Engineering hydrophobicity and manufacturability for optimized biparatopic antibody-drug conjugates targeting c-MET.

Optimal combinations of paratopes assembled into a biparatopic antibody have the capacity to mediate high-grade target cross-linking on cell membranes, leading to degradation of the target, as well as antibody and payload delivery in the case of an antibody-drug conjugate (ADC). In the work presented here, molecular docking suggested a suitable paratope combination targeting c-MET, but hydrophobic patches in essential binding regions of one moiety necessitated engineering. In addition to rational design of HCDR2 and HCDR3 mutations, site-specific spiking libraries were generated and screened in yeast and mammalian surface display approaches. Comparative analyses revealed similar positions amendable for hydrophobicity reduction, with a broad combinatorial diversity obtained from library outputs. Optimized variants showed high stability, strongly reduced hydrophobicity, retained affinities supporting the desired functionality and enhanced producibility. The resulting biparatopic anti-c-MET ADCs were comparably active on c-MET expressing tumor cell lines as REGN5093 exatecan DAR6 ADC. Structural molecular modeling of paratope combinations for preferential inter-target binding combined with protein engineering for manufacturability yielded deep insights into the capabilities of rational and library approaches. The methodologies of in silico hydrophobicity identification and sequence optimization could serve as a blueprint for rapid development of optimal biparatopic ADCs targeting further tumor-associated antigens in the future.

Effect of Bioabsorbable Poly (dl-Lactide ε-Caprolactone) on Healing of Experimentally Injured Acute Traumatic Middle Ear Mucosa Damage.

BACKGROUND: Postoperative adhesion is an important complication after middle-ear surgeries. Although many materials have been tried to prevent this complication, the use of Poly (dl-lactide ε-caprolactone) as an anti-adhesive material after middle-ear surgery has not yet been reported. The aim of this study was to evaluate the anti-adhesive effect of poly (dl-lactide ε-caprolactone) on the ears of rats with middle-ear mucosa damage. METHODS: In our study, 14 Wistar albino rats and 28 ears in total were used. The rats were randomly divided into 4 groups. Middle ear mucosa damage was performed in all groups with a transcanal approach under otomicroscopy in sterile conditions. The effects of poly (dl-lactide ε-caprolactone), silicone sheet, and absorbable gelatin sponge were compared histologically with the secondary healing group. In addition, hearing evaluation was performed before the procedure and on the 28th postoperative day. RESULTS: No significant difference was observed in transient otoacoustic emission and distortion product otoacoustic emissions tests performed before and after the surgical procedure when the groups were compared. While adhesion was observed in the tympanic membrane in the absorbable gelatin sponge group, no adhesion was observed in the other groups. In the absorbable gelatin sponge group, increased fibroblastic activity, inflammation, and neovascularization were observed in the middle-ear mucosa. No significant difference was observed in silicone sheet, poly (dl-lactide ε-caprolactone), and control groups in terms of fibroblastic activity, inflammation, and neovascularization. CONCLUSION: It can be concluded that absorbable poly (dl-lactide ε-caprolactone) is nonototoxic and biocompatible with the rat's middle ear cavity by short-term evaluation.

Does perivascular fibrin glue application have a preventive effect for the endothelial damage on saphenous vein graft? An experimental model.

BACKGROUND: The effect of tissue adhesives on coronary grafts in cardiac surgery is a controversial issue. OBJECTIVE: The aim of this study is to investigate the effect of fibrin glue (FG) applied around the saphenous vein grafts (SVG) in preventing cellular damage resulting from intraluminal pressure increase. METHODS: Twenty volunteer patients were included in this ex vivo study. The SVGs remained after coronary artery bypass grafting were connected to the arterial line of the cardiopulmonary bypass circuit. The grafts were divided into two segments and one segment received perivascular FG applied whereas the other part was used plain. SVGs were kept in circulation at 120 mmHg pressure 250 mL/min flow rate for 60 min. The tissues were sent for histopathological examination to determine the endothelial damage. RESULTS: Endothelial damage was more pronounced in the control group when compared with the FG group. In the FG group, no damage was seen in 13 samples and no Type 3 endothelial damage was observe whereas Type 1 injury was detected in seven specimens, Type 2 injury was observed in seven specimens, and Type 3 injury was detected in two specimens in the control group. CONCLUSION: Perivascular application of FG on the SVG showed a protective effect against endothelial damage resulting from increased intraluminal pressure.

ANTECEDENTES: El efecto de los adhesivos tisulares sobre los injertos coronarios en cirugía cardíaca es un tema controvertido. OBJETIVO: Investigar el efecto del pegamento de fibrina aplicado alrededor de los injertos de vena safena para prevenir el daño celular resultante del aumento de la presión intraluminal. MÉTODO: En este estudio ex vivo fueron incluidos 20 pacientes voluntarios. Los injertos de vena safena que quedaron después del injerto de derivación de la arteria coronaria se conectaron a la línea arterial del circuito de derivación cardiopulmonar. Los injertos se dividieron en dos segmentos y a uno de ellos se le aplicó pegamento de fibrina perivascular, mientras que la otra parte se usó sola. Los injertos de vena safena se mantuvieron en circulación a una presión de 120 mmHg y una velocidad de flujo de 250 ml/min durante 60 minutos. Los tejidos se enviaron para examen histopatológico para determinar el daño endotelial. RESULTADOS: El daño endotelial fue más pronunciado en el grupo de control que en el grupo de pegamento de fibrina. Se observó lesión de tipo 2 en siete muestras del grupo de pegamento de fibrina y lesión de tipo 3 en dos muestras del grupo de control. CONCLUSIONES: La aplicación perivascular de pegamento de fibrina en los injertos de vena safena mostró un efecto protector contra el daño endotelial resultante del aumento de la presión intraluminal.

Surgical treatment of caseous calcification of the mitral annulus causing mitral stenosis and mimicking the clinical picture of infective endocarditis: A case report.

Among masses involving the mitral valve and annulus, caseous calcification of the mitral annulus (CCMA) is a rare disease. CCMA accounts for .63% of all mitral annular calcification (MAC) cases. The pathophysiology is still unknown. The correct diagnosis and treatment of this disease is very important to prevent complications. We present a case of giant CCMA with advanced mitral stenosis and hypertrophic cardiomyopathy, presenting with symptoms of infection and therefore a preliminary diagnosis of infective endocarditis. Because of these features, we wanted to share our case as it is the 1st case in the literature.

Surgical treatment of recurrent subvalvular discrete membrane and left ventricular outflow tract stenosis in an adult patient with a history of congenital cardiac surgery.

Left ventricular outflow stenosis can develop at the supravalvular, valvular, and subvalvular levels. Resection of strictures at the diffuse subvalvular level is very difficult. In such pathologies, Konno-Rastan procedure provides very successful solutions as an anterior aortoventriculoplasty method. In this article, we performed anterior aortaventriculoplasty surgical treatment for tunnel type left ventricular outflow tract stenosis, recurrent subvalvular discrete membrane, and aortic regurgitation in an adult patient with a history of partial atrioventricular septal defect repair and subvalvular discrete membrane resection operation in early childhood. The Konno-Rastan procedure, which we applied to the redo case, which is rarely used in adult patients and rarely seen in the literature, is shared.

The predictive value of internal carotid artery wall thickness in computed tomography angiography to avoid complications of plaque removal failure in modified eversion carotid endarterectomy.

AIM: The benefits of computed tomography carotid angiography (CTA) in terms of evaluating the anatomical structure of the carotid arteries, surgical planning, and evaluating possible risks were reported in previous studies. This study aimed to calculate the predictive value of internal carotid wall thickness in CTA that can predict whether a modified carotid eversion endarterectomy (MCEE) will result in a successful or not. METHOD: This study was designed in a retrospective cross-sectional format. Consecutive 83 symptomatic carotid surgery patients who were operated in our hospital and had CTA were included in this study. The wall thickness of the internal carotid artery (ICA) 20 mm distal from the carotid bifurcation was calculated in axial sections using a three-dimensional imaging technique. In addition, all patients' characteristics and laboratory findings were recorded. Patients who failed MCEE and required classical carotid endarterectomy were compared with patients who had successful MCEE. RESULTS: MCEE technique was applied to 62 patients. In 21 patients, the MCEE technique failed and the classical endarterectomy technique was required. Preoperative clinical and laboratory characteristics were similar in both groups. The mean ICA wall thickness was 0.65 mm 20 mm distal to from the carotid bifurcation and it was lower in the group with successful MCEE (1.03 ± 0.21 mm vs. 0.56 ± 0.08 mm) (p < 0.001). The critical ICA wall thickness was calculated as 0.76 mm in the group that MCEE failed and classical carotid endarterectomy was required. Cut-off analysis of ICA wall thickness was calculated as 0.755 mm in ROC analysis (p < 0.001), (95% confidence interval, curve area; 0.985). CONCLUSION: Successful carotid endarterectomy with the MCEE method is associated with distal ICA wall thickness and distal extension of the atheroma plate. The use of ICA wall thickness 20 mm distal to from the bifurcation as a predictive value for the success of the MCEE technique is beneficial to avoid serious complications.

A rare complication of double prosthetic valve endocarditis; reconstructive surgical treatment of mitral-aortic intervalvular fibrosa pseudoaneurysm and left atrial fistula.

Mitral aortic intervalvular fibrosa or aorto-mitral curtain is a fibrous avascular skeletal structure located between the anterior leaflet of the mitral valve and the non-coronary and left coronary cusps of the aortic valve. Mitral and aortic valve endocarditis are rarely accompanied by mitral aortic intervalvular fibrosa pseudoaneurysm and left atrial fistula of the aorta. Pseudoaneurysm of mitral aortic intervalvular fibrosa is a fatal complication that can occur after valvular surgery, valvular endocarditis, or blunt trauma. In this article, reconstructive surgical management with the Commando technique of a case who developed mitral-aortic intervalvular fibrosa pseudoaneurysm to left atrial fistula after aortic and mitral prosthetic valve endocarditis is described. The important feature of this article is that it is a first in the literature as it is accompanied by persistent left superior vena cava.

Analyzing the relationship between product waste footprints and environmental damage - A life cycle analysis of 1,400+ products.

A major problem for the circular economy is monitoring improvements in environmental sustainability. Measuring how much waste reduction efforts contribute to the decrease of environmental impact is difficult, because knowledge on whether life cycle waste amounts correlate with environmental damage is limited. In this article, product waste footprints are used to explore structural similarities and differences in associations with environmental damage. Using the waste flows linked to the production system of 1487 reference products from the Ecoinvent database, we found significant regression equations with R2 of 0.75-0.89 between product waste footprints and potential impact on ecosystem diversity, human health and resource availability using log-transformed variables. For each 1 % increase in solid waste, potential impact on the environment increased by 0.75-0.84 %. This strong association between pre-consumer waste and environmental damage is particularly important for advocating for circular economy efforts at the point of consumption, where life cycle waste is invisible to consumers.

Systemic immune-inflammation index for predicting poor outcome after carotid endarterectomy: A novel hematological marker.

OBJECTIVE: To investigate the predictive role of systemic immune-inflammation index (SII) on postoperative poor outcome in patients undergoing carotid endarterectomy (CEA). METHODS: A total of 347 patients undergoing elective isolated CEA between March 2010 and April 2022 were included in this multicenter retrospective observational cohort and risk-prediction study and were divided into two groups as poor outcome group (n = 23) and favorable outcome group (n = 324). Poor outcome was defined as the presence of at least one of the complications within 30 days of surgery including stroke, myocardial infarction, and death. The patients' baseline clinical characteristics, comorbidities, and hematological indices were derived from the complete blood count (CBC) analysis, and perioperative data, outcomes, and complications were screened, recorded, and then compared between the groups. Multivariate logistic regression and receiver-operating characteristic (ROC) curve analyses were conducted following univariate analyses to detect the independent predictors of poor outcome as well as the cutoff values with sensitivity and specificity rates. RESULTS: A total of 23 patients out of 347 (6.6%) manifested poor outcome; and stroke, myocardial infarction, and death occurred in 13, 3, and 7 cases, respectively. There were no significant differences between the groups in terms of basic clinical characteristics, comorbidities, and perioperative data, except for lengths of intensive care unit and hospital stays. Although the median values of PLT, PLR, NLR, and SII of the poor outcome group were found to be significantly higher than the favorable outcome group in univariate analysis, only SII was detected to be a significant and independent predictor of poor outcome in multivariate logistic regression analysis (OR = 1.0008; 95% CI: 1.0004-1.0012; p = 0.002). ROC curve analysis revealed that SII of 1356 × 103/mm3 constituted the cutoff value for predicting poor outcome with 78.3% sensitivity and 64.5% specificity (AUC = 0.746; 95% CI: 0.64-0.851). CONCLUSIONS: Our study revealed for the first time in the literature that SII significantly predicted poor outcome after CEA.

Detection of residual varicose veins with near infrared light in the early period after varicose surgery and near infrared light assisted sclerotherapy.

OBJECTIVES: Varicose veins that cannot be seen with the naked eye can be easily detected with Near Infrared (NIR) light. With a minimally invasive procedure performed with NIR light guided, the need for reoperation is reduced, while optimal treatment of venous insufficiency and symptoms is provided. In this study, the detection of residual varicose veins after varicose vein surgery using NIR light and the results of treatment of sclerotherapy were investigated. METHODS: In this retrospective study, treatment and clinical outcomes of patients' who underwent NIR light-guided foam sclerotherapy for Clinical-Etiology-Anatomy-Pathophysiology (CEAP) (C1, C2) stage residual varicose veins after surgical varicose treatment between 2014 and 2017 were examined. Data of patients who underwent foam sclerotherapy with NIR light were collected and analyzed. RESULTS: A total of 151 patients and 171 lower extremity varicose veins were treated with surgery. 55 (35.7%) of the patients were male, and 96 (62.3%) were female. Their age ranges from 20 to 64, with an average age of 45.38. 4 (2.6%) of the patients had phlebectomy. 137 of patients (90.7%) had ligation of perforated veins, phlebectomy, and great saphenous vein (GSV) stripping, 10 of patients (6.6%) had GSV stripping, perforating vein ligation, phlebectomy, and small saphenous vein (SSV) surgery. No residual leakage was observed in the controls of GSV, SSV, and perforating veins by duplex ultrasonography (DUS). In the first month after varicose surgery, an average of 1.64 ± 1.05 sessions of sclerotherapy was applied to patients with CEAP C1, C2 stage residual varicose veins. 70 patients had one session of sclerotherapy, 37 patients had two sessions of sclerotherapy, 20 patients had three sessions of sclerotherapy, and 11 patients had four sessions of sclerotherapy administrated. The need for complementary therapy was required for all female patients; 13 of the male patients did not require complementary sclerotherapy. While single-session sclerotherapy was applied to most male patients (32 (58.18%), 10 (18.18%) patients received two sclerotherapy sessions. After completing sclerotherapy, 7 (4.63%) patients had superficial venous thrombosis, and 13 (8.60%) patients had hyperpigmentation. CONCLUSION: Surgical treatment is a safe and effective technique in venous insufficiency. Nevertheless, residual varicose veins may remain, and these can be detected noninvasively with NIR light. Foam sclerotherapy with NIR light is a minimally invasive and safe treatment method for small residual varicose veins after the operation. We think that sclerotherapy with NIR light as a complementary treatment is a practical, reliable, and demanding treatment for clinical improvement, especially in female patients.

Impact of tonsillectomy on COVID-19 pandemic: an observational study of the incidence and prognosis.

BACKGROUND: Due to many different reasons such as possible coronavirus colonization in tonsillar tissue, decreased enzymatic antiviral activity, decreased cytokine activity from palatine tonsil tissue and reduced humoral and cellular immune response, tonsillectomy may alter the incidence of Covid-19. AIMS/OBJECTIVES: To reveal the frequency of Covid-19 in patients who underwent tonsillectomy and to analyze the effect of tonsillectomy on the severity of the disease. MATERIALS AND METHODS: Patients aged between 15 and 65 and had a history of tonsillectomy were compared with control group in terms of incidence and severity of Covid-19 disease. RESULTS: A 4% Covid rRT-PCR test positivity rate was detected in patients with tonsillectomy whereas; it was 6.8% in the control group with a statistically significant difference. However, in terms of disease severity there was no difference between the two groups. CONCLUSIONS AND SIGNIFICANCE: It has been proven that tonsillectomy surgery does not pose an additional risk in terms of COVID 19 disease severity. The positive effect of tonsillectomy in terms of disease frequency has been even demonstrated for the first time in the literature.

Association between vitamin D levels and lower-extremity deep vein thrombosis: a case-control study.

BACKGROUND: Vitamin D has relationships with pathogenesis and inflammation pathways in many diseases. Its deficiency may make clinicians think not only of supplementation but also of presence of other diseases. OBJECTIVE: To investigate the relationship between vitamin D levels and deep vein thrombosis (DVT), given that reduced levels are related to increased risk of cardiovascular diseases. DESIGN AND SETTING: Case-control study conducted in the cardiovascular surgery and family medicine departments of a hospital in Turkey. METHODS: A total of 280 participants were included: 140 each in the DVT and control groups. Basic clinical characteristics, comorbidities and serum 25-hydroxyvitamin D (25(OH)D) levels were recorded and then compared between the groups. Serum 25(OH)D levels were also evaluated separately in three subgroups (sufficient, insufficient and deficient). RESULTS: Serum 25(OH)D levels were significantly lower in the DVT group than in the controls (P < 0.001). Females in the DVT group had lower 25(OH)D levels than those in the control group (P = 0.002). Nonetheless, the median 25(OH)D level (16.41 ng/ml) of the control group was still below the reference value. Logistic regression analysis showed that 25(OH)D was a significant predictor of DVT. Weight, height and body mass index, which all presented interaction, were significant in the logistic regression analysis but not in individual analyses. CONCLUSION: The serum vitamin D levels of DVT patients were lower than those of controls. If the results obtained from our study are supported by further large-scale randomized controlled trials, vitamin D replacement may be brought into the agenda for protection against DVT.

Association between vitamin D levels and lower-extremity deep vein thrombosis: a case-control study

ABSTRACT BACKGROUND: Vitamin D has relationships with pathogenesis and inflammation pathways in many diseases. Its deficiency may make clinicians think not only of supplementation but also of presence of other diseases. OBJECTIVE: To investigate the relationship between vitamin D levels and deep vein thrombosis (DVT), given that reduced levels are related to increased risk of cardiovascular diseases. DESIGN AND SETTING: Case-control study conducted in the cardiovascular surgery and family medicine departments of a hospital in Turkey. METHODS: A total of 280 participants were included: 140 each in the DVT and control groups. Basic clinical characteristics, comorbidities and serum 25-hydroxyvitamin D (25(OH)D) levels were recorded and then compared between the groups. Serum 25(OH)D levels were also evaluated separately in three subgroups (sufficient, insufficient and deficient). RESULTS: Serum 25(OH)D levels were significantly lower in the DVT group than in the controls (P < 0.001). Females in the DVT group had lower 25(OH)D levels than those in the control group (P = 0.002). Nonetheless, the median 25(OH)D level (16.41 ng/ml) of the control group was still below the reference value. Logistic regression analysis showed that 25(OH)D was a significant predictor of DVT. Weight, height and body mass index, which all presented interaction, were significant in the logistic regression analysis but not in individual analyses. CONCLUSION: The serum vitamin D levels of DVT patients were lower than those of controls. If the results obtained from our study are supported by further large-scale randomized controlled trials, vitamin D replacement may be brought into the agenda for protection against DVT.

Is Nasal Packing Necessary After Endoscopic Dacryocystorhinostomy Without Stent and Mucosal Flaps Preservation?

OBJECTIVE: This study aimed to evaluate the effect of nasal packing on the surgical success and postoperative complications of endoscopic dacryocystorhinostomy (EnDCR) without using stents and mucosal flaps. METHODS: The retrospective study comprised of 75 eyes of 65 consecutive patients undergoing EnDCR with the biting and removing technique. The patients were assigned to 2 groups depending on whether the biodegradable synthetic polyurethane foam was used or not (the packing group, 34 eyes; the nonpacking group, 41 eyes). At least 6 months after the EnDCR, the postoperative outcomes including anatomical and functional successes, and the postoperative complications such as synechia, granuloma, and bleeding were compared between the packing and nonpacking groups. RESULTS: Synechia was lower in the packing group (23.5% versus 24.4%) but it was not statistically significant (P = 0.93). There were also no significant differences in the granuloma and bleeding complications between the 2 groups (respectively, P = 0.72, P = 0.08). The success rates of anatomical and functional reached 88% in the packing group compared with 82.9%, and 75.6% in the nonpacking group (respectively, P = 0.74, P = 0.76). CONCLUSIONS: The present study findings suggest that both groups have no superiorities over each other in the surgical outcomes after the EnDCR. However, further randomized studies are recommended before the generalization can be made.

TET1 promotes growth of T-cell acute lymphoblastic leukemia and can be antagonized via PARP inhibition.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer characterized by skewed epigenetic patterns, raising the possibility of therapeutically targeting epigenetic factors in this disease. Here we report that among different cancer types, epigenetic factor TET1 is highly expressed in T-ALL and is crucial for human T-ALL cell growth in vivo. Knockout of TET1 in mice and knockdown in human T cell did not perturb normal T-cell proliferation, indicating that TET1 expression is dispensable for normal T-cell growth. The promotion of leukemic growth by TET1 was dependent on its catalytic property to maintain global 5-hydroxymethylcytosine (5hmC) marks, thereby regulate cell cycle, DNA repair genes, and T-ALL associated oncogenes. Furthermore, overexpression of the Tet1-catalytic domain was sufficient to augment global 5hmC levels and leukemic growth of T-ALL cells in vivo. We demonstrate that PARP enzymes, which are highly expressed in T-ALL patients, participate in establishing H3K4me3 marks at the TET1 promoter and that PARP1 interacts with the TET1 protein. Importantly, the growth related role of TET1 in T-ALL could be antagonized by the clinically approved PARP inhibitor Olaparib, which abrogated TET1 expression, induced loss of 5hmC marks, and antagonized leukemic growth of T-ALL cells, opening a therapeutic avenue for this disease.

Evaluation of nasal tip shape in patients with severe caudal septal deviation after modified extracorporeal endonasal septoplasty.

OBJECTIVES: The aim of this prospective study was to evaluate the effect of modified extracorporeal endonasal septoplasty on nasal tip shape and function in patients with severe caudal septal deviation. METHODS: The study population comprised of 55 patients undergoing modified extracorporeal endonasal septoplasty, which called marionette septoplasty. To analyse the aesthetic objective outcomes, postoperative photographs were measured for projection index (PI), tip projection (TP), nasolabial angle (NLA), tip deviation angle (TDA), nasofrontal angle (NFA), supratip height (STH), columellar height (CH), at three times (2 weeks, 3, and 6 months after surgery) and were compared with preoperative photographs. Functional and aesthetic outcomes were also evaluated using nasal obstruction symptom evaluation (NOSE) scale and standardized cosmesis and health nasal outcomes survey (SCHNOS). RESULTS: Between the pre- and post-operative 6th-month examinations, a significant increase in PI and TP were 7%, and 5% respectively. There was a significant alteration in the NLA and TDA values following the last examination (mean difference ± standard error of mean 9.68 ± 0.9° and 1.5 ± 0.8°, respectively). Moreover, the technique did not make a significant change in the final NFA, STH, and CH, measurements. Following surgery, the NOSE and SCHNOS scores were decreased significantly and the improvement continued over time until the last examination. CONCLUSION: The present study findings suggest that the marionette septoplasty technique is an effective to correct and stabilize severe caudal septal deviations. This technique also can provide tip support and protection with a low incidence of dorsal irregularity.

Histological Study of The Healing of Traumatic Tympanic Membrane Perforation After Vivosorb and Epifilm Application.

BACKGROUND: Untreated traumatic tympanic membrane perforations (TMPs) may lead to permanent perforations and hearing loss. There are many materials that have been previously used for repairing the TMPs. AIMS AND OBJECTIVES: The purpose of this study is to evaluate the clinical and histological effects of Vivosorb (Vv) and Epifilm on healing of TMPs in a rat model. MATERIAL AND METHODS: The posterior-inferior quadrant of the tympanic membranes (TMs) in right ears of 14 rats was perforated using a 20-g needle and then the animals were randomly divided into 2 equal groups (n = 7). The perforated right TMs were treated with either Vv (Vv group) or Epifilm (Ep group). The left TMs of 7 rats were perforated in same way and allowed to close spontaneously without any topical material applications (spontaneous closure group as sham control, SC). The left tympanic membranes of the other 7 rats were not perforated and used as normal controls (NC group). On postoperative 15th day, tympanic bullas were extracted from killed rats and examined morphometrically and histopathologically. RESULTS: Perforation closure rate was 85.7% (6/7) in both Vv and SC groups. Perforations of Ep group closed in 7/7 (100%) ears. The thicknesses of the perforated membranes were increased in SC and especially Vv groups. Also, connective tissue fibrosis, blood clots, and epithelial degenerations were detected in SC and Vv groups. The mean fibroblastic reaction scores of Vv, Ep, and SC groups were 2.14(+), 0.57(+), and 1.71(+) respectively, on comparison with NC group. The mean neovascularization score was 1.42(+) in Vv group, 0.14(+) in Ep group, and 0.57(+) in SC group. CONCLUSION AND SIGNIFICANCE: Vivosorb and especially Epifilm can improve the healing process in traumatic TMPs and additionally, Epifilm might be more preferred for the treatment of TMPs because of causing lesser fibrosis.

Comparison of the results of caloric and video head impulse tests in patients with Meniere's disease and vestibular migraine.

PURPOSE: To compare the results of video head impulse test (vHIT) and caloric testing (CT) in patients with vestibular migraine (VM) and Ménière's disease (MD) and to investigate the relationship between these two tests. METHODS: Patients with definite unilateral MD and VM were included in the study. All patients underwent both vHIT and CT. The vestibulo-ocular reflex (VOR) gains of lateral semicircular canals and saccadic waves in vHIT and the canal paresis factor for the CT were examined. RESULTS: CT was found abnormal in 39 (66.1%) patients with MD and in 17 (34%) patients with VM, while abnormal gain of the lateral canal was obtained in 23 MD (39%) patients and 9 (18%) VM patients. In all, 11.9% of patients with an abnormal vHIT had a normal CT, whereas 33.9% of those with an abnormal CT had a normal vHIT. CONCLUSION: Loss of VOR detected by caloric testing is more common and severe in MD than VM. Although vHIT is useful and can give complementary information, vestibular testing with the caloric test still seems more sensitive for detecting hVOR pathology.

Intratympanic Steroid Treatment of Bell's Palsy in Patients with Comorbid Disease: A Preliminary Report.

OBJECTIVES: This study evaluated the efficacy of intratympanic steroid injection (ITSI)as initial treatment and therecovery speed for Bell's palsy (BP)inpatients with diabetes mellitus (DM)and/or hypertension (HT). MATERIALS AND METHODS: In total,90 patients with comorbid diseases diagnosed with BP received either ITSI (study group, n=61) or systemic steroid treatment (SST) (control group, n=29).The facial nerve function was assessed using the House-Brackmann (HB) grading system for up to 6 months or until complete recovery from BP. To investigate a relationship with the complete recovery time from BP, hematologic and baseline characteristic parameters were analyzed. RESULTS: The complete recovery rate of the ITSI and SST groups was 47.5% and 44.8% at the 1st month, 70.5% and 89.7% at the 3rd month, and 96.7% and 100% at the 6th month of the study, respectively. Lymphocyte and neutrophil values were significantly associated with the complete recovery time from BP. No major adverse events from ITSI itself were noticed during the procedure and during the follow-up of the treatment. CONCLUSION: Both treatment types have no superiorities over each other in initial treatment for BP in patients with comorbid diseases. ITSI is effective and safe and may avoid the unwanted side effects associated with systemic steroids inthese patients.

Evaluation of the Effect of Diclofenac Sodium and 5-Fluourasil in a 3D Cholesteatoma Cell Culture Model.

INTRODUCTION: Middle ear cholesteatoma is a benign disease with invasive and destructive clinical behaviors. It increases the rate of both chronic otitis media complications and revision surgeries. The most effective treatment of middle ear cholesteatoma is surgical excision, and there is no medical treatment for this disease. Exploring new medical treatment options may help to create treatment alternatives instead of surgery. MATERIALS AND METHODS: Required cholesteatoma tissues for cell culture were excised from 4 different participants who underwent surgery in our clinic and agreed to give tissue for the study. Cholesteatoma-derived keratinocytes and fibroblasts were cocultured in temperature-sensitive culture dishes to make a three-dimensional (3D) cholesteatoma model. Then, the effects of 1% and 2% diclofenac sodium on viability and cell proliferation rates were examined using WST-1 and annexin-V tests. RESULTS: Cell viability and proliferation rates were found to be lower and apoptosis rates were higher in the diclofenac sodium group versus the negative and positive control groups. CONCLUSION: In this present study, we described a new 3D cholesteatoma cell culture model developed using cell sheet technology and demonstrated the efficacy of diclofenac sodium on cholesteatoma for the first time in the literature. It may be used in patients with chronic otitis media with cholesteatoma, but further studies investigating ototoxic and neurotoxic effects of this molecule are needed.