Orofacial neuralgia associated with a middle cerebral artery aneurysm

Chronic orofacial pain of neuropathic origin can present diagnostic and management dilemmas to dental practitioners and also affects the patient's quality of life. Intracranial aneurysms are a potential cause of stroke (e.g. sub‐arachnoid haemorrhage) that is usually associated with, high rates of mortality and morbidity. A patient who had been previously managed for symptoms of temporomandibular joint disorder (TMD) presented with sharp, shooting pain of moderate intensity. It was precipitated by swallowing, and radiated to the right throat, posterior border of the mandible, ear and temporomandibular joint. Clinical and radiological investigations ruled out odontogenic pain, TMD and other more common types of facial pain. Magnetic resonance imaging revealed a 7 × 6 mm aneurysm in the right middle cerebral artery (MCA) which was subsequently surgically clipped. Interestingly, the facial pain resolved after this procedure. Compression of the insular region of the brain innervated by the trigeminal, glossopharyngeal and vagus nerves provides a plausible explanation for the pain reported. To our knowledge, this is the first case of facial neuralgia associated with an aneurysm in the MCA which emphasizes the importance of a multidisciplinary approach in the diagnosis and management of unusual cases of chronic orofacial pain.     

Learning from preventable deaths: exploring case record reviewers' narratives using change analysis

Objective

To determine if applying change analysis to the narrative reports made by reviewers of hospital deaths increases the utility of this information in the systematic analysis of patient harm.

Design

Qualitative analysis of causes and contributory factors underlying patient harm in 52 case narratives linked to preventable deaths derived from a retrospective case record review of 1000 deaths in acute National Health Service Trusts in 2009.

Participants

52 preventable hospital deaths.

Setting

England.

Main outcome measures

The nature of problems in care and contributory factors underlying avoidable deaths in hospital.

Results

The change analysis approach enabled explicit characterisation of multiple problems in care, both across the admission and also at the boundary between primary and secondary care, and illuminated how these problems accumulate to cause harm. It demonstrated links between problems and underlying contributory factors and highlighted other threats to quality of care such as standards of end of life management. The method was straightforward to apply to multiple records and achieved good inter-rater reliability.

Conclusion

Analysis of case narratives using change analysis provided a richer picture of healthcare-related harm than the traditional approach, unpacking the nature of the problems, particularly by delineating omissions from acts of commission, thus facilitating more tailored responses to patient harm.     

MRI findings of intracranial anomalies associated with cephalocele—a case series

Introduction

Cephalocele is a relatively rare cranial dysraphism characterised by herniation of intracranial structures through the skull. Surgical management is primarily necessary where a risk of infection through communication of the lesion with the intracranial space exists, a risk of rupture, or for cosmetic purposes. Cephalocele is often associated with venous anomalies such as vertical embryonic positioning of the straight sinus, splitting of the superior sagittal sinus, vein of Galen elongation, along with tenting of the tentorium [Morioka et al. Childs Nerv Syst 25:309–315, 2009]

Patients

Here, we report four cases of cephalocele with pre-operative MRI imaging retrospectively studied, demonstrating associated venous anomalies. Three of these patients went on to have uncomplicated, corrective surgery, while one was managed conservatively.

Results

All four cases demonstrated the main venous drainage going through a persistent falcine sinus to drain into the superior sagittal sinus. Upward tenting of the tentorium was observed in three cases (cases 1, 3 and 4). Two of our cases demonstrated other venous anomalies frequently reported in the literature, namely splitting of the superior sagittal sinus and absence of the transverse sinus (case 1) and communication of the cephalocele with the superior sagittal sinus and absence of the straight sinus (case 2).

Conclusion

The association between cephalocele and venous anomalies suggests that pre-operative MRI should be mandatory for a full evaluation of a suspicious midline cranial lesion in order to evaluate the safety of corrective surgery.     

Economic Evaluation of a Web-Based Tailored Lifestyle Intervention for Adults: Findings Regarding Cost-Effectiveness and Cost-Utility From a Randomized Controlled Trial

Background

Different studies have reported the effectiveness of Web-based computer-tailored lifestyle interventions, but economic evaluations of these interventions are scarce.

Objective

The objective was to assess the cost-effectiveness and cost-utility of a sequential and a simultaneous Web-based computer-tailored lifestyle intervention for adults compared to a control group.

Methods

The economic evaluation, conducted from a societal perspective, was part of a 2-year randomized controlled trial including 3 study groups. All groups received personalized health risk appraisals based on the guidelines for physical activity, fruit intake, vegetable intake, alcohol consumption, and smoking. Additionally, respondents in the sequential condition received personal advice about one lifestyle behavior in the first year and a second behavior in the second year; respondents in the simultaneous condition received personal advice about all unhealthy behaviors in both years. During a period of 24 months, health care use, medication use, absenteeism from work, and quality of life (EQ-5D-3L) were assessed every 3 months using Web-based questionnaires. Demographics were assessed at baseline, and lifestyle behaviors were assessed at both baseline and after 24 months. Cost-effectiveness and cost-utility analyses were performed based on the outcome measures lifestyle factor (the number of guidelines respondents adhered to) and quality of life, respectively. We accounted for uncertainty by using bootstrapping techniques and sensitivity analyses.

Results

A total of 1733 respondents were included in the analyses. From a willingness to pay of €4594 per additional guideline met, the sequential intervention (n=552) was likely to be the most cost-effective, whereas from a willingness to pay of €10,850, the simultaneous intervention (n=517) was likely to be most cost-effective. The control condition (n=664) appeared to be preferred with regard to quality of life.

Conclusions

Both the sequential and the simultaneous lifestyle interventions were likely to be cost-effective when it concerned the lifestyle factor, whereas the control condition was when it concerned quality of life. However, there is no accepted cutoff point for the willingness to pay per gain in lifestyle behaviors, making it impossible to draw firm conclusions. Further economic evaluations of lifestyle interventions are needed.

Trial Registration

Dutch Trial Register NTR2168; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2168 (Archived by WebCite at http://www.webcitation.org/6MbUqttYB).     

Arginine deprivation alters microglial polarity and synergizes with radiation to eradicate non-arginine-auxotrophic glioblastoma tumors

New approaches for the management of glioblastoma (GBM) are an urgent and unmet clinical need. Here, we illustrate that the efficacy of radiotherapy for GBM is strikingly potentiated by concomitant therapy with the arginine-depleting agent ADI-PEG20 in a non-arginine-auxotrophic cellular background (argininosuccinate synthetase 1 positive). Moreover, this combination led to durable and complete radiological and pathological response, with extended disease-free survival in an orthotopic immune-competent model of GBM, with no significant toxicity. ADI-PEG20 not only enhanced the cellular sensitivity of argininosuccinate synthetase 1–positive GBM to ionizing radiation by elevated production of nitric oxide (˙NO) and hence generation of cytotoxic peroxynitrites, but also promoted glioma-associated macrophage/microglial infiltration into tumors and turned their classical antiinflammatory (protumor) phenotype into a proinflammatory (antitumor) phenotype. Our results provide an effective, well-tolerated, and simple strategy to improve GBM treatment that merits consideration for early evaluation in clinical trials.     

Real-world Treatment Patterns and Reasons for Therapy Selection in Patients with Advanced Hepatocellular Carcinoma in US Oncology Practices

BackgroundThe treatment landscape for advanced hepatocellular carcinoma (aHCC) is rapidly expanding beyond tyrosine kinase inhibitors (TKIs) in the first-line (1L) setting, with multiple TKIs and immune-checkpoint inhibitors (ICIs) now being evaluated in combination. Real-world evidence describing current treatment patterns and reasons for 1L and 2L treatment selection in aHCC is sparse.Patients and MethodsA retrospective cohort study with a cross-sectional survey element was conducted using Cardinal Health’s Oncology Provider Extended Network. U.S. medical oncologists identified adult aHCC patients initiating 1L systemic therapy between January 1, 2017 and July 31, 2019 and abstracted data from patient medical records. Data included provider characteristics, patient demographics and clinical characteristics, treatment regimens, and physician rationale for treatment regimen choice.ResultsA total of 44 medical oncologists provided data on 284 aHCC patients. The median age at 1L initiation was 61.5 years, and the majority were male (78%) and white (66%). Nearly half (47%) initiated 1L treatment in 2019, 34% were ECOG performance status 2+, and 63% were Child-Pugh Class B/C. Among the 284 aHCC patients, TKIs were used by 94% of patients in the 1L setting, comprised predominantly of sorafenib (54%) and lenvatinib (38%). ICIs were most common among the 90 patients (66%) who received 2L treatment.ConclusionIn the community-oncology practice setting, nearly all aHCC patients received sorafenib or lenvatinib in the 1L setting, while the majority of patients received an ICI in the 2L setting. With recent ICI approvals in aHCC, this marks the beginning of an increased use of ICIs in the 1L setting.     

Sorafenib in Dupuytren and Ledderhose Disease

Palmar and plantar fibromatosis are benign proliferative processes which present as a diffuse thickening or nodules of the hands and/or feet and may lead to flexion contractures, pain, and functional impairment known as Dupuytren and Ledderhose diseases, respectively. Current treatments are noncurative and associated with significant morbidity. Here, we report on the outcomes of 5 patients with advanced disease, no longer surgical candidates, treated with sorafenib. Sorafenib exhibited an expected safety profile. All 5 patients demonstrated objective responses as evaluated by a decrease in tumor size and/or tumor cellularity from baseline and all 5 patients reported subjective pain relief and/or functional improvement. Mechanistically, immunohistochemistry revealed patchy positivity for PDGFRβ, a known target of sorafenib. The outcomes of these 5 patients suggest the safety and efficacy of a relatively well-tolerated oral agent in the treatment of Dupuytren and Ledderhose diseases and suggest the need for future controlled studies.     

Leading article: Joint Advisory Group on Gastrointestinal Endoscopy (JAG) framework for managing underperformance in gastrointestinal endoscopy

Underperformance can be defined as performance which persistently falls below a desired minimum standard considered acceptable for patient care. Within gastrointestinal endoscopy, underperformance may be multifactorial, related to an individual’s knowledge, skills, attitudes, health or external factors. If left unchecked, underperformance has the potential to impact on care and ultimately patient safety. Managing underperformance should be a key attribute of high-quality endoscopy service, as recognised in the Joint Advisory Group on Gastrointestinal Endoscopy (JAG) accreditation process. However, it is recognised that not all services have robust mechanisms to do this.This article provides the JAG position on managing underperformance in endoscopy, defined through a practical framework. This follows a stepwise process of detecting underperformance, verification, identification of additional causative factors, providing support and reassessment. Detection and verification of issues may require use of multiple evidence sources, including performance data, feedback and appraisal reports. Where technical underperformance is identified, this should be risk stratified by potential risk to patient safety. Support should be tailored to each individual case based on the type of underperformance detected, any causative factors with an action plan developed. Support may include coaching, mentoring, training and upskilling. Wider support from the medical director’s office or external services may also be required. Monitoring and reassessment is a crucial part of the overall process.     

Fibroblast activation protein: Purification,epitope mapping and induction by growth factors

The human fibroblast activation protein (FAP) defined by monoclonal antibody (MAb) F19 is a cell surface antigen expressed in reactive stromal fibroblasts of breast, colorectal, lung and other epithelial cancers. In contrast to its stroma-specific localization in epithelial neoplasms, FAP is expressed in the malignant mesenchymal cells of bone and soft-tissue sarcomas. FAP is transiently expressed in some fetal mesenchymal tissues but is absent or expressed at low levels in most adult tissues. FAP is induced in cultured fibroblasts and, in these cells, consists of a M_r 95,000 subunit (FAPα) carrying the F19 epitope and a non-covalently bound M_r 105,000 subunit (FAPβ) lacking the F19 epitope. Using MAb F19 and 5 newly derived MAbs, we identify 3 distinct epitopes on FAPα and tentatively assign one epitope to FAPβ. Analysis of detergent extracts of a FAPα^highβ-sarcoma cell line by size exclusion–high performance liquid chromatography (HPLC) revealed that FAPα does not elute as a M_r, 95,000 species but as part of a high-molecular weight complex (M_r > 400,000) that dissociates into M_r 95,000 subunits in SDS gels. Immunoaffinity purification of FAPα followed by tryptic digestion, reversed-phase HPLC and microsequencing identified 3 unique FAPα peptides, with 2 showing sequence similarity (23/38 identical amino acids) to segments of CD26, a T-cell activation antigen. CD26 is a membrane-bound enzyme (dipeptidyl aminopeptidase IV), but immunopurified FAPα has little if any dipeptidase activity with typical CD26 substrates. Finally, studies with FAP^low leptomeningeal fibroblasts revealed that transforming growth factor-β, 12-O-tetradecanoyl phorbol-13-acetate and retinoids can upregulate FAP expression, whereas serum and several other factors had no or little effect on FAP levels. FAP and CD26 may belong to a family of structurally related but functionally distinct activation proteins that are expressed on different cell types and show unique modes of regulation in normal and malignant cells.