Optimal blocking screw placement for retrograde IM nail fixation of distal femur fracture: a standardized biomechanical study of "osteoporotic" synthetic bone.

PURPOSE: Intramedullary (IM) nail use for metaphyseal fracture management is problematic in long bones like the femur because the larger medullary cavity allows increased fracture motion and potentially increased implant failure and malunion/nonunion risk; Achieving effective distal femur fracture fixation is even more difficult in osteoporotic bone. Blocking screws to control IM nail movement are known to be effective for tibia fracture management. Few studies have evaluated IM nail and blocking screw use efficacy for distal femur fracture fixation in osteoporotic bone. METHODS: This study used an osteoporosis simulation synthetic bone model to evaluate retrograde IM nail fixation of a standardized non-comminuted, extra-articular distal femur fracture with and without blocking screws. The hypothesis was that use of one or two blocking screws would increase IM nail fixation stability as evidenced by greater peak IM nail load and lesser movement. A servohydraulic device under displacement control collected loading force versus movement deflection data. Shapiro-Wilk tests confirmed data normality. One-way analysis of variance and Tukey post hoc tests were used to compare condition specific loading force and movement differences. RESULT: In the coronal plane, blocking screw conditions displayed greater loading ranges (38.3 ± 2 vs. 19.1 ± 2 N, 100.5% difference) (p < 0.0001) and lesser movement (2.0 ± 0.3 vs. 6.86 ± 0.4 mm, 243% difference) (p < 0.0001). In the sagittal plane, the two blocking screw condition displayed a significantly greater loading magnitude (29.9 ± 6 vs. 20.8 ± 2.3 N, 43.8% difference) than the identical control condition without blocking screws (p = 0.018); however, movements were comparable (p = 0.82). Long-axis rotational loading failed to reveal load magnitude differences (p = 0.28); however, two different blocking screw conditions displayed decreased movement (1.32 ± 0.2 vs. 2.05 ± 0.3 mm, 53.8% difference) compared to other conditions (p ≤ 0.018). CONCLUSIONS: Use of one or two blocking screws on the medial and lateral sides of the IM nail decreased coronal plane movement in the intramedullary canal. Combining retrograde IM nail implantation with blocking screws reduced medial-lateral IM nail movement and increased fracture stability. These characteristics may help prevent fixation failure, malunion, and even nonunion in patients with a distal femur fracture in osteoporotic bone.

Inhibition of STEP61 ameliorates deficits in mouse and hiPSC-based schizophrenia models.

The brain-specific tyrosine phosphatase, STEP (STriatal-Enriched protein tyrosine Phosphatase) is an important regulator of synaptic function. STEP normally opposes synaptic strengthening by increasing N-methyl D-aspartate glutamate receptor (NMDAR) internalization through dephosphorylation of GluN2B and inactivation of the kinases extracellular signal-regulated kinase 1/2 and Fyn. Here we show that STEP61 is elevated in the cortex in the Nrg1+/- knockout mouse model of schizophrenia (SZ). Genetic reduction or pharmacological inhibition of STEP prevents the loss of NMDARs from synaptic membranes and reverses behavioral deficits in Nrg1+/- mice. STEP61 protein is also increased in cortical lysates from the central nervous system-specific ErbB2/4 mouse model of SZ, as well as in human induced pluripotent stem cell (hiPSC)-derived forebrain neurons and Ngn2-induced excitatory neurons, from two independent SZ patient cohorts. In these selected SZ models, increased STEP61 protein levels likely reflect reduced ubiquitination and degradation. These convergent findings from mouse and hiPSC SZ models provide evidence for STEP61 dysfunction in SZ.

Characterisation of an OCS-dependent severe asthma population treated with mepolizumab.

UNLABELLED: A subpopulation of patients with asthma treated with maximal inhaled treatments is unable to maintain asthma control and requires additional therapy with oral corticosteroids (OCS); a subset of this population continues to have frequent exacerbations. Alternate treatment options are needed as daily use of OCS is associated with significant systemic adverse effects that affect many body systems and have a direct association with the dose and duration of OCS use. We compared the population demographics, medical conditions and efficacy responses of the OCS-dependent group from the DREAM study of mepolizumab with the group not managed with daily OCS. TRIAL REGISTRATION NUMBER: NCT01000506.

The psychosocial and emotional experiences of cancer patients during the COVID-19 pandemic: A systematic review.

BACKGROUND: COVID-19 was declared a pandemic by the World Health Organization on March 11th, 2020. Global social lockdowns were instigated to reduce spread and prevent health-services from becoming overwhelmed. People having treatment for cancer are known to have heightened psychological/emotional burden. The combined impact of managing pandemic regulations alongside this may present additional burden. The purpose of this systematic review is to examine current evidence of the psychological and emotional impact of COVID-19 on people with cancer, early in the pandemic. METHODS: Five electronic databases were searched (Embase, Global Health, HMIC, PsychINFO, CINAHL) from September 2019 to October 2021. Qualitative, quantitative and mixed-method primary research studies exploring emotional and psychological impacts of COVID-19 on cancer patients, limited to English language, were included. Quality appraisal was conducted using the MMAT. RESULTS: Fifty-one papers, with 27,356 people from 21 countries treated for cancer, were included. 43 studies were quantitative with a survey method approach, six studies qualitative and four used a mixed methods design. MMAT score was mostly two or three. Four themes were identified: Emotional aspects and Quality of Life; Psychosocial aspects; Impact of COVID-19 on self; Impact of COVID-19 on cancer, with themes overlapping. CONCLUSION: Whilst emotional/psychological impacts such as anxiety, isolation, employment fears, and uncertainty about the future were potentially universal concerns early in the pandemic, they may have been particularly acute for people living with cancer and represent complex, overlapping factors. As COVID-19 continues to impact health-services and society, it is important to focus on any ongoing impact to the experience of cancer patients. Most of the studies reviewed used tools that do not provide deeper understanding of how and why emotional states of people with cancer were affected. Further qualitative work may reveal patterns of what was unique to cancer patients during the pandemic, compared to general populations.

Changes in striatal dopamine release, sleep, and behavior during spontaneous Δ-9-tetrahydrocannabinol abstinence in male and female mice.

Withdrawal symptoms are observed upon cessation of cannabis use in humans. Although animal studies have examined withdrawal symptoms following exposure to delta-9-tetrahydrocannabinol (THC), difficulties in obtaining objective measures of spontaneous withdrawal using paradigms that mimic cessation of use in humans have slowed research. The neuromodulator dopamine (DA) is affected by chronic THC treatment and plays a role in many behaviors related to human THC withdrawal symptoms. These symptoms include sleep disturbances that often drive relapse, and emotional behaviors like irritability and anhedonia. We examined THC withdrawal-induced changes in striatal DA release and the extent to which sleep disruption and behavioral maladaptation manifest during abstinence in a mouse model of chronic THC exposure. Using a THC treatment regimen known to produce tolerance, we measured electrically elicited DA release in acute brain slices from different striatal subregions during early and late THC abstinence. Long-term polysomnographic recordings from mice were used to assess vigilance state and sleep architecture before, during, and after THC treatment. We additionally assessed how behaviors that model human withdrawal symptoms are altered by chronic THC treatment in early and late abstinence. We detected altered striatal DA release, sleep disturbances that mimic clinical observations, and behavioral maladaptation in mice following tolerance to THC. Altered striatal DA release, sleep, and affect-related behaviors associated with spontaneous THC abstinence were more consistently observed in male mice. These findings provide a foundation for preclinical study of directly translatable non-precipitated THC withdrawal symptoms and the neural mechanisms that affect them.

Dysphonia--a rare early symptom of Ehlers--Danlos syndrome?

Ehlers-Danlos syndrome is a connective tissue disorder characterized by joint hypermobility, skin hyperextensibility and cutaneous fragility. It usually presents in young adults and is rarely diagnosed in children. Voice involvement in young children, to our knowledge, has not been reported in the literature. We present two cases with dysphonia from birth and an eventual diagnosis of Ehlers-Danlos syndrome. The syndrome and its relevance to voice pathology are discussed. We suggest that Ehlers-Danlos syndrome should be considered as an underlying diagnosis in atypical presentations of dysphonia in young children.

Analysis of intensive care admissions among paediatric obstructive sleep apnoea referrals.

Introduction The aim of this study was to identify the proportion of children referred to a paediatric tertiary referral centre who required admission to the paediatric intensive care unit (PICU) following surgery for obstructive sleep apnoea (OSA) and to establish risk factors for these admissions. Methods Retrospective review of case notes and the operative database was performed for all children undergoing adenotonsillectomy for sleep disordered breathing and OSA symptoms in Great Ormond Street Hospital over a 10-year period. Results Overall, 1,328 children underwent adenotonsillectomy for sleep disordered breathing and OSA. The mean age was 3.1 years (standard deviation [SD]: 1.7 years). A total of 37 (2.8%) were admitted to the PICU postoperatively (mean length of PICU stay: 1.2 days, standard deviation [SD]: 0.6 days) and 282 (21.2%) required nasopharyngeal airway (nasal prong) insertion intraoperatively. The mean length of stay on the ward following surgery was 1.4 days (SD: 0.8 days). Patients with severe OSA (apnoea-hypopnoea index [AHI] >10) and ASA (American Society of Anesthesiologists) grade ≥3 were more likely to require postoperative PICU admission (22/37 vs 381/1,291 [p<0.001] and 29/37 vs 660/1,291 [p=0.001] respectively). Severe OSA was also more common in children who required nasal prong insertion intraoperatively (186/282 vs 217/1,046, p<0.001). Conclusions Very few children referred to a paediatric tertiary referral centre actually require PICU admission following surgery. This may be in part due to the use of a nasopharyngeal airway in patients where postoperative obstruction is anticipated. In children with severe OSA (AHI >10) and an ASA grade of ≥3, nasopharyngeal airway insertion and potential admission to the PICU should be considered.

The Great Ormond Street Hospital paediatric cochlear implant programme 1992-2004. A review of surgical complications.

The authors present a review of surgical complications following cochlear implantation at Great Ormond Street Hospital, since inception of the programme in 1992 until June 2004. Complications are defined as major (resulting in re-operation, explantation, re-implantation or which resulted in permanent serious morbidity or mortality) or minor (where the implant was not threatened). A comparison of surgical complication rates is made both with an earlier study in the same institution and also with other cochlear implantation centres worldwide. The decrease in surgical complication rates is discussed along with the difficulties inherent in cochlear implantation in the paediatric population with coexisting medical complaints.

Safe balloon sizing for endoscopic dilatation of subglottic stenosis in children.

OBJECTIVES: To describe our experience and provide guidelines for maximum safe balloon sizes according to age in children undergoing balloon dilatation. METHOD: A retrospective review was conducted of children undergoing balloon dilatation for subglottic stenosis in a paediatric tertiary unit between May 2006 and February 2016. RESULTS: A total of 166 patients underwent balloon dilatation. Mean ( ± standard deviation) patient age was 4.5 ± 3.99 years. The median balloon size was 8 mm, the median balloon inflation pressure was 10 atm, and the mean balloon inflation time was 65.1 ± 18.6 seconds. No significant unexpected events occurred. The Pearson correlation co-efficient for the relationship between patient age and balloon size was 0.85 (p = 0.001), suggesting a strongly positive correlation. CONCLUSION: This study demonstrated that balloon dilatation is a safe procedure for airway stenosis. The results suggest using a balloon diameter that is equal to the outer diameter of the age-appropriate endotracheal tube +1 mm for the larynx and subglottis and +2 mm for the trachea.

The use of the Montgomery T-tube in difficult paediatric airways.

OBJECTIVE: We report our experience of using Montgomery T-tubes in children. METHOD: A retrospective review of medical records was performed. Data collected included particular clinical circumstances, the details of usage of the tube, and the eventual outcome. RESULTS: Between January 1999 and October 2003, our unit performed 293 tracheostomies, 76 laryngotracheal reconstructions and 31 other major airway procedures in children. 10 children have had a Montgomery T-tube inserted. Nine were boys. In eight cases, the T-tube was used because of severe granulations and subsequent fibrotic narrowing in the subglottis after laryngotracheal reconstruction surgery. These children had undergone between one and four major procedures prior to T-tube placement. In the other two cases, the T-tube was used to stent severe glottic and supraglottic stenosis (due to previous laser surgery for papillomas in one case and congenital ectodermal dysplasia in the other). At the time of T-tube placement the children were aged 2-18 years (median 8 years). The tube was initially fitted so as to protrude above the glottis in all cases. In one case, the T-tube was removed on the first post-operative day. One tube was removed after a week due to severe crusting. One tube blocked after 2 weeks. One child had re-stenosis in the supraglottis necessitating the placement of a T-tube with a longer upper limb. Two children have subsequently died from non-airway causes. Two children still have their T-tube in situ, one of whom is due to have it removed in the next few weeks. Six have been successfully decannulated and are well. CONCLUSIONS: The Montgomery T-tube provides a useful adjunct to the management of a small number of children with the most difficult airway problems. Its use can be problematic, however, and requires awareness of its specific complications. We have confined usage to complex stenoses where a reconstruction would be inappropriate, or (in one instance) to stent an unsupported larynx after revision reconstruction (tracheal resection).

The midfacial degloving approach to sinonasal tumours in children.

The midfacial degloving approach was originally described by Denker and Kahler in 1926 but has been little used in the paediatric population. The procedure allows access to benign and malignant lesions of the sinonasal region with the avoidance of an external scar. The advantages and application of this technique are presented in 9 paediatric patients, ranging from 3 months to 15 years of age with a mean follow-up of 7 months. Eight children had benign pathology. There were two juvenile angiofibromas, two nasal gliomas, one ossifying fibroma, one fibroma, one fibrous dysplasia and one benign myofibroblastic proliferation. One child had malignant disease in the form of recurrent embryonal rhabdomyosarcoma. All had excellent cosmetic results and no complications were encountered during follow-up.

Chondrodysplasia punctata: case report and review of audiological and ENT features.

Chondrodysplasia punctata is a term referring to a clinically heterogeneous group of bone and cartilage dysplasias which cause characteristic epiphyseal stippling. The condition can involve the ear, nose and throat in diverse ways at many levels. We present a case of X-linked brachytelephalangic chondrodysplasia punctata, which illustrates the features of this condition particularly relevant to the audiological physician, otolaryngologist and neonatologist.

Endocrine disorders among long-term survivors of childhood head and neck rhabdomyosarcoma.

PURPOSE: Head and neck rhabdomyosarcoma (HNRMS) survivors are at increased risk of developing pituitary dysfunction as an adverse event of radiotherapy. Our aim was to investigate the frequency and risk factors for pituitary dysfunction in these survivors. Secondly, we aimed to compare the prevalence of pituitary dysfunction between survivors treated with external beam radiation therapy (EBRT) and survivors treated with the ablative surgery, moulage technique after loading brachytherapy, and surgical reconstruction (AMORE) procedure. METHODS: Eighty HNRMS survivors treated in London (EBRT based) and Amsterdam (AMORE based: AMORE if feasible, otherwise EBRT) in the period 1990-2010 and alive ≥ 2 years post-treatment were evaluated. Survivors were evaluated in multidisciplinary late-effects clinics, with measurement of linear growth, determination of thyroid function, and growth hormone parameters. Additional data, such as baseline characteristics, anthropometrics, pubertal stage, and the results of additional laboratory investigations, were retrieved from patient charts. RESULTS: Pituitary dysfunction was diagnosed in 24 in 80 (30%) survivors, after a median follow-up time of 11 years. Median time to develop pituitary dysfunction after HNRMS diagnosis was 3.0 years. Risk factors were EBRT-based therapy (odds ratio [OR] 2.06; 95% confidence interval [CI] 1.79-2.46), parameningeal tumour site (OR 1.83; 95% CI 1.60-2.17) and embryonal RMS histology (OR 1.49; 95% CI 1.19-1.90). CONCLUSIONS: Radiotherapy used for the treatment of HNRMS confers a significant risk of the development of pituitary dysfunction. AMORE-based treatment in children with HNRMS resulted in less pituitary dysfunction than treatment with conventional EBRT. Our findings underscore the importance of routine early endocrine follow-up in this specific population.

Glucose isomerase: insights into protein engineering for increased thermostability.

Thermostable glucose isomerases are desirable for production of 55% fructose syrups at >90 degrees C. Current commercial enzymes operate only at 60 degrees C to produce 45% fructose syrups. Protein engineering to construct more stable enzymes has so far been relatively unsuccessful, so this review focuses on elucidation of the thermal inactivation pathway as a future guide. The primary and tertiary structures of 11 Class 1 and 20 Class 2 enzymes are compared. Within each class the structures are almost identical and sequence differences are few. Structural differences between Class 1 and Class 2 are less than previously surmised. The thermostabilities of Class 1 enzymes are essentially identical, in contrast to previous reports, but in Class 2 they vary widely. In each class, thermal inactivation proceeds via the tetrameric apoenzyme, so metal ion affinity dominates thermostability. In Class 1 enzymes, subunit dissociation is not involved, but there is an irreversible conformational change in the apoenzyme leading to a more thermostable inactive tetramer. This may be linked to reversible conformational changes in the apoenzyme at alkaline pH arising from electrostatic repulsions in the active site, which break a buried Arg-30-Asp-299 salt bridge and bring Arg-30 to the surface. There is a different salt bridge in Class 2 enzymes, which might explain their varying thermostability. Previous protein engineering results are reviewed in light of these insights.

Lithium Information Center. One model of a computer-based psychiatric information service.

The Lithium Information Center has been functioning as a specialized psychiatric information service for nearly ten years. Over the years, the center has disseminated information about the medical uses of lithium to psychiatrists and other physicians, to patients, to the family and friends of patients, and to a host of other individuals and organizations including pharmacists, lawyers, nurses, social workers, mental health centers, clinics, and support groups. To encourage the development of similar psychiatric information services, we outline the center's methods of acquiring, organizing, and disseminating lithium information.

The role of the anterior cricoid split in facilitating extubation in infants.

OBJECTIVE: The use of the anterior cricoid split (ACS) procedure has facilitated the extubation of children with early subglottic stenosis who may otherwise have required a tracheostomy. Criteria have been established for the evaluation of patients suitable for ACS and adherence to these guidelines has increased the extubation rate and reduced mortality. The objective of the study was to assess the use of the procedure at our tertiary referral centre. METHOD: In this retrospective clinical study, 33 patients were identified over an 11-year period between 1993 and 2004 with subglottic narrowing at the level of the cricoid ring, and who subsequently underwent an ACS. Demographic data, duration of intubation, indication and number of reintubations, success rate and complications were noted. Patients included in the study were infants who repeatedly failed trials of extubation and those who presented with persistent stridor. RESULTS: Twenty-nine out of 33 (88%) children were successfully extubated as a result of the cricoid split procedure. Four children failed extubation after the cricoid split. Three required a tracheostomy and one child remained intubated for a prolonged period. CONCLUSION: The anterior cricoid split procedure has revolutionised the management of early subglottic stenosis in selected neonates with failed extubation. It is a safe operation, and if successful it avoids the formation of a tracheostomy.

Maturation sutures for the paediatric tracheostomy--an extra safety measure.

OBJECTIVE: Displacement of the tracheostomy tube in paediatric patients is a potentially fatal complication. We describe an extra safety measure which facilitates tube replacement. SETTING: Tertiary referral specialist paediatric centre. MATERIALS AND METHODS: The method involves the placement of sutures between the anterior tracheal wall and skin to hasten the formation of a mature stoma (maturation sutures). We also undertook a retrospective case note review on patients from an academic tertiary referral centre. Thirty-five notes were reviewed. The most common indication for tracheostomy was airway obstruction (65 per cent). Fourteen patients had early and 10 had late complications with three tube displacements occurring. No added complications due to the use of sutures were found. CONCLUSIONS: Our complication rates compare well with those in the literature, and we recommend considering the use of such a technique.