Repurposing the prostaglandin analogue treprostinil and the calcium-sensing receptor modulator cinacalcet to revive cord blood as an alternate source of hematopoietic stem and progenitor cells for transplantation.

Objective: The expanding field of hematopoietic cell transplantation (HCT) for non-malignant diseases, including those amenable to gene therapy or gene editing, faces challenges due to limited donor availability and the toxicity associated with cell collection methods. Umbilical cord blood (CB) represents a readily accessible source of hematopoietic stem and progenitor cells (HSPCs); however, the cell dose obtainable from a single cord blood unit is frequently insufficient. This limitation can be addressed by enhancing the potency of HSPCs, specifically their capacity to reconstitute hematopoiesis.

Therapeutic strategies for uncomplicated cystitis in women.

Uncomplicated cystitis is affecting many women of all ages and has a great impact on the quality of life, especially in women suffering from recurrent, uncomplicated cystitis. By far the most frequent uropathogen, , may have acquired increasing resistance against a variety of oral antibiotics, which may differ between countries and regions. Therefore, local resistance data are important to be considered.

Thinking beyond Vaccination: Promising Add-On Strategies to Active Immunization and Vaccination in Pandemics-A Mini-Review.

There is little doubt that final victories over pandemics, such as COVID-19, are attributed to herd immunity, either through post-disease convalescence or active immunization of a high percentage of the world's population with vaccines, which demonstrate protection from infection and transmission and are available in large quantities at reasonable prices. However, it is assumable that humans with immune defects or immune suppression, e.g.

[Urolithiasis-Therapy and recurrence prevention taking into account gender-specific aspects].

The prevalence of urolithiasis is steadily increasing worldwide in both genders. Diet and lifestyle, such as the rising prevalence of obesity and other metabolic syndrome traits, are considered key factors in this trend. Gender differences as a result of interventional therapy for urolithiasis have not been observed.

Are there seasonal variations in renal colic in uric acid stone formers in Germany?

Purpose: Seasonal variations in renal colic have been described by many authors for different countries worldwide. In most studies, there was no differentiation with regard to stone composition. Recently, we demonstrated that there was no seasonal variation in renal colic and urine chemistry for calcium oxalate stone formers in Germany.

[Current aspects in pediatric urolithiasis treatment].

Compared with adults, urolithiasis is quite rare in children (1-2% of all urinary stones occur during childhood). In principle, all therapy modalities for adults can also be used in children. However, due to some anatomic and functional peculiarities in children, the differential indication for the various treatment modalities differ.

Regimen-dependent synergism and antagonism of treprostinil and vildagliptin in hematopoietic cell transplantation.

The cell dose in umbilical cord blood units is a major determinant for the outcome of hematopoietic cell transplantation. Prostaglandin analogs and dipeptidylpeptidase-4 (DPP4/CD26)-inhibitors enhance the ability of hematopoietic stem cells (HSCs) to reconstitute hematopoiesis. Here we explored the synergism between treprostinil, a stable prostaglandin agonist, and the DPP4/CD26-inhibitor vildagliptin.

[Update of the 2Sk guidelines on the diagnostics, treatment and metaphylaxis of urolithiasis (AWMF register number 043-025) : What is new?].

The increase of medical knowledge and technical innovations together with the demographic change represent a challenge for the new conception of guidelines and clinical studies. The present S2k guidelines, which are exclusively concerned with kidney and ureteral stones, should support the treatment of urolithiasis in hospitals and private practices and provide information on urolithiasis for patients. Increasing interdisciplinary collaboration in stone treatment is also demonstrated in the number of professional and working groups participating in the update of the new guidelines.

Chylothorax and Chylous-Like Diseases in Children: Clinical Management.

Chylothorax and chylous-like diseases are rare conditions and difficult to treat. But they may represent potentially life-threatening disorders and important causes of morbidity and prolonged hospitalization, especially in critically ill children. Conservative as well as surgical therapeutic management strategies are continuously performed at our institution, however the results have never been evaluated and no guidelines for treatment recommendations have been put into practice so far.

Treprostinil reduces endothelial damage in murine sinusoidal obstruction syndrome.

Sinusoidal obstruction syndrome (SOS) is a major complication after hematopoietic stem cell transplantation and belongs to a group of diseases increasingly identified as transplant-related systemic endothelial disease. Administration of defibrotide affords some protection against SOS, but the effect is modest. Hence, there is unmet medical need justifying the preclinical search for alternative approaches.

Extended use of the modified Berlin Definition based on age-related subgroup analysis in pediatric ARDS.

Background: Pediatric acute respiratory distress syndrome (pARDS) is a rare but very severe condition. Management of the condition remains a major challenge for pediatric intensive care specialists.

Objective: To perform a descriptive assessment of pARDS based on the modified Berlin Definition by using the SpO/FiO ratio in order to establish an extended patient registry divided into age-related subgroups.

Recent advances in understanding and managing urolithiasis.

During the last few years, there has been relevant progress in both understanding and managing urolithiasis. Our knowledge of stone formation has changed; although the importance of urine biochemistry was questioned by several investigators years ago, the decisive role of cellular processes (induced by oxidative stress) and the renal papilla has only recently been generally accepted as the most important step in stone formation. For calcium oxalate urolithiasis, the formation of papillary calcifications plays a key role and is of prognostic relevance.

Repurposing Treprostinil for Enhancing Hematopoietic Progenitor Cell Transplantation.

Activation of Gs-coupled receptors enhances engraftment of hematopoietic stem and progenitor cells (HSPCs). We tested the hypothesis that treprostinil, a prostacyclin analog approved for the treatment of pulmonary hypertension, can be repurposed to improve hematopoietic stem cell transplantation. Murine and human HSPCs were isolated from bone marrow and umbilical cord blood, respectively.

Influence of the Surfactant Tyloxapol on Mucociliary Clearance in Human Respiratory Cystic Fibrosis Cells.

Dehydration of the apical surface of cystic fibrosis (CF) airway epithelia leads to a greatly impaired mucociliary clearance function in CF patients. In an in vitro cell model of human airway epithelia taken from CF patients and cultivated for 60 days, mucociliary clearance was zero. Tyloxapol, a synthetic surfactant, is able to restore the mucociliary clearance of the CF epithelia.

Imaging in pediatric urolithiasis-what's the best choice?

The incidence of urolithiasis increased dramatically during the last decades in adults as well as in children. Today, when a urinary stone is suspected, the imaging modality used most frequently is non-contrast enhanced computed tomography (NCCT). Due to the high sensitivity and specifity, NCCT is regarded as the gold standard.

Papillary calcifications: a new prognostic factor in idiopathic calcium oxalate urolithiasis.

Metabolic evaluation is not suitable to forecast the course of the disease in idiopathic calcium oxalate stone formation (iCaOxU). An important pathway in CaOx stone formation is the overgrowth on interstitial apatite papillary plaques. Therefore, we studied whether the extent of such plaques may be used as a prognostic factor in CaOxU.

Economics of stone disease/treatment.

Objectives: Urolithiasis is a considerable economic burden for health systems, especially in industrialised countries where the incidence of stone disease has increased during the last few decades, and probably will further increase for several reasons.

Methods: The survey was based on investigations in collaboration with a German health insurance company and on a literature search (PubMed, and the author's collection of proceedings of urolithiasis conferences: The keywords included economics, cost, urolithiasis, nephrolithiasis, renal stone disease, metaphylaxis, recurrence) during 1999-2011. In all, 1221 articles were found but only those cited here were sufficient for the purpose of the study.

Overweight and obesity: risk factors in calcium oxalate stone disease?

Introduction. Several studies showed an association of overweight and obesity with calcium oxalate stone disease (CaOx). However, there are no sufficient data on the influence of body weight on the course of the disease and the recurrence rate.

[Secondary malignancies in urinary diversions].

In contrast to ureterosigmoidostomy no reliable clinical data exist for tumor risk in different forms of urinary diversion using isolated intestinal segments.In 44 German urological departments, operation frequencies, indications, patient age, and operation dates of the different forms of urinary diversion, operated between 1970 and 2007, could be registered. The secondary tumors up to 2009 were registered as well and related to the numbers of the different forms of urinary diversions resulting in tumor prevalences.

Urinary stone formers with hypocitraturia and 'normal' urinary pH are at high risk for recurrence.

Background: Citrate is one of the most important inhibitors in urolithiasis. Hypocitraturia is a common risk factor in stone formers. Citrate excretion is regulated - amongst others - by acidosis and protein intake.

[Recurrence prevention of urolithiasis with respect to economic aspects].

Recurrence prevention in urinary stone disease not only makes good medical but also economic sense. Up to 40% of recurrences can be prevented by a rational urinary stone metaphylaxis whereby not only treatment costs but also the cost of lost productive work time can be saved. Detailed knowledge of stone composition and medical history of the patient is a prerequisite for a rational metaphylaxis which according to the S2 guidelines results in assignment to the high or low risk group.

Overweight, insulin resistance and blood pressure (parameters of the metabolic syndrome) in uric acid urolithiasis.

Overweight, arterial hypertension and disturbances of the carbohydrate metabolism are important parameters of the metabolic syndrome (MS). The most important factor regarding renal pathophysiology is insulin resistance resulting in alterations of urine acidification and low urine pH. Since low urine pH is the main risk factor for uric acid urolithiasis (UAU), UAU may be regarded as a renal manifestation of the MS.