Tolerability and Preliminary Outcomes of Adjuvant T-DM1 in HER2-Positive Breast Cancer After Neoadjuvant Therapy: The ATD Study.

Background/objectives: HER2-positive breast cancer (HER2BC) is an aggressive subtype, with neoadjuvant treatment (NAT) aiming to achieve a pathological complete response (pCR) to improve long-term outcomes. Trastuzumab emtansine (T-DM1) has been established as the standard of care in the adjuvant setting for HER2BC patients who do not obtain pCR. The ATD study aimed to evaluate the real-world tolerability of T-DM1 in this setting.

[Effectiveness and tolerability of sacituzumab govitecan in elderly patient with advanced triple negative breast cancer.].

The triple-negative breast carcinoma (TNBC), despite representing a minority of all breast carcinoma cases, poses a significant problem due to its biological aggressiveness and the resulting unfavorable prognosis for affected patients. Until recently, the only therapeutic strategy available was chemotherapy. However, new therapeutic approaches have recently led to an improvement in the natural history of this disease.

Patients' perspectives on buprenorphine subcutaneous implant: a case series.

Background: Considering the enormous burden represented by the opioid use disorder (OUD), it is important to always consider, when implementing opioid agonist therapy (OAT), the potential impact on patient's adherence, quality of life, and detoxification. Thus, the purpose of the study is to evaluate how the introduction of a novel OAT approach influences these key factors in the management of OUD.

Case Presentation: This article marks the pioneering use of OAT through buprenorphine implant in Europe and delves into the experience of six patients diagnosed with OUD at a relatively young age.

The experience of buprenorphine implant in patients with opioid use disorder: a series of narrative interviews.

Background: This study used narrative medicine (NM) to assess the point of view of patients with opioid use disorder (OUD) and the impact that addiction and a new treatment approach via buprenorphine implant had on their daily lives as compared with previous oral Opioid Agonist Therapy (OAT).

Methods: Five patients with OUD undergoing treatment with a buprenorphine subcutaneous implant participated voluntarily and provided their anonymity by self-describing, in response to questions prompted by the clinician, their experience with this innovative therapy. The narratives were analyzed according to standard NM methodology.

Progesterone receptor status and clinical outcome in breast cancer patients with estrogen receptor-positive locoregional recurrence.

Aims And Background: The aim of this retrospective multicenter study was to evaluate the impact of progesterone receptor (PgR) loss on locoregional recurrence in patients with estrogen receptor (ER)-positive primary breast cancer and ER-positive locoregional recurrence.

Patients And Methods: Eight Italian oncology centers collected data from consecutive patients with ER-positive breast cancer and a subsequent ER-positive locoregional recurrence.

Results: Data were available for 265 patients diagnosed with breast cancer between 1990 and 2009.

Efficacy of a task-based training approach in the rehabilitation of three children with poor handwriting quality: a pilot study.

Evidence suggests that task-based training approaches can improve the performance of children with handwriting difficulties. The present case study tests the efficacy of the Handwriting Task Program (HTP). Three male children (9-10 yr.

Everolimus plus exemestane as first-line therapy in HR⁺, HER2⁻ advanced breast cancer in BOLERO-2.

The present exploratory analysis examined the efficacy, safety, and quality-of-life effects of everolimus (EVE) + exemestane (EXE) in the subgroup of patients in BOLERO-2 whose last treatment before study entry was in the (neo)adjuvant setting. In BOLERO-2, patients with hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2-negative (HER2(-)) advanced breast cancer recurring/progressing after a nonsteroidal aromatase inhibitor (NSAI) were randomly assigned (2:1) to receive EVE (10 mg/day) + EXE (25 mg/day) or placebo (PBO) + EXE. The primary endpoint was progression-free survival (PFS) by local assessment.

Health-related quality of life and disease symptoms in postmenopausal women with HR(+), HER2(-) advanced breast cancer treated with everolimus plus exemestane versus exemestane monotherapy.

Objective: Everolimus (EVE)+exemestane (EXE; n = 485) more than doubled median progression-free survival versus placebo (PBO) + EXE (n = 239), with a manageable safety profile and no deterioration in health-related quality-of-life (HRQOL) in patients with hormone-receptor-positive (HR(+)) advanced breast cancer (ABC) who recurred or progressed on/after nonsteroidal aromatase inhibitor (NSAI) therapy. To further evaluate EVE + EXE impact on disease burden, we conducted additional post-hoc analyses of patient-reported HRQOL.

Research Design And Methods: HRQOL was assessed using EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline and every 6 weeks thereafter until treatment discontinuation because of disease progression, toxicity, or consent withdrawal.

Distinctive properties of CXC chemokine receptor 4-expressing Cajal-Retzius cells versus GABAergic interneurons of the postnatal hippocampus.

The CXC chemokine receptor 4 (CXCR4) for the chemokine (C-X-C motif) ligand 12/stromal cell-derived factor-1 alpha (CXCL12/SDF-1 alpha) is highly expressed in the postnatal CA1 stratum lacunosum-moleculare. However, both the network events triggered by SDF-1 alpha in this microcircuit and the cellular targets of this chemokine remain virtually unexplored. Here, we have studied SDF-1 alpha-mediated neuromodulation of the stratum lacunosum-moleculare by directly comparing the properties of CXCR4-expressing Cajal-Retzius cells vs.

Aspects of the neuroendocrine cerebellum: expression of secretogranin II, chromogranin A and chromogranin B in mouse cerebellar unipolar brush cells.

Morphologically distinct neuron classes can be subdivided in sublineages by differential chemical phenotypes that correlate with functional diversity. Here we show by immunocytochemistry that chromogranin A (CgA) chromogranin B (CgB) and secretogranin II (SgII), the principal granins situated in neuronal secretory granules and large dense-core vesicles, are widely but differentially expressed in cells of the mouse cerebellum and terminals of cerebellar afferents. While CgA and CgB were nearly panneuronal, SgII was more restricted in distribution.

Dynamic metabotropic control of intrinsic firing in cerebellar unipolar brush cells.

Neuronal firing is regulated by the complex interaction of multiple depolarizing and hyperpolarizing currents; intrinsic firing, which defines the neuronal ability to generate action potentials in the absence of synaptic excitation, is particularly sensitive to modulation by currents that are active below the action potential threshold. Cerebellar unipolar brush cells (UBCs) are excitatory granule layer interneurons that are capable of intrinsic firing; here we show that, in acute mouse cerebellar slices, barium-sensitive background potassium channels of UBCs effectively regulate intrinsic firing. We also demonstrate that these channels are regulated by group II metabotropic glutamate receptors (mGluRs), which we show to be present in both of the known subsets of UBCs, one of which expresses calretinin and the other mGluR1alpha.

Oral melphalan, prednisone, and thalidomide for newly diagnosed patients with myeloma.

Background: Thalidomide is an immunomodulatory drug with strong antimyeloma activity. It is an effective treatment for multiple myeloma at disease recurrence and at diagnosis, both as a single agent and in combination with steroids or chemotherapy. No data are available on the association of thalidomide with oral melphalan and prednisone, still considered the standard treatment for elderly patients.

Correlation between fatigue and hemoglobin level in multiple myeloma patients: results of a cross-sectional study.

This cross-sectional study showed a positive correlation between fatigue-related quality of life, evaluated with the FACT-An questionnaire, and hemoglobin level in 1071 patients with multiple myeloma. Multiple regression analysis adjusting for several covariates was used. Improved FACT-An scores in women and men were associated with hemoglobin increase up to sex-specific normal values.

Merkel cells, corpuscular nerve endings and free nerve endings in the mouse palatine mucosa express three subtypes of vesicular glutamate transporters.

The hard palate of rodents is a mucous membrane covered by a keratinized epithelium that typically contains Merkel cell (MC)-neurite complexes. MCs have engendered considerable research activity because of their involvement in mechanoreception and possibly also Merkel cell carcinomas. MCs derive from the neural crest, differentiate under control of peripheral nerve factors, are enriched in large dense core vesicles, and secrete neuropeptides and other neuroactive molecules.

Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70: results of a randomized controlled trial.

High-dose therapy is an effective standard treatment for multiple myeloma patients. Evidence that intermediate-dose therapy improves survival is limited. At diagnosis, about 70% of patients are older than 65.

Vesicular glutamate transporters VGLUT1 and VGLUT2 define two subsets of unipolar brush cells in organotypic cultures of mouse vestibulocerebellum.

Different isoforms of a vesicular glutamate transporter (VGLUT) mediate glutamate uptake into synaptic vesicles of excitatory neurons. There is agreement that the VGLUTs are differentially expressed in brain, and that two isoforms, VGLUT1 and VGLUT2, are localized to excitatory axon terminals in the cerebellar cortex. While granule cells express solely VGLUT1, there is no report about the VGLUT(s) of the unipolar brush cell (UBC), the second type of glutamatergic interneuron residing in the cerebellar granular layer.

Differential expression of calretinin and metabotropic glutamate receptor mGluR1alpha defines subsets of unipolar brush cells in mouse cerebellum.

The unipolar brush cell (UBC) is a type of glutamatergic interneuron in the granular layer of the cerebellum. The UBC brush and a single mossy fiber (MF) terminal contact each other within a cerebellar glomerulus, forming a giant synapse. Many UBCs receive input from extrinsic MFs, whereas others are innervated by intrinsic mossy terminals formed by the axons of other UBCs.

Cerebellar input to magnocellular neurons in the red nucleus of the mouse: synaptic analysis in horizontal brain slices incorporating cerebello-rubral pathways.

We studied the synaptic input from the nucleus interpositus of the cerebellum to the magnocellular division of the red nucleus (RNm) in the mouse using combined electrophysiological and neuroanatomical methods. Whole-cell patch-clamp recordings were made from brain slices (125-150 microm) cut in a horizontal plane oriented to pass through both red nucleus and nucleus interpositus. Large cells that were visually selected and patched were injected with Lucifer Yellow and identified as RNm neurons.

Unipolar brush cells form a glutamatergic projection system within the mouse cerebellar cortex.

Unipolar brush cells (UBCs) of the mammalian vestibulocerebellum receive mossy fiber projections primarily from the vestibular ganglion and vestibular nuclei. Recently, the axons of UBCs have been shown to generate an extensive system of cortex-intrinsic mossy fibers, which resemble traditional cerebellar mossy fiber afferents and synapse with granule cell dendrites and other UBCs. However, the neurotransmitter used by the UBC axon is still unknown.

Unipolar brush cell axons form a large system of intrinsic mossy fibers in the postnatal vestibulocerebellum.

The unipolar brush cells (UBCs), a class of neurons recently identified in the granular layer of the vestibulocerebellum, receive excitatory synaptic input from mossy fibers (MFs) in the form of a giant glutamatergic synapse. UBCs are provided with axons that bear synaptic endings situated at the center of glomeruli, similar to cerebellar MF afferents. A single MF stimulus evokes a prolonged train of action potentials in the UBC (Rossi et al.

Compartmental organization of Purkinje cells in the mature and developing mouse cerebellum as revealed by an olfactory marker protein-lacZ transgene.

In a line of transgenic mice (HpY-1), the pattern of expression of an olfactory marker protein (OMP)-lacZ fusion gene was analyzed in the cerebellum, where, in adult mice, OMP-lacZ was expressed primarily in Purkinje cells (PCs) of the posterior lobe. The transgene-expressing PCs were organized in parasagittal bands, with a boundary of expression roughly corresponding to the primary fissure that separates the cerebellum into anterior and posterior compartments. The regional expression of the lacZ gene was also analyzed during embryonic and postnatal development of the cerebellum.

Unusual ultrastructural features in intrafascicular ganglion cells of the rat pelvic nerve.

The incidental finding of four ectopic ganglion cells within the pelvic nerve of a normal rat prompted a thorough electron microscopic investigation of the ultrastructural features of these neurons. They were found to enwrap presynaptic terminals inside crater-like invaginations; the appositional surfaces were made more complex by the presence of slender dendritic appendages and sheet-like processes of glial cells. The presynaptic elements contained both clear and dense-cored vesicles, and appeared similar to those characterizing SIF (paraneuronal) cells.