The arteriovenous fistula constitutes the vascular access of first choice in hemodialysis. We present three clinical cases that highlight the resolution in interventional radiology of venous stenosis, one of the major complications. Clinical monitoring and instrumental diagnostics with color Doppler ultrasound have prevented the failure of the AVF due to high risk of thrombosis. The angiographic interventions, thanks to the collaboration between Spoke and Hub, were completed without complications.

Hearing loss is an important health care concern. Pure Tone Audiometry (PTA) is considered  Gold Standard for audiometric evaluations though, there exist a huge variance between the demand and the actual services available. As smartphones are mobile, applications are upgradable, results are reproducible, the mobile applications may offer a good screening tool, especially in remote areas. There are many smartphone-based hearing applications which are already in use. However, effectiveness of such applications needs to be validated. To evaluate the reliability of \'Hearing Test\' a phone application against PTA for assessment of hearing thresholds in adults. We conducted a diagnostic study on a heterogenous group of 250 individuals irrespective of their hearing levels. The hearing thresholds for both ears were measured by PTA and phone app and then compared statistically. The agreement between the methods were statistically significant with respect to diagnosing hearing loss and the degree of hearing loss. Though, PTA remains Gold Standard for hearing evaluation but freely available,  highly reproducible & specific \'Hearing Test\' application could be used as a screening tool in remote areas and may help bridging the gap between the requirement and availability of diagnostic audiometric services.

Background: Due to the rapid development of treatment techniques of peripheral arterial disease (PAD) treatment is nowadays predominantly interventional. An exception are lesions of the common femoral artery (CFA), which should be treated surgically according to vascular guidelines. However, recent evidence has shown that endovascular techniques, e.g. stenting, have comparable clinical outcomes while causing fewer complications. The aim of the present analysis was to evaluate the therapeutic success of endovascular therapy of CFA lesions in a single center, all - comers registry. Patients and methods: All patients who were treated for a CFA lesion at the Department of Internal Medicine I of the University Hospital Jena in the period from 01/2017 to 12/2020 were included. Treatment success was determined by evaluating the ankle-brachial-index (ABI) pre- and post-interventional as well as after follow-up (FU), measuring walking distance (WD) and by target revascularization rate (TLR) and primary patency rate (PPR). Results: The analysis included 109 patients with a mean age of 73.4 years, with 67% (73) of those being men. 72 patients received interventional treatment, whereas 33 were treated surgically and 4 conservatively. Resting ABI in the overall cohort showed an increase from 0.5 to 0.7 post intervention (p=<0.05; mean FU-time: 6.5 months). In the interventional cohort ABI increases from 0.6 to 0.8 (p=<0.05; mean FU-time: 5,8 months) at FU and from 0.3 to 0.6 (p=<0.05; mean FU-time: 8,8 month) in the surgically treated group. The WD improved in the whole collective from 116.5 meter (m) to 152.5 m (p=<0.05). The TLR showed no significant difference with 8.1% after interventional treatment and 6.1% after vascular surgery in the present analysis (p=0.72) as well as PPR with 89.8% after EVT and 90.9% after surgical approach (p=0.87). The intra-/postinterventional complication rate was 5.5% in the intervention group, compared to postoperative complication rate of 15.2% in the surgically treated group. Conclusions: The present analysis demonstrates that even in a real-world, all-comers collective, interventional therapy for CFA lesions was safe and equally effective as the surgically treated patient cohort. Continuing to generate registry data is important to eventually initiate a paradigm shift.

BACKGROUND: WHO estimated the prevalence of disabling hearing loss is 5% of the world population (430 million). People with a risk of hearing loss from noise exposure, ototoxic drugs, and comorbidities need regular hearing assessments. It is done by pure tone audiometry (PTA), requiring a skilled audiologist, special equipment, and a soundproof room. Modern technologies can help in overcoming these barriers. This study aimed to fill the lacuna by developing a new android-based application \"Shravana Mitra\" (Hearing companion) with features of both air conduction (AC) and bone conduction (BC) testing.
OBJECTIVE: To develop, corroborate and compare smartphone application-based audiometry with PTA.
METHODS: This study was done in three phases -(i) development of a mobile application, (ii) app validation in healthy individuals (iii) testing and comparison of results with PTA in individuals visiting OPD. The third phase was done as a cross-sectional observational study including 780 individuals visiting OPD of 10-60 years of age.
RESULTS: The mean age of the study population was 32.89 years with female preponderance (57%). In AC testing, 83% of the pure tone average of the mobile application was within 5 dB of PTA thresholds and 99% was within 10 dB and for BC testing, 81% was within 5 dB of PTA thresholds and 98% within 10 dB.
CONCLUSIONS: Our user-friendly mobile application- Shravana Mitra is the first Indian application available in the google play store with both AC & BC testing, multiple language options and accuracy similar to PTA. Thus, it can be used as the best hearing screening tool in camps, high-risk individuals, or any healthcare setup requiring initial hearing assessment.

During veno-venous extracorporeal membrane oxygenation (vv ECMO) therapy, antimicrobial drugs are frequently used, and appropriate dosing is challenging due to there being limited data to support the dosage. Linezolid is effective against multidrug-resistant Gram-positive pathogens frequently isolated in ECMO patients. In total, 53 steady-state linezolid levels were obtained following 600 mg intravenous (IV) injections every 8 h, and these were used to develop a population pharmacokinetic (PopPK) model in patients with COVID-19-associated acute respiratory distress syndrome (CARDS) on vv ECMO. The data were analyzed using a nonlinear mixed-effects modelling approach. Monte Carlo simulation generated 5000 patients\' individual PK parameters and corresponding concentration-time profiles using the PopPK model, following the administration of 600 mg/8 h (a higher-than-standard dosing) and 600 mg/12 h (standard). The probabilities of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) and the cumulative fraction of responses (CFR) for three pathogens were calculated and compared between the two dosing scenarios. Linezolid 600 mg/8 h was predicted to achieve greater than or equal to 85%Tf>MIC in at least 90% of the patients with CARDS on vv ECMO compared to only approximately two thirds of the patients after dosing every 12 h at a minimal inhibitory concentration (MIC) of 2 mg/L. In addition, for the same MIC, fAUC24/MIC ≥ 80 was achieved in almost three times the number of patients following an 8-h versus a 12-h interval. PopPK simulation predicted that a significantly higher proportion of the patients with CARDS on vv ECMO would achieve the PK/PD targets following the 8-h dosing interval compared to standard linezolid dosing. Nevertheless, the safety concern, in particular, for thrombocytopenia, with higher-than-standard linezolid dosage is reasonable, and consequently, monitoring is essential.

Stenosis represents the most relevant arteriovenous fistula (AVF) pathology and can affects the entire conduit forming the fistula, from afferent artery to central venous vessels. Correction of vascular access stenosis significantly affects the survival and quality of life for end stage renal disease patients (ESRD) dependent on hemodialysis. Guidelines consider the procedure of percutaneous transluminal angioplasty (PTA) relevant for the primary treatment of these lesions with excellent results in restoring AVF immediately at the end of the procedure. From first AVF angioplasty in 1981 to now, wide scientific innovation has led to development of new devices, composed by different materials and technologies, specific for the site and the type of stenosis to be treated, able to manage resistant stenotic lesion and to reduce stenosis recurrences. International guidelines do not clearly specify all treatment possibilities in the individual case. In this review the authors want to provide specific information on most used devices for stenosis treatment based on literature evidence, showing when and where to use the various tools available with flow-chart treatment proposal.

Antibiotic development traditionally involved large Phase 3 programs, preceded by Phase 2 studies. Recognizing the high unmet medical need for new antibiotics and, in some cases, challenges to conducting large clinical trials, regulators created a streamlined clinical development pathway in which a lean clinical efficacy dataset is complemented by nonclinical data as supportive evidence of efficacy. In this context, translational Pharmacokinetic/Pharmacodynamic (PK/PD) plays a key role and is a major contributor to a \"robust\" nonclinical package. The classical PK/PD index approach, proven successful for established classes of antibiotics, is at the core of recent antibiotic approvals and the current antibacterial PK/PD guidelines by regulators. Nevertheless, in the case of novel antibiotics with a novel Mechanism of Action (MoA), there is no prior experience with the PK/PD index approach as the basis for translating nonclinical efficacy to clinical outcome, and additional nonclinical studies and PK/PD analyses might be considered to increase confidence. In this review, we discuss the value and limitations of the classical PK/PD approach and present potential risk mitigation activities, including the introduction of a semi-mechanism-based PK/PD modeling approach. We propose a general nonclinical PK/PD package from which drug developers might choose the studies most relevant for each individual candidate in order to build up a \"robust\" nonclinical PK/PD understanding.

UNASSIGNED: The article aimed to compare the efficiency and safety of atherectomy plus balloon angioplasty (BA) with BA alone for the treatment of infrapopliteal arterial disease.
UNASSIGNED: According to the inclusion and exclusion criteria, PubMed, Embase, and Cochrane Library database were searched for studies comparing atherectomy plus angioplasty and angioplasty alone in treating infrapopliteal artery lesions until November 2022. The endpoints included technical success, primary patency, clinically-driven target lesion revascularization (CD-TLR), periprocedural complications, distal embolization, target limb major amputation, and all-cause mortality.
UNASSIGNED: Ten studies met the requirements of our meta-analysis, including 7723 patients in the atherectomy plus BA group and 2299 patients in the BA alone group. The meta-analysis showed that atherectomy plus BA was associated with reduced CD-TLR (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.34, 0.78, p=0.002) and target limb major amputation (OR: 0.43, 95% CI: 0.19, 1.01, p=0.05) at 12-month follow-up. No statistically significant difference was found in technical success, primary patency, periprocedural complications, distal embolization, or all-cause mortality. Subgroup analysis found a higher rate of primary patency at 6 and 12 months (6 months: OR: 2.26, 95% CI: 1.11, 4.60, p=0.02; 12 months: OR: 2.38, 95% CI: 1.16, 4.86, p=0.02), and lower rates of CD-TLR (OR: 0.45, 95% CI: 0.25, 0.82, p=0.009) and target limb major amputation (OR: 0.43, 95% CI: 0.19, 1.01, p=0.05) at 12 months in patients treated with atherectomy plus drug-coated balloon (DCB) but not in patients treated with atherectomy plus plain old balloon angioplasty (POBA).
UNASSIGNED: This meta-analysis suggests that compared with BA alone, atherectomy plus BA may reduce the need for CD-TLR and the incidence of target limb major amputation at 12-month follow-up in the treatment of infrapopliteal artery occlusive lesions, even though there are no significant advantages in technical success, primary patency, periprocedural complications, distal embolization, or all-cause mortality. To go further, atherectomy plus DCB shows significant benefits in primary patency, CD-TLR, and target limb major amputation rate but atherectomy plus POBA does not\'. However, due to the limitations of this article, more randomized controlled trials (RCTs) are needed to confirm these conclusions.
CONCLUSIONS: According to our research, atherectomy combined with BA has the advantages of higher primary patency rate, lower CD-TLR and target limb significant amputation rate in treating infrapopliteal artery occlusive lesions, which may replace the current mainstream surgical method ---BA alone. For the clinician, although the surgery may take longer, it will significantly improve the prognosis and quality of life of patients and hold considerable significance for the management of patients with infrapopliteal arterial disease. Based on the characteristics of infrapopliteal artery disease, this study explored the feasibility of atherectomy combined with BA for infrapopliteal artery disease. Moreover, we found that atherectomy combined with DCB had better clinical efficacy, which should be the innovation of this study.

Introduction The study aims to determine the role of intratympanic dexamethasone (ITD) on the hearing profile of patients with head and neck cancer post-chemoradiotherapy. Study design This study employs a prospective case-control design. Subjects and methods In total 834 patients were evaluated for eligibility. Seven hundred and eleven were excluded because they didn\'t meet the inclusion criteria. A hundred cases out of 123 were diagnosed with head and neck cancer for which the treatment protocol included cisplatin concurrent to radiotherapy recruited. Before each cisplatin treatment session, ITD was injected into one ear (experimental ear) while the other ear of the same patient served as the control. Pure-tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAE) test results of the baseline and follow-up examinations in the sixth and 12th weeks were compared within and between the study and control ears. Results For pure tone thresholds, significant hearing threshold change was noticed at 8 kHz in the experimental group at six weeks and at ≥ 6 kHz in the control group. At 12 weeks, high frequencies were significantly affected at ≥ 4 kHz in the control group. When the baseline was compared across the groups in the 12th week, for otoacoustic emissions, high frequencies showed a loss in the control group more compared to the experimental side (Wilcoxon signed-rank test). Conclusion ITD functions less effectively at higher frequencies because the basal turn of the cochlea is more susceptible to cisplatin ototoxicity. ITD might have potential in the reduction of cisplatin-induced hearing loss.

OBJECTIVE: To study effects of chemoradiation therapy on hearing in patients with malignancy of head and neck.
METHODS: Patients receiving drugs other than cisplatin as well as those with any otology-related pathology or abnormalities were excluded from the study. Patients with primary biopsy-proven malignancy of the Nasopharynx, Oropharynx, Paranasal Sinuses, Oral Cavity, and Parotid with chemoradiation by cisplatin and different radiation modalities were all eligible. Areas of interest and OARs are indicated on CT images. All patients\' hearing was assessed using pure tone audiometry at the beginning of treatment, at its conclusion, and six months later. Variations in pure tone thresholds from baseline and CTCAE - Common Terminology Criteria for Adverse Events grading are related to cochlear dose.
RESULTS:  The study involves 75 patients. At cochlear dosage levels of more than 40 Gy, significant SNHL (>10 dB loss) is seen. Absolute PTA threshold values do not statistically differ from baseline to completion at any frequency. For 4000 and 8000 Hz, the absolute PTA threshold values differed from baseline to follow-up, but only for 8000 Hz was the difference statistically significant after six months of follow-up. Following treatment, 64% of patients had grade I CTCAE scoring and 16% and 12%, respectively, had otitis media with effusion and Eustachian tube dysfunction.
CONCLUSIONS:  The inner ear may be harmed in patients receiving radiation to the head and neck. Radiation-induced SNHL typically goes unreported in routine clinical practise because of its long-term nature. In the group of head and neck tumours with high-risk locations, nearly 90% of patients with SNHL were affected. Therefore, it\'s critical to reduce cochlear dosage in these patient populations. More investigation is needed to distinguish between cochlear and retro-cochlear types of sensorineural hearing loss.