Effect of antiangiogenic-based treatment and systemic inflammatory factors on outcomes in patients with BRAF v600-mutated metastatic colorectal cancer: a real-world study in Spain.

BACKGROUND: Outcomes are poorer in metastatic colorectal cancer (mCRC) patients with BRAF V600E mutations than those without it, but the effect of these mutations on treatment response is unclear. This real-world study assessed the effects of antiangiogenic-based treatment and systemic inflammatory factors on outcomes in patients with BRAF V600-mutated mCRC. METHODS: This real-world, multicenter, retrospective, observational study included patients with BRAF V600-mutated mCRC treated in eight hospitals in Spain. The primary endpoints were overall survival (OS) and progression-free survival (PFS); overall response rate (ORR) and disease control rate (DCR) were also assessed. The effect of first- and second-line treatment type on OS, PFS, ORR, and DCR were evaluated, plus the impact of systemic inflammatory markers on these outcomes. A systemic inflammation score (SIS) of 1-3 was assigned based on one point each for platelet-lymphocyte ratio (PLR) ≥200, neutrophil-lymphocyte ratio (NLR) ≥3, and serum albumin < 3.6 g/dL. RESULTS: Of 72 patients, data from 64 were analyzed. After a median of 69.1 months, median OS was 11.9 months and median first-line PFS was 4.4 months. First-line treatment was triplet chemotherapy-antiangiogenic (12.5%), doublet chemotherapy-antiangiogenic (47.2%), doublet chemotherapy-anti-EGFR (11.1%), or doublet chemotherapy (18.1%). Although first-line treatment showed no significant effect on OS, antiangiogenic-based regimens were associated with prolonged median PFS versus non-antiangiogenic regimens. Negative predictors of survival with antiangiogenic-based treatment were NLR, serum albumin, and SIS 1-3, but not PLR. Patients with SIS 1-3 showed significantly prolonged PFS with antiangiogenic-based treatment versus non-antiangiogenic-based treatment, while those with SIS=0 showed no PFS benefit. CONCLUSIONS: Antiangiogenic-based regimens, SIS, NLR, and albumin were predictors of survival in patients with mCRC, while SIS, NLR and serum albumin may predict response to antiangiogenic-based chemotherapy. TRIAL REGISTRATION: GIT-BRAF-2017-01.

Bilateral sympathectomy for treatment of refractory ventricular tachycardia.

Ventricular tachycardia (VT) commonly occurs in patients with ischemic or nonischemic cardiomyopathy and requires antiarrhythmic drugs, ablation, or advanced circulatory support. However, life-threatening VT may be refractory to these therapies, and may cause frequent implantable cardioverter defibrillator (ICD) discharges. Left cardiac sympathetic denervation reduces the occurrence of these fatal arrhythmias by inhibiting the sympathetic outflow to the cardiac tissue. We present a 69-year-old man with nonischemic cardiomyopathy, life-threatening VT, and hemodynamic instability with numerous ICD discharges, who remained refractory to antiarrhythmic drug therapy and ablation attempts. He was effectively treated with bilateral cardiac sympathectomy. Six months later, he remained free of VT with no ICD discharges.

Arrhythmogenic Right Ventricular Dysplasia: An Under-recognized Form of Inherited Cardiomyopathy.

We report a case of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVD) in order to evaluate the course of an under-recognized form of cardiomyopathy with a vast array of clinical manifestations. The patient is a 49-year-old white woman transferred from an outside hospital due to dyspnea and persistent hypoxia. She had a pertinent family history that included a sister who died suddenly in her 30s from unexplained heart failure. Initial work-up for hypoxia was unrevealing. Transthoracic echocardiography revealed isolated right ventricular dysfunction with dilation and multiple trabeculations. Further investigation, including cardiac computed tomography and magnetic resonance imaging, revealed fatty infiltration into the right ventricular wall suggestive of ARVD.

Good Clinical and Radiological Correlation from Standard Perfusion Computed Tomography Accurately Identifies Salvageable Tissue in Ischemic Stroke.

INTRODUCTION: It has been debated whether the penumbral pattern, as identified using multimodal imaging, is a specific marker of tissue viability in ischemic stroke. We assessed whether perfusion computed tomography (PCT) accurately identifies salvageable tissue and helps predict postreperfusion outcomes. METHODS: A retrospective study of patients with anterior circulation stroke undergoing reperfusion therapies who had a PCT before treatment and an assessment of vessel recanalization post treatment was conducted. Tissue at risk was considered as that with reduced cerebral blood flow, whereas the infarct core was the region of reduced cerebral blood volume, the mismatch region being salvageable tissue. The volume of hypodensity in slices corresponding to perfusion acquisition cage in 24-hour computed tomography (partial lesion volume [PLV]) was measured. Outcome variables were the amount of preserved tissue, that is, the difference between volumes of tissue at risk and PLV expressed as a percentage, and the modified Rankin Scale (mRS) score at 3 months. RESULTS: Patients (n = 34) meeting the inclusion criteria were included. Vessel recanalization was associated with a larger amount of tissue at risk preserved from definite lesion (89% [interquartile range {IQR}: 76-94] versus 46% [IQR: 23-86], P < .005). The amount of preserved tissue correlated with clinical outcome at 24 hours: for each 10% of preserved tissue, the National Institutes of Health Stroke Scale score improved by 3 points (95% confidence interval [CI]: -4.9 to -.8, P = .007) and was the only predictor of independency (mRS score 0-2) following adjustment for covariates (odds ratio 1.15, 95% CI: 1.04-1.28, P = .005). CONCLUSIONS: PCT provides accurate markers of viability of tissue in acute ischemic stroke and could help predict the degree of improvement following reperfusion.

Futile Interhospital Transfer for Endovascular Treatment in Acute Ischemic Stroke: The Madrid Stroke Network Experience.

BACKGROUND AND PURPOSE: The complexity of endovascular revascularization treatment (ERT) in acute ischemic stroke and the small number of patients eligible for treatment justify the development of stroke center networks with interhospital patient transfers. However, this approach might result in futile transfers (ie, the transfer of patients who ultimately do not undergo ERT). Our aim was to analyze the frequency of these futile transfers and the reasons for discarding ERT and to identify the possible associated factors. METHODS: We analyzed an observational prospective ERT registry from a stroke collaboration ERT network consisting of 3 hospitals. There were interhospital transfers from the first attending hospital to the on-call ERT center for the patients for whom this therapy was indicated, either primarily or after intravenous thrombolysis (drip and shift). RESULTS: The ERT protocol was activated for 199 patients, 129 of whom underwent ERT (64.8%). A total of 120 (60.3%) patients required a hospital transfer, 50 of whom (41%) ultimately did not undergo ERT. There were no differences in their baseline characteristics, the times from stroke onset, or in the delays in interhospital transfers between the transferred patients who were treated and those who were not treated. The main reasons for rejecting ERT after the interhospital transfer were clinical improvement/arterial recanalization (48%) and neuroimaging criteria (32%). CONCLUSIONS: Forty-one percent of the ERT transfers were futile, but none of the baseline patient characteristics predicted this result. Futility could be reduced if repetition of unnecessary diagnostic tests was avoided.

Depression predicts repeated heart failure hospitalizations.

OBJECTIVE: Management of depression, if it is independently associated with repeated hospitalizations for heart failure (HF), offers promise as a viable and cost-effective strategy to improve health outcomes and reduce health care costs for HF. The objective of this study was to assess the association between depression and the number of HF-related hospitalizations in patients with low-to-moderate systolic or diastolic dysfunction, after controlling for illness severity, socioeconomic factors, physician adherence to evidence-based medications, patient adherence to HF drug therapy, and patient adherence to salt restrictions. METHODS AND RESULTS: The Heart Failure Adherence and Retention Trial (HART) was a randomized behavioral trial to evaluate whether patient self-management skills coupled with HF education improved patient outcomes. Depression was measured at baseline with the Geriatric Depression Scale (GDS). The number of hospitalizations was analyzed with a negative binomial regression model that included an offset term to account for the differential duration of follow-up for individual subjects. The average unadjusted number of hospitalizations per year was 0.40 in the depressed group (GDS ≥10) and 0.33 in the nondepressed group (GDS <10). Depression was a strong predictor (incident rate ratio 1.45; P = .006) after adjusting for physician adherence to evidence-based medication use, patient adherence to HF drug therapy, patient adherence to salt restriction, illness severity, HF severity (6-minute walk <620 feet), and socioeconomic factors. CONCLUSIONS: Depression is a strong psychosocial predictor of repeated hospitalizations for HF. Compared with nondepressed individuals, those with depression were hospitalized for HF 1.45 times more often, even after controlling for physician adherence to evidence-based medications and patient adherence to HF drug therapy and salt restrictions. This finding suggests that clinicians should screen for depression early in the course of HF management.

Endovascular occlusion of iatrogenic lumbar artery pseudoaneurysm using liquid embolic agent: Case report.

We describe a case of iatrogenic pseudoaneurysm of the fourth lumbar artery as a complication after transpedicular screw fixation in the lumbar spine. The lesion was succesfully occluded with endovascular liquic embolic agent infusion and the patient was fully recovered.

Phase II study of celecoxib with cisplatin plus etoposide in extensive-stage small cell lung cancer.

We performed a phase II trial to test whether a cyclooxygenase (COX-2) inhibitor, celecoxib, added to standard first-line combination chemotherapy (CT) and as maintenance therapy would improve outcomes in extensive-stage (ES) small-cell lung cancer (SCLC). This was a multicenter trial in CT-naive patients with ES-SCLC. They received standard cisplatin and etoposide (EP) up to 6 cycles and celecoxib 400 mg PO bid continuously until disease progression. Primary end points were response rate (RR), time to progression (TTP), and toxicity. Secondary were overall survival (OS) and quality of life. Of 74 expected patients, only 24 were enrolled and the study stopped earlier because of the published safety concerns about celecoxib. The patients, all male, were between 38 and 74 years. A total of 130 cycles of CT were administered. Toxicity associated with celecoxib was minimal. The RR was 56.5%. Median TTP and OS were 8.6 and 11.3 months, respectively. These data suggest that celecoxib may safely be combined with EP for treatment of ES-SCLC. This combination showed a promising activity and, despite the safety concerns regarding celecoxib, it would be interesting to further evaluate this regimen.

Heart transplantation in a patient with chloroquine-induced cardiomyopathy.

We present the first report of a patient who underwent heart transplantation (HT) after endomyocardial biopsy (EMB) and revealed chloroquine-induced cardiomyopathy (CIC). This patient, who was treated with chloroquine for 6 years, developed a restrictive cardiomyopathy that progressed to congestive heart failure (CHF) resistant to medical management.

Increase in atrial size in long-term survivors of heart transplant.

Atrial size in recipients of orthotopic heart transplant (OHTX) who have long-term survival is not well described in the literature. We reviewed 2-dimensional echocardiograms of 14 recipients of OHTX who survived at least 5 years. Apical 4-chamber images were used for measurements starting at 1-year post-OHTX. The recipients of OHTX were 8 (57%) men and 6 (43%) women with a mean age of 43.6 +/- 12.1 (20-60) years and mean survival of 9.5 +/- 2.6 (5.8-14.4) years. All chambers increased with time post-OHTX (r > 0.83, P <.002). The changes in left atrium (LA) and right atrium (RA), remnants of donor LA and RA, and remnants of recipients' LA areas correlated inversely with patient survival post-OHTX (r > 0.83, P <.002). The change in RA recipient remnant area did not correlate with survival (r = 0.58, P =.06). In recipients of OHTX with long-term survival, there is a significant correlation between the echocardiographic size of LA and RA, and donor and recipient remnants with time and survival.

Does use of cell saver decrease the inflammatory response in cardiac surgery?

BACKGROUND: The role of a cell-saver device in the inflammatory response to cardiac surgery has not been well documented. We hypothesized that the use of a cell saver may reduce proinflammatory cytokine concentrations in patients undergoing cardiac surgery. METHODS: 57 patients presenting for first-time nonemergency cardiac surgery were prospectively randomized to control or cell salvage groups. Blood samples for inflammatory marker assays were collected from the arterial line on induction of anesthesia, at the end of cardiopulmonary bypass, 1 h after surgery, and 24 h after surgery. Plasma proinflammatory cytokines were analyzed using a sandwich solid-phase enzyme-linked immunosorbent assay. RESULTS: The highest cytokine levels were observed 1 h after surgery. When comparing serum interleukin levels in both patient groups during the different perioperative periods, we found a higher interleukin-8 concentration 24 h after the procedure, and higher concentrations of the p40 subunit of interleukin-12 at 1 h and 24 h postoperatively. The concentrations of interleukin-6 and p40 were greater in blood stored by the cardiotomy suction system than in blood processed by the cell saver (p = 0.01 in both cases). The interleukin-8 concentration was higher in the blood processed by the cell saver (p = 0.03). No significant differences were observed in interleukin-1 and interferon gamma levels in blood from both systems. Clinical outcomes were similar in both groups. CONCLUSIONS: Our results suggest that cell salvage in low-risk patients undergoing their first elective cardiac procedure does not decrease the inflammatory response after surgery.

Successful intra-arterial thrombolysis for acute ischemic stroke in the immediate postpartum period: case report.

Stroke in pregnancy and the puerperium is a rare but potentially devastating event. We present the case of a previously healthy woman who underwent a cesarean delivery and experienced a middle cerebral artery thrombosis in the immediate postpartum period that was subsequently lysed with intra-arterial urokinase. The patient made a complete neurologic recovery. To the best of our knowledge, this is the first reported case of successful intra-arterial thrombolysis for ischemic stroke in the postpartum period.

Endovascular treatment of a vertebral artery pseudoaneurysm following posterior C1-C2 transarticular screw fixation.

We present a case of vertebral artery pseudoaneurysm after a posterior C1-C2 transarticular screw fixation procedure that was effectively treated with endovascular coil occlusion. Vertebral artery pseudoaneurysm complicating posterior C1-C2 transarticular fixation is extremely rare, with only one previous case having been reported previously. Endovascular occlusion is better achieved in the subacute phase of the pseudoaneurysm, when the wall of the pseudoaneurysm has matured and stabilized. Further follow-up angiographies are mandatory in order to confirm that there is no recurrence of the lesion.

Sordera súbita. Hallazgos en la hemorragia coclear / Sudden deafness: findings in cochlear hemorrhage

La sordera súbita debida a hemorragia laberíntica es una entidad clínica relativamente poco frecuente, y puede ser el único hallazgo demostrable en el estudio de neuroimagen de la sordera súbita, bien como hecho aislado o ligado a una laberintitis, en forma de hiperintensidad laberíntica en secuencias potenciadas en T1 de la resonancia magnética (RM), sin objetivarse refuerzo laberíntico tras la administración de contraste. Presentamos un caso en el que la hemorragia coclear produjo una sordera súbita en una mujer de 22 años previamente asintomática. Revisamos la bibliografía y evaluamos el papel de la existencia de hiperintensidad en los estudios de RM craneal

Sudden deafness owing to labyrinth hemorrhage is a relatively rare clinical entity; labyrinth hemorrhage may be the only demonstrable finding in neuroimaging studies performed for sudden deafness, whether as an isolated finding or associated with labyrinthitis, manifesting as labyrinth hyperintensity in T1-weighted MRI sequences without enhancement after contrast administration. We present a case in which cochlear hemorrhage caused sudden deafness in a previously asymptomatic 22-year-old woman. We review the literature and evaluate the role of the presence of hyperintensity in cranial MRI