Pharmacogenomics at the center of precision medicine: challenges and perspective in an era of Big Data.

Pharmacogenomics (PGx) is one of the core elements of personalized medicine. PGx information reduces the likelihood of adverse drug reactions and optimizes therapeutic efficacy. St Catherine Specialty Hospital in Zagreb/Zabok, Croatia has implemented a personalized patient approach using the RightMed® Comprehensive PGx panel of 25 pharmacogenes plus Facor V Leiden, Factor II and MTHFR genes, which is interpreted by a special counseling team to offer the best quality of care. With the advent of significant technological advances comes another challenge: how can we harness the data to inform clinically actionable measures and how can we use it to develop better predictive risk models? We propose to apply the principles artificial intelligence to develop a medication optimization platform to prevent, manage and treat different diseases.

SPONTANEOUS HETEROTOPIC, ECTOPIC CERVICAL AND ECTOPIC TUBAL PREGNANCY - EVER PRESENT DIAGNOSTIC DIFFICULTY: THREE CASE REPORTS.

The incidence of heterotopic/ectopic pregnancy in recent times has increased partly due to the increase in assisted reproductive technologies, whereas such medical cases and cervical pregnancy in particular are extremely rare with spontaneous conception. We report on three patients referred to our department in one week: one patient each with spontaneous heterotopic pregnancy, cervical pregnancy and tubal pregnancy. All of them had conceived spontaneously and were properly diagnosed and treated, however, additional care is needed in diagnosing and managing the potentially fatal consequences of ectopic pregnancy if not recognized early and managed properly, despite its low incidence.

Effects of immune modulation therapy in the first Croatian infant diagnosed with Pompe disease: a 3-year follow-up study.

Pompe disease is a storage disorder characterized by deficient or absent activity of the enzyme acid alpha-glucosidase. As a result of ineffective metabolism, glycogen accumulates in muscle tissues. Patients with a classic infantile-onset form present by the first few months of life with hypertrophic cardiomyopathy and muscle weakness. If left untreated, these patients rapidly die of cardiorespiratory failure. A cross-reactive immunological material (CRIM)-negative status is predictive of high anti-alglucosidase alpha antibody titers. However, CRIM-positive patients also sometimes develop robust antibody titers. High antibody titers complicate therapeutic management, and those patients have a worse clinical outcome of enzyme replacement therapy (ERT).Four years ago, we successfully used an immune modulation therapy (IMT) protocol in a CRIM-positive infantile-onset patient with Pompe disease in whom ERT had to be discontinued because of severe infusion-associated reactions. She was found to be positive for anti-alglucosidase alpha antibodies. IMT (rituximab, methotrexate, and intravenous gammaglobulin) was started, and ERT was safely reintroduced during the IMT induction phase without any complications. Antibodies disappeared; IMT was tapered and discontinued; and cardiomyopathy steadily improved. During more than 3 years of follow-up, she remained ventilator dependent, and no gains in motor skills were noticed. The antibodies are still undetectable, and no adverse reactions associated with IMT had occurred. The cardiomyopathy is gradually increasing, but there is still ~ 50 % reduction as compared with the highest value measured. Although the reversal of clinical decline in our CRIM-positive and antibody-positive infant cannot be solely attributed to IMT, this protocol proved itself efficient and safe.

Modification of conservative treatment of heterotopic cervical pregnancy by Foley catheter balloon fixation with cerclage sutures at the level of the external cervical os: a case report.

INTRODUCTION: Conservative treatment of a heterotopic cervical pregnancy was performed with a modification of the fixation of a Foley catheter at the level of the external cervical os, followed by the ligature of the descending cervical branches of the uterine arteries and systemic methotrexate application. CASE PRESENTATION: A 34-year-old Caucasian woman was diagnosed with double gestation after 6 weeks of in vitro fertilization treatment. A gynecological examination and color Doppler ultrasound scan revealed intra-uterine and cervical gestational sacs both containing live fetuses. A Foley catheter balloon was inserted into the cervical canal, inflated and fixed by a cerclage suture at the level of the external cervical os, followed by ligation of the descending cervical branches of the uterine arteries. Systemic methotrexate was applied. Three days after removal of the Foley catheter, an evacuation of the intra-uterine gestational sac was performed. Hemorrhage from the implantation site was controlled immediately and a pregnancy termination was successfully performed. The procedure was uneventful and our patient was discharged with a preserved uterus. CONCLUSIONS: Conservative treatment of cervical pregnancy using a Foley catheter balloon is more efficacious if the Foley catheter balloon is attached in the correct position with a cerclage suture at the level of the external os, followed by ligation of the descending cervical branches of the uterine arteries, thereby exerting maximal pressure on the bleeding vessels.