Cochlear implantation in auditory neuropathy spectrum disorders: role of transtympanic electrically evoked auditory brainstem responses and serial neural response telemetry.

OBJECTIVE: To evaluate the utility of pre-operative transtympanic electrically evoked auditory brainstem responses and post-operative neural response telemetry in auditory neuropathy spectrum disorder patients. METHODS: Four auditory neuropathy spectrum disorder patients who had undergone cochlear implantation and used it for more than one year were studied. All four patients underwent pre-operative transtympanic electrically evoked auditory brainstem response testing, intra-operative and post-operative (at 3, 6 and 12 months after switch-on) neural response telemetry, and out-patient cochlear implant electrically evoked auditory brainstem response testing (at 12 months). RESULTS: Patients with better waveforms on transtympanic electrically evoked auditory brainstem response testing showed superior performance after one year of implant use. Neural response telemetry and electrically evoked auditory brainstem response measures improved in all patients. CONCLUSION: Inferences related to cochlear implantation outcomes can be based on the waveform of transtympanic electrically evoked auditory brainstem responses. Robust transtympanic electrically evoked auditory brainstem responses suggest better performance. Improvements in electrically evoked auditory brainstem responses and neural response telemetry over time indicate that electrical stimulation is favourable in auditory neuropathy spectrum disorder patients. These measures provide an objective way to monitor changes and progress in auditory pathways following cochlear implantation.

The Role of Chimeric Antigen Receptor-T Cell Therapy in the Treatment of Hematological Malignancies: Advantages, Trials, and Tribulations, and the Road Ahead.

Immunotherapy is the upcoming trend in cancer treatment. Traditional cancer treatment methods include surgical resection, radiotherapy, chemotherapy, small molecule targeted drugs, monoclonal antibodies, and hematopoietic stem cell transplantation (HSCT). Surgical resection is useful for early-stage patients but not for metastatic cancer cells; radiotherapy and chemotherapy are more common but produce substantial damage to normal tissues and have poor selectivity. Targeted drugs, including monoclonal antibodies, have better comprehensive efficacy but can also encourage gene mutation of tumor cells and drug tolerance. HSCT is effective, but choosing a donor is often difficult, and the graft is also prone to rejection. Thus, chimeric antigen receptor (CAR)-T cell therapy, a form of cellular/adoptive immunotherapy, is at the forefront of cancer therapy treatments due to its sustained remission, fewer side effects, and a better quality of life. CAR-T cell therapy involves genetically modifying the T cells and multiplying their numbers to kill cancer cells. This review article gives an insight into how the CAR-T cells have evolved from simple T cells with modest immune function to genetically engineered robust counterparts that brought great hope in the treatment of hematological malignancies. Much research has been undertaken during the past decade to design and deliver CAR-T cells. This has led to successful outcomes in leukemias, lymphomas, and multiple myeloma, paving the way for expanding CAR therapy. Despite tremendous progress, CAR-T cell therapies are faced with many challenges. Areas for improvement include limited T cell persistence, tumor escape, immunosuppressive components in the tumor microenvironment, cancer relapse rate, manufacturing time, and production cost. In this manuscript, we summarize the innovations in the design and delivery of CAR technologies, their applications in hematological malignancies, limitations to its widespread application, latest developments, and the future scope of research to counter the challenges and improve its effectiveness and persistence.

Cardiovascular Manifestations in Inflammatory Bowel Disease: A Systematic Review of the Pathogenesis and Management of Pericarditis.

Inflammatory bowel disease (IBD) is a chronic condition of the bowel that can be further categorized into ulcerative colitis and Crohn's disease. Rarely, this condition can be associated with pericarditis, which can be an extraintestinal manifestation of the disease or drug-induced. This review aims to determine the pathogenesis and management of pericarditis in IBD. In this review, the goal is to elucidate the pathogenesis of pericarditis in IBD and determine if pericarditis is an extraintestinal manifestation of IBD or a complication of current drug therapy used to manage IBD. Additionally, this review intends to explain the first-line management of pericarditis in IBD and explore the role of biologicals in attenuating pericarditis. An electronic search was conducted to identify relevant reports of pericarditis in IBD, and a quality assessment was conducted to identify high-quality articles according to the inclusion criteria. Full-text articles from inception to November 2020 were included, while non-English articles, gray literature, and animal studies were excluded. The majority of studies suggest that pericarditis arises as a complication of drug therapy by 5-aminosalicylic acid derivatives such as sulfasalazine, mesalamine, and balsalazide, and it occurs due to IgE-mediated allergic reactions, direct cardiac toxicity, cell-mediated hypersensitivity reactions, and humoral antibody response to therapy. Drug cessation or the initiation of a corticosteroid regimen seems to be the most effective means of managing pericarditis in IBD due to drug therapy or an extraintestinal manifestation.

The Importance of Sphingosine Kinase in Breast Cancer: A Potential for Breast Cancer Management.

Breast cancer management includes a combination of surgery, radiation therapy, and chemotherapy. While this management has proven effective, it is not perfect. To expand the umbrella of management to resistant breast cancer tumors, researchers have explored the idea of sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) as a potential target for treatment. In this article, we review the mechanism of the sphingosine kinase/sphingosine-1-phosphate (SphK/S1P) axis along with its effect on the tumor microenvironment (TME) and compounds that have been studied inhibiting the SphK/S1P axis. We searched for relevant articles in the last five years in Medline and PubMed Central. Inclusion criteria, exclusion criteria, and quality checklists were applied to identify the most relevant articles. We compiled the information that has been summarized in the respective tables and figures provided in this review. The metabolism of sphingolipids was summarized, followed by the SphK/S1P upregulation in breast cancer cells. The variety of effects by upregulation of SphK led to an increase in inflammation, growth, and metastasis in breast cancer tumors. The increase in S1P also impacted the TME, including the cells and surrounding tissue, allowing the breast tumors to thrive. The final point made was a summary of the compounds and drugs that inhibited the SphK/S1P axis. They have proven their effectiveness and show even greater efficacy in combination with docetaxel and doxorubicin in preclinical studies. In conclusion, what is known about the SphK/S1P axis within breast cancer cells is immense but incomplete as we summarize what is known so far. Having a complete picture will allow a faster transition to application in the clinical field but clinical trials have not commenced as of yet.

An unusual case of ear mould impression material as a foreign body in the middle ear: case report.

BACKGROUND: The occurrence of retained ear mould impression material is rare and can lead to complications. The current case report describes one such complication, where the silicone impression material used to take the impression of the ear canal flowed into the middle ear through the pre-existing tympanic membrane perforation. Five days later, the patient presented with worsened hearing and blood-tinged discharge from the ear. Ear microscopy revealed a greenish foreign body in the middle ear. CASE REPORT: The foreign body was removed by tympanotomy and the perforation repaired using a temporalis fascia graft. A hearing aid was prescribed after ensuring that the perforation had healed. CONCLUSION: It is essential that the audiologist perform a basic otological examination before prescribing a hearing aid and preparing an ear mould. A clinical approach algorithm for audiologists, for prior to taking an impression, is suggested.

Assessment of quality of life outcomes with the Glasgow Children's Benefit Inventory following cochlear implantation in children.

BACKGROUND: This study investigated health-related quality of life outcomes for children with cochlear implants in India using the Glasgow Children's Benefit Inventory questionnaire. Cochlear implantation is associated with improved language outcomes. Some studies show this gives higher quality of life after implantation. Previous research demonstrates that India presents unique circumstances that impact perspectives regarding cochlear implantation. METHOD: Children (aged under 18 years) who had undergone cochlear implantation were recruited from Vani Pradan Kendra, an organisation for individuals with hearing loss based in Bangalore, India. Demographic data including age, sex, duration of hearing loss and age at implant were collected, and the children's parents or caregivers completed the Glasgow Children's Benefit Inventory questionnaire. RESULTS: Sixty-nine children (mean age: 8.0 ± 3.89 years) were recruited, and all reported improved quality of life after cochlear implantation. There was no effect of age, gender or education on reported benefits. However, a younger age at implant and longer experience with an implant were associated with greater quality of life improvements. CONCLUSION: Cochlear implantation leads to improved quality of life, with greater improvements associated with earlier implantation. This supports early intervention in children with profound hearing loss.

Performance on a 1-week delayed recall task is associated with medial temporal lobe structures in neurologically normal older adults.

OBJECTIVE: Traditional episodic memory tests employ a delayed recall length ranging from 10 to 30 min. The neurobiological process of memory consolidation extends well beyond these time intervals, however, raising the possibility that these tests might not be fully sensitive to the subtle neurocognitive changes found in early disease or age-related decline. We aimed to determine the sensitivity of a 1-week delayed recall paradigm to medial temporal lobe (MTL) structure among neurologically normal older adults. METHODS: One hundred and forty functionally intact, older adults (mean age = 75.8) completed a story recall test in which participants learned to 90% criterion. Recall was tested after 30-min and 1-week. Participants also completed a standardized list learning task with a 20-min delay (n = 129) and a structural brain MRI. The MTL, including the parahippocampal gyrus, hippocampus, and entorhinal, was our primary region of interest. RESULTS: Controlling for age, education, gender and total intracranial volume, the standard 20- and 30-min recalls showed no significant relationship with MTL. In contrast, 1-week recall was uniquely associated with MTL structure (partial r = .24, p = .006), specifically entorhinal (partial r = .27; p = .001) and hippocampal (partial r = .21, p = .02) volumes. CONCLUSION: Memory paradigms that utilize 1-week delays are more sensitive than standard paradigms to MTL volumes in neurologically normal older adults. Longer delay periods may improve detection of memory consolidation abilities associated with age-related, and potentially pathological, neurobehavioral change.

Is "Learning" episodic memory? Distinct cognitive and neuroanatomic correlates of immediate recall during learning trials in neurologically normal aging and neurodegenerative cohorts.

Although commonly interpreted as a marker of episodic memory during neuropsychological exams, relatively little is known regarding the neurobehavior of "total learning" immediate recall scores. Medial temporal lobes are clearly associated with delayed recall performances, yet immediate recall may necessitate networks beyond traditional episodic memory. We aimed to operationalize cognitive and neuroanatomic correlates of total immediate recall in several aging syndromes. Demographically-matched neurologically normal adults (n=91), individuals with Alzheimer's disease (n=566), logopenic variant primary progressive aphasia (PPA) (n=34), behavioral variant frontotemporal dementia (n=97), semantic variant PPA (n=71), or nonfluent/agrammatic variant PPA (n=39) completed a neurocognitive battery, including the CVLT-Short Form trials 1-4 Total Immediate Recall; a majority subset also completed a brain MRI. Regressions covaried for age and sex, and MMSE in cognitive and total intracranial volume in neuroanatomic models. Neurologically normal adults demonstrated a heterogeneous pattern of cognitive associations with total immediate recall (executive, speed, delayed recall), such that no singular cognitive or neuroanatomic correlate uniquely predicted performance. Within the clinical cohorts, there were syndrome-specific cognitive and neural associations with total immediate recall; e.g., semantic processing was the strongest cognitive correlate in svPPA (partial r=0.41), while frontal volumes was the only meaningful neural correlate in bvFTD (partial r=0.20). Medial temporal lobes were not independently associated with total immediate recall in any group (ps>0.05). Multiple neurobehavioral systems are associated with "total learning" immediate recall scores that importantly differ across distinct clinical syndromes. Conventional memory networks may not be sufficient or even importantly contribute to total immediate recall in many syndromes. Interpreting learning scores as equivalent to episodic memory may be erroneous.

Delay in the Provision of Antiretroviral Therapy to HIV-infected TB Patients in Nigeria.

BACKGROUND: Nigeria has a high burden of HIV and tuberculosis (TB). To reduce TB-associated morbidity and mortality, the World Health Organization recommends that HIV-positive TB patients receive antiretroviral therapy (ART) within eight weeks of TB treatment initiation, or within two weeks if profoundly immunosuppressed (CD4<50 cell/µL). METHODS: TB and HIV clinical records from facilities in two Nigerian states between October 1st, 2012 and September 30th, 2013 were retrospectively reviewed to assess uptake and timing of ART initiation among HIV-positive TB patients. Healthcare workers were qualitatively interviewed to assess TB/HIV knowledge and barriers to timely ART. RESULTS: Data were abstracted from 4,810 TB patient records, of which 1,249 (26.0%) had HIV-positive or unknown HIV status documented, and the 574 (45.9%) HIV-positive TB patients were evaluated for timing of ART uptake relative to TB treatment. Among 484 (84.3%) HIV-positive TB patients not already on ART, 256 (52.9%, 95% CI: 45.0-60.8) were not initiated on ART during six months of TB treatment. 30.0% of 273 patients with a known CD4≥50cells/µL started ART within eight weeks, and 14.8% of 54 patients with a known CD4<50cells/µL started within the recommended two weeks. Only 42% of health workers interviewed reported knowing to interpret guidelines on when to initiate ART in HIV-positive TB patients based on CD4 cell count results. CD4 cell count significantly predicted timely ART uptake. CONCLUSION: A large proportion of HIV-positive TB patients were not initiated on ART early or even at all during TB treatment. Retraining of staff, and interventions to strengthen referral systems should be implemented to ensure timely provision of ART among HIV-positive TB patients in Nigeria.

Development of low fat potato chips through microwave processing.

Since snacks high in fats are known to be a significant source of fat and energy intake, these have been put in high dietary restraint category. Therefore, an attempt was made to process potato chips through microwave processing without incorporation of any oil in potato chips. Microwave processing of potato chips was done using microwave power varying from 180 to 600 W using constant sample size. Among eleven different drying models, Parabolic model was found to be the best fit through non-linear regression analysis to illustrate drying kinetics of potato chips. The structural, textural and colour attributes of microwaved potato chips were similar to commercial fried potato chips. It was found that at 600 W after 2.5-3.0 min of processing, potato chips gained the fracturability and crispiness index as that of commercial fried chips. Microwave processing was found suitable for processing of potato chips with low fat content (~3.09 vs 35.5 % in commercial preparation) and with acceptable sensory scores (≥7.6 on 9.0 point on hedonic scale vs 8.0 of control preparation).

Facile synthesis of pristine graphene-palladium nanocomposites with extraordinary catalytic activities using swollen liquid crystals.

Amazing conductivity, perfect honeycomb sp(2) arrangement and the high theoretical surface area make pristine graphene as one of the best materials suited for application as catalyst supports. Unfortunately, the low reactivity of the material makes the formation of nanocomposite with inorganic materials difficult. Here we report an easy approach to synthesize nanocomposites of pristine graphene with palladium (Pd-G) using swollen liquid crystals (SLCs) as a soft template. The SLC template gives the control to deposit very small Pd particles of uniform size on G as well as RGO. The synthesized nanocomposite (Pd-G) exhibited exceptionally better catalytic activity compared with Pd-RGO nanocomposite in the hydrogenation of nitrophenols and microwave assisted C-C coupling reactions. The catalytic activity of Pd-G nanocomposite during nitrophenol reduction reaction was sixteen times higher than Pd nanoparticles and more than double than Pd-RGO nanocomposite. The exceptionally high activity of pristine graphene supported catalysts in the organic reactions is explained on the basis of its better pi interacting property compared to partially reduced RGO. The Pd-G nanocomposite showed exceptional stability under the reaction conditions as it could be recycled upto a minimum of 15 cycles for the C-C coupling reactions without any loss in activity.

Clinical and epidemiological study of EGFR mutations and EML4-ALK fusion genes among Indian patients with adenocarcinoma of the lung.

BACKGROUND: Mutation in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) is a common feature observed in lung adenocarcinoma. A fusion gene between echinoderm microtubule-associated protein-like 4 (EML4) and the intracellular domain of anaplastic lymphoma kinase (ALK), named EML4-ALK, has been identified in a subset of non-small-cell lung cancer (NSCLC) tumors. The objective of this study was to determine the prevalence of EGFR mutations and EML4-ALK fusions in Indian patients with NSCLC (adenocarcinoma) as well as evaluate their clinical characteristics. PATIENTS AND METHODS: Patients with NSCLC, adenocarcinoma histology, whose tumors had been tested for EGFR mutational status, were considered for this study. ALK gene rearrangement was detected by fluorescence in situ hybridization using the Vysis ALK Break Apart Rearrangement Probe Kit. ALK mutation was tested in samples that were negative for EGFR mutation. RESULTS: A total of 500 NSCLC adenocarcinoma patients were enrolled across six centers. There were 337 (67.4%) men and 163 (32.6%) women with a median age of 58 years. One hundred and sixty-four (32.8%) blocks were positive for EGFR mutations, whereas 336 (67.2%) were EGFR wild-type. Of the 336 EGFR-negative blocks, EML4-ALK fusion gene was present in 15 (4.5%) patients, whereas 321 (95.5%) tumors were EML4-ALK negative. The overall incidence of EML4-ALK fusion gene was 3% (15/500). CONCLUSION: The incidence of EGFR mutations (33%) in this Indian population is close to the reported incidence in Asian patients. EML4-ALK gene fusions are present in lung adenocarcinomas from Indian patients, and the 3% incidence of EML4-ALK gene fusion in EGFR mutation-negative cases is similar to what has been observed in other Western and Asian populations. The mutual exclusivity of EML4-ALK and EGFR mutations suggests implementation of biomarker testing for tumors harboring ALK rearrangements in order to identify patients that can benefit from newer targeted therapies.

Hearing results of 1145 stapedotomies evaluated with Amsterdam hearing evaluation plots.

AIMS: To evaluate the hearing results of a large series of primary stapedotomies, according to American Academy of Otolaryngology, Head and Neck Surgery guidelines and Amsterdam hearing evaluation plots. STUDY DESIGN: Retrospective chart review. METHODS: The charts for 1369 consecutive stapedotomy cases were reviewed; 1145 cases of primary stapedotomy were included. Raw data from the audiometric database were evaluated using Amsterdam hearing evaluation plots. The effect on outcomes of using different audiological parameters was analysed. RESULTS: A significant improvement was demonstrated in mean post-operative air conduction and speech reception thresholds, with no change in bone conduction. Air-bone gap closure of 10 dB or more was achieved in 82 per cent of cases. A 'dead ear' occurred in one patient (0.1 per cent). CONCLUSION: This study reports the largest series of primary stapedotomies evaluated with Amsterdam hearing evaluation plots. This method enables visual identification of successful and unfavourable results, providing more accurate and detailed presentation of surgical outcomes.

Integrative analysis reveals 53BP1 copy loss and decreased expression in a subset of human diffuse large B-cell lymphomas.

p53-Binding protein 1 (53BP1) encodes a critical checkpoint protein that localizes to sites of DNA double-strand breaks (DSBs) and participates in DSB repair. Mice that are 53bp1 deficient or hemizygous have an increased incidence of lymphoid malignancies. However, 53BP1 abnormalities in primary human tumors have not been described. By combining high-density single nucleotide polymorphism (HD SNP) array data and gene expression profiles, we found 9 of 63 newly diagnosed human diffuse large B-cell lymphomas (DLBCLs) with single copy loss of the chromosome 15q15 region including the 53BP1 locus; these nine tumors also had significantly lower levels of 53BP1 transcripts. 53BP1 single copy loss found with the HD SNP array platform was subsequently confirmed by fluorescence in situ hybridization. These studies highlight the role of 53BP1 copy loss in primary human DLBCLs and the value of integrative analyses in detecting this genetic lesion in human tumors.

Anterior inferior cerebellar artery syndrome: fact or fiction.

A prospective analysis of patients referred by Otolaryngologists from a tertiary hospital for detailed assessment of the posterior cranial fossa was undertaken. The objectives were to evaluate radiological characteristics of the anterior inferior cerebellar artery (AICA) within the cerebellopontine angle (CPA) and the internal auditory canal (IAC), and to correlate these characteristics with ipsilateral auditory symptoms. Three hundred and thirty-two consecutive adult patients who presented with unilateral auditory symptoms were studied. All patients were referred by the Department of Otolaryngology at City Hospital, Birmingham, from October 1999 to October 2001. Magnetic resonance imaging (MRI) with three-dimensional Fourier Transformation Constructive Interference in Steady State (3D FT-CISS) was the imaging strategy used to investigate each patient. Six hundred and sixty-four sides were studied and the AICA loop was identified in all patients. Using a simple anatomical classification to type the loops: there were 412 type I loops (within the CPA), 202 type II loops (at the porus acousticus, extending up to 50% of IAC) and 50 type III loops (extending beyond 50% of IAC). There was a statistically significant association with unilateral hearing loss and type II and III AICA loops (P = 0.016 and P = 0.006 respectively). An association between the presence of a large diameter vascular loop in the CPA and unilateral auditory symptoms was not found to be significant (P > 0.05).

Iatrogenic perforation in endoscopic stapling diverticulotomy for pharyngeal pouches.

In pharyngeal pouch surgery, the relatively new technique of endoscopic stapling diverticulotomy has a number of advantages over more traditional surgical treatments, such as Dohlman's procedure and open pouch excision, and now seems to be the procedure of choice. However, a number of iatrogenic perforations and deaths have been reported with this procedure. We present three cases of iatrogenic perforations occurring during endoscopic stapling of a pharyngeal pouch by different surgeons in our unit, and review the management, causes and prevention of this potentially life-threatening complication.

A retrospective review of pharyngeal pouch surgery in 56 patients.

We retrospectively reviewed 56 consecutive patients treated surgically for a pharyngeal pouch at our institution between 1989-1999 (10 years). Various surgical procedures were performed including endoscopic stapling (20), external excision (23), Dohlman's procedure (9), pouch inversion (3), cricopharyngeal myotomy only (3), and pouch suspension (1). There were 12 patients (18%) with complications and one mortality (2%). Four patients (7%) had a recurrence with 2 requiring further surgery. Over the latter 3 years, endoscopic stapling has emerged as the primary procedure for pharyngeal pouch surgery in our unit; with the advantages of an earlier commencement of diet and earlier hospital discharge. However, results were not as good as for external excisions. Furthermore, there were difficulties with 3 cases that commenced as endoscopic stapling procedures but had to he converted to external excisions due to inaccessibility in one case and iatrogenic perforations in two cases. As with any new technique, problems may occur and a learning curve has been appreciated in our unit. Surgeons must he prepared, with informed consent, to convert to an external approach should difficulties arise during endoscopic stapling. Elderly and frail patients who are at risk from a general anaesthetic may benefit from endoscopic stapling. External excision of pharyngeal pouches may be more appropriate in the young, the medically fit, and when malignancy is a concern.

Minimum dataset for recording myringotomy and ventilation tube insertion.

A minimum dataset for recording of findings during myringotomy and ventilation tube insertion for cases of otitis media with effusion is presented. With increasing pressures on surgeons to audit existing practices and hence improve standards of health care, it is appropriate to produce such a set of guidelines for a surgery that is frequently performed world-wide. We believe that the data presented is not too exhaustive and can be readily incorporated into the operative notes.

Maffucci's syndrome: clinical and radiological features of a rare condition.

Maffucci's syndrome is a rare congenital non-inherited condition, characterized by multiple enchondromata, cutaneous haemangiomata and more recently spindle-cell haemangioma-endotheliomata. It is associated with an increased risk of malignancy including intracranial chondrosarcomas. Early diagnosis is crucial; screening patients with Ollier's disease is recommended. The treatment of choice for these intracranial cartilaginous tumours is complete surgical excision but this is often difficult to achieve due to difficult access and relationships with neurovascular structures. An alternative treatment is proton-beam therapy. We report a case of Maffucci's syndrome; illustrating the typical clinical and radiological features as well as the known complications of the condition.