The natural history of pregnancies with a diagnosis of Trisomy 18 or Trisomy 13; a retrospective case series

Background: Trisomy 18 (T18) and trisomy 13 (T13) are the second and third commonest autosomal aneuploidy syndromes respectively. While specific aspects of affected pregnancies have been documented in the literature, few studies document the overall natural history of the trisomies. This study aimed to examine the natural history (including diagnosis, pregnancy outcome, complications and survival) of T18 and T13 pregnancies in a setting where termination of pregnancy for fetal abnormality is not available. Methods: Cases were identified using birth registers, labour ward records, annual reports, medical records, ultrasound reports and reports from prenatal genetic testing. All identified T18 and T13 pregnancies in the study region from 2001 to 2012 were included. Individual chart reviews were performed for each case. Data were analysed using SPSS Version 20. Results: Forty-six T18 and twenty-four T13 pregnancies were identified. Most T18 cases (65%) were diagnosed prenatally, while only one third (33%) of T13 cases were prenatally diagnosed. Only three T18 pregnancies and one T13 pregnancy were electively terminated. A proportion of undiagnosed infants were delivered by emergency caesarean section. 48% (T18) and 46% (T13) infants survived following birth, for a median of 1.5 days (T18) and 7 days (T13). One T13 infant is currently alive over one year of age. Conclusions: This large series provides information for professionals and women regarding the natural histories of trisomies 18 and 13. These pregnancies can go undiagnosed antenatally without routine anomaly scanning. While many fetuses die in-utero, postnatal survival is possible

A rare case of melanotic hyperpigmentation of the tongue secondary to radiotherapy

Melanotic hyperpigmentation of the mucosa secondary to radiotherapy is a rare occurrence. It is a diagnosis of exclusion. Literature review has identified only two case reports published to date. We present a case of a patient treated at our institution. An 18-year-old male patient of Nigerian descent underwent radical radiotherapy (36 Gy in 18 daily fractions) to his right neck for paediatric type follicular lymphoma over a period of four weeks. He developed hyperpigmented tongue lesions during the third week of radiotherapy. There was no associated tongue discomfort, inflammation, infection, or pigmentation change elsewhere in the oral mucosa. Review of medications and past medical history did not demonstrate any potential contributing factors. Full blood count and biochemistry, morning cortisol levels and coagulation screen were all normal apart from mild neutropenia and lymphopenia. His oral cavity received a mean dose of 16.4 Gy, with the right side of his tongue receiving up to 37.5 Gy as this was within the planning target volume (PTV). He had an excellent response to radiotherapy and remains in remission. The tongue lesions resolved spontaneously 3 months post treatment

Anaplastic thyroid cancer: outcomes of trimodal therapy

BACKROUND: The purpose of this study is to assess the impact of trimodal therapy [surgery, chemotherapy and external beam radiotherapy (EBRT)] in patients with anaplastic thyroid cancer (ATC) treated with curative intent. MATERIALS AND METHODS: Retrospective review of patients with ATC treated at a tertiary referral centre between January 2009 and June 2020. Data were collected regarding demographics, histology, staging, treatment and outcomes. RESULTS: Seven patients (4 female) were identified. Median age was 58 years (range 52–83 years). All patients received EBRT with concurrent doxorubicin. Six patients received surgery followed by chemoradiotherapy (CRT), and one underwent neoadjuvant CRT followed by surgery. Median radiological tumour size was 50mm (range 40–90 mm). Six patients had gross extrathyroidal extension and three had N1b disease. Prescribed radiotherapy schedules were 46.4 Gy in 29 bidaily fractions (n = 2, treated 2010), 60 Gy in 30 daily fractions (n = 2), 66Gy in 30 fractions (n = 2) and 70 Gy in 35 fractions (n = 1; patient received neoadjuvant CRT). CRT was discontinued early for two patients due to toxicities. At median follow up of 5.8 months, 42.9% (3/7) patients were alive and disease-free. Only one patient developed a local failure. Three patients died from distant metastases without locoregional recurrence. CONCLUSIONS: Despite poor prognosis of ATC, selected patients with operable tumours may achieve high locoregional control rates with trimodal therapy, with possibility of long-term survival in select cases

Predicted cardiac and second cancer risks for patients undergoing VMAT for mediastinal Hodgkin lymphoma

Background and purpose: To predict treatment-related cardiovascular disease (CVD) and second cancer 30-year absolute mortality risks (AMR30) for patients with mediastinal Hodgkin lymphoma in a large multicentre radiation oncology network in Ireland. Material and methods: This study includes consecutive patients treated for mediastinal lymphoma using chemotherapy and involved site radiotherapy (RT) 2016–2019. Radiation doses to heart, left ventricle, cardiac valves, lungs, oesophagus, carotid arteries and female breasts were calculated. Individual CVD and second cancer AMR30 were predicted using Irish background population rates and dose–response relationships. Results: Forty-four patients with Hodgkin lymphoma were identified, 23 females, median age 28 years. Ninety-eight percent received anthracycline, 80% received 4–6 cycles ABVD. Volumetric modulated arc therapy (VMAT) ± deep inspiration breath hold (DIBH) was delivered, median total prescribed dose 30 Gy. Average mean heart dose 9.8 Gy (range 0.2–23.8 Gy). Excess treatment-related mean AMR30 from CVD was 2.18% (0.79, 0.90, 0.01, 0.13 and 0.35% for coronary disease, heart failure, valvular disease, stroke and other cardiac diseases), 1.07% due to chemotherapy and a further 1.11% from RT. Excess mean AMR30 for second cancers following RT were: lung cancer 2.20%, breast cancer in females 0.34%, and oesophageal cancer 0.28%. Conclusion: For patients with mediastinal lymphoma excess mortality risks from CVD and second cancers remain clinically significant despite contemporary chemotherapy and photon-RT. Efforts to reduce the toxicity of combined modality treatment, for example, using DIBH, reduced margins and advanced RT, e.g. proton beam therapy, should be continued to further reduce potentially fatal treatment effects

Validation of a quality metric score to assess the placement of hydrogel rectal spacer in patients treated with prostate stereotactic radiation therapy

PurposeTo evaluate the quality of the interspace between the prostate and rectum and assess the effect on the dose to the rectum by measuring the spacer quality score (SQS) before and after implanting a hydrogel rectal spacer.Methods and MaterialsThirty patients with prostate cancer were treated with stereotactic ablative body radiation therapy as part of the SPORT clinical trial. Each patient had a 10 mL polyethylene glycol hydrogel spacer inserted transperineally. Computed tomography scans were acquired before and after spacer insertion, 10MV flattening filter free (FFF) stereotactic ablative body radiation therapy (SABR) treatment plans were generated using each image set. To calculate the SQS, the prostate-rectal interspace (PRI) was measured in the anterior-posterior orientation, parallel to the anatomic midline at the prostate base, apex, and midgland on the prespacer and postspacer computed tomography. Measurements were taken in 3 transverse positions between the prostate and the rectum, and PRI scores of 0, 1, and 2 were assigned if the interspace between prostate and rectum was <0.3, 0.3 to 0.9, or ≥1 cm, respectively. The overall SQS was the lowest of the PRI scores. Differences between prespacer and postspacer PRIs and SQS were investigated by performing Fisher's exact test and differences between doses to the rectum were investigated by performing the paired samples Wilcoxon rank-sum test and Student t test.ResultsStatistically significant differences between prespacer versus postspacer patients were found when grouping patients according to their overall SQS. The PRI summary score did not reach statistical significance between prespacer and postspacer at the base but was significantly higher for the prostate midline and apex. Statistically significant differences in some rectum dose-volume metrics were found when grouping patients according to their PRIs and SQS.ConclusionsSQS before and after the spacer insertion was evaluated and was found to be correlated with pre- and postspacer rectal dosimetry. Sources of improvement of the SQS scoring metric and limitations are discussed

A randomised feasibility trial of stereotactic prostate radiotherapy with or without elective nodal irradiation in high-risk localised prostate cancer (SPORT Trial)

PURPOSE: To establish the feasibility of a randomised clinical trial comparing stereotactic ablative radiotherapy (SABR) to the prostate-only (P-SABR) or to prostate plus pelvic lymph nodes (PPN-SABR) in patients with unfavourable intermediate- or high-risk localised prostate cancer and explore potential toxicity biomarkers.MATERIALS &amp; METHODS: Thirty adult men with at least one of the following features; clinical MRI stage T3a N0 M0, Gleason score ≥ 7 (4+3), PSA &gt; 20 ng/mL were randomised 1:1 to P-SABR or PPN-SABR. P-SABR patients received 36.25Gy/5 fractions/29 days, PPN-SABR patients also received 25Gy/5 fractions to pelvic nodes with the final cohort receiving a boost to the dominant intraprostatic lesion of 45-50 Gy. γH2AX foci numbers, citrulline levels and circulating lymphocyte counts were quantified. Acute toxicity information (CTCAE v4.03) was collected weekly at each treatment and at six weeks and three months. Physician-reported late RTOG toxicity was recorded from 90 days to 36 months post-completion of SABR. Patient-reported quality of life (EPIC and IPSS) scores were recorded with each toxicity timepoint.RESULTS: The target recruitment was achieved and treatment successfully delivered in all patients.0% and 6.7% (P-SABR) and 6.7% and 20.0% (PPN-SABR) experienced acute grade ≥ 2 gastrointestinal (GI) and genitourinary (GU) toxicity respectively. At 3 years, 6.7% and 6.7% (P-SABR) and 13.3% and 33.3% (PPN-SABR) had experienced late grade ≥ 2 GI and GU toxicity respectively. One patient (PPN-SABR) had late grade 3 GU toxicity (cystitis and haematuria), no other grade ≥ 3 toxicity was observed. 33.3% and 60% (P-SABR) and 64.3% and 92.9% (PPN-SABR) experienced a minimally clinically important change (MCIC) in late EPIC bowel and urinary summary scores respectively. γH2AX foci numbers at 1 hour post-first fraction were significantly higher in PPN-SABR arm compared to P-SABR arm (p=0.04). Patients with late grade ≥ 1 GI toxicity had significantly larger falls in circulating lymphocytes (12 weeks post-radiotherapy, p=0.01), and a trend towards higher γH2AX foci numbers (p=0.09), than patients with no late toxicity. Patients with late grade ≥ 1 bowel toxicity and late diarrhoea experienced greater falls in citrulline levels (p=0.05).CONCLUSIONS: A randomised trial comparing P-SABR to PPN-SABR is feasible with acceptable toxicity. Correlations of γH2AX foci, lymphocyte counts and citrulline levels with irradiated volume and toxicity suggest potential as predictive biomarkers. This study has informed a multicentre UK randomised phase III clinical trial.</p

Validation of a Quality Metric Score to Assess the Placement of Hydrogel Rectal Spacer in Patients Treated With Prostate Stereotactic Radiation Therapy

Purpose: To evaluate the quality of the interspace between the prostate and rectum and assess the effect on the dose to the rectum by measuring the spacer quality score (SQS) before and after implanting a hydrogel rectal spacer. Methods and Materials: Thirty patients with prostate cancer were treated with stereotactic ablative body radiation therapy as part of the SPORT clinical trial. Each patient had a 10 mL polyethylene glycol hydrogel spacer inserted transperineally. Computed tomography scans were acquired before and after spacer insertion, 10MV flattening filter free (FFF) stereotactic ablative body radiation therapy (SABR) treatment plans were generated using each image set. To calculate the SQS, the prostate-rectal interspace (PRI) was measured in the anterior-posterior orientation, parallel to the anatomic midline at the prostate base, apex, and midgland on the prespacer and postspacer computed tomography. Measurements were taken in 3 transverse positions between the prostate and the rectum, and PRI scores of 0, 1, and 2 were assigned if the interspace between prostate and rectum was <0.3, 0.3 to 0.9, or ≥1 cm, respectively. The overall SQS was the lowest of the PRI scores. Differences between prespacer and postspacer PRIs and SQS were investigated by performing Fisher's exact test and differences between doses to the rectum were investigated by performing the paired samples Wilcoxon rank-sum test and Student t test. Results: Statistically significant differences between prespacer versus postspacer patients were found when grouping patients according to their overall SQS. The PRI summary score did not reach statistical significance between prespacer and postspacer at the base but was significantly higher for the prostate midline and apex. Statistically significant differences in some rectum dose-volume metrics were found when grouping patients according to their PRIs and SQS. Conclusions: SQS before and after the spacer insertion was evaluated and was found to be correlated with pre- and postspacer rectal dosimetry. Sources of improvement of the SQS scoring metric and limitations are discussed

Physical Chemistry of Milk Fat Globules

Many properties of milk and dairy products are determined by the behaviour and physical chemistry of milk fat globules. Allowed to stand, raw milk quickly separates into fat-enriched and fat-depleted phases, i.e. cream and skim milk, respectively. This is partly due to simple density differences between the emulsified fat globules and milk serum, but gravitational separation occurs at a rate ultimately determined by a complex series of colloidal interactions mediated by the milk fat globule membrane (MFGM) that lead to aggregation of fat globules, particularly at low temperatures (i.e. so-called cold agglutination). Creaming properties of milk differ between mammalian species, and processing of milk can profoundly alter the creaming properties of bovine milk, particularly homogenization and centrifugal separation, but also heat treatment. In this chapter, the principal physical properties of bovine milk fat globules are discussed, along with methods for their analysis and the impact of common dairy processes on their stability

Evolution over Time of Ventilatory Management and Outcome of Patients with Neurologic Disease∗

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p &lt; 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p &lt; 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p &lt; 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease