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Male breast cancer: an update.
No full textMale breast cancer (MBC) is rare, accounting for less than 1% of all breast cancer but the incidence has increased worldwide. Risk factors include increased longevity, obesity, testicular diseases and tumours, and germline mutations of BRCA2. BRCA2 carriers have 80 times the risk of the general population. Men generally present with breast cancer at an older age compared with women. Histologically, MBC is often of grade 2, hormone receptor positive, HER2 negative, and no special type carcinoma although in situ and invasive papillary carcinomas are common. Reporting and staging are similar to female breast cancer. Metastatic lesions to the male breast do occur and should be differentiated from primary carcinomas. Until recently, MBC was thought to be similar to the usual ER positive post-menopausal female counterpart. However, advances in MBC research and trials have highlighted significant differences between the two. This review provides an up to date overview of the biology, genetics, and histology of MBC with comparison to female breast cancers and differential diagnosis from histological mimics
Corrigendum to "European Resuscitation Council Guidelines 2021: Adult Advanced Life Support" [Resuscitation 161 (2021) 115-151].
No full textPulmonary arterial hypertension in adults with congenital heart disease: markers of disease severity, management of advanced heart failure and transplantation.
No full textINTRODUCTION
Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a progressive, life-limiting disease.
AREAS COVERED
In this paper, we review the classification and pathophysiology of PAH-CHD, including the mechanisms of disease progression and multisystem effects of disease. We evaluate current strategies of risk stratification and the use of biological markers of disease severity, and review principles of management of PAH-CHD. The indications, timing and the content of advanced heart failure assessment and transplant listing are discussed, along with a review of the types of transplant and other forms of available circulatory support in this group of patients. Finally, the integral role of advance care planning and palliative care is discussed.
EXPERT OPINION/COMMENTARY
All patients with PAH-CHD should be followed up in expert centers, where they can receive appropriate risk assessment, PAH therapy and supportive care. Referral for transplant assessment should be considered if there continue to be clinical high-risk features, persistent symptoms or acute heart failure decompensation despite appropriate PAH specific therapy. Expert management of PAH-CHD patients, therefore, requires vigilance for these features, along with a close relationship with local advanced heart failure services and a working knowledge of listing criteria, which may disadvantage congenital heart disease patients
TEVAR for complicated and uncomplicated type B aortic dissection-Systematic review and meta-analysis.
No full textBACKGROUND
Type B aortic dissection (TBAD), is defined as a dissection involving the aorta distal to left subclavian artery with the ascending aorta and the aortic arch not affected. TBAD is classified due to the time frame and presence of complications. Complicated TBAD (co-TBAD) patients have a greater mortality rate than uncomplicated TBAD (un-TBAD) and thoracic endovascular aortic repair (TEVAR) is considered the gold-standard intervention for these clinical challenges.
METHODS
We undertook a systematic review of the literature regarding TEVAR intervention in co-TBAD and un-TBAD. A comprehensive search was undertaken across four major databases and was evaluated and assessed until June 2020.
RESULTS
A total of 16,104 patients were included in the study (7772 patients co-TBAD and 8352 un-TBAD). A significantly higher proportion of comorbidities were seen in co-TBAD patients compared with un-TBAD. Acute dissection was more frequent in the co-TBAD group (73.55% vs. 66.91%), while chronic dissection was more common in un-TBAD patients (33.8% vs. 70.73%). Postprocedure stroke was higher in co-TBAD (5.85% vs. 3.92%; p < .01), while postprocedural renal failure was higher in un-TBAD patients (7.23 vs. 11.38%; p < .01). No difference was observed in in-hospital mortality however the 30 days mortality was higher in the co-TBAD group. One-year survival was higher in the uncomplicated group but this difference was not observed in the 5-year survival.
CONCLUSION
In our analysis we can appreciate that despite significantly higher comorbidities in the co-TBAD cohort, there was no difference in in-hospital mortality between the two groups and the 5-year survival did not have any difference
A Case of an Infant with Hydrops Fetalis and Hypoxic-Ischemic Encephalopathy Treated with Therapeutic Hypothermia.
No full textHydrops fetalis (HF) is a serious fetal condition. Infants born with HF are often critically unwell, requiring resuscitation and prolonged intensive care admission. Despite medical advances, morbidity and mortality remain high. Therapeutic hypothermia is the standard of care for term and late preterm infants with moderate-to-severe hypoxic-ischemic encephalopathy (HIE), as it improves neurodevelopmental outcomes in surviving infants. To our knowledge, the use of therapeutic hypothermia has not previously been reported in infants with HF. We report the case of a term infant with undiagnosed HF, who required resuscitation and received 72 hours of therapeutic hypothermia for moderate HIE. We describe the cardiovascular instability encountered during therapeutic hypothermia and how it was successfully managed. She responded well to treatment and was discharged home bottle-feeding, with normal neurology and a normal brain magnetic resonance imaging scan. From this case, therapeutic hypothermia in infants with HF and HIE is feasible and can be beneficial in carefully selected HF infants meeting cooling criteria
Serological responses to SARS-CoV-2 following non-hospitalised infection: clinical and ethnodemographic features associated with the magnitude of the antibody response.
No full textOBJECTIVE
To determine clinical and ethnodemographic correlates of serological responses against the SARS-CoV-2 spike glycoprotein following mild-to-moderate COVID-19.
DESIGN
A retrospective cohort study of healthcare workers who had self-isolated due to COVID-19.
SETTING
University Hospitals Birmingham NHS Foundation Trust, UK (UHBFT).
PARTICIPANTS
956 healthcare workers were recruited by open invitation via UHBFT trust email and social media between 27 April 2020 and the 8 June 2020.
INTERVENTION
Participants volunteered a venous blood sample that was tested for the presence of anti-SARS-CoV-2 spike glycoprotein antibodies. Results were interpreted in the context of the symptoms of their original illness and ethnodemographic variables.
RESULTS
Using an assay that simultaneously measures the combined IgG, IgA and IgM response against the spike glycoprotein (IgGAM), the overall seroprevalence within this cohort was 46.2% (n=442/956). The seroprevalence of immunoglobulin isotypes was 36.3%, 18.7% and 8.1% for IgG, IgA and IgM, respectively. IgGAM identified serological responses in 40.6% (n=52/128) of symptomatic individuals who reported a negative SARS-CoV-2 PCR test. Increasing age, non-white ethnicity and obesity were independently associated with greater IgG antibody response against the spike glycoprotein. Self-reported fever and fatigue were associated with greater IgG and IgA responses against the spike glycoprotein. The combination of fever and/or cough and/or anosmia had a positive predictive value of 92.3% for seropositivity in self-isolating individuals a time when Wuhan strain SARS-CoV-2 was predominant.
CONCLUSIONS AND RELEVANCE
Assays employing combined antibody detection demonstrate enhanced seroepidemiological sensitivity and can detect prior viral exposure even when PCR swabs have been negative. We demonstrate an association between known ethnodemographic risk factors associated with mortality from COVID-19 and the magnitude of serological responses in mild-to-moderate disease
Determining the effect of ocular chemical injuries on topical drug delivery.
No full textOcular chemical injuries (OCIs) commonly cause ocular damage and visual loss and treatment uses topical therapies to facilitate healing and limit complications. However, the impact of chemical injury on corneal barrier function and treatment penetration is unknown. Therefore, the aim of this study was to determine the effect of OCI on drug penetration and absorption. Porcine corneal explants were used to assess histological damage, electrical resistance, and the trans-corneal penetration/corneal adsorption of reference compounds (sodium fluorescein and rhodamine B) and dexamethasone. Corneal explants were injured with either 1 M sulfuric acid, or 1 M sodium hydroxide. Dexamethasone penetration was measured using high-performance liquid chromatography (HPLC) and that of fluorescein and rhodamine using fluorescence. Dexamethasone corneal adsorption was measured using enzyme-linked immunoabsorbant assay (ELISA). Both acid and alkaline injuries reduced trans-corneal electrical resistance. NaOH injury increased hydrophilic fluorescein penetration (NaOH 8.59 ± 1.50E-05 cm.min vs. Hanks' Balanced Salt Solution (HBSS) 1.64 ± 1.01E-06 cm.min) with little impact on hydrophobic rhodamine B (1 M NaOH 6.55 ± 2.45E-04 cm.min vs. HBSS 4.60 ± 0.972E-04 cm.min) and dexamethasone penetration (1 M NaOH 3.00 ± 0.853E-04 cm.min vs. HBSS 2.69 ± 0.439E-04 cm.min). By contrast, HSO decreased trans-corneal penetration of hydrophilic fluorescein (HSO 1.16 ± 14.2E-07 cm.min) and of hydrophobic dexamethasone (HSO 1.88 ± 0.646E-04 cm.min) and rhodamine B (HSO 4.60 ± 1.42E-05 cm.min). Acid and alkaline OCI differentially disrupted the corneal epithelial barrier function. Acid injury reduced penetration of hydrophobic dexamethasone and rhodamine B as well as hydrophilic fluorescein, which may translate clinically into reduced drug penetration after OCI, while alkaline injury increased fluorescein penetration, with minimal effect on dexamethasone and rhodamine B penetration
Correction to: Hyperkalemia in Chronic Kidney Disease in the New Era of Kidney Protection Therapies.
No full textEthnic differences in severe asthma clinical care and outcomes: an analysis of United Kingdom primary and specialist care.
No full textBACKGROUND
Understanding the effects of ethnicity in severe asthma is important for optimal personalised patient care.
OBJECTIVE
To assess ethnic differences in disease control, exacerbations, biological phenotype and treatment in UK severe asthma.
METHODS
We compared demographics, type-2 biomarkers, lung function, asthma control, medications and healthcare utilisation between White and ethnic minority group [EMG] patients in the UK Severe Asthma Registry (UKSAR) and Optimum Patient Care Research Database (OPCRD).
RESULTS
3,637 patients (665 EMG) were included from UKSAR and 10,549 (577 EMG) from OPCRD. EMG patients had higher levels of uncontrolled disease when measured using the asthma control questionnaire in UKSAR (OR:1.47, 95%CI: 1.12-1.93) and the Royal College of Physicians 3 Questions in OPCRD (OR:1.82, 95%CI: 1.27-2.60). Although exacerbation rates were similar, EMG patients were more likely to have recently attended ED (OR:1.55, 95%CI: 1.26-1.92) or been hospitalised (OR:1.31, 95% CI: 1.07-1.59) due to their asthma. Inflammatory biomarkers were consistently higher in EMG severe asthma including blood eosinophils in OPCRD (Ratio:1.12, 95%CI: 1.05-1.20) and in UKSAR blood eosinophils (Ratio:1.16, 95%CI: 1.06-1.27), FeNO (Ratio:1.14, 95%CI: 1.04-1.26) and IgE (Ratio:1.70, 95%CI: 1.47-1.97). EMG patients were more likely to be atopic in the UKSAR (OR:1.32; 95%CI: 1.07-1.63) and OPCRD (OR:1.67; 95%CI: 1.26-2.21), and less likely to be using maintenance oral corticosteroids at referral (OR:0.75 [95%CI: 0.61-0.92]).
CONCLUSIONS
Severe asthma patients from EMGs presented with higher disease burden and were more likely to attend ED. They had a distinct phenotypic presentation, and differences in medicine utilisation, with higher levels of type-2 biomarkers
Prognostic Models for Predicting Remission of Diabetes Following Bariatric Surgery: A Systematic Review and Meta-analysis.
No full textBACKGROUND
Remission of type 2 diabetes following bariatric surgery is well established, but identifying patients who will go into remission is challenging.
PURPOSE
To perform a systematic review of currently available diabetes remission prediction models, compare their performance, and evaluate their applicability in clinical settings.
DATA SOURCES
A comprehensive systematic literature search of MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) was undertaken. The search was restricted to studies published in the last 15 years and in the English language.
STUDY SELECTION
All studies developing or validating a prediction model for diabetes remission in adults after bariatric surgery were included.
DATA EXTRACTION
The search identified 4,165 references, of which 38 were included for data extraction. We identified 16 model development and 22 validation studies.
DATA SYNTHESIS
Of the 16 model development studies, 11 developed scoring systems and 5 proposed logistic regression models. In model development studies, 10 models showed excellent discrimination with area under the receiver operating characteristic curve ≥0.800. Two of these prediction models, ABCD and DiaRem, were widely externally validated in different populations, in a variety of bariatric procedures, and for both short- and long-term diabetes remission. Newer prediction models showed excellent discrimination in test studies, but external validation was limited.
LIMITATIONS
While the key messages were consistent, a large proportion of the studies were conducted in small cohorts of patients with short duration of follow-up.
CONCLUSIONS
Among the prediction models identified, the ABCD and DiaRem models were the most widely validated and showed acceptable to excellent discrimination. More studies validating newer models and focusing on long-term diabetes remission are needed