Multifunctional nano-in-micro delivery systems for targeted therapy in fundus neovascularization diseases.

Fundus neovascularization diseases are a series of blinding eye diseases that seriously impair vision worldwide. Currently, the means of treating these diseases in clinical practice are continuously evolving and have rapidly revolutionized treatment opinions. However, key issues such as inadequate treatment effectiveness, high rates of recurrence, and poor patient compliance still need to be urgently addressed. Multifunctional nanomedicine can specifically respond to both endogenous and exogenous microenvironments, effectively deliver drugs to specific targets and participate in activities such as biological imaging and the detection of small molecules. Nano-in-micro (NIM) delivery systems such as metal, metal oxide and up-conversion nanoparticles (NPs), quantum dots, and carbon materials, have shown certain advantages in overcoming the presence of physiological barriers within the eyeball and are widely used in the treatment of ophthalmic diseases. Few studies, however, have evaluated the efficacy of NIM delivery systems in treating fundus neovascular diseases (FNDs). The present study describes the main clinical treatment strategies and the adverse events associated with the treatment of FNDs with NIM delivery systems and summarizes the anatomical obstacles that must be overcome. In this review, we wish to highlight the principle of intraocular microenvironment normalization, aiming to provide a more rational approach for designing new NIM delivery systems to treat specific FNDs.

Proteomics-Based RT-qPCR and Functional Analysis of 18 Genes in Metronidazole Resistance of Bacteroides fragilis.

Previously, we reported that metronidazole MICs are not dependent on the expression levels of nim genes in B. fragilis strains and we compared the proteomes of metronidazole-resistant laboratory B. fragilis strains to those of their susceptible parent strains. Here, we used RT-qPCR to correlate the expression levels of 18 candidate genes in a panel of selected, clinical nim gene-positive and -negative B. fragilis strains to their metronidazole MICs. Metronidazole MICs were correlated with the expression of certain tested genes. Specifically, lactate dehydrogenase expression correlated positively, whereas cytochrome fumarate reductase/succinate dehydrogenase, malate dehydrogenase, phosphoglycerate kinase redox and gat (GCN5-like acetyltransferase), and relA (stringent response) regulatory gene expressions correlated negatively with metronidazole MICs. This result provides evidence for the involvement of carbohydrate catabolic enzymes in metronidazole resistance in B. fragilis. This result was supported by direct substrate utilization tests. However, the exact roles of these genes/proteins should be determined in deletion-complementation tests. Moreover, the exact redox cofactor(s) participating in metronidazole activation need to be identified.

Gut microbiota and inflammatory mediators differentiate IgE mediated and non-IgE mediated cases of cow's milk protein at diagnosis.

OBJECTIVE: Analyze fecal and blood samples at point of diagnosis in IgE mediated cow's milk protein allergy (CMPA) and non-IgE mediated (NIM)-CMPA patients to look for potential new biomarkers. PATIENTS AND METHODS: Fourteen patients with IgE mediated CMPA and 13 with NIM-CMPA were recruited in three hospitals in the north of Spain, and were compared with 25 infants from a control group of the same age range. To characterize intestinal microbiota, 16S rDNA gene and internal transcribed spacer amplicons of bifidobacteria were sequenced with Illumina technology. Fatty acids were analyzed by gas chromatography, meanwhile intestinal inflammation markers were quantified by enzyme-linked immunosorbent assay and a multiplex system. Immunological analysis of blood was performed by flow cytometry. RESULTS: The fecal results obtained in the NIM-CMPA group stand out. Among them, a significant reduction in the abundance of Bifidobacteriaceae and Bifidobacterium sequences with respect to controls was observed. Bifidobacterial species were also different, highlighting the lower abundance of Bifidobacterium breve sequences. Fecal calprotectin levels were found to be significantly elevated in relation to IgE mediated patients. Also, a higher excretion of IL-10 and a lower excretion of IL-1ra and platelet derived growth factor-BB was found in NIM-CMPA patients. CONCLUSIONS: The differential fecal parameters found in NIM-CMPA patients could be useful in the diagnosis of NIM food allergy to CM proteins.

Soft tissue injury events associated with neural integrity monitoring endotracheal tubes: A MAUDE database analysis.

OBJECTIVE: Neural integrity monitoring (NIM) endotracheal tubes are widely used to provide intraoperative monitoring of the recurrent laryngeal nerve during certain neck surgeries, especially thyroidectomy, in order to reduce the risk of nerve injury and subsequent vocal fold paralysis. The unique design of NIM tubes and the increased technical skill required for correct placement compared to standard endotracheal tubes may increase the risk of upper aerodigestive tract soft tissue injury. This study aims to describe adverse events related to NIM endotracheal tubes. STUDY DESIGN: Retrospective cross-sectional study. SETTING: The US Food and Drug Administration's MAUDE database (2010-2022); (Manufacturer and User Facility Device Experience). METHODS: The MAUDE database was queried for reports of adverse events that resulted in patient soft tissue injury involving the use of endotracheal tubes approved by the Food and Drug Administration. RESULTS: There were 28 reported soft tissue injuries, with all events being related to the NIM EMG family of endotracheal tubes manufactured by Medtronic Xomed, Inc. Overall, 24 were categorized as device-related adverse events, and 4 were unspecified in the event description. The most common soft tissue injuries were edema (n = 7) and perforation (n = 7), each accounting for 25 % of adverse events. The second most common injury type was laceration (n = 4), representing 14 % of all adverse events. Overall, 9 patients (32 %) in our cohort required a surgical intervention to treat their injuries, which consisted of 6 tracheotomies and 3 instances of suture repair. CONCLUSIONS: The most commonly reported types of soft tissue injury included edema and perforation, followed by laceration. Increased awareness of device-related patient injuries associated with NIM endotracheal tubes can be used to better inform surgeons and anesthesiologists during the process of intubation and surgical decision-making.

Intercomparison of neutron personal dose equivalent measured by thermoluminescence dosimeters.

An intercomparison of neutron personal dose equivalent measured by the Harshaw thermoluminescence neutron dosimeters (TLDs) between the National Institute of Metrology of China (NIM) and the Institute for Nuclear Science and Technology of Vietnam (INST) was performed. Three sets of TLDs (each set consisting of five TLDs) were prepared for each laboratory. Each set was then irradiated to the corresponding same nominal standard value of neutron personal dose equivalent, Hp(10)n-stdi, of 1.0, 2.0, and 3.0 mSv, respectively at these two laboratories. The irradiated TLDs were then read-out at the INST using the Harshaw 4500-type TLD reader to obtain neutron personal dose equivalents at the NIM, Hp(10)n-NIMi and at the INST, Hp(10)n-INSTi, which are corresponding to different values of Hp(10)n-stdi. The TLDs' responses to different scattered components of neutrons in these two fields are also discussed. Comparisons between the corresponding pair values of Hp(10)n-NIMi and Hp(10)n-INSTi show good agreements within 10% with the standard uncertainty of 12.5% (k = 1). The measured values of Hp(10)n-NIMi and Hp(10)n-INSTi are satisfied the Trumpet curve criteria. This implies that the TLDs can be used for safety assessment of occupational neutron personal dose equivalents. This intercomparison result also confirms the capabilities of these two laboratories (i.e., NIM, INST) on deliveries of neutron personal dose equivalent standard values for calibrations.

Partial Parotidectomy under Local Anaesthesia without Regional Block Assisted by Electromyographic Facial Nerve Monitoring - A Case Report.

The Rationale: This study describes a partial parotidectomy (PP) under local anaesthesia (LA) without regional block (LAwRB) assisted by electromyographic monitoring of the facial nerve, to consolidate the feasibility, efficacy and safety of these procedures without general anaesthesia (GA). Patient Concerns: An 82-year-old with a lump in the left parotid gland suspected for non-Hodgkin lymphoma (NHL) needed a histological examination to start chemotherapy. Diagnosis and Treatments: Because of multiple comorbidities, the authors performed a PP under LAwRB electromyographically guided by the NIM Vital (Medtronic)™. Outcomes: The procedure was quick and did not require conversion to GA. The histopathological examination confirmed the NHL. No haematoma, sialocoele, earlobe numbness and transient or permanent facial palsy were observed. Take-Away Lessons: The electrophysiologic monitoring of the facial nerve improves the efficacy, safety and feasibility of parotid surgery under LA, avoiding adverse effects of GA, need of regional block and reducing hospital stay.

The effects of identical nim gene-insertion sequence combinations on the expression of the nim genes and metronidazole resistance in Bacteroides fragilis strains.

In this study we examined whether the same nim gene-insertion sequence (IS) element combinations give rise to the same expression levels as they harbor shared IS element-borne promoters. From our quantitative analysis, we found that the expressions of the nimB and nimE genes with their cognate IS elements were similar, but the metronidazole resistance of these strains were more diverse.

Phenotypic and Genotypic Correlation of Antimicrobial Susceptibility of Bacteroides fragilis: Lessons Learnt.

Background Bacteroides fragilis is an opportunistic pathogen causing severe infections, including bacteremia. There have been increased reports of antimicrobial resistance in B. fragilis. However, phenotypic testing of susceptibility is time consuming and not cost effective for anaerobes. The present study investigates the correlation of phenotypic susceptibility with genotypic markers; to determine if these could be considered for deciding empirical therapy for B. fragilis. Material and methods Bacteroides fragilis isolates from various clinical samples including exudates, tissue, and body fluids were collected between November 2018 and January 2020 in the Department of Clinical Microbiology, Christian Medical College (CMC) Vellore. Species identification was done by Matrix Assisted Laser Desorption Ionization time of flight mass spectrometry (MALDI TOF) according to the manufacturer's instructions. A total number of 51 B. fragilis isolates were tested against metronidazole, clindamycin, piperacillin/tazobactam, and meropenem phenotypically by agar dilution method using Clinical & Laboratory Standards Institute (CLSI) 2019 guidelines and minimum inhibitory concentrations (MIC) were interpretated. The genotypic markers for antimicrobial resistance genes (nim, emrF, and cfiA) were studied by polymerase chain reaction (PCR) assay as per the standard protocol on all isolates to detect resistance genes. Results B. fragilis isolates in this study expressed 45%, 41%, and 16% phenotypic resistance to clindamycin, metronidazole, and meropenem, respectively, with least resistance to piperacillin/tazobactam (6%). Among the metronidazole resistant isolates, 52% harbored nim gene. Nim gene was also present in 76% (23/30) of the metronidazole susceptible isolates. Similarly, cfiA was present in all eight meropenem resistant isolates in addition to 22% (9/41) of the susceptible isolates. All cfiA negative isolates were phenotypically susceptible. Interestingly, 74% (17/23) of the clindamycin resistant isolates were positive for ermF. Conclusions Detection of a limited set of genes does not always correlate with phenotypic resistance to metronidazole and clindamycin due to the reported influence of insertion sequence (IS) elements, efflux, and other genetic determinants. Certainly, the absence of the cfiA gene can be employed to rule out meropenem resistance. However, redundant use of antibiotics such as meropenem along with metronidazole could be avoided for B. fragilis, which might otherwise elevate meropenem resistance. Recommendation of metronidazole requires prior phenotypic testing due to the reported 41% resistance.

Molecular study on metronidazole resistance in Bacteroides fragilis group isolates from a South Indian tertiary care center.

OBJECTIVE: Bacteroides species are an important part of human intestinal microbiota. They can cause infections of significant mortality and morbidity when moved out of their niche in the gut. The cornerstone drug for prophylaxis and therapy, metronidazole, is exhibiting signs of resistance, which are frequently attributed to nitroimidazole (nim) resistance genes. The aim of this study was to use Epsilometer test (E-test) to assess the metronidazole susceptibility and conventional PCR methodology to map the distribution of nim genes in Bacteroides fragilis group (BFG) isolates. METHODS: MALDI-TOF MS was used to identify BFG isolates. Using the E-test methodology, metronidazole minimum inhibitory concentrations (MICs) were determined. The presence of nim genes in these isolates were checked by conventional PCR methodology. Sequencing was done on selected amplicons for determining the nim gene types. RESULTS: Bacteroides fragilis accounted for 55.3% of the total 273 BFG members identified. Of these, 196 (71.8%) were susceptible, 43 (15.8%) intermediate and 34 (12.5%) resistant to metronidazole as determined by the E-test. nim gene was present in 101 (37%) of the total 273 isolates. Out of the 34 phenotypically resistant isolates (MIC ≥32 µg/ml), 29 harboured nim gene (Chi-square test, p < 0.0000001) but nim gene was absent in 5 (14.7%) isolates. Also, nim gene was detected in 72 (30.1%) of the 239 isolates with susceptible and intermediate metronidazole MIC. Sequencing of 20 amplicons gave a nimE gene type. CONCLUSIONS: In view of the rising metronidazole resistance among BFG and its close association with nim genes, there is a need for implementing routine metronidazole susceptibility testing and more researches are needed to find the molecular basis of these nim genes.

PDE6D Mediates Trafficking of Prenylated Proteins NIM1K and UBL3 to Primary Cilia.

Mutations in PDE6D impair the function of its cognate protein, phosphodiesterase 6D (PDE6D), in prenylated protein trafficking towards the ciliary membrane, causing the human ciliopathy Joubert Syndrome (JBTS22) and retinal degeneration in mice. In this study, we purified the prenylated cargo of PDE6D by affinity proteomics to gain insight into PDE6D-associated disease mechanisms. By this approach, we have identified a specific set of PDE6D-interacting proteins that are involved in photoreceptor integrity, GTPase activity, nuclear import, or ubiquitination. Among these interacting proteins, we identified novel ciliary cargo proteins of PDE6D, including FAM219A, serine/threonine-protein kinase NIM1 (NIM1K), and ubiquitin-like protein 3 (UBL3). We show that NIM1K and UBL3 localize inside the cilium in a prenylation-dependent manner. Furthermore, UBL3 also localizes in vesicle-like structures around the base of the cilium. Through affinity proteomics of UBL3, we confirmed its strong interaction with PDE6D and its association with proteins that regulate small extracellular vesicles (sEVs) and ciliogenesis. Moreover, we show that UBL3 localizes in specific photoreceptor cilium compartments in a prenylation-dependent manner. Therefore, we propose that UBL3 may play a role in the sorting of proteins towards the photoreceptor outer segment, further explaining the development of PDE6D-associated retinal degeneration.

Mitochondrial Permeability Transition in Stem Cells, Development, and Disease.

The mitochondrial permeability transition (mPT) is a process that permits rapid exchange of small molecules across the inner mitochondrial membrane (IMM) and thus plays a vital role in mitochondrial function and cellular signaling. Formation of the pore that mediates this flux is well-documented in injury and disease but its regulation has also emerged as critical to the fate of stem cells during embryonic development. The precise molecular composition of the mPTP has been enigmatic, with far more genetic studies eliminating molecular candidates than confirming them. Rigorous studies in the recent decade have implicated central involvement of the F1Fo ATP synthase, or complex V of the electron transport chain, and continue to confirm a regulatory role for Cyclophilin D (CypD), encoded by Ppif, in modulating the sensitivity of the pore to opening. A host of endogenous molecules have been shown to trigger flux characteristic of mPT, including positive regulators such as calcium ions, reactive oxygen species, inorganic phosphate, and fatty acids. Conductance of the pore has been described as low or high, and reversibility of pore opening appears to correspond with the relative abundance of negative regulators of mPT such as adenine nucleotides, hydrogen ion, and divalent cations that compete for calcium-binding sites in the mPTP. Current models suggest that distinct pores could be responsible for differing reversibility and conductance depending upon cellular context. Indeed, irreversible propagation of mPT inevitably leads to collapse of transmembrane potential, arrest of ATP synthesis, mitochondrial swelling, and cell death. Future studies should clarify ambiguities in mPTP structure and reveal new roles for mPT in dictating specialized cellular functions beyond cell survival that are tied to mitochondrial fitness including stem cell self-renewal and fate. The focus of this review is to describe contemporary models of the mPTP and highlight how pore activity impacts stem cells and development.

Small vestibular schwannoma presented with trigeminal neuralgia: illustrative case.

BACKGROUND: A vestibular schwannoma (VS) presenting with paroxysmal facial electric shock pain, that is, trigeminal neuralgia (TN), is relatively rare. Furthermore, TN is extremely rare in small VSs. OBSERVATIONS: Herein, the authors report the case of a 52-year-old woman with a complaint of right TN. Magnetic resonance (MR) imaging revealed a right VS of 12-mm diameter that compressed the trigeminal nerve. Although she did not report any hearing impairment, audiometry revealed decreased high-frequency range on the right side. The tumor was excised using the right retrosigmoid approach, and TN was confirmed to be caused by direct compression of the trigeminal nerve by the VS. Sufficient decompression of trigeminal nerve was done. The proximity of the trigeminal nerve root to the vestibular nerve root was the cause of TN. TN disappeared immediately after surgery, and there was no worsening of hearing impairment and facial paralysis. LESSONS: It is important to remember that TN may occur with direct tumor compression, even in small VSs. A preoperative 3-dimensional MR cisternogram/angiogram fusion image clearly showed direct tumor compression of the trigeminal nerve and the absence of responsible vessels, which was useful for surgical planning.

Modulation of Iron Import and Metronidazole Resistance in Bacteroides fragilis Harboring a nimA Gene.

Bacteroides fragilis is a commensal of the human gut but can also cause severe infections when reaching other body sites, especially after surgery or intestinal trauma. Bacteroides fragilis is an anaerobe innately susceptible to metronidazole, a 5-nitroimidazole drug that is prescribed against the majority of infections caused by anaerobic bacteria. In most of the cases, metronidazole treatment is effective but a fraction of B. fragilis is resistant to even very high doses of metronidazole. Metronidazole resistance is still poorly understood, but the so-called nim genes have been described as resistance determinants. They have been suggested to encode nitroreductases which reduce the nitro group of metronidazole to a non-toxic aminoimidazole. More recent research, however, showed that expression levels of nim genes are widely independent of the degree of resistance observed. In the search for an alternative model for nim-mediated metronidazole resistance, we screened a strain carrying an episomal nimA gene and its parental strain 638R without a nim gene for physiological differences. Indeed, the 638R daughter strain with the nimA gene had a far higher pyruvate-ferredoxin oxidoreductase (PFOR) activity than the parental strain. High PFOR activity was also observed in metronidazole-resistant clinical isolates, either with or without a nim gene. Moreover, the strain carrying a nimA gene fully retained PFOR activity and other enzyme activities such as thioredoxin reductase (TrxR) after resistance had been induced. In the parental strain 638R, these were lost or very strongly downregulated during the development of resistance. Further, after induction of high-level metronidazole resistance, parental strain 638R was highly susceptible to oxygen whereas the daughter strain with a nimA gene was hardly affected. Ensuing RT-qPCR measurements showed that a pathway for iron import via hemin uptake is downregulated in 638R with induced resistance but not in the resistant nimA daughter strain. We propose that nimA primes B. fragilis toward an alternative pathway of metronidazole resistance by enabling the preservation of normal iron levels in the cell.

Comparison of a Handheld Device vs Endotracheal Tube-Based Neuromonitoring for Recurrent Laryngeal Nerve Stimulation.

OBJECTIVE: To measure the effect of thyroidectomy difficulty on intraoperative neuromonitoring false loss of signal (LOS) and to compare intraoperative endotracheal tube-based neuromonitoring (ETNM) and Checkpoint palpation-based direct stimulation (pDS) signals with postoperative laryngoscopy. We hypothesized that pDS has higher a positive predictive value for postdissection confirmation of recurrent laryngeal nerve function than ETNM and that this difference is accentuated with increasing thyroidectomy difficulty. STUDY DESIGN: Prospective single-arm cross-sectional study comparing ETNM and pDS for patients undergoing hemi-, total, or completion thyroidectomy from July 2018 to March 2020. SETTING: Single-surgeon series at a tertiary care hospital. METHODS: Percentage concordance and positive and negative predictive values were measured. Each thyroidectomy was assigned a validated thyroidectomy difficulty score, and recorded recurrent laryngeal nerve signals were compared with postoperative vocal fold mobility. RESULTS: Percentage concordance was 90.09%. Positive and negative predictive values were 0.19 (95% CI, 0.09-0.31) and 1.0 for ETNM and 0.59 (95% CI, 0.35-0.82) and 1.0 for pDS. The difference in positive predictive value was significant (0.40 [95% CI, 0.33-0.47], P < .001). False LOS rates for ETNM and pDS were 13.19% versus 3.30% (9.89% [95% CI, 1.80%-18.62%], P = .0155), 44.11% versus 0% (44.11% [95% CI, 25.80%-60.54%], P < .001), and 73.33% versus 13.33% (60% [95% CI, 24.76%-78.46%], P = .001) for the second through fourth thyroidectomy difficulty score quartiles, respectively. False LOS with ETNM was linearly correlated with increasing difficulty (R2 = 0.97). CONCLUSION: ETNM was subject to high rates of postdissection false LOS that increased with thyroidectomy difficulty score. pDS is a reliable alternative that has higher positive predictive value than ETNM, particularly in more challenging cases such as those with posteriorly fixed thyroid cancers and fibrotic glands. EVIDENCE LEVEL: 2.

Effect of remimazolam on intraoperative neuromonitoring during thyroid surgery: a case series.

Intraoperative neuromonitoring is widely used to prevent accidental injury during thyroid surgery. Anesthesia should be performed without muscle relaxant or agents with high muscle-relaxant potency. Remimazolam, a novel intravenous anesthetic, became available for clinical use in 2020. Remimazolam is an ultra-short-acting benzodiazepine with a very high clearance rate. However, there are very few data regarding its effect on currently used intraoperative neurological monitoring. Five patients underwent thyroid surgery using intraoperative recurrent laryngeal neuromonitoring. In all cases, intubation was performed after the administration of rocuronium. Anesthesia was maintained by continuous administration of remimazolam at the recommended dose and remifentanil, and no additional rocuronium or sugammadex was administered. Recurrent laryngeal nerve activity could be detected at the first stimulus after surgery was started, and monitoring continued thereafter. Intraoperative monitoring was performed without problems and all surgeries were completed without any complications. Anesthesia with remimazolam at the normal dose did not prolong the time to first positive electromyogram in patients undergoing thyroid surgery, and enables intraoperative recurrent laryngeal nerve monitoring to be performed without any serious perioperative adverse events. Remimazolam may provide a comparable quality of anesthesia to that of existing drugs for neuromonitoring during thyroid surgery.

The Role of Nitroreductases in Resistance to Nitroimidazoles.

Antimicrobial resistance is a major challenge facing modern medicine, with an estimated 700,000 people dying annually and a global cost in excess of $100 trillion. This has led to an increased need to develop new, effective treatments. This review focuses on nitroimidazoles, which have seen a resurgence in interest due to their broad spectrum of activity against anaerobic Gram-negative and Gram-positive bacteria. The role of nitroreductases is to activate the antimicrobial by reducing the nitro group. A decrease in the activity of nitroreductases is associated with resistance. This review will discuss the resistance mechanisms of different disease organisms, including Mycobacterium tuberculosis, Helicobacter pylori and Staphylococcus aureus, and how these impact the effectiveness of specific nitroimidazoles. Perspectives in the field of nitroimidazole drug development are also summarised.

Genetic Approach to Elucidate the Role of Cyclophilin D in Traumatic Brain Injury Pathology.

Cyclophilin D (CypD) has been shown to play a critical role in mitochondrial permeability transition pore (mPTP) opening and the subsequent cell death cascade. Studies consistently demonstrate that mitochondrial dysfunction, including mitochondrial calcium overload and mPTP opening, is essential to the pathobiology of cell death after a traumatic brain injury (TBI). CypD inhibitors, such as cyclosporin A (CsA) or NIM811, administered following TBI, are neuroprotective and quell neurological deficits. However, some pharmacological inhibitors of CypD have multiple biological targets and, as such, do not directly implicate a role for CypD in arbitrating cell death after TBI. Here, we reviewed the current understanding of the role CypD plays in TBI pathobiology. Further, we directly assessed the role of CypD in mediating cell death following TBI by utilizing mice lacking the CypD encoding gene Ppif. Following controlled cortical impact (CCI), the genetic knockout of CypD protected acute mitochondrial bioenergetics at 6 h post-injury and reduced subacute cortical tissue and hippocampal cell loss at 18 d post-injury. The administration of CsA following experimental TBI in Ppif-/- mice improved cortical tissue sparing, highlighting the multiple cellular targets of CsA in the mitigation of TBI pathology. The loss of CypD appeared to desensitize the mitochondrial response to calcium burden induced by TBI; this maintenance of mitochondrial function underlies the observed neuroprotective effect of the CypD knockout. These studies highlight the importance of maintaining mitochondrial homeostasis after injury and validate CypD as a therapeutic target for TBI. Further, these results solidify the beneficial effects of CsA treatment following TBI.

Endoscopic endonasal extreme far-medial approach for a lower clivus osteochondroma in a patient with hereditary multiple exostoses: illustrative case.

BACKGROUND: The authors reported on the use of endoscopic endonasal surgery (EES) for clivus osteochondroma in a patient with hereditary multiple exostoses (HME), a rare pediatric disorder characterized by the formation of osteochondromas adjacent to the growth plates of the axial and appendicular skeletal elements. OBSERVATIONS: A 26-year-old man with a family history of HME reported progressive hoarseness and dysphagia over the previous 6 months. He was referred to us after magnetic resonance imaging (MRI) showed a bone tumor in the lower clivus. MRI revealed tumor proliferation in the lower clivus and its extension to the bilateral occipital condyle and jugular tubercle. The hypoglossal canal and jugular foramen were encased on the right side, whereas the medulla oblongata was compressed. The tumor was subtotally resected with EES, and the brainstem was successfully decompressed. The pathological diagnosis was exostoses. Transient postoperative worsening of dysphagia improved within 1 month without other neurological deficits. The patient underwent posterior occipitoaxial fixation 3 months after EES to correct instability and local lateral tilt of the right atlanto-occipital joint. LESSONS: The authors' experience showed that EES is effective for resection of lower clivus osteochondromas, including the cartilaginous cap, and may improve clinical outcomes in patients with HME.

Endoscopy-assisted transoral resection of a parapharyngeal space schwannoma without mandibular dissection.

Of the schwannomas that arise from the parapharyngeal space, those in the high cervical region are particularly invasive, requiring mandibular dissection. Because these tumors are benign, however, excessive surgical invasion and postoperative neurological complications should be avoided. Postoperative dropout symptoms may be avoided by intracapsular extraction, including nerve integrity monitoring (NIM) and narrow-band imaging (NBI). Video laryngoscopy surgery is reported to be useful for transoral resection of pharyngeal and laryngeal tumors. This report describes the transoral removal of a giant schwannoma located in the high cervical region from a 74-years-old man using a surgical support device without mandibular dissection. The tumor was located on the right lateral pharyngeal wall and extended from the upper oropharynx to the hypopharynx while compressing the epiglottis to the skull base. No separation was observed between the internal jugular vein and the internal carotid artery. The tumor was diagnosed as a schwannoma with no malignancy on the basis of the histology of a core needle biopsy (CNB), and was completely and safely removed endoscopically using NIM and NBI, with no need for an external incision or mandibular dissection. This case illustrates that even a huge sympathetic schwannoma located in the parapharyngeal space at a high cervical position can be excised transorally using video-laryngoscopic surgery (TOVS) without mandibular dissection.