Approaches to management of rhabdomyolysis as the adverse effect of drug interaction between atorvastatin and sacubitril/valsartan: a case report.

Background: Atorvastatin and sacubitril/valsartan (Entresto™) have been cornerstones in managing patients with coronary artery disease and heart failure (HF). We report a case of life-threatening rhabdomyolysis associated with the co-administration of atorvastatin and sacubitril/valsartan. Case summary: A 58-year-old male with coronary heart disease and chronic HF treated with the optimal dose of atorvastatin and other cardiovascular medications was frequently admitted for acute decompensation of HF. We decided to optimize his condition by adding sacubitril/valsartan to his treatment regime. He presented to our outpatient clinic with worsening myalgia and oliguria 6 days later. He was readmitted with markedly elevated serum creatinine kinase (CK) (94 850 U/L; normal range 32-294 U/L), deranged liver function tests, and acute kidney injury. We withheld atorvastatin and sacubitril/valsartan and treated him with renal replacement therapy. Discussion: Sacubitril inhibits the excretion of statins, thereby elevating serum statin concentration and increasing the likelihood of developing muscle-related toxicity. Co-administration of atorvastatin and sacubitril/valsartan should be monitored closely with laboratory investigations of CK and liver and renal function. The physician may consider starting low-dose atorvastatin at 20 mg daily in combination with sacubitril/valsartan 24 mg/26 mg twice daily and titrating accordingly to optimal doses. Rosuvastatin could be an alternative to atorvastatin, as it has less drug-drug interaction with sacubitril, thereby reducing the adverse effect.

Management of Takotsubo Syndrome: A Comprehensive Review.

Takotsubo syndrome (TTS), also known as Takotsubo cardiomyopathy, is a transient left ventricular wall dysfunction that is often triggered by physical or emotional stressors. Although TTS is a rare disease with a prevalence of only 0.5% to 0.9% in the general population, it is often misdiagnosed as acute coronary syndrome. A diagnosis of TTS can be made using Mayo diagnostic criteria. The initial management of TTS includes dual antiplatelet therapy, anticoagulants, beta-blockers, angiotensin-converting enzyme inhibitors or aldosterone receptor blockers, and statins. Treatment is usually provided for up to three months and has a good safety profile. For TTS with complications such as cardiogenic shock, management depends on left ventricular outflow tract obstruction (LVOTO). In patients without LVOTO, inotropic agents can be used to maintain pressure, while inotropic agents are contraindicated in patients with LVOTO. In TTS with thromboembolism, heparin should be started, and patients should be bridged to warfarin for up to three months to prevent systemic emboli. Our comprehensive review discussed the management in detail, derived from the most recent literature from observational studies, systematic review, and meta-analyses.

Evolving trends in infective endocarditis in a developing country: a consequence of medical progress?

BACKGROUND: Staphylococcus has replaced streptococcus as the most common cause of infective endocarditis (IE) in developed health care systems. The trend in developing countries is less clear. AIM: To examine the epidemiological trends of infective endocarditis in a developing nation. METHODS: Single-centre, retrospective study of patients admitted with IE to a tertiary hospital in Malaysia over a 12-year period. RESULTS: The analysis included 182 patients (n = 153 Duke's definite IE, n = 29 possible IE). The mean age was 51 years. Rheumatic heart disease was present in 42%, while 7.6% were immunocompromised. IE affected native valves in 171 (94%) cases. Health-care associated IE (HCAIE) was recorded in 68 (37.4%). IE admission rates increased from 25/100,000 admissions (2012) to 59/100,000 admissions (2017). At least one major complication on admission was detected in 59 (32.4%) patients. Left-sided IE was more common than right-sided IE [n = 159 (87.4%) vs. n = 18 (9.9%)]. Pathogens identified by blood culture were staphylococcus group [n = 58 (40.8%)], streptococcus group [n = 51 (35.9%)] and Enterococcus species [n = 13 (9.2%)]. staphylococcus infection was highest in the HCAIE group. In-hospital death occurred in 65 (35.7%) patients. In-hospital surgery was performed for 36 (19.8%) patients. At least one complication was documented in 163 (85.7%). CONCLUSION: Staphylococcus is the new etiologic champion, reflecting the transition of the healthcare system. Streptococcus is still an important culprit organism. The incidence rate of IE appears to be increasing. The rate of patients with underlying rheumatic heart disease is still high.

Swallow syncope: a case report and review of literature.

BACKGROUND: Swallow or deglutition syncope is an unusual type of neurally-mediated syncope associated with life-threatening bradyarrhythmia and hypotension. It is a difficult condition to diagnose with commonly delayed diagnosis and management. There is lack of review articles that elucidate the basic demographics, clinical characteristics and management of this rare condition. This publication systematically reviews the 101 case reports published since 1793 on swallow syncope. CASE PRESENTATION: A 59-year-old man presented with the complaint of recurrent dizziness associated with meals. A 24-h ambulatory ECG recording confirmed an episode of p-wave asystole at the time of food intake. Oesophagogastroduodenoscopy with balloon inflation in the mid to lower oesophagus resulted in a 5.6 s sinus pause. The patient's symptoms resolved completely following insertion of a permanent dual chamber pacemaker. CONCLUSIONS: Swallow syncope is extremely rare, but still needs to be considered during diagnostic workup. It is commonly associated with gastro-intestinal disease. Permanent pacemaker implantation is the first line treatment.

Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma.

Repeat tumor biopsies to study genomic changes during therapy are difficult, invasive and data are confounded by tumoral heterogeneity. The analysis of circulating tumor DNA (ctDNA) can provide a non-invasive approach to assess prognosis and the genetic evolution of tumors in response to therapy. Mutation-specific droplet digital PCR was used to measure plasma concentrations of oncogenic BRAF and NRAS variants in 48 patients with advanced metastatic melanoma prior to treatment with targeted therapies (vemurafenib, dabrafenib or dabrafenib/trametinib combination) or immunotherapies (ipilimumab, nivolumab or pembrolizumab). Baseline ctDNA levels were evaluated relative to treatment response and progression-free survival (PFS). Tumor-associated ctDNA was detected in the plasma of 35/48 (73%) patients prior to treatment and lower ctDNA levels at this time point were significantly associated with response to treatment and prolonged PFS, irrespective of therapy type. Levels of ctDNA decreased significantly in patients treated with MAPK inhibitors (p < 0.001) in accordance with response to therapy, but this was not apparent in patients receiving immunotherapies. We show that circulating NRAS mutations, known to confer resistance to BRAF inhibitors, were detected in 3 of 7 (43%) patients progressing on kinase inhibitor therapy. Significantly, ctDNA rebound and circulating mutant NRAS preceded radiological detection of progressive disease. Our data demonstrate that ctDNA is a useful biomarker of response to kinase inhibitor therapy and can be used to monitor tumor evolution and detect the early appearance of resistance effectors.

Circulating Melanoma Cell Subpopulations: Their Heterogeneity and Differential Responses to Treatment.

Metastatic melanoma is a highly heterogeneous tumor; thus, methods to analyze tumor-derived cells circulating in blood should address this diversity. Taking this into account, we analyzed, using multiparametric flow cytometry, the co-expression of the melanoma markers melanoma cell adhesion molecule and melanoma-associated chondroitin sulphate proteoglycan and the tumor-initiating markers ATP-binding cassette sub-family B member 5 (ABCB5), CD271, and receptor activator of NF-κß (RANK) in individual circulating tumor cells (CTCs) from 40 late-stage (III-IV) and 16 early-stage (I-II) melanoma patients. CTCs were heterogeneous within and between patients, with limited co-expression between the five markers analyzed. Analysis of patient matched blood and metastatic tumors revealed that ABCB5 and RANK subpopulations are more common among CTCs than in the solid tumors, suggesting a preferential selection for these cells in circulation. Pairwise comparison of CTC subpopulations longitudinally before and 6-13 weeks after treatment initiation showed that the percentage of RANK(+) CTCs significantly increased in the patients undergoing targeted therapy (N=16, P<0.01). Moreover, the presence of ⩾5 RANK(+) CTCs in the blood of patients undergoing targeted therapies was prognostic of shorter progression-free survival (hazards ratio 8.73, 95% confidence interval 1.82-41.75, P<0.01). Taken together, our results provide evidence of the heterogeneity among CTC subpopulations in melanoma and the differential response of these subpopulations to targeted therapy.