Bilateral Disease Common Among Slovenian CHEK2-Positive Breast Cancer Patients.

BACKGROUND: Currently, data on pathogenic variants in the CHEK2 gene and their impact on cancer risk are lacking. This study aimed to explore the characteristics of breast cancer (BC) patients from families with CHEK2 pathogenic variants in Slovenia. METHODS: In the years 2014 to 2019, CHEK2 pathogenic variants/likely pathogenic variants (PV/LPVs) were found in probands from 50 different families who underwent genetic counseling and testing using a multigene panel at the authors' institution. Altogether, the study enrolled 75 individuals from 50 CHEK2 families who were carriers of a CHEK2 PV/LPV. The clinical data on 41 BC patients with CHEK2 PV/LPV and other carriers of CHEK2 PV/LPV from Slovenia were collected and analyzed. RESULTS: Breast cancer was diagnosed in 41 of 75 CHEK2 PV/LPV carriers (40 females, 1 male). The mean age at BC diagnosis was 42.8 years (range, 21-63 years), and 27 (65.8%) of the 41 of patients with BC had a positive family history for BC. Contralateral BC (CBC) was observed in 8 (19.5%) of the 41 patients (mean age, 55.6 years). Of 12 patients with human epidermal growth factor receptor 2 (HER2)-positive tumor type, a c.444+1G > A PV/LPV was detected in 4 patients, c.349A > G in 3 patients, deletion of exons 9-10 in 3 patients, deletion of exon 8 in 1 patient, and c.1427C > T PV/LPV in 1 patient. CONCLUSION: Bilateral BC was diagnosed in as many as 19.5% of the Slovenian BC patients with CHEK2 PV/LPVs. Breast cancer associated with a germline CHEK2 PV/LPV occurs in younger patients compared with sporadic BC.

The TREAT-NMD Duchenne muscular dystrophy registries: conception, design, and utilization by industry and academia.

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease, caused by the absence of the dystrophin protein. Although many novel therapies are under development for DMD, there is currently no cure and affected individuals are often confined to a wheelchair by their teens and die in their twenties/thirties. DMD is a rare disease (prevalence <5/10,000). Even the largest countries do not have enough affected patients to rigorously assess novel therapies, unravel genetic complexities, and determine patient outcomes. TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients. The harmonized implementation of national and ultimately global patient registries has been central to the success of TREAT-NMD. For the DMD registries within TREAT-NMD, individual countries have chosen to collect patient information in the form of standardized patient registries to increase the overall patient population on which clinical outcomes and new technologies can be assessed. The registries comprise more than 13,500 patients from 31 different countries. Here, we describe how the TREAT-NMD national patient registries for DMD were established. We look at their continued growth and assess how successful they have been at fostering collaboration between academia, patient organizations, and industry.

Antibiotic resistance of Helicobacter pylori in pediatric patients -- 10 years' experience.

The aim of this study was to assess the pattern of evolution of resistance to antibiotics in Helicobacter pylori isolated from children who underwent upper endoscopy with antral biopsy during a 10-year period (2001-2010). We retrospectively analyzed data of all children (n = 3,008) who underwent upper endoscopy during the observed period at the Children's Hospital Zagreb, a university tertiary medical center. We calculated the rate, antibiotic susceptibility and risk factors for the H. pylori infection in our cohort. Antral biopsy was performed in 2,313 (76.89%) patients. Altogether, 382 (16.51%) children had positive biopsy for H. pylori (histology and/or culture). There was no significant difference in the incidence of H. pylori during 10 years of observation (p = 0.21). Infected children compared to non-infected group were older (p = 0.005), and had more often antral nodularity (p < 0.0001), and duodenal ulcer (p = 0.002). Altogether, 22.4% of treatment-naïve patients had strains resistant to tested antibiotics: majority to azithromycin (17.9%), followed by clarithromycin (11.9%), metronidazole (10.1%) and amoxicillin (0.6%). In the eradication failure group, 9/11 of children had strains resistant to tested antibiotics, mostly to metronidazole (7/11), followed by azithromycin (3/11) and clarithromycin (1/11). No correlation was found between age or gender and antibiotic resistance (p = 0.32, for both). In conclusion, our data strongly support current guidelines which recommend antibiotic susceptibility testing prior to eradication therapy. Based on our results we recommend the use of amoxicillin-metronidazole-based regimen as the first-line therapy in our study population.

Threatening Fracture of Intraosseous Lipoma Treated by Internal Fixation Case Report and Review of the Literature.

Intraosseous lipomas are rare benign bone neoplasms with an incidence of less than 0.1%; origin in the calcaneus has been reported in only a few patients. First-line treatment remains conservative, but several surgical techniques have also been described. We describe a 44-year-old woman with increasing pain in her left heel for a year and a half, who noticed swelling on the lateral side of the calcaneus. The patient underwent radiography, magnetic resonance imaging, and computed tomography of her left foot, which was suspicious for an intraosseous lipoma with a threatening calcaneal fracture. We performed a surgical procedure, curettage of the tumor, spongioplastics (by autologous bone transplant and ß-tricalcium phosphate), and internal stabilization with a calcaneal plate considering the goal of immediate postoperative weightbearing. Histologic examination confirmed an intraosseous lipoma of the calcaneus. The patient's pain was relieved immediately after surgery. Internal stabilization of the calcaneus allowed the patient to immediately fully weightbear and to return to usual daily activities. Although a benign bone tumor, intraosseous lipoma can cause many complications, such as persistent pain, decreased function, or even pathologic fracture as a result of calcaneal bone weakening. Choosing an appropriate treatment is still controversial. Conservative treatment is the first option, but for patients with severe problems and threatening fracture, surgery is necessary. Internal fixation for stabilization enables immediate postoperative weightbearing and shortens recovery time.

Phototherapy with LED Shows Promising Results in Healing Chronic Wounds in Diabetes Mellitus Patients: A Prospective Randomized Double-Blind Study.

OBJECTIVE: The study examined the influence of phototherapy with light-emitting diodes (LEDs) on chronic diabetic wound healing. BACKGROUND: Chronic diabetic wounds are very difficult to treat due to underlying conditions such as angiopathy and neuropathy, resulting in slow healing rates. Conventional treatment options are often insufficient and do not provide satisfactory outcomes. Phototherapy with LED enhances the healing processes through mechanisms of energy exchange between incoming photons and their target, the main one being cytochrome-c oxidase in mitochondria. METHODS: A double-blind, randomized study included 60 patients with a chronic diabetic wound treated at the University Medical Center Ljubljana between October 1, 2012 and December 1, 2014. Patients were randomized into either an active group (LED group) or a control group (Co-group). The active group was treated with LED 2.4 J/cm2 (wavelengths 625, 660, 850 nm) three times a week for 8 weeks. The Co-group was treated with light that simulated LED. Healing was evaluated using the Falanga wound bed score and wound surface area. RESULTS: The average baseline wound surface before treatment was 1315 mm2 in the LED group and 1584 mm2 in the Co-group (p = 0.80). After 8 weeks, the mean surface in the LED group was 56% of the baseline surface and 65% in the Co-group (p > 0.05). Falanga score evaluation showed significantly faster wound bed healing in the LED group compared with the Co-group (p < 0.05). CONCLUSIONS: According to our results, LED significantly improves healing of chronic diabetic wounds and prepares the wound bed for further coverage options.

Bifidobacterium animalis subsp. lactis in prevention of common infections in healthy children attending day care centers - Randomized, double blind, placebo-controlled study.

BACKGROUND & AIMS: The aim of our study was to investigate the role of Bifidobacterium animalis subsp. lactis (BB-12(®)) in the prevention of common (gastrointestinal and respiratory) infections in healthy children who attend day care centers. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 210 children who attend day care centers. They were randomly allocated to receive placebo (Placebo group, n = 106) or BB-12(®) at a dose of 10(9) colony-forming units (CFU) (Intervention group, n = 104) during the 3-month intervention period. RESULTS: Intention to treat analysis was used. There were overall 99 infections in Placebo group and 97 in Intervention group (incidence rate ratio = 1.0014, p = 0.992, Poisson regression model). Overall 65 children (61.3%) in Placebo group and 67 (64.4%) in Intervention group had common infections (p = 0.642). Mean number of infections per child was 0.93 (range 0-3) in Placebo group and 0.93 (range 0-3) in Intervention group (p = 0.898). There was no difference in secondary (duration of symptoms, number of children with gastrointestinal and respiratory tract infections, absence from day care center due to infections, use of antibiotics) and exploratory (type of gastrointestinal and respiratory tract infection) endpoints between groups. CONCLUSION: Results of performed study show that BB-12(®) has no effect on the prevention of gastrointestinal and respiratory tract infections in healthy children who attend day care centers.

Reasons for refusing kidney transplantation among chronic dialysis patients.

The aim of the prospective clinical study was to evaluate the reasons for refusing kidney transplantation among chronic dialysis patients. A total of 164 adult chronic dialysis patients participated in the study. They were asked to complete a detailed questionnaire on specific issues regarding transplantation. The mean age was 60.9 ± 16.0 (20-89) years, 61.6% were male, 11.6% had had a previous transplant. The majority, that is, 72.0%, of the patients believed that transplantation improved the quality of life, and 55.5% believed that transplantation prolonged life. Nevertheless, 45.0% of the patients wanted to be transplanted, 35.0% refused transplantation, and 20.0% were undecided. Patients refusing transplantation were significantly older compared to the patients wanting to be transplanted (67 ± 16 vs. 57 ± 16 years; P < 0.001). The main reasons for refusing transplantation (57 patients) were the side-effects of immunosuppressive therapy (31.6%), unpredictability of transplant outcome (29.8%), and unfavorable outcomes in fellow patients (28.1%). The side-effects of immunosuppressive therapy that patients were most concerned about included mobility problems (29.8%), new-onset diabetes (26.3%), increased risk of severe infections (26.3%), problems with vision (22.8%), and increased risk of cancer (21.1%). Many patients did not want to accept organs from expanded criteria donors (ECD) (44.6% of the patients wanting and 64.9% of those refusing transplantation). The majority believed that patients should be informed if an organ from an ECD donor is being offered (64.9% of patients wanting and 63.2% of those refusing transplantation). The main reasons for refusing kidney transplantation were the side-effects of immunosuppressive therapy, unpredictability of transplant outcome, and unfavorable outcomes in fellow patients.