Shorter infusion time of ocrelizumab: Results from the randomized, double-blind ENSEMBLE PLUS substudy in patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Ocrelizumab is an approved intravenously administered anti-CD20 antibody for multiple sclerosis (MS). Shortening the 600 mg infusion to 2 hours reduces the total site stay from 5.5-6 hours (approved infusion duration including mandatory pre-medication and post-infusion observation) to 4 hours. The safety profile of shorter-duration ocrelizumab infusions was investigated using results from ENSEMBLE PLUS. METHODS: ENSEMBLE PLUS is a randomized, double-blind substudy to the single-arm ENSEMBLE study (NCT03085810). In ENSEMBLE, patients with early-stage relapsing-remitting MS received ocrelizumab 600 mg infusions every 24 weeks for 192 weeks. In ENSEMBLE PLUS, ocrelizumab 600 mg administered over the approved 3.5-hour infusion time (conventional duration) is compared with a 2-hour infusion (shorter duration); the durations of the initial infusions (2×300 mg, 14 days apart) were unaffected. The primary endpoint was the proportion of patients with infusion-related reactions (IRRs) following the first Randomized Dose. RESULTS: From November 1, 2018, to December 13, 2019, 745 patients were randomized 1:1 to the conventional or shorter infusion group. At the first Randomized Dose, 99/373 patients (26.5%) in the conventional and 107/372 patients (28.8%) in the shorter infusion group experienced IRRs. The majority of IRRs were mild or moderate; >99% of all IRRs resolved without sequelae in both groups (conventional infusion group, 99/99; shorter infusion group, 106/107). No IRRs were serious, life-threatening, or fatal. No IRR-related discontinuations occurred. During the first Randomized Dose, 22/373 (5.9%) and 39/372 (10.5%) patients in the conventional and shorter infusion groups, respectively, had IRRs leading to infusion slowing/interruption. Adverse events were consistent with the known safety profile of ocrelizumab. CONCLUSION: The rates and severity of IRRs were similar between conventional and shorter infusions. No new safety signals were detected. Shortening the infusion time to 2 hours reduces the total site stay time (including mandatory pre-medication/infusion/observation) from 5.5-6 hours to 4 hours, and may reduce patient and site staff burden. A short video summarizing the key results is provided in supplemental material.

Oncoplastic Level 2 Mammoplasty for Large DCIS: 5-Year Results.

BACKGROUND: Oncoplastic surgery (OPS) allows wider resections with immediate breast reshaping by mammoplasty. This study reviews our experience with level 2 mammoplasties in patients with histology-proven pure ductal carcinoma in situ (DCIS). METHOD: From a prospectively maintained database of 392 consecutive oncoplastic level 2 mammoplasties, 68 patients presented with pure DCIS. Involved margin rates and locoregional recurrence rates were calculated, with 76 months (0-166 months) median follow-up. RESULTS: The mean pathological tumor size was 34 mm (median 26 mm, range 2-106 mm). The mean resection weight was 191 g (median 131 g, range 40-1150 g). Margins were clear in 58 cases (85.3%) and involved in 10 cases (14.7%). Margins were involved in 1 out of 54 (1.9%) cases with tumor size under 50 mm and in 9 out of 14 (64.3%) cases with tumor size higher than 50 mm (p < 0.001). On multivariable analysis, only tumor size > 50 mm [odds ratio (OR) 95.400; p < 0.001] was independently associated with involved margins. Seven patients had mastectomy. The overall breast conservation rate was 89.4%, and 100% for tumors less than 5 cm. There were three local recurrences. The 5-year cumulative incidence for local recurrence was 5.5% (0-11.5%). CONCLUSIONS: OPS is a safe solution for large DCIS up to 50 mm, with an involved margin rate of only 1.9%, and can thus reduce the mastectomy rate in this group. As margin involvement significantly increases for tumors larger than 5 cm, better preoperative localization and/or wider excisions are necessary in this group.

[Prophylactic hysterectomy in Lynch syndrome: Feasibility and outcomes]. / Faisabilité et résultats de l'hystérectomie prophylactique dans le syndrome de Lynch.

OBJECTIVES: Lynch syndrome (LS) is a hereditary predisposition to cancers, first of all, colo-rectal and endometrial cancers in women. Although recommended, gynecologic screening has never proven its benefit. Prophylactic surgery can be considered once the parental project is completed. There are few data regarding the assessment of prophylactic surgery. The objectives of our study were to evaluate the feasibility and morbidity of prophylactic hysterectomy in patients with Lynch syndrome. METHODS: This is a descriptive retrospective study of consecutive patients with LS undergoing prophylactic hysterectomy at the Georges-Pompidou European Hospital from 2002 to 2016. We collected demographic characteristics, results of preoperative assessment, intra- and postoperative data, final pathologic result as well as postoperative follow-up data. RESULTS: Forty patients were included in the study, and seventeen women had a history of colon cancer surgery. All hysterectomies were performed by laparoscopy, with two cases of laparoconversion. Two intraoperative complications occurred: serosal small bowel injuries and superficial bladder injury. Two early postoperative complications occurred (a peritonitis on small bowel perforation and a peritonitis on left ureteral injury) and two late complications (vesico-vaginal fistula and adhesive small bowel obstruction). All operative specimens were benign. With a median follow-up of 28 months [5-52], no patient had peritoneal cancer. CONCLUSIONS: Our study shows that prophylactic hysterectomy in Lynch syndrome should be done with caution. Per and postoperative complication rates appear to be higher than in general population, probably related to a more frequent history of colorectal cancer. However, total hysterectomy with bilateral salpingo-oophorectomy appears to be an effective strategy for preventing gynecological cancers in women with the Lynch syndrome.

What about sentinel lymph node biopsy for early breast cancer during pregnancy?

Pregnancy-associated breast cancer is rare, but this clinical situation arises in 1/10,000-1/3000 pregnancies. In patients presenting an early-stage breast tumor devoid of clinically pathological lymph node, sentinel lymph node (SLN) biopsy has not yet been validated as a routine procedure for pregnant women due to the lack of data in the literature. The blue dye injection is not recommended because of 2% theoretical risk of anaphylactic shock. Several studies have shown that Tc99m injection at conventional dose between 12.1 and 18.5MBq exposed the fetus to an irradiation between 0.011 and 0.0245mSv much below the 50mSv recommended threshold. As evidenced by lymphoscintigraphy scans, the dose of injected Tc99m is localized at the injection site and in the SLN. According to the literature, the SLN technique does not seem to impact the fetal or obstetrical prognosis. Studies involving larger cohorts are required to confirm these data and to indicate this technique in pregnant women. Considering the benefit for the patient and the low risk incurred on both fetal and obstetrical levels, it appears reasonable to discuss the indication of SLN on a case-by-case basis in multidisciplinary oncologic meetings.

A prospective randomized study comparing centrifugation and sedimentation for fat grafting in breast reconstruction.

BACKGROUND: Fat grafting is an efficient method to correct large volumetric defects after mastectomy. There is an ongoing debate regarding the best method of processing the harvested fat before fat grafting. This study aimed to introduce a new MRI model and to compare two fat processing techniques measuring the gain in soft tissue thickness after fat grafting to the chest wall. METHODS: Fifty-one mastectomy patients (one double sided), who required delayed implant reconstruction, with poor skin conditions were proposed fat grafting prior to implant reconstruction. At the time of fat grafting, patients were randomly assigned to centrifugation or sedimentation of the aspirated fat. The trial was undertaken in a single-center private practice setting. The gain in soft tissue thickness of the chest wall was measured using an MRI model, with 12 predefined points for measurement. Two MRIs were performed, one prior to fat grafting and one 8 weeks thereafter. The radiologist was blinded to the fat graft processing method used. RESULTS: Seven cases were excluded because they did not complete their second MRI. The analyses were thus based on 44 patients (one double sided). Centrifugation was performed in 21 cases and sedimentation in 24 cases. The mean gain in soft tissue thickness was +7.0 mm in the centrifugation group and +8.8 mm in the sedimentation group (p = .268). The mean operative time was 88 min in the centrifugation group and 78 min in the sedimentation group (p = .11). There were no adverse events for any of the patients. CONCLUSIONS: We developed a simple and reproducible MRI model to objectively measure and evaluate different fat processing techniques prior to fat grafting. At a median time of 8 weeks after one session of fat grafting, there was no benefit of centrifugation over sedimentation.

Upper outer boundaries of the axillary dissection. Result of the SENTIBRAS protocol: Multicentric protocol using axillary reverse mapping in breast cancer patients requiring axillary dissection.

BACKGROUND: Two thirds of node-positive breast cancer patients have limited pN1 disease and could benefit from a less extensive axillary lymph node dissection (ALND). METHODS: 172 breast cancers patients requiring an ALND were prospectively enrolled in the Sentibras Protocol of Axillary Reverse Mapping (ARM). Radioisotope was injected in the ipsilateral hand the day before surgery. ALND was standard. Removed lymph nodes were classified into non radioactive nodes and radioactive nodes (ARM nodes). Among ARM nodes, nodes located in the upper outer part of the axilla, above the second intercostal brachial nerve and lateral to the lateral thoracic vein were identified as "zone D ARM nodes". The main objective was: feasibility of identification of the zone D ARM nodes. Secondary objectives were: metastatic involvement and lymphedema rate. RESULTS: 100% of patients had ARM nodes identified. The "zone D ARM nodes" were identified in 92% of cases. The rate of metastatic nodes was 60% in the all cohort, 31% in ARM nodes and 9% in zone D ARM nodes. Among those, metastatic rate was 6% in patients undergoing ALND for a positive sentinel node biopsy, 6% in case of primary ALND versus 14% after neo-adjuvant chemotherapy (p < 0.05). After 34 months of median follow up, 27% of interviewed patients had a lymphedema. CONCLUSION: The ARM technique reliably identifies the "zone D ARM nodes". These nodes can also easily be identified using knowledge of axillary anatomy. In selected patients, a selective ALND sparing the zone D ARM nodes could be performed.

[Axillary management in breast cancer: The French practice versus recommendations in the post-2011 era]. / Ganglion sentinelle et curage axillaire dans le cancer du sein : la pratique française face aux recommandations à l'ère post-2011.

OBJECTIVES: Today, according to St-Gallen and ASCO clinical guidelines, axillary lymph node dissection (ALND) should be avoided in patients who meet the ACOSOG Z011 criteria. In French guidelines, ALND is still recommended in case of macrometastasis in sentinel lymph node (SLN) and in case of micrometastasis without systemic treatment. We performed a survey of the French practices in the management of the axilla. MATERIAL AND METHODS: A questionnaire was sent to 454 breast surgeons between June 2014 and January 2015. Questionnaire included items about: indications of SLN biopsy, frequency of ALND in case of metastatic SLN and modality of radiotherapy in case of metastatic SLN without ALND. RESULTS: A total of 169 surgeons (37%) answer the questionnaire. Twenty-one percent of surgeons avoid ALND in case of macrometastasis. Thirty-two percent do not perform extemporaneous examination of SLN. Only 8.4% of practionners performed a SLN biopsy after neoadjuvant chemotherapy. Fourteen percent performed a SLN biopsy in case of multicentric tumors, while it is not recommended. In case of positive SLN without ALND completion, radiotherapy does not change in 34% while irradiation fields are expanded in 44%. CONCLUSIONS: Significant unconformities are observed towards national recommendations. The divergence between French and international guidelines leads to heterogeneous surgical practices.

Significant clinical worsening after natalizumab withdrawal: Predictive factors.

We aimed to single out multiple sclerosis (MS) cases with poor outcome after natalizumab withdrawal and to identify predictive variables. We ascertained 47 withdrawals, and compared their pre- and post-natalizumab periods. We objectively defined significant clinical worsening after natalizumab withdrawal as a 2-step increase in Expanded Disability Status Scale (EDSS). We performed regression models. As a group, post-natalizumab annualized relapse rate (ARR) was lower in the post-natalizumab period, and there were no differences in the mean number of gadolinium (Gd)-enhancing lesions between pre- and post-natalizumab magnetic resonance imaging (MRI). Corticosteroid treatment did not change the outcomes. Eight patients (19%) presented significant clinical worsening after natalizumab withdrawal, which was predicted by a higher baseline EDSS and a 1-step EDSS increase while on natalizumab.

A randomized clinical trial of oral versus intravenous methylprednisolone for relapse of MS.

BACKGROUND: Steroids improve multiple sclerosis (MS) relapses but therapeutic window and dose, frequency and administration route remain uncertain. OBJECTIVE: The objective of this paper is to compare the clinical and radiologic efficacy, tolerability and safety of intravenous methylprednisolone (ivMP) vs oral methylprednisolone (oMP), at equivalent high doses, for MS relapse. METHODS: Forty-nine patients with moderate or severe relapse within the previous 15 days were randomized in a double-blind, noninferiority, multicenter trial to receive ivMP or oMP and their matching placebos. Expanded Disability Status Scale (EDSS) scores were determined at baseline and weeks 1, 4 and 12. Brain MRI were assessed at baseline and at weeks 1 and 4. Primary endpoint was a noninferiority assessment of EDSS improvement at four weeks (noninferiority margin of one point), with further key efficacy assessments of number and volume of T1 gadolinium-enhancing (Gd+), and new or enlarged T2 lesions at four weeks' post-treatment initiation. Secondary outcomes were safety and tolerability. RESULTS: The study achieved the main outcome of noninferiority at four weeks for improved EDSS score. No differences were found between ivMP and oMP in the number of Gd+ lesions (0 (0-1) vs 0 (0-0.5), p = 0.630), volume of Gd+ lesions (0 (0-88.0) vs 0 (0-32.9) mm(3), p = 0.735), or new or enlarged T2 lesions (0 (0-194) vs 0 (0-123), p = 0.769). MP was well tolerated, and no serious adverse events were reported. CONCLUSIONS: This study provides confirmatory evidence that oMP is not inferior to ivMP in reducing EDSS, similar in MRI lesions at four weeks for MS relapses and is equally well tolerated and safe. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00753792.

Clinical impact of early brain atrophy in clinically isolated syndromes.

BACKGROUND: The impact of global and tissue-specific brain atrophy on conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS) is not fully gauged. OBJECTIVES: We aimed to determine the magnitude and clinical relevance of brain volume dynamics in the first year after a CIS. METHODS: We assessed 176 patients with CIS within 3 months of onset, clinically and by conventional magnetic resonance imaging (MRI) scans, at baseline and 1 year after clinical onset. We determined the percentage of brain volume change (PBVC) and the brain parenchymal (BPF), grey matter (GMF) and white matter (WMF) fractions. RESULTS: The mean follow-up time was 53 months (SD = 16.8): 76 patients (43%) experienced a second attack, 32 (18%) fulfilled MRI-only 2005 McDonald criteria and 68 (39%) remained as CIS. Statistically significant decreases in the volume measures tested were observed in patients with a second attack, for BPF and PBVC; in both MS groups for GMF; whereas in all groups, the WMF was unchanged. Patients with a second attack had larger PBVC decreases (- 0.65% versus + 0.059%; p < 0.001). PBVC decreases below - 0.817% independently predicted shorter times to a second attack. CONCLUSIONS: Global brain and grey matter volume loss occurred within the first year after a CIS; brain volume loss predicted conversion to MS.

Diagnostic accuracy of hand-assisted laparoscopy in predicting resectability of peritoneal carcinomatosis from gynecological malignancies.

OBJECTIVES: Residual disease after excision surgery is the main prognostic factor in advanced ovarian cancer. Open surgery can delay neoadjuvant chemotherapy initiation. Therefore, a minimally invasive method for evaluating resectability would be of great interest. Aim of our study is to evaluate a new technique for assessing the extent of peritoneal carcinomatosis, combining manual palpation and standard laparoscopy. METHODS: Prospective single-center study from October 2008 to January 2010. Patients with peritoneal carcinomatosis from gynecological malignancies were investigated by standard laparoscopy followed by laparoscopy plus manual palpation using Lapdisc(®) (Ethicon Inc.), at 43 abdominopelvic sites. When both techniques indicated resectability, standard cytoreduction surgery was performed via a midline laparotomy. The Fagotti, modified Fagotti, and Sugarbaker scores were computed. The diagnostic performance of each evaluation criterion was assessed by computing sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver-operating characteristic curves (ROC-AUCs). RESULTS: Of the 29 included patients, 18 (62.1%) were considered to have resectable disease. Fourteen (14/18, 77.8%) had macroscopically complete cytoreduction. With Lapdisc(®), sensitivity was 100%, specificity 73.3%, PPV 77.8%, NPV 100%, and ROC-AUC 0.87. Corresponding values were as follows: laparoscopy, 100%, 40%, 60.9%, 100%, and 0.70; Fagotti and modified Fagotti scores, 100%, 46.7%, 63.6%, 100%, and 0.73; Sugarbaker score, 64.3%, 93.3%, 90%, 73.7%, and 0.79. The ROC-AUCs showed significantly better performance of Lapdisc(®) than of standard laparoscopy (P = 0.008). CONCLUSION: Hand-assisted laparoscopy may perform better than laparoscopy alone for predicting the resectability of peritoneal carcinomatosis by increasing the number of sites evaluated.

A new level 1 oncoplastic technique for breast conserving surgery: rotation glandular flap.

BACKGROUND: When performing conservative surgery for breast cancer, breast reshaping can be a challenging procedure. Level 1 oncoplastic surgery (OPS) techniques, i.e., advancement or rotation of glandular flaps, should be performed when less than 20 per cent breast volume is excised. OBJECTIVE: A new Level 1 OPS technique is described. A wide centro-lateral glandular flap is created after extensive undermining of the skin and nipple-areolar complex, and rotated into the cavity. DISCUSSION: This rotation glandular flap is a new technique for use following a wide excision, in glandular, not fatty, breasts, and when standard closure of the cavity would not leave a satisfactory cosmetic result.

Complications of lymphadenectomy for gynecologic cancer.

INTRODUCTION: Symptomatic postoperative lymphocysts (SPOLs) and lower-limb lymphedema (LLL) are probably underestimated complications of lymphadenectomy for gynecologic malignancies. Here, our objective was to evaluate the incidence and risk factors of SPOLs and LLL after pelvic and/or aortocaval lymphadenectomy for gynecologic malignancies. METHODS: Single-center retrospective study of consecutive patients who underwent pelvic and/or aortocaval lymphadenectomy for ovarian cancer, endometrial cancer, or cervical cancer between January 2007 and November 2008. The incidences of SPOL and LLL were computed with their 95% confidence intervals (95%CIs). Multivariate logistic regression was performed to identify independent risk factors for SPOL and LLL. RESULTS: We identified 88 patients including 36 with ovarian cancer, 35 with endometrial cancer, and 17 with cervical cancer. The overall incidence of SPOL was 34.5% (95%CI, 25-45) and that of LLL was 11.4% (95% confidence interval [95%CI], 5-18). Endometrial cancer was independently associated with a lower risk of SPOL (adjusted odds ratio [aOR], 0.09; 95%CI, 0.02-0.44) and one or more positive pelvic nodes with a higher risk of SPOL (aOR, 4.4; 95%CI, 1.2-16.3). Multivariate logistic regression failed to identify factors significantly associated with LLL. CONCLUSION: Complications of lymphadenectomy for gynecologic malignancies are common. This finding supports a more restrictive use of lymphadenectomy or the use of less invasive techniques such as sentinel node biopsy.

Increase in the prevalence of multiple sclerosis over a 17-year period in Osona, Catalonia, Spain.

The prevalence of multiple sclerosis in the south of Europe seems to be higher than previously considered. This study aimed to probe a possible increase in the prevalence of multiple sclerosis (MS) in Osona over the past 17 years. This was a cross-sectional study including MS-confirmed cases from several sources of information. Crude and adjusted prevalence rates were obtained. One hundred and twenty patients fulfilled the study criteria. The crude prevalence of MS was 79.9 (95% CI: 66.3-95.6) per 100,000 inhabitants and 91.2 (95% CI: 75.5-109.2) per 100,000 among Spanish born individuals. The prevalence of multiple sclerosis cases in Osona has increased over the past 17 years to being one of the highest reported in Spain.

[Autologous fat grafting to the postmastectomy irradiated chest wall prior to breast implant reconstruction: a series of 68 patients]. / Transfert de tissu adipeux autologue préalable à la reconstruction mammaire par implant après mastectomie et irradiation : à propos d'une série de 68 cas.

INTRODUCTION: After radiotherapy, breast reconstruction with an implant carries a high risk of failure and complication. Clinical and experimental studies have demonstrated that grafting adipose tissue (lipofilling) in an irradiated area enhances skin trophicity. Thus, we have started performing preliminary fat grafting to the irradiated chest wall prior to implant reconstruction in order to limit complications and failure risk. PATIENTS AND METHODS: Patients were included in this study from 2007 to 2011. All patients had had mastectomy and irradiation for breast cancer. They all had one or more sessions of lipofilling prior to breast implant reconstruction. These patients were prospectively followed up in order to collect the following data: postoperative complications; cosmetic result; local breast cancer recurrences. RESULTS: Sixty-eight patients were included. The mean number of fat grafting sessions was 2.3 (range 1-6). An average volume of 115mL (70-275) was injected each time. The mean volume of breast implants was 300mL (185-400). The mean follow-up was 23months (450). No breast cancer local recurrence was diagnosed during follow-up. Implant explantation was performed in one case (1.47%) The mean cosmetic result was 4.5/5. CONCLUSION: Fat grafting to the irradiated chest wall prior to implant placement might be an alternative to flap reconstruction for patients who are not suitable or who refuse this option.

Oncoplastic surgery for breast cancer based on tumour location and a quadrant-per-quadrant atlas.

BACKGROUND: The majority of published techniques for oncoplastic surgery rely on an inverted-T mammoplasty, independent of tumour location. These techniques, although useful, cannot be adapted to all situations. A quadrant-per-quadrant atlas of mammoplasty techniques for large breast cancers was developed in order to offer breast surgeons a technique dependent on tumour location, which reduces the risk of postoperative complications and delay to adjuvant therapy. METHODS: From 2005 to 2010, a series of eligible women with breast cancer were treated by quadrant-specific oncoplastic techniques. All complications and any delay to adjuvant treatment were recorded prospectively, along with local and distant cancer recurrences. Cosmetic outcome was evaluated using a five-point scale. RESULTS: A total of 175 patients were analysed. The median tumour size, after histological examination, was 25 (range 4-90) mm. Twenty-three patients (13.1 per cent) had involved margins. Seventeen of these patients were treated by mastectomy and three had a re-excision. Complications occurred in 13 patients (7.4 per cent), which led to a delay to adjuvant treatment in three (1.7 per cent). After a median follow-up of 49 (range 23-96) months, three patients had developed a local recurrence. The mean score after cosmetic evaluation was 4.6 of 5. CONCLUSION: A quadrant-per-quadrant approach to oncoplastic techniques for breast cancer was developed that tailors the mammoplasty for each tumour location. This panel of techniques should be a useful guide for breast surgeons, and extends the possibilities for breast conservation for large or poorly limited cancers, with a low complication rate and good cosmetic results.

Value of NMO-IgG determination at the time of presentation as CIS.

BACKGROUND: Despite the availability of diagnostic criteria, an overlap between neuromyelitis optica (NMO) and multiple sclerosis (MS) exists, particularly in the early stage of the disease. OBJECTIVE: To study the value of NMO-immunoglobulin G (IgG) determination in Caucasian patients with a first demyelinating episode who develop a relapsing form of optic neuritis or myelitis. METHODS: This study was based on a prospectively acquired cohort of patients regarded as having a clinically isolated syndrome (CIS) at the time of presentation. From this cohort, 2 different groups were selected: group 1 (NMO phenotype), consisting of a first attack involving the optic nerve or the spinal cord, and at least a second event affecting either topography, and group 2 (negative control group), consisting of a first attack involving the brainstem or the cerebral hemispheres and at least 1 relapse in any topography. Group 3 was composed of patients with NMO according to the 2006 revised diagnostic criteria. Serum NMO-IgG was determined by indirect immunofluorescence. RESULTS: A total of 3.1 of the group 1 patients were positive for NMO-IgG in comparison to 3.9% of group 2 and 44.5% of group 3, NMO. One of the positive patients in group 1 evolved to NMO. CONCLUSIONS: NMO-IgG determination is crucial in detecting patients who will develop NMO; however, its value as a routine test in cases presenting with symptoms of the type seen in MS is low, and should only be performed in those patients in which the initial diagnosis is not clear.

Change in the clinical activity of multiple sclerosis after treatment switch for suboptimal response.

BACKGROUND: Therapy for multiple sclerosis (MS) has a partial efficacy, and a significant proportion of treated patients will develop a suboptimal response with first-line disease-modifying drugs (DMD). Therapy switch in patients with MS can be a strategy after a treatment failure. We studied the change in clinical activity after switching of first-line DMD because of a treatment failure. METHODS: Relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon-beta (IFNB) or glatiramer acetate (GA) were divided into (i) patients without change in DMD, (ii) patients with a change in DMD because of a poor response, and (iii) those with a change in DMD without relation with response. Annualized relapse rate (ARR) and relapse-free proportions were analyzed. RESULTS: We identified 923 patients with RRMS. Of the 180 who experienced a change because of suboptimal response, 90 switched to another first-line DMT, 38 to mitoxantrone, and 52 to natalizumab. Median ARR in the pre-DMD period on first DMD and second DMD was the following: 1, 1, and 0 for switchers from IFNB to another IFNB (P = 0.0001); 0.67, 1, and 0 for switchers from GA to IFNB (P = 0.01); 1, 1, and 0 for switchers from an IFNB to GA (P = 0.02); 1.1, 1.5, 0.2 for switchers from IFNB or GA to mitoxantrone (P = 0.0001); 0.9, 1, 0 for switchers from IFNB or GA to natalizumab (P = 0.0001). CONCLUSIONS: In patients with RRMS who have a poor response, switch to another DMD may reduce the clinical activity of the disease.

Hirano body-rich subtypes of Creutzfeldt-Jakob disease.

BACKGROUND: In definite Creutzfeldt-Jakob disease (CJD), morphological and immunohistochemical patterns are useful to identify molecular subtypes. Severe cerebellar pathology and hippocampal involvement helps to identify VV subtypes. The rare VV1 variant (<1%), more frequent in young individuals, is additionally characterized by the presence of ballooned neurones in affected areas. In 1985, Cartier et al. described a family cluster of three individuals with an ataxic CJD form, showing, in addition to severe cerebellar and hippocampal involvement, the presence of frequent Hirano bodies (HB) in CA1 pyramidal neurones. HB are frequently found in aged individuals with Alzheimer pathology although they are not a specific finding. AIMS AND METHODS: In this study, we evaluated the presence of HB in hippocampi of 54 genetically and molecularly characterized CJD cases, aiming to elucidate whether additional morphological features could be helpful to point to molecular subtypes. RESULTS: We identified nine cases (four VV1, one out of three MV2K, three out of six MV2K+2C and one MV carrying a 96-base pair insertion) with abundant, partly bizarre and clustered HB in CA1 sector, not observed in other subtypes. The presence of HB was independent of hippocampal involvement by the disease itself. CONCLUSIONS: Clusters of abundant HB might be found in rare CJD subtypes such as VV1, MV2K/MV2K+2C and some genetic cases. In addition to histopathological and PrP immunohistochemical deposition patterns, their presence might be a useful additional morphologic feature that could point to the molecular subtype, especially when genetic and/or Western blot analyses are not available.

Reconstrucción mamaria por turbo tram: estudio prospectivo, comparativo / Tram breast reconstruction by turbo

Hoy una reconstrucción mamaria (RM) por cualquierade los métodos deben ser consideradas en casi todoslos casos. El colgajo autólogo que corresponde al excesograso-cutáneo abdominal inferior ligado al músculo rectoanterior, ocupa un lugar importante en reconstrucción delseno, visto sus ventajas cosméticas y de estabilidad en eltiempo. . En los casos deriesgo de necrosis se ha optado en el servicio por la opciónde una micro-anastomosis de tal manera a mejorar laperfusión y drenaje del colgajo.Este estudio prospectivo realizado en el InstitutoCurie esta basado en 35 casos de reconstrucciones mamariaspor CMC (colgajo músculo-cutáneo) del recto anterior del abdomen según dos modalidades; monopediculadossimples (14 pacientes), monopediculado turbo(21 pacientes). Se ha evaluado la fuerza de la pared abdominalen pre y posoperatorio, considerando dos gruposmusculares. (Recto anterior y oblicuos). Así mismolas complicaciones y resultados cosméticos a nivel de lapared abdominal y del seno reconstruido. Hemos constatado25% de eventraciones y seudo-eventraciones, todoscasos de utilización de mallas reabsorvibles para el cierreabdominal. La evaluación pre operatoria de la fuerza dela porción supra umbilical (PSU) de recto anterior del abdomenmuestra que el 80% de los pacientes obtuvieronpuntuaciones satisfactorias según la escala de Lacote. Entanto que para la porción infla umbilical (PIU), más del90% de los pacientes obtuvieron igual puntaje. Las cifrasdel postoperatorio se alejan, revelando estabilidad de lospuntajes en apenas 30% de casos para la PSU, contra 80%para la PIU. Los análisis evidencian una deterioración superioral 50% para la PSU del recto anterior, alcanzandoapenas el 30 para la PIU. Confirmamos en este estudio que la disminución dela fuerza muscular del recto anterior es más marcada parala PSU que para la PIU, independientemente del tipo detécnica de TRAM utilizada.