Gadoxetic acid in hepatocellular carcinoma and liver metastases: pearls and pitfalls.

Gadoxetic disodium (Primovist) is a hepatocyte-specific magnetic resonance imaging (MRI) contrast agent with increasing popularity with its unique dual dynamic and excretory properties in focal liver lesion detection and characterisation. In-depth knowledge of its diagnostic utility and pitfalls in hepatocellular carcinoma (HCC) and liver metastases is crucial in facilitating clinical management. The current article reviews the pearls and pitfalls in these aspects with highlights from the latest research evidence. Pearls for common usage of Primovist in HCC includes detection of precursor cancer lesions in cirrhotic patients. Hepatobiliary phase hypointensity precedes arterial phase hyperenhancement (APHE) in hepatocarcinogenesis. Hepatobiliary phase hypointense nodules without APHE can represent early or progressed hepatocellular carcinoma (HCC) and high-grade dysplastic nodules. In addition, Primovist is useful to differentiate HCC from pseudolesions. Pitfalls in diagnosing HCC include transient tachypnoea in the arterial phase, rare hepatobiliary phase hyperintense HCC, and decompensated liver cirrhosis compromising image quality. Primovist is currently the most sensitive technique in diagnosing liver metastases before curative hepatic resection. Other patterns of enhancement of liver metastases, "disappearing" liver metastases are important pitfalls. Radiologists should be aware of the diagnostic utility, limitations, and potential pitfalls for the common usage of hepatobiliary specific contrast agent in liver MRI.

Fat necrosis in the breast: a multimodality imaging review of its natural course with different aetiologies.

Fat necrosis of the breast is a commonly encountered condition in daily practice. It is a benign pathology, but it can have variable manifestations and patterns that may sometimes mimic malignancy, depending on its stage of evolution and its underlying cause. This review demonstrates the wide spectrum of appearances of fat necrosis on mammography, digital breast tomosynthesis (DBT), ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), and positron-emission tomography (PET). Sequential follow-up images are included in some cases to illustrate the temporal change of the findings. The typical location and distribution of fat necrosis from a comprehensive list of aetiologies are discussed. Improved knowledge of the multimodality imaging features of fat necrosis could enhance diagnostic accuracy and clinical management, thus avoiding unnecessary invasive investigations.

The house is a machine for everything: the role of the built environment in group homes during the COVID-19 pandemic.

OBJECTIVES: Individuals living in group homes during the COVID-19 pandemic faced unique challenges and health risks related to living in shared spaces. This study aimed to assess the experiences of living and working in a group home during the pandemic and to explore the role of the built environment. STUDY DESIGN AND METHODS: We conducted longitudinal working groups with group home residents with intellectual and developmental disabilities and serious mental illness, group home staff, and families/caregivers of residents from December 2020 through December 2022. Common themes highlighting ways in which group home residents, staff, and caregivers perceived the built environment to impact living in a group home during the COVID-19 pandemic were identified. RESULTS: Resonant themes centered around increased risk of COVID-19 infection, ad hoc spatial adaptations for infection control, space-related challenges due to isolation and quarantine requirements, and limited access to public spaces. CONCLUSION: Group home residents and staff experienced multiple health and wellness challenges during the COVID-19 pandemic related to their surrounding built environment. Mechanisms to engage group home residents in modifications of their built environment may improve the effectiveness of infection control policies while acknowledging individual autonomy.

Multimodality imaging of extra-nodal lymphoma in the head and neck.

Malignant lymphomas represent approximately 5% of all malignant neoplasms of the head and neck. The head and neck region is the second most frequent anatomical site of extra-nodal lymphomas (after the gastrointestinal tract). Most are non-Hodgkin's lymphomas of B-cell lineage, and overall diffuse large B-cell lymphoma is the most common type. They can present in highly variable appearances in different anatomical subsites in the head and neck. There is little literature on their imaging appearances on different imaging methods including ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), and integrated positron-emission tomography (PET)/CT. The review aims to illustrate the presentation of histopathological-proven extra-nodal lymphoma in the head and neck using various imaging methods.

The ins and outs of male breast and anterior chest wall lesions from childhood to adulthood.

Physiological and pathological processes arising from the breast and anterior chest wall may share similar clinical presentations because of the small volume of male breasts. Therefore, imaging is frequently required to localise and characterise the lesion and guide biopsy when radiological findings are equivocal or suspicious. Mammography or digital breast tomosynthesis (DBT) and ultrasound are the mainstays of breast imaging work-up. Other imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI) and positron-emission tomography (PET) can sometimes augment the investigation and aid treatment planning. This article reviews the key imaging features of a wide spectrum of benign and malignant conditions that involve the male breast and anterior chest wall across various age groups. Familiarisation with the salient radiological findings is essential for reaching an accurate diagnosis and optimising management.

Safety and efficacy of magnetic seed localisation of non-palpable breast lesions: pilot study in a Chinese population.

INTRODUCTION: A magnetic seed marker system (Magseed, Endomagnetics, Cambridge, United Kingdom) is used as a localisation method for non-palpable breast lesions in the United States, Europe, and Hong Kong. It overcomes many limitations of conventional techniques and allows scheduling flexibility. We sought to evaluate its efficacy and safety in the Chinese population. METHODS: We retrospectively reviewed all Chinese women who underwent magnetic seed marker-guided breast lesion excision from June 2019 to February 2020 at a single institution. Placement success (final target-to-seed distance <10 mm) was evaluated by imaging on the day of surgery. Specimen radiographs and pathology reports were reviewed for magnetic seed markers and target removal. Margin clearance and re-excision rates were analysed. RESULTS: Twenty two magnetic seed markers were placed in 21 patients under sonographic or stereotactic guidance to localise 21 target lesions. One target lesion required two magnetic seed markers for bracketing. There was no migration of nine markers placed 6 to 56 days before the day of surgery. Placement success was achieved in 20 (90.9%) cases. Mean final target-to-seed distance was 3.1 mm. Two out of 21 (9.5%) lesions required alternative localisation due to marker migration ≥10 mm, while 19 (90.5%) lesions underwent successful magnetic seed marker-guided excision. Three of these 19 lesions (15.8%) were excised with therapeutic intent, one of which (33%) required re-excision due to a close margin. All 22 magnetic seed markers were successfully removed. No complications were reported. CONCLUSION: Magnetic seed markers demonstrated safety and efficacy in Chinese women for breast lesion localisation and excision.

HIV care cost in England: a cross-sectional analysis of antiretroviral treatment and the impact of generic introduction.

OBJECTIVES: Reliable and timely HIV care cost estimates are important for policy option appraisals of HIV treatment and prevention strategies. As HIV clinical management and outcomes have changed, we aimed to update profiles of antiretroviral (ARV) usage pattern, patent/market exclusivity details and management costs in adults (≥ 18 years old) accessing HIV specialist care in England. METHODS: The data reported quarterly to the HIV and AIDS Reporting System in England was used to identify ARV usage pattern, and were combined with British National Formulary (BNF) prices, non-ARV care costs and patent/market exclusivity information to generate average survival-adjusted lifetime care costs. The cumulative budget impact from 2018 to the year in which all current ARVs were expected to lose market exclusivity was calculated for a hypothetical 85 000 (± 5000) person cohort, which provided an illustration of potential financial savings afforded by bioequivalent generic switches. Price scenarios explored BNF70 (September 2015) prices and generics at 10/20/30/50% of proprietary prices. The analyses took National Health Service (NHS) England's perspective (as the payer), and results are presented in 2016/2017 British pounds. RESULTS: By 2033, most currently available ARVs would lose market exclusivity; that is, generics could be available. Average per person lifetime HIV cost was ~£200 000 (3.5% annual discount) or ~£400 000 (undiscounted), reducing to ~£70 000 (3.5% annual discount; ~£120 000 undiscounted) with the use of generics (assuming that generics cost 10% of proprietary prices). The cumulative budget to cover 85 000 (± 5000) persons for 16 years (2018-2033) was £10.5 (± 0.6) billion, reducing to £3.6 (± 0.2) billion with the use of generics. CONCLUSIONS: HIV management costs are high but financial efficiency could be improved by optimizing generic use for treatment and prevention to mitigate the high cost of lifelong HIV treatment. Earlier implementation of generics as they become available offers the potential to maximize the scale of the financial savings.

Where do we diagnose HIV infection? Monitoring new diagnoses made in nontraditional settings in England, Wales and Northern Ireland.

OBJECTIVES: The objectives of the study were to describe 10-year trends in HIV diagnosis setting and to explore predictors of being diagnosed outside a sexual health clinic (SHC). METHODS: Analyses of national HIV surveillance data were restricted to adults (aged ≥ 15 years) diagnosed in 2005-2014 in England, Wales and Northern Ireland. Logistic regression identified factors associated with diagnosis outside an SHC (2011-2014). RESULTS: Between 2005 and 2014, 63 599 adults were newly diagnosed with HIV infection; 83% had a diagnosis setting reported. Most people were diagnosed in SHCs (69%) followed by: medical admissions/accident and emergency (A&E; 8.6%), general practice (6.4%), antenatal services (5.5%), out-patient services (3.6%), infectious disease units (2.7%) and other settings (4.0%). The proportion of people diagnosed outside SHCs increased from 2005 to 2014, overall (from 27% to 32%, respectively) and among men who have sex with men (MSM) (from 14% to 21%) and black African men (from 25% to 37%) and women (from 39% to 52%) (all trend P < 0.001). Median CD4 increased across all settings, but was highest in SHCs (384 cells/µL) and lowest in medical admissions/A&E (94 cells/µL). Predictors of being diagnosed outside SHCs included: acquiring HIV through heterosexual contact [adjusted odds ratio (aOR) 1.99; 95% confidence interval (CI) 1.81-2.18] or injecting drug use (aOR: 3.28; 95% CI: 2.56-4.19; reference: MSM), being diagnosed late (< 350 cells/µL) (aOR: 2.55; 95% CI: 2.36-2.74; reference: diagnosed promptly) and being of older age at diagnosis (35-49 years: aOR: 1.60; 95% CI: 1.39-1.83; ≥ 50 years: aOR: 2.48; 95% CI: 2.13-2.88; reference: 15-24 years). CONCLUSIONS: The proportion of HIV diagnoses made outside SHCs has increased over the past decade in line with evolving HIV testing guidelines. However, the rate of late diagnosis remains high, indicating that further expansion of testing is necessary, as many people may have had missed opportunities for earlier diagnosis.

Delayed diagnosis of tuberculosis: risk factors and effect on mortality among older adults in Hong Kong.

OBJECTIVE: To assess the risk factors and effects of delayed diagnosis on tuberculosis (TB) mortality in Hong Kong. METHODS: All consecutive patients with TB notified in 2010 were tracked through their clinical records for treatment outcome until 2012. All TB cases notified or confirmed after death were identified for a mortality survey on the timing and causes of death. RESULTS: Of 5092 TB cases notified, 1061 (20.9%) died within 2 years of notification; 211 (4.1%) patients died before notification, 683 (13.4%) died within the first year, and 167 (3.3%) died within the second year after notification. Among the 211 cases with TB notified after death, only 30 were certified to have died from TB. However, 52 (24.6%) died from unspecified pneumonia/sepsis possibly related to pulmonary TB. If these cases are counted, the total TB-related deaths increases from 191 to 243. In 82 (33.7%) of these, TB was notified after death. Over 60% of cases in which TB diagnosed after death involved patients aged ≥80 years and a similar proportion had an advance care directive against resuscitation or investigation. Independent factors for TB notified after death included female sex, living in an old age home, drug abuse, malignancy other than lung cancer, sputum TB smear negative, sputum TB culture positive, and chest X-ray not done. CONCLUSIONS: High mortality was observed among patients with TB aged ≥80 years. Increased vigilance is warranted to avoid delayed diagnosis and reduce the transmission risk, especially among elderly patients with co-morbidities living in old age homes.

The effects of neighborhood views containing multiple environmental features on road traffic noise perception at dwellings.

The importance of non-acoustical factors including the type of visual environment on human noise perception becomes increasingly recognized. In order to reveal the relationships between long-term noise annoyance and different types of neighborhood views, 2033 questionnaire responses were collected for studying the effect of perceptions of different combinations of views of sea, urban river, greenery, and/or noise barrier on the annoyance responses from residents living in high-rise apartments in Hong Kong. The collected responses were employed to formulate a multivariate model to predict the probability of invoking a high annoyance response from residents. Results showed that views of sea, urban river, or greenery could lower the probability, while views of noise barrier could increase the probability. Views of greenery had a stronger noise moderation capability than views of sea or urban river. The presence of an interaction effect between views of water and views of noise barrier exerted a negative influence on the noise annoyance moderation capability. The probability due to exposure to an environment containing views of noise barriers and urban rivers would be even higher than that due to exposure to an environment containing views of noise barriers alone.

Posaconazole in lung transplant recipients: use, tolerability, and efficacy.

BACKGROUND: Fungal infection is a common cause of mortality and morbidity in lung transplant recipients (LuTR). Treatment failure to first-line antifungals because of resistance or intolerance is an increasing problem. Posaconazole (PCZ), a triazole antifungal, is an attractive treatment option. METHODS: We performed a single-center retrospective study to describe the use, tolerability, efficacy, and drug interaction effect (with tacrolimus) of PCZ oral suspension in LuTR. RESULTS: Seventy-eight patients were treated with PCZ oral suspension for prophylaxis (n = 15), pre-emptive treatment (n = 31), and treatment of possible (n = 7) and probable (n = 25) invasive fungal infection. A range of fungal isolates was encountered. Resolution was observed in 52.4% (probable, possible, and pre-emptive treatment groups). Aggregate all-cause 1-year mortality was 12.8%. PCZ was well tolerated with 11.5% of patients experiencing adverse effects. Despite dose adjustment strategies, 11.7% of patients experienced supratherapeutic tacrolimus levels, which in 5 cases was associated with a rise (mean 21.6 µmol/L) in serum creatinine. CONCLUSIONS: PCZ is well tolerated and appears effective in the management of fungal infection after lung transplantation. Patients receiving concurrent tacrolimus require careful therapeutic drug monitoring.

MTHFR c.677C>T is a risk factor for non-syndromic cleft lip with or without cleft palate in Chile.

OBJECTIVE: The functional variant within the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene c.677C>T, producing alterations in folate metabolism, has been associated with the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P). We assessed this association in a Chilean population using a combined analysis of case-control and case-parent trio samples. SUBJECTS AND METHODS: Samples of 165 cases and 291 controls and 121 case-parent trios (sharing the cases) were genotyped. Odds ratio (OR) was estimated for case-control (allele and genotype frequency differences), and this result was confirmed by allele transmission distortion in trios. Due to that these samples are not independent, a combined OR was also computed. Maternal genotype effect was additionally evaluated based on a log-linear method. RESULTS: Borderline but not significant OR (1.28; CI 0.97-1.69) was observed for risk allele (T) in the case-control sample. However, triad sample showed a significant association (OR 1.56: CI 1.09-2.25) which was confirmed by the combined OR (1.37; CI 1.11-1.71). Maternal genotype has been also associated with the phenotype (P = 0.002). CONCLUSIONS: In contrast to previous reports considering Chilean subjects, our results demonstrated that the offspring and maternal genotypes for MTHFR c.677C>T variant are strongly associated with NSCL/P in this Chilean population.

Treatment outcome and patterns of relapse following adjuvant carboplatin for stage I testicular seminomatous germ-cell tumour: results from a 17-year UK experience.

BACKGROUND: Following inguinal orchidectomy, management options for patients with stage I seminoma include initial surveillance or treatment with adjuvant radiotherapy or chemotherapy. The anticipated relapse rate for patients followed by surveillance alone is ∼15%, with adjuvant treatment this risk is reduced to ∼4%-5% at 5 years. After carboplatin treatment, follow-up strategies vary and there are no validated, predictive markers of relapse. PATIENTS AND METHODS: We conducted a retrospective analysis of all patients presenting with stage I seminoma who received a single cycle of adjuvant carboplatin in South Central England between 1996 and 2013. We report on outcome and the results of univariate and multivariate analysis evaluating possible risk factors for post carboplatin relapse. RESULTS: A total of 517 eligible patients were identified. All underwent nuclear medicine estimation of glomerular filtration rate before treatment with carboplatin (dosed at area under the curve × 7). With a median follow-up of 47.2 months (range 0.4-214 months), 21/517 patients have relapsed resulting in a 5-year estimated relapse-free survival of 95.0% (95% confidence interval 92.8% to 97.3%). Median time to relapse was 22.7 months (range 12.5-109.5 months). Relapse beyond 3 years was rare (4/517; 0.8%). Twenty of 21 (95%) relapsed patients had retroperitoneal lymph node metastases. The majority (16/21; 76%) of patients had elevated tumour markers at relapse. Twenty of 517 (3.9%) patients developed a new contralateral testicular germ-cell cancer. There were no seminoma-related deaths. Tumour size was the only variable significantly associated with an increased risk of relapse. CONCLUSIONS: Overall results for this large cohort of patients confirm an excellent prognosis for these patients with outcomes equivalent to those seen in prospective clinical trials. Increasing tumour size alone appears to be associated with an increased risk of post chemotherapy relapse.

Clinical outcomes following neoadjuvant cisplatin-based chemotherapy for bladder cancer in elderly compared with younger patients.

Bladder cancer is a disease of the elderly. Older patients might potentially be undertreated due to assumptions about benefit versus risk. Our objective was to determine outcomes in older patients receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC). We hypothesised that appropriately selected elderly patients (≥70 years) with MIBC could have similar clinical outcomes, and be safely treated, with standard neoadjuvant chemotherapy prior to definitive cystectomy or radiotherapy. We utilised a single institution case series analysis of patients with T2-4a N0 M0 transitional cell carcinoma of the bladder treated with cisplatin-based neoadjuvant chemotherapy between 2005 and 2011. Eighty-three patients were eligible. Median age was 68 (range 48-80), 33 patients (40%) were ≥70 years. Overall survival at 3 years was 65.8% (≥70) and 63.2% (<70) (P = 0.653), relapse-free survival at 3 years was 61.6% and 54.8% respectively (P = 0.471). The rates going forward to definitive local therapy (87.9% ≥ 70 and 84.0% < 70) and the pathological complete response rate (31.3% ≥ 70 and 40% < 70) were similar. Disease relapse rate was also similar (63.6% ≥ 70 vs. 60% < 70, P = 0.906). Elderly patients with good functional status and limited comorbidities diagnosed with MIBC receiving standard neoadjuvant chemotherapy followed by cystectomy or radiotherapy can have similar clinical outcomes as their younger counterparts. Prospective studies evaluating the optimum curative management in this elderly population are warranted.

Serum total hCGß level is an independent prognostic factor in transitional cell carcinoma of the urothelial tract.

BACKGROUND: Serum total human chorionic gonadotrophin ß subunit (hCGß) level might have prognostic value in urothelial transitional cell carcinoma (TCC) but has not been investigated for independence from other prognostic variables. METHODS: We utilised a clinical database of patients receiving chemotherapy between 2005 and 2011 for urothelial TCC and an independent cohort of radical cystectomy patients for validation purposes. Prognostic variables were tested by univariate Kaplan-Meier analyses and log-rank tests. Statistically significant variables were then assessed by multivariate Cox regression. Total hCGß level was dichotomised at < vs ≥2 IU l(-1). RESULTS: A total of 235 chemotherapy patients were eligible. For neoadjuvant chemotherapy, established prognostic factors including low ECOG performance status, normal haemoglobin, lower T stage and suitability for cisplatin-based chemotherapy were associated with favourable survival in univariate analyses. In addition, low hCGß level was favourable when assessed either before (median survival not reached vs 1.86 years, P=0.001) or on completion of chemotherapy (4.27 vs 0.42 years, P=0.000002). This was confirmed in multivariate analyses and in patients receiving first- and second-line palliative chemotherapy, and in a radical cystectomy validation set. CONCLUSIONS: Serum total hCGß level is an independent prognostic factor in patients receiving chemotherapy for urothelial TCC in both curative and palliative settings.

Epidemiology and risk factors for severe respiratory syncytial virus infections requiring pediatric intensive care admission in Hong Kong children.

PURPOSE: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infection in young children. However, there are limited data on severe RSV infection requiring pediatric intensive care unit (PICU) admission. This retrospective study described features of RSV-associated PICU admissions in Hong Kong and investigated factors for mortality and duration of PICU stay. METHODS: Children with laboratory-confirmed RSV infection and admitted to the PICUs of all eight government hospitals in Hong Kong between January 2009 and June 2011 were identified from computerized auditing systems and PICU databases. RSV in respiratory samples was detected by direct immunofluorescence and/or viral culture. The relationships between mortality and PICU duration and demographic and clinical factors were analyzed. RESULTS: A total of 118 (2.4 %) PICU admissions were identified among 4,912 RSV-positive pediatric cases in all hospitals. Sixty-five (55.6 %) patients were infants. PICU admissions were higher between October and March. Eight (6.8 %) patients died, but only two were infants. RSV-associated mortality was related to prior sick contact, presence of older siblings, neurodevelopmental conditions, chromosomal and genetic diseases, and bacterial co-infections, but none was significant following logistic regression analyses (odds ratio 9.36, 95 % confidence interval 0.91-96.03 for prior sick contact, p = 0.060). Chronic lung disease was the only risk factor for the duration of PICU admission (ß = 0.218, p = 0.017). CONCLUSIONS: The majority of RSV-infected children do not require PICU support. There is winter seasonality for RSV-associated PICU admission in Hong Kong. Prior sick contact is the only risk factor for RSV-associated mortality, whereas the presence of chronic lung disease is associated with longer PICU stay. The current risk-based approach of RSV prophylaxis may not be effective in reducing severe RSV infections.

Angiogenesis in spontaneous tumors and implications for comparative tumor biology.

Blood supply is essential for development and growth of tumors and angiogenesis is the fundamental process of new blood vessel formation from preexisting ones. Angiogenesis is a prognostic indicator for a variety of tumors, and it coincides with increased shedding of neoplastic cells into the circulation and metastasis. Several molecules such as cell surface receptors, growth factors, and enzymes are involved in this process. While antiangiogenic therapy for cancer has been proposed over 20 years ago, it has garnered much controversy in recent years within the scientific community. The complex relationships between the angiogenic signaling cascade and antiangiogenic substances have indicated the angiogenic pathway as a valid target for anticancer drug development and VEGF has become the primary antiangiogenic drug target. This review discusses the basic and clinical perspectives of angiogenesis highlighting the importance of comparative biology in understanding tumor angiogenesis and the integration of these model systems for future drug development.