bluuebunny/crossref_metadata_2025 huggingface dataset:
P038 Is it all in the eyes?
Authors: Gharatya Anil , Wajed Julekha , Cernovschi Natalia , Christidis Dimitrios
Published: April 2021

Background/Aims 

The ocular manifestations of giant cell arteritis (GCA) and ocular myasthenia gravis (OMG) have significant overlap, which can lead to clinical uncertainty in the absence of awareness and routine diagnostic testing.

Methods 

We present the case of a 63-year-old male patient with a strong family history of autoimmune disease. He presented to the Rheumatology department in 2009 with symptoms of polymyalgia rheumatica (PMR) and was treated successfully with a reducing regime of Prednisolone. In 2013, he presented to the Ophthalmology department with blurred vision and diplopia. Giant cell arteritis was suspected and a high dose of Prednisolone was started. His temporal artery biopsy was normal and inflammatory markers were not raised, but there was a complete resolution of his symptoms since starting steroids. Under the care of the Rheumatology department, reducing regimes of Prednisolone were attempted and a steroid sparing agent, Methotrexate was introduced. Unfortunately, he continued to have recurring symptoms of blurred vision and diplopia, particularly at Prednisolone doses less than 20mg. Over the course of a few years, there was a progression of his ocular symptoms. He developed a horizontal diplopia, monocular ptosis and a 4th nerve palsy. He was referred back to the Ophthalmology department, where alternate diagnoses were investigated. Anti-acetylcholine receptor antibodies (AChR) were strongly positive at 35 mU/L (normal <0.44 mU/L). MRI head was normal, and CT chest showed no thymoma. Single fibre EMG confirmed severe OMG. Our patient was subsequently commenced on Pyridostigmine, with which symptoms improved.

Results 

The literature on OMG mimicking GCA is sparse. The prevalence of an exclusively ophthalmic presentation in patients with GCA is 1 in 5. Ocular signs and symptoms in GCA can vary drastically due to the propensity of the disease to affect different structures within the eye. Transient and permanent visual loss, affects 10-30% of GCA patients due to anterior ischemic optic neuropathy. Diplopia affects 5% of GCA patients. In comparison, OMG can be the only presenting feature in 15% of patients with Myasthenia Gravis, and is characterised by unilateral ptosis, oculomotor paresis and binocular diplopia.

Conclusion 

This case highlights the clinical similarities of OMG and GCA, and that OMG should be considered as a differential diagnosis when the clinical picture of GCA does not truly fit. In patients presenting with GCA with ocular symptoms, normal inflammatory markers and no systemic features, OMG should be considered and AChR antibody testing be performed. More awareness of OMG is needed. We also propose that OMG should be included as a differential diagnosis, in the British Society of Rheumatology guidelines for GCA.

Disclosure 

A. Gharatya: None. J. Wajed: None. N. Cernovschi: None. D. Christidis: None.
P043 Fascinating phosphate: seek and you will find
Authors: Bakshi Jyoti , Batten Clare
Published: April 2021

Background/Aims 

A 62-year-old accountant was referred to the metabolic bone clinic with a 2 year history of thoracic back pain and a persistently raised ALP. There were no associated red flags for her back pain. She had a history of a gluteal lump, thought to be benign, for which she had declined excision. She has hypertension and had a previous navicular fracture. Medications included bendroflumethiazide and Adcal D3. She had restriction in neck movements and was tender to percussion in the thoracic spine. There was no proximal weakness or focal neurology. Systems and joint exam were unremarkable.

Methods 

The case is discussed below.

Results 

Salient abnormal results on presentation were a raised ALP of 207 and corrected calcium of 2.34. PTH was elevated at 8.2 (NR:1.6-6.9), Vitamin D 79 and a low phosphate of 0.34 (NR:0.8-1.50). Alkaline phosphatase isoenzymes showed the raised level came from bone. Protein and urine electrophoresis were normal. A bone density scan was normal, and a recent thoracic MRI showed only degenerative change. An isotope bone scan was requested and was reported to show increased activity in the nasal bone, maxilla and both orbits, raising the possibility of Paget’s disease. However, when reviewed in the Radiology meeting with a skull x-ray, the appearances were not felt to be in keeping with Paget’s. Despite physiotherapy, hydrotherapy, acupuncture and neuropathic medication the patient’s back pain continued. Her phosphate remained low and her calculated tubular reabsorption of phosphate from a 24h urine collection (TmP/GFR) was low at 0.42mmol/l (NR 0.80-1.35). She was started on phosphate replacement and calcitriol, and Adcal D3 was continued. The Fibroblast Growth Factor (FGF) 23 levels were sent and came back significantly elevated at 1380 (NR < 100). A 68Ga DOTA-TATE scan (whole body PET/CT scan), confirmed the right gluteal lump as the source of the FGF 23. The patient went on to have an excision biopsy and histology confirmed a mesenchymal tumour of the right buttock. Her phosphate replacement was gradually weaned, but on reducing the dose phosphate levels dropped and her symptoms returned. The repeat TmP/GFR was again low at 0.61, and FGF 23 levels were still raised at 204. A repeat 68Ga DOTA-TATE scan, 4 years after the first one, showed recurrence of the right gluteal lesion and a possible small lesion in the left gluteal muscle. She has been sent for further excision.

Conclusion 

Tumour induced osteomalacia (TIO) is a rare condition and should be considered in cases of hypophosphataemia. Classical symptoms are proximal weakness and muscle and bone pain. They are typically associated with small benign tumours (most commonly mesenchymal tumours) which may be difficult to find. Excision is curative but if small amounts of tumour remain, relapses may occur.

Disclosure 

J. Bakshi: None. C. Batten: None.
P063 SystmOne clinical reporting to identify high-risk rheumatology patients for shielding
Authors: Kirby David , Nadesalingam Kavitha
Published: April 2021

Background/Aims 

At the start of the COVID-19 pandemic, shielding guidance was issued by Public Health England with a risk stratification guide developed by the BSR to assist with patient identification. At BTHFT we benefited with all GP practices in the region using TPP SystmOne (S1) for medical records. We describe how we used S1 to help identify high risk patients under our care.

Methods 

We did not appreciate the full extent we could use S1 to identify patients in our initial shielding identification process. As such, we reviewed notes of patients on biologic prescriptions and SC MTX from Homecare prescription lists. To capture patients on high dose prednisolone, we identified patients with a recent diagnosis of GCA and patients with recent prescriptions of > 20mg prednisolone through pharmacy records. On recognising the ability of S1 to identify patients that had glucocorticoid exposure through primary care and/or on cDMARDS we used S1 reporting mechanisms to identify these patients. Clinical record sharing enabled BTHFT’s rheumatology department to access S1 for all patients under their care. S1’s clinical reporting function was used to search for patients within at least one of the following cohorts before being combined in a single cohort of ‘at risk’ patients (heart, lung or kidney disease, ≥70 years, diabetes or hypertension [including pulmonary artery hypertension]). Reports were created for patients on any DMARD issued within primary care within the previous 12 weeks. High dose steroid use was more challenging to demonstrate, but a report was devised to include all patients with an issued prescription for prednisolone 5mg tablets within the preceding 8 weeks (for any reason). An additional report was created for patients with a rheumatological diagnosis co-existing with an interstitial lung disease. Using S1's report joining function, the different drugs and ‘at risk’ cohorts were combined to provide an accurate list of patients with features increasing their vulnerability to COVID-19. This list was easily modifiable and searches were re-run to update lists once inclusion on the shielding list was updated.

Results 

Patients meeting the criteria for shielding were then advised in writing including signposting to BTHFT’s rheumatology website and helpline for further information if required. By searching for all prednisolone prescriptions, this would have included patients given prednisolone for other reasons. 5mg tablet strength ensured patients on low dose were excluded, but we recognise some patients were likely over-recruited into this cohort.

Conclusion 

We can update our searching methods to easily include patients on biologics and SC MTX by some additional bulk coding in preparation for future shielding specifications thereby bypassing the need to review individual notes for patients. We were able to achieve an accurate shielding list in a relatively short space of time to reduce patient risk.

Disclosure 

D. Kirby: None. K. Nadesalingam: None.
P108 Anti-nerve growth factor (anti-NGF) antibodies as analgesia in the management of osteoarthritis
Authors: Rammanohar Jashmitha , Sutton James , Seah K T Matthew , Khan Wasim S , To Kendrick
Published: April 2021

Background/Aims 

Osteoarthritis is a major cause of morbidity and disability. Much of this comes from joint pain, which is exacerbated by movement and exercise. Pharmacological analgesia therefore not only has the obvious benefit of alleviating pain, but in doing so, it also facilitates exercise (a pillar of conservative management). Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are currently the main analgesics used in this context. However, these agents can cause unwanted side effects and are contraindicated in some patients. We thus conducted a systematic review and meta-analysis using the Cochrane collaboration criteria to evaluate the efficacy of anti-nerve growth factor (anti-NGF) antibodies as potential alternative analgesics in osteoarthritis of the hip and/or knee. Whilst tanezumab has been studied extensively and monoclonal anti-NGF antibodies have been reviewed in other pain states, this is the first systematic review of three key anti-NGF antibodies: tanezumab, fulranumab and fasinumab in symptomatic hip and/or knee osteoarthritis.

Methods 

An interdisciplinary work group conducted a literature search across seven electronic databases for the use of anti-NGF antibodies in osteoarthritis. All hip/knee osteoarthritis studies investigating anti-NGF antibodies regardless of dose regimen or phase of trial were included. Studies in which participants received NSAIDs or analgesics other than anti-NGF antibodies, or studies in which the only intervention was the administration of anti-NGF antibodies in combination with NSAIDs or other analgesics were excluded. The Jadad Scale score was used to assess the quality of each study.

Results 

Thirteen studies involving 8,145 patients with a diagnosis of hip and/or knee osteoarthritis were analysed. Demographic information including duration of disease and Kellgren-Lawrence grades were also extracted. Anti-NGF antibodies showed significant improvements compared to placebo as rated on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scales for pain (SMD= -0.50, 95% CI -0.71 to -0.28, P < 0.00001; I2 = 88%), physical function (SMD= -0.82, 95% CI -1.09 to -0.55, P < 0.00001; I2 = 94%) and stiffness (SMD= -0.88, 95% CI -1.22 to -0.54, P < 0.00001; I2 = 95%). These agents were not associated with a significant increase in serious adverse events but were associated with a significant increase in discontinuation due to adverse events, abnormal peripheral sensations and peripheral neuropathy.

Conclusion 

Anti-NGF antibodies appear very promising with regard to alleviating osteoarthritic hip/knee pain but more studies are needed to determine the optimal dosage and the overall risk-to benefit ratio, particularly with long-term use.

Disclosure 

J. Rammanohar: None. J. Sutton: None. K. Seah: None. W.S. Khan: None. K. To: None.
P167 IgG4 related disease: response to immunosuppressive therapy: a single centre retrospective study in the United Kingdom
Authors: Sangle Shirish , Morton Neil T , Casian Alina , Nel Louise , Hanna Jennifer , Fernando Archana , Bell Rachel , Taylor Peter , Pattison James , O'Brien Tim , D'Cruz David
Published: April 2021

Background/Aims 

IgG4 related disease (IgG4-RD) is a rare immune-mediated condition, increasingly being recognised as a multi-organ disorder. It is a relatively new entity and the precise prevalence is not known. It is a chronic fibro-inflammatory condition with raised circulating levels of immunoglobulin G4 and accumulation of plasma cells and fibrosis in the affected tissue. We report a retrospective observational study of patients with IgG4 related disease (IgG4-RD).

Methods 

We conducted a retrospective observational study of patients seen at Guy’s and St Thomas’ NHS Foundation Trust Hospitals, London, UK. The data collected was analysed for clinical presentation, laboratory markers of inflammation, immunoglobulin subsets, autoantibody profiles, imaging and histopathology and compared to the 2019 ACR/EULAR criteria to determine a confirmed diagnosis of IgG4-RD. Data was also collected post standard-of-care treatment, including patient clinical outcomes and possible improvement.

Results 

The study included a multi-ethnic cohort of 83 patients with multi-organ involvement. Fifty-nine of the eighty-three patients were classified as confirmed IgG4-RD (71%). Seventy one patients had biopsies of which 49 of the 59 (91%) confirmed IgG4-RD patients had biopsies consistent with IgG4-RD. Fifty patients underwent PET-CT scanning of which uptake was seen in 76% of those with confirmed IgG4-RD (26/34). Immunoglobulin IgG subclass analysis showed significantly higher IgG4 levels in the confirmed IgG4-RD group as compared to possible IgG4. Treatments were with corticosteroids and immunosuppressants such as azathioprine, methotrexate, mycophenolate, cyclophosphamide and rituximab. P167 Table 1:IgG4 levels and inflammatory markers for pre and post treatment groupsPre-RxPost-Rxp-valueCRPmean29 mg/l9 mg/l0.0298*Range0-300 mg/l1-70 mg/lESRmean35 mm/hr17 mm/hr0.0002*Range2-131 mm/hr1-74 mm/hrSerum IgG4mean4.9 g/L2.83 g/L0.0001*Range0.1-24.2 g/L0.02-13.3 g/L

Conclusion 

IgG4-RD is a fibro-inflammatory disorder involving multiple organs. If not treated adequately may develop severe organ damage. It often responds to corticosteroids but may require other immunosuppressive therapy. Treatment with biologics such as B cell depletion therapy results are encouraging.

Disclosure 

S. Sangle: None. N.T. Morton: None. A. Casian: None. L. Nel: None. J. Hanna: None. A. Fernando: None. R. Bell: None. P. Taylor: None. J. Pattison: None. T. O'Brien: None. D. D'Cruz: None.
Perceived Isolation among Family Caregivers of People with Mental Illness
Authors: Labrum Travis , Newhill Christina Evangeline
Published: April 2021

Family members (who are overwhelmingly women) providing caregiving for individuals with mental illness (MI) are known to experience significant burden. Little research, however, has addressed how such burden can affect caregivers’ personal time and perceived isolation. Using data from a survey of 1,505 family caregivers of adults with MI, authors examined the extent to which factors related to caregivers, care recipients, caregiving, and treatment are associated with caregivers’ perceived isolation and the mediating role of caregivers’ inadequate personal time. A series of multivariate logistic regression models and Sobel testing were performed. Half of caregivers perceived being isolated. Perceived isolation was positively associated with care recipients having a serious mental health problem, coresiding, effects of stigma, and caregivers having inadequate time for themselves. Perceived isolation was negatively associated with the ability to rely on others for help, caregivers being satisfied with the amount of community mental health services, and caregivers having received education on caregiving. Caregivers having inadequate time for themselves was most strongly related to perceived isolation. Female caregivers were more likely to experience isolation; however, this relationship was mediated through caregivers having less time for themselves than preferred. The article concludes with a discussion of the implications for social work practice.
Cultural adaptation of two school-based smoking prevention programs in Bogotá, Colombia
Authors: Sánchez-Franco Sharon , Arias Luis Fernando , Jaramillo Joaquin , Murray Jennifer M , Hunter Ruth F , Llorente Blanca , Bauld Linda , Good Sally , West Judith , Kee Frank , Sarmiento Olga L
Published: April 2021

Smoking prevention among adolescents is a public health challenge that is even more significant in low- and middle-income countries where local evidence is limited and smoking rates remain high. Evidence-based interventions could be transferred to low- and middle-income country settings but only after appropriate cultural adaptation. This paper aims to describe the process of the cultural adaptation of two school-based smoking prevention interventions, A Stop Smoking in Schools Trial and Dead Cool, to be implemented in Bogotá, Colombia. A recognized heuristic framework guided the cultural adaptation through five stages. We conducted a concurrent nested mixed-methods study consisting of a qualitative descriptive case study and a quantitative pre- and post quasi-experiment without a control. Contextual, content, training, and implementation modifications were made to the programs to address cultural factors, to maintain the fidelity of implementation, and to increase the pupils’ engagement with the programs. Modifications incorporated the suggestions of stakeholders, the original developers, and local community members, whilst considering the feasibility of delivering the programs. Involving stakeholders, original program developers, and community members in the cultural adaptation of evidence-based interventions is essential to properly adapt them to the local context, and to maintain the fidelity of program implementation.
The Use of Once-monthly Injectable Buprenorphine for the Treatment of Opioid Use Disorder in Postpartum Women: A Case Series
Authors: Shadowen Caroline , Moeller Frederick Gerard , Martin Caitlin E.
Published: April 2021

Objectives:

For women with opioid use disorder (OUD), the postpartum period is an especially vulnerable period. Buprenorphine (BUP) improves OUD outcomes during this timeframe. Once-monthly injectable BUP (XRI-BUP) is a newer formulation for which evidence of use in postpartum women is extremely limited. We present a case series of 9 women who transitioned from sublingual (SL-BUP) to XRI-BUP in their first year postpartum.

Methods:

We conducted a retrospective chart review of our institution's medical record for patients who received at least one administration of XRI-BUP in their first year postpartum (January 2017–March 2020). Data were collected from baseline through mean follow-up of 281.4 days (range 235–417) for participant outcomes.

Results:

The most common indications for initiating XRI-BUP were participant preference (n = 9) followed by challenges taking SL-BUP (n = 6). Four of the 9 participants transitioned back from XRI- to SL-BUP during the study timeframe, for reasons including incarceration and undesired side effects. Preliminary treatment outcomes demonstrated that participants remained on SL- (n = 4) or XRI-BUP (n = 5) through follow-up. The 5 participants who remained on XRI-BUP had consistent negative urine drug tests for nonprescribed opioids during the study period.

Conclusions:

To our knowledge, this is the first study that reviews the feasibility of using XRI-BUP in postpartum women. Our results suggest that XRI-BUP is a viable treatment option, which should be further investigated in future studies of postpartum women with OUD.
Outpatient Treatment of Chronic Designer Benzodiazepine Use: A Case Report
Authors: Hauck Tanya S. , Rochon Stephanie , Bahra Parminder , Selby Peter
Published: April 2021

Background:

Novel psychoactive substances, such as designer benzodiazepines unapproved for therapeutic purposes, are an emerging concern worldwide. They have unknown or unpredictable pharmacological properties. Using a case example, we discuss the use of “Xanax bars,” which now generally do not contain the pharmaceutical alprazolam. We describe the difficulty in detecting these substances and the development of a use disorder including adverse outcomes such as seizures when stopped. The evidence for management is anecdotal.

Case:

We describe the case of a male of approximately 25 years of age with alcohol and sedative-hypnotic use disorder related to illicit “Xanax bars,” whose point of care urinalysis did not identify benzodiazepines and whose broad-spectrum urinalysis identified the presence of flualprazolam, a novel designer benzodiazepine. He suffered a subacute withdrawal seizure and responded to treatment with loading doses of diazepam and naltrexone.

Discussion:

Although previous literature has focused on poisoning and intoxication (including coma), there are few studies examining treatment options for chronic designer benzodiazepine use. Standard approaches, such as conversion to a longer-acting benzodiazepine with a prolonged taper, are risky with designer benzodiazepines due to the unknown level of tolerance and risk of overdosing the patient. Illicit “Xanax” is not equivalent to prescribed alprazolam and cannot be converted and tapered. To be cautious, supervised benzodiazepine tapers or anticonvulsants should be explored as treatment strategies, based on their use in pharmaceutical benzodiazepine use disorders. Inpatient acute withdrawal management should be considered, and anticonvulsants may play a role in the first 4 to 6 weeks of treatment.
Multi-directional Cranial Distraction Osteogenesis for Treating Sagittal Synostosis with Frontometaphyseal Dysplasia: A Case Report
Authors: Morishita Yuya , Sunaga Ataru , Gomi Akira , Hatade Alice , Morita Yuhei , Yoshimura Kotaro
Published: April 2021

Frontometaphyseal dysplasia (FMD), also known as Gorlin-Cohen syndrome, is a rare genetic syndrome. This syndrome affects the skeletal system and connective tissue, and causes a wide spectrum of manifestations of the skull, tubular bones, cardiovascular system, urinary system, and/or gastrointestinal system. Craniofacial findings of FMD are characterized by protruding supraorbital ridge, broad nasal bridge, hypertelorism, down-slanting palpebral fissures, and/or micrognathia. We describe a case of a 2-year-old girl diagnosed with sagittal synostosis accompanied with FMD. She presents anterior sagittal synostosis cranial form, compressed cerebrospinal fluid space (which suggested increased intracranial pressure), and the supraorbital hyperostosis. She underwent multi-directional cranial distraction osteogenesis in the calvaria and shaving of the supraorbital ridges. Despite concerns about bone fragility associated with FMD, the surgery was accomplished as usual. The patient had no intra- and postoperative complications. After 6 months of follow-up, the cranial shape has improved and the cerebrospinal fluid space has widened, but the supraorbital ridge has protruded again. Re-protrusion of the supraorbital ridge appears to be due to age-appropriate vigorous osteogenesis. The multi-directional cranial distraction osteogenesis procedure has been useful for treating sagittal synostosis even concomitant with FMD.
Acute Onset Optic Disc Hemorrhage Following Pharmacologic Mydriasis
Authors: Scott Jessica A. , Liebmann Jeffrey M.
Published: April 2021

Purpose:

The aim was to report 2 unusual cases of optic disc hemorrhage (DH) occurring following pharmacologic mydriasis.

Observation:

A 78-year-old woman and 60-year-old man with primary open angle glaucoma developed optic DHs shortly after pupillary dilation.

Conclusion and Importance:

Cycloplegia may cause subtle shifts in vitreous and lamina cribrosa position that may result in the formation of optic DHs in susceptible glaucomatous eyes.
Plasma Metabolic Profiling in Patients With Silicosis and Asbestosis
Authors: Zhou Mi , Xue Changjiang , Fan Yali , Wu Na , Ma Jing , Ye Qiao
Published: April 2021

Objectives:

To explore the circulating metabolites and related pathways in silicosis and asbestosis exposure to different mineral dust.

Methods:

Plasma of 30 silicosis, 30 asbestosis, and 20 healthy controls was analyzed using liquid chromatography-mass spectrometry. Metabolic networks and the relevance of the identified metabolic derangements were explored.

Results:

Compared with healthy controls, 37 and 39 dysregulated plasma metabolites were found in silicosis and asbestosis, respectively, of which the levels of 22 metabolites differed. Three major pathways were identified, among which arginine and proline metabolism was identified as the most closely related metabolic pathway.

Conclusions:

The types and quantities of up-regulated metabolites including lipids, amino acids, and carnitines differed between silicosis and asbestosis. Pathways inducing lung fibrosis were common to mineral dust exposure, while pathways related to oxidative stress and tumorigenesis differed between silicosis and asbestosis.
Respiratory Disease in Migrant Farmworkers
Authors: Bethuel Nancy W. , Wasson Kai , Scribani Melissa , Krupa Nicole , Jenkins Paul , May John J.
Published: April 2021

Introduction:

Respiratory problems are prevalent among persons who work in agriculture, however, publications examining the respiratory status in LatinX farmworkers are limited. The purpose of this study is to assess the respiratory status of LatinX farmworkers across New York State.

Methods:

This is a retrospective analysis of data gathered from Spanish language OSHA respiratory questionnaires completed between January 2017 and March 2019. The best of three peak flows were compared with predicted normal values derived from regressions using age, gender, and height.

Results:

Key information was present in 162 Spanish questionnaires. Rates of reported respiratory symptoms were low, less than 2%; 11.7% farmworkers smoked. Best of three peak flows showed a mean of 97.2 ± 16.8% of predicted.

Discussion:

New York LatinX farmworkers do not appear to have abnormal rates of respiratory symptoms or low peak flows.
Association of Metformin With Volumetric Tumor Growth of Sporadic Vestibular Schwannomas
Authors: Armstrong Michael F. , Lohse Christine M. , Lees Katherine A. , Carlson Matthew L.
Published: April 2021

Objective:

Recent research demonstrates a potential association between metformin use and reduced sporadic vestibular schwannoma (VS) growth in patients undergoing conservative observation. The current study was designed to elucidate the effect of metformin on tumor growth in sporadic VS using volumetric analyses.

Study Design:

Retrospective cohort.

Setting:

Tertiary referral center.

Patients:

Patients with sporadic VS who elected initial conservative treatment with at least two serial magnetic resonance imaging (MRI) scans were included.

Interventions:

Metformin use among patients with observed sporadic VS.

Main Outcome Measures:

Tumor growth, defined as an increase in volume of at least 20% from the initial MRI.

Results:

A total of 361 patients were evaluated. Thirty-four patients (9%) had a diagnosis of diabetes at baseline. Nineteen patients (5%) were taking metformin at the time of the initial MRI. Metformin use was not significantly associated with a reduced risk of volumetric tumor growth in a univariable analysis in all patients undergoing observation for VS (hazard ratio [HR] 0.75; 95% confidence intervals [CI] 0.40–1.42; p = 0.38) or within the diabetic subset (HR 0.79; 95% CI 0.34–1.83; p = 0.58). Additionally, diabetes status, insulin dependence, hemoglobin A1c value, and metformin dose were not significantly associated with volumetric tumor growth.

Conclusion:

Despite promising initial results in several previous studies, our data suggest that metformin use does not significantly reduce the risk of volumetric tumor growth in sporadic VS.
Length of the Narrow Bony Channels May Not be the Sole Cause of Differential Involvement of the Nerves in Vestibular Neuritis
Authors: Büki Béla , Ward Bryan K.
Published: April 2021

Objective:

To measure the vestibular nerve bony channels, applying a 3D measurement to account for the oblique trajectory of the singular nerve.

Background:

The clinical syndrome vestibular neuritis affects structures innervated by the superior vestibular nerve more commonly than the inferior vestibular nerve. Anatomical differences such as a longer, narrower bony channel of the superior vestibular nerve may increase its susceptibility to entrapment.

Main Outcome Measure(s):

Length of the narrow segment of each vestibular nerve in which the nerve occupies more than 80% of the bony channel was measured.

Results:

Forty six normal ears sectioned in the axial plane were measured. The narrow channel for the lateral semicircular canal (SCC, mean [SD] 2.94 ± 0.54) mm was longer than that of the singular nerve innervating the posterior SCC (1.95 ± 0.58 mm [p < 0.0001]), which also exceeded that of the utricular nerve (1.45 ± 0.36 mm [p < 0.0001]). The nerve to the superior part of the saccule (i.e., Voit's nerve) was 1.14 ± 0.48 mm and that of the inferior saccule was 0.52 ± 0.37 mm.

Conclusions:

The length of the narrow bony channel for the singular nerve is longer than previously reported and exceeds the utricular nerve. Comparing these data with the frequency of clinical lesions in recent literature suggests that, although bony channel length may contribute to differential involvement of the vestibular nerves, other factors may increase susceptibility of the superior vestibular nerve, including redundancy in innervation of the saccule and posterior SCC and anastomoses between the facial nerve and the superior vestibular nerve through which reactivated herpes virus may spread.
Real-Time Ventricular Volume Measured Using the Intracardiac Electromyogram
Authors: Schmid Daners Marianne , Hall Sophie , Sündermann Simon , Cesarovic Nikola , Kron Mareike , Falk Volkmar , Starck Christoph , Meboldt Mirko , Dual Seraina A.
Published: April 2021

Left ventricular end-diastolic volume (EDV) is an important parameter for monitoring patients with left ventricular assist devices (LVADs) and might be useful for automatic LVAD work adaptation. However, continuous information on the EDV is unavailable to date. The depolarization amplitude (DA) of the noncontact intracardiac electromyogram (iEMG) is physically related to the EDV. Here, we show how a left ventricular (LV) volume sensor based on the iEMG might provide beat-wise EDV estimates. The study was performed in six pigs while undergoing a series of controlled changes in hemodynamic states. The LV volume sensor consisted of four conventional pacemaker electrodes measuring the far-field iEMG inside the LV blood pool, using a novel unipolar amplifier. Simultaneously, noninvasive measurements of EDV and hematocrit were recorded. The proposed EDV predictor was tested for statistical significance using a mixed-effect model and associated confidence intervals. A statistically significant (p = 3e–07) negative correlation was confirmed between the DA of the iEMG and the EDV as measured by electric impedance at a slope of –0.069 (–0.089, –0.049) mV/mL. The DA was slightly decreased by increased hematocrit (p = 0.039) and moderately decreased with the opening of the thorax (p = 0.003). The DA of the iEMG proved to be a significant, independent predictor of EDV. The proposed LV volume sensor is simple to integrate into the inflow cannula of an LVAD and thus has the potential to inform the clinician about the state of LV volume in real time and to automatically control the LVAD.
Ketogenic diets and appetite regulation
Authors: Roekenes Jessica , Martins Catia
Published: April 2021

Purpose of review

The popularity of ketogenic diets in the treatment of obesity has increased dramatically over the last years, namely due to their potential appetite suppressant effect. The purpose of this review was to examine the latest evidence regarding the impact of ketogenic diets on appetite.

Recent findings

The majority of the studies published over the last 2 years adds to previous evidence and shows that ketogenic diets suppress the increase in the secretion of the hunger hormone ghrelin and in feelings of hunger, otherwise see when weight loss is induced by non-ketogenic diets. Research done using exogenous ketones point out in the same direction. Even though the exact mechanisms by which ketogenic diets suppress appetite remain to be fully determined, studies show that the more ketotic participants are (measured as β-hydroxybutyrate plasma concentration), the smaller is the increase in ghrelin and hunger and the larger is the increase in the release of satiety peptides. Further evidence for a direct effect of ketones on appetite comes from studies using exogenous ketones.

The appetite suppressant effect of ketogenic diets may be an important asset for improving adherence to energy restricted diets and weight loss outcomes.
Multidisciplinary management of perianal Crohn's disease
Authors: Abushamma Suha , Ballard David H. , Smith Radhika K. , Deepak Parakkal
Published: April 2021

Purpose of review

Multiple new medications with novel mechanisms of action are now available to treat Crohn's disease (CD). However, they have varying effectiveness in the management of perianal CD. Identifying the most appropriate therapy and optimizing it is essential to maximize effectiveness of therapy. Additionally, the management of perianal CD requires imaging of the perianal area to identify the fistula anatomy and local complications such as abscesses that require surgical drainage. Initial surgical assessment is key to drain abscesses and allow fistula healing with medical therapy.

Recent findings

Although anti-tumor necrosis factor (TNFs) remain the most effective medications to treat perianal CD, real-world data suggests that ustekinumab may be a 2nd-line option in patients nonresponsive to an anti-TNF or having contraindications. Mesenchymal stem cells are an emerging therapeutic approach that is currently in Phase 3 trials in the United States and poised to play a major role in the treatment algorithm.

The management of perianal CD requires a multidisciplinary approach with a combination of initial imaging and surgical assessment to adequately control local sepsis, optimization of biological therapy with adjunct antibiotics or immunomodulators, and close clinical follow-up with imaging to evaluate response to therapy and guide further surgical management options.
The impact of race and ethnicity on lipoprotein(a) levels and cardiovascular risk
Authors: Reyes-Soffer Gissette
Published: April 2021

Purpose of review

Lipoprotein(a) [Lp(a)] is a plasma circulating apoB100 (apoB) containing lipoprotein. It has a unique glycoprotein bound to the apoB100, apolipoprotein(a) [apo(a)]. The majority of the population expresses two apo(a) isoforms, when bound to apoB100 they create two circulating Lp(a) particles. Lp(a) levels are genetically determined and epidemiological studies have established elevated levels of Lp(a) to be a causal risk factor of cardiovascular disease (CVD). Lp(a) levels differ across racial groups and Blacks of Sub-Saharan decent have higher levels when compared to white. In comparison to white populations, studies in minorities are less represented in the published literature. Additionally, there is a lack of standardization in the commercial assays used to measured Lp(a) levels, and hence it is difficult to assess risk based on individual Lp(a) levels, but risk seems to occur in the upper percentiles of the population.

Recent findings

A recent study using data from the UK biobank highlights the racial differences in Lp(a) levels and the increase risk in CVD amongst all races.

This review will highlight Lp(a) biology and physiology with a focus on available data from racially diverse cohorts. There is a need to perform studies in diverse populations to understand if they are at higher risk than whites are.
Current opinion in pediatric heart transplantation
Authors: Cleveland John D. , Kumar S. Ram
Published: April 2021

Purpose of review

Cardiac transplant remains the most effective therapy for children with end-stage heart disease. Outcomes remain better than any alternative therapy for this condition, but its use is limited by donor organ availability. As a result, waitlist times and mortality on the waiting list remain unacceptably high. Novel approaches are necessary to address this problem.

Recent findings

Organ Procurement and Transplant Network/United Network for Organ Sharing readjusted the pediatric heart allocation system in 2016 to prioritize children at highest risk of mortality, encourage judicious listing, and improve appropriate donor organ utilization. Subsequent studies have aligned with these priorities to help risk-stratify patients at the time of listing and identify the importance that should be assigned to donor-specific factors. In addition, many authors are advocating for increased utilization of hearts donated after cardiac death. Pediatric Ventricular Assist Device (VAD) application has also been increasing to help decrease waitlist mortality. Although results have significantly improved, there remain important limitations to widespread use of VADs in the pediatric population. This has prompted novel techniques such as pulmonary artery banding to improve cardiac function and, in some cases, promote recovery. The demand for cardiac replacement continues to increase with an ageing population of patients with congenital heart disease, presenting new challenges and stressors to the system.

Pediatric cardiac transplant outcomes are excellent but remain plagued by the limited supply of donor organs. Recent strategies to combat this problem have focused on judicious listing, maximal utilization of available donor organs, and safely extending the lives of patients on the waitlist. New demands on the organ supply chain will continue to stress the system, making these efforts of the highest importance.

Clinical Trial Registry Number not applicable.
Refractory Stage M Ganglioneuroblastoma With Bone Metastases and a Favorable, Chronic Course of Disease: Description of a Patient Cohort
Authors: Tas Michelle L. , Molenaar Jan J. , Peek Annemarie M.L. , Lequin Maarten H. , Verdijk Rob M. , de Krijger Ronald R. , Tytgat Godelieve A.M. , van Noesel Max M.
Published: April 2021

Refractory stage M neuroblastoma (NB) is associated with a poor prognosis and a progressive course of disease. Here, we describe a unique group of patients with a discrepant clinical course. Seven histologically confirmed ganglioneuroblastoma (GNB) (n=6) and differentiating NB (n=1) patients were identified who were diagnosed with stage M disease based on iodine-123-metaiodobenzylguanidine avid bone metastases. Six patients started on high-risk treatment, without tumor response (stable disease). Treatment was discontinued before the start of consolidation treatment because of refractory response in all patients. Unexpectedly, after cessation of treatment no progression of disease occurred. In 2 patients, the primary tumors expanded (>25%) very slowly during 1.5 and 3 years, and remained stable thereafter. Metabolically, a slow decrease of urinary homovanillic acid and vanillylmandelic acid levels and iodine-123-metaiodobenzylguanidine avidity was observed. All patients are alive with presence of metastatic disease after a median follow-up of 17 years (range: 6.7 to 27 y). Interestingly, at diagnosis, 6 patients were asymptomatic, 6 patients had GNB morphology, and 5 patients had meningeal metastases. These are all features seen in only a small minority of stage M patients. This GNB entity illustrates the clinical heterogeneity of neuroblastic tumors and can be used to further study the developmental origin of different NB subtypes.
Evaluation of Risk Factors Causing Ototoxicity in Childhood Cancers Located in the Head and Neck Region Treated With Platinum-based Chemotherapy
Authors: Olgun Yüksel , Çakir Kizmazoğlu Deniz , İnce Dilek , Ellidokuz Hülya , Güneri Enis A. , Olgun Nur , Kirkim Günay
Published: April 2021

The aim of this study is to evaluate risk factors contributing to the development of ototoxicity in children who received platinum-based chemotherapy for malignancies located in the head and neck region. Eighty-four children who received platinum-based chemotherapy were included. Audiologic evaluations were performed before and after each chemotherapy session through pure tone audiometry, distortion product otoacoustic emissions, and auditory brainstem response tests. Ototoxicity was evaluated using Brock, Muenster, and Chang classifications. Factors such as cranial irradiation, cumulative doses of cisplatin, age, sex, cotreatment with aminoglycosides, schedule of platinum, and type of chemotherapeutic agent were analyzed. Using χ2 tests, all risk factors were matched with the 3 ototoxicity classifications, and multivariate analyses were conducted using statistically significant risk factors. In univariate analyses, being between 5 and 12 years of age, cranial irradiation and being treated with both cisplatin and carboplatin were found to be related to ototoxicity in all 3 classifications. Logistic regression modeling analyses with these 3 risk factors showed that being between 5 and 12 years of age and being treated with both cisplatin and carboplatin significantly increased the risk of ototoxicity.
Quantifying the Psychosocial Benefits of Masculinizing Mastectomy in Trans Male Patients with Patient-Reported Outcomes: The University of California, San Francisco, Gender Quality of Life Survey
Authors: Alcon Andre , Kennedy Adrienne , Wang Eric , Piper Merisa , Loeliger Kelsey , Admassu Natnaelle , Lentz Rachel , Kim Esther A.
Published: April 2021

Background:

Gender-affirming surgery is a medically necessary treatment to alleviate gender dysphoria for transgender patients. Although previous studies suggest improved psychosocial outcomes after gender-affirming surgery, there are no transgender-specific instruments available to assess its effects on patient quality of life.

Methods:

Using qualitative methods, the authors developed the first quality-of-life survey, the University of California, San Francisco, Gender Quality of Life (UCSF Gender QoL) survey, for trans male patients undergoing gender-affirming mastectomy. The UCSF Gender QoL survey was then administered prospectively to 51 trans male patients undergoing inframammary mastectomy with free nipple grafting at the University of California, San Francisco. The brief version of the World Health Organization Quality of Life survey was also given as a measure of external validity. The Cronbach alpha was value calculated to measure internal validity.

Results:

Thirty-six patients completed surveys 6 weeks after surgery, and 22 patients completed surveys 1 year after surgery, for response rates of 71 percent and 43 percent, respectively. The UCSF Gender QoL survey detected a significant improvement in quality of life 6 weeks and 1 year after chest surgery. The effect sizes were large, and the Cronbach alpha exhibited excellent internal validity.

Conclusions:

This study establishes the UCSF Gender QoL survey as one of the first patient-reported outcomes tools for evaluating quality of life in trans male patients after gender-affirming chest reconstruction. Although the study is limited by a small cohort at a single center, establishing the validity of the UCSF Gender QoL survey provides an invaluable tool for future research into various aspects of gender-affirming chest surgery.
Flap Closure of Spinal Defects in High-Risk Patients
Authors: Kenny Elizabeth M. , James Isaac B. , Bengür Fuat Barış , Zammerilla Lauren L. , Manders Ernest K. , Russavage James M. , Acartürk Tahsin Oğuz
Published: April 2021

Background

Complication rates after spinal surgery are high, in part because of surgical advancements that have made procedures available to a broader range of medically complicated patients. The high rates of infection, hematoma, and dehiscence resulting in open wounds after spinal surgery often warrant plastic surgery involvement. In this study, we aim to examine the effects of preoperative and operative risk factors on complication rates, reoperation rates, and hospital length of stay after flap reconstruction of spinal defects.

Methods

A retrospective review was performed of 373 patients who required flap reconstruction for spinal wound closure at our institution between 2003 and 2013. Data regarding demographics, comorbidities, operative variables, and postreconstructive course were collected.

Results

Of the 373 patients, 97.3% had at least 1 comorbid condition associated with poor wound healing, 91.2% had a significant wound condition at the time of reconstruction, and 81.8% had a history of 2 or more spinal surgeries. After reconstruction, average hospital stay was 14 days, with 35% of patients developing complications and 30% requiring reoperation. Risk factors including elevated body mass index, diabetes, tobacco use, steroid use, low prealbumin level, therapeutic anticoagulation, infection, history of spine surgery, multilevel spinal reconstruction, and spinal hardware were associated with complications, reoperations, and prolonged length of stay.

Conclusions

Local muscle flap coverage is an effective strategy for the reconstruction of spinal defects in medically complex patients. To reduce the inherently high risks associated with paraspinous reconstruction in this challenging population, special consideration should be given to preoperative and operative variables associated with poor outcomes. Early coordination between spine and plastic surgeons should be considered in patients at high-risk of wound complications.
Structured illumination microscopy artefacts caused by illumination scattering
Authors: Mo Yanquan , Feng Fan , Mao Heng , Fan Junchao , Chen Liangyi
Published: April 2021

Despite its wide application in live-cell super-resolution (SR) imaging, structured illumination microscopy (SIM) suffers from aberrations caused by various sources. Although artefacts generated from inaccurate reconstruction parameter estimation and noise amplification can be minimized, aberrations due to the scattering of excitation light on samples have rarely been investigated. In this paper, by simulating multiple subcellular structure with the distinct refractive index from water, we study how different thicknesses of this subcellular structure scatter incident light on its optical path of SIM excitation. Because aberrant interference light aggravates with the increase in sample thickness, the reconstruction of the 2D-SIM SR image degraded with the change of focus along the axial axis. Therefore, this work may guide the future development of algorithms to suppress SIM artefacts caused by scattering in thick samples.

This article is part of the Theo Murphy meeting issue ‘Super-resolution structured illumination microscopy (part 1)'.