Mastoid cavity obliteration using bone pâté versus bioactive glass granules in the management of chronic otitis media (squamous disease): a prospective comparative study.

OBJECTIVE: To compare the efficacy of bone pâté versus bioactive glass in mastoid obliteration. METHOD: This randomised parallel groups study was conducted at a tertiary care centre between September 2017 and August 2019. Sixty-eight patients, 33 males and 35 females, aged 12-56 years, randomly underwent single-stage canal wall down mastoidectomy with mastoid obliteration using either bone pâté (n = 35) or bioactive glass (n = 33), and were evaluated 12 months after the operation. RESULTS: A dry epithelised cavity (Merchant's grade 0 or 1) was achieved in 65 patients (95.59 per cent). Three patients (4.41 per cent) showed recidivism. The mean air-bone gap decreased to 16.80 ± 4.23 dB from 35.10 ± 5.21 dB pre-operatively. The mean Glasgow Benefit Inventory score was 30.02 ± 8.23. There was no significant difference between the two groups in these outcomes. However, the duration of surgery was shorter in the bioactive glass group (156.87 ± 7.83 vs 162.28 ± 8.74 minutes; p = 0.01). CONCLUSION: The efficacy of both materials was comparable.

Multiregion whole-exome sequencing of matched primary and metastatic tumors revealed genomic heterogeneity and suggested polyclonal seeding in colorectal cancer metastasis.

BACKGROUND: Distant metastasis accounts for 90% of deaths from colorectal cancer (CRC). Genomic heterogeneity has been reported in various solid malignancies, but remains largely under-explored in metastatic CRC tumors, especially in primary to metastatic tumor evolution. PATIENTS AND METHODS: We conducted high-depth whole-exome sequencing in multiple regions of matched primary and metastatic CRC tumors. Using a total of 28 tumor, normal, and lymph node tissues, we analyzed inter- and intra-individual heterogeneity, inferred the tumor subclonal architectures, and depicted the subclonal evolutionary routes from primary to metastatic tumors. RESULTS: CRC has significant inter-individual but relatively limited intra-individual heterogeneity. Genomic landscapes were more similar within primary, metastatic, or lymph node tumors than across these types. Metastatic tumors exhibited less intratumor heterogeneity than primary tumors, indicating that single-region sequencing may be adequate to identify important metastasis mutations to guide treatment. Remarkably, all metastatic tumors inherited multiple genetically distinct subclones from primary tumors, supporting a possible polyclonal seeding mechanism for metastasis. Analysis of one patient with the trio samples of primary, metastatic, and lymph node tumors supported a mechanism of synchronous parallel dissemination from the primary to metastatic tumors that was not mediated through lymph nodes. CONCLUSIONS: In CRC, metastatic tumors have different but less heterogeneous genomic landscapes than primary tumors. It is possible that CRC metastasis is, at least partly, mediated through a polyclonal seeding mechanism. These findings demonstrated the rationale and feasibility for identifying and targeting primary tumor-derived metastasis-potent subclones for the prediction, prevention, and treatment of CRC metastasis.

[Discontinuation or tapering strategies of biologics in rheumatoid arthritis in remission]. / Stratégies d'arrêt ou de réduction des biomédicaments dans la polyarthrite rhumatoïde en rémission.

The arrival of new drugs and new therapeutic strategies allowed to reach sustained remission in an increasing number of patients with rheumatoid arthritis. The study of biologic disease-modifying anti-rheumatic drugs (bDMARDs) adaptation strategies is a need to optimize the benefit/risk balance and cost/effectiveness ratio of these molecules. Current recommendations such as EULAR 2016 propose tapering bDMARDs, especially when combined with a csDMARD, when the patient is in remission after stopping persistent glucocorticoids. The analysis of literature comprising 22 studies shows that a bDMARD adaptation is possible in established rheumatoid arthritis when clinico-biological and ultrasound remission is maintained over six months. Priority should be given to a progressive tapering strategy doses controlled by disease activity while maintaining "tight control" to identify and effectively treat a relapse, a retreatment being usually favorable.

Caregiver's perception of epilepsy treatment, quality of life and comorbidities in an international cohort of CDKL5 patients.

OBJECTIVE: CDKL5 is a genetic condition associated with drug-resistant epilepsy and intellectual disability. There is limited information on its natural history. We investigated the natural history, complications, and the effectiveness of current treatment strategies. METHODS: This study was conducted in conjunction with the CDKL5-UK Charity, with patients recruited from the USA and Europe. Online questionnaires were completed by parents/carers and included information relating to demographics, growth, development, epilepsy, comorbid conditions, and efficacy and side effects of antiepileptic treatments. RESULTS: Thirty-nine of the 44 patients were female. Median age was five years (range five months to 31 years), and all had a history of epilepsy. All patients had developmental delay, with 4/21 able to run and 4/22 able to climb. Gastrointestinal problems were reported in 31/43. Cardiac arrhythmia was seen in 11/29. Over one-quarter of the patients had tried ten or more antiepileptic medications. Vigabatrin was reportedly the most effective AED (antiepileptic drug) in 12/23; clobazam (most effective in 6/14); sodium valproate (most effective in 5/27), and levetiracetam (most effective in 3/27). VNS (Vagal Nerve Stimulator) was reported to be effective in 9/12. One year after VNS insertion, 9/12 reported improved (QoL), and there were improvements in mood, school achievement and concentration in (9/11). The ketogenic diet was considered effective and to have improved QoL in (12/23). CONCLUSION: Vigabatrin appears to be more effective than other AEDs. VNS and ketogenic diet are also relatively effective. Gastrointestinal and cardiovascular system complications are common. The results may help to guide management of epilepsy in CDKL5. It highlights a possible link between CDKL5 and potentially treatable life-threatening complications such as cardiac arrhythmia. More research in this area may help us develop a more systematic approach to treating these patients. HIPPOKRATIA 2017, 21(3): 130-135.

Chronic Recurrent Multifocal Osteomyelitis: A Diagnostic Dilemma: A Case Report and Review of the Literature.

CASE: Chronic recurrent multifocal osteomyelitis, a misnomer in itself, is a rare disorder that presents infrequently to orthopaedic units. The differential diagnosis is wide, including neoplastic lesions and infection, which may lead to unnecessary interventional and surgical procedures. We present a case that exhibited the hallmark features of this condition-recurrent, multifocal, aseptic osteitis in a 9-year-old girl-and our rationalized management including imaging, nonsteroidal anti-inflammatory drugs, and bisphosphonates. CONCLUSION: With increased awareness by orthopaedic surgeons, patients may be diagnosed and managed appropriately, enabling a benign course and limiting morbidity.

Hypoglycemia due to 3ß-Hydroxysteroid Dehydrogenase type II Deficiency in a Newborn.

BACKGROUND: 3ß-hydroxysteroid dehydrogenase type II deficiency results in decreased production of all three groups of adrenal steroids. Recurrent hypoglycemia as a presenting feature of this disorder has not been reported earlier. CASE CHARACTERISTICS: A genotypically and phenotypically normal female newborn delivered by in-vitro fertilization presenting with recurrent hypoglycemia. Primary adrenal insufficiency with insignificant mineralocorticoid deficiency and slightly elevated levels of 17-hydro-xyprogesterone, dehydroepian-drosterone sulphate and testosterone. OUTCOME: Successfully managed only with corticosteroid replacement. MESSAGE: Congenital adrenal hyperplasia can rarely cause recurrent hypoglycemia in newborns.

Ocular infections caused by Candida species: Type of species, in vitro susceptibility and treatment outcome.

PURPOSE: To report clinical and microbiological profile of patients with ocular candidiasis. MATERIALS AND METHODS: Patients with ocular candidiasis were retrospectively identified from microbiology records. Significant isolates of Candida species were identified by Vitek 2 compact system. Minimum inhibitory concentration (MIC) of antifungal agents such as amphotericin B, itraconazole, voriconazole, fluconazole and caspofungin was determined by E test and of natamycin by microbroth dilution assay. Data on treatment and outcome were collected from medical records. RESULTS: A total of 42 isolates of Candida were isolated from patients with keratitis-29, endophthalmitis-12 and orbital cellulitis-1. The most common species isolated was Candida albicans (12-keratitis, 4-endophthalmitis, 1-orbital cellulitis). All except one isolate were susceptible to amphotericin B. MIC of caspofungin was in the susceptible range in 28 (96.5%) corneal isolates while 12 out of 29 (41.3%) corneal isolates were sensitive to fluconazole. Resistance to voriconazole was seen in four corneal isolates. All isolates were susceptible to natamycin and all except two isolates were resistant or susceptible dose-dependent to itraconazole. Outcome of healed ulcer was achieved in 12/18 (66.6%) patients treated medically, while surgical intervention was required in 11 patients. Among the isolates from endophthalmitis patients, 11/12 were susceptible to amphotericin B, 6/12 to voriconazole and all to natamycin. Ten out of 11 patients (one patient required evisceration) with endophthalmitis were given intravitreal amphotericin B injection with variable outcome. CONCLUSIONS: Ocular candidiasis needs early and specific treatment for optimal results. Candida species continue to be susceptible to most commonly available antifungals including amphotericin B, voriconazole and natamycin.

In vitro and in vivo evaluation of 2-chloroethylnitrosourea derivatives as antitumor agents.

AIM: To evaluate potential of Naphthal-NU, Napro-NU and 5-Nitro-naphthal-NU, 2-chloroethylnitrosourea compounds with substituted naphthalimide in the pre-clinical studies. MATERIALS AND METHODS: In vitro cytotoxicity of three nitrosoureas was determined in human and mouse tumor cell lines by MTT assays. In vivo anti-tumor potential was evaluated in Sarcoma-180 (S-180) and Ehrlich's carcinoma (EC) solid tumors. Apoptosis in S-180 cells was analyzed by using Annexin V-Propidium Iodide (PI). Histological analysis of liver and kidney was performed at optimum dose (50 mg/kg). Expression status of CD4(+), CD8(+) and CD25(+) cells in treated mouse were also examined. RESULTS: Significant tumor growth retardation by the compounds was noted in early and advanced disease groups, as the life span of drug treated mice increased considerably. Drug induced killing was observed by induction of apoptosis. Naphthal-NU and 5-Nitro-naphthal-NU were effective to normalize the tumor induced structural abnormalities of liver and kidney. The compounds have no immunotoxic effect on CD4(+) and CD8(+) T cells and down regulate CD4(+)CD25(+) regulatory T cells. CONCLUSION: Overall data holds promise for the antitumor activity with lower toxicity of the compounds that can be utilized for the treatment of human malignant tumors.

The psychosocial impact of hearing aids in children with otitis media with effusion.

BACKGROUND: In children, otitis media with effusion is treated using grommets or hearing aids. Parents considering treatment options express concerns regarding the psychosocial impact of hearing aids in terms of self-esteem and bullying. This study assessed the psychosocial impact of hearing aid use. METHODS: A cross-sectional study was undertaken comparing hearing aid users to non hearing aid users with regard to their attitudes towards hearing aids. All subjects, who had been diagnosed with otitis media with effusion, were aged less than 16 years, were without disability and attended mainstream schools. A questionnaire was designed and utilised. RESULTS: The study comprised 47 children with hearing aids and 50 with grommets. Significant between-group differences (p < 0.05) were noted with regard to perceptions related to bullying, feelings of inadequacy and embarrassment. The overall negative perceptions of non hearing aid users were not reported by hearing aid users. CONCLUSION: Children with hearing aids do not suffer from bullying or low self-esteem to the extent perceived by parents. This information is useful for informed decisions regarding treatment of otitis media with effusion.

Communicating hydrocephalus in systemic lupus erythematosus.

BACKGROUND: Central nervous system involvement is common in systemic lupus erythematosus but hydrocephalus, especially in children, is rare. CASE CHARACTERISTICS: 6-year-old girl with systemic lupus erythematosus with nephritis, on treatment for four months prior to the presentation with features of raised intracranial pressure. OBSERVATION: Computed tomography revealed communicating hydrocephalus without any evidence of granulomatous lesion, infarction or thrombosis, with no features of lupus flare. Ventriculoperitoneal shunting provided symptomatic relief after failed medical management. MESSAGE: Hydrocephalus may be seen in systemic lupus erythematosus without tuberculosis or major vessel vasculitis.

Anaphylaxis: incidence, presentation, causes and outcome in patients in a tertiary-care hospital in Karachi, Pakistan.

BACKGROUND: Anaphylaxis is a potentially fatal condition requiring immediate resuscitation. Data regarding the epidemiology of anaphylaxis are limited and inconsistent. A reason for the variability was unavailability of a universally acceptable case definition till 2005. We reviewed cases using this new definition AIM: To review the incidence, clinical presentation, cause and outcome of anaphylaxis at a tertiary-care centre in a low-income country. DESIGN: Retrospective, case series METHODS: Chart review of all patients discharged from Aga Khan University Hospital between January 1988 and December 2012 (24 years) with anaphylaxis definition as per second National Institute of Allergy and Infection disease/Food Allergy and Anaphylaxis Network Symposium RESULTS: Total of 129 cases were found with mean age of 41.6 years (SD 18.8). Majority of patients had cutaneous features (76.7%), followed by respiratory (68.9%), cardiac (64.3%) and gastrointestinal (20.9%) symptoms, respectively. About 22.4% of patients had positive history for allergens out of which 31% (n = 9) were exposed to the same allergens. The common causes identified for anaphylaxis were drugs (60.5%), food (16.3%) and intravenous contrast (10.9%), respectively. Only 22.5% of cases received epinephrine as a part of their initial management. In four patients (3.1%) the cause of death was attributed to anaphylaxis. CONCLUSION: Anaphylaxis is a rare but life-threatening condition. Though cutaneous features are most common, their absence does not exclude the diagnosis. Drugs were the most common cause and epinephrine was not commonly used as first-line agent for its management.

Ultrasound-guided infraclavicular axillary vein cannulation: a useful alternative to the internal jugular vein.

BACKGROUND: Ultrasound (US) guidance reduces complications and increases accuracy during internal jugular vein (IJV) cannulation. The subclavian vein (SCV) is popular but is less amenable to US guidance. The axillary vein (AxV), a direct continuation of the SCV, is an alternative, but to date, experience with US is limited to small case series. METHODS: Retrospective procedural data were collected on 2586 sequential patients referred for insertion of tunnelled central venous access at a UK tertiary centre from 2004 to 2011. RESULTS: A total of 99.8% of patients tolerated the procedure with local anaesthesia ± sedation; six patients had general anaesthesia. Twenty-six (1%) patients had uncorrected coagulopathy or thrombocytopenia. A total of 2572 (99.5%) of patients were cannulated successfully: right AxV 1644 cases, left AxV 279, right IJV 547, left IJV 89, other techniques 13, and 14 (0.5%) cases failed. The initial site chosen was successful in 96%. In patients who previously underwent long-term cannulation, 93.3% of lines were sited easily. Forty-eight (1.9%) procedural complications occurred. CONCLUSIONS: In this large analysis of US-guided central venous access in a complex patient group, the majority of patients were cannulated successfully and safely. The subset of patients undergoing AxV cannulation demonstrated a low rate of complications. The AxV route of access appears to be a safe and effective alternative to the IJV.

A comparison of Rapydan® patch and Ametop® gel for venous cannulation.

Ametop(®) gel (4% tetracaine) is used to provide topical anaesthesia for venous cannulation. Rapydan(®) patch (7% lidocaine and 7% tetracaine) has been developed to provide topical anaesthesia by a different mechanism, that of heat assisted delivery. We compared the topical anaesthetic effect of these agents for venous cannulation. One hundred healthy adults undergoing day-case surgery were randomly assigned to receive either Rapydan (n = 50) or Ametop (n = 50) before venous cannulation. Pain on insertion was scored on a visual analogue scale between 0 and 100 (where 100 = unbearable pain). Median(IQR[range]) pain scores were not different between groups with 11 (5-20 [0-72]) for Rapydan and 10 (5-24 [0-95]) for Ametop (p = 0.63). Adequate topical anaesthesia was achieved in over 90% of patients in both groups. Rapydan produces topical anaesthesia comparable with Ametop for venous cannulation.

Mortality from childhood stroke in England and Wales, 1921-2000.

OBJECTIVE: Stroke is an important but under-recognised cause of childhood mortality. The authors aimed to describe the trends in mortality from childhood stroke in England and Wales between 1921 and 2000. DESIGN: The study searched the Office for National Statistics mortality database for the years 1921-2000 using appropriate, previously validated International Classification of Diseases codes. Mortality rates were analysed by period of death, gender, age at death, birth cohort and stroke subtype. RESULTS: 6029 deaths from childhood stroke were found between 1921 and 2000. Analysis by period of death demonstrated an initial decline in mortality followed by a steep rise in the 1940s. Subsequently, rates declined from the late 1960s onwards. At all time points males had a higher mortality rate than females. Infants had a relatively high mortality rate (24.5 per million person years) but rates fell steeply in early childhood (2.5 per million person years at age 5-9 years) before rising again in late adolescence (7.5 per million person years at age 15-19 years). An increased rate was found for males at all ages (RR = 1.24, p<0.0001) but was greatest in infancy (RR = 1.45, p<0.0001). Haemorrhagic stroke accounted for 71% of stroke deaths. Birth cohort analysis showed a trend of declining mortality with each successive generation since the 1950s. CONCLUSIONS: This study describes characteristics and temporal changes in childhood stroke mortality in the 20(th) century. In particular, the higher mortality rates in males and infants, the importance of deaths from haemorrhagic stroke and the finding of a decline in birth cohort mortality since the 1950s provide aetiological insights.

Reducing the economic impact of carpal tunnel surgery.

A nurse-led carpal tunnel service was started in Leicester in 1999. Many developments in the service have been patient-driven. A large proportion of our patients are not salaried and many had expressed concerns about the amount of time taken off work after surgery. This therefore prompted us to encourage immediate hand function after surgery. Subsequently, in 494 patients studied prospectively, we have seen 93% of patients return to work by 2 weeks and 99% by 4 weeks. This has obvious benefits in terms of reducing loss of income. Furthermore there is potential for considerable economic savings.

Cerebral venous sinus thrombosis: a case series including thrombolysis.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) in children is associated with a high incidence of serious morbidity and mortality. The presenting features are variable. It can be diagnostically challenging and the optimal treatment is uncertain. AIM: To describe the features of a series of children with CVST treated in a single paediatric neurology centre and to discuss the role of local thrombolysis. METHODS: Electronic databases were searched using diagnostic labels and International Classification of Diseases (ICD) codes to identify children aged 1 month to under 17 years with CVST. Their records were reviewed. RESULTS: 21 children were identified over a period of 8.25 years with a median age of 7.1 years. The presenting symptoms included headache (15 children), vomiting (14 children) and visual disturbance (eight children). Signs found included papilloedema (16 children), fever (six children) and sixth nerve palsy (six children). The most common underlying condition was middle ear infection (13 children). All cases received unfractionated heparin and four severe cases received local pharmacological thrombolysis. 48% of cases had an adverse outcome (death, chronic intracranial hypertension, residual hemiparesis or sixth nerve palsy). DISCUSSION: CVST has non-specific presenting features and a high risk of significant morbidity. CVST is typically found in association with a predisposing condition. Although heparin is the mainstay of treatment, thrombolysis may reverse deterioration as seen in three cases in this series. However, there is insufficient evidence to recommend the routine use of thrombolysis at present.

Escheriosomes entrapped DNA vaccine co-expressing Cu-Zn superoxide dismutase and IL-18 confers protection against Brucella abortus.

In the present study, we evaluated prophylactic prospective of liposome based DNA vaccine co-expressing Cu-Zn superoxide dismutase (SOD) along with interleukin-18 (IL-18) against experimental murine brucellosis. The immunization schedule involves liposome-mediated delivery of pVsod (encoding SOD of Brucella abortus) and pVIL18-sod (encoding IL-18 of mouse and SOD of B. abortus) DNA constructs. The data highlight potential of Escherichia coli lipid liposome (escheriosome) based DNA delivery vehicle to induce SOD specific humoral and cellular immune responses in the immunized mice. The co-expression of SOD along with IL-18 ensued in higher lymphoproliferative response and IFN-gamma production in comparison to the group of animals that were immunized with free form of SOD-DNA. Antibody response developed upon immunization with both DNA vaccines was of IgG2a type mainly. The results of the present study show that co-expression of IL-18 along with SOD polarized the antigen specific immune responses toward Th-1 direction, a desirable feature to control intracellular pathogens.

Pre-emptive Novalung-assisted carbon dioxide removal in a patient with chest, head and abdominal injury.

A young man sustained traumatic lung, head and abdominal injuries. Despite mechanical ventilation, deteriorating respiratory function resulted in severe hypoxia and hypercapnia, with high P(a)co(2) compounding an already raised intracranial pressure (ICP). The Novalung was pre-emptively used without anticoagulation, prior to laparotomy, to remove carbon dioxide and to allow for cerebral and lung protective strategies. This facilitated control of ICP thereby limited possible secondary brain injury.