Clinical signs associated with severe ST segment elevation in three cats with a hypertrophic cardiomyopathy phenotype.

Three cats were presented for unusual collapsing episodes. Echocardiography revealed a hypertrophic cardiomyopathy (HCM) phenotype in each cat. Continuous electrocardiographic monitoring showed that the clinical signs coincided with periods of severe ST-segment elevation in each cat. The first cat was treated with amlodipine and diltiazem but did not improve and was euthanized due to poor quality of life. Postmortem examination revealed cardiac lymphoma without obstructive coronary disease. The second cat was thought to have cardiac lymphoma, based on pericardial effusion cytology, and was euthanized before starting therapy. The third cat was diagnosed with HCM and left ventricular outflow tract obstruction and was treated with atenolol and diltiazem. This treatment reduced the frequency of episodic clinical signs, but the cat subsequently developed congestive heart failure and was euthanized. This case series describes clinical signs associated with severe ST elevation in cats with an HCM phenotype, and their outcomes. Continuous electrocardiographic monitoring was necessary to detect transient ST elevation in each case.

Intravenous Diltiazem Versus Metoprolol in Acute Rate Control of Atrial Fibrillation/Flutter and Rapid Ventricular Response: A Meta-Analysis of Randomized and Observational Studies.

BACKGROUND: Atrial fibrillation (AF) and/or atrial flutter (AFL) with rapid ventricular response (RVR) is a condition that often requires urgent treatment. Although guidelines have recommendations regarding chronic rate control therapy, recommendations on the best choice for acute heart rate (HR) control in RVR are unclear. METHODS: A systematic search across multiple databases was performed for studies evaluating the outcome of HR control (defined as HR less than 110 bpm and/or 20% decrease from baseline HR). Included studies evaluated AF and/or AFL with RVR in a hospital setting, with direct comparison between intravenous (IV) diltiazem and metoprolol and excluded cardiac surgery and catheter ablation patients. Hypotension (defined as systolic blood pressure less than 90 mmHg) was measured as a secondary outcome. Two authors performed full-text article review and extracted data, with a third author mediating disagreements. Random effects models utilizing inverse variance weighting were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Heterogeneity was assessed using the I2 test. RESULTS: A total of 563 unique titles were identified through the systematic search, of which 16 studies (7 randomized and 9 observational) were included. In our primary analysis of HR control by study type, IV diltiazem was found to be more effective than IV metoprolol for HR control in randomized trials (OR 4.75, 95% CI 2.50-9.04 with I2 = 14%); however, this was not found for observational studies (OR 1.26, 95% CI 0.89-1.80 with I2 = 55%). In an analysis of observational studies, there were no significant differences between the two drugs in odds of hypotension (OR 1.12, 95% CI 0.51-2.45 with I2 = 18%). CONCLUSION: While there was a trend toward improved HR control with IV diltiazem compared with IV metoprolol in randomized trials, this was not seen in observational studies, and there was no observed difference in hypotension between the two drugs.

Role of magnesium alone or in combination with diltiazem and/or amiodarone in prevention of atrial fibrillation following off-pump coronary artery bypass grafting.

Objectives: In this study the authors have tried to examine the role of magnesium alone or in combination with diltiazem and / or amiodarone in prevention of atrial fibrillation (AF) following off-pump coronary artery bypass grafting (CABG). Background: AF after CABG is common and contributes to morbidity and mortality. Various pharmacological preventive measures including magnesium, amiodarone, diltiazem, and combination therapy among others have been tried to lower the incidence of AF. Most of the studies have been performed in patients undergoing conventional on-pump CABG. In this uncontrolled trial, efficacy of magnesium alone or in combination with amiodarone and / or diltiazem has been studied in patients undergoing off-pump CABG. Methods: One hundred and fifty patients undergoing off-pump CABG were divided into 3 groups, Group M (n=21) received intraoperative magnesium infusion at 30mg/ kg over 1 hour after midline sternotomy; Group MD (n=78) received magnesium infusion in similar manner with diltiazem infusion at 0.05 µg/kg/hr throughout the intraoperative period; Group AMD (n=51) received preoperative oral amiodarone at a dose of 200 mg three times a day for 3 days followed by 200 mg twice daily for another 3 days followed by 200 mg once daily till the day of surgery along with magnesium and diltiazem infusion as in other groups. AF lasting more than 10 min or requiring medical intervention was considered as AF. Results: The overall incidence of postoperative AF was 12.6% with 11.7% in group AMD, 19% in group M, and 11.5% in group MD, which was not statistically significant. Conclusions: It is concluded that the use of amiodarone and/or diltiazem in addition to magnesium did not result in additional benefit of lowering the incidence of AF.

Impact of posaconazole and diltiazem on pharmacokinetics of encorafenib, a BRAF V600 kinase inhibitor for melanoma and colorectal cancer with BRAF mutations.

Encorafenib is a potent and selective ATP competitive inhibitor of BRAF V600-mutant kinase approved for patients with BRAF-mutant melanoma and colorectal cancer. Encorafenib is mainly metabolized by cytochrome P450 (CYP) 3A4 in vitro and may be susceptible to drug-drug interactions when co-administered with CYP3A inhibitors or inducers. The primary objective was to assess the impact of the strong CYP3A inhibitor posaconazole (part 1) and the moderate CYP3A and P-gp inhibitor diltiazem (part 2) on encorafenib pharmacokinetics in healthy volunteers following a single 50-mg dose. A total of 32 participants were enrolled (16 each in parts 1 and 2). The area under the curve extrapolated to infinity (AUCinf ) and maximum plasma concentration (Cmax ) geometric mean for encorafenib increased by 183% and 68.4%, respectively, when co-administered with posaconazole. Apparent encorafenib clearance decreased from 26.0 to 9.2 L/h when coadministered with posaconazole, and plasma terminal half-life (t½ ) of encorafenib increased from 4.3 to 7.3 h. The AUCinf and Cmax geometric mean for encorafenib increased by 83.0% and 44.7%, respectively, when co-administered with diltiazem. Similarly, the apparent encorafenib clearance decreased from 29.0 to 16.0 L/h when co-administered with diltiazem, and plasma t½ of encorafenib increased from 6.6 to 7.9 h. There were no deaths, serious adverse events (AEs), or patient discontinuations due to AEs in parts 1 or 2. The most frequently reported treatment-related AEs were erythema (n = 14; 88%) and headache (n = 11; 69%) in part 1 and headache (n = 7; 44%) in part 2. The results of this study indicate that co-administration of encorafenib with strong or moderate CYP3A4 inhibitors should be avoided.

Effect of Nicorandil, Diltiazem, or Isosorbide Mononitrate for Oral Antispastic Therapy After Coronary Artery Bypass Grafting Using Radial Artery Grafts-A Pilot Randomized Controlled Trial (ASRAB-Pilot): Rationale and Study Protocol.

INTRODUCTION: The current evidence for chronic oral antispastic medication use after coronary artery bypass grafting using radial artery grafts (RA-CABG) is controversial. Calcium channel blockers, such as diltiazem, are the most commonly used antispastic medications after RA-CABG; other options include nitrates and nicorandil, but to date no sufficiently powered randomized controlled trials have been conducted to compare their efficacy. METHODS: This is a single-center, open-label, parallel three-arm, pilot randomized controlled trial. Patients without contraindications to any study medications and who successfully underwent RA-CABG surgery will be consecutively screened. Eligible patients will be randomized in a ratio of 1:1:1 (a total of 150 patients, 50 per arm) to receive nicorandil 5 mg orally thrice daily, diltiazem 180 mg orally once daily, or isosorbide mononitrate 50 mg orally once daily for 24 weeks. The primary outcomes are RA graft failure at week 1 and week 24. The secondary outcomes include major adverse cardiovascular event (MACE, a composite of all-cause death, myocardial infarction, stroke, and unplanned revascularization) and angina recurrence. The safety outcomes include hypotension occurrence, withdrawal of renin angiotensin aldosterone system inhibitors, serious adverse events, and other concerned adverse events within 24 weeks. CONCLUSION: This pilot trial will compare the preliminary effects of nicorandil, diltiazem, and isosorbide mononitrate on angiographic and clinical outcomes in patients who have undergone RA-CABG. Recruitment began in June 2020, and the estimated primary completion date is early 2023. Results of this study will provide much needed information for design of large confirmatory trials on the effectiveness of oral antispastic medications after RA-CABG.

Managing life-threatening 5-fluorouracil cardiotoxicity.

5-Fluorouracil (5-FU), a known cardiotoxin, is the backbone for the treatment of colorectal cancer. It is associated with arrhythmias, myocardial infarction and sudden cardiac death. Most commonly, it is associated with coronary vasospasm secondary to direct toxic effects on vascular endothelium.A woman with metastatic colon cancer, originally treated with a 5-FU infusion as part of the FOLFIRI (Folinic acid, 5-Fluorouracil, Irinotecan) regimen, was unable to tolerate the chemotherapy due to chest pain. She was transitioned from infusional 5-FU to inferior 1-hour bolus 5-FU, in an attempt to minimise cardiotoxicity, but had disease progression. A multidisciplinary decision was made to again trial 5-FU infusion and pretreat with diltiazem. She tolerated chemotherapy without adverse events. A multidisciplinary discussion is recommended for co-management of reversible 5-FU-associated cardiotoxicity. After coronary artery disease (CAD) risk stratification and treatment, empiric treatment with calcium channel blockers and/or nitrates may allow patients with suspected coronary vasospasm, from 5-FU, to continue this vital chemotherapy.

Allopurinol, dipyridamole and calcium channel blockers in the treatment of bipolar disorder - A nationwide cohort study.

BACKGROUND: Improved treatments for bipolar disorder (BD) are needed. Drug repurposing aims to find novel targets for drugs that have been used for other indications. This study investigated the risk of psychiatric hospitalization associated with use of calcium-channel blockers (CCBs; dihydropyridines, diltiazem, verapamil) and adenosine modulators (allopurinol, dipyridamole) in BD in within-individual design. METHODS: Individuals diagnosed with BD (ICD-10: F30-F31) were identified from the inpatient, specialized outpatient, sickness absence, and disability pension registers during 1996-2018 in Finland (N = 60,045). The main outcome was hospitalization due to affective symptoms (ICD-10: F30-F39). Within-individual models in stratified Cox regression were used and adjusted hazard ratios (aHR) with 95 % confidence intervals (CIs) reported. RESULTS: Use of CCBs was associated with a decreased risk of hospitalization due to affective symptoms (aHR 0.83, 95 % CI 0.78-0.88) when all CCBs were analyzed together. Of specific CCBs, use of diltiazem (0.71, 0.55-0.91) and dihydropyridines (0.83, 0.78-0.89) were associated with a decreased risk but verapamil was not (0.93, 0.73-1.19). Use of adenosine modulators in general was associated with a decreased risk of hospitalizations due to affective symptoms (0.87, 0.79-0.96). Both allopurinol (0.85, 0.74-0.97) and dipyridamole (0.89, 0.78-1.00) were associated with a marginally decreased risk. Thiazide diuretic use as a negative control was not associated with the risk of hospitalization due to affective symptoms (0.97, 0.83-1.13). LIMITATIONS: Due to the observational nature of this study, causation cannot be confirmed. CONCLUSIONS: Dihydropyridines and diltiazem were associated with a decreased risk of psychiatric hospitalization in bipolar disorder. Results for allopurinol and dipyridamole were inconclusive.

PD-1 Inhibitor-Induced Thyrotoxicosis Associated with Coronary Artery Spasm and Ventricular Tachycardia.

Programmed cell death protein 1 (PD-1) inhibitors open a new era of cancer immunotherapy, but they are associated with immune-related adverse events (irAEs) involving multiple endocrine organs of which thyroid dysfunction is the most common An uncommon condition of coronary artery spasm and ventricular tachycardia associated with thyrotoxicosis, induced by a PD-1 inhibitor, is discussed in this case. A 60-year-old male patient with a 1-week history of chest tightness and palpitation at rest was referred to us in July 2021. No obvious abnormalities were noted on physical examination and electrocardiography. He was being treated with a PD-1 inhibitor (camrelizumab, 200 mg) for lung metastasis of liver cancer; treatment stopped because he was found to have hyperthyroidism. Holter recorded intermittent STsegment arch back raised 0.5-14 mm upward lasting for 1-5 min, accompanied by ventricular tachycardia. He was treated with antivasospasm drugs (isosorbide mononitrate and diltiazem). Thyroid function was reexamined and revealed elevated FT3 and FT4 levels, decreased TSH levels, and negative thyroid-associated antibodies. After antivasospasm treatment and iodine taboo diet, his symptoms were relieved, and ST-segment elevation and ventricular tachycardia were disappeared. This case adds to our knowledge of the association between coronary artery spasms and thyrotoxicosis, which is an irAE induced by a PD-1 inhibitor. Patients treated with PD-1 inhibitors need regular follow-ups for cardiac complications, especially those with a history of heart disease.

In vitro and in vivo impacts of nifedipine and diltiazem on praziquantel chemotherapy in murine Schistosoma mansoni.

AIM: This study was planned to evaluate the in vitro and in vivo antischistosomal effects of the widely used antihypertensive drugs, nifedipine (NIF) and diltiazem (DTZ), and their combinations with praziquantel (PZQ) on early and late Schistosoma (S.) mansoni infections 21- and 45- days old stages. METHODS: In the In vitro study, Calcium channel blockers (CCBs), NIF and DTZ were added to schistosomula and adult worm cultures in different concentrations 10, 20 and 30 mg/ml. The mortality percentage was calculated 1, 12 and 24 h after incubation. In vivo, NIF and DTZ either alone or combined with PZQ were used to treat male albino mice. The parasitological and total immunoglobulin (Ig) G and IgM anti-soluble egg antigen (SEA) were assessed to demonstrate the disease severity. RESULTS: In the In vitro study, 10 mg/ml NIF induced 100% mortality percentage of both schistosomula and adult worms after 24 h incubation, while DTZ induced similar mortality percentage at 30 mg/ml concentration. In vivo results showed that early or late combination of 30 mg/kg of NIF, but not DTZ, significantly (P <0.05) enhanced the reductive efficacy of PZQ based on the parasitological data. The maximal reduction (P <0.05) of anti-SEA IgM and IgG levels was developed during NIF-PZQ administration 21- (1.12 ± 0.06 and 1.09 ± 0.04, respectively) or 45- (1.00 ± 0.03 and 0.8 ± 0.06, respectively) days post infection (PI), compared to either PZQ or NIF individual treatments. The decreased concentration of anti-SEA antibodies was correlated with the diminished granulomatous diameter and disease severity. CONCLUSION: Nifedipine improved PZQ chemotherapy targeting either early or late S. mansoni infection in mice compared to the PZQ mono-therapy. Administering NIF can be considered as a promising drug candidate for schistosomiasis chemotherapy.

Botulinum Toxin Injection Plus Topical Diltiazem for Chronic Anal Fissure: A Randomized Double-Blind Clinical Trial and Long-term Outcome.

BACKGROUND: Chemical sphincterotomy avoids the risk of permanent incontinence in the treatment of chronic anal fissure, but it does not reach the efficacy of surgery and recurrence is high. Drug combination has been proposed to overcome these drawbacks. OBJECTIVE: This study aimed to compare the clinical, morphological, and functional effects of combined therapy with botulinum toxin injection and topical diltiazem in chronic anal fissure and to assess the long-term outcome after healing. DESIGN: This is a randomized, controlled, double-blind, 2-arm, parallel-group trial with a long-term follow-up. SETTINGS: This study was conducted at a tertiary care center. PATIENTS: A total of 70 consecutive patients were referred to the gastroenterology department of a hospital in Valencia, Spain. INTERVENTION: After botulinum toxin injection (20 IU), patients were randomly assigned to local diltiazem (diltiazem group) or placebo gel (placebo group) for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome was fissure healing (evaluated by video register by 3 independent physicians). Secondary outcomes included symptomatic relief (30-day diary), effect on anal sphincters (manometry), safety, and long-term recurrence (24 months and 10 years). RESULTS: Healing was achieved per protocol in 13 of 25 (52%) patients of the diltiazem group and 11 of 30 (36.7%) patients of the placebo group (p = 0.25); on an intention-to-treat basis in 37.1% and 31.4% (p = 0.61). Both groups displayed significant reduction of anal pressures. Thirty percent reported minor and transitory incontinence, without differences between groups. Nine (69.2%) of the diltiazem group and 6 (54.5%) of the placebo group experienced a relapse at 24 months (p = 0.67). The overall recurrence rate at 10 years was 83.3% (20/24 patients). LIMITATIONS: This study was limited by the loss of patients during the trial. The low healing rate led to a small cohort to assess recurrence. CONCLUSIONS: Combined botulinum toxin injection and topical diltiazem is not superior to botulinum toxin injection in the treatment of chronic anal fissure. Both options offer suboptimal healing rates. Long-term recurrence is high (>80% at 10 years) and might appear at any time after healing. See Video Abstract at http://links.lww.com/DCR/B527. INYECCIN DE TOXINA BOTULNICA MS DILTIAZEM TPICO EN FISURA ANAL CRNICA UN ENSAYO CLNICO ALEATORIZADO DOBLE CIEGO Y RESULTADOS A LARGO PLAZO: ANTECEDENTES:La esfinterotomía química evita el riesgo de incontinencia permanente en el tratamiento de la fisura anal crónica, pero no alcanza la eficacia de la cirugía y la recurrencia es alta. Se ha propuesto la combinación de fármacos para superar estos inconvenientes.OBJETIVO:Comparar los efectos clínicos, morfológicos y funcionales de la terapia combinada con inyección de toxina botulínica y diltiazem tópico en fisura anal crónica y evaluar el resultado a largo plazo después de la cicatrización.DISEÑO:Ensayo aleatorizado, controlado, doble ciego, de dos brazos, de grupos paralelos con un seguimiento a largo plazo.ESCENARIO:Estudio realizado en un centro de atención terciaria.PACIENTES:Un total de 70 pacientes consecutivos referidos al servicio de gastroenterología de un hospital de Valencia, España.INTERVENCIÓN:Después de la inyección de toxina botulínica (20UI), los pacientes fueron asignados al azar a diltiazem local (grupo de diltiazem) o gel de placebo (grupo de placebo) durante 12 semanas.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la cicatrización de la fisura (evaluado por registro de video por tres médicos independientes). Los resultados secundarios incluyeron alivio sintomático (diario de 30 días), efecto sobre los esfínteres anales (manometría), seguridad y recurrencia a largo plazo (24 meses y 10 años).RESULTADOS:La curación se logró por protocolo en 13/25 (52%) en el grupo de Diltiazem y 11/30 (36,7%) en el grupo de Placebo (p = 0.25); por intención de tratar en el 37.1% y el 31.4%, respectivamente (p = 0.61). Ambos grupos mostraron una reducción significativa de las presiones anales. El 30% refirió incontinencia leve y transitoria, sin diferencias entre grupos. 9 (69.2%) del grupo de Diltiazem y 6 (54.5%) del grupo de placebo recurrieron a los 24 meses (p = 0.67). La tasa global de recurrencia a los 10 años fue del 83.3% (20/24 pacientes).LIMITACIONES:La pérdida de pacientes a lo largo del ensayo. La baja tasa de curación llevó a una pequeña cohorte para evaluar la recurrencia.CONCLUSIONES:La inyección combinada de toxina botulínica y diltiazem tópico no es superior a la inyección de TB en el tratamiento de la fisura anal crónica. Ambas opciones ofrecen tasas de curación subóptimas. La recurrencia a largo plazo es alta (> 80% a los 10 años) y puede aparecer en cualquier momento después de la curación. Consulte Video Resumen en http://links.lww.com/DCR/B527.

Comparison of the Apoptotic Effects of Topically Applied Papaverine, Diltiazem, and Nitroprusside to Internal Thoracic Artery.

OBJECTIVE: To detect and to compare the apoptotic effects of intraoperatively topically applied diltiazem, papaverine, and nitroprusside. METHODS: Internal thoracic artery segments of ten patients were obtained during coronary bypass grafting surgery. Each internal thoracic artery segment was divided into four pieces and immersed into four different solutions containing separately saline (Group S), diltiazem (Group D), papaverine (Group P), and nitroprusside (Group N). Each segment was examined with both hematoxylin-eosin and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in order to determine and quantify apoptosis. RESULTS: Apoptotic cells were counted in 50 microscopic areas of each segment. No significant difference was observed among the four groups according to hematoxylin-eosin staining. However, the TUNEL method revealed a significant increase in mean apoptotic cells in the diltiazem group when compared with the other three groups (Group S=4.25±1.4; Group D=13.31±2.8; Group N=9.48±2.09; Group P=10.75±2.37). The differences between groups were significant (P=0.0001). No difference was observed between the samples of the diabetic and non-diabetic patients in any of the study groups. CONCLUSION: The benefit of topically applied vasodilator drugs must outweigh the potential adverse effects. In terms of apoptosis, diltiazem was found to have the most deleterious effects on internal thoracic artery graft segments. Of the analyzed medical agents, nitroprusside was found to have the least apoptotic activity, followed by papaverine. Diabetes did not have significant effect on the occurrence of apoptosis in left internal thoracic artery grafts.

Comparison of the apoptotic effects of topically applied papaverine, diltiazem, and nitroprusside to internal thoracic artery

Abstract Objective: To detect and to compare the apoptotic effects of intraoperatively topically applied diltiazem, papaverine, and nitroprusside. Methods: Internal thoracic artery segments of ten patients were obtained during coronary bypass grafting surgery. Each internal thoracic artery segment was divided into four pieces and immersed into four different solutions containing separately saline (Group S), diltiazem (Group D), papaverine (Group P), and nitroprusside (Group N). Each segment was examined with both hematoxylin-eosin and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in order to determine and quantify apoptosis. Results: Apoptotic cells were counted in 50 microscopic areas of each segment. No significant difference was observed among the four groups according to hematoxylin-eosin staining. However, the TUNEL method revealed a significant increase in mean apoptotic cells in the diltiazem group when compared with the other three groups (Group S=4.25±1.4; Group D=13.31±2.8; Group N=9.48±2.09; Group P=10.75±2.37). The differences between groups were significant (P=0.0001). No difference was observed between the samples of the diabetic and non-diabetic patients in any of the study groups. Conclusion: The benefit of topically applied vasodilator drugs must outweigh the potential adverse effects. In terms of apoptosis, diltiazem was found to have the most deleterious effects on internal thoracic artery graft segments. Of the analyzed medical agents, nitroprusside was found to have the least apoptotic activity, followed by papaverine. Diabetes did not have significant effect on the occurrence of apoptosis in left internal thoracic artery grafts.

Comparative efficacy of medical treatment versus surgical sphincterotomy in the treatment of chronic anal fissure.

BACKGROUND: Anal fissure which is defined as a longitudinal tear in anoderm below the dentate line is one of the most common benign diseases of anorectal area. Severe pain during the defecation and emotional stress that it causes may reduce people's quality of life. AIMS: In this randomized clinical trial, we aimed to compare the efficiency of the topical ointment with medical treatment and surgical lateral internal sphincterotomy. METHOD: This is a randomized clinical trial of 550 patients who were treated for chronic anal fissure. Patients were randomly divided into 4 groups according to the treatment type they received. RESULTS: In a vast majority of the patients, the primary complaint was pain (92.3%) and bleeding during defecation (62%). Both pain relief and healing of the fissure, which are the components of response to treatment, had not been observed in 56 (37.3%) patients of topical nitroglycerin ointment group until the second month. Among the recalcitrant patients in both topical nitroglycerin (56) and topical diltiazem ointment (47) groups, 27 (48.2%), and 36 (76.5%) patients underwent surgery, respectively. The best response to treatment was also obtained in lateral internal sphincterotomy group. CONCLUSION: LIS is still the gold standard for the treatment of chronic anal fissure when the physicians would like to avoid recurrence and obtain the best pain relief.

New perspectives in the pharmacological treatment of hypertrophic cardiomyopathy. / Novas perspetivas no tratamento farmacológico da miocardiopatia hipertrófica.

Hypertrophic cardiomyopathy is an inherited cardiac disease and a major cause of heart failure and sudden death. Even though it was described more than 50 years ago, sarcomeric hypertrophic cardiomyopathy still lacks a disease-specific treatment. The drugs routinely used alleviate symptoms but do not prevent or revert the phenotype. With recent advances in the knowledge about the genetics and pathophysiology of hypertrophic cardiomyopathy, new genetic and pharmacological approaches have been recently discovered and studied that, by influencing different pathways involved in this disease, have the potential to function as disease-modifying therapies. These promising new pharmacological and genetic therapies will be the focus of this review.

Diltiazem Prophylaxis for the Prevention of Atrial Fibrillation in Patients Undergoing Thoracoabdominal Esophagectomy: A Retrospective Cohort Study.

BACKGROUND: Atrial fibrillation (AF) represents the most frequent arrhythmic disorder after thoracoabdominal esophageal resection and is associated with a significant increase in perioperative morbidity and mortality. METHODS: In this retrospective cohort study, 167 patients who underwent thoracoabdominal esophagectomy at a large university hospital were assessed. We compared patients who received a 14-day postoperative course of diltiazem with a control group of patients who did not undergo diltiazem prophylaxis. Diltiazem therapy started immediately upon admission to the intensive care unit (ICU) with a loading dose of 0.25 mg/kg bodyweight (i.v.) followed by continuous infusion (0.1 mg/kg bodyweight/h) for 40-48 h. Oral administration (Dilzem® 180 mg uno retard, once a day) was started on postoperative day 3. RESULTS: A total of 117 patients were assessed. Twelve (10.3%) of all patients developed postoperative new-onset atrial fibrillation in the first 30 days after surgical intervention. Prevalence of new-onset AF showed no significant differences between the diltiazem group and control group (p = 0.74). The prevalence of bradycardia (14.7% vs. 3.6%; p = 0.03) and dose of norepinephrine required (0.09 vs. 0.04 µg/kg bodyweight/min; p = 0.04) were higher in the diltiazem group. There were no significant differences between the groups for the median postoperative duration of hospital/ICU stay or mortality. CONCLUSIONS: A prophylactic 14-day postoperative course of diltiazem was not associated with a reduction in new-onset AF or 30-day mortality following thoracoabdominal esophagectomy. Prophylactic diltiazem therapy was associated with drug-related adverse effects such as bradycardia and increased requirement of norepinephrine. German Clinical Trial Registration Number: DKRS00016631.

A prospective, double-blind, randomized, placebo-controlled trial comparing the efficacy of polyethylene glycol versus polyethylene glycol combined with topical diltiazem for treating anal fissure in children.

BACKGROUND: Anal fissure (AF) in children is usually treated with laxatives and/or topical agents such as calcium channel blockers. We hypothesize that owing to the superior efficacy of Polyethylene glycol (PEG) in treating constipation in children, adding diltiazem (DTZ) might not improve healing of AF. METHODS: Children ≤14 years with anal fissure presented to the pediatric surgery clinic between November 2014 and March 2016 were recruited. Randomization was performed to either PEG with DTZ or PEG with placebo. Study personnel, patients, and their families were blinded. Primary outcome was resolution of symptoms. Secondary outcomes were constipation and treatment complications at 12-week follow up. RESULTS: 48 patients were randomized: 24 to PEG + DTZ and 24 to PEG + placebo. Both groups were similar in their baseline characteristics. At week 12, majority of patients' symptoms have improved without significant difference between groups; painful defecation at week 12: 20.8% and 8.3% (p-value 0.41), blood per rectum at week 12: 4.2% and 8.3% (p value 0.58) in the DTZ and placebo groups, respectively. Additionally, there was similar improvement in constipation in both groups. CONCLUSION: PEG alone was associated with similar improvement in anal fissure symptoms in children compared to PEG and topical diltiazem combined. LEVEL OF EVIDENCE: I.

Takayasu arteritis in a rural hospital in Indonesia.

Takayasu arteritis (TA) is a rare chronic granulomatous inflammation of the aorta or its branches and is prevalent all around the world. It causes stenosis of large arteries and ischaemic damage to target organs. There is usually a delay in recognising TA because of the rarity and unfamiliarity with the disease, unspecific early symptoms and lack of diagnostic equipment for early diagnosis. In this report, we present a case of an 18-year-old woman from Pasuruan, East Java, Indonesia, with recurrent fever, headache, claudication of extremities and postprandial abdominal pain. She was diagnosed clinically with suspicion of TA and was sent to a tertiary hospital to confirm the diagnosis. Arteriography revealed that the patient had narrowing of the thoracic and abdominal aorta until the level of the aortic bifurcation. The patient was started on high-dose corticosteroid, cyclosporine A and diltiazem. The patient then showed improvement in her symptoms.

Treatment of calcinosis cutis in systemic sclerosis and dermatomyositis: A review of the literature.

BACKGROUND: We have limited data on the treatment of calcinosis cutis associated with systemic sclerosis and dermatomyositis. OBJECTIVE: To assess the efficacy and tolerance of available treatments for calcinosis cutis based on previously published studies. METHODS: We performed a systematic review of studies published in Medline, Embase, and the Cochrane library during 1980-July 2018. The strength of clinical data was graded according to the modified Oxford Centre for Evidence-Based Medicine levels of evidence. RESULTS: In all, 30 studies (288 patients) were included. Eleven therapeutic classes, surgery, and physical treatments were identified as potential treatment options for calcinosis cutis. On the basis of results of a small randomized controlled trial and 4 retrospective studies, low-dose warfarin should not be used for calcinosis cutis (level IB evidence). The results of several studies suggest diltiazem and bisphosphonates might be useful treatment options (level IV). Considering biologic therapies, rituximab has shown promising results in treating both dermatomyositis and systemic sclerosis, whereas tumor necrosis factor inhibitors might be useful for treating juvenile dermatomyositis (level IV). Intralesional sodium thiosulfate might be a promising alternative (level IV). LIMITATIONS: Few included studies had a high level of evidence. CONCLUSION: This study highlights the efficacy and tolerance profiles of available treatments for calcinosis cutis, with a focus on level of evidence.