BACKGROUND

Observational studies have increasingly reported transthyretin amyloid cardiomyopathy (ATTR-CM) as an under-recognized cause of heart failure. We report the first ATTR-CM diagnosed via multi-modality imaging in the Philippines signifying an important milestone in recognition and management of this formerly believed rare disease, locally. Utilization of non-invasive imaging such as echocardiography, cardiac MRI and technetium-99m pyrophosphate scintigraphy (PYP) demonstrates the potential for accurate diagnosis as well as timely and appropriate treatment strategies.

An 81/M Filipino with a history of carpal tunnel surgery, post-percutaneous coronary intervention (PCI), had three months’ history of refractory heart failure symptoms despite optimized medical treatment. His 2D-echo showed an ejection fraction (EF): 45%-50%, increased left ventricular (LV) posterior wall thickness with mild basal inferior wall hypokinesia and ECG: atrial fibrillation with low voltage. Speckle tracking imaging showed average global longitudinal strain: - 6.5% with cherry-on-top pattern on polar strain map. Cardiac MRI demonstrated diffuse late gadolinium enhancement from endocardial to transmural layers of biventricular and biatrial walls, highly suggestive of cardiac amyloidosis (CA). Light-chain amyloidosis was excluded by negative serum/urine protein electrophoresis/immunofixation. Tc-99m PYP scan revealed greater myocardial-than-bone uptake with a Perugini score 3 and calculated heart-to-contralateral ratio of 1.7. Congestion was controlled with intravenous loop diuretics and he was discharged stable with metoprolol succinate, dapagliflozin and apixaban. At the time of paper submission, he is currently being evaluated for tafamidis treatment.

The case highlighted the advantage of multi-modality imaging for noninvasive yet accurate identification of the disease. A tailored approach is required in slowing the disease progression and improving outcomes.

Humans ; Arthritis, Psoriatic/drug therapy* ; Interleukin-17 ; Interleukin Inhibitors ; Antirheumatic Agents/therapeutic use* ; Tumor Necrosis Factor-alpha/therapeutic use* ; Interleukin-23/therapeutic use*

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are currently the first-line standard of care for patients with non-small cell lung cancer (NSCLC) that harbor EGFR mutations. Nevertheless, resistance to EGFR-TKIs is inevitable. In recent years, although immune checkpoint inhibitors (ICIs) have significantly shifted the treatment paradigm in advanced NSCLC without driver mutation, clinical benefits of these agents are limited in patients with EGFR-mutated NSCLC. Compared with wild-type tumors, tumors with EGFR mutations show more heterogeneity in the expression level of programmed cell death ligand 1 (PD-L1), tumor mutational burden (TMB), and other tumor microenvironment (TME) characteristics. Whether ICIs are suitable for NSCLC patients with EGFR mutations is still worth exploring. In this review, we summarized the clinical data with regard to the efficacy of ICIs in patients with EGFR-mutated NSCLC and deciphered the unique TME in EGFR-mutated NSCLC.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; ErbB Receptors/metabolism* ; Immunotherapy ; Mutation ; B7-H1 Antigen/genetics* ; Protein Kinase Inhibitors/pharmacology* ; Tumor Microenvironment

INTRODUCTION: The pandemic caused by coronavirus disease 2019 (COVID-19) posed a serious challenge to all health care systems in the world. It has been found to be harmful in people with underlying cardiovascular diseases, particularly in patients with systemic hypertension, which may be due to upregulation of angiotensin-converting enzyme 2 (ACE2) expression, which may lead to increased severe acute respiratory syndrome coronavirus 2 virulence. Renin-angiotensin system inhibitor (RASI) acts by blocking the angiotensin-converting enzyme and angiotensin II type 1 receptors, which in turn affects the production of the ACE2 protein. Hence, there have been arguments on whether to continue or discontinue this medication. Given the widespread use of RASIs globally and the fact that they are generally cardioprotective, research into the safety of continuing these maintenance medications in patients hospitalized with mild to moderate COVID-19 is immensely needed. METHODS: This meta-analysis involved review of observational studies among hypertensive patients on maintenance ACE inhibitor or angiotensin-receptor blocker with confirmed mild to moderate COVID-19 infection. Analyses were performed to determine the adjusted hazard ratio of each event using the raw data obtained from each study. Random-effects model and Cochran-Mantel-Haenszel method were utilized at 95% confidence interval. To check for heterogeneity, χ2 test and I2 statistic were calculated. Cochrane ReviewManager (RevMan version 5.3) was used for data analysis, and forest plots were generated. RESULTS: At 95% confidence interval, the adjusted hazard ratios for all-cause mortality and intensive care unit (ICU) admission at 95% confidence interval were 1.64 (1.22, 2.21) and 1.93 (1.34, 2.79), respectively. The tests of overall estimate effect for both outcomes were P < 0.0001 for all-cause mortality and P = 0.0003 for ICU admission. CONCLUSION Discontinuation of maintenance RASI during hospitalization is associated with increased all-cause mortality and ICU admission among hypertensive patients with mild to moderate COVID-19 infection.
Angiotensin-Converting Enzyme Inhibitors ; Coronavirus:COVID-19

OBJECTIVES

This study aimed to determine the clinical profile of non thyroidal cancer patients with thyroid dysfunction associated with tyrosine kinase inhibitor (TKI) therapy at the University of Santo Tomas Hospital (USTH), Philippines.

This is a retrospective observational study of TKI initiated adult non-thyroidal cancer patients with thyroid function testing from 2013 to 2018.

Forty percent (95% CI: 26.2% - 58.61%) of the sixty individuals who had thyroid function tests (TFT) had incident thyroid dysfunction. Thirty percent had hypothyroidism (i.e., 25% overt [mean TSH 16.64 uIU/mL]; 5% subclinical [mean TSH 6.62 uIU/mL]). The median time at risk was 8 and 16 months for overt and subclinical hypothyroidism, respectively. Fifty-six percent had persistent hypothyroidism (median TSH 16.75, p = 0.009). The average time to recovery of transient hypothyroidism was 39 months. Ten percent had hyperthyroidism with a median time at risk of 1.5 months. Non-small cell lung cancer and renal cell carcinoma were possible associated risk factors of thyroid dysfunction.

TKI-induced thyroid dysfunctions are common. Screening and monitoring for thyroid abnormalities during TKI therapy is important.

Objectives: Bioequivalence studies provide evidence that generic drugs can produce the same blood levels as the innovator, suggesting similar efficacy and safety and indicating interchangeability without the need to titrate dosing. This study aimed to compare the rate and extent of absorption of two simvastatin 20 mg tablets of Pascual Laboratories, Inc. with two Zocor 20 mg tablets of Merck Sharp & Dohme (I.A.) Corp. in healthy Filipinos. The study also monitored the safety and tolerability of the medications, under the same conditions. Proof of bioequivalence is required by FDA Philippines to establish the interchangeability of generic products and their innovators. Methods: Twenty-four healthy participants were administered with a single oral dose of two 20 mg simvastatin tablets under fasting conditions, in a randomized, open-label, blind-endpoint analysis, two-way crossover study, with a washout period of one week. Pharmacokinetic blood sampling was done up to 24 h post-dose. Simvastatin was measured using Liquid Chromatography-Tandem Mass Spectrometry with a validated method. The geometric mean ratios for maximum plasma concentration (Cmax) and area under the plasma-concentration-time curve from time zero to the last observed concentration at time 24 h (AUC0-24) were used for bioequivalence. Results: All 24 participants, 12 males and 12 females, completed the study. Mean age was 24.21 years, mean weight was 58.81 kg, and mean BMI was 23.16 kg/m2. The ratios of Cmax and AUC0-24 were 102.17% (90% CI: 89.19-117.03), and 101.29% (90% CI: 86.87-118.10), respectively, and were both within the bioequivalence limits of 80% to 125%. No adverse event was reported and both formulations were well-tolerated. Conclusions Simvastatin 20 mg tablet of Pascual Laboratories, Inc. and the innovator Zocor 20 mg tablet are bioequivalent. Single two-tablet doses of both products are safe and well tolerated.
Simvastatin ; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Background: Current medical management of endometriosis leads to suppression of ovulation and will not be helpful for women with endometriosis who are desirous of pregnancy. Thus, drugs that can both treat endometriosis and its associated infertility are highly warranted. Objective: Anti-angiogenic agents are potential drugs for patients with endometriosis and infertility. Among these drugs, dopamine agonist (DA) is promising since it does not interfere with ovulation, is safe, and not teratogenic. The aim of the study is to determine the efficacy and safety of DA for improving reproductive outcomes in women with endometriosis and infertility. Methods: A qualitative narrative review was done from inception to July 31, 2022 using the appropriate MeSH terms in PubMed, Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, ClinicalTrial.gov, and World Health Organization International Clinical Trials Registry Platform. Date analysis was through qualitative analysis and synthesis of researches and their outcome measures. Results: No studies used the core outcomes for trials evaluating treatments for infertility associated with endometriosis. All the included articles in the review supported the possible anti-angiogenic effects of DA on the vascular endothelial growth factor [VEGF] /VEGF receptor system. The use of DA does not have an effect on ovulation and menstrual cyclicity. Studies on safety profile of DA were consistent with existing data. Conclusion Most of studies reviewed demonstrated that DA were effective in reducing endometriotic lesions. However, further research is required to establish whether this anti-angiogenic effect can improve reproductive outcomes in women with endometriosis-associated infertility.
Endometriosis ; Dopamine Agonists ; Infertility ; Angiogenesis Inducing Agents ; Angiogenesis Inhibitors

Humans ; Cardiovascular Diseases/drug therapy* ; Consensus ; Lymphoma, B-Cell ; Lymphoma, Mantle-Cell ; Tyrosine Protein Kinase Inhibitors/therapeutic use*

Poly ADP-ribose polymerase inhibitors (PARPi), which approved in recent years, are recommended for ovarian cancer, breast cancer, pancreatic cancer, prostate cancer and other cancers by The National Comprehensive Cancer Network (NCCN) and Chinese Society of Clinical Oncology (CSCO) guidelines. Because most of PARPi are metabolized by cytochrome P450 enzyme system, there are extensive interactions with other drugs commonly used in cancer patients. By setting up a consensus working group including pharmaceutical experts, clinical experts and methodology experts, this paper forms a consensus according to the following steps: determine clinical problems, data retrieval and evaluation, Delphi method to form recommendations, finally formation expert opinion on PARPi interaction management. This paper will provide practical reference for clinical medical staff.
Male ; Female ; Humans ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology* ; Consensus ; Ovarian Neoplasms/drug therapy* ; Drug Interactions ; Adenosine Diphosphate Ribose/therapeutic use*

Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/pathology* ; Anaplastic Lymphoma Kinase ; Neoadjuvant Therapy ; Protein Kinase Inhibitors