Intra-osseous basivertebral nerve radiofrequency ablation (BVA) for the treatment of vertebrogenic chronic low back pain.

STUDY DESIGN: Prospective experimental uncontrolled trial. BACKGROUND: Vertebrogenic pain is a frequently underestimated cause of chronic low back pain (LBP). Vertebral endplate degeneration, characterized by cortical bone damage and subchondral bone inflammatory reaction, is a significant source of LBP, the responsible of the pain transmission being the Basivertebral Nerve (BVN). Radiofrequency ablation of the BVN (BVA) leads to thermal injury of nerve tissue and interruption of the of chronic vertebrogenic pain transmission. PURPOSE: The aim of this study is to evaluate the effectiveness, in terms of pain and disability reduction, of percutaneous (BVA) in treating patients affected by vertebrogenic chronic LBP. Moreover, as a secondary endpoint, the purpose is to assess the feasibility and safety of a percutaneous CT-guided technique. METHODS: We performed percutaneous CT-guided BVN ablation in 56 consecutive patients presenting with vertebrogenic chronic LBP in local anesthesia using an articulating bipolar radiofrequency electrode (STAR™ Tumor Ablation System Merit). A 1-month follow-up MRI was performed to evaluate the ablation area in order to assess the target success of the procedure. A 3-month follow-up CT study was performed to evaluate bone mineral density in order to exclude structural bone abnormalities that might have been induced by the treatment. Pre- and post-procedure pain and disability levels were measured using the visual analogue scale (VAS) and Oswestry Disability Index (ODI). A 2-cm improvement threshold was set as clinical success for the VAS score and a 10-point improvement threshold was set as clinical success for the ODI score. RESULTS: At 3- and 12-month follow-up, VAS and ODI scores decreased significantly compared to baseline. Clinical success was reached in 54/56 patients (96.5%) for pain and 54/56 patients (96.5%) for disability, exceeding significantly the MCID. CT-assisted targeting of the ablation zone was determined successful in 100% of patients. Mean operative time was 32 min. No immediate or delayed complications were detected. CONCLUSIONS: Percutaneous CT-guided intra-osseous BVA seems to be a safe, fast, and powerful technique for pain relief in patients with vertebrogenic chronic LBP, when the selection of patients is based on a multidisciplinary approach including both conventional Diagnostic Radiology and Nuclear Medicine imaging.

Achieving the critical view of safety in the difficult laparoscopic cholecystectomy: a prospective study of predictors of failure.

BACKGROUND: Bile duct injury rates for laparoscopic cholecystectomy (LC) remain higher than during open cholecystectomy. The "culture of safety" concept is based on demonstrating the critical view of safety (CVS) and/or correctly interpreting intraoperative cholangiography (IOC). However, the CVS may not always be achievable due to difficult anatomy or pathology. Safety may be enhanced if surgeons assess difficulties objectively, recognise instances where a CVS is unachievable and be familiar with recovery strategies. AIMS AND METHODS: A prospective study was conducted to evaluate the achievability of the CVS during all consecutive LC performed over four years. The primary aim was to study the association between the inability to obtain the CVS and an objective measure of operative difficulty. The secondary aim was to identify preoperative and operative predictors indicating the use of alternate strategies to complete the operation safely. RESULTS: The study included 1060 consecutive LC. The median age was 53 years, male to female ratio was 1:2.1 and 54.9% were emergency admissions. CVS was obtained in 84.2%, the majority being difficulty grade I or II (70.7%). Displaying the CVS failed in 167 LC (15.8%): including 55.6% of all difficulty grade IV LC and 92.3% of difficulty grade V. There were no biliary injuries or conversions. CONCLUSION: All three components of the critical view of safety could not be demonstrated in one out of 6 consecutive laparoscopic cholecystectomies. Preoperative factors and operative difficulty grading can predict cases where the CVS may not be achievable. Adapting instrument selection and alternate dissection strategies would then need to be considered.

One-session laparoscopic management of Mirizzi syndrome: feasible and safe in specialist units.

BACKGROUND: To evaluate the laparoscopic management of Mirizzi syndrome, seldom diagnosed preoperatively causing difficulty when performing cholecystectomy and increasing complication risks. METHODS: Analysis of a prospective single-surgeon database of 5700 laparoscopic cholecystectomies found 58 Mirizzi syndrome cases. They were managed with an intention to treat during the index admission according to protocol of single-session management of bile duct stones. RESULTS: 38/58 patients were females (65.5%). The median age was 55 years. 53 cases were emergency admissions. 34 cases (58.6%) only had ultrasound scanning. Operative difficulty was Grade IV in 34 cases (58.6%) and Grade V in 20 (34.5%) (Nassar Scale). There were 33 Mirizzi Type IA, 7 Type IB, 16 Type II and one each of Type III and Type IV. Bile duct exploration was performed in 94.8% through choledochotomy/ transfistula in 58.6% or transcystic in 36.2%. Four cases required conversion to open. Postoperative morbidity occurred in 29%. Two 30-day mortalities occurred from pneumonia in two elderly patients who were late referrals. CONCLUSION: Although the utilization of the laparoscopic approach in managing bile duct stones is not currently widely practiced it was safer in this series than in reported series of open surgery in Mirizzi Syndrome. The optimal approach to Mirizzi Type II is via cholecystocholedochal fistula to explore the bile duct then drain with T-tube through the fistula. It is unnecessary to perform bilioenteric bypass in majority of cases, reducing the morbidity and mortality.

Quality of life with rivaroxaban in patients with non-valvular atrial fibrilation by therapeutic compliance.

OBJECTIVE: To assess the quality of life (QOL) with rivaroxaban in patients with non-valvular atrial fibrilation (NVAF) related to therapeutic compliance. METHODS: Prospective, longitudinal, multicenter study was developed in 160 Spanish primary or specialized care centers. We included 412 patients treated with rivaroxaban, prescribed for stroke prevention. Three visits were conducted: baseline, 6 and 12 months. Compliance was measured by electronic monitoring systems. QOL was measured by a specific questionnaire. We calculated the percentage of compliance means, the percentage of daily compliers and the score of QOL. RESULTS: Three hundred and seventy patients finished the study (mean age 75.19 SD: 7.5 years). Daily compliance was 83.5% (CI 78.53-88.57%) (n = 309) and 80% (CI 74.65-85.35%) at 6 and 12 months, respectively. Average QOL rating was 112.85 (SD 29.31) in non-compliant and 111.80 (SD 29.31) in the compliant group (p = Not significant), and after 12 months of 124.67 (SD 30.78) and 83.47 (SD 26.44), respectively (p < 0.0001), with a decrease in the score compliers (p < 0.01) and an increase in non-compliant group (p < 0.05). A higher number of drugs consumed, as well as the number of diseases/conditions suffered, the older age of the patients and having been previously treated with VKA were associated with a higher overall score (worse QOL). CONCLUSIONS: QOL in NVAF patients treated with rivaroxaban improved significantly over the study group at the expense of compliers. A worse QOL was associated with pluripathology, polymedication, older patients and previous treatment with VKA.

Gender and plasma iron biomarkers, but not HFE gene mutations, increase the risk of colorectal cancer and polyps.

A cohort study of patients included in the Basque Country colorectal cancer (CRC) screening programme was carried out to assess the risk of adenomatous polyps and CRC (P-CRC) associated with HFE gene mutations, with gender and with iron biomarkers (serum ferritin (SF), iron (Fe) and transferrin saturation index (TSI)). Among 432 included patients (mean age 59.8 years), 263 were men (60.9 %) and 169 women (39.1 %). P-CRC were identified in 221 patients (51.2 %) and no polyps (NP) in 211 patients (48.8 %). HFE mutations were identified in 43.8 % of the patients. C282Y/wt genotypic frequency was 6.8 % in the P-CRC group and 1.4 % in the NP group (p < 0.05). The allelic frequency was 3.8 versus 1.2 % (p < 0.05). For laboratory, all three iron biomarkers showed a statistically significant difference: mean Fe, 91.29 ± 34 for P-CRC and 80.81 ± 30.59 for NP group. Mean TSI for P-CRC was 24.95 ± 8.90 and 22.74 ± 8.79 for NP group. Mean SF 308.09 ± 536.32 for P-CRC and 177.55 ± 159.95 for NP group. In a multivariate logistic regression analysis, only male gender (odds ratio (OR) = 2.04, 1.29-3.22), SF (OR = 1.001, 1.0004-1.003) and Fe (OR = 1.01, 1.004-1.02) were related with the presence of CRC and adenoma. Men gender and raised serum iron biomarkers increase the risk of P-CRC.

Diagnostic performance of fecal immunochemical test and sigmoidoscopy for advanced right-sided colorectal neoplasms.

BACKGROUND: Colorectal cancer screening effect on right-sided colorectal neoplasia is limited. We compared fecal immunochemical test and simulated sigmoidoscopy diagnostic accuracy for advanced right-sided neoplasia detection. METHODS: We analyzed 1,292 individuals with complete screening colonoscopy with a fecal immunochemical test determination before colonoscopy. Sigmoidoscopy and "hybrid strategy" (sigmoidoscopy or fecal hemoglobin concentration ≥ 20 µg hemoglobin/g) diagnostic yield were simulated according to UK Flexible Sigmoidoscopy, Screening for COlon REctum (SCORE), and Norwegian Colorectal Cancer Prevention (NORCCAP) trials criteria to complete colonic examination. We compared sensitivity and specificity of both strategies and of "hybrid strategy" for advanced right-sided neoplasia with McNemar test. RESULTS: An advanced right-sided neoplasia was detected in 47 (3.6 %) subjects. A fecal hemoglobin concentration ≥ 20 µg hemoglobin/g was determined in 6.6 % of the subjects and 10.1, 12.7, and 23.5 % met UK, SCORE, and NORCCAP criteria, respectively. Fecal immunochemical test was statistically more specific than sigmoidoscopy strategies (93.8 %, UK 90.3 %, SCORE 87.7 %, NORCCAP 77.8 %; p < 0.001). In contrast, fecal immunochemical test sensitivity for advanced right-sided neoplasia (17 %) was not statistically different than UK (21.3 %; p = 0.7) or SCORE (23.4 %; p = 0.5), although it was inferior than NORCCAP strategy (42.5 %; p < 0.001). Adding fecal immunochemical test to sigmoidoscopy increased number of positives (8.5-25.7 %), sensitivity (10-30 %), and significantly reduced advanced right-sided neoplasia specificity (p < 0.001). CONCLUSIONS: Fecal immunochemical test and sigmoidoscopy diagnostic yield for advanced right-sided neoplasia are low. Fecal immunochemical test is more specific than sigmoidoscopy but less sensitive than sigmoidoscopy according to NORCCAP criteria.

Hemoglobin in large vessel occlusion: Look further than collaterals.

BACKGROUND: Abnormal hemoglobin (Hb) levels lead to poorer outcomes in ischemic stroke, though the mechanisms remain elusive. We aimed to study the role of Hb on imaging and clinical outcomes, namely on collaterals as it is a known mediator of infarct growth. METHODS: Retrospective cohort study of patients with large vessel occlusion ischemic stroke admitted to our center. Demographics, clinical and imaging variables were collected, particularly baseline hemoglobin, presence of anemia and collateral score. Collaterals were scored from 0 to 3 and defined as poor if 0-1. Multivariable analyses were performed for collateral score and clinical outcomes (3-month mortality and good prognosis). RESULTS: We included 811 patients, 215 (26.5 %) with anemia. Patients with anemia were older, had more comorbidities and more severe strokes. Hemoglobin levels and anemia were not associated with collateral score (OR 0.97, 95 % CI 0.89-1.05, p = 0.414 and OR 0.89, 95 % CI 0.64-1.24, p = 0.487, respectively) nor with poor collaterals (OR 0.96, 95 % CI 0.88-1.05, p = 0.398 and OR 0.86, 95 % CI 0.60-1.23, p = 0.406, respectively). Hb levels were associated with 3-month mortality (OR 0.85, 95 % CI 0.76-0.96, p = 0.008). CONCLUSION: Hemoglobin or anemia were not found to be associated with collateral status. Our results raise further questions regarding the pathophysiology of anemia and outcomes in ischemic stroke, highlighting the need for future research.

Relationship of colonoscopy-detected serrated polyps with synchronous advanced neoplasia in average-risk individuals.

BACKGROUND: Serrated cancers account for 10% to 20% of all colorectal cancers (CRC) and more than 30% of interval cancers. The presence of proximal serrated polyps and large (≥10 mm) serrated polyps (LSP) has been correlated with colorectal neoplasia. OBJECTIVE: To evaluate the prevalence of serrated polyps and their association with synchronous advanced neoplasia in a cohort of average-risk population and to assess the efficacy of one-time colonoscopy and a biennial fecal immunochemical test for reducing CRC-related mortality. This study focused on the sample of 5059 individuals belonging to the colonoscopy arm. DESIGN: Multicenter, randomized, controlled trial. SETTING: The ColonPrev study, a population-based, multicenter, nationwide, randomized, controlled trial. PATIENTS: A total of 5059 asymptomatic men and women aged 50 to 69 years. INTERVENTION: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Prevalence of serrated polyps and their association with synchronous advanced neoplasia. RESULTS: Advanced neoplasia was detected in 520 individuals (10.3%) (CRC was detected in 27 [0.5%] and advanced adenomas in 493 [9.7%]). Serrated polyps were found in 1054 individuals (20.8%). A total of 329 individuals (6.5%) had proximal serrated polyps, and 90 (1.8%) had LSPs. Proximal serrated polyps or LSPs were associated with male sex (odds ratio [OR] 2.08, 95% confidence interval [CI], 1.76-4.45 and OR 1.65, 95% CI, 1.31-2.07, respectively). Also, LSPs were associated with advanced neoplasia (OR 2.49, 95% CI, 1.47-4.198), regardless of their proximal (OR 4.15, 95% CI, 1.69-10.15) or distal (OR 2.61, 95% CI, 1.48-4.58) locations. When we analyzed subtypes of serrated polyps, proximal hyperplasic polyps were related to advanced neoplasia (OR 1.61, 95% CI, 1.13-2.28), although no correlation with the location of the advanced neoplasia was observed. LIMITATIONS: Pathology criteria for the diagnosis of serrated polyps were not centrally reviewed. The morphology of the hyperplasic polyps (protruded or flat) was not recorded. Finally, because of the characteristics of a population-based study carried out in average-risk patients, the proportion of patients with CRC was relatively small. CONCLUSION: LSPs, but not proximal serrated polyps, are associated with the presence of synchronous advanced neoplasia. Further studies are needed to determine the risk of proximal hyperplastic polyps.

Non-ketotic hyperglycaemia induced occipital reflex focal seizures.

A myriad of neurological manifestations can occur in association with ketotic and non ketotic hyperglycaemic states. Contrary to diabetic coma, which is a universal complication under relatively established metabolic circumstances, the pathophysiology beyond hyperglycaemic-associated positive neurological manifestations, including seizures, remains to be elucidated. The occurrence of symptomatic focal epilepsy as a manifestation of diabetes-related hyperglycaemia is seldom reported. Herein, we present a case of focal epilepsy with alternating positive and negative neurological manifestations as the initial manifestation of diabetes-related hyperglycaemia. The electroencephalogram confirmed the diagnosis of focal occipital seizures, and the brain magnetic resonance imaging depicted the associated typical transient imaging findings in the occipital lobe. Seizures were refractory to antiepileptics, and symptomatic control was achieved after achieving normoglycemia. On follow-up, complete clinical and imaging recovery occurred. Reflex focal epilepsy in the context of hyperglycaemic states is a rare condition, and the possibility of misdiagnosis is likely high. As reported in similar cases, seizures can be resistant to antiepileptics. An important message to highlight is that seizures associated with hyperglycaemic status can be resistant to antiepileptic treatment and only cease with glycaemic control.

Coccygeoplasty: preliminary experience with this new alternative treatment of refractory coccydynia in patients with coccyx hypermobility.

BACKGROUND: Coccydynia has many causes, including fracture, subluxation, and hypermobility of sacrococcygeal segments. Existing treatments are limited in their effectiveness. Coccygeoplasty (CP) is a relatively new, minimally invasive treatment that appears to address this difficult clinical challenge. OBJECTIVE: To describe clinical results at the time of the procedure and at 3- and 12-months' follow-up of patients with coccydynia related to subluxation and coccyx hypermobility treated with the CP technique. Additionally, to determine if there is any correlation between the final imaging and clinical results at 3- and 12-months' follow-up. METHODS: A prospectively maintained database was used, and all patients who underwent CP for chronic coccydynia between January 2005 and October 2018 were retrospectively reviewed. All the patients had painful hypermobility (greater than 25°) with anterior flexion confirmed on radiological imaging. Alternative causes of coccydynia were excluded using CT and MRI. Procedures were performed under local anesthesia with combined fluoroscopic and CT guidance. Clinical follow-up was performed at two time points: 3 and 12 months after treatment using the Visual Analogue Scale (VAS). RESULTS: Twelve patients were treated in a single center. No procedural complications occurred. At 3- and 12-months' follow-up, the majority (75%) of patients had significantly lower VAS scores than at baseline, with mean changes of 3.5 and 4.9, respectively. There was no pain recurrence at 12 months and just one patient had no improvement of the pain. Follow-up CT images confirmed fixation of the sacrococcygeal bone segments in nine patients; however, no correlation was found between final imaging results and clinical outcome (p=0.1). CONCLUSIONS: Patients with refractory painful coccyx subluxation and hypermobility undergoing CP have a favorable clinical response at 3- and 12-months' follow-up. Further studies are required to validate this technique and to identify predictors of treatment response. Coccygeoplasty may be considered a reasonable alternative to coccygectomy.

Diagnosis of Whipple's disease using molecular biology techniques.

The diagnosis of Whipple's disease (WD) is based on the existence of clinical signs and symptoms compatible with the disease and in the presence of PAS-positive diastase-resistant granules in the macrophages of the small intestine. If there is suspicion of the disease but no histological findings or only isolated extraintestinal manifestations, species-specific PCR using different sequences of the T. whippleii genome from different tissue types and biological fluids is recommended.This study reports two cases: the first patient had diarrhea and the disease was suspected after an endoscopic examination of the ileum, while the second patient had multi-systemic manifestations,particularly abdominal, thoracic, and peripheral lymphadenopathies. In both cases, the diagnosis was confirmed using molecular biology techniques to samples from the small intestine or from a retroperineal lymph node, respectively.

Cystic Lymph Node Identification Is More Reliable Than Critical View of Safety in Difficult Cholecystectomies.

BACKGROUND: The cystic lymph node (CLN) represents an anatomic safety marker and a surrogate marker of technique during laparoscopic cholecystectomy (LC). We aim to demonstrate the value of CLN in comparison to the critical view of safety (CVS) and study the effects of increasing difficulty on the 2 approaches. METHODS: A prospective study of consecutive LC was conducted. Patient demographics, type of admission, clinical presentation, operative difficulty grade, visualization of CLN, identification of CVS, operative time, and complications were recorded and analyzed. RESULTS: Of 393 LCs, half of the admissions were emergencies. Thirty-four percent had obstructive jaundice or acute cholecystitis. The CLN was visually identified in 81.7% with a small difference between operative difficulty grades 1 to 3 versus 4 to 5. Although CVS was unachievable in 62 patients, 43 (69.4%) still had an identifiable CLN. The median operating time was 68 minutes with 1 mortality but no conversions or intraoperative complications. CONCLUSIONS: Identifying the CLN during LC could compliment the CVS in avoiding major ductal injury. Dissecting lateral to the CLN to commence the process of displaying the cystic pedicle structures may be a strategy in safely achieving the CVS. During the more difficult LC where displaying the CVS is impossible, the CLN may be the key anatomic landmark.

[Plasma levels of folate and vitamin B(12) in patients with chronic liver disease]. / Niveles plasmáticos de la vitamina B(12) y ácido fólico en pacientes con hepatopatía crónica.

BACKGROUND: Patients with liver disease frequently experience changes in their nutritional status. OBJECTIVE: To determine changes in vitamin B12 and folic acid plasma levels in patients with chronic cirrhosis and to assess whether these parameters may be useful in the etiologic diagnosis of this disease. PATIENTS AND METHODS: Thirty-nine patients admitted for decompensated cirrhosis (29 with alcoholic etiology and 10 with non-alcoholic etiology) and 35 controls were prospectively studied. Plasma levels of vitamin B(12), folate acid, mean corpuscular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT ratio, and gamma-glutamyltransferase (GGT), among other parameters, were measured. RESULTS: Vitamin B(12) levels were 1151+/-568pg/ml in patients with decompensated cirrhosis and 440+/-133pg/ml in controls (p<0.05). Plasma folate levels were 8.57+/-3.8ng/ml in controls and 6.68+/-2.74ng/ml in patients with cirrhosis (p<0.05). Folate levels were lower in patients with alcoholic cirrhosis (mean value, 5.7+/-2.1) than in those with non-alcoholic cirrhosis (9.3+/-2.6; p<0.0005). The vitamin B(12)/folate ratio discriminated alcoholic etiology better than other parameters such as AST, ALT, MCV, AST/ALT ratio and GGT. CONCLUSIONS: Plasma levels of vitamin B12 in patients with decompensated chronic liver disease are high, whereas plasma folate levels are low. The ratio between vitamin B12 and folic acid may be useful in the differential diagnosis of the etiology of chronic liver disease.

Posterior reversible encephalopathy syndrome associated with the use of chemotherapeutic agents: a rare complication after treatment with vinorelbine.

The posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome characterised by a combination of headache, encephalopathy, seizures and visual disturbances, associated with high-intensity abnormalities on T2-weighted images affecting subcortical white and grey matter of the occipital and parietal lobes. Among other causes, PRES has been associated with the use of several medications including chemotherapeutic agents. Here we report a case of a 65-year-old patient with squamous cell carcinoma of the lung treated with cisplatin/vinorelbine. Following the second administration of vinorelbine, she was admitted to the hospital for a generalised seizure. Blood pressure was just slightly elevated and, except for drowsiness, she had a near-normal neurological examination. MRI corroborated the diagnosis. Vinorelbine-induced PRES has been reported only once in the literature, also in association with cisplatin. Our case underlines the role of vinorelbine and suggests that its association with cisplatin in this setting may enhance the risk of PRES.

A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA1), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration.

Neuropathic pain (NP) is a complex chronic pain state with a prevalence of almost 10% in the general population. Pharmacological options for NP are limited and weakly effective, so there is a need to develop more efficacious NP attenuating drugs. Activation of the type 1 lysophosphatidic acid (LPA1) receptor is a crucial factor in the initiation of NP. Hence, it is conceivable that a functional antagonism strategy could lead to NP mitigation. Here we describe a new series of LPA1 agonists among which derivative (S)-17 (UCM-05194) stands out as the most potent and selective LPA1 receptor agonist described so far (Emax = 118%, EC50 = 0.24 µM, KD = 19.6 nM; inactive at autotaxin and LPA2-6 receptors). This compound induces characteristic LPA1-mediated cellular effects and prompts the internalization of the receptor leading to its functional inactivation in primary sensory neurons and to an efficacious attenuation of the pain perception in an in vivo model of NP.

[Clinicopathological characteristics and survival outcome of esophageal cancer. Results from a series of 200 patients]. / Características clinicopatológicas y supervivencia de los pacientes con cáncer de esófago. Resultados de 200 casos consecutivos.

BACKGROUND AND OBJECTIVE: The esophageal cancer (EC) is a slightly frequent but serious disease. Our aim is to describe the characteristics of the patients with EC in our Hospital. PATIENTS AND METHOD: We included 200 patients consecutively diagnosed and/or treated for CE between between January, 2003 and December, 2007. The location of the tumor was analyzed, the histological type, the proofs realized for to establish the classification, the treatments, the survival and the morbi-mortality of the surgery. RESULTS: The endoscopic ultrasonography (EUS) modified the therapeutic strategy in 12% of the patients. The survival to the year, 3 years and 5 years was 48%, 25% and 21%, respectively. 74 (32%) patients were operated, 48 (65%) of them was treated with neoadjuvant chemoradiotherapy. The postsurgical mortality was 8% (6 patients) and the morbidity was 57% (114 patients). In multivariate analysis, after adjustment for traditional risk factors, were the location in the average third ( [HR, hazard ratio]=2.3; confidence interval [IC] of 95%, 1.3-4.1) and not accomplishment of surgery after the chemotherapy and radiotherapy (HR=1.9; IC to 95%, 1.15-3). CONCLUSIONS: The diagnosis is realized very later. The EUS has contributed a better therapeutic strategy to our patients. The mortality continues being high.