New variants expand the neurological phenotype of COQ7 deficiency.

The protein encoded by COQ7 is required for CoQ10 synthesis in humans, hydroxylating 3-demethoxyubiquinol (DMQ10) in the second to last steps of the pathway. COQ7 mutations lead to a primary CoQ10 deficiency syndrome associated with a pleiotropic neurological disorder. This study shows the clinical, physiological, and molecular characterization of four new cases of CoQ10 primary deficiency caused by five mutations in COQ7, three of which have not yet been described, inducing mitochondrial dysfunction in all patients. However, the specific combination of the identified variants in each patient generated precise pathophysiological and molecular alterations in fibroblasts, which would explain the differential in vitro response to supplementation therapy. Our results suggest that COQ7 dysfunction could be caused by specific structural changes that affect the interaction with COQ9 required for the DMQ10 presentation to COQ7, the substrate access to the active site, and the maintenance of the active site structure. Remarkably, patients' fibroblasts share transcriptional remodeling, supporting a modification of energy metabolism towards glycolysis, which could be an adaptive mechanism against CoQ10 deficiency. However, transcriptional analysis of mitochondria-associated pathways showed distinct and dramatic differences between patient fibroblasts, which correlated with the extent of pathophysiological and neurological alterations observed in the probands. Overall, this study suggests that the combination of precise genetic diagnostics and the availability of new structural models of human proteins could help explain the origin of phenotypic pleiotropy observed in some genetic diseases and the different responses to available therapies.

Frontline Therapy in Chronic Lymphocytic Leukemia.

BACKGROUND: The treatment landscape of chronic lymphocytic leukemia (CLL) has tremendously evolved in the last decades, thanks to the introduction of more effective therapies. SUMMARY: Frontline therapy for patients with CLL includes chemoimmunotherapy (CIT) and pathway inhibitors (PIs) (i.e., bruton tyrosine kinase inhibitors and BCL2 inhibitors); the latter has proved to be more effective than CIT mainly in patients with high-risk features (e.g., TP53 aberrations and unmutated IGHV) with acceptable toxicity. Combinations of PIs are playing the protagonist role as frontline therapy for CLL. KEY MESSAGES: In this article, the management of treatment-naïve patients with CLL is discussed.

Sequence matters: Total body irradiation (TBI)-based myeloablative conditioning with post-transplant cyclophosphamide may reduce the early nonrelapse mortality compared with pretransplant cyclophosphamide plus TBI.

OBJECTIVES: High-dose total body irradiation (TBI) is considered a cornerstone of myeloablative conditioning for allogeneic stem cell transplantation (allo-SCT). We retrospectively compared the main outcomes of an HLA matched or 1-allele mismatched related or unrelated allo-SCT in adult patients affected by acute leukemia (AL) or myelodysplastic syndromes (MDS). METHODS: Fifty-nine patients received cyclophosphamide (Cy)-TBI (13.5 Gy) and graft-versus-host disease (GVHD) prophylaxis with a calcineurin-inhibitor plus methrotrexate (CyTBI group) and 28 patients received fludarabine-TBI (8.8-13.5 Gy) and GVHD prophylaxis with PTCy and tacrolimus (FluTBI-PTCy group). RESULTS: Median follow-up for survivors was 82 and 22 months. The 12-month probability of overall survival and progression-free survival were similar (p = .18, p = .7). The incidence of Grades 2-4 and 3-4 acute GVHD, and the incidence of moderate-to-severe chronic GVHD were higher in the CyTBI group (p = .02, p < .01and p = .03). Nonrelapse mortality (NRM) at 12 months posttransplant was higher in the CyTBI group (p = 0.05), while the incidence of relapse was similar in both groups (p = 0.7). The number of GVHD-free and relapse-free patients without systemic immunosuppression (GRFS) at 1-year posttransplant was higher in the FluTBI-PTCy group (p = 0.01). CONCLUSIONS: The study confirms the safety and efficacy of a novel FluTBI-PTCy platform with reduced incidence of severe acute and chronic GVHD, and early improvement of NRM.

Outcomes from a Spanish Expanded Access Program on cannabidiol treatment in pediatric and adult patients with epilepsy.

AIM: To evaluate the effectiveness and tolerability of cannabidiol (CBD) in patients with developmental and epileptic encephalopathies, including Dravet syndrome (DS), and Lennox-Gastaut syndrome (LGS), in a Spanish Expanded Access Program (EAP). METHODS: This was a multicenter, retrospective, observational study of patients treated with purified CBD in 14 hospitals across Spain. Patients with (1) written informed consent and (2) at least 6 months follow-up before the closure of the database were included. Primary effectiveness endpoints included reductions (100 %, ≥75 %, ≥50 %, ≥25 %, or 0 %) or worsening in seizure frequency (all seizure types and most disabling seizures) at 1-, 3-, 6-, and 12-month visits and at the last visit, and median relative seizure reduction between baseline and last visit. Secondary effectiveness endpoints included retention rate, reduction in seizure severity, status epilepticus, healthcare utilization, and quality of life. Primary safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. RESULTS: One hundred and two patients (DS 12 %; LGS 59 %; other epilepsy syndromes 29 %) with a mean age of 15.9 years were enrolled. Patients were highly refractory to antiseizure medications (ASMs); mean number of prior failed ASMs was 7.5 (SD 3.7). The mean CBD dose was 13.0 mg/kg/day at the last visit. The proportion of patients with ≥50 % reduction in the total number of seizures from baseline was 44.9 % at 6 months and 38.9 % at 12 months. The median number of total seizures per month reduced by 47.6 % from baseline to the last visit. At 12 months, seizure severity was lower in 33/54 patients (61.1 %) and unchanged in 17/54 patients (31.5 %). Quality of life, based on the CAVE scale, increased from a mean score of 17.9 ± 4.7 (n = 54) at baseline to 21.7 ± 5.5 (n = 51) at the last patient visit (21.2 % improvement). The mean treatment retention time was 10.3 months. There were no statistically significant changes in the number of status epilepticus episodes, but lower healthcare utilization was observed. Adverse events occurred in sixty-eight patients (66.7 %), and the most common were somnolence (34.3 %) and diarrhea (12.7 %). Cannabidiol was discontinued exclusively due to AEs in 7.8 % of patients, increasing to 25.5 % when both lack of efficacy and AEs were considered together. CONCLUSIONS: Cannabidiol demonstrated promising effectiveness and tolerability in patients with developmental and epileptic encephalopathies taking part in a Spanish EAP.

Effectiveness of proprioceptive neuromuscular facilitation therapy and strength training among post-menopausal women with thumb carpometacarpal osteoarthritis. A randomized trial.

BACKGROUND: Thumb carpometacarpal osteoarthritis (CMC OA) greatly affects post-menopausal women. It is characterized by pain and functional deficits that limit the performance of activities of daily life and affect quality of life. PURPOSE: Analyze the effects of 4/weeks strength training, with and without proprioceptive neuromuscular facilitation (PNF) on the disability among post-menopausal women with thumb CMC OA. Secondly, analyze the effects on pain, mobility, and strength. STUDY DESIGN: Superiority randomized clinical trial. METHODS: 42 women were randomly allocated to strength training program (SEG, n = 21) and to a strength training plus PNF therapy program (PNFG, n = 21). The Disability (disabilities of the arm, shoulder and hand questionnaire), pain (visual analogue scale), mobility (Kapandji Test), and hand strength were evaluated pre, post intervention (at 4 weeks) and follow-up (at 8 weeks). RESULTS: Disability was significantly reduced in both groups after intervention, but reduction was statistically superior in PNFG (between-group mean difference [MD] = -16.69 points; CI = -21.56:-11.82; P<.001; d = 2.14). Similar results were observed for secondary outcomes: pain (MD = -2.03; CI = -2.83:-1.22; P<.001; d = 1.58), mobility (MD = 0.96; CI = 0.52:1.38; P<.001; d = 1.40) and strength (grip: MD = 3.47kg; CI = 1.25:5.69; P = .003; d = 0.97, palmar: MD = 0.97kg; CI = 0.14:1.80; P = .024; d = 0.72, tip: MD = 1.12kg; CI = 0.41:1.83; P = .003; d = 0.99 and key pinch: MD = 0.85kg; CI = 0.001:1.70; P = .049; d = 0.62). These improvements were maintained at follow-up. CONCLUSIONS: The combination of PNF exercises and strength training is more effective for reducing disability pain and improve mobility and strength in post-menopausal women with CMC OA than a programme based solely on strength.

The road to chemotherapy-free treatment in chronic lymphocytic leukaemia.

PURPOSE OF REVIEW: The treatment landscape of chronic lymphocytic leukaemia (CLL) has tremendously evolved in the last decades, from chemo to chemoimmunotherapy (CIT) and, eventually, to pathway inhibitors that target critical pathways for leukaemic cells survival. Also, treatment goals are moving towards achieving undetectable minimal residual disease with little toxicity. RECENT FINDINGS: We performed a thorough review of the history of treatment approvals by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This review especially focuses on therapies that are currently approved by both agencies. The indications and particular characteristics of each drug are examined. SUMMARY: Currently available treatment approaches for CLL offer the opportunity to individualize therapy for every single patient with CLL. Inhibitors of B-cell receptor (BCR) signalling pathways and antiapoptotic proteins are nowadays the treatment of choice for most CLL patients, but CIT can be an option for younger and fit patients with low-risk disease [mutated IGHV, no del(11q) or del(17p)/TP53 mutations].

Hidden etiology of cerebral palsy: genetic and clinical heterogeneity and efficient diagnosis by next-generation sequencing.

Cerebral palsy (CP) is a heterogeneous neurodevelopmental disorder that causes movement and postural disabilities. Recent research studies focused on genetic diagnosis in patients with CP of unknown etiology. The present study was carried out in 20 families with one family member affected with idiopathic CP. Chromosomal microarray and exome sequencing techniques were performed in all patients. Chromosomal microarray analysis did not show any pathological or probable pathological structural variant. However, the next-generation sequencing study showed a high diagnostic yield. We report 11/20 patients (55%) with different pathogenic or potentially pathogenic variants detected by exome sequencing analysis: five patients with mutations in genes related to hereditary spastic paraplegia, two with mutations in genes related to Aicardi-Goutières syndrome, three with mutations in genes related to developmental/epileptic encephalopathies, and one with a mutation in the PGK1 gene. The accurate and precise patients' selection, the use of a high-throughput genetic platform, the selection of adequate target genes, and the application of rigorous criteria for the clinical interpretation are the most important elements for a good diagnostic performance. Based on our findings, next-generation sequencing should be considered in patients with cryptogenic CP as the first line of genetic workup. IMPACT: Sequencing techniques in CP of uncertain etiology provides a diagnostic yield of 55%. The appropriate selection of cases optimizes the diagnostic yield. NGS facilitate better understanding of new phenotypes of certain genetic diseases.

Clinical and molecular diagnosis of non-phosphomannomutase 2 N-linked congenital disorders of glycosylation in Spain.

The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment. They affect multiple organ/systems, but non-specific symptoms render the diagnosis of the different CDG very challenging. Phosphomannomutase 2 (PMM2)-CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought. The present work reports the clinical and mutational spectrum of 25 non-PMM2 CDG patients. The most common clinical symptoms were hypotonia (80%), motor or psychomotor disability (80%) and craniofacial dysmorphism (76%). Based on their serum transferrin isoform profile, 18 were classified as CDG-I and 7 as CDG-II. Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4). Overall, 27 variants were identified, 12 of which are novel. The results highlight the importance of combining genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders.

Experiences of women and men living with urinary incontinence: A phenomenological study.

AIMS: To explore and understand, from a gender-based perspective, the quality-of-life experiences of men and women who suffer from urinary incontinence. BACKGROUND: Urinary incontinence (UI) is a major health problem with significant social, psychological, occupational, sexual and economic effects leading to a substantial decrease in quality of life. Although this condition is increasingly frequent in men, research has tended to focus on women, adopting a quantitative approach. DESIGN: The data were examined using interpretive phenomenological analysis (IPA). METHODS: The data were collected through a semi-structured interview conducted between January and June 2016. An inductive discourse content analysis was performed in three stages: preparation, organization and report. Participants were recruited until data saturation was achieved. FINDINGS: A sample of 33 participants was recruited: 17 women and 16 men. Gender-specific features were found. Six categories emerged: (i) normalization of incontinence; (ii) verbalization of the problem; (iii) social isolation; (iv)experienced feelings and emotions; (v) impact on daily routine; (vi) self-care strategies to address the problem in the most suitable way. CONCLUSION: Urinary incontinence has a negative effect on the quality of life of men and women. However, there are gender differences as to how this phenomenon is experienced, particularly with regard to its psychological and social dimensions. A comprehensive, targeted assessment of the needs of these men and women is required on the part of professional nurses.

Anterior intercostal artery perforator flap in immediate breast reconstruction: Anatomical study and clinical application.

BACKGROUND: Although the use of lateral intercostal artery perforator (ICAP) flaps for immediate breast reconstruction has been widely described, data on the use of the anterior ICAP (AICAP) flaps for this indication are limited. In this context, we describe the results of anatomical study and our clinical experience with AICAP flaps for breast reconstruction. METHODS: In this study, the location and characteristics of the AICAPs were dissected in 12 female adult formalin-preserved hemitrunks and two fresh-frozen cadavers. Fourteen patients (mean BMI 23) underwent partial breast resection for a quadrant breast cancer followed by breast reconstruction with an intercostal perforator flap. The mean resection size was 6 × 5 × 5.5 cm (range 3-8 × 3.5-7 × 4-8 cm).The main outcome measures were pre-operative and postradiotherapy health-related quality of life assessed with the BREAST-Q reconstruction survey. RESULTS: According to anatomical study, at least one perforator was found in each third of hemitrunks dissected. The mean of perforator size was in diameter 0.42 ± 0.05 mm and in length 3.1 ± 0.36 cm. In clinical outcomes, the mean of flap size was 16 × 5 × 3 cm (range 14-19 × 3-8 × 2-5 cm). The mean surgical time was 120 min (range 109-125 min). Only one partial flap failure was detected. No postoperative changes in breast size were observed, although soft tissue changes were observed in four patients after radiotherapy. The mean BREAST-Q scores changes were 0 in satisfaction with the breast, 5 in satisfaction with outcome, 0 in psychosocial well-being, 6.15 in sexual well being, and 34.69 in physical well-being. CONCLUSIONS: Based on this anatomical and clinical study, we found AICAP flap has a consistent vascularization with good perforators. And moreover, it is suitable for partial breast reconstruction (quadrantectomy) and does not appear to negatively impact patient satisfaction.

[OROPHARYS CANCER: THE SQUAMOUS CELL]. / CÁNCER OROFARINGEO: LA CÉLULA ESPINOSA.

The Diffuse Large B-Cell Lymphoma is the most frequent non Hodgkin Lymphoma. The role of CT/PET in this relatively homogeneous group of lymphomas is controversial. It rarely changes the management of the patients in the initial staging. Recents publications, clinical trials and experts consensus meetings have demonstrated its utility in the evaluation of the response at the end of the treatment. The interest of CT/PET in the evaluation of the response during the treatment, with the objective of implement a "Risk Adapted Therapy", in increasing.

Evolution in the frontline treatment of patients with chronic lymphocytic leukemia: experience from one European center.

Treatment of chronic lymphocytic leukemia (CLL) has dramatically evolved over the last decades thanks to the introduction of targeted therapies. We aimed to describe retrospectively the evolution in the frontline prescription in the CLL patients from our institution. As a secondary objective, the impact of frontline therapy on the time-to-next-treatment (TTNT) and overall survival (OS). After a median of 6.4 years (0.1-36.4) of follow-up from diagnosis, 323 of 780 CLL patients (41.4%) required therapy. Alkylating agents in monotherapy (chlorambucil) were the most used until 2012, and from then, chemoimmunotherapy. Since 2018, targeted therapies were the most common therapeutic strategy (74.1%). Patients who received targeted therapies had significantly longer TTNT compared to other regimens. In the multivariable analyses, mutated IGHV genes targeted therapies and chemoimmunotherapy regimens were related to longer TTNT, and sex female, age younger than 65, and mutated IGHV genes were associated with better OS.

Successful Outcome in Patients with Myelofibrosis Undergoing Allogeneic Donor Hematopoietic Cell Transplantation Using Reduced Doses of Post-Transplantation Cyclophosphamide: Challenges and Review of the Literature.

Engraftment and nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT) depend greatly on the transplantation platform in patients with myelofibrosis (MF). We report outcomes of 14 consecutive MF patients who received reduced doses of post-transplantation cyclophosphamide (PTCy; 60 mg/kg total dose) and tacrolimus as graft-versus-host disease (GVHD) prophylaxis as part of a new standardized allo-HCT protocol. The median patient age at allo-HCT was 59 years (range, 41 to 67 years), and the median interval from diagnosis to HCT was 19 months (range, 2 to 114 months). All patients received ruxolitinib before HCT, and 71% had no response. Most patients (78%) had symptomatic splenomegaly at HCT. Eighty-six percent received reduced-intensity conditioning, and 64% underwent allo-HCT from an unrelated donor. There were no graft failures, and neutrophil and platelet recovery occurred at a median of 21 days and 31 days, respectively. The cumulative incidence of grade II-IV acute GVHD was 28.6%, and that of grade III-IV acute GVHD was 7%. The 2-year incidence of overall and moderate-severe chronic GVHD was 36% and 14%, respectively. Only 1 patient relapsed after transplantation, and NRM was 7% at 100 days and 14% at 2 years. The GVHD-free/relapse-free and immunosuppression-free incidence at 1 year was 41%. With a median follow-up for survivors of 28 months (range, 8 to 55 months), the 2-year overall survival and progression-free survival were 86% and 69%, respectively. Reduced doses of PTCy as GVHD prophylaxis for high-risk MF patients showed promising results by reducing the incidence of GVHD without any cases of graft failure.

Copper(I)-catalyzed [3+1] cycloaddition of alkenyldiazoacetates and iminoiodinanes: easy access to substituted 2-azetines.

The copper(I)-catalyzed reaction of alkenyldiazoacetates and iminoiodinanes affords functionalized azetine derivatives. This process is consistent with the formation of an aziridinyldiazoacetate intermediate, which gives rise to the four-membered heterocycles by metal-catalyzed ring expansion. The resulting azetine structure is a direct precursor of azeditine-2-carboxylic acid derivatives (EWG = electron-withdrawing group).

Cardiac MRI evaluation of hypertrophic cardiomyopathy: left ventricular outflow tract/aortic valve diameter ratio predicts severity of LVOT obstruction.

PURPOSE: To evaluate if left ventricular outflow tract/aortic valve (LVOT/AO) diameter ratio measured by cardiac magnetic resonance (CMR) imaging is an accurate marker for LVOT obstruction in patients with hypertrophic cardiomyopathy (HCM) compared to Doppler echocardiography. MATERIALS AND METHODS: In all, 92 patients with HCM were divided into three groups based on their resting echocardiographic LVOT pressure gradient (PG): <30 mmHg at rest (nonobstructive, n = 31), <30 mmHg at rest, >30 mmHg after provocation (latent, n = 29), and >30 mmHg at rest (obstructive, n = 32). The end-systolic dimension of the LVOT on 3-chamber steady-state free precession (SSFP) CMR was divided by the end diastolic aortic valve diameter to calculate the LVOT/AO diameter ratio. RESULTS: There were significant differences in the LVOT/AO diameter ratio among the three subgroups (nonobstructive 0.60 ± 0.13, latent 0.41 ± 0.16, obstructive 0.24 ± 0.09, P < 0.001). There was a strong linear inverse correlation between the LVOT/AO diameter ratio and the log of the LVOT pressure gradient (r = -0.84, P < 0.001). For detection of a resting gradient >30 mmHg, the LVOT/AO diameter ratio the area under the receiver operating characteristic (ROC) curve was 0.91 (95% confidence interval [CI] 0.85-0.97). For detection of a resting and/or provoked gradient >30 mmHg, the LVOT/AO diameter ratio area under the ROC curve was 0.90 (95% CI 0.84-0.96). CONCLUSION: The LVOT/AO diameter ratio is an accurate, reproducible, noninvasive, and easy to use CMR marker to assess LVOT pressure gradients in patients with HCM.

Assessment of distribution and evolution of mechanical dyssynchrony in a porcine model of myocardial infarction by cardiovascular magnetic resonance.

BACKGROUND: We sought to investigate the relationship between infarct and dyssynchrony post- myocardial infarct (MI), in a porcine model. Mechanical dyssynchrony post-MI is associated with left ventricular (LV) remodeling and increased mortality. METHODS: Cine, gadolinium-contrast, and tagged cardiovascular magnetic resonance (CMR) were performed pre-MI, 9 ± 2 days (early post-MI), and 33 ± 10 days (late post-MI) post-MI in 6 pigs to characterize cardiac morphology, location and extent of MI, and regional mechanics. LV mechanics were assessed by circumferential strain (eC). Electro-anatomic mapping (EAM) was performed within 24 hrs of CMR and prior to sacrifice. RESULTS: Mean infarct size was 21 ± 4% of LV volume with evidence of post-MI remodeling. Global eC significantly decreased post MI (-27 ± 1.6% vs. -18 ± 2.5% (early) and -17 ± 2.7% (late), p < 0.0001) with no significant change in peri-MI and MI segments between early and late time-points. Time to peak strain (TTP) was significantly longer in MI, compared to normal and peri-MI segments, both early (440 ± 40 ms vs. 329 ± 40 ms and 332 ± 36 ms, respectively; p = 0.0002) and late post-MI (442 ± 63 ms vs. 321 ± 40 ms and 355 ± 61 ms, respectively; p = 0.012). The standard deviation of TTP in 16 segments (SD16) significantly increased post-MI: 28 ± 7 ms to 50 ± 10 ms (early, p = 0.012) to 54 ± 19 ms (late, p = 0.004), with no change between early and late post-MI time-points (p = 0.56). TTP was not related to reduction of segmental contractility. EAM revealed late electrical activation and greatly diminished conduction velocity in the infarct (5.7 ± 2.4 cm/s), when compared to peri-infarct (18.7 ± 10.3 cm/s) and remote myocardium (39 ± 20.5 cm/s). CONCLUSIONS: Mechanical dyssynchrony occurs early after MI and is the result of delayed electrical and mechanical activation in the infarct.

Direct access to ß-oxodiazo compounds by copper(II)-catalyzed oxidative rearrangement of stabilized vinyl diazo derivatives.

The copper(II)-catalyzed reaction of alkenyldiazo compounds with iodosylbenzene leading to ß-oxodiazo derivatives is reported. This process occurs via an unprecedented 1,2-shift of the diazoacetate function. A selection of the synthetic applications of a representative member of this new class of functionalized diazo derivatives in the regioselective synthesis of substituted 1,4-dicarbonyl compounds is also reported.

[Giant cell in maxillary pseudotumors]. / La célula gigante en los seudotumores maxilares.

A research on lesions apparently tumorous that appear on jawbones and are not exactly tumors is developed. These lesions are clinically silent, although they produce deformity and, perhaps because of that, an early diagnosis with biopsy or other procedures is needed. The image research can be very characteristic or otherwise, it can be very complex, non specific and not provide everything expected to make the diagnosis. The difference between radiolucent and radiopaque images that produce the querubism-fibrous displasia, prove both extremes in which the diagnosis judgment made by image can or cannot be significant. We have to highlight the presence of giant cells with an osteoclastic nature in most of these pseudo tumorous lesions.

Advantages of preoperative localization and surgical resection of metastatic axillary lymph nodes using magnetic seeds after neoadjuvant chemotherapy in breast cancer.

PURPOSE: To assess the safety and effectiveness of magnetic seeds in preoperative localization and surgical dissection of metastatic axillary lymph nodes (LN+) in breast cancer patients with axillary involvement, after neoadjuvant chemotherapy (NAC). In addition, to assess the impact of targeted axillary dissection (TAD) in reducing the rate of false negatives (FN) in sentinel lymph node biopsy (SLNB). MATERIALS AND METHODS: A cross-sectional prospective cohort study was conducted from April 2017 to September 2019, including breast cancer patients with axillary lymph node involvement treated with NAC. Prior to NAC, the LN+ were marked by ultrasound-guided clip insertion. After NAC, a magnetic seed (Magseed®) was inserted in the clip-marked lymph node (MLN). During surgery, the MLN was located and removed with the aid of a magnetic detection probe (Sentimag®) and the sentinel lymph node was removed. Axillary lymph node dissection (ALND) was used to determine the rate of FN for SLNB alone and the combination of SLNB and MLN dissection, called TAD. RESULTS: The study included 29 patients (mean age, 55; range, 30-78 years). Selective preoperative localization and surgical dissection were successful for all 30 MLNs (100%). The MLN corresponded to the SLN in 50% of cases. After ALND, there were 21.4% (3/14) FN with SLNB alone and 5.9% (1/17) with TAD. CONCLUSIONS: Following NAC, selective surgical removal of MLN by preoperative localization using magnetic seeds is a safe and effective procedure with a success rate of 100%. Adding TAD reduces the rate of FN associated with SLNB alone.

Pyridine activation via copper(I)-catalyzed annulation toward indolizines.

The copper(I)-catalyzed regioselective [3 + 2] cyclization of pyridines toward alkenyldiazoacetates leading to functionalized indolizine derivatives is reported. A broad range of pyridine derivatives (including quinoline and isoquinoline) is compatible with this cyclization reaction. The process represents the first successful example of metal-catalyzed cyclization of a π-deficient heterocyclic system with alkenyldiazo compounds.