Anaerobic sulfur oxidation underlies adaptation of a chemosynthetic symbiont to oxic-anoxic interfaces

Chemosynthetic symbioses occur worldwide in marine habitats, but comprehensive physiological studies of chemoautotrophic bacteria thriving on animals are scarce. Stilbonematinae are coated by thiotrophic Gammaproteobacteria. As these nematodes migrate through the redox zone, their ectosymbionts experience varying oxygen concentrations. However, nothing is known about how these variations affect their physiology. Here, by applying omics, Raman microspectroscopy, and stable isotope labeling, we investigated the effect of oxygen on “Candidatus Thiosymbion oneisti.” Unexpectedly, sulfur oxidation genes were upregulated in anoxic relative to oxic conditions, but carbon fixation genes and incorporation of (13)C-labeled bicarbonate were not. Instead, several genes involved in carbon fixation were upregulated under oxic conditions, together with genes involved in organic carbon assimilation, polyhydroxyalkanoate (PHA) biosynthesis, nitrogen fixation, and urea utilization. Furthermore, in the presence of oxygen, stress-related genes were upregulated together with vitamin biosynthesis genes likely necessary to withstand oxidative stress, and the symbiont appeared to proliferate less. Based on its physiological response to oxygen, we propose that “Ca. T. oneisti” may exploit anaerobic sulfur oxidation coupled to denitrification to proliferate in anoxic sand. However, the ectosymbiont would still profit from the oxygen available in superficial sand, as the energy-efficient aerobic respiration would facilitate carbon and nitrogen assimilation. IMPORTANCE Chemoautotrophic endosymbionts are famous for exploiting sulfur oxidization to feed marine organisms with fixed carbon. However, the physiology of thiotrophic bacteria thriving on the surface of animals (ectosymbionts) is less understood. One longstanding hypothesis posits that attachment to animals that migrate between reduced and oxic environments would boost sulfur oxidation, as the ectosymbionts would alternatively access sulfide and oxygen, the most favorable electron acceptor. Here, we investigated the effect of oxygen on the physiology of “Candidatus Thiosymbion oneisti,” a gammaproteobacterium which lives attached to marine nematodes inhabiting shallow-water sand. Surprisingly, sulfur oxidation genes were upregulated under anoxic relative to oxic conditions. Furthermore, under anoxia, the ectosymbiont appeared to be less stressed and to proliferate more. We propose that animal-mediated access to oxygen, rather than enhancing sulfur oxidation, would facilitate assimilation of carbon and nitrogen by the ectosymbiont

Humoral immunity to SARS-CoV-2 mRNA vaccination in multiple sclerosis: the relevance of time since last rituximab infusion and first experience from sporadic revaccinations

Introduction The effect of disease-modifying therapies (DMT) on vaccine responses is largely unknown. Understanding the development of protective immunity is of paramount importance to fight the COVID-19 pandemic. Objective To characterise humoral immunity after mRNA-COVID-19 vaccination of people with multiple sclerosis (pwMS). Methods All pwMS in Norway fully vaccinated against SARS-CoV-2 were invited to a national screening study. Humoral immunity was assessed by measuring anti-SARS-CoV-2 SPIKE RBD IgG response 3–12 weeks after full vaccination, and compared with healthy subjects. Results 528 pwMS and 627 healthy subjects were included. Reduced humoral immunity (anti-SARS-CoV-2 IgG <70 arbitrary units) was present in 82% and 80% of all pwMS treated with fingolimod and rituximab, respectively, while patients treated with other DMT showed similar rates as healthy subjects and untreated pwMS. We found a significant correlation between time since the last rituximab dose and the development of humoral immunity. Revaccination in two seronegative patients induced a weak antibody response. Conclusions Patients treated with fingolimod or rituximab should be informed about the risk of reduced humoral immunity and vaccinations should be timed carefully in rituximab patients. Our results identify the need for studies regarding the durability of vaccine responses, the role of cellular immunity and revaccinations. This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.publishedVersio

STA-MCA Bypass in Carotid Stenosis after Radiosurgery for Cavernous Sinus Meningioma

Cavernous sinus meningiomas (CSM) are mostly non-surgical tumors. Stereotactic radiosurgery (SRS) or radiotherapy (SRT) allow tumor control and improvement of pre-existing cranial nerve (CN) deficits. We report the case of a patient with radiation-induced internal carotid artery (ICA) stenosis. We complete the picture with a review of the literature of vascular and non-vascular complications following the treatment of CSMs with SRS or SRT

Squamous cell carcinoma of the paranasal sinuses: a single center experience

Objective  Squamous cell carcinoma (SCC) of the paranasal sinuses is usually diagnosed at an advanced stage, making curative therapy difficult. The goal of this study was to evaluate the management and outcomes of patients with SCC treated at our institution. Methods  In a population-based consecutive prospective cohort, we conducted an analysis of all patients treated for SCC between 1988 and 2017. Results  A total of 72 patients were included, follow-up was 100%. Mean follow-up was 57 months for the entire cohort, and 108 months for patients with no evidence of disease. Eighty-two percent of all patients had high-stage (T4) disease. Fifty-seven patients underwent treatment with curative intent; consisting of surgery with or without oncologic treatment in 34, and of oncologic treatment only in 23 cases. Fifteen patients received palliative treatment. The rates of overall survival for the entire cohort were 55% at 2, 41% at 5, and 32% at 10 years, and corresponding disease-specific survival (DSS) rates were 55, 45, and 34%, respectively. DSS rates after surgical treatment with curative intent were 81% at 2, 65% at 5, and 54% at 10 years. Retromaxillary involvement and nonradical surgery were negative prognostic factors. Best survival was achieved with the combination of radical surgery and adjuvant oncologic treatment. Conclusion  Surgical resection with a curative intent yielded 65% at 5-year DSS even in this cohort of patients with high-stage SCC and is still considered as the treatment of choice, preferably in combination with adjuvant radiation therapy and chemotherapy

Craniofacial resection of malignant tumors of the anterior skull base: a case series and a systematic review

Background: Craniofacial resection (CFR) is still considered as the gold standard for managing sinonasal malignancies of the anterior skull base (ASB), while endoscopic approaches are gaining credibility. The goal of this study was to evaluate outcomes of patients who underwent CFR at our institution and to compare our results to international literature. Method: Retrospective analysis of all patients undergoing CFR between 1995 and 2017, and systematic literature review according to the PRISMA statement. Results: 41 patients with sinonasal malignancy (81% with stage T4) of the ASB were included. There was no operative mortality. Complications were observed in 9 cases. We obtained 100% follow-up with mean observation 100 months. Disease-specific survival rates were 90%, 74% and 62% and recurrence-free survival was 85% at two, 72% at five and ten years follow-up, respectively. CFR as primary treatment, en bloc resection, and resection with negative margins correlated to better survival. Recursive partition analysis identified the latter as the most important prognostic factor, regardless surgical technique. The relative risk of non-radicality was significantly higher after piecemeal resection compared to en bloc resection. Compared to 15 original articles, totaling 2603 patients, eligible for review, the present study has the longest follow-up time, the second highest 5-year OS and the third highest 5-year DSS, despite having a higher proportion of patients with high-stage disease. Conclusion: CFR in true en bloc fashion can still be considered as the treatment of choice in cases of advanced-stage sinonasal malignancies invading the ASB

Olfactory neuroblastoma: a single-center experience

Olfactory neuroblastoma (ONB) is a potentially curable disease, despite being an aggressive malignancy with a poor natural history. Our goal was to evaluate management outcomes for patients with ONB treated at our institution. Our prospective database for brain tumors and the pathology registry of head and neck cancers at Oslo University Hospital were searched to identify all patients treated for ONB between 1998 and 2016. Variables extracted from these databases, supplemented by retrospective chart reviews, underwent thorough analysis. All cases were formally re-examined by a dedicated head and neck pathologist. Twenty patients were identified. Follow-up was 100%. Mean follow-up was 81.5 months for the entire cohort and 120.3 months for patients with no evidence of disease. Fourteen patients underwent treatment of choice including craniofacial resection (CFR) with or without radiotherapy (XRT). Six patients could only receive less extensive treatment; three patients underwent lateral rhinotomy (LR) with or without XRT after being deemed medically unsuitable for CFR, while another three patients received only supportive, non-surgical treatment (due to positive lymph node status in two and to extensive tumor size in one case). Overall and disease-specific survival rates were 100% after 10 years of follow-up when negative surgical margins were achieved by CFR. Positive margins were associated with poorer outcome with no patients surviving longer than 44 months. Long-term survival was also achieved in two cases among patients not eligible for CFR: one case after radical LR and one case after radio-chemotherapy. Advanced disease at presentation (tumor size ≥40 mm, Kadish grades C and D, or TNM IVa and IVb) and positive surgical margins were correlated to significantly dismal survival. Our study suggests that CFR with or without adjuvant XRT is safe and leads to excellent long-time overall and disease-specific survival. Negative surgical margins, tumor size <40 mm, Kadish stage A/B, and TNM stages I-III are independent prognostic predictors of outcome

Multimodal Treatment of Osteogenic Sarcoma of the Jaw

Osteosarcomas (OSs) account for 40 to 60% of primary malignant bone tumors. About 10% occur in the head and neck region, frequently in the mandibula or maxilla. We treated a 30-year-old patient with 26-month history of right-sided facial pain and paresthesia. Investigation showed high-grade OS of the right mandibular coronoid process, affecting the mandibular nerve, middle cranial fossa, internal jugular vein, and internal carotid artery (ICA). True en bloc resection was performed after upfront adjuvant chemotherapy. The ICA was trap-ligated intradurally, whereafter the floor of the middle fossa, including the mandibular nerve and the glenoid fossa, was detached from the skull base in one piece. Subsequently, a hemimandibulectomy, total parotidectomy, ICA sacrifice, and removal of the pterygoid plates and muscles were performed, and the abovementioned structures were removed as a solitary specimen, including the facial nerve branches overlying the tumor. A sural nerve graft was interposed between five major facial nerve branches to reanimate the face. The patient had an uneventful recovery, is able to eat, and has a partial facial nerve palsy. He has no tumor recurrence 26 months after surgery. OS of the jaw should be treated with radical surgery as the primary modality

Treatment of Sinonasal Adenocarcinoma: A Population-Based Prospective Cohort Study

Objectives Sinonasal adenocarcinoma (AC) is a potentially curable disease despite being an aggressive malignancy. Long-term survival can be achieved with early diagnosis and adequate multidisciplinary treatment. Our goal was to evaluate outcomes for patients with AC treated at our institution. Design In a population-based consecutive prospective cohort, we conducted an analysis of all patients treated for surface epithelial AC between 1995 and 2018. Results Twenty patients were included, and follow-up was 100%. The mean follow-up time was 89 months for the entire cohort (112 months for patients with no evidence of disease). Intestinal-type AC was found in 65%, whereas nonintestinal-type AC was found in 35% of all cases; 75% had stage T3/4 disease. Tumor grade was intermediate/high in 65%. Eighteen patients underwent treatment with curative intent (craniofacial resection [CFR] in 61%, transfacial approach in 39%, adjuvant radiotherapy in 89%), achieving negative margins in 56% of cases. Overall survival (OS) rates were 90, 68, and 54% after 2, 5, and 10 years of follow-up, respectively, and the corresponding disease-specific survival (DSS) rates were 90, 73, and 58%. Age over 60 years, tumor with a maxillary origin, and microscopic bone invasion were negative prognostic factors. Radical CFR was correlated with better OS and DSS. Conclusion The high probability of achieving radicality with CFR, the low complication rate, the acceptable toxicity of modern irradiation modalities, and the promising survival rates indicate that this strategy might be considered a safe and an effective option for treating patients with very advanced sinonasal AC