Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune neurological disorder primarily affecting the peripheral nervous system. It is important to recognize because treatment with immunomodulators can improve symptoms. We present the case of a 61-year-old man who developed a saddle pulmonary embolus as well as right-sided deep venous thrombi following left knee arthroplasty. Two months later, he had persistent pre-syncopal symptoms with exertion and had developed paraesthesias in both feet. Invasive cardiopulmonary exercise testing revealed preload failure with no evidence of pulmonary hypertension. He was then referred to neurology where clinical history, physical examination, autonomic battery, and nerve biopsy were consistent with a diagnosis of CIDP with autonomic dysfunction. Extensive venous thromboembolism may be a unique presentation of CIDP. The mechanisms, which may lead to hypercoagulability in CIDP, include the presence of systemic inflammation and denervation of peripheral vasculature leading to stasis. Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune neurological disorder, affecting 1 in 200,000. It classically presents as a symmetric motor neuropathy causing proximal and distal muscle weakness. However, up to 50% of patients can have atypical presentations, including asymmetric sensorimotor, primary sensory, distal and sensory predominant, and sensory polyradiculopathy . AlthougOn a pathological level, CIDP is characterized by an aberrant immune response against peripheral nerves and nerve roots. Nerve biopsies frequently show lymphocytic infiltration of affected nerves and areas of segmental demyelination and remyelination. Both environmental and genetic factors have been implicated in the development of CIDP. Several different mechanisms have been proposed regarding how CIDP may develop following an immune stimulus such as an infection. There may be cross-reactivity between the epitopes of the organism causing the infection and self-antigens (i.e. molecular mimicry). If a pathogen cannot be totally eradicated it may trigger an excessive immune response leading to tissue damage and the subsequent presentation of self-antigens via antigen-presenting cells, leading to epitope spreading. Infection can also activate a non-specific immune response which can further contribute to tissue damage and self-antigen presentation. In terms of genetic factors, genome-wide association studies have identified polymorphisms in several HLA genes and in genes involved in the immune response to be overrepresented in CIDP. CIDP has been reported to co-occur with many other autoimmune disorders. Patients with CIDP have also been found to have altered activity of T cell subsets in the blood and CSF and altered cytokine production. A subset of CIDP patients has even been demonstrated to possess autoantibodies against myelin antigens. All of this evidence points to CIDP being an autoimmune disorder ,5. ReseaThe risk of VTE in CIDP patients has not been previously studied. However, there have been multiple reported cases of CIDP associated with membranous glomerulonephritis (MGN) . The ass2), and osteoarthritis underwent a left knee arthroplasty (LKA) without complication. After undergoing surgery, he received DVT prophylaxis with two days of low molecular weight heparin while hospitalized and was then discharged home on 81 mg of aspirin daily. Prior to surgery, the patient led an active lifestyle, including regular elliptical use and golfing. Following his LKA he attended all physical therapy sessions. One month following surgery, he abruptly became lightheaded and dyspneic, with no relief of symptoms upon rest. He presented to his local emergency department where he was noted to have sinus tachycardia and hypoxia. CT pulmonary angiogram revealed a large saddle pulmonary embolism with an extension of the clot into multiple lobar and segmental branches  in the right popliteal and peroneal veins and a head CT due to dizziness which showed no acute process. He remained hemodynamically stable and supplemental oxygen was weaned. Intravenous anticoagulation therapy with heparin was transitioned to apixaban. He was discharged home on day 6.The patient presented to our center’s chronic thromboembolic pulmonary hypertension (CTEPH) clinic approximately three and a half months after his submassive pulmonary embolism because of persistent symptoms of postural dizziness and chest pain. He also reported paraesthesias along the back of his head, legs, and feet. His ongoing symptoms were limiting his participation in these activities, and he was unable to return to work as a hospital food service director.He had no history of prior pulmonary emboli or deep venous thrombi and no known risk factors for VTE, other than recent surgery. Although knee arthroplasty is a known risk factor for VTE, the patient received anticoagulant prophylaxis and remained active post-operatively engaging in frequent physical therapy sessions. Furthermore, the patient developed a DVT in the contralateral leg, making it unlikely that recent orthopedic surgery alone accounted for his significant VTE burden. His risk factors for pulmonary hypertension  included obesity (a risk factor for heart failure with preserved ejection fraction), recreational methamphetamine use 40 years prior to presentation, and anorexigen use for six months 20 years prior to presentation. Surgical history was notable for left knee and hip replacements. His family history was notable for one brother who had a pulmonary embolism. He denied current tobacco or drug use and drank one glass of wine per day. The physical exam at this time was normal.His chronic thromboembolic pulmonary disease evaluation included blood work (largely unremarkable - including negative anticardiolipin and beta-2-glycoprotein antibodies), imaging and pulmonary and hemodynamic testing. Ventilation-perfusion scan demonstrated no defects, though CT pulmonary angiogram showed chronic thromboemboli in multiple lobar arteries. Transthoracic echo was unremarkable, including normal right ventricular size and function. Pulmonary function tests and a six-minute walk test were also normal.2). With exercise, he developed a pattern consistent with preload failure caused by inadequate cardiac venous return that limits the normal stroke volume increase during activities [He underwent an invasive cardiopulmonary exercise test (iCPET) to understand the hemodynamic significance of his chronic thromboemboli. Baseline/resting right heart catheterization revealed mild post-capillary pulmonary hypertension  with preserved cardiac index  ratio consistent with cardiovagal dysfunction.Electromyography and lumbar puncture could not be safely performed due to the patient’s need for continuous anticoagulation. A right sural nerve biopsy was performed to further investigate the etiology of the sensory neuropathy. It showed perivascular chronic inflammation with non-necrotizing vasculitis Figure  and mildCIDP is a chronic immune-mediated neurological disease. It can affect patients of all ages, but the peak incidence is among patients aged 50-70. Approximately two-third of patients will have a continuously progressive form of disease, while the other third will have a relapsing-remitting course. One study found that six years after disease onset, 56% had a good outcome, 24% no longer responded to treatment, and 11% died due to disease complications. There are three front-line treatments, corticosteroids, plasmapheresis, and IVIG. 50%-70% of patients will respond to their first treatment. However, increasingly in clinical practice, IVIG is being used as a first-line treatment, due to the preferable side effect profile. Indeed, a randomized control trial comparing IVIG to IV methylprednisolone showed that IVIG was more effective and better tolerated than steroids during the first six-month of treatment. Corticosteroids have a plethora of long-term side effects most notably vertebral compression fractures, obesity, diabetes, hypertension, and cataracts. Plasmapheresis requires secure vascular access, and the placement of a central venous catheter can be complicated by pneumothorax, hematoma, brachial plexus injury, and serious infection. Adverse reactions to IVIG tend to be minor  and occur in less than 10% of patients. Thrombotic events such a stroke, MI, retinal vein occlusion, and DVT can also occur. Risk factors for thrombotic events include cardiovascular risk factors, increased serum viscosity, and infusion rates >0.4 g/kg/day [CIDP is characterized by an aberrant immune response against the peripheral nervous system, which may occur due to molecular mimicry secondary to an immune stimulus or epitope spreading secondary to an overactive immune response. Evidence of CIDP being an autoimmune disorder includes overrepresentation of polymorphisms in genes involved in the immune response among patients with CIDP, the co-occurrence of CIDP with other autoimmune disorders, and the presence of autoantibodies to myelin antigens in a subset of CIDP patients ,5.CIDP was not included in either the Swedish or English cohorts, and the risk of VTE in CIDP patients has not been well studied. However, there have been multiple reported cases of CIDP associated with MGN . MGN is Virchow’s triad defines the three major factors which lead to VTE as stasis, changes in blood coagulability, and alterations in the vessel wall . SystemiPrior to being diagnosed with CIDP, the patient was diagnosed with preload failure. Preload failure is characterized by an impairment in venous return to the heart, a limitation that becomes clinically relevant when performing activities in the upright position, given the increase in venous pooling with gravity. A reduced venous return can lead to inadequate stroke volume causing symptoms such as dyspnea as well as a postural dizziness-the predominant symptom in our patient. Dyspnea may be explained by different mechanisms, but an increase in the pulmonary ventilation/perfusion mismatch, due to lower flow in the lung apices, is the predominant hypothesis. Preload failure has not previously been described in conjunction with CIDP but has been associated with neuroendocrine disorders including postural orthostatic tachycardia syndrome (POTS), adrenal insufficiency, and autonomic neuropathy . In our It is interesting that our patient presented with extensive thromboembolism two months prior to developing any neurological symptoms. However, even in the absence of clinical weakness patients with sensory predominant CIDP can demonstrate significant motor conduction slowing on nerve conduction studies . This inAn increased risk of VTE has been reported in autoimmune neurological disorders such as multiple sclerosis and myasthenia gravis, but to our knowledge, no cases have previously been reported of VTE associated with CIDP . It is iHowever, our patient had not received any therapies or experienced significant mobility impairment prior to presenting with VTE, indicating that underlying systemic inflammation and peripheral denervation leading to venous stasis were the most likely potential mechanisms in this patient. Our case suggests an association between VTE and CIDP. Further studies will be required to determine whether CIDP patients are truly at increased risk for VTE.To our knowledge, no cases have previously been reported of VTE associated with CIDP. It is imperative to determine whether CIDP patients are at increased risk because patients often have decreased mobility which can further increase thromboembolic risk. However, our patient had not experienced significant mobility impairment prior to presenting with VTE, indicating that underlying systemic inflammation and peripheral denervation leading to venous stasis were the most likely potential mechanisms. Our case suggests an association between VTE and CIDP. Further studies are required to determine whether CIDP patients are truly at increased risk for VTE.


In addition, different concentrations and types of coexisting anions have a weak effect on TCs adsorption. The original TCs adsorption capacities of Fe(III)@CNFs remained stable (greater than 92%) after five cycles when UV + H2O2 was used as the regeneration method. Four adsorption mechanisms  were obtained for the endothermic adsorption of TCs, among which surface complexation between Fe(III) and TCs always dominates. The practically applicable Fe(III)@CNFs adsorbents are promising for TCs enrichment and remediation in engineering applications.The non-toxic and completely biodegradable cellulose within bamboo is one of the most abundant agricultural polysaccharide wastes worldwide, and can be processed into cellulose nanofibres (CNFs). Iron(III)-loaded CNFs (Fe(III)@CNFs) derived from bamboo were prepared to improve the adsorption of tetracycline (TC), chlortetracycline (CTC) and oxytetracycline (OTC) from an aqueous solution. The preparation conditions of Fe(III)@CNFs suitable for the simultaneous adsorption of three tetracycline antibiotics (TCs) were investigated. Various analyses proved the abundance of oxygen-containing functional groups and the existence of Fe(III) active metal sites in Fe(III)@CNFs. In batch experiments, Fe(III)@CNFs were applied under a wide pH range and the maximum adsorption capacities were 294.12, 232.56 and 500.00 mg g TetracyNumerous approaches have been used to remove TCs, including biodegradation , membran2, the hybrid nanocomposites of zero-valent iron-loaded activated carbon, α-iron oxide/reduced graphene oxide, the graphene nanoplatelet-based and the nanosized ZnO-based [et al. [et al. [Adsorption performance is closely related to adsorbents types . Many adnO-based ,28–33, anO-based . Bamboo nO-based ,35. CNFsnO-based –38. CNFsnO-based . ModifienO-based , heavy mnO-based , carbon nO-based , phenol nO-based , radioacnO-based  and volanO-based . Current [et al.  used gra [et al. . In our  [et al. , the TEM [et al.  optimize [et al. , but no In this study, Fe(III)@CNFs were prepared to adsorb TCs from wastewater. This study aimed to (i) explore the optimal preparation conditions of Fe(III)@CNFs suitable for TCs removal, (ii) investigate the effects of various factors on the adsorption of TCs by Fe(III)@CNFs, (iii) evaluate different regeneration methods and determine the regeneration performance after multiple cycles, and (iv) estimate the fitting data of kinetic and isotherm models to comprehend the adsorption process and propose the potential mechanism of TCs adsorption by Fe(III)@CNFs. Through the design, a renewable and non-sintered adsorbent with stable adsorption performance is desired to solve the scientific problem of simultaneous adsorption of TC, CTC and OTC.. 2. 2.122H24N2O8 · HCl), CTC (C22H23ClN2O8 · HCl) and OTC (C22H24N2O9 · HCl) were purchased from Aladdin Biochemical Technology Co., Ltd (China). Iron nitrate (Fe(NO3)3 · 9H2O), iron chloride (FeCl3 · 6H2O), aluminium chloride (AlCl3) and potassium permanganate (KMnO4) were purchased from Kelon Company (China). Iron sulfate (Fe2(SO4)3) was purchased from Xilong Chemical Co., Ltd (China). All other chemicals were purchased from Kelon Company. All chemicals were of analytical grade. Ultrapure water was used for all the experiment.Wet bamboo pulp was purchased from Yongfeng Paper Co., Ltd (China). USP grade TC , (ii) three iron salt modifiers 3 and Fe2(SO4)3), and (iii) various metal salt/CNFs mass ratios .CNFs were prepared using the mechanical shearing method and were derived from wet bamboo pulp by employing the specific steps followed by Luo et al. . The pre3-modified CNFs are hereinafter referred to as Fe(III)@CNFs.Regarding the preparation of modified CNFs. First, the iron salt modifier was weighed and mixed with 1 wt% CNFs suspension in a certain mass ratio at room temperature, and the mixture was stirred for 24 h, and NaOH (1 M) was slowly added to the mixture during stirring. Second, deionized water was added to the mixed solution, and the solution was centrifuged at 8000 r.p.m. Then, the obtained modified material was washed with deionized water. Finally, the washed material was freeze-dried with a vacuum freeze dryer  for 48 h, and the dried modified CNFs were stored at room temperature. FeCl. 2.32 adsorption–desorption experiment was performed. The specific surface area and pore size analyser  and the Brunauer–Emmett–Teller method were used to measure the specific surface area, pore volume and pore size. X-ray photoelectron spectroscopy (XPS)  was used to examine the binding energy under the Al K-alpha X-ray of a monochromator with an excitation source of 150 W. The XPS data were treated using XPSPEAK software for peak splitting. The surface functional groups of Fe(III)@CNFs and TCs-adsorbing Fe(III)@CNFs were measured using a Fourier-transform infrared (FTIR) spectrum analyser . The isoelectric point (IEP) of Fe(III)@CNFs was tested using a zeta potential/nanoparticle size analyser . The iron content in the leachate was tested and analysed by atomic absorption spectrophotometer ; specific parameters were designed as follows: air flow rate is 7.6 l min−1, acetylene flow rate is 1.3 l min−1, 370 V, 10 mA and measurement was performed at a wavelength of 248.3 nm. The thermal stability was tested by Thermogravimetric analysis-differential scanning calorimetry (TGA-DSC)  under 0–1000°C; specific parameters are designed as follows: nitrogen atmosphere, heating rate 20°C min−1. The crystalline phases in CNFs and Fe(III)@CNFs samples were tested and analysed by X-ray diffraction (XRD) ; specific parameters are designed as follows: Cu target, 40 kV, 40 mA, within the 2θ angle range of 3–90°, patterns were recorded at scan step size of 0.039 and time per step of 20.91. TGA-DSC and XRD analyses were detected by Analytical and Testing Center, Sichuan University, China.The dried CNFs and Fe(III)@CNFs were coated with gold by using a vacuum sputter coater . Subsequently, the morphological characteristics of CNFs and Fe(III)@CNFs were observed through scanning electron microscopy (SEM)  at 15 kV. Energy-dispersive X-ray spectroscopy (EDS) was used to analyse element contents. CNFs and Fe(III)@CNFs were treated with vacuum heat for 4 h, and N. 2.4−1). Subsequently, the working solutions were placed in a constant temperature shaking box  at 298 K and were shaken for 24 h in the absence of light until an equilibrium was attained. Finally, the supernatant was filtered using a 0.45 µm filter after precipitation and quantified using an ultraviolet–visible spectrophotometer  at the wavelengths of 275 nm (for TC and OTC) and 227 nm (for CTC). The ultraviolet spectrum of TC, CTC and OTC was scanned in the wavelength range of 190–400 nm using ultraviolet–visible spectrophotometer  and the wavelength corresponding to the strongest absorbance value was obtained. In addition, the concentration of TCs has an excellent linear relationship with absorbance at the corresponding wavelength. Unless otherwise stated, this regular adsorption experiment was completed at 298 K and pH 7.In the adsorption experiment, 50 mg of adsorbent was separated added to 100 ml of TC, CTC and OTC solutions  was used to assess the pH value. The impact of adsorbent dosage (10–100 mg) on TCs adsorption was investigated at optimal pH. Moreover, the influence of different concentrations of several anions  on TCs adsorption was examined, and the adsorbent was added to the TCs solution with two coexisting anion concentrations (1 and 10 mM) at optimal pH. All the experiments were conducted in triplicate, and the mean values were used for the subsequent data analysis.To obtain the applicable pH range of adsorbents, the initial pH was adjusted from 3 to 12 (increment by 1) by using 0.1 M NaOH and HCl solutions. A digital multimeter  equipped with a pH electrode (SenTix. 2.5−1), sampling points (after adsorption reached equilibrium) and temperature .To determine adsorption kinetic characteristics, sampling must be conducted at different time points  at optimal pH. The experimental conditions of adsorption isotherm features were mostly consistent with those for the determination of adsorption kinetic characteristics, except for the initial concentration of TCs . In the first method, 100 ml of 1 mol l−1 NaOH solution was added to the flask. In the second method, 100 ml of deionized water and 1 ml of H2O2 were added to the flask. Then, the flask was subjected to magnetic stirring, and the solution was desorbed for 2 h under UV light. In the third method, 100 ml of 1 mol l−1 NaOH solution was added to the flask and sonicated for 2 h. After the selection of the optimal regeneration method, the effects of regeneration time on adsorption were investigated. The regenerated Fe(III)@CNFs were filtered and washed repeatedly with deionized water. The washed Fe(III)@CNFs were dried and re-used in the regular adsorption experiments. The regeneration–adsorption experiments were performed in five cycles with the optimal regeneration method.A total of 1 g of TCs-saturated Fe(III)@CNFs was placed in a 250 ml flask for regeneration experiments. Three regeneration methods were employed  formulaeeq is the adsorption capacity for TCs at equilibrium (mg g−1), C0 and eC are the initial and equilibrium concentrations, respectively, of TCs (mg l−1), V is the volume of TCs solutions (l) and m is the mass of the adsorbent (g).Equations (2.1) and (2.2) present the TCs removal rate (RR%) and adsorption capacity 3 and Fe2(SO4)3 were used to modify CNFs. The results are presented in figure 1b. The CNFs modified with FeCl3 exhibited the optimum adsorption performance for all the three TCs. The adsorption capacities for TC, CTC and OTC were 16.81, 16.90 and 17.91 mg g−1, respectively. Iron salt (III)-modified CNFs can be ranked in terms of their TCs adsorption capacities as follows: FeCl3-modified CNFs > Fe(NO3)3-modified CNFs > Fe2(SO4)3-modified CNFs. Therefore, the adsorption properties of only FeCl3-modified CNFs, namely Fe(III)@CNFs, were investigated under various operational conditions in the following experiments. Iron-rich materials are effective adsorbents for TCs [3-modified CNFs exhibit high TCs adsorption capacities.Based on the TCs adsorption results of CNFs modified with different metal salts, the effects of different iron salt (III) modifiers were studied. FeCl for TCs , but the. 3.1.2−1 for TC, CTC and OTC, respectively) when the Fe(III)/CNFs mass ratio was 2.5. The amount of Fe(III) loaded on the surface of Fe(III)@CNFs increased, thereby leading to an increase in the number of binding sites of adsorbents for TCs. However, when the Fe(III)/CNFs mass ratio increased further, the TCs adsorption amount became stable. Because the loading of Fe(III) on limited CNFs was saturated, the adsorption capacity of Fe(III)@CNFs did not further increase with an increase in the Fe(III)/CNFs mass ratio. Considering the adsorption capacities and chemical consumption, the Fe(III)/CNFs mass ratio of 2.5 was selected as the fixative value for the subsequent experiments.Fe(III)@CNFs-adsorbed TC, CTC and OTC showed the same trend when the Fe(III)/CNFs mass ratios varied from 0.5 to 4 . The adsorption capacity of Fe(III)@CNFs initially increased gradually with an increase in the Fe(III)/CNFs mass ratio and then reached the maximum point . By contrast, the surface of Fe(III)@CNFs was rough and uneven and exhibited abundant dot-like holes (figure 2b). Compared with the SEM results of Fe(III)@CNFs obtained by Luo et al. [2 g−1 and 0.180 cm3 g−1) were 6.8 and 4.5 times higher, respectively, than those of the original CNFs (25.3 m2 g−1 and 0.0400 cm3 g−1). The Barrett–Joyner–Halenda (BJH) average pore diameter of Fe(III)@CNFs was 5.44 nm, which was smaller than that of the original CNFs. According to a study, the molecular diameter of TC is 1.27 nm [The surface morphology and microstructure of CNFs and Fe(III)@CNFs were observed through SEM . The surfigure 2o et al. , the Fe@CNFs . The C 1s region was fitted into three peaks located at 284.44, 286.33 and 287.96 eV, which corresponded to the carbon–carbon (C–C)/carbon–hydrogen (C–H), carbon–carbon–oxygen (C–C–O) and carbon–oxygen (C=O)/oxygen–carbon–oxygen (O–C–O) bonds ,59. The Fe 2p1/2 . This fi[3+ form , which c [et al.  investig [et al. . HoweverTGA-DSC was conducted to examine the thermal stability of CNFs and Fe(III)@CNFs . For the TGA of the CNFs and Fe(III)@CNFs heated in the air, the weight loss below 250°C is attributed to the evaporation of adsorbed water . A sharp. 3.3. 3.3.1−1 for TC, CTC and OTC, respectively. The adsorption capacity only slightly decreased, and the removal rate of TCs remained greater than 80% for a wide pH range. Specifically, the removal rates of TC, CTC and OTC were 84–93%, 81–91% and 81–92%, respectively, for the pH of 3–11, 4–8 and 3–9, respectively. The adsorption performance of TC, CTC and OTC sharply decreased when pH exceeded 11, 10 and 10, respectively. These results can be explained by the surface charge of the adsorbent and the influence of initial pH on the existing form of the adsorbate [dsorbate . Furtherdsorbate ,62,63. Idsorbate ; thus, F−1, while the iron content at pH 3.07 was 0.241 mg l−1. Although Fe(III)@CNFs has iron leaching at low pH, the leaching amount is very low. In addition, the adsorbent is mostly used in sewage with neutral pH, so the stability of the composites can be guaranteed.In addition, the leaching content of iron was tested to verify the stability of the Fe(III)@CNFs. The experimental results showed that the iron content of Fe(III)@CNFs at pH 7.05 and 12.00 was less than 0.03 mg l. 3.3.2Because the adsorbent dose influences TCs adsorption performance by affecting the number of active sites, it must be optimized. −1, respectively. The higher was the dosage of the adsorbent, the higher was the unsaturation of the surface active sites of the unit adsorbent. Similar trends were observed in other studies [The removal rate of TCs tends to increase with the dosage of Fe(III)@CNFs of 10–50 mg, and the removal rates of TC, CTC and OTC increased from 46.96%, 64.90% and 63.87% to 86.65%, 99.69% and 94.05%, respectively. After an adsorbent dosage of over 50 mg, the removal rate curve tended to become balanced with the increase in the adsorbent dosage. The rapid increase in removal rate in the initial stage was caused by a large increase in adsorption active sites. By contrast, when the dosage of Fe(III)@CNFs increased, the amount of TCs adsorbed per unit of the adsorbent sharply decreased. When the dosage of Fe(III)@CNFs was 50 mg, the adsorption capacities for TC, CTC and OTC were 17.29, 19.51 and 18.96 mg g studies . In view. 3.3.3−, CO32− and SO42− coexisting anions on adsorption was inspected , the adsorption capacities for TC, CTC and OTC increased by 2.25%, 3.40% and 1.80%, respectively; and in the presence of high concentration of Cl− (10 mM), the adsorption capacities for TC, CTC and OTC increased by 3.00%, 5.56% and 0.67%, respectively.For TC, low concentrations of CO−, CO32− and SO42− ions were below 5.56%, and the negative impact was below 3.71%. The results indicated that the influences of the three coexisting ions on the TCs adsorption process were insignificant, and the inner spherical complex was barely affected by coexisting ions [et al. [et al. [In general, under different ion types and concentrations, the positive effects of Cling ions . Zhang e [et al.  found th [et al.  reached  [et al.  after st. 3.4a). The adsorption capacities of Fe(III)@CNFs regenerated using NaOH and ultrasound + NaOH considerably decreased. However, Fe(III)@CNFs regenerated using UV + H2O2 maintained high adsorption capacities for the three TCs . The regeneration performance of UV + H2O2 is excellent due to three reasons. First, the hydroxyl, carboxyl and carbonyl groups of Fe(III)@CNFs are protonated under the acidic condition of pH 4, and protons can easily replace bonded TC ions [2O2 generates hydroxyl radicals with strong oxidizing ability to destroy the bridge between TCs and adsorbent surface functional groups through oxidation and desorption, and thus, Fe(III)@CNFs return to the original state [2O2 was selected as the optimum regeneration method for Fe(III)@CNFs.Adsorbent reusability is highly significant for large-scale commercial applications. The commonly used regeneration methods include pyrolysis, gasification, chemical solvents, microorganisms, electrochemistry, ultrasound and wet air oxidation . Conspicfigure 6 TC ions . Second,al state . Finallyal state . In addib shows that the adsorption capacities of Fe(III)@CNFs increased with an increase in the regeneration time. Maximum adsorption capacities were attained when the regeneration time was 2 h, and then, the adsorption capacity tended to become stable. The regeneration time affects TCs oxidation and desorption. When the regeneration time was 2 h, UV + H2O2 could perfectly restore the adsorption performance of Fe(III)@CNFs. Consequently, the UV + H2O2 regeneration treatment time was set to 2 h.The determination of an appropriate regeneration time leads to not only the restoration of the original state of the adsorbent to the highest extent but also the improvement of the efficiency of the actual engineering treatment. Figure 62O2 regeneration (c). Compared with the TCs adsorption capacities of original Fe(III)@CNFs, those of Fe(III)@CNFs after five cycles remained greater than 92%. The results of regeneration performance showed that Fe(III)@CNFs can be effectively regenerated and re-used, and thus, they can be widely used for removing TCs from actual wastewater.After repeated regeneration, an adsorbent that can maintain stable adsorption performance is required for practical applications. Five regeneration–adsorption cycles were conducted using UV + Hneration c. Compar. 3.5The exploration of adsorption kinetics is a crucial part of reflecting the rate change of the adsorption process and providing the potential adsorption mechanism . Figure R2). On comparing R2, the pseudo-second-order kinetic model (R2 > 0.99) was found to be more apt for describing TCs adsorption on Fe(III)@CNFs than the pseudo-first-order kinetic model . Thus, the pseudo-second-order kinetic model represents the adsorption process of TCs on Fe(III)@CNFs, which is consistent with the findings of many TCs studies [k2) of TC, CTC and OTC were compared, and their order was as follows: CTC > OTC > TC, which indicated that Fe(III)@CNFs can adsorb CTC fastest.The obtained kinetic experimental data were fitted to the pseudo-first-order kinetic, pseudo-second-order kinetic, Morris–Weber intra-particle diffusion and simple Elovich models . Table 1 studies ,72,73. Td). Before the adsorption equilibrium, tq and t1/2 presented two linearities. In the rapid adsorption stage, the TCs were stacked on the outer surface of Fe(III)@CNFs, and the rate-limiting step was liquid film diffusion. In the slow adsorption stage, the rate-limiting step was intra-particle diffusion. In addition, intra-particle diffusion can be only considered the rate control step if the fitting straight line passes through the origin [Cpi > 0 of the Morris–Weber intra-particle diffusion model manifests that TCs are rapidly adsorbed onto Fe(III)@CNFs [R2: 0.931, 0.889 and 0.947) can also describe adsorption. This model assumes that the surface adsorption energy is uniformly distributed and that there is no desorption [The Morris–Weber intra-particle diffusion model was employed to explore the actual rate-limiting step  figure d. Beforee origin . HoweverII)@CNFs . The simsorption ,75.. 3.6R2. On comparing R2, the Langmuir model was found to be more appropriate for describing TCs adsorption because the R2 of the Langmuir model (varying between 0.917 and 0.998) is higher than that of other models under most conditions. Compared with the D–R model, the R2 of Temkin was higher, which indicated that electrostatic attraction and heterogeneous pores caused the exothermic reaction [mq) of Fe(III)@CNFs for TC, CTC and OTC calculated using the Langmuir model were 294.12, 232.56 and 500.00 mg g−1, respectively. The difference of chemical structure among OTC, TC and CTC is the substituent. The adding amount of hydroxyl in OTC resulted in the increase of combination sites with Fe(III)@CNFs. Fe(III)@CNFs contain carboxyl groups and hydroxyl functional groups that can lead to the formation of a hydrogen bond with hydroxyl of OTC [−1. Comparing with CTC, Fe(III)@CNFs can form the more complex with OTC and TC.The experimental data were applied to four adsorption isotherm models: Langmuir, Freundlich, Temkin and D–R models. reaction . Hence, reaction . At 308 l of OTC . Thus, tl of OTC ; therefoet al. [et al.  has highG0), entropy (ΔS0) and enthalpy (ΔH0), were calculated from the thermodynamic equation. G0 of the three TCs was less than 0 and decreased with an increase in temperature. Thus, adsorption is spontaneous [S0 of greater than 0 indicates that the surface structure of the adsorbents changes and that the disorder of the adsorption process increases, which is favourable for adsorption [H0 of greater than 0 indicates not only that adsorption of TCs on Fe(III)@CNFs is endothermic but also that this adsorption is a chemical process [To further study the impact of temperature on TCs adsorption, the relevant thermodynamic parameters, such as Gibbs free energy @CNFs is more in line with the chemical process represented by the pseudo-second-order kinetic model. Surface complexation always dominates adsorption in each situation between Fe(III)@CNFs and TCs. The hydrogen bond and electrostatic interactions play a secondary role in adsorption. In addition, van der Waals forces participate in this process . Figure 2O3). Adsorption sites were also simulated force fields, which protonated carbonyl and amino groups of TCs that can bind cations effectively and form complexes [The surface complex reaction between Fe(III) and TCs is of considerable significance for TCs adsorption onto Fe(III)@CNFs. Compared with the original CNFs, the loading of Fe(III) on the CNFs framework significantly improved the adsorption of TCs . TCs havomplexes . Fe(III)omplexes . The Fe@CNFs [The functional groups of Fe(III)@CNFs can contribute to the adsorption of TCs by forming hydrogen bonds. Fe(III)@CNFs contain carboxyl and hydroxyl functional groups (see §3.2.2) that can lead to hydrogen bond formation with phenolic hydroxyl, amine, hydroxyl and ketene moieties of TCs . In addiII)@CNFs .Kas) that delimit cationic (TCs+), zwitterionic (TCs±) and anionic (TCs− and TCs− −) species. The pKa values of TC are 3.30, 7.68 and 9.30, those of CTC are 3.30, 7.44 and 9.27, and those of OTC are 3.27, 7.32 and 9.11 [Ka1 and pKa2 values (Ka1), TCs+ and Fe(III)@CNFs both had positive charges, which led to electrostatic repulsion. For Z1 to Z2 (pKa1 < pH < pKa2), TCs± caused by the deprotonation of the tricarbonylamide group was the dominant species, and electrostatic repulsion weakened, thereby highly enhancing the adsorption capacities for TCs. In this stage (Z1 to Z2), the electrostatic condition was unfavourable, and the adsorption capacities for TCs were mainly maintained through surface complexation [Ka2 < pH < IEP), the dominant TCs species changed from TCs± to TCs− due to the deprotonation of the phenolic diketone group of TCs and electrostatic attraction between Fe(III)@CNFs and TCs. However, the adsorption capacity slightly decreased in this situation, and the effect of electrostatic attraction was indistinct. For Z3–Z4 (pH > IEP), when the alkalinity of the solutions increased, the negatively charged Fe(III)@CNFs and anionic species (TCs− and TCs− −) led to strong electrostatic repulsion. Furthermore, immoderate OH− in the solution competed with TCs− for active sites on Fe(III)@CNFs. The variations in the adsorption capacities and removal rates of TC, CTC and OTC at different pH values may be attributed to different pKa values and chemical groups [The surface charge of the adsorbent and the influence of initial pH on the existing form of the adsorbate can be used to explore electrostatic interactions. The pH corresponding to the IEP of Fe(III)@CNFs was 8.37 . TCs species are characterized by three acid dissociation constants @CNFs, and the original TCs adsorption capacities of Fe(III)@CNFs remained stable (greater than 92%) after five cycles. The characteristics of not being easily affected by coexisting ions, the strong reproducibility and firm Fe(III) greatly broaden the application possibilities of Fe(III)@CNFs in actual sewage treatment. The fitting data of kinetic, isotherm and thermodynamic proved that the spontaneous and endothermic adsorption mainly resulted from monolayer chemical adsorption, and the maximum adsorption capacities of Fe(III)@CNFs for TC, CTC and OTC were 294.12, 232.56 and 500.00 mg g−1, respectively. The potential adsorption mechanisms of TCs onto Fe(III)@CNFs involved inner spherical surface complexation, hydrogen bonding, electrostatic interaction and van der Waals forces between the functional groups of TCs and Fe(III)@CNFs. The cost-effective Fe(III)@CNF adsorbents with excellent adsorption performance in a wide pH range and outstanding regeneration performance can be used to remove TCs from wastewater.In this study, a renewable and non-sintered adsorbent with Fe(III) incorporated into CNFs was prepared and applied to adsorb TCs  from an aqueous solution. After comparing the impact of various modifiers and Fe(III)/CNFs mass ratios on TCs adsorption, the preparation parameters of Fe(III)@CNFs suitable for three TCs adsorption simultaneously were obtained. The adsorbents showed a clear and rough pore structure, and the physical parameters changed after Fe(III) modification. Spectroscopic evidence indicated that Fe(III)@CNFs have multiple oxygen-containing functional groups and Fe(III) metal sites. The batch experiments with different pH values indicated that the manufactured Fe(III)@CNFs exhibited stable adsorption and excellent tolerance in a wide pH range that tend to reduce the cost of pH adjustment. Different types and concentrations of coexisting ions have various effects on TCs adsorption, and these effects are relatively weak. UV + HClick here for additional data file.


This study investigated the long-term surgical outcomes of functional cholesteatoma surgery with canal wall reconstruction using autologous bone grafts as the primary material in patients with acquired cholesteatoma.Medical charts were retrospectively reviewed for all patients admitted to one institution for surgical intervention between 2010 and 2018. We analyzed 66 patients (66 ears) who underwent functional tympanomastoidectomy involving the use of autologous bone grafts for canal wall defect reconstruction. Surgical outcomes were evaluated by comparing preoperative audiometric results with follow-up data (at least 36 months after surgery). Logistic regression analyses were performed to determine prognostic factors related to long-term hearing success. These factors included classification and stage of cholesteatoma, stapes condition, ossicular chain damage, active infection of the middle ear, state of the contralateral ear, preoperative hearing thresholds, gender, and age.p < 0.001). Air–bone gaps significantly improved from 26.26 ± 10.53 to 17.58 ± 8.21 dB HL (p < 0.001). In multivariate logistic regression analysis, early-stage disease (p = 0.021) and pars flaccida cholesteatoma (p = 0.036) exhibited statistically significant correlations with successful hearing preservation.The mean follow-up period was 49.2 months. The recidivism rate was 6% (four of 66 ears). The pure-tone average significantly improved from 50.78 ± 19.98 to 40.81 ± 21.22 dB hearing level (HL; Functional cholesteatoma surgery with autologous bone grafts reconstruction is an effective approach to significantly improve hearing with low recidivism rates. Localized disease and pars flaccida cholesteatoma were two independent predictors of successful hearing preservation. Surgical removal of cholesteatoma is the standard treatment once the diagnosis is established . HoweverMastoid obliteration and canal wall reconstruction, followed by disease removal, are mandatory to prevent leaving a cavity . VariousThis retrospective study evaluated patients with acquired middle ear cholesteatoma who were admitted for functional tympanomastoidectomy in a single tertiary hospital between 2010 and 2018 with a minimum follow-up of 3 years. A total of 116 patients were assessed for eligibility, and of these 116 patients, 50 were excluded. Finally, 66 patients (66 ears) aged between 18 and 74 years were enrolled in this study. All of the surgeries were performed by a single surgeon. Exclusion criteria were as follows: (1) unavailability of complete audiometry data or follow-up hearing examination data for less than 3 years postoperatively, (2) revised surgery, (3) presence of congenital cholesteatoma, (4) diagnosis other than cholesteatoma, (5) undergoing a procedure other than functional tympanomastoidectomy, and (6) cholesteatoma of the external auditory canal. The study flow diagram is shown in The following detailed information was collected for each patient: age, sex, affected ear, follow-up duration, types of tympanoplasty, group and stage of cholesteatoma, severity of ossicle destruction, presence of the stapes suprastructure, state of the contralateral ear, and infection at the time of surgery . The groAudiometric data were recorded at the time of admission before treatment and every 3 months after surgery in the first year and then every 6 months in the second year. Patients who did not undergo follow-up hearing tests for more than 3 years were excluded. During the treatment, hearing changes were examined by comparing hearing test results obtained before the treatment with those obtained at the latest follow-up. Pure-tone thresholds for air and bone conduction were conducted at the frequencies of 0.25, 0.5, 1, 2, 4, and 8 kHz. The pure-tone average (PTA) was determined by calculating the mean of the 0.5, 1, 2, and 4 kHz thresholds of air conduction. Air–bone gaps (ABGs) were calculated on the basis of air and bone conduction results obtained at the thresholds of 0.5, 1, 2, and 4 kHz. The mean preoperative and postoperative PTA and ABGs as well as improvements in the PTA and ABGs were recorded.In this study, meeting the following criteria indicated successful hearing preservation after functional tympanomastoidectomy: (1) no recurrent or residual cholesteatoma during the follow-up period and (2) gain of at least 15 dB in the PTA when compared with preoperative data or conservation of the hearing value in patients with normal preoperative hearing (PTA ≤ 25 dB). Cholesteatoma recidivism was suspected via otoscope examination and deteriorated audiometry during follow-up period, and was established following revised surgery. The success rate of the hearing conservation was analyzed using the criteria suggested by the Japan Clinical Otology Committee . AccordiTo determine the factors that predict successful hearing preservation, the following variables were analyzed: age at surgery (≤45 years or >45 years), sex , preoperative PTA (≤40 dB or >40 dB), cholesteatoma groups , cholesteatoma stage (stage I or stage II–IV), active infection at the time of surgery (absence or presence of otorrhea), ossicular chain destruction , stapes condition (presence or absence of the suprastructure), and state of the contralateral ear . One study evaluated the influence of the age factor on the prognosis for tympanoplasty revealed that the group aged under 45 years had a trend for higher hearing success, so we decided on 45 years as a criterion for two groups of patients . We put Functional tympanomastoidectomy was performed similar to the procedure reported in previous studies . Under gTympanoplasty was performed as a single-stage procedure in all cases after the removal of cholesteatoma by using functional tympanomastoidectomy. Patients in this study underwent three types of tympanoplasty: type I, type III –2D, and t test was performed to compare numerical variables and determine significant differences between preoperative and postoperative hearing results. One-way analysis of variance and Fisher’s exact test were used to compare hearing gains and the rate of successful hearing preservation, respectively, among different tympanoplasty types. Univariate and multivariate logistic regression analyses were performed to determine factors that were related to long-term hearing success. A p value of <0.05 was considered statistically significant.Statistical analyses were performed using SPSS version 24.0 . A paired-samples The mean age of patients was 46.8 ± 13.9 years (range: 18–74 years). Among 66 patients (66 ears), 28 were aged <45 years. Of 66 patients, 30 (45.5%) were men. The left and right ears were involved in 33 and 33 patients, respectively. Among 66 patients, 46 (69.7%) presented with more than mild hearing loss preoperatively (PTA >40 dB). The mean follow-up period was 49.2 ± 21.6 months (range: 36–114 months). Type I tympanoplasty was conducted in 20 (30.3%) of 66 ears. Type III tympanoplasty with the minor columella and type III tympanoplasty with the major columella were performed in 37 (56.1%) of 66 ears and 7 (10.6%) of 66 ears, respectively. Type IV tympanoplasty was performed in 2 (3%) of 66 ears. All patients were classified as pars flaccida, pars tensa, or a combination of pars flaccida and pars tensa according to tympanic membrane status. Of the 66 ears with cholesteatoma, 59 (89.4%), 5 (7.6%), and 2 (3.0%) were included in the groups of pars flaccida, pars tensa, and a combination of both pars flaccida and pars tensa, respectively. In this study, cases of pars tensa and the combined type were classified into the pars tensa group. A total of 29 (43.9%), 33 (50.0%), 4 (6.1%), and 0 (0%) patients had stage I, stage II, stage III, and stage IV disease, respectively. Of four patients with stage III disease, three had labyrinthine fistulas and one had delayed facial palsy. The contralateral ear was normal in 40 (60.6%) of 66 patients, and otitis media with effusion/atelectasis/ eardrum perforation was found in 26 (39.4%) of 66 patients. The ossicular chain status was confirmed surgically. A total of 27 (40.9%), 28 (42.4%), and 11 (16.7%) patients had normal ossicles or destruction in one ossicle, destruction in two ossicles, and destruction in three ossicles, respectively. Furthermore, 16 (24.2%) patients presented with active ear infection at the time of surgery, manifesting as otorrhea. Destruction of the stapes suprastructure was observed in 9 (13.6%) of 66 patients, and remained stapes integrity was noted in 57 (86.4%) patients. According to the criteria used to determine successful hearing preservation in this study, 33 (50.0%) patients were included in the successful hearing group and 33 (50.0%) patients were included in the unsuccessful hearing group.p < 0.001). ABGs (mean ± SD) significantly improved from 26.26 ± 10.53 dB HL to 17.58 ± 8.21 dB HL  significantly improved from 50.78 ± 19.98 dB hearing level (HL) to 40.81 ± 21.22 dB HL . Postoperative gains in ABGs (mean ± SD) were 6.44 ± 9.86, 9.43 ± 10.41, 10.54 ± 12.46, and 4.38 ± 0.88 dB HL in type I, type III-m, type III-M, and type IV tympanoplasties, respectively. No significant differences in postoperative gains in ABGs were noted among different tympanoplasty types (p = 0.646). The preoperative PTA was compared between different tympanoplasty types to validate the reliability of the aforementioned results. A statistically significant difference in the baseline PTA was noted (p = 0.003), and the post hoc test results indicated that patients who received type III-M tympanoplasty had poorer preoperative hearing performance than did those who received type I tympanoplasty. The rates of successful hearing preservation were 55.0%, 51.4%, 28.6%, and 50.0% in type I, type III-m, type III-M, and type IV tympanoplasties, respectively. No significant differences in the rate of successful hearing preservation were observed between different tympanoplasty types  were 9.06 ± 11.52, 9.86 ± 13.35, 13.39 ± 23.03, and 8.75 ± 13.73 dB HL in type I, type III-m, type III-M, and type IV tympanoplasties, respectively. No significant differences in the improvement of the PTA were observed among different tympanoplasty types (p = 0.028). There was a trend toward higher probability of successful hearing preservation in patients with pars flaccida cholesteatoma  and those without otorrhea at the time of surgery . Hearing success was not predicted by age (p = 0.619), sex (p = 0.324), preoperative PTA (p = 0.593), ossicular chain destruction (p = 0.389), integrity of the stapes (p = 0.290), and state of the contralateral ear (p = .315). The findings of multivariate logistic regression indicated that early-stage disease  and pars flaccida cholesteatoma  were significantly correlated with successful hearing preservation. Other variables were not found to be related to hearing success in multivariate analysis.Logistic regression analysis was performed to predict factors that are related to long-term hearing success, and the results are listed in The rate of postoperative complications was 13.6% (9 of 66 ears). Delayed facial palsy was noted in one patient (1.5%) on postoperative day 7, but this patient exhibited complete recovery 1 month postoperatively. Two (3%) patients developed dry eardrum perforation, and two (3%) patient developed otitis media with effusion during the follow-up period. Four patients (6%) experienced recidivism during the follow-up period: three patients (4.5%) developed recurrence, and one patient (1.5%) had residual disease. The sites of recurrence in the three patients were all in the epitympanum region. A residual keratin pearl in the external auditory canal (EAC) was found in one patient. All four patients who experienced recidivism received revised surgery and recovered well without any new adverse events. Accumulation of keratin debris and purulent discharge in EAC were frequently noted during preoperative otoscope evaluation . At 12 mThe results of this study revealed that patients with acquired cholesteatoma presented significant overall hearing recovery with satisfactory recidivism occurrence rates after undergoing functional tympanomastoidectomy involving the use of autologous bone grafts as the primary material for reconstruction.The use of the inside-out technique with the removal of the posterior auditory canal wall for exposure and eradication of cholesteatoma, followed by the reconstruction of the open cavity, has been proposed in several studies . HoweverIn their retrospective study conducted in 2004, Dornhoffer evaluated the long-term results of retrograde mastoidectomy, followed by the reconstruction of the auditory canal wall defect using the cymba cartilage . The harTo the best of our knowledge, few studies have examined the long-term treatment efficacy and safety of applying autologous bone grafts as the primary material for reconstructing tympanomastoid defects in functional cholesteatoma surgery. Our retrospective study results showed that functional mastoidectomy followed by canal wall reconstruction with bone grafts significantly improved hearing and led to a low recidivism rate. An ideal surgical procedure should be quick and simple. Using bone grafts harvested from the healthy mastoid cortex for EAC defect reconstruction and mastoid obliteration without additional materials can improve operational efficiency.p < 0.001) and ABGs  were noted. In their retrospective study, Haeusler et al. reported that 586 patients (604 ears) received inside-out cholesteatoma surgery with cartilaginous reconstruction of the canal wall  showed a significant correlation with postoperative ABGs of 30 dB or lower in more than 80% of patients in one study; by contrast, this correlation was observed in only 70% of patients who underwent type IV tympanoplasty . No signPatients and surgeons should know possible predictive factors related to successful hearing preservation after surgery. Multiple variables were included in univariate and multivariate logistic regression analyses. Early-stage cholesteatoma and pars flaccida cholesteatoma were determined to be independent predictors of hearing success in the multivariate analysis. This finding is consistent with that of a study conducted in 2020 by The rate of recidivism in this study was 6% (4 of 66 ears): three (4.5%) patients developed recurrence and one (1.5%) patient had residual disease. A recent meta-analysis reported that the recidivism rate ranged from 5% to 17% in patients who underwent CWD mastoidectomy and 9% to 70% in patients who underwent CWU mastoidectomy . AccordiThe major limitation of this study is the lack of comparison groups. Second, the retrospective analysis performed in this study may be a potential source of selection bias. Third, making comparisons among studies is difficult when evaluating hearing-related prognostic factors because no standard definition of successful hearing preservation is available. In the future, prospective trials that incorporate a standard definition of hearing recovery and a unified cholesteatoma staging system are needed. Studies examining the long-term outcomes of functional tympanomastoidectomy using primary autologous bone grafts for reconstruction are warranted because recurrence rates are highly related to the length of follow-up.Functional cholesteatoma surgery with the use of autologous bone grafts for reconstruction could significantly improve hearing outcomes with low recidivism rates. Early-stage disease and pars flaccida cholesteatoma were two independent positive prognostic factors for successful hearing preservation. The combined use of staging and classification may provide patients and surgeons with valuable information on hearing outcomes.10.7717/peerj.12522/supp-1Supplemental Information 1All patients with cholesteatoma admitted for functional tympanomastoidectomy using only bone chips for reconstruction in a single tertiary hospital between 2010 and 2018.Click here for additional data file.10.7717/peerj.12522/supp-2Supplemental Information 2Click here for additional data file.


When they originate from neural elements within the vestibule or cochlea, they are defined as intralabyrinthine schwannomas (ILSs). Cochlear implant (CI) has been reported as a feasible solution for hearing restoration in these patients. (2) Methods: Two patients with single-sided deafness (SSD) due to sudden sensorineural hearing loss and ipsilateral tinnitus were the cases. MRI detected an ILS. CI was positioned using a standard round window approach without tumor removal. (3) Results: The hearing threshold was 35 dB in one case and 30 dB in the other 6 mo after activation. Speech audiometry with bisillables in quiet was 21% and 27% at 65 dB, and the tinnitus was completely resolved or reduced. In the localization test, a 25.9° error azimuth was obtained with CI on, compared to 43.2° without CI. The data log reported a daily use of 11 h and 14 h. In order to not decrease the CI’s performance, we decided not to perform tumor exeresis, but only CI surgery to restore functional binaural hearing. (4) Conclusions: These are the sixth and seventh cases in the literature of CI in patients with ILS without any tumor treatment and the first with SSD. Cochlear implant without tumor removal can be a feasible option for restoring binaural hearing without worsening the CI’s performance. Schwannomas of the vestibulocochlear nerve are benign, slow-growing tumors, arising from the Schwann cells or neurolemmocytes that support the neurons. Usually, they originate in the internal auditory canal (IAC) or in the cerebellopontine angle cistern (CPA), but they can occur anywhere along the nerve. In the rare case that these tumors originate primarily from the most terminal portion of the eight cranial nerves , they can be considered a distinct clinical-pathological disease defined as intralabyrinthine schwannomas (ILSs) .The first case was described in 1917 during an autopsy of a deaf and mentally disabled patient , but it A 48-year-old male patient was referred to our department with a 6 year history of left ear complete deafness and ipsilateral tinnitus  when rotating the patient’s head towards his left side. The caloric reflex test, performed with hot water (44 °C), showed an areflective left labyrinth. These results were also confirmed in the video Head Impulse Test (vHIT), where a 41% relative asymmetry was detected when the lateral semicircular canals were stimulated, with the left one hyporeflective and with the presence of saccades (gain of 0.61 on the left side and 1.04 on the right). The same pathological result on the left side was obtained at the Suppression Head Impulse Test (SHIMP). The cervical vestibular evoked myogenic potentials were absent on the left side (due to the deafness), while being evocable on the right side until 90 dB.The Dizziness Handicap Inventory score was 42 , which cA CI (Cochlear Model CI512 with a contour advance electrode) was positioned using a standard round window approach. After drilling the round window niche and opening the secondary tympanic membrane, an intracochlear bleeding formation was seen and biopsied through the round window, with histopathological confirmation of an ILS (S100+). The electrode insertion was complete and carried out slowly, with mild resistance aided by a stiff stylet. The intraoperative electrophysiological tests and impedances were normal, and their values remained stable during follow-up. A post-op CT scan was performed, showing a full insertion without tip fold-over.The second case was a 50-year-old male patient, with a 1 year history of severe right pantonal hearing loss due to sudden sensorineural hearing loss and normal hearing with just 30 dB sensorineural deficit at 4 kHz and 8 kHz on the left side. He also had sub-continuous right tinnitus and no vertigo. A 3 Tesla MRI with gadolinium showed an ILS located on the cochlear basal turn . He stopThe first patient complained of some episodes of self-remitting objective vertigo, which occurred during the first post-operative week. At the time of activation, only a slight dizziness was reported. CI was activated 1 mo after surgery using the following parameters , and the implanted ear threshold was 50 dB in the free-field audiometry test. There was no need for a higher current level to stimulate through the tumor compared to standard CI users. We decreased the stimulation rate because it was better tolerated by the patient compared to the usual rate of 900 Hz. Vestibular exams were carried out again with results comparable to the pre-operative ones, both with the implant turned on and off, with just a slight increase in VOR asymmetry in the vHIT (57% vs. 41%) and in the SHIMP (54% vs. 44%). Because of the long-lasting dizziness, we started a vestibular rehabilitation protocol. No facial nerve or other non-auditory stimulation was experienced by the patient.Tests showed an improvement in the audiological threshold on the implanted ear (40 dB) with a 21% word recognition at 65 dB 1 mo after activation. Dizziness did not change in intensity nor characteristics. The whole test battery was performed again three months and six months after activation. The hearing threshold was 35 dB. Speech audiometry remained the same; however, the tinnitus was completely solved (0 THI score), and the subjective dizziness impairment decreased (12 DHI score), even if the vestibular impairment remained stable at the instrumental examination (asymmetry of 64% in the vHIT and of 65% in the SHIMP). No episode of hearing fluctuation was reported by the patient. A great benefit was observed in the 180° localization test, where a 25.9° azimuth error was obtained when the test was performed with CI on, compared to a value of 43.2° without CI. The data log reported 14 h of daily use.The second patient reached a 30 dB hearing threshold on the right side 1 mo after activation . He suffered a benign paroxysmal positional vertigo that was solved with one repositioning maneuver. At the last follow-up visit 1 year after the surgery, he reached 27% word recognition at 65 dB on the right ear . The THI score was 24. The SSQ questionnaire average score improved in the Speech and Spatial items , whereas a small decrease was registered in the Qualities area . The aveILSs account for about 10% of all eight cranial nerve schwannomas . The SchThe first ILS classification was proposed by Kennedy et al., in 2004 , with a ILS’s symptoms are aspecific and mimic the ones typical of Mèniére’s syndrome. Hearing loss is present in almost all patients (>95%) with different types of onset, from sudden 15–32%) to slowly progressive and also fluctuating . Hearing5–32% to Despite an increasing awareness of ILSs, the delay in diagnosis seems to be still significant with a mean diagnostic delay varying from 3–8 year, according to the clinical symptoms, where hearing loss has significantly shorter delays than vertigo .It is still unclear whether there is a correlation between the involved site and the symptoms. Salzman et al.  reportedMRI with gadolinium is the gold standard exam for diagnosis. The first MRI description of ILSs was published by Mafee et al. in 1990 . ILSs apAs for all schwannomas, also ILSs seem to have a very slow growth tendency, with a different growing rate reported in the literature, varying from 15–59% ,14,15,16The first case of tumor removal and cochlear implantation was described by Kronenber et al. in 1999 .Many papers about tumor exeresis and hearing rehabilitation by CI in ILS patients have since been published, describing both synchronous or staged surgeries, where a dummy electrode is placed inside the cochlea after tumor removal and before CI insertion, in order to prevent cochlear ossification and subsequent obliteration. In our opinion, ILS tumor exeresis should be performed only in the case of the initial extension into the IAC or when vestibular untreatable symptoms are present.In the case series described by Plontke , after tAschendorff et al. reported a group of eight implanted patients in which the tumor was removed. Considering the four with at least 6 mo of audiological follow-up, the average score at 65 dB for monosyllabic word recognition was 39%, with a wide range varying from 10% to 95% .To the best of our knowledge, there is only one other report of CI without ILS removal, where ten patients were described, but only five had never received any treatment before implantation . DespiteStereotactic radiosurgery seems to have an indication only in very selected cases: older or inoperable patients with a growing tumor. Plontke et al.  suggesteA recent study described eight patients affected by neurofibromatosis 2 and ILS that were treated by CI without tumor removal. They described a wide range of results (from 0–100% for the sentence test), with higher current levels of stimulation required for patients previously treated with radiotherapy . AccordiThe limitations to our study were the small number of patients, the possibility of a difficult schwannoma follow-up (but this can be solved using the abovementioned technique), the limited follow-up time, and the absence of a comparison with audiological results of patients treated by radiosurgery and then IC, but to the best of our knowledge, no study exists about this therapeutic approach.These two cases are the sixth and seventh cases in the literature of CI in patients with ILS without any tumor treatment, but the first concerning single-sided deafness. MRI is mandatory in the case of asymmetric progressive or sudden hearing loss. Apart from the CPA and the intracanalicular portion of the eight cranial nerves, attention must be paid also to the labyrinth in order to rule out the presence of an ILS. Cochlear implant without tumor removal can be a feasible option for restoring binaural hearing without worsening the CI’s performances, also in the case of single-sided deafness.


The 22q11.2 deletion syndrome (22q11.2DS), caused by a microdeletion on the long arm of chromosome 22, is characterized by congenital heart disease, hypoparathyroidism, immunodeficiency, developmental delay, and velopharyngeal insufficiency. Anatomic malformations of the middle and inner ears are frequently present, leading to high prevalence of hearing impairment. We present a first case of 22q11.2DS showing fluctuating hearing loss with recurrent vertigo attacks, resembling Ménière's disease. A 38-year-old male known to have 22q11.2DS developed recurrent vertigo, tinnitus, and fluctuating hearing loss in the left ear during a 10-year follow-up period. During vertigo attack, he had spontaneous left-beating nystagmus with downbeat components, but bithermal caloric and video head impulse tests showed normal vestibulo-ocular reflex functions. Sequential pure tone audiograms demonstrated fluctuating sensorineural hearing loss (SNHL) in both ears, which finally progressed to permanent hearing loss in the left ear. Computed tomography imaging of the temporal bone exhibited bilaterally malformed lateral semicircular canals, and delayed 3D-FLAIR sequences revealed cochlear endolymphatic hydrops with dilation of the scala media in the left ear. This case shows that acute vertigo with SNHL can be one of the audiovestibular presentations in 22q11.2DS caused by disturbance of endolymphatic flow. The 22q11.2 deletion syndrome (22q11.2DS), also known as DiGeorge syndrome, is caused by a microdeletion on the long arm of chromosome 22 . While aA 38-year-old male known to have 22q11.2DS presented with recurrent vertigo lasting for hours and fluctuating tinnitus in the left ear. He had a history of neonatal seizure, hypocalcemia due to hypoparathyroidism, and intellectual disability, and underwent cardiac surgery due to congenital heart disease  at 15 years of age. On examination, the patient showed characteristic facial features of 22q11.2DS such as hypertelorism, a short and broad nose, and a deeply grooved philtrum. There was no spontaneous nystagmus between vertigo attacks, and bedside head impulse and bithermal caloric tests were normal. The pure tone audiogram (PTA) demonstrated sensorineural hearing loss (SNHL) in the left ear . ComputeFive years after his initial presentation, the patient developed recurrent vertigo, hearing loss, and tinnitus in the left ear again. A physical examination demonstrated spontaneous left-beating nystagmus with downbeat components that increased during left eccentric gaze. Bithermal caloric tests were normal, and video head impulse tests showed normal vestibulo-ocular reflex (VOR) gains for all six semicircular canals (SCCs). PTA revealed profound SNHL in the left ear . TreatmeTBX1 is responsible for the main features of the disease, such as heart problems, hypoplasia of the thymus and parathyroid glands, and velopharyngeal insufficiency (TBX1 is also expressed in the otic vesicle and the periotic mesenchyme during development, and was shown to be necessary for the development of the inner ear in mice (TBX1 mutant mice developed inner ear malformations that are characterized by an absent or hypoplastic vestibular apparatus with poorly developed SCCs, and a lack of coiled cochlear duct (Among the affected genes in 22q11.2DS, deletion of ficiency . TBX1 is in mice . Thus, hear duct , 7. Likeear duct . Posturaear duct .TBX1 may cause phenotypic variability of audiovestibular dysfunction in 22q11.2DS. A recent study found that non-coding variants in CRKL were significantly associated with risk for conotruncal heart defects in individuals with 22q11.2DS (TBX1 in 22q11.2DS.Remarkably, our patient presented with Ménière's disease-like symptoms such as whirling-type vertigo with nystagmus, fluctuating hearing loss, and tinnitus. He had bilaterally widened vestibules and LSCCs with an abnormally small bony island, but his VOR functions were spared. These anatomic malformations may have contributed to the development of Ménière's disease-like symptoms in our patient, presumably due to the formation of EH. This hypothesis is supported by the presence of cochlear EH on 3D-FLAIR images, which is concordant with PTA finding showing total deafness in the left ear. Because the patient was maintaining a vertigo-free state with normal VOR functions at the time of MRI examination, vestibular EH might not have been observed. Ménière's disease-like symptoms have been reported in patients with LSCC dysplasia, and histopathologic study revealed EH with hypoplastic endolymphatic sacs , 10. MRI2q11.2DS . Many ge2q11.2DS –16. It iEven though it is a rare occurrence, the case described herein shows that acute vertigo with SNHL can be one of the audiovestibular presentations in 22q11.2DS.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.All experiments followed the tenets of the Declaration of Helsinki, and informed consents were obtained after the nature and possible consequences of this study had been explained to the participants. This study was approved by the institutional review boards of Pusan National University Yangsan Hospital.K-DC conducted the interpretation of the data and wrote the manuscript. J-YK, S-YC, EO, H-ML, and JR contributed to the interpretation and analysis of the data. J-HC conducted the design, conceptualized the study, interpreted the data, and revised the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Neuropsychological tests indicated that hearing loss patients presented significant cognitive decline. Pearson’s correlation analysis indicated that changes of nodal degrees and the shortest causal connectivity paths were significantly related with poor cognitive performances. We also found a cross-modal reorganization between associative visual cortex and auditory cortex in patients with hearing loss. Additionally, we noted that visual and auditory signals had different effects on neural activities of Broca’s area, respectively. These results suggest that changes in brain causal connectivity network are an important neuroimaging mark of cognitive decline. Our findings provide some implications for rehabilitation of hearing loss patients.It remains poorly understood how brain causal connectivity networks change following hearing loss and their effects on cognition. In the current study, we investigated this issue. Twelve patients with long-term bilateral sensorineural hearing loss  and 12 matched normally hearing controls  participated in this experiment. We constructed and analyzed the causal connectivity networks based on functional magnetic resonance imaging data of these participants. Two-sample  Behavioral studies have reported that individuals with early or congenitally hearing loss are highly reliant on their remaining intact sensory modalities to interact with their surrounding environment  and dispAn animal study indicated that those improvements in visual performances were caused by cross-modal functional reorganization of auditory cortex in individuals with early or congenitally hearing loss, and several experimental approaches had been used to localize individual visual functions in discrete portions of reorganized auditory cortex . ProjectStudies of hearing loss in human beings have revealed neural activity changes associated with cortical plasticity. Previous investigations have demonstrated cross-modal recruitment of auditory cortical areas in subjects with profoundly hearing loss viewing sign language . Visual Written informed consent was obtained from all participants according to a protocol approved by the Institutional Ethics Committee of Shandong First Medical University. In the current study, the severity levels of the hearing loss are labeled according to the Global Burden of Disease (GBD) 2013 and World report on hearing  . The lesA clinical audiologist performed pure tone audiometry (PTA) using an Astera audiometer in the Department of Otorhinolaryngology and Head-neck Surgery of the Second Affiliated Hospital of Shandong First Medical University. Hearing level (HL) was defined as a speech-frequency pure tone average of air conduction thresholds at 0.25, 0.5, 1.0, and 2 kHz. All of the normally hearing participants had a HL of less than 27 dB, while all of the hearing loss patients had a HL of more than 30 dB. Non-aided audiograms based on pure-tone audiometry for these participants are shown in Participants were excluded if their head movements were greater than 2.5 mm or 2.5° during imaging. No participants were excluded in the present study.Mini-mental state examination (MMSE) is sensitive for measuring cognitive impairment . In thisIt has been demonstrated that hearing impairment negatively impacts cognitive test performance . To miniWe acquired MRI data of 24 participants using a GE Discovery MR 750 3-T scanner. MRI data of 21 participants had been from a previously published study . FunctioAll of the participants underwent a functional magnetic resonance scan during a conscious resting state with their eyes closed. To reduce noise and disturbance, these participants wore earplugs and headphones and were instructed to keep still, as motionless as possible and not to think about anything in particular. Head movement was minimized by placing soft pads at the sides of the head. The light was switched off during the resting-state scanning.1. Slice timing, motion correction, space normalization, and spatial smoothing (8 mm × 8 mm × 8 mm) were first executed. Segmentation for structural images generated white matter, gray matter, and cerebrospinal fluid images. Full details of all preprocessing steps are provided in the previously published study (2 for the preprocessed data: (1) the removal of linear and quadratic trends; (2) regressing out covariates including realignment parameters, mean white matter, and cerebrospinal fluid signals; (3) band-pass temporal filtering (0.01–0.1 Hz); and (4) calculating the interregional causal connections of each participant. Finally, we obtained the nodal degrees and the shortest causal connectivity paths.All of the MRI data were firstly preprocessed by using the software package spm8ed study . Then, wIn the current study, causal connectivity was realized by entropy connectivity method, as defined in a previous study , and thek →n denote the length of the shortest causal connectivity path from brain region BA k to n, then Lk →n was defined as:Let, LSi →j denotes the strength of causal connectivity from brain region BA i to j. BA i and BA j are two adjacent brain regions in the shortest causal connectivity path from BA k to n . A false-negative probability is the exact probability of committing a type II error  as a significant level in a statistical hypothesis testing for all samples and obtain n positive effects 1A,A2, ⋯, nA; (2) randomly select k samples and repeat the statistical hypothesis testing; (3) repeat step (2) M times; (4) if the positive effect iA occurs im times, then the reproducible rate iR of the positive effect iA is defined asIn statistical hypothesis testing, a type I error is the incorrect rejection of a true null hypothesis , while a type II error is the failure to reject a false null hypothesis . A false positive probability is regarded as the exact probability of committing a type I error or the exact level of significance , and a p < 0.05 was considered to indicate a significant difference in any single analysis. A p < 0.05 (FDR corrected) is considered as a significant difference across the hearing loss and normally hearing control group for the two-sample t-tests of neuropsychological performance scores.We performed two-sample p < 0.05, FDR corrected) in MMSE, VF, and BDS, but significantly increased test scores  in TMTA, SCWTA, SCWTB, and SCWTC. A lower score means a worse performance for MMSE, VF, and BDS. A higher score means a worse performance for TMTA, SCWTA, SCWTB, and SCWTC. No significant difference was observed in other tests across the two groups.The results of neuropsychological tests are summarized in We studied changes of causal connections and nodal degrees in patients with hearing loss, as well as the relationships between nodal degrees and cognitive performance scores. The strength of interregional causal connectivity was corrected using the positive reproducible test (PRT) method. Only those significant changes and correlations are described as follows.We found that the right secondary visual cortex (BA 18R) presented enhanced synchronous output causal connections with the left anterior entorhinal cortex (BA 34L) and right temporopolar area (BA 38R) ; the rigt-tests and found significant changes  in hearing loss patients. The results are shown in In order to observe whether causal connectivity changes had an impact on nodal degrees, we studied the nodal degree utilizing two-sample Compared with normally hearing subjects, patients with hearing loss presented increased synchronous output nodal degrees in BA 18R ; increasThe shortest causal connectivity path from one brain region to the other reflects the strongest causal interaction between these two brain regions. It is unclear whether the change of nodal degree also leads to the change of the shortest causal connectivity path; we studied this issue. Our study focused on the shortest causal connectivity paths between the visual cortex, auditory cortex, and those brain areas associated with speech processing. The results are shown in p < 0.0001, two-sided, two-sample t-test, uncorrected) and a bigger transfer probability  from BA 18R to Broca’s area (BA 45L)  . In addi(BA 45L) ; BA 19L (BA 45L) ; BA 19L (BA 45L) ; and BA (BA 45L) . The traIn order to investigate whether nodal degree changes can contribute to cognitive decline, we studied the relationship of cognitive performance scores with nodal degrees utilizing Pearson’s correlation analysis method. The results are described as follows. VF test scores exhibited a significant negative correlation with synchronous output nodal degrees of BA 18R ; TMTA teIn addition, we also analyzed the correlations of cognitive performance scores with lengths of the shortest causal connectivity paths from BA 18R to Broca’s area (BA 45L). We found that both MMSE and VF test scores were positively correlated with lengths of the shortest causal connectivity paths from BA 18R to BA 45L . On the In this study, we have mixed controls and hearing loss subjects into one set and computed correlations , 7. ThisTo further explore the influence of hearing loss on causal connectivity network, we also studied the relationships between nodal degrees and durations of hearing loss. Pearson’s correlation analysis revealed that the asynchronous output nodal degree of BA 23L strongly negatively related with the duration of hearing loss ; similarThe present study investigated adult-onset hearing loss and its effects on the connectivity in the brain using resting-state functional magnetic resonance imaging (fMRI). The main findings of the study are described as follows. Patients with hearing loss presented increased synchronous input causal connectivity for the right associative visual cortex with the auditory cortex and exhibited a shorter causal connectivity path from the right secondary visual cortex to Broca’s area. These findings were consistent with cross-modal reorganization. Moreover, we also observed nodal degree changes in the right secondary visual cortex, associative visual cortex, right dorsolateral prefrontal cortex, left subgenual cortex, and the left cingulate cortex. These changes were significantly related with poor cognitive performances. In addition, we also noted that changes of neural signal in the visual cortex had negative effects on neural activity of Broca’s area but, in the auditory cortex, had positive effects on neural activity of Broca’s area through the shortest causal connectivity paths.via cortico-cortical inhibitory circuits  enhanced neural activity of Broca’s area through the shortest causal connectivity path with big transfer probability. Auditory language is adaptive for speech processing; thus current findings support the opinion that intensive and rigorous oral language training can improve language performance of patients with hearing loss following restorative strategies .Behavior studies found that hearing loss was associated with incident all-cause dementia  and poorHearing loss contributes to changes in the brain network associated with cognitive processing. Resting-state fMRI studies reported increased functional connectivity and abnormal neural activities in the default mode network (DMN) of individuals with hearing loss compared with normally hearing subjects . In addiIn a word, our findings suggest that changes in brain causal connectivity networks are an important mark of cognitive decline in patients with hearing loss. Auditory and visual language signals might have different effects on speech processing. Our research provides some implications for rehabilitation of patients with hearing loss.Our study has a lower limit of sample size; therefore, significant effects observed may also be the consequence of small power. Hearing loss during development and hearing loss in adulthood may have different effects. The aim of the present study was to investigate adult-onset long-term bilateral mild-to-severe sensorineural hearing loss. However, the use of auditorily presented cognitive tests might have biased the results. In addition, we only investigated resting-state causal connectivity, and these results might be different with stimulus-related connectivity .The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by The Institutional Ethics Committee of Shandong First Medical University. The patients/participants provided their written informed consent to participate in this study.G-YZ and L-CX designed the general approach and wrote the manuscript. W-BZ, GZ, and YZ collected the clinical data. M-FZ and L-CX collected the MRI data. G-YZ, Y-FC, D-SZ, and L-MH processed the MRI data. P-CW and X-YW advised on the experimental design. GZ, P-CW, and X-YW revised the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To evaluate the visibility of colorectal lesions using a novel image processing algorithm, texture and color enhancement imaging (TXI), that allows the acquisition of brighter images with enhanced color and surface structure.During August–September 2019, patients referred for endoscopic treatment were prospectively recruited. Electronic data acquired while observing colorectal lesions using white light imaging (WLI) were obtained and recorded: WLI, TXI mode1 (with color enhancement), and TXI mode2 (without color enhancement) videos were constructed. The lesions were also recorded using narrow‐band imaging (NBI) from the same perspective as WLI. Four video clips  were made per lesion. Thereafter, video files for evaluations were prepared by randomly arranging all video clips. Finally, visualization scores were evaluated by four endoscopists, and the WLI, TXI mode1, TXI mode2, and NBI results were compared.Overall, 22 patients with 68 lesions were recruited; the video file for evaluation subsequently comprised 272 randomly arranged video clips. Mean visualization scores using WLI, TXI mode1, TXI mode2, and NBI were 70.0 (±20.1), 80.5 (±18.6), 75.6 (±18.1), and 69.0 (±20.6), respectively. Mean visualization scores for flat lesions using WLI, TXI mode1, TXI mode2, and NBI were 64.1 (±21.2), 76.5 (±20.18), 71.8 (±19.4), and 64.2 (±22.0), respectively. Visualization scores using TXI mode1 were significantly better than those using WLI, TXI mode2, or NBI.TXI enables improved visualization of colorectal lesions, even flat lesions, than WLI and NBI. TXI may allow better detection of colorectal lesions, although further prospective studies are required. The incidence of post‐colonoscopy colorectal cancer is estimated to be 0.7–1.7 cases per person‐years,This study was a retrospective study using prospectively collected videos. The study protocol was approved by the research ethics committee of our institution and was registered in the University Hospital Medical Network Clinical Trials Registry (UMIN 000039073). From August to September 2019, patients were prospectively recruited. The inclusion criteria of this study were as follows: the patients with known colorectal lesions, the patient who was directly referred to the Endoscopy division of the Jikei Medical University Hospital, and the patient agreed to receive endoscopic treatment and to be enrolled in this study. Written informed consent for endoscopic treatment and enrollment of this study was obtained from all patients before enrollment in this study. All patients were administered a polyethylene glycol solution and underwent colonoscopy using a video processor system  and a colonoscope . The electronic data obtained during observation of colorectal lesions using white light imaging (WLI) were recorded. WLI, TXI mode1 (with color enhancement), and TXI mode2 (without color enhancement) videos were constructed using the recorded electronic data. In addition, the lesions were observed and recorded using narrow‐band imaging (NBI) from the same view as WLI, and NBI videos. Four video clips  were made per lesion. Thereafter, video files for the evaluation were made by randomly arranging all video clips. Finally, visualization scores were evaluated by four endoscopists (two experts with the experience of IEE >1000 and two trainees with the experience of endoscopy <1000) on the basis of a visual analog scale   brightness in the dark area, (2) texture such as subtle surface elevation or depression, and (3) color such as slight color changes in the image. TXI was designed to enhance these factors by applying an image processing technology based on the Retinex theory.The flowchart of TXI principles is shown in Figure Figure t‐test. A p‐value <0.05 was considered statistically significant and a p‐value <0.1 was interpreted as a tendency.Statistical analysis was performed using Minitab for Windows . Normally distributed parametric data are expressed as mean (± SD), and non‐parametric data are expressed as the median (range). To determine differences in the visualization scores, comparisons among the groups were performed by one‐way analysis of variance, followed by multiple comparison testing using the Bonferroni–Dunn method. Normally distributed parametric data were analyzed using a Overall, 22 patients were recruited and enrolled in this study. In total, 68 lesions were detected during colonoscopy, and all lesions were resected endoscopically. The median patient age was 63 (37–87) years, the male‐to‐female ratio was 1:0.47, and the mean lesion size was 7.1 (±4.79) mm. Histologically, of the 68 lesions, there were eight hyperplastic polyps (11.8%), six sessile serrated lesions (8.8%), 46 tubular adenomas (67.6%), six mucosal cancers (8.8%), and 2 submucosal tumors (2.9%). Regarding macroscopic types, 41 lesions were flat elevated (60.3%) and 27 were protruded/others (39.7%). Tumor location showed 38 lesions (55.9%) in the right colon  and 40 (44.1%) in the left colon  , 80.5 (±18.6), 75.6 (±18.1), and 69.0 (±20.6) Figure , respectThis report is the first to evaluate the efficacy of TXI for improving the visibility of colorectal lesions, although visibility evaluation of early gastric cancer, pharynx, and esophageal carcinoma suspicious lesions have been reported.This study clarified that TXI enables improved visualization of colorectal lesions, both protruded and flat. TXI, especially TXI mode1, allows better visualization of colorectal neoplasia than WLI and NBI, and this result implies that TXI can detect more colorectal lesions.Small sample size, potential selection bias, single‐center study, subjective evaluation method, use of reconstructed video, non‐blinded study, omission of sample size calculation, and video clips of NBI recorded from non‐identical viewpoint should be considered as the limitation of this study. In addition, improvement of the visibility of colorectal lesions might not allow better detection of colorectal lesions.In conclusion, our study demonstrated that the novel IEE TXI enables improved visualization of colorectal lesions compared to WLI and NBI for both protruded and flat lesions. TXI may allow better detection of colorectal lesions, although further prospective study is required.Kazuki Sumiyama is a Deputy Editor‐in‐Chief of DEN Open. The rest of the authors do not have any conflict of interest.This study received no specific grant from any funding agency in the public, commercial, or not‐for‐profit sectors.Video1. Constructed videos of Intramucosal adenocarcinoma (IIa) lesion located in the transverse colon visualized using WLI, TXI mode1, and TXI mode2.Click here for additional data file.