Timely integration of palliative care. the reality check. a retrospective analysis.

PURPOSE: A large volume of literature suggests that timely integration of palliative care (PC) enhances the well-being, quality of life and satisfaction of patients and their families. It may also positively impact clinical outcomes and healthcare costs throughout the disease trajectory. Therefore, reviewing clinical practice to reflect real-life situations regarding timely PC integration is essential. METHODS: This study, conducted at the Vienna General Hospital between March 2016 and August 2022, retrospectively examined PC consultation (PCC) requests. It aimed to assess the timeliness of PC integration by analysing the duration between diagnosis and the first PCC request, as well as the interval between the first PCC request and death. RESULTS: This study included 895 PCCs. The median time from diagnosis to the first PCC was 16.6 (interquartile range (IQR): 3.9-48.4) months, while the median time from the first PCC to death was 17.2 (IQR: 6.1-50.7) days. The median time from diagnosis to first PCC was 10.4 months in females (confidence interval (CI): 6.0-14.8) compared to 10.6 months in males (CI: 8.1-13.1; p = 0.675). There were no gender disparities in the time from first PCC to death, with a median of 23.3 days (CI: 15.6-31.0) for females and 22.3 days (CI: 16.2-28.4) for males (p = 0.93). Fifty percent of patients died between 5 and 47 days after the first PCC. CONCLUSION: These findings highlight the discrepancy between the clinical perception of PC as end-of-life care and the existing literature, thereby emphasising the importance of timely PC integration.

[Planning tools and indications for "virtual surgery" for the Bonebridge bone conduction system. German version]. / Planungstools und Indikationen zur "virtuellen Chirurgie" beim Knochenleitungssystem Bonebridge.

BACKGROUND: Implantation of the Bonebridge (MED-EL, Innsbruck, Austria), an active semi-implantable transcutaneous bone conduction hearing system, involves the risk of impression or a lesion in intracranial structures, such as the dura or sigmoid sinus. Therefore, determining the optimal implant position requires careful preoperative radiological planning. OBJECTIVE: The aim of this study was to provide an overview of the possibilities for preoperative radiological planning for the Bonebridge implantation and to evaluate their indications and feasibility. MATERIALS AND METHODS: A systematic literature search was conducted in the PubMed/MEDLINE database for all studies with preoperative planning or implant placement as the primary endpoint or that secondarily mention preoperative planning. RESULTS: Of 558 studies, 49 fulfilled the inclusion criteria. In 18 studies, preoperative planning and floating mass transducer (FMT) placement were the primary endpoints, whereas in 31 studies, preoperative planning was described secondarily. CONCLUSION: There are both freely available and commercial tools involving different time commitments for preoperative three-dimensional (3D) planning and intraoperative transfer. Preoperative 3D planning can increase the safety of Bonebridge implantation.

Planning tools and indications for "virtual surgery" for the Bonebridge bone conduction system.

BACKGROUND: Implantation of the Bonebridge (MED-EL, Innsbruck, Austria), an active semi-implantable transcutaneous bone conduction hearing system, involves the risk of impression or a lesion in intracranial structures, such as the dura or sigmoid sinus. Therefore, determining the optimal implant position requires careful preoperative radiological planning. OBJECTIVE: The aim of this study was to provide an overview of the possibilities for preoperative radiological planning for the Bonebridge implantation and to evaluate their indications and feasibility. MATERIALS AND METHODS: A systematic literature search was conducted in the PubMed/MEDLINE database for all studies with preoperative planning or implant placement as the primary endpoint or that secondarily mention preoperative planning. RESULTS: Of 558 studies, 49 fulfilled the inclusion criteria. In 18 studies, preoperative planning and floating mass transducer (FMT) placement were the primary endpoints, whereas in 31 studies, preoperative planning was described secondarily. CONCLUSION: There are both freely available and commercial tools involving different time commitments for preoperative three-dimensional (3D) planning and intraoperative transfer. Preoperative 3D planning can increase the safety of Bonebridge implantation.

Implantation of a new active bone conduction hearing device with optimized geometry.

Here, we describe the surgical technique for implanting a new, active, transcutaneous bone conduction hearing aid. The implant technology is based on a system that has been in use reliably since 2012. The geometry of the new implant has been adapted based on experience with previously introduced implants. The surgery was feasible, standardized, and safe. Due to the optimized geometric design that improved the bone fit, it is not necessary to use specialized, detailed preoperative planning, except in challenging anatomical conditions; e.g., in young children, malformations, poor pneumatization, or after a canal wall down mastoidectomy.

[Implantation of a new active bone conduction hearing device with optimized geometry. German version]. / Implantation eines neuen, aktiven, knochenverankerten elektronischen Hörimplantats mit verkleinerter Geometrie.

Here, we describe the surgical technique for implanting a new, active, transcutaneous bone conduction hearing aid. The implant technology is based on a system that has been in use reliably since 2012. The geometry of the new implant has been adapted based on experience with previously introduced implants. The surgery was feasible, standardized, and safe. Due to the optimized geometric design that improved the bone fit, it is not necessary to use specialized, detailed preoperative planning, except in challenging anatomical conditions; e.g., in young children, malformations, poor pneumatization, or after a canal wall down mastoidectomy.

Five-year results from the prospective European multicentre cohort study on radiofrequency segmental thermal ablation for incompetent great saphenous veins.

BACKGROUND: This was a prospective study of radiofrequency segmental thermal ablation (RFA) for the treatment of incompetent varicose great saphenous veins (GSVs). The present report describes long-term follow-up at 5 years. METHODS: The 5-year follow-up of this multicentre European study included assessment of the Venous Clinical Severity Score (VCSS), and GSV occlusion and reflux on duplex imaging. RESULTS: A total of 225 patients had 295 GSVs treated by RFA, achieving an initial vein occlusion rate of 100 per cent. With 80·0 per cent compliance, Kaplan-Meier analyses showed a GSV occlusion rate of 91·9 per cent and a reflux-free rate of 94·9 per cent at 5 years. Among the 15 GSVs noted with reflux during follow-up, only three showed full recanalization of the GSV at 1 week, 6 months and 3 years. Of the 12 legs with partial recanalization, reflux originated at the saphenofemoral junction in ten, with a mean length of the patent segment of 5·8 (range 3·2-10) cm; only six patients were symptomatic. Mean(s.d.) VCSS scores improved from 3·9(2·1) at baseline to 0·6(1·2), 0·9(1·3) and 1·3(1·7) at 1, 3 and 5 years. CONCLUSION: At 5 years RFA proved to be an efficient endovenous treatment for incompetent GSVs in terms of sustained clinical and anatomical success for the vast majority of treated patients.

High uterosacral vault suspension vs Sacrocolpopexy for treating apical defects: a randomized controlled trial with twelve months follow-up.

INTRODUCTION AND HYPOTHESIS: The high uterosacral vault suspension (HUVS) is a vaginal approach for treating apical prolapse that provides shorter operative and recovery times and is associated with lower morbidity rates. Success rates reported for this technique are comparable with the abdominal sacrocolpopexy (SCP); however, to date, there are no prospective randomized studies comparing HUVS to SCP. The aim of the study was to compare the anatomical objective cure rates for the apical compartment in patients undergoing either HUVS or SCP at 12 months' follow-up. METHODS: We performed a single-center parallel randomized controlled trial in patients with severe apical defect defined as Pelvic Organ Prolapse Quantification (POP-Q) point C ≥ stage 3. Based on the center's previous experience, a sample size of 124 patients was required to show a 20% cure rate difference between both techniques with 80% power and using a two-tailed 5% level of significance. One hundred and ten patients were available for analysis; 54 were allocated to abdominal SCP and 56 to HUVS. The primary outcome was to evaluate surgical objective success defined as POP-Q point C stage<2. The Pelvic Floor Distress Inventory (PFDI-20), the Perceived Quality of Life Scale (P-QOL), and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12) questionnaires were used for subjective assessment. RESULTS: The objective success rate for apical suspension at 12 months' follow-up was 100% for abdominal SCP and 82.5% for HUVS (log-rank p 0.033). Both techniques showed a significant improvement with regards to prolapse symptoms, quality of life (QOL), and sexual function. The significant improvement in postoperative questionnaires was comparable between both surgeries at 12 months' follow-up. CONCLUSIONS: Abdominal SCP has statistically significant better anatomical results when compared with HUVS for correcting apical defects at 12 months.

Radiation induced a supra-additive cytotoxic effect in head and neck carcinoma cell lines when combined with plant extracts from Brazilian Cerrado biome.

OBJECTIVES: Antineoplastic effects of molecules derived from plants have recently gained increasing attention as an additive to traditional therapies. The aim of this study was to evaluate the cytotoxic activity of plant extracts from the Brazilian Cerrado biome associated with radiotherapy in head and neck carcinoma cells (HNSCC). MATERIALS AND METHODS: Fifteen extracts derived from five Cerrado plants were tested in HNSCC cell lines (SCC-25, SCC-9, FaDu) and keratinocyte cells (HaCat). Cell cytotoxicity of extracts and association extract/radiation (2Gy/min) was assessed by MTT assay. Cisplatin (50 µg/mL) was used as a positive control. Extracts with the major cytotoxic activity were selected and their IC50 concentrations were defined. Apoptosis was assessed using flow cytometric analysis. RESULTS: Ten isolated extracts resulted in moderate cytotoxicity (>20 and ≤ 50 % of viable cells), while three extracts induced severe cytotoxic effects (≤ 20 % of viable cells). Plant extracts treatment improved radiotherapy cytotoxicity in all cell lines. Although plant extracts are not as potent as cisplatin plus radiation, in FaDu cells, seven extracts associated with irradiation showed cytotoxic activity similar or better than the association of cisplatin and radiation. Hexanic extract of Erythroxylum daphinites could induce apoptosis in oral cancer cells; however, necrosis was the prevalent kind of death in FaDu cells treated with hexanic extract of Erythroxylum suberosum. CONCLUSIONS: Pre-treatment of HNSCC cells with the extract derived from Cerrado plants followed by irradiation induced a supra-additive cytotoxic effect. CLINICAL RELEVANCE: This study highlights the potential biological relevance of the Cerrado biome when associated with traditional therapy for cancer.

A favorable donor site in microsurgery: Nerve and vein graft harvest from the dorsum of the foot.

BACKGROUND AND OBJECTIVES: In complex hand traumas nerves and vessels are often destructed without the possibility for primary repair. For bridging defects of nerves, veins and arteries grafts are necessary. Commonly nerve and vein grafts from adjacent donor sites as the wrist, forearm or cubital region are harvested. METHODS: This study is a retrospective cohort study. Between 2017 and 2019, 10 patients with complex hand injuries were treated. There were 8 males and 2 females, with an average age of 39 years (range 8-63 years). In all cases grafts were used of the dorsum of the foot for reconstructing of the severed digital nerves and arteries. All donor sites could be closed primarily. RESULTS: In 100% of cases nerves and veins of the dorsum of the foot showed a good size match as well as adequate length for a sufficient repair. The overall Hand Injury Severity Score (HISS) was determined with a median of 86 (range 57 to 286). In the area of the donor site no relevant complications were seen. CONCLUSIONS: In complex hand injuries the dorsum of the foot is a favorable donor site for nerve and vein graft harvest.

Necrosis-inducing proteins of Rhynchosporium commune, effectors in quantitative disease resistance.

The barley pathogen Rhynchosporium commune secretes necrosis-inducing proteins NIP1, NIP2, and NIP3. Expression analysis revealed that NIP1 transcripts appear to be present in fungal spores already, whereas NIP2 and NIP3 are synthesized after inoculation of host plants. To assess the contribution of the three effector proteins to disease development, deletion mutants were generated. The development of these fungal mutants on four barley cultivars was quantified in comparison with that of the parent wild-type strain and with two fungal strains failing to secrete an "active" NIP1 avirulence protein, using quantitative polymerase chain reaction as well as microscopic imaging after fungal green fluorescent protein tagging. The impact of the three deletions varied quantitatively depending on the host genotype, suggesting that the activities of the fungal effectors add up to produce stronger growth patterns and symptom development. Alternatively, recognition events of differing intensities may be converted into defense gene expression in a quantitative manner.

Ectopic divisions in vascular and ground tissues of Arabidopsis thaliana result in distinct leaf venation defects.

Leaf venation patterns vary considerably between species and between leaves within a species. A mechanism based on canalization of auxin transport has been suggested as the means by which plastic yet organized venation patterns are generated. This study assessed the plasticity of Arabidopsis thaliana leaf venation in response to ectopic ground or procambial cell divisions and auxin transport inhibition (ATI). Ectopic ground cell divisions resulted in vascular fragments between major veins, whereas ectopic procambial cell divisions resulted in additional, abnormal vessels along major veins, with more severely perturbed lines forming incomplete secondary and higher-order venation. These responses imply limited vascular plasticity in response to unscheduled cell divisions. Surprisingly, a combination of ectopic ground cell divisions and ATI resulted in massive vascular overgrowth. It is hypothesized that the vascular overproduction in auxin transport-inhibited wild-type leaves is limited by simultaneous differentiation of ground cells into mesophyll cells. Ectopic ground cell divisions may negate this effect by providing undifferentiated ground cells that respond to accumulated auxin by differentiation into vascular cells.

WITHDRAWN: The use of integrated indocyanine green fluorescence microscope camera for intraoperative lymphography of supermicrosurgery.

Ahead of Print article withdrawn by publisher.

Fulvestrant ('Faslodex') in pre-treated patients with advanced breast cancer: a single-centre experience.

Fulvestrant ('Faslodex') is a new oestrogen receptor (ER) antagonist with no agonist effects. This report describes the experience of a single centre including 126 postmenopausal women with advanced breast cancer (ABC) in a fulvestrant Compassionate Use Programme. All patients had previously received endocrine treatment for early or ABC. Patients received fulvestrant as first- (n=7), second- (n=51), third- (n=50) or fourth-line endocrine therapy (n=18) for ABC (median duration of treatment: 4 months [range 3-27(+) months], follow-up: 13 months [range 1-38(+) months]). Twelve patients had partial responses (PR) and 43 patients experienced stable disease (SD) > or = 6 months (objective response rate: 9.5%; clinical benefit [CB] rate: 43.6%). Ten of 12 patients with a PR had HER2-negative tumours, and 9/12 had ER-positive and progesterone receptor (PgR)-positive disease (two patients had unknown HER2 status and one had unknown ER and PgR status). Nine of the 18 patients with HER2-positive tumours experienced CB with fulvestrant. Although CB rates were similar when fulvestrant was given as first- to fourth-line endocrine treatment, the proportion of those experiencing CB who had a PR appeared to decrease when fulvestrant was used later in the sequence. Fulvestrant was well tolerated; six patients experienced adverse events (all grade I/II). These data demonstrate that fulvestrant is an effective and well-tolerated therapy for patients with ABC progressing on prior therapies.

TP53 mutation and p53 overexpression for prediction of response to neoadjuvant treatment in breast cancer patients.

The value of p53 to predict the cytotoxic effect of two commonly used chemotherapy regimens was assessed in patients with advanced breast cancer. Response to a DNA-damaging combination therapy [fluorouracil, epirubicin, cyclophosphamide (FEC] considered to induce p53-dependent apoptosis was compared with a microtubule stabilizing therapy (paclitaxel) expected to be independent of p53 function. The p53 status of the patients' breast tumors was assessed using both immunohistochemistry (IHC) and direct sequencing of the entire p53 gene. p53 findings were correlated with treatment response, and linkage between p53 function and cellular response was assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. In a series of 67 breast tumors, 19% had TP53 gene mutations, 40% had a positive p53 IHC, and 12% had both. In the FEC group, treatment failure was related to both the presence of TP53 gene mutations (P = 0.0029) and a positive IHC (P < 0.0001). Apoptosis was almost exclusively found in tumors having normal p53 in both parameters (P < 0.0001). In the paclitaxel group, treatment response was neither related to apoptosis nor to normal p53. Combination of sequencing and IHC results revealed a significant association between abnormal p53 and response to paclitaxel (P = 0.011). We found TP53 mutations, as well as p53 protein overexpression, to be associated with response to chemotherapy. Whereas clinical response to FEC was found to be dependent on normal p53, the cytotoxicity of paclitaxel was related to defective p53. The efficiency of paclitaxel during mitosis might be supported by lack of G1 arrest due to p53 deficiency. Therefore, patients with p53-deficient tumors may benefit from paclitaxel.

Urodynamic study in women with pure stress urinary incontinence.

OBJECTIVE: To describe the results of urodynamic study in women with pure stress urinary incontinence symptoms, including the characteristics of the overactive detrusor. No other clinical assessments were taken into account. MATERIAL AND METHODS: A retrospective study in women with urinary incontinence consecutively evaluated by urodynamic study. From a total of 710 women, only 108 (15%) with pure stress urinary incontinence symptoms were selected. Women with prior urinary incontinence surgery, pelvic organ prolapse (stage ≥iii), pelvic radiotherapy, using medication active on the lower urinary tract and neurological diseases were excluded. Infusion rate was 70 ml/min. Detrusor overactivity was induced only by cough. A standardized cough stress test with progressive cough intensity was carried out. RESULTS: Reference urodynamic values for stress incontinent women are described. Urodynamic stress incontinence was observed in 79 women (73.1%), detrusor overactivity in 4 (3.7%) and mixed urodynamic diagnosis in 15 (13.8%). Test was inconclusive in 10 patients (9.2%). Two women had detrusor overactivity incontinence (1.9%). One patient had detrusor overactivity induced by cough without urodynamic stress incontinence (0.9%). There was an association between detrusor overactivity and nocturia ≥2 (P=.002; odds ratio: 3.74; 95% confidence interval: 1.22-11.39). One woman had a bladder outlet obstruction (0.9%). CONCLUSIONS: In women with pure stress urinary incontinence, without knowing the outcome of other clinical assessments, urodynamic study can provide useful information to define the proper therapy.

Sequential steroid hormone receptor measurements in primary breast cancer with and without intervening primary chemotherapy.

The objective of this analysis was to determine the accuracy of steroid receptor measurement in large core needle biopsies compared with surgically removed specimens and the influence of preoperative chemotherapy on hormone receptor status. We consecutively performed 722 large core needle biopsies in palpable lesions of the breast. The diagnosis of breast cancer was confirmed upon biopsy in 450 patients; 236 women underwent immediate surgery, and 214 patients received preoperative chemotherapy. We assessed estrogen (ER) and progesterone receptor (PR) in biopsy tissue and surgically removed specimens and calculated accuracy, sensitivity, specificity, the weighted kappa value and Spearman's rank correlation. The modulation of steroid receptor status in preoperatively treated patients was tested by Cochran-Mantel-Haenszel statistics. The accuracy of ER evaluation in the biopsy material of patients without intervening chemotherapy was 91%, sensitivity and specificity were 94% and 80% respectively. Accuracy, sensitivity and specificity were 86% in patients treated preoperatively. In terms of PR assessment, we obtained slightly inferior results: accuracy, sensitivity and specificity were 80%, 73% and 85% respectively in patients without preoperative treatment, and 79%, 48% and 92% respectively in patients undergoing preoperative therapy. Following preoperative chemotherapy, patients showed a significant increase in ER-negative (P=0.02) and PR-negative (P=0.0005) measurements. We have concluded from our results that ER and PR receptor measurement in core needle biopsy is a reliable basis in clinical practice for selecting patients for neoadjuvant endocrine treatment. Preoperative cytotoxic chemotherapy induced a significant extent of variation in the steroid receptor expression of breast cancer cells.

Crosslinking of Dam methyltransferase with S-adenosyl-methionine.

Highly purified DNA-adenine methyltransferase was irradiated in the presence of different concentrations of radiolabelled S-adenosyl-methionine (AdoMet) with a conventional Mineralight UV-lamp from several minutes up to 1 h while incubating in ice. Incorporation of radioactivity was monitored by electrophoresis of the crosslink between S-adenosyl-methionine and Dam methylase on SDS-polyacrylamide gels followed by fluorography. Crosslinking reached a maximum in presence of 10 microM S-adenosyl-methionine; it was inhibited in the presence of substances which competitively inhibit methylation of DNA by Dam methylase, like sinefungin or S-adenosyl-homocysteine, but not in the presence of non-inhibitors like ATP or S-isobutyl-adenosine. The crosslink obtained was resistant against a wide range of even drastic conditions commonly used in protein and peptide chemistry. Proteins, which do not bind S-adenosyl-methionine, as well as heat inactivated Dam methylase were not photolabelled. After limited proteolysis the radioactive label appeared only in certain of the peptides obtained. From Western blots carried out with polyclonal antibodies produced against a synthetic peptide corresponding in its sequence to amino acids 92-106 of the Dam methylase, the crosslinking of AdoMet could be tentatively mapped at a position after amino acid 106.

Clinical outcome at six months of coronary stenting followed by ticlopidine monotherapy.

Antiplatelet therapy has been shown to be superior to oral anticoagulation after coronary stent implantation. Different regimens for postinterventional antiplatelet therapy have been proposed. A combination of ticlopidine and aspirin has gained the most widespread use. The relative merit of the different compounds in this combination remains unclear. There are several, partly conflicting, reports on coronary stent implantation followed by aspirin alone, but data on ticlopidine monotherapy are scarce. We conducted a prospective trial of elective coronary stenting followed by ticlopidine monotherapy in 263 consecutive, unselected patients. One-, 2-, and 3-vessel disease was present in 42.9%, 42.6%, and 14.5% of patients, respectively. We deployed a total of 322 stents. All patients received 250 mg of ticlopidine twice daily for up to 6 months. The clinical end points encountered during the hospital stay and at 5.9+/-2.9 months, respectively, were: death (2 [0.8%] and 2 [0.8%]); myocardial infarction (5 [1.9%] and 4 [1.5%]); target vessel occlusion (2 [0.8%] and 4 [1.5%]); bypass surgery (0 and 2 [0.8%]); and repeat angioplasty (2 [0.8%] and 52 [19.8%]). There was 1 vascular surgery (0.4%) and 4 (1.5%) non-procedure-related ischemic cerebrovascular events at follow-up. We conclude that coronary stent deployment followed by ticlopidine monotherapy is safe and effective in an unselected population. The overall clinical outcome at 6 months is good and comparable to that of patients treated with combined antiplatelet therapy. Ticlopidine monotherapy may be a safe alternative for patients with contraindications to aspirin.

Phosphate-solubilizing bacteria associated with proteoid roots of seedlings of waratah [Telopea speciosissima (Sm.) R.Br.].

Bacteria isolated from proteoid roots and non-proteoid lateral roots of Telopea speciosissima (Sm.) R.Br. seedlings were able to acidify the medium and solubilize calcium phosphates when grown in culture in the presence of ammonium salts and an appropriate carbon source. In general this activity was not detected when NO3 - was substituted for NH4 + , and it is proposed that protons were secreted in exchange for ammonium ions. Cation exchange between these protons and calcium in the medium is a possible cause of the calcium phosphate solubilizing activity. The relevance of these data to phosphate-solubilizing activity in natural environments is discussed.