1.Omicron SARS-CoV-2 outcomes in vaccinated individuals with heart failure and ischaemic heart disease.
Liang En WEE ; Enoch Xueheng LOY ; Jue Tao LIM ; Yew Woon CHIA ; Shir Lynn LIM ; Jonathan YAP ; Khung Keong YEO ; Derek J HAUSENLOY ; Mark Yan Yee CHAN ; David Chien Boon LYE ; Kelvin Bryan TAN
Annals of the Academy of Medicine, Singapore 2025;54(5):270-282
INTRODUCTION:
Outcomes after SARS-CoV-2 Omicron infection in patients with heart failure (HF) and ischaemic heart disease (IHD) remain poorly defined.
METHOD:
In a highly vaccinated cohort of adult Singapore citizens and permanent residents, we used Cox proportional hazards models (adjusted for sociodemographic variables and comorbidities) to compare the risks of Omicron infection, COVID-19- related hospitalisation, and severe COVID-19 between indivi-duals with HF or IHD and matched controls without these conditions.
RESULTS:
From national databases, we identified 15,426 HF patients matched 1:∼3 to 41,221 controls, and 110,442 IHD patients matched 1:∼2 to 223,843 controls. Over 80% of HF and IHD patients had received at least 3 vaccine doses. During the Omicron-predominant period, both HF and IHD cohorts demonstrated higher adjusted risks of COVID-19 hospitalisation compared with matched controls (HF: adjusted hazard ratio [aHR] 1.77, 95% confidence interval [CI] 1.65-1.90; IHD: aHR 1.21, 95% CI 1.17-1.26). Among those with at least 1 HF-or IHD-related admission in the prior year, hospitalisation risk was further elevated (HF: aHR 1.27, 95% CI 1.13-1.42; IHD: aHR 1.11, 95% CI 1.01-1.23). Receipt of ≥3 vaccine doses was associated with substantially lower risk of severe COVID-19 versus only 2 doses (HF: aHR 0.35, 95% CI 0.28-0.43; IHD: aHR 0.27, 95% CI 0.23-0.32). A fourth dose conferred additional reductions in infection and adverse outcomes, though CIs for infection overlapped with those for 3 doses.
CONCLUSION
During Omicron predominance, HF and IHD patients experienced greater risk of COVID-19 hospitalisation and severe COVID-19 versus matched controls. Booster vaccinations attenuated these risks. Individuals with recent HF/IHD admissions should be prioritised for receipt of booster vaccine doses.
Humans
;
COVID-19/complications*
;
Male
;
Heart Failure/complications*
;
Myocardial Ischemia/complications*
;
Female
;
Middle Aged
;
Hospitalization/statistics & numerical data*
;
Aged
;
COVID-19 Vaccines/administration & dosage*
;
Singapore/epidemiology*
;
SARS-CoV-2
;
Proportional Hazards Models
;
Adult
;
Case-Control Studies
;
Vaccination/statistics & numerical data*
2.Intracerebral hemorrhage in a child with renal artery stenosis and COVID-19
Paul Lawrence C. Filomeno ; Joyce Gillian A. Tiam-Lee ; Bryan Nicole M. Reyes ; Jonah Mikka B. Dorado ; Ma. Micaela Therese J. Pimentel ; Marissa B. Lukban
Acta Medica Philippina 2024;58(7):182-186
Pediatric intracerebral hemorrhage is a rare condition among children. We discuss the case of a 7-year-old Filipino male with generalized tonic seizures and diagnosed to have both SARS-CoV-2 infection and hypertension secondary to renal arterial stenosis. The occurrence of intracerebral hemorrhage in children, though commonly caused by arteriovenous malformations, may be secondary to an acute hypertensive episode. In this case, the presence of COVID-19 in the patient may have been contributory to the development of spontaneous intracerebral hemorrhage due to its direct endothelial effects, as well as its dysregulatory action on the renin-angiotensin-aldosterone system.
COVID-19
;
Hypertensive Crisis
;
Renal Artery Obstruction
3.Comparative accuracy of four guidelines to predict high-grade dysplasia or malignancy in surgically resected pancreatic intraductal papillary mucinous neoplasms:Small nuances between guidelines lead to vastly different results
Irene C. PEREZ ; Andrew BIGELOW ; Vanessa M. SHAMI ; Bryan G. SAUER ; Andrew Y. WANG ; Daniel S. STRAND ; Alexander J. PODBOY ; Todd W. BAUER ; Victor M. ZAYDFUDIM ; Allan TSUNG ; Ross C. D. BUERLEIN
Annals of Hepato-Biliary-Pancreatic Surgery 2024;28(4):483-493
Background:
s/Aims: The guidelines regarding the management of intraductal papillary mucinous neoplasms (IPMNs) all have slightly different surgical indications for high-risk lesions. We aim to retrospectively compare the accuracy of four guidelines in recommending surgery for high-risk IPMNs, and assess the accuracy of elevated CA-19-9 levels and imaging characteristics of IPMNs considered high-risk in predicting malignancy or high-grade dysplasia (HGD).
Methods:
The final histopathological diagnosis of surgically resected high-risk IPMNs during 2013−2020 were compared to preoperative surgical indications, as enumerated in four guidelines: the 2015 American Gastroenterological Association (AGA), 2017 International Consensus, 2018 European Study Group, and 2018 American College of Gastroenterology (ACG). Surgery was considered “justified” if histopathology of the surgical specimen showed HGD/malignancy, or there was postoperative symptomatic improvement.
Results:
Surgery was postoperatively justified in 26/65 (40.0%) cases. All IPMNs with HGD/malignancy were detected by the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines. The combined (“high-risk stigmata” and “worrisome features”) 2017 International guideline missed 1/19 (5.3%) IPMNs with HGD/malignancy. The 2015 AGA guideline missed the most cases (11/19, 57.9%) of IPMNs with HGD/malignancy. We found the features most-associated with HGD/malignancy were pancreatic ductal dilation, and elevated CA-19-9 levels.
Conclusions
Following the 2015 AGA guideline results in the highest rate of missed HGD/malignancy, but the lowest rate of operating on IPMNs without these features; meanwhile, the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines result in more operations for IPMNs without HGD/malignancy, but the lowest rates of missed HGD/malignancy in IPMNs.
4.Comparative accuracy of four guidelines to predict high-grade dysplasia or malignancy in surgically resected pancreatic intraductal papillary mucinous neoplasms:Small nuances between guidelines lead to vastly different results
Irene C. PEREZ ; Andrew BIGELOW ; Vanessa M. SHAMI ; Bryan G. SAUER ; Andrew Y. WANG ; Daniel S. STRAND ; Alexander J. PODBOY ; Todd W. BAUER ; Victor M. ZAYDFUDIM ; Allan TSUNG ; Ross C. D. BUERLEIN
Annals of Hepato-Biliary-Pancreatic Surgery 2024;28(4):483-493
Background:
s/Aims: The guidelines regarding the management of intraductal papillary mucinous neoplasms (IPMNs) all have slightly different surgical indications for high-risk lesions. We aim to retrospectively compare the accuracy of four guidelines in recommending surgery for high-risk IPMNs, and assess the accuracy of elevated CA-19-9 levels and imaging characteristics of IPMNs considered high-risk in predicting malignancy or high-grade dysplasia (HGD).
Methods:
The final histopathological diagnosis of surgically resected high-risk IPMNs during 2013−2020 were compared to preoperative surgical indications, as enumerated in four guidelines: the 2015 American Gastroenterological Association (AGA), 2017 International Consensus, 2018 European Study Group, and 2018 American College of Gastroenterology (ACG). Surgery was considered “justified” if histopathology of the surgical specimen showed HGD/malignancy, or there was postoperative symptomatic improvement.
Results:
Surgery was postoperatively justified in 26/65 (40.0%) cases. All IPMNs with HGD/malignancy were detected by the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines. The combined (“high-risk stigmata” and “worrisome features”) 2017 International guideline missed 1/19 (5.3%) IPMNs with HGD/malignancy. The 2015 AGA guideline missed the most cases (11/19, 57.9%) of IPMNs with HGD/malignancy. We found the features most-associated with HGD/malignancy were pancreatic ductal dilation, and elevated CA-19-9 levels.
Conclusions
Following the 2015 AGA guideline results in the highest rate of missed HGD/malignancy, but the lowest rate of operating on IPMNs without these features; meanwhile, the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines result in more operations for IPMNs without HGD/malignancy, but the lowest rates of missed HGD/malignancy in IPMNs.
5.Comparative accuracy of four guidelines to predict high-grade dysplasia or malignancy in surgically resected pancreatic intraductal papillary mucinous neoplasms:Small nuances between guidelines lead to vastly different results
Irene C. PEREZ ; Andrew BIGELOW ; Vanessa M. SHAMI ; Bryan G. SAUER ; Andrew Y. WANG ; Daniel S. STRAND ; Alexander J. PODBOY ; Todd W. BAUER ; Victor M. ZAYDFUDIM ; Allan TSUNG ; Ross C. D. BUERLEIN
Annals of Hepato-Biliary-Pancreatic Surgery 2024;28(4):483-493
Background:
s/Aims: The guidelines regarding the management of intraductal papillary mucinous neoplasms (IPMNs) all have slightly different surgical indications for high-risk lesions. We aim to retrospectively compare the accuracy of four guidelines in recommending surgery for high-risk IPMNs, and assess the accuracy of elevated CA-19-9 levels and imaging characteristics of IPMNs considered high-risk in predicting malignancy or high-grade dysplasia (HGD).
Methods:
The final histopathological diagnosis of surgically resected high-risk IPMNs during 2013−2020 were compared to preoperative surgical indications, as enumerated in four guidelines: the 2015 American Gastroenterological Association (AGA), 2017 International Consensus, 2018 European Study Group, and 2018 American College of Gastroenterology (ACG). Surgery was considered “justified” if histopathology of the surgical specimen showed HGD/malignancy, or there was postoperative symptomatic improvement.
Results:
Surgery was postoperatively justified in 26/65 (40.0%) cases. All IPMNs with HGD/malignancy were detected by the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines. The combined (“high-risk stigmata” and “worrisome features”) 2017 International guideline missed 1/19 (5.3%) IPMNs with HGD/malignancy. The 2015 AGA guideline missed the most cases (11/19, 57.9%) of IPMNs with HGD/malignancy. We found the features most-associated with HGD/malignancy were pancreatic ductal dilation, and elevated CA-19-9 levels.
Conclusions
Following the 2015 AGA guideline results in the highest rate of missed HGD/malignancy, but the lowest rate of operating on IPMNs without these features; meanwhile, the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines result in more operations for IPMNs without HGD/malignancy, but the lowest rates of missed HGD/malignancy in IPMNs.
6.An adolescent female with intentional ingestion of a large amount of metformin requiring extracorporeal membrane oxygenation and continuous renal replacement therapy
Kaila LESSNER ; Lauren MCKINNEY ; Ilana ANDERSON ; Chie-Youn SHIH ; J. Bryan CARMODY ; Meaghan DOMINY
Pediatric Emergency Medicine Journal 2023;10(4):149-154
Acute overdose of metformin can show potentially fatal lactic acidosis. Management should be directed towards close monitoring of renal function and hemodynamics. Patients may require dialysis or extracorporeal membrane oxygenation in cases of hemodynamic instability. This case presents an adolescent with massive metformin ingestion estimated at 100 g leading to metformin-associated lactic acidosis and subsequent respiratory failure, cardiovascular collapse, and acute kidney injury. The complications were successfully managed with venoarterial extracorporeal membrane oxygenation, continuous renal replacement therapy, and mechanical ventilation.
7.A literature review and clinical consensus guidelines on the management of Bullous Pemphigoid
Clarisse G. Mendoza ; Josef Symon S. Concha ; Cybill Dianne C. Uy ; Bryan K. Guevara ; Evelyn R. Gonzaga ; Maria Jasmin J. Jamora ; Jamaine L. Cruz‑Regalado ; Katrina C. Estrella ; Melanie Joy D. Ruiz ; Rogelio A. Balagat ; Mae N. Ramirez‑Quizon ; Johanna Pauline L. Dizon ; Marie Eleanore O. Nicolas
Journal of the Philippine Dermatological Society 2023;32(2):63-76
Bullous pemphigoid (BP) is the most common autoimmune blistering disease primarily characterized by
tense blisters and occasionally with urticarial plaques, affecting the skin and mucous membranes. These are
caused by autoantibodies against BP180 and BP230 which target antigens on the basement membrane zone.
The diagnosis relies on the integration of clinical, histopathological, immunopathological, and serological
findings. The management depends on the clinical extent and severity. We present in this article a literature
review and the clinical consensus guidelines of the Immunodermatology Subspecialty Core Group of the
Philippine Dermatological Society in the management of BP.
Pemphigoid, Bullous
8.Sex and ethnicity modified high 1-year mortality in patients in Singapore with newly diagnosed atrial fibrillation.
Eugene S J TAN ; Huili ZHENG ; Joanna Zhi Jie LING ; Ganga GANESAN ; Zheng Yi LAU ; Kelvin Bryan TAN ; Toon Wei LIM
Annals of the Academy of Medicine, Singapore 2022;51(9):540-552
INTRODUCTION:
We investigated sex and ethnic differences in the incidence, clinical characteristics and 1-year mortality of patients with newly diagnosed AF in a multi-ethnic population.
METHOD:
This retrospective cohort study of patients diagnosed with AF from 2008 to 2015 was based on medical claims, casemix and subvention data submitted to the Ministry of Health. Patients with AF were matched with controls without AF for age (3-year bands), sex and ethnicity, and categorised as middle-aged (45-64 years) or elderly (≥65 years) among major ethnic groups in Singapore (Chinese, Malay and Indian).
RESULTS:
Among 40,602 adults with AF (elderly 74%), Malays had the highest age-standardised incidence rate of AF, followed by Chinese and Indians; and the rate was higher in men. Despite having the worst cardiovascular risk profile, Indians had the lowest prevalence and incidence of AF. The 1-year mortality rate after newly diagnosed AF was 22-26 deaths per 100 people. Newly diagnosed AF was independently associated with increased 1-year all-cause mortality among middle-aged (adjusted odds ratio [AOR] 9.08, 95% confidence interval [CI] 7.36-11.20) and elderly adults (AOR 3.60, 95% CI 3.40-3.80) compared with those without AF. Sex differences in mortality among patients with AF were limited to elderly adults (men: AOR 1.17, 95% CI 1.11-1.24), while Indians were associated with a 30% increased odds of mortality compared with Chinese regardless of age (middle-aged: AOR 1.27, 95% CI 1.09-1.548 elderly: AOR 1.33, 95% CI 1.22-1.45).
CONCLUSION
Variations in incidence, clinical profile and 1-year mortality of patients with AF in a nationwide cohort were influenced by sex and ethnicity. Newly diagnosed AF portends a worse prognosis and is a marker of high mortality within the first year.
Adult
;
Aged
;
Atrial Fibrillation/complications*
;
Ethnicity
;
Female
;
Humans
;
Incidence
;
Male
;
Middle Aged
;
Retrospective Studies
;
Risk Factors
;
Singapore/epidemiology*
9.Prevalence of tumor BRCA1 and BRCA2 dysfunction in unselected patients with ovarian cancer
Roshni D. KALACHAND ; Ciaran O’RIAIN ; Sinead TOOMEY ; Aoife CARR ; Kirsten M. TIMMS ; Sharon O’TOOLE ; Stephen MADDEN ; Mark BATES ; John J. O’LEARY ; Noreen GLEESON ; Dearbhaile O’DONNELL ; Liam GROGAN ; Oscar BREATHNACH ; Angela FARRELLY ; Britta STORDAL ; Bryan T. HENNESSY
Obstetrics & Gynecology Science 2020;63(5):643-654
Objective:
The therapeutic benefits of poly(ADP-ribose) polymerase inhibitors highlight the need to evaluate BRCA1/2 defects in tubal/ovarian cancer (OC). We sought to determine the pattern and disease characteristics associated with tumor BRCA1/2 mutations and BRCA1 methylation in women with OC.
Methods:
We obtained 111 OC specimens from 2 university hospitals and assessed BRCA1/2 mutations and BRCA1 methylation in tumor DNA. The frequency and pattern of BRCA1/2 defects were examined. Associations between patient/disease characteristics and BRCA1/2 defects were ascertained (Fisher’s exact test). Platinum-free interval (PFI), progression-free survival (PFS), and overall survival (OS) based on the underlying BRCA1/2 defect were determined (Kaplan-Meier analysis [log-rank test]).
Results:
We observed a BRCA1/2 dysfunction rate of 40% (28/70) in high-grade serous tubal/ovarian cancer (HGSC), including 14.3% BRCA1 methylation (n=10), 7.1% BRCA1 mutation (n=5), and 18.6% BRCA2 mutation (n=13). Defects in BRCA1/2 genes were associated with stage III/IV HGSC (BRCA1 methylation: P=0.005 [stage III/IV] and P=0.004 [HGSC]; BRCA1/2 mutation: P=0.03 [stage III/IV] and P<0.001 [HGSC]). Patients with BRCA1/2-mutated cancers showed improved OS (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43–0.99; P=0.045) and a trend toward improved PFI (HR, 0.48; 95% CI, 0.22–1.06; P=0.07) and PFS (HR, 0.72; 95% CI, 0.51–1.03; P=0.07). No survival differences were observed between BRCA1-methylated and BRCA1/2 wild-type non-BRCA1-methylated cancers.
Conclusion
We observed a high tumor BRCA1/2 dysfunction rate in HGSC with a unique predominance of BRCA2 over BRCA1 mutations. While BRCA1/2 mutations conferred survival benefits in OC, no such association was observed with BRCA1 methylation.
10.Prevalence of tumor BRCA1 and BRCA2 dysfunction in unselected patients with ovarian cancer
Roshni D. KALACHAND ; Ciaran O’RIAIN ; Sinead TOOMEY ; Aoife CARR ; Kirsten M. TIMMS ; Sharon O’TOOLE ; Stephen MADDEN ; Mark BATES ; John J. O’LEARY ; Noreen GLEESON ; Dearbhaile O’DONNELL ; Liam GROGAN ; Oscar BREATHNACH ; Angela FARRELLY ; Britta STORDAL ; Bryan T. HENNESSY
Obstetrics & Gynecology Science 2020;63(5):643-654
Objective:
The therapeutic benefits of poly(ADP-ribose) polymerase inhibitors highlight the need to evaluate BRCA1/2 defects in tubal/ovarian cancer (OC). We sought to determine the pattern and disease characteristics associated with tumor BRCA1/2 mutations and BRCA1 methylation in women with OC.
Methods:
We obtained 111 OC specimens from 2 university hospitals and assessed BRCA1/2 mutations and BRCA1 methylation in tumor DNA. The frequency and pattern of BRCA1/2 defects were examined. Associations between patient/disease characteristics and BRCA1/2 defects were ascertained (Fisher’s exact test). Platinum-free interval (PFI), progression-free survival (PFS), and overall survival (OS) based on the underlying BRCA1/2 defect were determined (Kaplan-Meier analysis [log-rank test]).
Results:
We observed a BRCA1/2 dysfunction rate of 40% (28/70) in high-grade serous tubal/ovarian cancer (HGSC), including 14.3% BRCA1 methylation (n=10), 7.1% BRCA1 mutation (n=5), and 18.6% BRCA2 mutation (n=13). Defects in BRCA1/2 genes were associated with stage III/IV HGSC (BRCA1 methylation: P=0.005 [stage III/IV] and P=0.004 [HGSC]; BRCA1/2 mutation: P=0.03 [stage III/IV] and P<0.001 [HGSC]). Patients with BRCA1/2-mutated cancers showed improved OS (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43–0.99; P=0.045) and a trend toward improved PFI (HR, 0.48; 95% CI, 0.22–1.06; P=0.07) and PFS (HR, 0.72; 95% CI, 0.51–1.03; P=0.07). No survival differences were observed between BRCA1-methylated and BRCA1/2 wild-type non-BRCA1-methylated cancers.
Conclusion
We observed a high tumor BRCA1/2 dysfunction rate in HGSC with a unique predominance of BRCA2 over BRCA1 mutations. While BRCA1/2 mutations conferred survival benefits in OC, no such association was observed with BRCA1 methylation.


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