Liver growth prediction in ALPPS - A multicenter analysis from the international ALPPS registry.

BACKGROUND: While ALPPS triggers a fast liver hypertrophy, it is still unclear which factors matter most to achieve accelerated hypertrophy within a short period of time. The aim of the study was to identify patient-intrinsic factors related to the growth of the future liver remnant (FLR). METHODS: This cohort study is composed of data derived from the International ALPPS Registry from November 2011 and October 2018. We analyse the influence of demographic, tumour type and perioperative data on the growth of the FLR. The volume of the FLR was calculated in millilitre and percentage using computed-tomography (CT) scans before and after stage 1, both according to Vauthey formula. RESULTS: A total of 734 patients were included from 99 centres. The median sFLR at stage 1 and stage 2 was 0.23 (IQR, 0.18-0.28) and 0.39 (IQR: 0.31-0.46), respectively. The variables associated with a lower increase from sFLR1 to sFLR2 were age˃68 years (p = .02), height ˃1.76 m (p ˂ .01), weight ˃83 kg (p ˂ .01), BMI˃28 (p ˂ .01), male gender (p ˂ .01), antihypertensive therapy (p ˂ .01), operation time ˃370 minutes (p ˂ .01) and hospital stay˃14 days (p ˂ .01). The time required to reach sufficient volume for stage 2, male gender accounts 40.3% in group ˂7 days, compared with 50% of female, and female present 15.3% in group ˃14 days compared with 20.6% of male. CONCLUSIONS: Height, weight, FLR size and gender could be the variables that most constantly influence both daily growths, the interstage increase and the standardized FLR before the second stage.

Isolated Spleen Metastases of Endometrial Cancer: A Case Report.

BACKGROUND: Isolated splenic metastases from endometrial cancer, which is a relatively common malignancy, are extremely rare findings; to date, only 14 cases have been reported in the literature. CASE SUMMARY: We report a patient with isolated splenic metastases of endometrial cancer 3 years after radical surgery of the primary tumor. The patient was successfully treated by splenectomy and six cycles of paclitaxel. Fifty months after splenectomy, she was alive and well, and with no evidence of disease. CONCLUSION: Isolated spleen metastasis of endometrial cancer is very rare. Radical surgery and adjuvant therapy may offer excellent long-term survival.

Subcutaneous and Intraosseous Fat Necrosis Associated with Chronic Pancreatitis.

Background: Extra-abdominal manifestations of fat necrosis, like subcutaneous fat necrosis, polyarthritis, and polyserositis may appear with an occurrence rate of about 0.8%, wherein intraosseous fat necrosis is a more rare complication of pancreatitis, with few reports in English literature. Case report: A 34-year-old male with a 15-year-history of alcohol abuse was hospitalized several times in the last few years because of attacks of relapsed chronic pancreatitis. After the last attack, pancreatitis came in a stable state ("burned out") with no symptoms and signs of the disease. The patient had been free of symptoms for 28 months since the last admission when he came with sub-febrile temperature, huge pain, swelling, and erythema in the area of the left lateral malleolar region with propagation in the foot. Blood biochemistry was normal. Conventional radiography showed multiple sites of osteolysis in the left calcaneus. Images on multislice computed tomography (MSCT) with 3D reconstruction revealed hypodense focuses that corresponded to osteonecrosis areas and bone marrow edema in the left calcaneus. Conclusions: The possibility of intraosseous fat necrosis should be considered in situations of unexplained polyarthritis or panniculitis, particularly in individuals with alcohol abuse or pancreatic disease.

Incidence and mortality rates of Guillain-Barré syndrome in Serbia.

Guillain-Barré syndrome (GBS) is an acute auto-immune polyradiculoneuropathy. A huge variety of GBS incidence and mortality rates has been noted across the world. The objective of the present multi-centric study was to assess the incidence and mortality rates of GBS during a 10-year period in Serbia. We collected data of adult GBS patients who were hospitalized from 2009 to 2018 in all five tertiary healthcare centers in Serbia. The incidence rates per 100 000 inhabitants with 95% confidence intervals (CI) were calculated and further corrected for the estimated number of patients hospitalized in secondary centers. Mortality rates were also assessed. GBS was considered severe if patients were not able to walk at least 10 m without assistance. Six hundred and forty GBS patients were registered in tertiary centers in a 10-year period. The proportion of severe cases was 75% at nadir, and 52% on discharge. GBS incidence rate in Serbia was 1.1 per 100 000 inhabitants, and estimated incidence if patients from secondary centers included 1.2 per 100 000. Peak incidence was observed during the sixth decade of life. During the acute phase, 5.6% of GBS patients died, while overall 9.7% of them died during 6-month period from disease onset. This study contributes to our knowledge about GBS epidemiology. Results will allow us to improve the diagnosis and treatment of GBS patients in Serbia.

Employment status of patients with chronic inflammatory demyelinating polyradiculoneuropathy.

It has been previously shown that patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who are unemployed or retired have worse quality of life. The aim of this study was to assess predictors of early retirement in CIDP. One hundred five patients with CIDP were included. Following measures were used: questionnaire on employment status, Medical Research Council Sum Score, INCAT disability score, Beck Depression Inventory, and Krupp's Fatigue Severity Scale. At the moment of testing, 2% of patients were students, 15% were employed, 9% were unemployed due to CIDP, 9% were unemployed but not due to CIDP, 28% were retired early due to disability caused by CIDP, and finally 37% were in old-age pension. Mean age when patients retired due to CIDP was 50 ± 8 years. Mean time from CIDP onset to retirement was 2.7 ± 2.3 years. Older age at onset, lower education, and more severe weakness at the time of diagnosis were significant predictors of early retirement due to CIDP. Retired patients were 12 times more likely to suffer from depression, compared to employed patients (OR = 12.2, 95% CI = 1.41-100, P < 0.01), and eight times more likely to have fatigue (OR = 8.2, 95% CI = 1.89-35.82, P < 0.01). Older patients with lower education and more severe weakness at the time of diagnosis were most likely retired due to CIDP. Early retirement was associated with depression and fatigue. Therefore, maintaining employment should be an important aim in the management of CIDP patients.

Neuromuscular disease-specific questionnaire to assess quality of life in patients with chronic inflammatory demyelinating polyradiculoneuropathy.

To date, generic questionnaires have been used to investigate quality of life (QoL) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients. Although these measures are very useful, they are not usually precise enough to measure all specific characteristics of the disease. Our aim was to investigate QoL using the neuromuscular disease-specific questionnaire (individualized neuromuscular quality of life, INQoL) in a large cohort of patients with CIDP. Our study comprised 106 patients diagnosed with CIDP. INQoL questionnaire, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, Visual Analogue Pain Scale, Beck Depression Inventory, and Krupp's Fatigue Severity Scale were used in our study. Physical domains of INQoL were more affected than mental, and the overall score was 57 ± 25. Significant predictors of higher INQoL score in our patients with CIDP were severe fatigue (ß = 0.35, p < 0.01), higher INCAT disability score at time of testing (ß = 0.29, p < 0.01), and being unemployed/retired (ß = 0.22, p < 0.05). QoL was reduced in our cohort of CIDP patients, which was more pronounced in physical segments. Patients with fatigue, more severe disability, and unemployed/retired need special attention of neurologists because they could be at greater risk to have worse QoL.

Predictors of Mortality in Long-Term Follow-Up of Patients with Terminal Alcoholic Cirrhosis: Is It Time to Accept Remodeled Scores?

OBJECTIVE: To identify the prognostic score that is the best predictor of outcome in patients hospitalized with decompensated liver cirrhosis. MATERIAL AND METHODS: In this prospective study, 126 patients were enrolled and followed up for 29 months. For each patient, prognostic scores were calculated; these included the Child-Turcotte-Pugh score (CTP score), CTP creatinine-modified I score, CTP creatinine-modified II score, Model for End-Stage Liver Disease (MELD score), MELD model for end-stage liver disease sodium-modified score, Integrated MELD score, updated MELD score, United Kingdom MELD, and the MELD score remodeled by serum sodium index (MESO index). Cox regression analysis was used to assess the ability of each of the scores for predicting mortality in patients with alcoholic cirrhosis. Their discriminatory ability was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: The updated MELD score had the highest predictive value (3.29) among the tested scores (95% CI: 2.26-4.78). ROC curve analysis demonstrated that the MELD score of 22.50 (AUC = 0.914, 95% CI: 0.849-0.978; p < 0.001) had the best discriminative ability for identifying patients with a high risk of mortality; the next best was the MESO index of 16.00 (AUC = 0.912, 95% CI: 0.847-0.978; p < 0.001). CONCLUSION: The risk of mortality was highest in patients with the highest updated MELD score, and those with MELD scores >22.50 and a MESO index >16.00.

Laparotomy site implantation metastasis of carcinoma of the papilla of Vater.

Introduction Carcinomas of the papilla of Vater make up a heterogeneous group of tumours arising from different types of epithelium. Regional lymph nodes, liver and lungs are the primary sites of metastatic progression of these tumours. Case presentation We present a patient with an abdominal incision site metastasis of low-grade (mixed type) adenocarcinoma of the papilla of Vater one year after pylorus-preserving pancreaticoduodenectomy. Implantation metastasis of low-grade ampullary carcinoma in the laparotomy wound after open Whipple's procedure is unusual. Conclusion Adjuvant chemoradiation might be considered for patients with low-grade localised disease as a potentially preventative measure vs. metastatic progression.

Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial.

BACKGROUND: The anti-CD52 monoclonal antibody alemtuzumab reduced disease activity in a phase 2 trial of previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of first-line alemtuzumab compared with interferon beta 1a in a phase 3 trial. METHODS: In our 2 year, rater-masked, randomised controlled phase 3 trial, we enrolled adults aged 18-50 years with previously untreated relapsing-remitting multiple sclerosis. Eligible participants were randomly allocated in a 2:1 ratio by an interactive voice response system, stratified by site, to receive intravenous alemtuzumab 12 mg per day or subcutaneous interferon beta 1a 44 µg. Interferon beta 1a was given three-times per week and alemtuzumab was given once per day for 5 days at baseline and once per day for 3 days at 12 months. Coprimary endpoints were relapse rate and time to 6 month sustained accumulation of disability in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00530348. FINDINGS: 187 (96%) of 195 patients randomly allocated interferon beta 1a and 376 (97%) of 386 patients randomly allocated alemtuzumab were included in the primary analyses. 75 (40%) patients in the interferon beta 1a group relapsed (122 events) compared with 82 (22%) patients in the alemtuzumab group (119 events; rate ratio 0·45 [95% CI 0·32-0·63]; p<0.0001), corresponding to a 54·9% improvement with alemtuzumab. Based on Kaplan-Meier estimates, 59% of patients in the interferon beta 1a group were relapse-free at 2 years compared with 78% of patients in the alemtuzumab group (p<0·0001). 20 (11%) of patients in the interferon beta 1a group had sustained accumulation of disability compared with 30 (8%) in the alemtuzumab group (hazard ratio 0·70 [95% CI 0·40-1·23]; p=0·22). 338 (90%) of patients in the alemtuzumab group had infusion-associated reactions; 12 (3%) of which were regarded as serious. Infections, predominantly of mild or moderate severity, occurred in 253 (67%) patients treated with alemtuzumab versus 85 (45%) patients treated with interferon beta 1a. 62 (16%) patients treated with alemtuzumab had herpes infections (predominantly cutaneous) compared with three (2%) patients treated with interferon beta 1a. By 24 months, 68 (18%) patients in the alemtuzumab group had thyroid-associated adverse events compared with 12 (6%) in the interferon beta 1a group, and three (1%) had immune thrombocytopenia compared with none in the interferon beta 1a group. Two patients in the alemtuzumab group developed thyroid papillary carcinoma. INTERPRETATION: Alemtuzumab's consistent safety profile and benefit in terms of reductions of relapse support its use for patients with previously untreated relapsing-remitting multiple sclerosis; however, benefit in terms of disability endpoints noted in previous trials was not observed here. FUNDING: Genzyme (Sanofi) and Bayer Schering Pharma.

The effect of ursodeoxycholic acid on oxidative stress level and DNase activity in rat liver after bile duct ligation.

Accumulation of hydrophobic bile acids (BAs) during cholestasis plays an important role in apoptosis initiation as well as oxidative stress increase in liver cells. Ursodeoxycholic acid (UDCA) acts as a protector in BA-induced cell injury.The aim of the study was to evaluate the effect of UDCA on oxidative stress level and DNase I and II activity caused by liver injury in bile duct ligation (BDL) rats.Wistar rats were divided in four groups: group 1, control (sham-operated); group 2, sham-operated and injected with UDCA (30 mg/kg); group 3,animals with BDL; and group 4,UDCA-treatedcholestatic rats. Animals were sacrificed after 9 days. Malondialdehyde (MDA; lipid peroxidation end-product) level and protein-molecule oxidative modification (carbonyl group content) significantly increased in BDL rat liver. Catalase (CAT) activity in liver tissue was found to be decreased in BDL rats. In addition, xanthine oxidase (XO) activity, which is thought to be one of the key enzymes producing reactive oxygen species, was found to be increased in the cholestatic group. The apoptotic effect in cholestasis was probably triggered by the increased activation of DNase I and II. The protective effect of UDCA on liver tissue damage in BDL rats, in comparison to cholestatic liver, were 1) decrease of MDA levels, 2) increased CAT activity, 3) reduced XO activity, and 4) effect on terminal apoptotic reaction, shown as a decrease in DNase I and II activity.Therefore, UDCA may be useful in the preservation of liver function in cholestasis treatment.

Nonfunctional retroperitoneal paraganglioma presenting as acute upper gastrointestinal hemorrhage.

Paragangliomas are very rare tumors arising from extraadrenal chromaffin cells. Clinical presentation of benign retroperitoneal nonfunctional paraganglioma is unspecific. Symptoms may occur when tumor attains a remarkable size or when complications arise. This article reports a case of nonfunctional retroperitoneal paraganglioma as a cause of acute upper gastrointestinal hemorrhage which represents the unusual urgent clinical manifestation of these tumors. The presented case emphasizes the necessity to include extraadrenal paraganglioma in the differential diagnosis in all patients with retroperitoneal mass found even in the presence of at first appearance non-related emergency condition like acute upper gastrointestinal bleeding.

Disability and quality of life in Guillain-Barré syndrome - Longitudinal study.

Longitudinal health-related quality of life (QoL) data in Guillain-Barré (GBS) patients are still scarce. We, therefore, investigated health- related QoL in GBS patients from Serbia and surrounding countries during a six-month follow-up period, and analyzed its association with patients' disability. Our study comprised 74 adult patients diagnosed with GBS from May 2017 until May 2018 in seven tertiary healthcare centers. Health-related QoL was investigated using the SF-36 questionnaire, and compared with functional disability assessed by the GBS disability scale (GDS). Tests were performed at day 14, day 28, month 3 and month 6 from disease onset. GDS and SF-36 scores improved over time (p < 0.01). GDS scores were different at all four time points, while SF-36 did not differ between day 14 and day 28. Pooled SF-36 scores (especially physical ones) correlated with pooled GDS scores, except for Bodily Pain and Role Emotional scores. We found that GDS score at day 14 was an independent predictor of GDS score at month 6 (ß = +0.52, p < 0.01), while SF-36 score at day 14 was an independent predictor of SF-36 score at month 6 (ß = +0.51, p < 0.01). Neurologists should look not only on disability but also on QoL in GBS patients, since these two measures provide us with important complementary items of information.

Three cases of death caused by shots from blank cartridge.

The authors describe 3 cases of lethal injuries caused by 7.62 mm blank cartridge shots from military automatic rifle of domestic origin (AK 47, 7.62 mm). In 1 case, the cartridge was fired from a weapon that had been leaned on the head, with subsequent destruction of brain, and in other 2 cases, the weapon had been leaned on the chests, which led to destruction of heart parts. The injuries were caused by the action of striking wave of gunpowder explosion, the air blast type. The cases demonstrate that the gas pressure from the exploding propellant of blank cartridge is powerful enough to penetrate the thoracic wall and the skull.

Reversal of effects of acidosis on contraction of rat heart myocytes by CGP-48506.

In experiments reported here, we tested the ability of CGP-48506 to reverse the depressed cardiac contractility associated with hypercapnic acidosis in isolated rat cardiac myocytes. CGP-48506 is a cardiotonic agent that directly and specifically promotes the actin-cross-bridge reaction. Myocytes superfused at pH 6.8 demonstrated a significantly reduced extent of cell shortening, but an increase in the peak amplitude of the Ca2+ transient. Moreover, cells in acidosis showed small, but significant, decreases in time to peak shortening to 50 percent relaxation. Superfusion of the cells with 3, 7, and 10 micro-molar CGP-48506 restored the inhibited contractility as a function of concentration with no significant effects on the Ca2+-transient. Moreover, 10 micro-molar CGP-48506 completely reversed the depressed myocyte contraction associated with an increase in time to peak shortening and time to 50 percent and 75 percent relaxation. Our results indicate that the depression of contractility associated with acidosis is due to a reduced myofilament response to Ca2+, which can be overcome by agents working downstream from troponin C through a direct effect on the actin-myosin interaction.

Large retroperitoneal schwannoma: a rare cause of chronic back pain.

Schwannomas are tumours that arise from Schwann cells of the peripheral nerve sheath and rarely occur in the retroperitoneum. We report a 45-year-old woman who presented with a 2-year history of continuous progressive right-sided lower back and dull flank pain radiating into her posterolateral thigh. Abdominal magnetic resonance imaging showed a homogenous soft-tissue tumour with thick capsular lining, which lay in the right retroperitoneum. The tumour was removed at surgery. A histological examination confirmed the diagnosis of benign encapsulated cellular schwannoma. Complete tumour excision should be regarded as the treatment of choice for benign retroperitoneal schwannomas. Successful treatment of these tumours requires thorough preoperative planning and a multidisciplinary approach.

Histopathologic differentiation as a prognostic factor in patients with carcinoma of the hepatopancreatic ampulla of Vater.

OBJECTIVE: Periampullary carcinomas are a group of neoplasms with variable histopathology that originate from the anatomical junction of different epithelial types including the bile duct, pancreatic duct, and duodenal mucosa. This study was performed to determine whether the histopathologic type of these tumors should be considered an independent prognostic factor. METHODS: We analyzed the specimen histopathology of 37 patients who underwent radical cephalic pancreatoduodenectomy for carcinoma of the ampulla of Vater during a 5-year period. We excluded patients with other tumors with an indication for Whipple's procedure and those in whom R0 resection was not achieved. RESULTS: The carcinomas of the hepatopancreatic ampulla were intestinal in 23 (62%) patients, pancreatobiliary in 13 (35%), and mixed type in 1 (3%). The analysis demonstrated significantly more advanced local tumor spread, a more aggressive lymph node metastasizing pattern, and more frequent lymphatic and perineural invasion in patients with pancreatobiliary than intestinal and mixed type tumors. CONCLUSION: Pancreatobiliary type of ampullary carcinoma is associated with a poorer prognosis than intestinal and mixed types because of its more aggressive behavior. Histopathology should be regarded as an independent predictor of survival and may have therapeutic and prognostic implications for patients.

A Prospective, Randomized, Phase III Study to Evaluate the Efficacy and Safety of Fibrin Sealant Grifols as an Adjunct to Hemostasis as Compared to Cellulose Sheets in Hepatic Surgery Resections.

BACKGROUND: Local hemostatic agents have a role in limiting bleeding complications associated with liver resection. METHODS: In this randomized, phase III study, we compared the efficacy and safety of Fibrin Sealant Grifols (FS Grifols) with oxidized cellulose sheets (Surgicel®) as adjuncts to hemostasis during hepatic resections. The primary efficacy endpoint was the proportion of patients achieving hemostasis at target bleeding sites (TBS) within 4 min (T4) of treatment application. Secondary efficacy variables were time to hemostasis (TTH) at a later time point if re-bleeding occurs and cumulative proportion of patients achieving hemostasis by time points T2, T3, T5, T7, and T10. RESULTS: The rate of hemostasis by T4 was 92.8% in the FS Grifols group (n = 163) and 80.5% in the Surgicel® group (n = 162) (p = 0.01). The mean TTH was significantly shorter (p < 0.001) in the FS Grifols group (2.8 ± 0.14 vs. 3.8 ± 0.24 min). The rate of hemostasis by T2, T5, and T7 was higher and statistically superior in the FS Grifols group compared to Surgicel®. No substantial differences in adverse events (AE) were noted between treatment groups. The most common AEs were procedural pain (36.2 vs. 37.7%), nausea (20.9 vs. 23.5%), and hypotension (14.1 vs 6.2%). CONCLUSIONS: FS Grifols was safe and well tolerated as a local hemostatic agent during liver resection surgeries. Overall, data demonstrate that the hemostatic efficacy of FS Grifols is superior to Surgicel® and support the use of FS Grifols as an effective local hemostatic agent in these surgical procedures.

Quality of life predictors in patients with chronic inflammatory demyelinating polyradiculoneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic disease which can lead to many functional impairments, and like most other chronic disorders it might significantly affect quality of life (QoL). Information about QoL in patients with CIDP from developing countries is still lacking. We, therefore, sought to complete these data mosaic by investigating QoL in patients with CIDP from Serbia and surrounding countries. Our study comprised 106 patients diagnosed with CIDP. QoL was investigated using the Serbian version of the SF-36 questionnaire. The Medical Research Council 0-5 point scale, INCAT motor and sensory scores, Krupp's Fatigue Severity Scale, and Beck Depression Inventory were also used. Factors that significantly correlated with SF-36 total score in univariate analysis were included in the multiple linear regression analysis. Physical domains of the SF-36 were more affected than mental, and the overall score was 56.6 ± 25.4. Significant predictors of worse SF-36 score in our patients with CIDP were severe fatigue (ß = - 0.331, p < 0.01), higher INCAT motor score (ß = - 0.301, p < 0.01), depression (ß = - 0.281, p < 0.01), being unemployed/retired (ß = - 0.188, p < 0.05), and shorter duration of CIDP (ß = + 0.133, p < 0.01). QoL was reduced in CIDP patients, especially in physical domains. Patients with presence of fatigue and depression, with more severe motor disability, unemployed/retired ones, and those with shorter duration of the disease need special attention of clinicians since they could be at higher risk to have worse QoL.

Triple gastric peptic ulcer perforation.

Patients with advanced or metastatic cancer have compromised nutritional, metabolic, and immune conditions. Nevertheless, little is known about gastroduodenal perforation in cancer patients. Described in the present report is the case of a 41-year old woman with stage IV recurrent laryngeal cancer, who used homeopathic anticancer therapy and who had triple peptic ulcer perforation (PUP) that required surgical repair. Triple gastric PUP is a rare complication. Self-administration of homeopathic anticancer medication should be strongly discouraged when evidence-based data regarding efficacy and toxicity is lacking.

Superior MRI outcomes with alemtuzumab compared with subcutaneous interferon ß-1a in MS.

OBJECTIVE: To describe detailed MRI results from 2 head-to-head phase III trials, Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis Study I (CARE-MS I; NCT00530348) and Study II (CARE-MS II; NCT00548405), of alemtuzumab vs subcutaneous interferon ß-1a (SC IFN-ß-1a) in patients with active relapsing-remitting multiple sclerosis (RRMS). METHODS: The impact of alemtuzumab 12 mg vs SC IFN-ß-1a 44 µg on MRI measures was evaluated in patients with RRMS who were treatment-naive (CARE-MS I) or who had an inadequate response, defined as at least one relapse, to prior therapy (CARE-MS II). RESULTS: Both treatments prevented T2-hyperintense lesion volume increases from baseline. Alemtuzumab was more effective than SC IFN-ß-1a on most lesion-based endpoints in both studies (p < 0.05), including decreased risk of new/enlarging T2 lesions over 2 years and gadolinium-enhancing lesions at year 2. Reduced risk of new T1 lesions (p < 0.0001) and gadolinium-enhancing lesion conversion to T1-hypointense black holes (p = 0.0078) were observed with alemtuzumab vs SC IFN-ß-1a in CARE-MS II. Alemtuzumab slowed brain volume loss over 2 years in CARE-MS I (p < 0.0001) and II (p = 0.012) vs SC IFN-ß-1a. CONCLUSIONS: Alemtuzumab demonstrated greater efficacy than SC IFN-ß-1a on MRI endpoints in active RRMS. The superiority of alemtuzumab was more prominent during the second year of both studies. These findings complement the superior clinical efficacy of alemtuzumab over SC IFN-ß-1a in RRMS. CLINICALTRIALSGOV IDENTIFIER: NCT00530348 and NCT00548405. CLASSIFICATION OF EVIDENCE: The results reported here provide Class I evidence that, for patients with active RRMS, alemtuzumab is superior to SC IFN-ß-1a on multiple MRI endpoints.