Differences in skull base thickness exist in SCSF patients, but whether this predisposes to such leaks or is a consequence of the underlying pathophysiology remains unknown. The endoscopic endonasal approach provides a highly effective means of repairing such leaks with success rates comparable with the endoscopic repair of other leak types. Adjuvant measures including weight reduction, lumbar drain, and acetazolamide use may increase success rates and should be considered in their management.
Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on‐going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA‐4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first‐line treatment for metastatic NPC (PFS 68% at 1‐year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1‐year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non‐PD1 checkpoint inhibitors but 11 on‐going studies include alternative targets (e.g. PD‐L1/CTLA‐4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti‐PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.
Patients treated with RAI exhibited an increased risk for sialadenitis as well as a reduction in swallowing-related and global head and neck quality of life. Our findings suggest these patients should be screened for salivary morbidity and may benefit from both pre-RAI prophylaxis and post-RAI intervention.
Gore-tex thyroplasty provides durable improvement in subjective and perceptual voice outcomes for patients with nonparalytic GI. Patients treated for hypomobility/paresis have the most durable vocal outcomes followed by atrophy and lastly, scar.
The Bloom syndrome helicase, BLM, has numerous functions that prevent mitotic crossovers. We used unique features of Drosophila melanogaster to investigate origins and properties of mitotic crossovers that occur when BLM is absent. Induction of lesions that block replication forks increased crossover frequencies, consistent with functions for BLM in responding to fork blockage. In contrast, treatment with hydroxyurea, which stalls forks, did not elevate crossovers, even though mutants lacking BLM are sensitive to killing by this agent. To learn about sources of spontaneous recombination, we mapped mitotic crossovers in mutants lacking BLM. In the male germline, irradiation-induced crossovers were distributed randomly across the euchromatin, but spontaneous crossovers were nonrandom. We suggest that regions of the genome with a high frequency of mitotic crossovers may be analogous to common fragile sites in the human genome. Interestingly, in the male germline there is a paucity of crossovers in the interval that spans the pericentric heterochromatin, but in the female germline this interval is more prone to crossing over. Finally, our system allowed us to recover pairs of reciprocal crossover chromosomes. Sequencing of these revealed the existence of gene conversion tracts and did not provide any evidence for mutations associated with crossovers. These findings provide important new insights into sources and structures of mitotic crossovers and functions of BLM helicase. MEIOTIC recombination was discovered 100 years ago by T. H. Morgan and his students in classic studies of Drosophila genetics (Morgan 1911). Since that time, a great deal has been learned about the functions, molecular mechanisms, and regulation of meiotic recombination. This process is initiated through the introduction of programmed DNA doublestrand breaks (DSBs), which are then repaired through highly regulated homologous recombination (HR) pathways such that a substantial fraction of repair events produce reciprocal crossovers (reviewed in Kohl and Sekelsky 2013). The chiasmata that form at sites of crossovers help to ensure accurate segregation of homologous chromosomes. In addition, crossovers generate chromosomes with novel combinations of alleles at linked loci, leading to increased genetic diversity.A quarter century after the discovery of meiotic recombination, Curt Stern, also working with Drosophila, found that crossovers can occur in somatic cells (Stern 1936). This phenomenon is usually called "mitotic recombination," although most such events are thought to occur during interphase rather than in mitosis per se. Compared to meiotic recombination, little is known about mitotic recombination. Except in some specialized cases, like antibody gene rearrangement, mitotic recombination occurs in response to DNA damage (spontaneous or exogenously induced). Mitotic recombination, like meiotic recombination, can be initiated by DSBs, but it is unclear whether DSBs constitute a substantial fraction of the events that initiate spontan...
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