Orbital preservation in the treatment of acute invasive fungal sinusitis.

Acute invasive fungal sinusitis (AIFS) is an aggressive disease with significant mortality and morbidity. Surgical debridement is a mainstay of treatment. However, orbital involvement may limit its efficacy and is an independent risk factor for mortality. Traditionally, orbital exenteration has been utilized in cases with orbital invasion and ophthalmoplegia or vision loss. Retrobulbar liposomal amphotericin B injection may improve disease control and has the potential to spare the morbidity associated with exenteration. In this video article, we document the use of serial endonasal debridement with retrobulbar injections to salvage the eye in a patient with significant orbital involvement. A 28-year-old immunocompromised female patient presented with acute onset restricted right extraocular movement, progressive orbital pain, V2 trigeminal numbness, and 20/40 vision. The patient underwent recurrent debridement and retrobulbar injections of liposomal amphotericin B. Her serial exams, including changes in extraocular muscle appearance and gradual improvement in extraocular movement, were documented. The exam six months after initial presentation demonstrated 20/20 vision, minimal extraocular movement restriction, and proper healing of the orbit and ethmoid. The salvage of the patient's orbit suggests that liposomal amphotericin B injections with debridement may be a viable treatment alternative in patients with acute invasive fungal sinusitis and orbital involvement.

Extranodal marginal zone lymphoma of the larynx: A case report and scoping review.

BACKGROUND: This scoping review aims to review cases of extranodal marginal zone lymphoma (MZL) of the larynx to establish best management practices for this rare clinical entity. METHODS: In this paper, we report a case of laryngeal MZL, in accordance with CARE guidelines. We then performed a scoping review according to PRISMA-ScR criteria of published cases of MZL involving the larynx. The following data were collected for each case: age, sex, size, location(s) involved, stage, treatment, follow-up, and recurrence duration. RESULTS: Sixty-six patients with laryngeal MZL, first reported in 1990, were identified. Characterized by its low-grade histological appearance and indolent course, laryngeal MZL is generally confined to the larynx and has an excellent prognosis with radiation used as first-line therapy. CONCLUSIONS: It is imperative for clinicians to consider lymphoma in the differential diagnosis of a laryngeal tumor from any subsite, as certain pathologies may carry high risks of metastasis.

Chronic Rhinosinusitis Risk after Maxillectomy with Microvascular Reconstruction.

INTRODUCTION: Chronic rhinosinusitis (CRS) can be associated with tumors involving the maxillary sinus, but outcomes after undergoing maxillectomy with free flap reconstruction remain unclear. METHODS: A retrospective analysis of medical records was performed to evaluate evidence of CRS in patients who underwent maxillectomy with free flap reconstruction at a single tertiary care academic institution from 2013 through 2020. RESULTS: Eighty-four patients were assessed. Nineteen (22.6%) patients were diagnosed with CRS after surgery, 23 (27.4%) patients were treated for sinus symptoms, and 49 (58.3%) had radiographic evidence of sinus inflammation for more than 6 months. Risk factors for requiring sinus treatment included adjuvant or neoadjuvant chemotherapy (p = 0.002) and pre-operative use of sinus medication (p < 0.001). Radiographic evidence of sinusitis 6 months after surgery is also closely associated with sinusitis treatment (p = 0.051). CONCLUSIONS: CRS may be underdiagnosed in patients undergoing maxillectomy with microvascular reconstruction. Further evaluation into patient sinus disease and symptoms following neoplastic surgery may lead to a higher quality of life in some long-term survivors.

Mechanical and biochemical feedback combine to generate complex contractile oscillations in cytokinesis.

The actomyosin cortex is an active material that generates force to drive shape changes via cytoskeletal remodeling. Cytokinesis is the essential cell division event during which a cortical actomyosin ring closes to separate two daughter cells. Our active gel theory predicted that actomyosin systems controlled by a biochemical oscillator and experiencing mechanical strain would exhibit complex spatiotemporal behavior. To test whether active materials in vivo exhibit spatiotemporally complex kinetics, we imaged the C. elegans embryo with unprecedented temporal resolution and discovered that sections of the cytokinetic cortex undergo periodic phases of acceleration and deceleration. Contractile oscillations exhibited a range of periodicities, including those much longer periods than the timescale of RhoA pulses, which was shorter in cytokinesis than in any other biological context. Modifying mechanical feedback in vivo or in silico revealed that the period of contractile oscillation is prolonged as a function of the intensity of mechanical feedback. Fast local ring ingression occurs where speed oscillations have long periods, likely due to increased local stresses and, therefore, mechanical feedback. Fast ingression also occurs where material turnover is high, in vivo and in silico. We propose that downstream of initiation by pulsed RhoA activity, mechanical feedback, including but not limited to material advection, extends the timescale of contractility beyond that of biochemical input and, therefore, makes it robust to fluctuations in activation. Circumferential propagation of contractility likely allows for sustained contractility despite cytoskeletal remodeling necessary to recover from compaction. Thus, like biochemical feedback, mechanical feedback affords active materials responsiveness and robustness.

An exploration into the relationship between insomnia and repetitive negative thinking among cancer survivors.

OBJECTIVE: Insomnia and repetitive negative thinking (RNT) are both prevalent among cancer survivors, yet little work has investigated their interrelationship. To explore the hypothesis that RNT and insomnia are related, we conducted secondary analyses on data from a pilot clinical trial of cognitive behavioral therapy for insomnia (CBT-I) for cancer survivors. METHODS: This study analyzed survey data from 40 cancer survivors with insomnia who participated in a pilot randomized trial of CBT-I. Correlations and linear regression models were used to determine associations between aspects of RNT and related constructs (fear of cancer recurrence [FCR], cancer-specific rumination, worry, and intolerance of uncertainty) and sleep (insomnia and sleep quality), while accounting for psychiatric symptoms such as anxiety and depression. Treatment-related change in RNT was examined using a series of linear mixed models. RESULTS: Evidence for an association between RNT and insomnia among cancer survivors emerged. Higher levels of FCR and cancer-related rumination were correlated with more severe insomnia symptoms and worse sleep quality. Notably, FCR levels predicted insomnia, even after controlling for anxiety and depression. Results identified potential benefits and limitations of CBT-I in addressing RNT that should be examined more thoroughly in future research. CONCLUSIONS: RNT is a potential target to consider in insomnia treatment for cancer survivors.

A phase 3b study of venetoclax and azacitidine or decitabine in an outpatient setting in patients with acute myeloid leukemia.

Venetoclax, a highly selective BCL-2 inhibitor, combined with hypomethylating agents (HMAs) azacitidine or decitabine, is approved for the treatment of newly diagnosed acute myeloid leukemia (ND AML) in patients who are ineligible to receive intensive chemotherapy. Previous clinical studies initiated venetoclax plus HMA in an inpatient setting owing to concerns of tumor lysis syndrome (TLS). This study (NCT03941964) evaluated the efficacy and safety of venetoclax plus HMA in a United States community-based outpatient setting in patients with ND AML (N = 60) who were treatment naïve for AML, ineligible to receive intensive chemotherapy, had no evidence of spontaneous TLS at screening, and were deemed as appropriate candidates for outpatient initiation of venetoclax plus HMA by the investigator. Patients received venetoclax in combination with azacitidine (75 mg/m2) or decitabine (20 mg/m2) for up to 6 cycles during the study. With a median time on study of 18.3 weeks, the best response rate of composite complete remission was 66.7%, and the overall post-baseline red blood cell (RBC) and platelet transfusion independence rate was 55.0%, consistent with results of studies in which treatment was initiated in an inpatient setting. Key adverse events included nausea, anemia, thrombocytopenia, neutropenia, and white blood cell count decrease of any grade (≥50% of patients). The observed safety profile was generally consistent with that of venetoclax plus HMA observed in inpatient AML studies. With close monitoring, 2 cases of TLS were identified, appropriately managed, and the patients were able to continue study treatment. CLINICAL TRIALS REGISTRATION: This study is registered at ClinicalTrials.gov. The registration identification number is NCT03941964.

Characterization of the Pristionchus pacificus "epigenetic toolkit" reveals the evolutionary loss of the histone methyltransferase complex PRC2.

Comparative approaches have revealed both divergent and convergent paths to achieving shared developmental outcomes. Thus, only through assembling multiple case studies can we understand biological principles. Yet, despite appreciating the conservation-or lack thereof-of developmental networks, the conservation of epigenetic mechanisms regulating these networks is poorly understood. The nematode Pristionchus pacificus has emerged as a model system of plasticity and epigenetic regulation as it exhibits a bacterivorous or omnivorous morph depending on its environment. Here, we determined the "epigenetic toolkit" available to P. pacificus as a resource for future functional work on plasticity, and as a comparison with Caenorhabditis elegans to investigate the conservation of epigenetic mechanisms. Broadly, we observed a similar cast of genes with putative epigenetic function between C. elegans and P. pacificus. However, we also found striking differences. Most notably, the histone methyltransferase complex PRC2 appears to be missing in P. pacificus. We described the deletion/pseudogenization of the PRC2 genes mes-2 and mes-6 and concluded that both were lost in the last common ancestor of P. pacificus and a related species P. arcanus. Interestingly, we observed the enzymatic product of PRC2 (H3K27me3) by mass spectrometry and immunofluorescence, suggesting that a currently unknown methyltransferase has been co-opted for heterochromatin silencing. Altogether, we have provided an inventory of epigenetic genes in P. pacificus to compare with C. elegans. This inventory will enable reverse-genetic experiments related to plasticity and has revealed the first loss of PRC2 in a multicellular organism.

Newly identified nematodes from the Great Salt Lake are associated with microbialites and specially adapted to hypersaline conditions.

Extreme environments enable the study of simplified food-webs and serve as models for evolutionary bottlenecks and early Earth ecology. We investigated the biodiversity of invertebrate meiofauna in the benthic zone of the Great Salt Lake (GSL), Utah, USA, one of the most hypersaline lake systems in the world. The hypersaline bays within the GSL are currently thought to support only two multicellular animals: brine fly larvae and brine shrimp. Here, we report the presence, habitat, and microbial interactions of novel free-living nematodes. Nematode diversity drops dramatically along a salinity gradient from a freshwater river into the south arm of the lake. In Gilbert Bay, nematodes primarily inhabit reef-like organosedimentary structures built by bacteria called microbialites. These structures likely provide a protective barrier to UV and aridity, and bacterial associations within them may support life in hypersaline environments. Notably, sampling from Owens Lake, another terminal lake in the Great Basin that lacks microbialites, did not recover nematodes from similar salinities. Phylogenetic divergence suggests that GSL nematodes represent previously undescribed members of the family Monhysteridae-one of the dominant fauna of the abyssal zone and deep-sea hydrothermal vents. These findings update our understanding of halophile ecosystems and the habitable limit of animals.

Analysis of the Technical Accuracy of a Patient-Specific Stereotaxy Platform for Brain Biopsy.

The use of stereotactic frames is a common practice in neurosurgical interventions such as brain biopsy and deep brain stimulation. However, conventional stereotactic frames have been shown to require modification and adaptation regarding patient and surgeon comfort as well as the increasing demand for individualized medical treatment. To meet these requirements for carrying out state-of-the-art neurosurgery, a 3D print-based, patient-specific stereotactic system was developed and examined for technical accuracy. Sixteen patient-specific frames, each with two target points, were additively manufactured from PA12 using the Multi Jet Fusion process. The 32 target points aim to maximize the variability of biopsy targets and depths for tissue sample retrieval in the brain. Following manufacturing, the frames were measured three-dimensionally using an optical scanner. The frames underwent an autoclave sterilization process prior to rescanning. The scan-generated models were compared with the planned CAD models and the deviation of the planned target points in the XY-plane, Z-direction and in the resulting direction were determined. Significantly lower (p < 0.01) deviations were observed when comparing CAD vs. print and print vs. sterile in the Z-direction (0.17 mm and 0.06 mm, respectively) than in the XY-plane (0.46 mm and 0.16 mm, respectively). The resulting target point deviation (0.51 mm) and the XY-plane (0.46 mm) are significantly higher (p < 0.01) in the CAD vs. print comparison than in the print vs. sterile comparison (0.18 mm and 0.16 mm, respectively). On average, the results from the 32 target positions examined exceeded the clinically required accuracy for a brain biopsy (2 mm) by more than four times. The patient-specific stereotaxic frames meet the requirements of modern neurosurgical navigation and make no compromises when it comes to accuracy. In addition, the material is suitable for autoclave sterilization due to resistance to distortion.

Reconstruction of the Anterior Skull Base Using the Nasoseptal Flap: A Review.

The nasoseptal flap is a workhorse reconstructive option for anterior skull base defects during endonasal surgery. This paper highlights the versatility of the nasoseptal flap. After providing a brief historical perspective, this review will focus on the relevant primary literature published in the last ten years. We will touch upon new applications of the flap, how the flap has been modified to expand its reach and robustness, and some of the current limitations. We will conclude by discussing what the future holds for improving upon the design and use of the nasoseptal flap in anterior skull base reconstruction.