, recurrences, reoperations and chronic complications. RESULTS: A cohort of 172 patients was analysed: 75% elective surgery, 25% emergency cases. Mean age was 68 years with mean body mass index (BMI) of 28.6 kg/m2. Wound classification: 6.4% clean; 85% clean-contaminated; 1.2% contaminated and 8.1% dirty. Follow-up of patients was up to 8 years (mean: 5 ± 1.6). Two meshes were removed due to chronic infection in first six postoperative months. Of the 13 patients (9.02%) who developed IH, 5 of them have been reoperated for IH repair without any difficulty related to previous mesh. During follow-up, 8 patients have been reoperated for other reasons and the integrity of abdominal wall was also checked. After the comparative study, higher BMI and emergency surgery were still risk factors for IH despite PMP. CONCLUSIONS: In our setting, the use of polypropylene prophylactic meshes in MLs is safe, efficient and durable.

Profile of BAFF and its receptors' expression in lupus nephritis is associated with pathological classes.

Background/Objective B-cell activating factor (BAFF) plays an important role in the pathogenesis of systemic lupus erythematosus. However, the role of BAFF in lupus nephritis (LN) is not understood. Our aim was to evaluate the expression of BAFF and its three receptors in renal biopsy samples from patients with LN and investigate a relationship with pathological class. Methods We conducted a prospective descriptive study (2011-2014) on 52 kidney biopsy samples from patients with LN. Immunohistochemistry for BAFF, its receptors (transmembrane activator and calcium modulator and cyclophilin ligand interaction (TACI), protein maturation of B cells (BCMA), and BAFF-receptor (BAFF-R)), and CD20 expression was performed. Samples were scored according to the percentage of cells with positive expression. Results In class II LN, BAFF-R and TACI were not expressed, whereas BCMA and BAFF were lowly expressed in the interstitial inflammatory infiltrates. Proliferative class III/IV had elevated BAFF expression in the glomeruli, and TACI was expressed in interstitial inflammatory infiltrates and the glomeruli. Interestingly, the class IV cases with vasculopathy ( n = 4) had endothelial BAFF expression, which was not visible in thrombotic microangiopathy ( n = 4). Class V was characterized by low BAFF expression in interstitial inflammatory infiltrates and by BAFF, TACI, and BCMA expression in the glomeruli. BAFF expression was associated with inflammatory scores and CD20 positive infiltrates, mainly in class IV. Conclusions Expression patterns of BAFF and its receptors differ according to LN class. Our study provides evidence that BAFF could be used as a routine marker in LN biopsies and to determine which patients will benefit from anti-BAFF therapy.

¿Tienen algún rol los cannabinoides en el control del glaucoma? / Do cannabinoids play a role in the control of glaucoma?

INTRODUCCIÓN: El uso de cannabinoides en diversas condiciones clínicas es hoy un tema de debate. Se ha planteado su uso para el control del glaucoma. Sin embargo, existe controversia sobre su real efectividad y seguridad. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos cinco revisiones sistemáticas que en conjunto incluyen 3 estudios primarios, todos correspondientes a ensayos aleatorizados. Concluimos que, si bien los cannabinoides podrían disminuir la presión intraocular, lo hacen de forma transitoria y se asocian a efectos adversos frecuentes.

INTRODUCTION: The use of cannabinoids in diverse clinical conditions is today a subject of debate. Its use has been proposed for the control of glaucoma. However, there is controversy about its real effectiveness and safety. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified five systematic reviews including three studies overall, all of them randomized controlled trials. We concluded that although cannabinoids could decrease intraocular pressure, the effect would be transient and associated with frequent adverse effects.

From Waldenström's macroglobulinemia to aggressive diffuse large B-cell lymphoma: a whole-exome analysis of abnormalities leading to transformation.

Transformation of Waldenström's macroglobulinemia (WM) to diffuse large B-cell lymphoma (DLBCL) occurs in up to 10% of patients and is associated with an adverse outcome. Here we performed the first whole-exome sequencing study of WM patients who evolved to DLBCL and report the genetic alterations that may drive this process. Our results demonstrate that transformation depends on the frequency and specificity of acquired variants, rather than on the duration of its evolution. We did not find a common pattern of mutations at diagnosis or transformation; however, there were certain abnormalities that were present in a high proportion of clonal tumor cells and conserved during this transition, suggesting that they have a key role as early drivers. In addition, recurrent mutations gained in some genes at transformation (for example, PIM1, FRYL and HNF1B) represent cooperating events in the selection of the clones responsible for disease progression. Detailed comparison reveals the gene abnormalities at diagnosis and transformation to be consistent with a branching model of evolution. Finally, the frequent mutation observed in the CD79B gene in this specific subset of patients implies that it is a potential biomarker predicting transformation in WM.