Impact of the COVID-19 Pandemic on Outcomes for Patients with Lung Cancer Receiving Curative-intent Radiotherapy in the UK.

AIMS: Previous work found that during the first wave of the COVID-19 pandemic, 34% of patients with lung cancer treated with curative-intent radiotherapy in the UK had a change to their centre's usual standard of care treatment (Banfill et al. Clin Oncol 2022;34:19-27). We present the impact of these changes on patient outcomes. MATERIALS AND METHODS: The COVID-RT Lung database was a prospective multicentre UK cohort study including patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between April and October 2020. Data were collected on patient demographics, radiotherapy and systemic treatments, toxicity, relapse and death. Multivariable Cox and logistic regression were used to assess the impact of having a change to radiotherapy on survival, distant relapse and grade ≥3 acute toxicity. The impact of omitting chemotherapy on survival and relapse was assessed using multivariable Cox regression. RESULTS: Patient and follow-up forms were available for 1280 patients. Seven hundred and sixty-five (59.8%) patients were aged over 70 years and 603 (47.1%) were female. The median follow-up was 213 days (119, 376). Patients with stage I-II non-small cell lung cancer (NSCLC) who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.859) or death (P = 0.884); however, they did have increased odds of grade ≥3 acute toxicity (P = 0.0348). Patients with stage III NSCLC who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.216) or death (P = 0.789); however, they did have increased odds of grade ≥3 acute toxicity (P < 0.001). Patients with stage III NSCLC who had their chemotherapy omitted had no significant increase in distant relapse (P = 0.0827) or death (P = 0.0661). CONCLUSION: This study suggests that changes to radiotherapy and chemotherapy made in response to the COVID-19 pandemic did not significantly affect distant relapse or survival. Changes to radiotherapy, namely increased hypofractionation, led to increased odds of grade ≥3 acute toxicity. These results are important, as hypofractionated treatments can help to reduce hospital attendances in the context of potential future emergency situations.

Does medical futility matter in 'do not attempt CPR' decision-making?

The current demographical trend towards an increasingly elderly population combined with advances in end of life care calls for a deeper understanding and common terminology about the concept of futility and additional influences on the resuscitation decision-making process. Such improved understanding of medical futility and other contributing factors when making DNACPR orders would help to ensure that clinicians make appropriate and thoughtful decisions on whether to recommend resuscitation in a patient. When estimating medical futility a physician should consider the chance of survival over different time periods and balance this against the chance of adverse outcomes. This information can then be offered to the patient (or the relatives) so that the patient's views about what is acceptable for the survival chance, length and type of survival can be factored into the eventual decision. Given the lack of evidence in this area and the poor level of patient knowledge and the emotive nature of the topic, it is not surprising that clinicians find such discussions hard.

Germline SMARCB1 mutation and somatic NF2 mutations in familial multiple meningiomas.

BACKGROUND: Multiple meningiomas occur in <10% of meningioma patients. Their development may be caused by the presence of a predisposing germline mutation in the neurofibromatosis type 2 (NF2) gene. The predisposing gene in patients with non-NF2 associated multiple meningiomas remains to be identified. Recently, SMARCB1 was reported to be a potential predisposing gene for multiple meningiomas in a family with schwannomatosis and multiple meningiomas. However, involvement of this gene in the development of the meningiomas was not demonstrated. RESULTS: Five affected members of a large family with multiple meningiomas were investigated for the presence of mutations in SMARCB1 and NF2. A missense mutation was identified in exon 2 of SMARCB1 as the causative germline mutation predisposing to multiple meningiomas; furthermore, it was demonstrated that, in accordance with the two-hit hypothesis for tumourigenesis, the mutant allele was retained and the wild-type allele lost in all four investigated meningiomas. In addition, independent somatically acquired NF2 mutations were identified in two meningiomas of one patient with concomitant losses of the wild-type NF2 allele. CONCLUSION: It is concluded that, analogous to the genetic events in a subset of schwannomatosis associated schwannomas, a four-hit mechanism of tumour suppressor gene inactivation, involving SMARCB1 and NF2, might be operative in familial multiple meningiomas associated meningiomas.

Diagnosis of distal 22q11.2 deletion syndrome in a patient with a teratoid/rhabdoid tumour.

We report an 18 year old patient with mild intellectual disability who was diagnosed with a late onset teratoid/rhabdoid tumour by histological and immunohistochemical studies. Array-CGH studies, performed on a peripheral blood sample, showed a 3.4Mb deletion of chromosome 22q11.2, distal to the common DiGeorge syndrome (DGS) or Velocardiofacial syndrome (VCFs) region. This deletion is consistent with a diagnosis of distal 22q11.2 deletion syndrome. The deletion encompasses the INI1/SMARCB1 tumour suppressor gene. Biallelic inactivation of this gene is characteristic of atypical teratoid/rhabdoid tumours. Although several constitutional chromosome conditions are known to have increased susceptibility to various forms of cancer, very little is known regarding the magnitude of risk for malignancy associated with distal 22q11.2 deletion syndrome. In view of this finding we suggest that patients diagnosed with distal 22q11.2 deletion syndrome undergo careful prolonged monitoring for this type of tumour. This case demonstrates the need to carefully assess regions found to be deleted in individuals, referred for dysmorphia and/or developments delay, by array-CGH for the presence of genes known to be implicated in malignancy.

Facial injury patterns in a UK paediatric population aged under 13 years.

BACKGROUND: The aims of this study were to present the demographics and mechanisms of facial injury in UK children, and to establish the nature and anatomical location of facial injury in this age group. METHODS: Patient data were collected retrospectively over 1 year from a paediatric Emergency Department in South East Scotland. Medical notes were examined for all patients coded on the electronic patient record as having any facial injury. RESULTS: 593 patients attended with a facial injury. The median age of patients was 4.7 years. (IQR 2.4-7.5 years.), and the male to female ratio of facial injuries was 2:1. Injuries were predominantly from falls. Assault or violence was uncommon. Most common sites of facial injury were the lower third of the face and dento-alveolar injury. Facial fractures were rare and radiographic facial imaging was infrequently performed. Only eight facial fractures were diagnosed. 4.5% of all patients were admitted to hospital; 23% of the children were referred on to other specialities for follow-up, of these over half were to a dentist. CONCLUSIONS: A large number of children presented with facial injuries during the study period. Facial lacerations, oral trauma and dental trauma were the most common injuries. The majority of patients were dealt with without admission or referral to another speciality.

Frenal injury in children is not pathognomic of non-accidental injury.

Upper labial frenal tear in infants is classically taught as having associations with non-accidental injury. Collection of data for a 12-month period in our paediatric facial injury study revealed that this injury pattern is common in ambulant children and was associated with other facial trauma. In assessing the possibility of this injury being due to abuse, the importance of the mobility of the child and the mechanism of the injury are paramount.

Hybridization between escaped domestic and wild American mink (Neovison vison).

The release of domesticated organisms into natural populations may adversely affect these populations through predation, resource competition, and the introduction of disease. Additionally, the potential for hybridization between wild and domestic conspecifics is of great concern because it can alter the evolutionary integrity of the affected populations. Wild American mink (Neovison vison) populations may be threatened not only by competition for resources with domestic mink originating from farms, but by breeding with such escapees. Using 10 microsatellite loci, we genotyped mink from Ontario, Canada, sampled from two farms, two putatively mixed populations in regions surrounding the mink farms, and two wild populations with no recent history of mink farming. Using individual-based Bayesian population assignment, we identified four population clusters, including one wild, and three domestic populations. The latter were not clustered by farm but rather by distinct line-bred colour phases. Population clustering also identified domestic and hybrid mink in the free-ranging populations. Nearly two-thirds of the mink sampled in the two putatively mixed populations (78% and 43%) were either farm escapees or descendants of escapees. Principal components analysis of allele frequencies supported our Bayesian assignment results. The power of our assignment test was assessed using simulated hybrid genotypes which suggested that our overall correct classification rate was 96.2%. The overwhelming presence of domestic animals and their hybridization with mink in natural populations is of great concern for the future sustainability of wild mink populations.

A case of amyoplasia in a monochorionic twin pregnancy: a sequela from twin-twin transfusion syndrome?

OBJECTIVE: To present and discuss the sonographic and clinical findings in one twin of a monochorionic pair affected by amyoplasia. METHODS: On ultrasound examination at 21 weeks in a monochorionic twin pregnancy, twin I was smaller, hydropic, with multiple contractures consistent with amyoplasia and oligohydramnios. Twin II was anatomically normal with polyhydramnios. RESULTS: The twins were delivered at 28 weeks' gestation. The clinical findings were consistent with twin-twin transfusion syndrome (TTTS). CONCLUSION: It is postulated that TTTS may be a causative factor in the excessive incidence of amyoplasia in monozygotic twin pregnancy.

Isolation and characterization of polymorphic microsatellite loci in muskrat, Ondatra zibethicus.

We describe the isolation and characterization of 12 highly polymorphic microsatellite loci for the muskrat, Ondatra zibethicus. Microsatellite markers from three other rodent species were cross-amplified in muskrat and one of them was polymorphic. We observed moderate to high levels of genetic variability in these 13 polymorphic loci (five to 22 alleles per locus) with observed heterozygosity ranging from 0.48 to 0.96. These markers will be useful for further studies on population genetic structure in muskrat and potentially in other rodent species.

A case of thanatophoric dysplasia: the early prenatal 2D and 3D sonographic findings and molecular confirmation of diagnosis.

OBJECTIVE: To present the early 2D and 3D ultrasound findings and the molecular confirmation in a case of thanatophoric dysplasia. METHODS: On ultrasound examination, there was frontal bossing, increased nuchal translucency and short limbs at 12 weeks' gestation and a small thorax and short and bowed long bones on 3D at 16 weeks. Amniocentesis and DNA analysis confirmed the mutation of FGFR3 gene indicating thanatophoric dysplasia. RESULTS: After medical termination of pregnancy, the postmortem X-ray and pathology examination findings were consistent with the diagnosis. CONCLUSION: 3D anatomy scan and molecular confirmation may be helpful in early diagnosis and genetic counseling of thanatophoric dysplasia.

Radiological characterisation of photon radiation from ultra-high-intensity laser-plasma and nuclear interactions.

With the increasing number of multi-terawatt (10(12) W) and petawatt (10(15) W) laser interaction facilities being built, the need for a detailed understanding of the potential radiological hazards is required and their impact on personnel is of major concern. Experiments at a number of facilities are being undertaken to achieve this aim. This paper describes the recent work completed on the Vulcan petawatt laser system at the CCLRC Rutherford Appleton Laboratory, where photon doses of up to 43 mSv at 1 m per shot have been measured during commissioning studies. It also overviews the shielding in place on the facility in order to comply with the Ionising Radiation Regulations 1999 (IRR99), maintaining a dose to personnel of less than 1 mSv yr(-1) and as low as reasonably practicable (ALARP).

Growth, behavior, and clinical findings in 27 patients with Kabuki (Niikawa-Kuroki) syndrome.

This study was undertaken to document the phenotype of Kabuki (Niikawa-Kuroki) syndrome in patients from Australia and New Zealand, with particular emphasis on growth patterns, behavior, and relationship between head circumference and intellectual level. Data on 27 children and adults with Kabuki (Niikawa-Kuroki) syndrome from Australia and New Zealand were collected by questionnaire and clinical assessment. The patients ranged in age from 7 months to 36 years with a mean age of 7 years and 2 months. The mean age at diagnosis was 3(5/6) years, but in most cases, the facial phenotype was evident from infancy. The minimum birth prevalence was calculated at 1 in 86,000. Three of our patients died. Parents reported a behavior phenotype characterized by an excellent long-term memory and avoidance of eye contact. No correlation was found between head circumference and severity of intellectual disability. Eight of 14 patients over the age of 5 years were overweight or obese. Six of these eight patients had failure to thrive in infancy. One patient developed insulin-dependent diabetes mellitus in adolescence. Some individuals with Kabuki (Niikawa-Kuroki) syndrome show a characteristic growth profile with failure to thrive in infancy progressing to obesity or overweight in middle childhood or adolescence. A behavior phenotype was noted which requires further investigation. Head size is not a predictor of degree of intellectual disability.

Occult cancer of the fallopian tube in a BRCA2 germline mutation carrier at prophylactic salpingo-oophorectomy.

BACKGROUND: Women with a germline BRCA1 or BRCA2 mutation have a significantly increased risk of developing ovarian cancer compared with women in the general population and may consider bilateral prophylactic oophorectomy as a risk-reducing option. CASE: We report a case of occult fallopian tube cancer diagnosed at prophylactic surgery in a patient with a BRCA2 mutation. CONCLUSIONS: This report acts as a reminder of the importance of removing as much of the fallopian tube as possible during prophylactic surgery in BRCA1 and BRCA2 carriers and of the need for careful pathological examination of surgical specimens after surgery.

Diagnostic criteria, clinical characteristics, and natural history of Cohen syndrome.

Cohen syndrome is a rare, recessively inherited condition associated with facial dysmorphism, developmental delay, and visual disability. A delay in making the diagnosis commonly occurs, contributed to by the lack of a definitive molecular test and the clinical variability of published case reports. A specific clinical phenotype has been delineated in a homogeneous cohort of Finnish Cohen syndrome patients, but the applicability of their diagnostic criteria to non-Finnish patients has been debated. Detailed delineation of Cohen syndrome in patients from outside Finland is therefore warranted. We report on the clinical features of 33 non-Finnish Cohen syndrome patients. Variability within the clinical spectrum is identified and the natural history of Cohen syndrome described. Diagnostic guidelines for facilitating accurate and early diagnosis are discussed. Results from molecular genetic analysis using markers located within the previously mapped COH1 critical region support allelic but not genetic heterogeneity in this UK cohort.