Background The objective of this study is to compare the oncologic outcomes of CO 2 transoral laser microsurgery (TLM) and radiotherapy (RT) for treatment of T1 glottic carcinoma. Methods A literature search was conducted in the following databases: Medline/PubMed, Web of Science, EMBASE, and the Cochrane Library. Search results were screened, and publications comparing oncologic outcomes of T1N0M0 glottic carcinoma treated with TLM or RT were included. Data was extracted independently by two authors, and publication quality was graded according to the Oxford Centre for Evidence-based Medicine. Meta-analysis was performed for overall survival, disease specific survival, laryngeal preservation, and local control. Results Sixteen studies were included in the meta-analysis, the majority being retrospective cohort studies with two prospective cohort studies. Included studies were rated as either Level II or III evidence. Meta-analysis favoured treatment with TLM for T1 glottic carcinoma patients for the following outcomes: overall survival (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.07–2.14; P = 0.02), disease specific survival (OR, 2.70; CI, 1.32–5.54; P = 0.007), and laryngeal preservation (OR, 6.31; CI, 3.77–10.56; P < 0.00001). There was no difference in local control between TLM and RT in T1 glottic cancer (OR, 1.19; CI, 0.79–1.81; P = 0.40). Discussion Our study provides a current and thorough comparison of TLM and RT outcomes in T1 glottic carcinoma. Limitations of our study include lack of randomized control trials, and non-randomized allocation of patients to treatment groups. Our meta-analysis suggests that TLM is the superior modality in terms of overall survival, disease specific survival, and laryngeal preservation. Future prospective randomized controlled studies are required for confirming these findings and developing appropriate clinical practice guidelines. Level of evidence 2A; as per the Centre of Evidence Based Medicine.
Trigeminal Neuralgia (TN) is a chronic neuropathic pain syndrome characterized by paroxysmal unilateral shock-like pains in the trigeminal territory most frequently attributed to neurovascular compression of the trigeminal nerve at its root entry zone. Recent advances in the study of TN suggest a possible central nervous system (CNS) role in modulation and maintenance of pain. TN and other chronic pain patients commonly experience alterations in cognition and affect, as well as abnormalities in CNS volume and microstructure in regions associated with pain perception, emotional modulation, and memory consolidation. However, the microstructural changes in the hippocampus, an important structure within the limbic system, have not been previously studied in TN patients. Here, we use grey matter analysis to assess whether TN pain is associated with altered hippocampal subfield volume in patients with classic TN. Anatomical magnetic resonance (MR) images of twenty-two right-sided TN patients and matched healthy controls underwent automated segmentation of hippocampal subfields using FreeSurfer v6.0. Right-sided TN patients had significant volumetric reductions in ipsilateral cornu ammois 1 (CA1), CA4, dentate gyrus, molecular layer, and hippocampus-amygdala transition area – resulting in decreased whole ipsilateral hippocampal volume, compared to healthy controls. Overall, we demonstrate selective hippocampal subfield volume reduction in patients with classic TN. These changes occur in subfields implicated as neural circuits for chronic pain processing. Selective subfield volume reduction suggests aberrant processes and circuitry reorganization, which may contribute to development and/or maintenance of TN symptoms.
Autophagy is an evolutionarily conserved lysosomal degradation pathway that plays important roles in cell maintenance, expansion and differentiation. Removal of genes essential for autophagy from embryonic neural stem and precursor cells reduces the survival and inhibits neuronal differentiation of adult-generated neurons. No study has modified autophagy within the adult precursor cells, leaving the cell-autonomous role of autophagy in adult neurogenesis unknown. Here we demonstrate that autophagic flux exists in the adult dividing progenitor cells and their progeny in the dentate gyrus. To investigate the role of autophagy in adult hippocampal neurogenesis, we genetically deleted Autophagy-related gene 5 (Atg5) that reduced autophagic flux and the survival of the progeny of dividing progenitor cells. This significant reduction in survival of adult-generated neurons is accompanied by a delay in neuronal maturation, including a transient reduction in spine density in the absence of a change in differentiation. The delay in cell maturation and loss of progeny of the Atg5-null cells was not present in mice that lacked the essential pro-apoptotic protein Bax (Bcl-2-associated X protein), suggesting that Atg5-deficient cells die through a Bax-dependent mechanism. In addition, there was a loss of Atg5-null cells following exposure to running, suggesting that Atg5 is required for running-induced increases in neurogenesis. These findings highlight the cell-autonomous requirement of Atg5 in the survival of adult-generated neurons.
Mutations in the presenilin genes (PS1 and PS2) are a major cause of familial-Alzheimer’s disease (FAD). Presenilins regulate neurogenesis in the developing brain, with loss of PS1 inducing aberrant premature differentiation of neural progenitor cells, and additional loss of PS2 exacerbating this effect. It is unclear, however, whether presenilins are involved in adult neurogenesis, a process that may be impaired in Alzheimer’s disease within the hippocampus. To investigate the requirement of presenilins in adult-generated dentate granule neurons, we examined adult neurogenesis in the PS2−/− adult brain and then employ a retroviral approach to ablate PS1 selectively in dividing progenitor cells of the PS2−/− adult brain. Surprisingly, the in vivo ablation of both presenilins resulted in no defects in the survival and differentiation of adult-generated neurons. There was also no change in the morphology or functional properties of the retroviral-labeled presenilin-null cells, as assessed by dendritic morphology and whole-cell electrophysiology analyses. Furthermore, while FACS analysis showed that stem and progenitor cells express presenilins, inactivation of presenilins from these cells, using a NestinCreERT2 inducible genetic approach, demonstrated no changes in the proliferation, survival, or differentiation of adult-generated cells. Therefore, unlike their significant role in neurogenesis during embryonic development, presenilins are not required for cell-intrinsic regulation of adult hippocampal neurogenesis.
Background The objective of this study was to examine how surgery interest groups (SIGs) across Canada function and influence medical students’ interest in surgical careers. Methods Two unique surveys were distributed using a cross sectional design. The first was sent to SIG executives and the second to SIG members enrolled at a Canadian medical school in the 2016/17 academic year. The prior focused on the types of events hosted, SIG structure/ supports, and barriers/ plans for improvement. The second questionnaire focused on student experience, involvement, and suggestions for improvement. Results SIG executives became involved in SIG through classmates and colleagues (8/17, 47%). Their roles focused on organizing events (17/17, 100%), facilitating student contact with resident/surgeons (17/17, 100%), and organizing funding (13/17, 76%). Surgical skills events were among the most successful and well received by students (15/17, 88%). Major barriers faced by SIG executives during their tenure included time conflicts with other interest groups (13/17, 76%), lack of funding (8/17, 47%), and difficulty booking spaces for events (8,17, 47%). SIGs were found to facilitate improvement in basic surgical skills ( μ = 3.89/5 ± 0.70) in a comfortable environment ( μ = 4.02/5, ±0.6), but were not helpful with final block examinations ( μ = 2.98/5, ±0.80). Members indicated that more skills sessions, panel discussion and shadowing opportunities would be beneficial additions. Overall, members felt that SIGs increased their interest in surgical careers ( μ = 3.50/5, ±0.79). Conclusion Canadian SIGs not only play a critical role in early exposure, but may provide a foundation to contribute to student success in surgery. Electronic supplementary material The online version of this article (10.1186/s12909-019-1502-5) contains supplementary material, which is available to authorized users.
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