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Pancreatic adenocarcinoma: imaging techniques for diagnosis and management.
No full textPancreatic cancer is a leading cause of death from cancer but only a minority of patients with pancreatic ductal adenocarcinomas are eligible for curative resection. The increasing role of neoadjuvant therapy provides hope of improving outcomes. However, progress is also reliant on advances in imaging that can identify disease earlier and accurately assess treatment response. Computed tomography remains the cornerstone in evaluation of resectability, offering excellent spatial resolution. However, in high-risk patients, additional magnetic resonance imaging and positron emission tomography-computed tomography may further guide treatment decisions. Conventional computed tomography can be limited in its ability to determine disease response after neoadjuvant therapy. Dual-energy computed tomography and computed tomography or magnetic resonance imaging perfusion studies emerging as potentially better alternatives. Combined with pioneering advances in radiomic analysis, these modalities also show promise in analysing tumour heterogeneity and thereby more accurately predicting outcomes. This article reviews these imaging techniques
Arterial and venous thromboembolism in critically ill, COVID 19 positive patients admitted to Intensive Care Unit.
No full textEffect of priming interval on reactogenicity, peak immunological response, and waning after homologous and heterologous COVID-19 vaccine schedules: exploratory analyses of Com-COV, a randomised control trial.
No full textBACKGROUND
Priming COVID-19 vaccine schedules have been deployed at variable intervals globally, which might influence immune persistence and the relative importance of third-dose booster programmes. Here, we report exploratory analyses from the Com-COV trial, assessing the effect of 4-week versus 12-week priming intervals on reactogenicity and the persistence of immune response up to 6 months after homologous and heterologous priming schedules using the vaccines BNT162b2 (tozinameran, Pfizer/BioNTech) and ChAdOx1 nCoV-19 (AstraZeneca).
METHODS
Com-COV was a participant-masked, randomised immunogenicity trial. For these exploratory analyses, we used the trial's general cohort, in which adults aged 50 years or older were randomly assigned to four homologous and four heterologous vaccine schedules using BNT162b2 and ChAdOx1 nCoV-19 with 4-week or 12-week priming intervals (eight groups in total). Immunogenicity analyses were done on the intention-to-treat (ITT) population, comprising participants with no evidence of SARS-CoV-2 infection at baseline or for the trial duration, to assess the effect of priming interval on humoral and cellular immune response 28 days and 6 months post-second dose, in addition to the effects on reactogenicity and safety. The Com-COV trial is registered with the ISRCTN registry, 69254139 (EudraCT 2020-005085-33).
FINDINGS
Between Feb 11 and 26, 2021, 730 participants were randomly assigned in the general cohort, with 77-89 per group in the ITT analysis. At 28 days and 6 months post-second dose, the geometric mean concentration of anti-SARS-CoV-2 spike IgG was significantly higher in the 12-week interval groups than in the 4-week groups for homologous schedules. In heterologous schedule groups, we observed a significant difference between intervals only for the BNT162b2-ChAdOx1 nCoV-19 group at 28 days. Pseudotyped virus neutralisation titres were significantly higher in all 12-week interval groups versus 4-week groups, 28 days post-second dose, with geometric mean ratios of 1·4 (95% CI 1·1-1·8) for homologous BNT162b2, 1·5 (1·2-1·9) for ChAdOx1 nCoV-19-BNT162b2, 1·6 (1·3-2·1) for BNT162b2-ChAdOx1 nCoV-19, and 2·4 (1·7-3·2) for homologous ChAdOx1 nCoV-19. At 6 months post-second dose, anti-spike IgG geometric mean concentrations fell to 0·17-0·24 of the 28-day post-second dose value across all eight study groups, with only homologous BNT162b2 showing a slightly slower decay for the 12-week versus 4-week interval in the adjusted analysis. The rank order of schedules by humoral response was unaffected by interval, with homologous BNT162b2 remaining the most immunogenic by antibody response. T-cell responses were reduced in all 12-week priming intervals compared with their 4-week counterparts. 12-week schedules for homologous BNT162b2 and ChAdOx1 nCoV-19-BNT162b2 were up to 80% less reactogenic than 4-week schedules.
INTERPRETATION
These data support flexibility in priming interval in all studied COVID-19 vaccine schedules. Longer priming intervals might result in lower reactogenicity in schedules with BNT162b2 as a second dose and higher humoral immunogenicity in homologous schedules, but overall lower T-cell responses across all schedules. Future vaccines using these novel platforms might benefit from schedules with long intervals.
FUNDING
UK Vaccine Taskforce and National Institute for Health and Care Research
Letter: non-selective beta-blockers in cirrhosis-effect beyond portal hypertension. Authors' reply.
No full textMetabolic dysfunction and cancer in HCV: Shared pathways and mutual interactions.
No full textHCV hijacks many host metabolic processes in an effort to aid viral replication. The resulting hepatic metabolic dysfunction underpins many of the hepatic and extrahepatic manifestations of chronic hepatitis C (CHC). However, the natural history of CHC is also substantially influenced by the host metabolic status: obesity, insulin resistance and hepatic steatosis are major determinants of CHC progression toward hepatocellular carcinoma (HCC). Direct-acting antivirals (DAAs) have transformed the treatment and natural history of CHC. While DAA therapy effectively eradicates the virus, the long-lasting overlapping metabolic disease can persist, especially in the presence of obesity, increasing the risk of liver disease progression. This review covers the mechanisms by which HCV tunes hepatic and systemic metabolism, highlighting how systemic metabolic disturbance, lipotoxicity and chronic inflammation favour disease progression and a precancerous niche. We also highlight the therapeutic implications of sustained metabolic dysfunction following sustained virologic response as well as considerations for patients who develop HCC on the background of metabolic dysfunction
Congenital Mastoid Cholesteatoma.
No full textOBJECTIVE
Congenital cholesteatomas account for just up to 5% of all cholesteatomas and most commonly arise in the petrous apex and middle ear. Congenital cholesteatomas arising in the mastoid are rare and typically present late.
METHODS
We report a case series of three cases managed in our Department between 2006 and 2021 and present a summary of the current literature Results: Three cases of congenital cholesteatoma of mastoid origin were managed in our Department since 2006. Of our three cases, two were managed surgically and one conservatively. Congenital cholesteatomas arising in the mastoid is a rare finding and even amongst reported cases, not all are clearly mastoid in origin. Their location allows for considerable growth before symptoms develop. Pain and localised swelling in the temporal area are the most common presenting symptoms which can lead to diagnostic challenges. Our cases, show that although surgery is often appropriate, conservative management may be suitable in certain situations.
CONCLUSION
Congenital cholesteatoma of mastoid origin is a rare and can present a diagnostic challenge. Greater awareness is important to facilitate early detection. A high index of suspicion is needed in those presenting with retro-auricular pain and swelling in the context of a normal ontological examination
Global Current Practice Patterns for the Management of Central Retinal Artery Occlusion.
No full textGlobal practice paradigms for central retinal artery occlusion (CRAO) were summarized. Responses were collected from specialists via survey. Management patterns for CRAO rely on physician and center-level preferences given the lack of evidence-based international guidelines
Metformin and risk of age-related macular degeneration in individuals with type 2 diabetes: a retrospective cohort study.
No full textBACKGROUND
Age-related macular degeneration (AMD) in its late stages is a leading cause of sight loss in developed countries. Some previous studies have suggested that metformin may be associated with a reduced risk of developing AMD, but the evidence is inconclusive.
AIMS
To explore the relationship between metformin use and development of AMD among patients with type 2 diabetes in the UK.
METHODS
A large, population-based retrospective open cohort study with a time-dependent exposure design was carried out using IQVIA Medical Research Data, 1995-2019. Patients aged ≥40 with diagnosed type 2 diabetes were included.The exposed group was those prescribed metformin (with or without any other antidiabetic medications); the comparator (unexposed) group was those prescribed other antidiabetic medications only. The exposure status was treated as time varying, collected at 3-monthly time intervals.Extended Cox proportional hazards regression was used to calculate the adjusted HRs for development of the outcome, newly diagnosed AMD.
RESULTS
A total of 173 689 patients, 57% men, mean (SD) age 62.8 (11.6) years, with incident type 2 diabetes and a record of one or more antidiabetic medications were included in the study. Median follow-up was 4.8 (IQR 2.3-8.3, range 0.5-23.8) years. 3111 (1.8%) patients developed AMD. The adjusted HR for diagnosis of AMD was 1.02 (95% CI 0.92 to 1.12) in patients prescribed metformin (with or without other antidiabetic medications) compared with those prescribed any other antidiabetic medication only.
CONCLUSION
We found no evidence that metformin was associated with risk of AMD in primary care patients requiring treatment for type 2 diabetes
Impaired neutralisation of SARS-CoV-2 delta variant in vaccinated patients with B cell chronic lymphocytic leukaemia.
No full textBACKGROUND
Immune suppression is a clinical feature of chronic lymphocytic leukaemia (CLL), and patients show increased vulnerability to SARS-CoV-2 infection and suboptimal antibody responses.
METHOD
We studied antibody responses in 500 patients following dual COVID-19 vaccination to assess the magnitude, correlates of response, stability and functional activity of the spike-specific antibody response with two different vaccine platforms.
RESULTS
Spike-specific seroconversion post-vaccine was seen in 67% of patients compared to 100% of age-matched controls. Amongst responders, titres were 3.7 times lower than the control group. Antibody responses showed a 33% fall over the next 4 months. The use of an mRNA (n = 204) or adenovirus-based (n = 296) vaccine platform did not impact on antibody response. Male gender, BTKi therapy, prophylactic antibiotics use and low serum IgA/IgM were predictive of failure to respond. Antibody responses after CD20-targeted immunotherapy recovered 12 months post treatment. Post-vaccine sera from CLL patients with Spike-specific antibody response showed markedly reduced neutralisation of the SARS-CoV-2 delta variant compared to healthy controls. Patients with previous natural SARS-CoV-2 infection showed equivalent antibody levels and function as healthy donors after vaccination.
CONCLUSIONS
These findings demonstrate impaired antibody responses following dual COVID-19 vaccination in patients with CLL and further define patient risk groups. Furthermore, humoural protection against the globally dominant delta variant is markedly impaired in CLL patients and indicates the need for further optimisation of immune protection in this patient cohort
Opinions and Attitudes of Pulmonologists About Augmentation Therapy in Patients with Alpha-1 Antitrypsin Deficiency. A Survey of the EARCO Group.
No full textBackground
Augmentation therapy (AT) is the only specific treatment licensed for patients with alpha-1 antitrypsin deficiency (AATD) associated lung disease. Since patients with severe AATD may have a very different prognosis and AT requires intravenous infusions for life, the decision to initiate AT may be challenging.
Methods
This survey was conducted on 63 experts in AATD from 13 European countries about their opinions and attitudes regarding AT. Participants were asked to rank the importance of 11 identified factors related with the prescription of AT. In addition, each participant was asked to respond to the indication of AT for 30 out of 500 hypothetical cases developed with the combinations of the 11 factors. Each case was evaluated by 3 experts to check the concordance.
Results
The variables that scored higher on preferences for initiating AT were AAT genotype (score 8.6 from a Likert scale 0-10 (SD: 1.7)), AATD serum level (8.2 (SD:2.4)) and FEV1 (%) decline (7.9 (SD:2.4)). Among the 500 different cases, there was an agreement in indication of AT among the 3 experts in 291 (58.2%). Regarding the variables associated with AT, it was indicated to 81.9% of Pi*ZZ, 52.4% of Pi*SZ and 9.8% of Pi*MZ (p < 0.0001). For Pi*ZZ patients, multivariate analysis identified younger age, reduced FEV1 (%), higher FEV1 decline and worse emphysema as significantly associated with prescription (AUC = 0.8114); for Pi*SZ variables were younger age, worse FEV1 (%) and worse emphysema (AUC = 0.7414); and for Pi*MZ younger age, worse DLCO (%), higher DLCO decline and dyspnea (AUC = 0.8387).
Conclusion
There is a high variability in the criteria for prescription of AT among European experts. Most cases were recommended AT according to guidelines, but a significant number of patients with genotype Pi*SZ and almost 10% Pi*MZ were recommended to initiate AT despite the lack of evidence of efficacy in these genotypes