Homologous recombination repair deficiency (HRD) testing in newly diagnosed advanced-stage epithelial ovarian cancer: A Belgian expert opinion.

Ovarian cancer (OC) has a poor prognosis as most patients present with non-specific symptoms and the disease is mostly diagnosed at advanced stages. Approximately 90% of cases are classified as epithelial OC (EOC), a category comprising histologically and molecularly distinct tumours. Identifying reliable biomarkers and employing personalised therapies in OC subgroups is crucial for battling the disease. EOCs are often characterised by homologous recombination repair deficiency (HRD), frequently caused by inactivation of the breast cancer susceptibility (BRCA) genes. These findings have led to the development of poly- (adenosine diphosphate [ADP])- ribose polymerase inhibitors (PARPi), which are synthetically lethal to HRD tumour cells. Both patients with HRD and non-HRD tumours can benefit from PARPi therapy in the recurrent setting. Moreover, recent phase III trials in patients with newly diagnosed advanced-stage OC have demonstrated greater clinical benefit from PARPi in treating HRD than non-HRD tumours. These findings offer new opportunities for the use of PARPi as maintenance therapy after first-line chemotherapy based on the presence of HRD. In the current article, we provide recommendations for HRD testing and treatment of patients with newly diagnosed advanced-stage EOC.

Prosthetic and Surgical Reconstruction of the Atrophic Anterior Maxilla with Iliac Bone Grafting and Malo Bridge Design: A Case Report.

Alveolar bone loss subsequent to long-term edentulism and trauma may be severe and treatment plan is always an esthetic and functional challenge. Implant supported hybrid prosthesis is widely regarded as an effective treatment option for patients with excessive and irregular bone loss. However, implant placement is occasionally impossible without surgical procedures in such cases. This case report presents rehabilitation of 19-year-old maxillary anterior edentulous male patient with maxillary anterior bone defect and excessive cross-bite anterior closure with multidisciplinary approach. The patient was rehabilitated with implant supported hybrid prosthesis with Malo Bridge design following autogeneous iliac bone augmentation, teeth leveling with orthodontic treatment, and surgical placement of three implants. Esthetics, pleasing phonetics and function were achieved as desired with this treatment option and no complications were observed.

Rehabilitation of the completely edentulous young patient with the "Malo Bridge": A case report.

It is possible to rehabilitate fully edentulous patients with implantsupported fixed or removable prostheses; however, implantsupported fixed prostheses are the gold standard for patients who not prefer to use removable dentures. This case report, prosthetic rehabilitation of a completely edentulous young patient with an implantsupported fixed hybrid prosthesis using the "Malo Bridge" technique is described. A 18 years old male patient was referred to the clinic with complaints of tooth loss, aesthetics, function, and phonetic. A total of 5 implants were placed in both the jaws. Considering that screw holes may cause aesthetic problems due to the Class III occlusion, these problems have been solved with the implant-supported hybrid prosthesis called Malo bridge. With the Malo Bridge design, the patient's aesthetic, functional and phonetic loss was eliminated, patient comfort and quality of life were improved, and patient expectations were met. It is a viable treatment option to rehabilitate completely edentulous jaws with a cross relationship and increase interarch distance using Malo Bridge to support a fixed prosthesis.

Concealed Coronary Atherosclerosis In Idiopathic Paroxysmal Atrial Fibrillation is Associated with Imminent Cardiovascular Diseases.

BACKGROUND: Previous research showed a significant difference in the presence of subclinical coronary artery disease (CAD) on cardiac CT angiography (CTA) between patients with idiopathic paroxysmal atrial fibrillation (iAF) versus a matched sinus rhythm population (iSR). Here we present 5-year follow-up data and the consequences of subclinical CAD on baseline CTA on the development of cardiovascular disease in iAF. METHODS: In 99 iAF patients (who underwent CTA as part of work-up for pulmonary vein isolation) and 221 matched iSR controls (who underwent CTA for CAD assessment), the incidence of hypertension, diabetes and major cardiovascular events (MACCE) during follow-up was obtained. Multivariable Cox regression analysis was used to reveal predictors of incident cardiovascular disease in the iAF group. RESULTS: During a follow-up of 68±11 months, over one third of patients developed cardiovascular disease, with no difference between iAF and iSR (log-rank p=0.56), and comparable low rates of MACCE (4.0% vs 5.0%,p=0.71). Within the iAF group, age (HR1.12(1.03-1.20);p=0.006), left atrial diameter (HR1.16(1.03-1.31);p=0.01), Segment Involvement Score (total number of coronary segments with atherosclerotic plaque; HR1.43(1.09-1.89);p=0.01) and the number of calcified plaques on CTA (HR0.53(0.30-0.92);p=0.01) were independent predictors of incident cardiovascular disease. CONCLUSIONS: Subclinical coronary disease on CTA may be useful to identify the subset of patients with iAF that harbour concealed cardiovascular risk factors and need intensive clinical follow-up to ensure timely initiation of appropriate therapy once CV disease develops, including anticoagulation and vascular prophylactic therapy.

Effect of surface treatments to remove temporary cement remnants on the bond strength between the core composite and resin cement.

BACKGROUND: There was no enough data about the appropriate surface cleaning of core composite material after temporary cementation. AIM: To evaluate the effects of surface cleaning techniques on initial shear bond strength (SBS) between core composite material and resin nanoceramic crown materials after temporary cementation. MATERIAL AND METHODS: Cubic specimens were prepared from prosthetic materials, including Lava Ultimate. Cylinder-shaped composites were cemented to glass slides with eugenol-free temporary cement, resulting in a total of 44 cylinders (n = 11). The surfaces of composite cylinders were then cleaned with an Er, Cr:YSGG laser, 37% orthophosphoric acid, yellow tape diamond bur, or dental explorer. Cleaned cylinders were bonded to cubic specimens with resin cement. Initial SBS tests were performed with a universal testing machine at 0.5 mm/min crosshead speed. One-way ANOVA and post hoc Tukey tests were used to analyze the obtained data (P =0.05). RESULTS: Initial SBS values were significantly affected by the different surface cleaning methods (P <.05). The highest SBS value was obtained with the laser group (SBS = 17.14), while the lowest was obtained with dental explorer group (SBS = 5.95). There was no significant difference between the diamond bur group and the laser group (P =0.982). CONCLUSIONS: Laser irradiation or yellow tape diamond bur cleaning of the core composite surface could be recommended to strengthen bond strength between the resin luting cement and the core composite. Before adhesive or conventional cementation of prosthetic restoration, the core composite surface should be cleaned.

Presence and extent of cardiac computed tomography angiography defined coronary artery disease in patients presenting with syncope.

BACKGROUND: In syncope patients, presence of coronary artery disease (CAD) is associated with poor prognosis. However, data concerning CAD prevalence in syncope patients without known cardiovascular disease are lacking. Therefore, the aim of this study was to investigate presence and extent of CAD in syncope patients. METHODS: We included 142 consecutive patients presenting with syncope at the outpatient cardiology clinic who underwent coronary computed tomography (CT) angiography. Syncope type was ascertained by two reviewers, blinded for coronary CT angiography results. Of the patients, 49 had cardiac syncope (arrhythmia or structural cardiopulmonary disease) and 93 had non-cardiac syncope (reflex [neurally-mediated], orthostatic or of unknown cause). Cardiac syncope patients were compared with matched stable chest pain patients regarding age, gender, smoking status, diabetes mellitus type 2 and systolic blood pressure. RESULTS: Distribution of CAD presence and extent in cardiac and non-cardiac syncope patients was as follows: 72% versus 48% any CAD; 31% versus 26% mild, 8% versus 14% moderate and 33% versus 7% severe CAD. Compared with non-cardiac syncope, patients with cardiac syncope had a significantly higher CAD presence and extent (p = 0.001). Coronary calcium score, segment involvement and stenosis score were also higher in cardiac syncope patients (p-values ≤0.004). Compared to the chest pain control group, patients with cardiac syncope showed a higher, however, non-significant, prevalence of any CAD (72% versus 63%) and severe CAD (33% versus 19%). CONCLUSION: Patients with cardiac syncope show a high presence and extent of CAD in contrast to non-cardiac syncope patients. These results suggest that CAD may play an important role in the occurrence of cardiac syncope.

Dentists' knowledge of occlusal splint therapy for bruxism and temporomandibular joint disorders.

AIMS: The aim of this study was to investigate dentist's approaches to the use of splint therapy for myofascial pain, bruxism, and temporomandibular joint (TMJ) disorders and to assessment of treatment modalities. MATERIALS AND METHODS: A 12-item questionnaire was developed to determine dentists' knowledge of TMJ disorders and approaches for occlusal splint treatments. The researchers spoke with each dentist included in the study at his/her clinic or by telephone to assess their immediate knowledge and approach to the TMJ disorders. Chi-squared test was performed to analyze the values. The confidence interval was set as 95%. RESULTS: A total of 370 dentists working in Turkey were participated in this study. The most common splint application reason for occlusal splint treatment was bruxism (77.8%) while TMJ pain was very rare (%1.4). The use of hard splint ratios for 0-5 years of professional experience was 57.0%, 42.4.0%, and 26.8% for the experience of 5-15 years and over 15 years groups, respectively (P < 0.001). While the dentists' with sufficient knowledge soft splint application rates were 11.6%, hard splint application rates were 43.4% for the dentists with sufficient knowledge. Occlusion adjustment rate of dentists who practice in all three groups was under 16.0%. CONCLUSIONS: The knowledge of the dentists about TMJ disorders and occlusal splint therapy were found to be insufficient. Their knowledge decreased with increasing experience.

Neoadjuvant endocrine treatment in early breast cancer: An overlooked alternative?

During the last decade neoadjuvant endocrine therapy (NET) has moved from being reserved for elderly and frail non-chemotherapy candidates to a primary systemic modality in selected patients with hormone sensitive breast cancer. Neoadjuvant hormonal treatment in patients with hormone receptor positive, HER-2 negative early breast cancer is proven to be an effective and safe option; it is associated with a higher rate of breast conserving surgery (BCS), may reduce the need for adjuvant chemotherapy and enables a delay of surgery for medical or practical reasons. Clinical responses range from 13% to 100% with at least 3 months of NET. Methods of assessing response should include MRI of the breast, particularly in lobular tumours. In studies comparing tamoxifen with aromatase inhibitors (AI), AI proved to be superior in terms of tumour response and rates of BCS. Change in Ki67 is accepted as a validated endpoint for comparing endocrine neoadjuvant agents. Levels of Ki67 during treatment are more closely related to long-term prognosis than pretreatment Ki67. Neoadjuvant endocrine therapy provides a unique opportunity for studies of endocrine responsiveness and the development of new experimental drugs combined with systemic hormonal treatment.

Ductal carcinoma in situ: a disease entity that merits more recognition.

Ductal carcinoma in situ (DCIS) is a non-invasive breast carcinoma that remains in the milk ducts. It is a poorly understood disease and its natural history is not well known. This is because once diagnosed, DCIS is usually treated. It is known however that ductal carcinoma is a precursor of invasive breast carcinoma, as 14-53% can become invasive over a period of 10 years, if left untreated. With increasing knowledge about the molecular biology of DCIS, more insight is given in its relation to invasive breast cancer. Diagnosis of ductal carcinoma in situ is increasing in the last few years. This is likely caused by the increased mammographic screening for breast cancer and the higher quality of mammographic images. DCIS represents about one fifth of all mammographically detected breast cancers. Risk factors for the development of ductal carcinoma in situ are: low parity, late age at first birth and menopause, and Body Mass Index. The Van Nuys Prognostic Index is a useful scoring system to grade DCIS. DCIS is graded by scoring four characteristics: patient's age, margin width, tumor size and pathological classification. It allows us to divide DCIS lesions into different groups according to risk of local recurrence: low risk, intermediate risk and high risk. Each group requires a different treatment, respectively: local excision of the tumor; local excision and radiotherapy; and mastectomy. The use of tamoxifen in the treatment of DCIS is still controversial, but research so far has encouraging results. Interesting developments have been made in the use of Her-2 pulsed dendritic cell vaccination before DCIS surgery.

The socio-economical impact of intravenous (IV) versus subcutaneous (SC) administration of trastuzumab: future prospectives.

Trastuzumab was the first targeted therapy for HER2 positive breast cancer. It has become the standard of care for HER2 positive metastatic breast cancer since 2000 and in the adjuvant setting since 2006. Adjuvant it is given for a year and in patients with metastatic disease until progression. The standard mode of administration is intravenous. Recently a subcutaneous form has become available. A phase III study showed that there is no difference between the intravenous and subcutaneous form in terms of safety and efficacy. The patient's preference however significantly favoured the subcutaneous form. It is estimated that the use of the SC form could contribute to a cost saving between 758 and 2576 euro per annual course. For Belgium alone this could mean an estimated saving of 1.4 to 4.6 million euros per year. The potential benefit of the SC administration for healthcare facilities could be further increased when applied in a LEAN working day-care chemotherapy unit. After reviewing the existing literature we suggest to further validate the potential financial impact of SC trastuzumab compared to the traditional IV form and to introduce a scientific proposal incorporating the benefits of this formulation in a LEAN working healthcare unit.

Effect of dentin desensitizing procedures on methyl methacrylate diffusion through dentin.

BACKGROUND: Acrylic and bisacryl resins are widely used both during the temporization phase as well as for provisional restorations and the effect of external agents on dentin sensitivity can be reduced by the obliteration of the tubules. OBJECTIVE: The purpose of this study was to evaluate diffusion of methyl methacrylate monomer through dentin by high performance liquid chromatography (HPLC) after three different desensitizing procedures during the fabrication of two different provisional crown materials. MATERIALS AND METHODS: Forty extracted restoration and caries free human premolar teeth were used in this study. Thermoplastic vacuum formed material was used as a matrix to fabricate provisional restorations for each tooth before crown preparation. Teeth were prepared for a metal supported ceramic crown with 1 mm shoulder margins and then crown parts were separated from cementoenamel junction with a carborundum disk perpendicular to the long axis of the teeth. To the cementoenamel junction of each tooth a polypropylene chamber was attached that contains 1.5 cm 3 of deionized distilled water. Prepared teeth were divided into four groups ( n = 10) including control, desensitizing agent (DA) application, neodymium-doped yttrium aluminum garnet (Nd: YAG) laser irradiation (LI), and LI after DA application groups. After application of DA (except control) each group were divided into two subgroups for fabrication of provisional restorations ( n = 5). Two autopolymerizing provisional materials (Imident (Imicryl) and Systemp C and B (Ivoclar, vivadent)) were used to fabricate provisional restorations using the strips. Water elutes were analyzed by HPLC at 10 min and 24 h. RESULTS: The monomer diffusion values varied statistically according to desensitizing procedures, provisional resin systems, and the time periods. Monomer diffusion through dentin surfaces desensitized with Nd: YAG LI after DA application was the lowest. CONCLUSIONS: Nd: YAG LI in association with DA application is an effective combination to eliminate monomer diffusion through dentin to pulpal chamber.

Current view on ductal carcinoma in situ and importance of the margin thresholds: A review.

Ductal carcinoma in situ (DCIS) is a heterogeneous group of diseases that differ in biology and clinical behaviour. Until 1980, DCIS represented less than 1% of all breast cancer cases. With the increased utilization of mammography, DCIS now accounts for 15% to 25% of newly diagnosed breast cancer cases. The Van Nuys Prognostic Index (VPNI) is a commonly used tool for ductal carcinoma in situ (DCIS) treatment approach. Patient age, tumour size, tumour margins and pathological grade are used in order to stratify patients into three groups pertaining to risk of local recurrence: low-, intermediate- and high risk. Patients in the low-risk subgroup will always be treated with excision alone, while in the highest subgroup mastectomy is the safest option. Just like invasive breast cancer (IBC) there might be a curative dilemma in the intermediate-risk group. Many trials confirm that tumour margins are the most important prognostic factor of local recurrence for DCIS patients treated with breast conserving surgery alone or with breast conserving surgery plus radiotherapy. In this article we focused specifically on the literature concerning margin thresholds.

Benchmarking and audit of breast units improves quality of care.

Quality Indicators (QIs) are measures of health care quality that make use of readily available hospital inpatient administrative data. Assessment quality of care can be performed on different levels: national, regional, on a hospital basis or on an individual basis. It can be a mandatory or voluntary system. In all cases development of an adequate database for data extraction, and feedback of the findings is of paramount importance. In the present paper we performed a Medline search on "QIs and breast cancer" and "benchmarking and breast cancer care", and we have added some data from personal experience. The current data clearly show that the use of QIs for breast cancer care, regular internal and external audit of performance of breast units, and benchmarking are effective to improve quality of care. Adherence to guidelines improves markedly (particularly regarding adjuvant treatment) and there are data emerging showing that this results in a better outcome. As quality assurance benefits patients, it will be a challenge for the medical and hospital community to develop affordable quality control systems, which are not leading to excessive workload.

Determining the influence of fibre post light transmission on polymerization depth and viscoelastic behaviour of dual-cured resin cement.

AIM: To evaluate the effect of quartz-fibre posts on the depth of polymerization of a dual-cure resin cement using Raman spectroscopy and to determine the physical properties of the polymerized cement using a dynamic mechanical analyzer (DMA). METHODOLOGY: Twenty-five fibre and 25 CrNi posts were used to evaluate depth of polymerization. Posts were cemented with dual-cure resin into root canals formed from silicone moulds, without using bonding or etching agents. After polymerization, resin layers on each sample were removed using a curette and cut into three equal parts (apical, middle and coronal). All resin specimens for every third were gathered and crushed. Resin powder samples were analysed using Dynamic Mechanical Analysis and Raman spectroscopy for each third. RESULTS: The numerical data revealed that the thermal transitions of the materials took place at higher temperatures from the apical to the coronal sections in both groups. C=C double bond intensity was lower in fibre post-resin cement samples when compared to their intensity in metal post-resin cement samples. CONCLUSION: Dual-cured resin cements had more rigid properties and better polymerization for fibre posts when compared with metal posts. Polymerization quantity was affected by position in the canal.

Ear, nose and throat involvement in patients with pemphigus vulgaris: correlation with severity, phenotype and disease activity.

BACKGROUND: Pemphigus vulgaris (PV) is the most common clinical form of pemphigus that is characterized by easily ruptured or loose bulla formation on skin and/or mucosa. The frequency of the ear, nose and throat involvement of PV is not clearly defined. OBJECTIVES: To evaluate the frequency of ear, nose and throat (ENT) involvement in patients suffering from PV who had been recently diagnosed or exacerbated under follow up and to determine the association with ENT symptoms, clinical involvement, severity and duration of pemphigus vulgaris. MATERIALS AND METHODS: The study group included a total of 38 PV patients comprising 24 new patients and 14 patients who showed exacerbations while on complete remission or under treatment. All patients were asked about ENT symptoms and endoscopic examination were performed to evaluate the presence of nasal, pharynx, larynx and ear involvement. RESULTS: Of the 38 patients, 33 (87%) had active PV lesions on endoscopic evaluation. Twenty-five patients (66%) had lesions on pharynx, twenty-one (55%) on larynx, twenty-nine (76%) on nasal mucosa and four (10%) on the ear mucosa. ENT involvement was not associated with the severity and the clinical involvement of the disease. Pharyngeal and nasal involvement was significantly associated with symptoms, while laryngeal and ear involvement was not found to be significantly associated with symptoms. Nasal and ear involvement was not associated with the duration of the disease while pharyngeal and laryngeal involvement favored newly diagnosed patients. CONCLUSIONS: Our results revealed that high number of patients with PV may present with active ENT lesions, furthermore patients with ear, nose and throat involvement may be asymptomatic and active lesions may be found in patients without any ENT symptoms. Therefore it should be considered that to understand the real extent of PV involvement, endoscopic ENT evaluation should be performed in patients with or without symptoms.

High myopia associated with colour vision deficiency:a family report / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate genetic characteristics and clinical findings in a family with high myopia and colour vision deficiency (CVD).METHOD: Eight affected subjects of 42 members in four generations of the same family underwent a complete ophthalmic examination. Classical and computer adapted Ishihara Plates and Farnsworth-Munsell 100 Hue (FM100H)tests were used for determining the red-green CVD and full-field electroretinography (ERG) was performed to evaluate retinal function.RESULTS: Eight affected subjects had subnormal visual acuity due to high myopia. The results of colour vision tests were consistent with red-green CVD in six of these affected subjects. Fundus examination showed degenerative myopic changes characterized with generalized chorioretinal atrophy.Abnormal cone and rod dark-adaptation and diminished cone response in ERG were found in two subjects. According to family pedigree, it has been suggested that red-green CVD has X-linked recessive inheritance.CONCLUSION: The concurrence of high myopia with CVD in the members of this family may show a possible evidence for an associate genetic basis on different disorders.

Intravascular large B-cell lymphoma or intravascular lymphomatosis: report of a case diagnosed by testicle biopsy.

Intravascular large B-cell lymphoma or intravascular lymphomatosis (IVL) is an extremely rare form of non-Hodgkin's lymphoma. The most common clinical sign is fever of unknown origin (FUO). Histologically, there is proliferation of malignant lymphoid cells within vascular lumina. Cytologically, the cells have features similar to those found in classical large cell lymphoma. Examination of pulmonary artery blood showed the presence of this abnormal population in our patient; to the best of our knowledge there are only four other. reports of detection of circulating tumor cells in IVL. The outcome is very poor. The diagnosis is most frequently made after biopsy of skin or brain but is often established post mortem. We present what is--to our knowledge--the first reported case of IVL diagnosed after biopsy of a testicle. In the event of FUO and suspicion of a malignancy, IVL--although very rare--should be one of the differential diagnoses.

Changes in knot-holding capacity of sliding knots in vivo and tissue reaction.

OBJECTIVES: To evaluate and compare the in vivo strength, knot efficiency, and knot security of 4 types of sliding knots, and to assess tissue reaction to study the effect of knot configuration, knot volume, and suture size. DESIGN: Randomized trial. SETTING: Experimental Medical Research Institute, Istanbul, Turkey. SUBJECTS: Wistar rats. INTERVENTION: To assess the tissue reaction, a midline laparotomy incision was made in 112 rats and sutured with various interrupted knots in silk and nylon sutures of 2/0 and 4/0 (United States Pharmacopeia) sizes. Suture loops were implanted in subcutaneous pouches in the rat abdomen. Sutures were all extracted at days 4, 7, 11, and 20 to determine their knot-holding capacity. MAIN OUTCOME MEASURES: Knot efficiency and percentage decrease in knot-holding capacity were examined. Knot, tissue reaction, and inflammatory sheath volumes were measured. RESULTS: The 4/0 knots lost more strength than the 2/0 knots. The alternating knots with different patterns were more efficient and secure than the simple alternating ones. The alternating parallel knot was found to be unreliable. The tissue response to all the knots, except 2/0 nylon, was similar. The inflammatory sheath volume varied depending on the knot volume, suture size, and knot configuration. CONCLUSION: The use of alternating sliding knots with different patterns is recommended to replace simple alternating sliding knots.