Heat-killed Mycobacterium tuberculosis induces trained immunity in vitro and in vivo administered systemically or intranasally.

Trained immunity (TI) represents a memory-like process of innate immune cells. TI can be initiated with various compounds such as fungal ß-glucan or the tuberculosis vaccine, Bacillus Calmette-Guérin. Nevertheless, considering the clinical applications of harnessing TI against infections and cancer, there is a growing need for new, simple, and easy-to-use TI inducers. Here, we demonstrate that heat-killed Mycobacterium tuberculosis (HKMtb) induces TI both in vitro and in vivo. In human monocytes, this effect represents a truly trained process, as HKMtb confers boosted inflammatory responses against various heterologous challenges, such as lipopolysaccharide (Toll-like receptor [TLR] 4 ligand) and R848 (TLR7/8 ligand). Mechanistically, HKMtb-induced TI relies on epigenetic mechanisms in a Syk/HIF-1α-dependent manner. In vivo, HKMtb induced TI when administered both systemically and intranasally, with the latter generating a more robust TI response. Summarizing, our research has demonstrated that HKMtb has the potential to act as a mucosal immunotherapy that can successfully induce trained responses.

The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2.

Chemotherapy often generates intratumoral senescent cancer cells that strongly modify the tumor microenvironment, favoring immunosuppression and tumor growth. We discovered, through an unbiased proteomics screen, that the immune checkpoint inhibitor programmed cell death 1 ligand 2 (PD-L2) is highly upregulated upon induction of senescence in different types of cancer cells. PD-L2 is not required for cells to undergo senescence, but it is critical for senescent cells to evade the immune system and persist intratumorally. Indeed, after chemotherapy, PD-L2-deficient senescent cancer cells are rapidly eliminated and tumors do not produce the senescence-associated chemokines CXCL1 and CXCL2. Accordingly, PD-L2-deficient pancreatic tumors fail to recruit myeloid-derived suppressor cells and undergo regression driven by CD8 T cells after chemotherapy. Finally, antibody-mediated blockade of PD-L2 strongly synergizes with chemotherapy causing remission of mammary tumors in mice. The combination of chemotherapy with anti-PD-L2 provides a therapeutic strategy that exploits vulnerabilities arising from therapy-induced senescence.

Spontaneously ruptured hepatocellular carcinoma on non-cirrhotic liver: A prospective case series.

BACKGROUND AND AIMS: Spontaneous ruptured hepatocellular carcinoma is an uncommon complication, and there are scarce data about non-cirrhotic patients. Tumor treatment is not standardized and the risk of peritoneal dissemination is unclear. AIM: we analyzed the treatment and survival in patients with rHCC on non-cirrhotic liver. METHODS: One hundred and forty-one non-cirrhotic patients with hepatocellular carcinoma diagnosed by histology were included in a multicenter prospective registry (2018-2022). Seven of them (5%) presented with hemoperitoneum due to spontaneous rupture. RESULTS: Liver disease was associated in three patients (42.9%). A single nodule was detected in three cases (42.9%). One patient had vascular invasion and none extrahepatic spread. Initial hemostatic therapy and sequential treatment was individualized. Patients with single nodule were treated: resection (one case) with recurrence at 4 months treated with TACE and sorafenib. TACE/TAE followed by surgery (two cases) one in remission 43 months later, the other had liver recurrence at 18 months and was transplanted. Patients with multiple lesions were treated: TAE/emergency surgery and subsequent systemic therapy (two cases), one received lenvatinib (1-year survival) and the other sorafenib (5-month survival). TAE and surgery with subsequent systemic therapy (one case). Initial hemostatic surgery, dying on admission (one case). No patient developed intraperitoneal metastasis. All patients with multiple lesions died by tumor. The 3-year survival rate was 42.9%. CONCLUSIONS: Initial hemostasis was achieved in all patients by TAE/TACE or surgery. Subsequent treatment was individualized, based on tumor characteristics, regardless of rupture. Long-time remission could be achieved in single nodule patients.

Thiosulfinate-Enriched Allium sativum Extract Exhibits Differential Effects between Healthy and Sepsis Patients: The Implication of HIF-1α.

Garlic (Allium sativum) has historically been associated with antioxidant, immunomodulatory, and microbiocidal properties, mainly due to its richness in thiosulfates and sulfur-containing phytoconstituents. Sepsis patients could benefit from these properties because it involves both inflammatory and refractory processes. We evaluated the effects of thiosulfinate-enriched Allium sativum extract (TASE) on the immune response to bacterial lipopolysaccharide (LPS) by monocytes from healthy volunteers (HVs) and patients with sepsis. We also explored the TASE effects in HIF-1α, described as the key transcription factor leading to endotoxin tolerance in sepsis monocytes through IRAK-M expression. Our results showed TASE reduced the LPS-triggered reactive oxygen species (ROS) production in monocytes from both patients with sepsis and HVs. Moreover, this extract significantly reduced tumor necrosis factor (TNF)-α, interleukin-1ß, and interleukin-6 production in LPS-stimulated monocytes from HVs. However, TASE enhanced the inflammatory response in monocytes from patients with sepsis along with increased expression of human leukocyte antigen-DR. Curiously, these dual effects of TASE on immune response were also found when the HV cohort was divided into low- and high-LPS responders. Although TASE enhanced TNFα production in the LPS-low responders, it decreased the inflammatory response in the LPS-high responders. Furthermore, TASE decreased the HIF-1α pathway-associated genes IRAK-M, VEGFA and PD-L1 in sepsis cells, suggesting HIF-1α inhibition by TASE leads to higher cytokine production in these cells as a consequence of IRAK-M downregulation. The suppression of this pathway by TASE was confirmed in vitro with the prolyl hydroxylase inhibitor dimethyloxalylglycine. Our data revealed TASE's dual effect on monocyte response according to status/phenotype and suggested the HIF-1α suppression as the possible underlying mechanism.

Bromelain-based enzymatic burn debridement: Spanish multidisciplinary consensus.

Background: Bromelain-based enzymatic debridement is gaining increased interest from burn specialists in the last few years. The objective of this manuscript is to update the previous, first Spanish consensus document from 2017 (Martínez-Méndez et al. 43:193-202, 2017), on the use of enzymatic debridement with NexoBrid® in burn injuries, adding the clinical experience of a larger panel of experts, integrating plastic surgeons, intensivists, and anesthesiologists. Methods: A consensus guideline was established by following a modified Delphi methodology of a 38-topic survey in two rounds of participation. Items were grouped in six domains: general indication, indication in critical patients, pain management, conditions for NexoBrid® application, NexoBrid® application technique, and post-debridement wound care. Results: In the first round, experts established consensus (strongly agree or agree) on 13 of the 38 statements. After the second round, a consensus was reached on 24 of the 25 remaining statements (97.2%). Conclusions: The present updated consensus document provides recommendations on the use of bromelain-based enzymatic debridement NexoBrid®, integrating the extensive clinical experience of plastic surgeons, intensivists, and anesthesiologists in Spain. Further clinical trials and studies are required to corroborate, modify, or fine tune the current statements.

Therapy-Induced Senescence Enhances the Efficacy of HER2-Targeted Antibody-Drug Conjugates in Breast Cancer.

Antibody-drug conjugates (ADC) are antineoplastic agents recently introduced into the antitumor arsenal. T-DM1, a trastuzumab-based ADC that relies on lysosomal processing to release the payload, is approved for HER2-positive breast cancer. Next-generation ADCs targeting HER2, such as [vic-]trastuzumab duocarmazine (SYD985), bear linkers cleavable by lysosomal proteases and membrane-permeable drugs, mediating a bystander effect by which neighboring antigen-negative cells are eliminated. Many antitumor therapies, like DNA-damaging agents or CDK4/6 inhibitors, can induce senescence, a cellular state characterized by stable cell-cycle arrest. Another hallmark of cellular senescence is the enlargement of the lysosomal compartment. Given the relevance of the lysosome to the mechanism of action of ADCs, we hypothesized that therapies that induce senescence would potentiate the efficacy of HER2-targeting ADCs. Treatment with the DNA-damaging agent doxorubicin and CDK4/6 inhibitor induced lysosomal enlargement and senescence in several breast cancer cell lines. While senescence-inducing drugs did not increase the cytotoxic effect of ADCs on target cells, the bystander effect was enhanced when HER2-negative cells were cocultured with HER2-low cells. Knockdown experiments demonstrated the importance of cathepsin B in the enhanced bystander effect, suggesting that cathepsin B mediates linker cleavage. In breast cancer patient-derived xenografts, a combination treatment of CDK4/6 inhibitor and SYD985 showed improved antitumor effects over either treatment alone. These data support the strategy of combining next-generation ADCs targeting HER2 with senescence-inducing therapies for tumors with heterogenous and low HER2 expression. SIGNIFICANCE: Combining ADCs against HER2-positive breast cancers with therapies that induce cellular senescence may improve their therapeutic efficacy by facilitating a bystander effect against antigen-negative tumor cells.

Dectin-1 Signaling Update: New Perspectives for Trained Immunity.

The C-type lectin receptor Dectin-1 was originally described as the ß-glucan receptor expressed in myeloid cells, with crucial functions in antifungal responses. However, over time, different ligands both of microbial-derived and endogenous origin have been shown to be recognized by Dectin-1. The outcomes of this recognition are diverse, including pro-inflammatory responses such as cytokine production, reactive oxygen species generation and phagocytosis. Nonetheless, tolerant responses have been also attributed to Dectin-1, depending on the specific ligand engaged. Dectin-1 recognition of their ligands triggers a plethora of downstream signaling pathways, with complex interrelationships. These signaling routes can be modulated by diverse factors such as phosphatases or tetraspanins, resulting either in pro-inflammatory or regulatory responses. Since its first depiction, Dectin-1 has recently gained a renewed attention due to its role in the induction of trained immunity. This process of long-term memory of innate immune cells can be triggered by ß-glucans, and Dectin-1 is crucial for its initiation. The main signaling pathways involved in this process have been described, although the understanding of the above-mentioned complexity in the ß-glucan-induced trained immunity is still scarce. In here, we have reviewed and updated all these factors related to the biology of Dectin-1, highlighting the gaps that deserve further research. We believe on the relevance to fully understand how this receptor works, and therefore, how we could harness it in different pathological conditions as diverse as fungal infections, autoimmunity, or cancer.

Characteristics and survival of hepatocellular carcinoma in non-cirrhotic liver.

INTRODUCTION: the characteristics, screening, and survival of hepatocellular carcinoma (HCC) for patients without cirrhosis have not been fully studied. METHODS: A retrospective cohort study was performed in non-cirrhotic patients with histological HCC, between January 2004 and October 2018. Their characteristics, treatment, follow-up and overall survival were described. RESULTS: 25 of the 332 patients with HCC met the inclusion criteria (7.5%), 76% were males and the median age was 69.9 years. The main etiology of liver disease was the hepatitis B virus (HBV) (32%), followed by non-alcoholic steatohepatitis (NASH) (20%). Liver fibrosis was mild (0-1) in 44% of cases. The nodule was diagnosed by ultrasonography in 32% of cases, 60% were found incidentally and 8% due to clinical symptoms. The Barcelona Clinic Liver Cancer (BCLC) staging was 0 in 4% of cases, A in 88%, B in 4% and C in 4%. The main initial treatment was surgical resection (76%) and 8% refused to be treated. Percutaneous ethanol injection, chemoembolization, sorafenib and palliative care were each performed in 4% of cases. There were some complications in 21% of patients treated with surgery, half of them were severe. The median follow-up was 22.2 (2.9-150.6) months and 56% were in remission and the median overall survival was 57.4 ± 29.8 months. The overall cumulative survival at 1, 3 and 5 years was 84%, 61.6% and 47.9%, respectively. CONCLUSION: 7.5% of HCC presented without cirrhosis and almost half of patients had mild fibrosis. HBV was the main cause of HCC, followed by NASH. The most frequent BCLC stage at diagnosis was early stage and surgery was the most common treatment. Overall cumulative survival at 5 years was almost 50%.

[Epidemiology of invasive pneumococcal disease in Tarragona, Spain, 2012-2015: incidence, lethality and serotype-coverage for distinct antipneumococcal vaccine formulations]. / Epidemiología de la enfermedad neumocócica invasiva en la región de Tarragona, 2012-2015: Incidencia, letalidad y cobertura de serotipos para las distintas formulaciones vacunales antineumocócicas.

OBJECTIVE: Nowadays, after licensure of the second generation new pneumococcal conjugate vaccines (PCV10/PCV13). The epidemiology of the pneumococcal disease must be re-evaluated. The present study described incidence, lethality and serotype distribution of invasive pneumococcal disease (IPD) in the general population of Tarragona's region (Spain) after licensure of these vaccines. METHODS: Retrospective study that included all cases of IPD (pneumococcus isolated in sterile sites) diagnosed among all-age individuals in the Spanish region of Tarragona (Tarragonés, Alt Camp and Baix Penedés counties) from 01/01/2012 to 31/12/2015. Incidence and lethality rates were estimated by age strata and globally. Similarly, it was determined the prevalence of IPD cases caused by serotypes included in the distinct formulations of multivalent conjugate vaccines (pcv7), PCV10 and PCV13) or 23-valent polysaccharide vaccine (PPV23). RESULTS: A total of 171 IPD cases were observed, which means a global incidence (per 100,000 persons-year) of 10.82 (7.86 in ≤14 years, 5.94 in 15-64 years and 36.46 in ≥65 years; p<0.001). Overall lethality rate was 6.8% (none in children, 9,3% in people 15-64 years and 6.9% in people ≥65 years). A serotype was identified in 132 (77.2%) of the 171 studied samples. Serotype-vaccine coverages (cases due to vaccine-type serotypes) were 14.4%, 26.5%, 42.4% and 78.8% for the PCV7, PCV10, PCV13 and PPV23, respectively (p<0.001). CONCLUSIONS: Incidence and lethality of IPD were intermediate-low in the region of Tarragona throughout 2012-2015. During this period, Serotype- vaccine coverage was almost double for the 23-valent than for the 13-valent vaccine.

OBJETIVO: En la actualidad, tras la comercialización de las nuevas vacunas neumocócicas conjugadas de segunda generación (VNC10/VNC13), la epidemiología de la enfermedad neumocócica debe ser reevaluada. El presente estudio tuvo como objetivo describir la incidencia, letalidad y distribución serotípica de la enfermedad neumocócica invasiva (ENI) en la población general del área de Tarragona durante el cuatrienio posterior a la introducción de estas vacunas. METODOS: Estudio observacional retrospectivo que incluyó todos los casos de ENI (Streptococcus pneumoniae aislado en sangre, líquido cefalorraquídeo, líquido pleural/articular/peritoneal o muestras de tejidos profundos obtenidas de forma estéril mediante punción-aspiración o biopsia) diagnosticados en el área de Tarragona (comarcas del Tarragonés, Alt Camp y Baix Penedés) entre 01/01/2012 y 31/12/2015. Se estimaron tasas de incidencia y letalidad (globalmente y por estratos etarios) y se determinó la prevalencia de casos causados por serotipos incluidos en las distintas formulaciones de vacunas antineumocócicas conjugadas heptavalente (VNC7), decavalente (VNC10), tridecavalente (VNC13) y polisacárida tricosavalente (VNP23). RESULTADOS: Se observaron 171 casos de ENI, lo que representó una incidencia (por 100.000 personas-año) de 10,82 (7,86 en ≤14 años, 5,94 en 15-64 años y 36,46 en ≥65 años; p<0,001). La letalidad fue del 6,8% (ninguna en niños, 9,3% en 15-64 años y 6,9% en personas ≥65 años; p<0,001). El serotipo responsable fue identificado en 132 (77,2%) de las 171 muestras estudiadas. La cobertura serotípica (casos causados por serotipos vacunales) fue del 14,4%, 26,5%, 42,4% y 78,8% para la VNC7, VNC10, VNC13 y VNP23, respectivamente (p<0,001). CONCLUSIONES: Durante el periodo 2012-2015 la incidencia y letalidad por ENI fue intermedia-baja en el área de Tarragona, destacando que la cobertura serotípica fue casi doble para la vacuna 23-valente que para la 13-valente.

Sleep quality and psychosocial characteristics of patients with painful post-traumatic trigeminal neuropathies.

OBJECTIVES: The aim of this study was to explore how pain and psychological distress influence the sleep quality of patients with painful post-traumatic trigeminal neuropathy (PPTN). STUDY DESIGN: Thirty-two patients with a diagnosis of PPTN according to the International Classification for Headache Disorders of the International Headache Society were enrolled. All patients completed a number of questionnaires that examined sleep quality, psychological distress, and quality of life. RESULTS: The global Pittsburg Sleep Quality Index (PSQI) score was "5" or greater in 75% of the patients. Additionally, the Symptom Check List-90-Revised (SCL-90-R) global severity index (GSI) revealed that 71.9% of the study sample reported values of psychological distress over the level of clinical significance. Sleep quality was analyzed through a linear regression model of global PSQI (dependent variable) that included gender, age, pain intensity, and pain duration (independent variables). This model revealed a significant positive association between the PSQI global score and the SCL-90-R GSI that was independent of age, gender, pain intensity, and duration. CONCLUSIONS: Patients with PPTN present higher levels of sleep disturbance and psychological distress compared with the general population. Sleep quality disturbances and levels of psychological distress are strongly associated and seem to be independent of age, gender, medication use, pain intensity and duration.

Antibiotic prescription for the prevention and treatment of postoperative complications after routine dental implant placement. A cross-sectional study performed in Spain.

BACKGROUND: As there are no established guidelines for antibiotic prescription after dental implant placement a study was made to determine the current prescribing habits of several groups of practitioners regarding antibiotics to prevent and/or treat postoperative complications - early failures and infections - in relation to routine dental implant placement. MATERIAL AND METHODS: An electronic survey was sent to postgraduate students and professionals with experience in routine dental implant placement who practice in Spain. The questions asked were related to whether antibiotics were routinely prescribed either pre- or postoperatively to prevent and/or treat postoperative complications during routine dental implant placement, and, if so, what antibiotics, dosage, frequency, and duration were used. Descriptive and bivariate analyses of the data were performed. RESULTS: Two hundred and forty-seven responses were obtained. Preventively, 17 respondents (6.9%) prescribed antibiotics only preoperatively (95% confidence interval (CI): 3.7 to 10.0%), 100 (40.5%) preferred to give them exclusively during the postoperative period (95%CI 34.4 to 46.6%) and 94 practitioners (38.1%) prescribed antibiotics both pre- and post-operatively (95%CI 32.0 to 44.1%). The most common preoperative regime was amoxicillin 2 g given orally 1 hour before the procedure (21.6%, n = 24) following amoxicillin 750 mg given orally 1 day prior to surgery (21.6%, n = 24). The most common routine postoperative regime was amoxicillin 750 mg given orally for 7 days (34.0%, n = 66). To treat postoperative infections during the osseointegration period, 233 respondents (93.2%) prescribed antibiotics (95%CI 91.4 to 97.2%). The most common regime used was amoxicillin and potassium clavulanate 875/125 mg, given orally for 7 days (51.9%, n = 121). CONCLUSIONS: There is no consensus among dental clinicians regarding antibiotic use during routine dental implant placement to prevent postoperative complications and/or early failures. Moreover, the most commonly-prescribed regimes differ from that recommend in the latest published studies. Key words:Antibiotics, dental implants, oral implantology, complications, postoperative wound infection, early failure.

Prevalence of neuropathic pain and sensory alterations after dental implant placement in a university-based oral surgery department: A retrospective cohort study.

OBJECTIVE: To determine the prevalence and the clinical features of patients with neuropathic pain and sensory alterations after dental implant placement. BACKGROUND: Literature is very scarce concerning the prevalence of neuropathic pain after dental implant placement. PATIENTS AND METHODS: A retrospective cohort study was made in patients submitted to dental implant placement in the Dental Hospital of the University of Barcelona. A descriptive analysis of the data was made, and the 95% confidence intervals (95% CI) were calculated for the prevalences. RESULTS: The study sample was composed of 1156 subjects of whom, 1012 patients (3743 dental implants) met the study inclusion criteria. Four hundred and seventeen patients (41.2%) were male and 595 (58.8%) were female, with a mean age of 60.7 years (range 16-90 years). Three patients were diagnosed as having painful post-traumatic trigeminal neuropathy (PPTN), which corresponds to a prevalence of 0.3% (95% CI: 0%-0.6%). Additionally, 5 patients (0.5%; 95% CI: 0%-1.07%) presented trigeminal neuropathy without pain (TNWP). The combined prevalence of both disorders was 0.8% (95% CI: 0.02%-1.3%). All patients with PPTN and TNWP were 60 years old or older, with a total combined prevalence of 1.48% (95% CI: 0.46%-2.5%) in this age group. Additionally, the prevalence in this age group for women was 1.85% (95%CI: 0.38%-3.31%). CONCLUSIONS: Neuropathic pain after dental implant placement is very infrequent (0.3%) in a University Oral Surgery department. However, the presence of trigeminal neuropathies can be slightly higher and can affect up to 0.5% of patients. Older female patients seem to be more prone to this rare and disabling complication.

Characteristics and course of chronic hepatitis B e antigen-negative infection. / Características y evolución de la infección crónica por virus de la hepatitis B antígeno e negativo.

OBJECTIVE: To describe the epidemiological, analytical and histological characteristics and clinical course of hepatitis B virus (HBV) carriers with negative HBe antigen. MATERIAL AND METHODS: Observational, retrospective cohort study of HBV carriers with negative HBe antigen (2005-2012), with no other causes of liver disease. RESULTS: One hundred and thirty-eight patients were included, with mean age 40.5±12.2 years; 54% were women, and 38% were of foreign origin; the number of foreign patients significantly increased (P<.001) over the years. Transaminases were normal in nearly 75% and HBV-DNA was <2,000IU/ml in 56% of patients at diagnosis. There was a gradual decrease in HBV-DNA levels in inactive carriers over the study period. Fibrosis study was performed in 47% of patients by Fibroscan® or liver biopsy: 55.4% normal histology and 6.1% cirrhosis. Just over three quarters of patients (77.77%) were inactive carriers. Treatment was required in 15.5% of patients (20% because of cirrhosis and 80% HBeAg-negative chronic hepatitis B). Five patients cleared HBsAg (annual rate .94%), all of whom presented HBV-DNA <2,000IU/ml at diagnosis. Five patients developed complications (3.6%), 4 of them hepatocellular carcinoma (HCC), of which only 2 had cirrhosis. There was 1 HBV-related death (.72%). CONCLUSION: Among HBV carriers with negative HBe antigen, inactive HBs-Ag carriers are predominant. HBV-DNA gradually decreases in the first few years after diagnosis. Morbidity and mortality are low, especially if glutamic pyruvic transaminase (GPT) is normal and HBV-DNA levels are low at diagnosis. Treatment is needed in a considerable number of patients. HCC is the most frequent complication, even in the absence of cirrhosis.

Uso de packing preperitoneal en paciente politraumatizado / Use of preperitoneal packing in politraumatized patient

Objetivo Reportar un caso de grave fractura pélvica y sangrado masivo tratado inicialmente con packing pélvico. Caso clínico Paciente precipitado hemodinámicamente debido a varias fracturas abiertas, entre las que se incluye fractura pélvica con importante diástasis púbica. Se decide intervención quirúrgica procediendo a fijación externa de la pelvis, y posteriormente se realiza un packing extraperitoneal dado el gran hematoma extraperitoneal con sangrado en sábana. Finalmente, se practica arteriografía donde se ve sangrado arterial activo dependiente del tronco pudendo obturador y de la arteria glútea superior izquierda que se embolizan, con posterior estabilización hemodinámica. Conclusión La arteriografía puede mejorar el control de la hemorragia en los pacientes con sangrado arterial y hemodinámicamente estables, pero el packing tiene prioridad en los pacientes con fracturas de pelvis e inestabilidad hemodinámica.

Aim To report a case of severe pelvic fracture and massive bleeding initially treated with pelvic packing. Clinical case Patient who falls off a high place, hemodynamically unstable due to several open fractures including a pelvic fracture with significant pubic diastasis. It is decided to operate on the patient, proceeding to external fixation of the pelvis and performing, afterwards, an extraperitoneal packing due to the large extraperitoneal hematoma with oozing hemorrhage. Lastly an arteriography is done, where active arterial bleeding is observed localized at the obturator pudendal trunk and the left superior gluteal artery, which are embolized with hemodynamic stabilization. Conclusion Arteriography can improve hemorrhage control in hemodynamically stable patients with arterial bleeding, but packing has the priority on patients with pelvic fractures and hemodynamic instability.

[Percutaneous ablation of hepatocellular carcinoma in older patients in clinical practice]. / Tratamiento percutáneo del carcinoma hepatocelular en pacientes con edad avanzada en la práctica clínica.

INTRODUCTION: A high percentage of older patients with early-stage hepatocellular carcinoma (HCC) are potential candidates for percutaneous ablation. MATERIAL AND METHODS: We prospectively assessed data from patients older than 70 years with HCC. We determined their demographic and clinical characteristics, the treatment provided and the response, complications and survival among those treated with radiofrequency ablation (RFA) and/or percutaneous ethanol injection (PEI). RESULTS: Of 194 patients with HCC, 84 were older than 70 years (43.3%). The mean age was 76.8 ± 4.5 years. Seventy-five percent were male and 91.7% had cirrhosis. Cancer was initially identified by a surveillance program in 61.9%. According to the Barcelona Clinic Liver Cancer staging system, 60.7% were classified as having early stage cancer (0-A), 19% as stage B, 12% as stage C, and 8.3% as stage D. Potentially curative initial treatment was provided in 38.2% (surgical resection in 4.8%, PEI in 22.6%, RFA in 4.8%, PEI+RFA in 6%), transarterial chemoembolization in 20.2%, and sorafenib in 3.6%. Twenty-five percent of patients were not treatment candidates and 13% refused the recommended treatment. The median follow-up after percutaneous ablation was 23 months (IQR 14.2-40.6). The mean number of sessions was 3.5 ± 2.2 for PEI and 1.8 ± 1.6 for RFA. The complications rate per session was 4%. Remission was achieved in 35.7%. The overall median survival was 45.7 months (95% CI 20.8-70.6). CONCLUSIONS: Almost half of the patients with HCC in our sample were elderly and more than half were diagnosed at an early stage. Percutaneous ablation was performed in one-third of the sample, achieving remission in 37.5%. There were few complications. Therefore, these patients should be assessed for percutaneous ablation.

The value of the Barcelona Clinic Liver Cancer and alpha-fetoprotein in the prognosis of hepatocellular carcinoma.

INTRODUCTION AND OBJECTIVES: presently, the reference staging system to evaluate the prognosis of hepatocellular carcinoma (HCC) patients is "The Barcelona Clinic Liver Cancer" (BCLC) system. The value of alpha-fetoprotein (AFP) has not been properly defined. The aim of this study was to evaluate the BCLC classification in our clinical practice and to know what the prognostic value of AFP is. MATERIAL AND METHODS: 136 consecutive HCC patients were prospectively included in this study. The diagnosis of HCC was based on the recommendation of international guidelines. The patients were studied and managed according to usual clinical practice. Survival curves were estimated using the Kaplan-Meier method and predictors of survival were identified using the Cox model. RESULTS: 110 patients (80.9%) were male. The mean age of the patients was 66.62 + or - 11.68 years. Liver cirrhosis was present in 91.2%. The most frequent cause of liver disease was hepatitis C infection (38.97%). Serum AFP was - or = 20 ng/mL in the 57%, > 20-200 ng/mL in the 20%, and > 200 ng/mL in 23%. According to the BCLC staging system, 79 patients were classified as stage A (58.09%), 29 (21.32%) stage B, 17 (12.50%) stage C and 11 patients (8.09%) as stage D. The overall median survival time was 26.52 months (95% CI 16.7-36.3). The median survival according to BCLC system was: BCLC A 62.27, BCLC B 12.72, BCLC C 4.83, and BCLC D 0.62 months (p < 0.0001); and according to serum AFP was: AFP - or = 20: 62.27 months, > 20-200: 22.08 months, and > 200 ng/mL: 5.39 months (p < 0.0001). Multivariate analysis showed that AFP, BCLC classification and treatment were independent prognostic factors. CONCLUSIONS: our results confirm that the BCLC is a good prognostic system. The AFP has prognosis value in HCC patients. The addition of AFP could improve the BCLC system. Future studies are needed to confirm our results and also the best way to combine BCLC and AFP properly.

[Clinical characteristics, staging and treatment of patients with hepatocellular carcinoma in clinical practice. Prospective study of 136 patients]. / Características clínicas, estadificación y tratamiento de los pacientes con carcinoma hepatocelular en la práctica clínica. Estudio prospectivo de una serie de 136 pacientes.

UNLABELLED: Hepatocellular carcinoma (HCC) is the most frequent cause of mortality in patients with liver cirrhosis. There are no prospective series from a single tertiary hospital in Spain. MATERIAL AND METHODS: We performed a prospective study of patients with HCC in our center. Clinical and epidemiological characteristics, diagnostic method, staging according to the Barcelona Clinic Liver Cancer (BCLC) system and treatment were analyzed. RESULTS: A total of 136 patients were included (80.9% men). The mean age was 66.62 ± 11.68 years and 91.2% were cirrhotic. Hepatitis C virus (HCV) was the leading cause of liver disease (38.97%). The suspected diagnosis was established by a surveillance program in 63.2%. Noninvasive American Association criteria for the Study of Liver Diseases (AASLD) were the main diagnostic method (73.5%). According to the BCLC, 58.1% were in the early stage (0-A), 21.3% in stage B, 12.5% in stage C and 8.1% in stage D. Early stage patients had followed a surveillance program more frequently than those with non-early stages (79.75% versus 44.35%, p <0.001). Potentially curative initial treatment was used in 45.58%, the most common treatment being percutaneous ethanol injection (23.13%). CONCLUSIONS: Most patients with HCC in our hospital have cirrhosis, the most frequent cause being HCV. HCC surveillance in at-risk patients could increase diagnosis of HCC at an early stage. We achieved an early diagnosis in more than half of cases. The most common initial treatment was percutaneous therapy.

Amyloidosis and Crohn´s disease.

Secondary amyloidosis is a rare but serious complication of inflammatory bowel disease that may influence the prognosis even more than the underlying disease. Due to a better knowledge of the association of secondary amyloidosis to inflammatory bowel disease, early diagnosis of this complication is becoming more frequent, but its treatment continues to pose a challenge. We report 4 cases of patients with Crohn´s disease and amyloidosis diagnosed in the inflammatory bowel disease Units of Toledo and Ciudad Real, which represent 0.68% of the patients with Crohn´s disease of our health areas. There have been not cases of amyloidosis in patients with ulcerative colitis. In our 4 patients the secondary amyloidosis was clearly related to Crohn´s disease,which was often of fistulising type. The predominant clinical picture of amyloidosis was nephrotic syndrome. The patients responded to medical and surgical treatment of Crohn´s disease and colchicine, which improved renal function in all cases except in one who required kidney transplantation.

Propranolol for infantile hemangiomas.

Propranolol has been used successfully in a limited number of children with infantile hemangiomas. This multicenter retrospective study describes the efficacy and adverse effects of propranolol in infantile hemangioma. Seventy-one infants with infantile hemangiomas were treated with oral propranolol, 1 mg/kg/12 hours, for at least 12 weeks. A photograph based severity scoring assessment was performed by five observers to evaluate efficacy, utilizing a scoring system of 10 as the original infantile hemangioma before treatment and 0 as completely normal skin. The mean of the five independent measurements was used in the analysis. Propranolol was a rapid and effective treatment for infantile hemangiomas at 4 weeks (p < 0.001), at 8 weeks (p < 0.001 compared to the 4 wks value), at 12 weeks (p < 0.05 compared to the 8 wks value), and thereafter up to 32 weeks (p < 0.01 compared to the 16 wks value). The response of infantile hemangiomas to propranolol was similar regardless of sex, age at onset of treatment, type of involvement (segmental and nonsegmental), facial segments affected, special locations (eyelid, nasal tip, and parotid region), ulceration, and depth of infantile hemangiomas. Very few side effects were reported; mainly agitated sleep in 10 of 71 patients. In the series of patients in this study, oral propranolol 2 mg/kg/day was a well-tolerated and effective treatment for infantile hemangiomas. Prospective studies are needed to establish the exact role of propranolol in the treatment of infantile hemangiomas.