Efficacy of haematopoietic stem cell boost as a rescue for poor graft function after haematopoietic stem cell transplantation: A multicentre retrospective study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC).

Haematopoietic stem cell reinjection may be a curative option for poor graft function after haematopoietic stem cell transplantation; however, literature supporting its use remains limited. We conducted a multicentre retrospective study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy, including 55 patients. We demonstrated response rates of nearly 40% and two-year survival of more than 60% in the context of an otherwise deadly complication and we observed that the timing of injection and the degree of cytopenia are strongly associated with outcomes. This study shows the feasibility of the procedure informing on its epidemiology, outcomes and prognostic factors, setting the stage for future guidelines.

[Urine retention-From the symptom to the structure]. / Harnverhalt ­ vom Symptom zur Struktur.

Urinary retention describes the inability to urinate. Based on the symptoms and the amount of the initial residual urine formation, a differentiation can be made between acute and chronic forms. The cause can be a subvesical obstruction or a bladder atony. In addition to emergency treatment in the form of initial relief of the strain on the bladder by insertion of a catheter, the indication for a definitive treatment with a clarification of the question whether an acute or chronic event is present is also important. Although the selection of the catheter is subject to few criteria, the further structured approach is complex. Both decision trees are presented in this article.

A Randomized Placebo-Controlled Efficacy Study of a Prime Boost Therapeutic Vaccination Strategy in HIV-1-Infected Individuals: VRI02 ANRS 149 LIGHT Phase II Trial.

In this placebo-controlled phase II randomized clinical trial, 103 human immunodeficiency virus type 1 (HIV-1)-infected patients under cART (combined antiretroviral treatment) were randomized 2:1 to receive either 3 doses of DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag, and gp160) at week 0 (W0), W4, and W12, followed by 2 doses of LIPO-5 vaccine containing long peptides from Gag, Pol, and Nef at W20 and W24, or placebo. Analytical treatment interruption (ATI) was performed between W36 to W48. At W28, vaccinees experienced an increase in functional CD4+ T-cell responses (P < 0.001 for each cytokine compared to W0) measured, predominantly against Gag and Pol/Env, and an increase in HIV-specific CD8+ T cells producing interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α) (P = 0.001 and 0.013, respectively), predominantly against Pol/Env and Nef. However, analysis of T-cell subsets by mass cytometry in a subpopulation showed an increase in the W28/W0 ratio for memory CD8+ T cells coexpressing exhaustion and senescence markers such as PD-1/TIGIT (P = 0.004) and CD27/CD57 (P = 0.044) in vaccinees compared to the placebo group. During ATI, all patients experienced viral rebound, with the maximum observed HIV RNA level at W42 (median, 4.63 log10 copies [cp]/ml; interquartile range [IQR], 4.00 to 5.09), without any difference between arms. No patient resumed cART for CD4 cell count drop. Globally, the vaccine strategy was safe. However, a secondary HIV transmission during ATI was observed. These data show that the prime-boost combination of DNA and LIPO-5 vaccines elicited broad and polyfunctional T cells. The contrast between the quality of immune responses and the lack of potent viral control underscores the need for combined immunomodulatory strategies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01492985.)IMPORTANCE In this placebo-controlled phase II randomized clinical trial, we evaluated the safety and immunogenicity of a therapeutic prime-boost vaccine strategy using a recombinant DNA vaccine (GTU-MultiHIV B clade) followed by a boost vaccination with a lipopeptide vaccine (HIV-LIPO-5) in HIV-infected patients on combined antiretroviral therapy. We show here that this prime-boost strategy is well tolerated, consistently with previous studies in HIV-1-infected individuals and healthy volunteers who received each vaccine component individually. Compared to the placebo group, vaccinees elicited strong and polyfunctional HIV-specific CD4+ and CD8+ T-cell responses. However, these immune responses presented some qualitative defects and were not able to control viremia following antiretroviral treatment interruption, as no difference in HIV viral rebound was observed in the vaccine and placebo groups. Several lessons were learned from these results, pointing out the urgent need to combine vaccine strategies with other immune-based interventions.

Anticholinergic burden and comorbidities in patients attending treatment with trospium chloride for overactive bladder in a real-life setting: results of a prospective non-interventional study.

BACKGROUND: Elderly people are representative for the patients most likely to be treated with anticholinergics for overactive bladder (OAB). They often receive further drugs with anticholinergic properties for concomitant conditions. This increases the risk for side effects, including central nervous system disorders. Data on comorbidities and baseline anticholinergic burden of OAB patients seen in urological practice is scarce. Therefore, we included an epidemiological survey on these issues in our study which assessed the effectiveness and tolerability of trospium chloride (TC) in established dosages under routine conditions. METHODS: Outpatients (≥ 65 years of age), for whom treatment with TC was indicated, were eligible to participate in this non-interventional, prospective study performed in 162 urological practices in Germany. Epidemiological questions were evaluated by the Anticholinergic Burden (ACB) scale and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) at baseline. Efficacy was assessed by changes in symptom-related variables of OAB after treatment. Dosage regimen, duration of treatment, adverse events, withdrawals, and ease of subdivision of the prescribed SNAP-TAB tablet were documented. Patients and physicians rated efficacy and tolerability of treatment. Statistics were descriptive. RESULTS: Four hundred fourty-five out of 986 (47.54%) patients in the epidemiological population had a baseline ACB scale score > 0, 100 (24.72%) of whom a score ≥ 3. The median CIRS-G comorbidity index score for all patients was 5. 78.55% (608/774) of patients in the efficacy population received a daily dose of 45 mg TC. 60.03% (365/608) of them took this dose by dividing the SNAP-TAB tablet in three equal parts. Before-after-comparisons of the core symptoms of OAB showed clear improvements. An influence of the dosage scheme (1 × 45 mg TC/d vs 3 × 15 mg TC/d) on clinical outcome could not be observed. Most urologists and patients rated TC treatment as effective and well tolerated. 44 (4.37%) out of 1007 patients in the safety collective ended their treatment prematurely, while 75 patients (7.45%) experienced adverse events. CONCLUSIONS: Anticholinergic burden and comorbidities in elderly OAB patients are frequent. The acceptance of the SNAP-TAB tablet, which facilitates flexible dosing with TC, was high, which is supportive in ensuring adherence in therapy. TRIAL REGISTRATION: This non-interventional study was registered on October 29, 2014 with the number DRKS00007109 at the German Register of Clinical Studies (DRKS).

[Potential cognitive alterations after treatment of benign prostate syndrome. Investigations on transurethral electroresection and 180 W GreenLight XPS laser therapy]. / Potenzielle kognitive Veränderungen nach Behandlung des benignen Prostatasyndroms. Untersuchungen zu transurethraler Elektroresektion oder 180-Watt-XPS-Greenlight-Laserung.

OBJECTIVE: The study was carried out to detect possible changes in cognition after transurethral resection of the prostate (TURP) and 180 W GreenLight-XPS laser treatment of the prostate. METHODS: Cognitive capacity was assessed by the mini-mental state examination (MMSE) and the clock test preoperatively and on postoperative day 2 in addition to documentation of clinical parameters, such as patient age, prostate size, duration of surgery, comorbidities, co-medications and alterations in hemoglobin (Hb) and sodium concentrations. RESULTS: Patients treated with TURP (n = 88) and 180 W GreenLight-XPS laser treatment of the prostate (n = 114) were comparable regarding age, prostate size and duration of surgery. Baseline characteristics of the patients treated by laser showed an increased potential for postoperative cognitive changes with an average of 3.8 comorbidities (TURP 3.11, p = 0.005) and were using an average of 6.79 multiple medications (TURP 5.24, p < 0.001); however, neither the MMSE nor the clock test demonstrated a decrease in the average postoperative score (difference between postoperative and preoperative MMSE + 0.6 ± 1.6 for 180 W GreenLight-XPS laser treatment and + 0.6 ± 1.6 for TURP, p = 0.944; difference postoperative and preoperative clock test + 0.43 ± 1.44 for 180 W GreenLight-XPS laser treatment and 0.13 ± 1.17 for TURP, p = 0.097). Neither postoperative hemoglobin nor sodium concentrations, as safety relevant parameters, demonstrated clinically relevant changes. The differences between the surgical procedures were not statistically significant. DISCUSSION: Neither 180 W GreenLight-XPS laser treatment of the prostate nor TURP demonstrated changes in cognition by comparing the preoperative MMSE and the clock test scores. In this study, the baseline characteristics of laser-treated patients showed a higher number of comorbidities and a higher use of medications, particular those with anticholinergic potency; therefore, 180 W GreenLight-XPS laser treatment of the prostate appears particularly safe for elderly patients.

[Urogeriatric thinking using the example of antiandrogen therapy for prostate cancer]. / Urogeriatrisches Denken am Beispiel der antiandrogenen Therapie des Prostatakarzinoms.

The geriatric patient is defined by an age of over 75 years and multimorbidity or by an age of over 80 years. These patients exhibit a particular vulnerability, which, in the incidence of side effects or complications, leads to a loss of autonomy. Treatment sequalae, once they have arisen, can no longer be compensated. It is important to recognize and document treatment requirements among geriatric patients with the help of screening instruments such as the Identification of Seniors at Risk (ISAR) and Geriatric 8 (G8) scores. If a treatment requirement is identified, oncologic treatment should not be commenced uncritically but rather a focus placed on identification of functional deficits relevant to treatment, ideally using a geriatric assessment but at least based on a detailed medical history. These deficits can then be presented in a structured, examiner-independent, and forensically validated manner using special assessments. A planned treatment requires not only consideration of survival gains, but also knowledge of specific side effects and, in geriatric patients in particular, their impact on everyday life. These considerations should be compared with the patient's individual risk profile in order to prevent side effects from negating the effect of the treatment, for example by worsening the patient's self-help status. With regard to androgen deprivation in prostate cancer-which often is used uncritically-it is important to consider possible side effects such as osteoporosis, sarcopenia, anemia, and cognitive impairment in terms of a possible fall risk; an increase in cardiovascular mortality and the triggering of a metabolic syndrome on the basis of preexisting cardiac diseases or risk constellations; and to carry out a careful risk-benefit analysis.

Undiagnosed phenylketonuria in parents of phenylketonuric patients, is it worthwhile to be checked?

In our phenylketonuria (PKU) cohort of 120 patients, we uncovered a couple of cases of undiagnosed mild phenylketonuria (mPKU)/hyperphenylalaninemia (mHPA) in maternal parents of the PKU cohort. This finding prompted us to evaluate the risk of either mild phenylketonuria or mild hyperphenylalaninemia in the parent population whose children were diagnosed with hyperphenylalaninemia (HPA). Taking into account the phenylalanine hydroxylase (PAH) mutation carrier frequency and the PAH mild mutation rate, we estimated that the prevalence of the parental mPKU/mHPA varied widely, from 1/74 in Turkey to 1/708 in Lithuania. The benefits of the parental detection procedure described here are the prevention of further maternal PKU syndrome, the follow-up of the newly detected patients and the accuracy of the genetic counseling provided to these families. This very simple procedure should be incorporated into neonatal PKU management of the hospitals in countries where a routine systematic neonatal screening is operational.

Which clinical risk factors determine a pathological urodynamic evaluation in patients with multiple sclerosis? an analysis of 100 prospective cases.

BACKGROUND: Urinary tract symptoms are an underestimated problem in multiple sclerosis (MS). OBJECTIVE: Hundred urodynamics of MS patients have been evaluated prospectively. DESIGN, SETTING AND PARTICIPANTS: In an inpatient rehabilitation, all persons with MS who also suffered from urinary tract symptoms received a voiding diary, post-void sonography and an urodynamic examination according to International Continence-Society-Standard. RESULTS AND LIMITATIONS: Between 10/2009 and 3/2011, 100 patients (79 women; 21 men; mean EDSS, 4.52 ± 2.26) were examined who had primary progressive MS (9×), relapsing-remitting MS (41×), secondary progressive MS (43×) and CIS (1×). The mean duration of MS was 10.26 ± 10.09 years and mean duration of LUTS, 6.9 ± 7.75 years. Urodynamic testing showed normal findings in 22 patients, detrusor overactivity in 7, increased bladder sensation without detrusor overactivity in 21, detrusor-sphincter dyssynergia in 26, detrusor hypocontractility in 12, detrusor acontractility in 4 and unclear diagnosis in 8 patients. Statistically significant risk factors for pathological urodynamic findings were as follows: wheelchair dependency, use of more than one incontinence pad per day and a MS type other than relapsing-remitting. CONCLUSIONS: The urodynamic investigation at hand showed urinary tract dysfunction in 78 of 100 MS patients with lower urinary tract symptoms (LUTS). The long latency between the occurrence of MS and/or the beginning of LUTS and the first neuro-urological evaluation indicates a deficit in treatment. Beyond national guidelines, all MS patients should at regular intervals be questioned about LUTS and receive urodynamic assessment especially according to the presented risk profile.

[Urine retention-From the symptom to the structure]. / Harnverhalt ­ vom Symptom zur Struktur.

Urinary retention describes the inability to urinate. Based on the symptoms and the amount of the initial residual urine formation, a differentiation can be made between acute and chronic forms. The cause can be a subvesical obstruction or a bladder atony. In addition to emergency treatment in the form of initial relief of the strain on the bladder by insertion of a catheter, the indication for a definitive treatment with a clarification of the question whether an acute or chronic event is present is also important. Although the selection of the catheter is subject to few criteria, the further structured approach is complex. Both decision trees are presented in this article.

[Complications of the 180 Watt XPS™ GreenLight laser-results of 1283 procedures]. / Komplikationen der 180-W-XPS™-GreenLight-Laserung ­ Ergebnisse bei 1283 Prozeduren.

BACKGROUND: The aim of this study was to classify and analyze postoperative complications under a new inspection method. This study assessed all patients who presented to the urologic ward within the first 3 months after their surgery. METHODS: A total of 170 patients suffered from complications due to the surgery; 29 patients experienced complications that were not directly correlated with the surgery. Age, American Society of Anesthesiologists (ASA) score, the emitted laser energy of the 180 Watt XPS™ GreenLight laser measured in joules, and the complications which led to the renewed hospitalization such as hematuria, urinary retention, and infection were analyzed and compared in the two groups of patients. RESULTS: Most complications that occurred were urinary retention and hematuria (50.6% and 49.4% of all patients, respectively). Of the patients with hematuria, 86.75% were under anticoagulant therapy medication. CONCLUSION: Compared with the reference approval study (Goliath trial) that included 135 multicentric patients (14.07% of patients presented with a complication classified as Clavien-Dindo II), the rate of complications was similar. This outcome is surprising because the patients treated with the GreenLight laser in the present study were classified as geriatric patients not only according to their age but also in their ASA score which is an indication of multiple other pathologies and administered medications. To achieve long-term postoperative success for these patients, the interface between the ambulatory and the hospital care should be optimized.

[Polypharmacy and medication review in the context of prehabilitation]. / Polypharmazie und Medikamentencheck im Kontext der Prähabilitation.

Against the background of typical geriatric multimorbidity and with the particular vulnerability of geriatric patients, polypharmacy deserves special attention. In accordance with the guidelines, medication should not only be reviewed regularly, but also on an ad hoc basis and with each hospital stay-and also in the context of prehabilitation. Thus, not only substances that interfere with the currently planned intervention, anesthesia, or risk of bleeding should be considered, but any medication that increases common risks for geriatric patients. These include drugs that cause or increase a tendency to fall, induce delirium, or alter the comedication through potential drug-drug interactions. Measures to minimize the risk include the following: exact documentation of medications, structured and complete transfer of information, patient and family training about any side effects that may occur, a recall system for possible laboratory checks, and compliance with the instructions for taking the medication.

Immune response to pertussis vaccine in COPD patients.

Exacerbation triggered by respiratory infection is an important cause of morbidity and mortality in chronic obstructive pulmonary disease (COPD) patients. Strategies aiming to preventing infection may have significant public health impact. Our previous study demonstrated decreased immunological response to seasonal flu vaccination in COPD patients, questioning the efficiency of other vaccines in this group of patients. We performed a prospective, monocenter, longitudinal study that evaluated the humoral and cellular responses upon pertussis vaccination. We included 13 patients with stable COPD and 8 healthy volunteers. No difference in circulating B and T cell subsets at baseline was noted. Both groups presented similar levels of TFH, plasmablasts and pertussis specific antibodies induction after vaccination. Moreover, monitoring T cell immunity after ex-vivo peptide stimulation revealed equivalent induction of functional and specific CD4+ T cells (IFNγ, TNFα and IL-2-expressing T cells) in both groups. Our results highlight the immunological efficiency of pertussis vaccination in this particularly vulnerable population and challenge the concept that COPD patients are less responsive to all immunization strategies. Healthcare providers should stress the necessity of decennial Tdap booster vaccination in COPD patients.

Dorsal rhizotomy in cerebral palsy: How root sectioning is influenced by intraoperative neuromonitoring?

INTRODUCTION AND OBJECTIVE: Dorsal rhizotomy is a controversial procedure for treating spasticity in children with cerebral palsy, particularly regarding the influence of intraoperative neuromonitoring (ION). The objective of this study was to evaluate the influence of ION in adjusting root sectioning compared the preoperative program established by the multidisciplinary team. MATERIAL AND METHODS: Twenty-four consecutive children with spastic diplegia or quadriplegia, operated on between 2017 and 2020 in the University Hospital of Nancy, France, were studied. All underwent the same procedure: Keyhole Intralaminar Dorsal rhizotomy (KIDr) with enlarged multilevel interlaminar openings to access all roots from L2 to S2. The Ventral Root (VR) was stimulated to map radicular myotomes, and the Dorsal Root (DR) to test excitability of the segmental circuitry. Muscle responses were observed independently by the physiotherapist and by EMG-recordings. The study compared final root sectioning per radicular level and per side after ION versus the preoperative program determined by the multidisciplinary team. RESULTS: ION resulted in significant differences in final percentage root sectioning (P<0.05), with a decrease for L2 and L3 and an increase for L5. ION modified the symmetry of sectioning, with 32% instead of 5% in preoperative program. Only 5 children showed change in GMFC score 6 months after surgery. CONCLUSION: The use of ION during dorsal rhizotomy led to important modifications of root sectioning during surgery, which justifies individual control of each root, level by level and side by side, to optimize the therapeutic effect.

[Quality of life for wearers of a suprapubic or transurethral bladder catheter as lifelong permanent care]. / Lebensqualität bei Trägern eines suprapubischen oder transurethralen Harnblasenkatheters als lebenslange Dauerversorgung.

BACKGROUND: The insertion of a Foley catheter (FC) or a suprapubic catheter (SPC) in lifelong intent is an intervention with significant complications, comorbidities and impact on the further life that has not yet been analyzed. METHODOLOGY: The analysis was based on a validated assessment of catheter-related QoL with 25 items in 5 domains and applied to patients with a Foley or suprapubic catheter in lifelong indication and with the catheter in place for at least 3 months. Assessment data were enriched with information on the type and diameter of the catheter as well as demographic data. RESULTS: Questionnaires from 357 patients (260 male, 97 female, 193 with suprapubic catheter, 162 with Foley catheter, 2 no information) were included in the study. Patients with a Foley catheter were significantly older than patients with a suprapubic catheter (78.9 ± 11.1 years vs. 74.4. ± 12.6 years, p < 0.001). The average QoL score was 4.1 points on a scale from 1 (maximum impairment of QoL) to 5 (no impairment of QoL) indicating a moderately negative impact on QoL. Scores below the average were mainly driven and accompanied by a fear of urine leakage, urine odor, painful catheter changes and urinary infections increasing with age. Additionally, patients were worried about negative effects on their daily life activities due to the catheter. These worries seemed to be more pronounced in females with urinary incontinence, patients with a catheter size ≥ 18 Ch. and with an age of < 70 years. The type of catheter showed a greater impact on the QoL in females with suprapubic catheters when compared with males in contrast to patients with transurethral catheters. CONCLUSION: The results of the study provide further information for the medical clarification for patients and caregivers, having to decide between a lifelong catheter drainage or alternatives, such as provision of an aid or surgical recanalization.

[Guidelines for consultations regarding incontinence care products]. / Leitlinie Hilfsmittelberatung bei Harninkontinenz.

An investigation of the German consumer organisation "Stiftung Warentest" in 2017 confirmed significant deficiencies in the information, advice and supply of incontinence care products received by urinary incontinence patients. The German Society of Urology (DGU) thereupon drafted and later published guidelines concerning the consultation of patients in the context of incontinence care. Important aspects of the consultation process include the determination of the type of incontinence as well as its severity, clinical examination, and advice regarding possible curative treatments. However, the advice appointment takes centre stage and should ideally be conducted by a qualified person in a separate room granting sufficient privacy and time. Furthermore, repeated supply of a selection of samples for differing degrees and types of incontinence, accommodating the patient's individual preferences and anatomical features, is crucial in order to ensure optimal incontinence care. In the case of commercial health care service providers, transparency relating to the financial implications of e.g. expensive products is key, which is what has been intended by German health insurance providers. The new guidelines concerning urinary incontinence care consultation constitute a step towards the improvement and structuring of processes in the consultation regarding, and the supply of, incontinence care products.

[Comparison of catheter-associated quality of life in external urinary diversion: nephrostomy vs. suprapubic catheter]. / Vergleich der katheterassoziierten Lebensqualität bei externen Harnableitungen: Nephrostomie vs. suprapubischer Katheter.

INTRODUCTION: A percutaneous nephrostomy (PCN) affects the integrity of the patient due to the requirement of an external drainage bag and regular changes. The catheter-associated quality of life (QOL) was evaluated using a validated assessment and compared to similar patients with suprapubic bladder drainage. METHODS: A validated assessment analyzing catheter-related QOL for 5 domains and 25 individual items (first published by Mary Wilde) was completed during a catheter change appointment by patients who had their unilateral or bilateral PCN for a minimum of 3 months in life-long indication. RESULTS: In 66 patients (unilateral PCN: 42 patients), a moderate impairment of their catheter-related QOL was shown. The overall QOL score was median 4.0 on a scale of 0-5. This was rated lower-indicating a stronger impairment of QOL-than in patients with a suprapubic bladder catheter, who had a median score of 4.3. Significant differences were found related to the catheter type in the items "feeling of humiliation due to the PCN", "conflicts with the medical or nursing staff", "fear of painful catheter changes", "feeling ill", "being handicapped in activities of daily living" and "concern of not being able to do what one wants to do" and "fear of catheter leakages". The indication for the PCN due to a malignant or benign underlying disease was not associated with the catheter-related QOL. CONCLUSION: For the first time, the catheter-related QOL was found to be moderately impaired in patients with a PCN using a validated assessment. Affected individuals report feeling "ill" and "limited/disabled" in activities of daily living; thus, the surgical indication should be strict. Fear of painful catheter changes and of catheter leakages indicates the need of technically correct catheter changes.

How do the FIFA World Cup 2018 and the 2016 UEFA championships impact a pediatric emergency department?

INTRODUCTION: In France, soccer is the most popular sport, which today attracts a huge television audience with millions of spectators in the case of international competitions. During certain games with European top clubs, the attendance of adult emergencies is impacted. However, the impact of international soccer competitions on pediatric emergency department (PED) activity has not been evaluated. METHODS: We performed a retrospective analysis of attendance in the PED of a tertiary university hospital in Nancy (France) during the UEFA 2016 championship and the FIFA 2018 World Cup. Games were represented by 2.5-h blocks and the tournament period was compared with the same period in the previous year. RESULTS: Considering all games, we did not observe an impact of PED attendance. The admission rate was significantly lower during the final phase (11.1 patients per match vs. 13.9, P=0.037). We observed a decrease in consultations for trauma (4.9 vs. 6.7, P=0.006). The effects were higher during games involving the national French team, with a decrease in less severe admissions (P=0.034), attendance of older children (P=0.016), and the presence of the father as accompanying adult (P=0.002). During the two final matches, we observed a decrease of 14% in the total activity. CONCLUSION: We found significant differences in PED attendance during two international soccer tournaments. It would be interesting to study this effect in countries other than France or in countries with different sport habits.

Murine AML12 hepatocytes allow Salmonella Typhimurium T3SS1-independent invasion and intracellular fate.

Numerous studies have demonstrated the key role of the Salmonella Pathogenicity Island 1-encoded type III secretion system (T3SS1) apparatus as well as its associated effectors in the invasion and intracellular fate of Salmonella in the host cell. Several T3SS1 effectors work together to control cytoskeleton networks and induce massive membrane ruffles, allowing pathogen internalization. Salmonella resides in a vacuole whose maturation requires that the activity of T3SS1 subverts early stages of cell signaling. Recently, we identified five cell lines in which Salmonella Typhimurium enters without using its three known invasion factors: T3SS1, Rck and PagN. The present study investigated the intracellular fate of Salmonella Typhimurium in one of these models, the murine hepatocyte cell line AML12. We demonstrated that both wild-type Salmonella and T3SS1-invalidated Salmonella followed a common pathway leading to the formation of a Salmonella containing vacuole (SCV) without classical recruitment of Rho-GTPases. Maturation of the SCV continued through an acidified phase that led to Salmonella multiplication as well as the formation of a tubular network resembling Salmonella induced filaments (SIF). The fact that in the murine AML12 hepatocyte, the T3SS1 mutant induced an intracellular fate resembling to the wild-type strain highlights the fact that Salmonella Typhimurium invasion and intracellular survival can be completely independent of T3SS1.

Volatile fatty acid platform - a cornerstone for the circular bioeconomy.

Annually, the EU produces more than 100 million tonnes of urban biowaste, which is largely under-valorized and in some cases even still landfilled without any energy or material recovery. If Europe wants to be ready for the future, it will need to make better use of this large biomass potential within a circular economy approach. The research project funded by the European Commission under the Horizon 2020 programme entitled 'VOLATILE-Biowaste derived volatile fatty acid platform for biopolymers, bioactive compounds and chemical building blocks' aimed to produce volatile fatty acids (VFAs) from biowaste for reprocessing into products, materials or substances to close the material loop. During the project, the partners were able to obtain average volatile fatty acid yields of 627 g COD/kg organic matter (OM) for food waste, 448 g COD/kg OM for separately collected vegetable, garden and fruit waste (VGF) and 384 g COD/kg OM for the organic fraction of municipal solid waste (OF-MSW) at concentrations ranging from 12 to 48 g/L, 6 to 40 g/L and 13 to 26 g/L, respectively. A membrane filtration cascade consisting of micro-, ultra- and nano-filtration followed by reverse osmosis was identified as a feasible way to purify and concentrate the VFA effluent, making them a suitable carbon source for further fermentation processes. Besides technical optimization, socio-economic and legal aspects associated with this platform technology were also studied and show that although this technology is still in development, it is providing an answer to changing societal and market expectations both regarding organic waste treatment and bio-based production strategies. Based on the current technological, economic and market evolutions, it is expected that the VFAP will play an important role in organic waste treatment in the coming years.

[Macrohematuria as the leading symptom in geriatric urology patients]. / Makrohämaturie als Leitsymptom bei geriatrischen Patienten in der Urologie.

BACKGROUND: Macrohematuria is a frequent reason for hospitalization of elderly urologic patients. Anticoagulants and long-term catheterization often play a role and are characterized in the current paper. METHODS: In all, 162 patients hospitalized due to macrohematuria and older than 75 years were retrospectively observed concerning demographic data, clinical risk factors, potential reasons for macrohematuria and the necessary interventions. RESULTS: The observed patients were on average 84.74 years old and had a medium score of 2.72 in the geriatric screening as "with geriatric need of action". A total of 65.4% had a Foley or suprapubic catheter. Initial measures included continuous bladder irrigation in 42.6% and catheter replacement in 39.5%. The amount of blood loss was 1.27 mg/dl hemoglobin. There was no significant difference in bacterial bladder infection in patients with or without a catheter (51.7 vs. 42.6%, p = 0.51). In all, 75.3% of the patients were under anticoagulation therapy; of these, 40.6% were undertreated with vitamin K antagonists, 28.1% overtreated and 31.2% were in the target range. Urologic workup diagnosed 25.3% of patients with tumors of the urinary bladder, the prostate or ureter. CONCLUSION: A bladder catheter is a risk factor for more intensive macrohematuria. Contrary to expectations, overdosage was not the leading reason for hematuria for patients taking vitamin K antagonists. Even for elderly, geriatric patients under anticoagulation, the urologic diagnostic workup demonstrated a high percentage of significant malignancies. Diagnostic procedures should not be neglected even for these patients.