Supplementary orthopaedic screening for children and adolescents to prevent permanent skeletal deformities - protocol for the "OrthoKids" study.

BACKGROUND: Skeletal deformities (SD) in children and adolescents can lead to arthritic conditions, impairment of quality of life, and high treatment costs in the long term. However, comprehensive data on the prevalence of SDs in children and adolescents are limited and it remains therefore unclear whether there is a healthcare gap. "OrthoKids" is a project that addresses this evidence gap by implementing an orthopaedic screening for children and adolescents that supplements existing detection examinations within statutory standard care in Germany. OBJECTIVE: To detect SDs so that they can be treated as needed at an early stage. METHODS: The implementation of the supplementary orthopaedic screening will be evaluated through an exploratory cohort study that is set up in the German state Baden-Wuerttemberg. 20,000 children and adolescents aged 10 to 14 years will be recruited as a prospective cohort. A retrospective control cohort will be formed based on claims data provided by two cooperating statutory health insurances (SHIs). Participating children and adolescents receive a one-time orthopaedic screening. If at least one SD is diagnosed, treatment will be provided as part of the statutory standard care. Within the scope of the project, a follow-up examination will be performed after one year. An IT-platform will complement the study. The primary outcome measure is the point prevalence of scoliosis, genu varum/valgum, hip dysplasia, and flat feet. Secondary outcome measures are (i) the point prevalence of further less common SDs, (ii) health-related quality of life (HRQoL), (iii) sports ability based on activity (physical/athletic), physical constraints, and (sports) injuries, as well as (iv) monetary consequences of the orthopaedic screenings' implementation. Implementation determinants will be evaluated, too. DISCUSSION: If the supplementary orthopaedic screening proves to be viable, it could be considered as a supplementary examination for children and adolescents within the frame of SHI in Germany. This could relieve the burden of disease among children and adolescents with SDs. In addition, it could disburden SHIs in the medium to long term. TRIAL REGISTRATION: The OrthoKids study was registered in the German Clinical Trials Registry (Deutsches Register Klinischer Studien (DRKS)) on 26th July 2022 under the number 00029057.

[Safety and efficacy of en bloc vs. conventional transurethral resection of bladder tumors: a meta-analysis and systematic review]. / Sicherheit und Effizienz der en bloc vs. konventionellen transurethralen Resektion von Blasentumoren: eine Metaanalyse und systematic Review.

BACKGROUND: En bloc tumor resection of bladder tumors (ERBT) is a novel alternative procedure to conventional resection of bladder tumor (cTURBT), which might help to address common problems of the standard method, such as inadequate detrusor muscle in specimens, high re-resection rates and high recurrence rates. OBJECTIVE: To analyze current data on ERBT in efficacy and safety compared to cTURBT. DATA SOURCES: PubMed. STUDY SELECTION: Two independent authors identified trials based on keywords and inclusion criteria. A third author was consulted in case of discrepancies. Screening keywords: ERBT, en bloc transurethral resection of bladder tumor, TURBT en bloc. A meta-analysis of 13 studies was performed. The effect size was estimated based on odds ratios and mean differences including their corresponding two-sided 95% confidence intervals. DATA SYNTHESIS: The analyzed studies comprised a homogenous collective in terms of tumor size, tumor multiplicity and tumor stage. Operation time did not significantly differ between the methods. Differences were observed in hospitalization and catheterization time in favor of ERBT. Reported complications did not show clear differences. There was significantly more detrusor muscle in the specimens in the ERBT group. No significant differences were found in recurrence up to 2 years of follow-up. CONCLUSION: ERBT is a safe alternative to conventional TURBT with promising features regarding effective resection of detrusor muscle. More standardized data on recurrence rates, different resection modalities and resection margin results are needed.

[Transurethral resection of bladder tumors (TURBT)]. / Transurethrale Resektion von Blasentumoren (TUR-B).

Transurethral resection of bladder tumors (TURBT) is the standard of care for the diagnostics and primary treatment of bladder tumors. These are removed by fragmentation using loop diathermy. The resection area is coagulated for hemostasis. An important aspect is always a complete resection with an adequate amount of detrusor muscle in the specimen. Postoperative intravesical instillation of single-shot chemotherapy has been proven to reduce recurrence rates. Methods for improved tumor visualization (particularly photodynamic diagnostics) are used to enhance tumor detection rates particularly in multifocal tumors or carcinoma in situ (CIS). Thus, recurrence and progression rates can be reduced. Depending on the histological examination of the TURBT specimen, follow-up treatment for non-muscle invasive bladder tumors are adjuvant instillation treatment using chemotherapy or Bacillus Calmette-Guérin (BCG), second look TURBT and early cystectomy or for muscle invasive bladder tumors, radical cystectomy or (oncologically subordinate) trimodal treatment with renewed TURBT, radiotherapy and chemotherapy are indicated. Possible complications of TURBT include bleeding with bladder tamponade, extraperitoneal or intraperitoneal bladder perforation and infections of the urogenital tract.

Endoscopic enucleation of the prostate (EEP). The same but different-a systematic review.

PURPOSE: Various techniques for EEP exist. They differ by surgical steps and the source of energy. It is assumed that the latter is of minor importance, whereas adherence to the anatomical enucleation template determines the postoperative result. So far, no systematic review highlights the differences between the energy sources in use for anatomical EEP. This study will address selfsame topic. METHODS: A systematic review of the literature was completed on September 1st, 2020. Studies comparing HoLEP, ThuLEP, DiLEP, or BipolEP with TUR-P providing 12 months of postoperative follow-up were included. Two frequentist network meta-analyses were created to compare the techniques of EEP indirectly. RESULTS: 31 studies, including 4466 patients, were found eligible for our meta-analysis. Indirect pairwise comparison showed differences in surgery time between BipolEP and HolEP (MD - 16.72 min., 95% CI - 27.75 to - 5.69) and DiLEP and HoLEP (MD - 22.41 min., 95% CI - 39.43 to - 5.39). No differences in the amount of resected prostatic tissue, major and minor complications and postoperative catheterization time were found. The odds for blood transfusions were threefold higher for BipolEP than for HoLEP (OR 3.27, 95% CI 1.02-10.5). The difference was not statistically significant when comparing prospective trials and matched-pair analysis only (OR 3.25, 95% CI 0.94-11.18). The Qmax 12 months after surgery was 2 ml/sec. higher for BipolEP than for DiLEP (MD 2.00, 95% CI 0.17-3.84) and 1.94 ml/sec. lower for DiLEP than for HoLEP (MD - 1.94, 95% CI - 3.65 to - 0.22). CONCLUSION: The energy source used for EEP has an impact on the intervention itself. BipolEP promotes surgical efficiency; laser techniques lower the risk of bleeding. REGISTRY: This meta-analysis is registered in the PROSPERO international prospective register registry with the registration number CRD42020205836.

[Surgical treatment of benign prostatic obstruction (BPO) in patients under anticoagulation: a review of the bleeding risks of established techniques]. / Die chirurgische Therapie der benignen Prostataobstruktion (BPO) beim antikoagulierten Patienten: eine Übersichtsarbeit über die Blutungsrisiken etablierter Techniken.

BACKGROUND: In an aging society an increase of benign prostatic obstruction (BPO) requiring treatment is to be expected and the proportion of patients with cardiovascular comorbidities under anticoagulation is also increasing. As the operative treatment of BPO can be problematic, the hemostatic effect of the techniques is of particular importance. OBJECTIVE: This review article discusses the data situation on the bleeding risk of established surgical techniques and the statement of the European Association of Urology (EAU) guidelines "EAU guidelines on management of non-neurogenic male lower urinary tract symptoms (LUTS), incl. benign prostatic obstruction (BPO)" on this topic. MATERIAL AND METHODS: Data analysis from PubMed. RESULTS: The EAU guidelines favor transurethral laser vaporization of the prostate using "greenlight", thulium or diode laser and laser enucleation using a holmium or thulium laser in this patient collective. The bipolar is superior to monopolar transurethral resection (TUR-P) in hemostasis. In the future bipolar enucleation of the prostate (BipoLEP) can be an alternative under good hemostasis. Bleeding is a rare complication after recently established minimally invasive techniques, such as Urolift®, I­TIND© and Rezum™, the same applies to prostate artery embolization. Aqua-ablation/AquaBeam® seems to be unsuitable due to frequent hematuria. Surgical adenomectomy can be associated with a high risk of bleeding. CONCLUSION: According to current data, transurethral laser vaporization and enucleation of the prostate are the treatment of choice for patients under anticoagulation; however, other transurethral techniques, such as BipoLEP have an acceptable risk of bleeding and can be an alternative depending on local resources. Newer minimally invasive approaches could become more important in the future.

On-site CAD templates reduce surgery time for complex craniostenosis repair in infants: a new method.

INTRODUCTION: The surgical correction of craniostenosis in children is a time-consuming and taxing procedure. To facilitate this procedure, especially in infants with complex craniostenosis, we refined the computer-aided design and manufacturing technique (CAD/CAM) based on computed tomography (CT)-generated DICOM data. We used cutting guides and molding templates, which allowed the surgeon to reshape and fixate the supraorbital bar extracorporeally on a side table and to control the intracorporal fit without removing the template. METHOD AND PATIENTS: To compare our traditional concept with the possibility of preoperative virtual planning (PVP) technique, the surgical treatment and courses of 16 infants with complex craniostenosis following fronto-orbital advancement (FOA) (age range 8-15 months) were analyzed in two groups (group 1: traditional, control group n = 8, group 2: CAD/CAM planned, n = 8). RESULTS: While in both groups, the head accurately reshaped postoperatively during the follow-up; the CAD group 2 showed a significantly shorter operating time with a mean of 4 h 25 min compared with group 1 with a mean of 5 h 37 min (p = 0.038). Additionally, the CAD group 2 had a significantly lower volume of blood loss (380 ml vs. 575 ml mean, p = 0.047), lower blood transfusion volume (285 ml vs. 400 ml mean, p = 0.108), lower fresh frozen plasma (FFP) volume (140 ml vs. 275 ml mean, p = 0.019), shorter stay in the pediatric intensive care unit (PICU) (3 vs. 5 days mean (p = 0.002), and shorter total length of hospital stay (6 days vs. 8 days mean, p = 0.002). CONCLUSION: CAD/CAM cutting guides and templates offer optimizing operative efficiency, precision, and accuracy in craniostenosis surgery in infants. As shown in this single-center observational study, the use of on-site templates significantly accelerates the reconstruction of the bandeau. The virtual 3D planning technique increases surgical precision without discernible detrimental effects.

Anticoagulation management during multivessel coronary artery bypass grafting: a randomized trial comparing individualized heparin management and conventional hemostasis management.

BACKGROUND: Individualized heparin management (IHM) uses heparin dose-response curves to improve hemostasis management during cardiac surgery as compared with activated clotting time-based methods. OBJECTIVES: IHM was compared with conventional hemostasis management (CHM) in a randomized, prospective study (ID DRKS00007580). METHODS: One-hundred and twenty patients undergoing multivessel coronary artery bypass grafting (CABG) were enrolled. Heparin and protamine consumption, blood losses, blood transfusions and administration of hemostatic agents were recorded. Time courses of platelet counts and of coagulation parameters were determined. Coagulation was analyzed at intensive care unit (ICU) arrival by thromboelastometry. RESULTS: IHM patients received significantly lower initial heparin doses (289.3IU kg(-1) [interquartile range (IQR) 221.5-376.2 IU kg(-1) ] versus 350.5 IU kg(-1) [IQR 346.8-353.7 IU kg(-1) ], P < 0.0001) but similar total heparin doses (418.5 IU kg(-1) [IQR 346.9-590.5 IU kg(-1) ] versus 435.8 IU kg(-1) [IQR 411.7-505.1 IU kg(-1) ]). IHM patients received significantly less protamine, resulting in protamine/total heparin ratios of 0.546 [IQR 0.469-0.597] versus 0.854 [IQR 0.760-0.911] in CHM patients (P < 0.0001). Activated partial thromboplastin time (50.5 s [IQR 40.0-60.0 s] versus 37.0 s [IQR 33.0-40.0 s], P < 0.0001), activated clotting time (136 s [IQR 129.0-150.5 s] versus 126.5 s [IQR 120.3-134.0 s], P = 0.0002) and INTEM clotting times (215 s [IQR 192-237] versus 201 s [IQR 191-216 s], P = 0.0397) were significantly longer in IHM patients than in CHM patients at ICU arrival, with no difference in prothrombin time (P = 0.538). IHM patients lost significantly more blood within 12 h postoperatively (420 mL [IQR 337.5-605.0 mL] versus 345 mL [IQR 230.0-482.5 mL], P = 0.0041), and required significantly more hemostatic agents to control bleeding. Red blood cell transfusion requirements and time courses of platelet counts did not differ between groups. CONCLUSIONS: Multivessel CABG patients did not benefit from IHM in comparison with our established protocol based on activated clotting time.

[MALDI mass spectrometry of the meniscus. Objectification of morphological findings]. / MALDI-Massenspektrometrie am Meniskus. Objektivierung morphologischer Befunde.

BACKGROUND: The classification of meniscal lesions requires correlation with clinical data. For the standardization of histopathology reports a discrimination between normal, low-grade lesions and high-grade lesions is feasible. This classification can be further specified using other methods. MATERIAL AND METHODS: Formalin-fixed, paraffin-embedded specimens of meniscal tissue from 68 patients were analyzed by matrix-assisted laser desorption ionization (MALDI) imaging. RESULTS: The classification of meniscal lesions and differentiation between low-grade and high-grade and acute versus non-acute degeneration is possible by determination of the differential expression of mass-to-charge ratios by statistical comparisons using the P-value from combined Wilcoxon and Kruskal-Wallis (PWKW) tests and a predefined average two-fold difference in intensity. CONCLUSION: The concept of a "meniscus report" is introduced for documentation of meniscus tissue specimens integrating histological, histochemical and proteomic data, thereby specifying the degree of degeneration and the assessment of acute or non-acute lesions. Mass spectrometry contributes to an objective histopathology report. An advisory opinion should always be based on close correlation of clinical and morphological evaluations.

MALDI imaging of predictive ferritin, fibrinogen and proteases in haemophilic arthropathy.

Arthropathy as a result of repeated joint bleeding is a severe complication in patients with haemophilia. In the evaluation of synovial tissue specimens, histology alone is non-specific and there is considerable morphological overlap with other joint diseases. Formalin-fixed paraffin-embedded specimens are available in pathological institutes and can be studied to understand the pathogenesis of haemophilic arthropathy. A powerful technique to identify hundreds of proteins in a tissue section combining proteomics with morphology is imaging mass spectrometry (IMS). We determined whether matrix-assisted laser desorption/ionization (MALDI) IMS can be used to identify and map protein signatures in the synovial tissue of patients with haemophilic arthropathy. MALDI IMS was applied to synovial tissue of six patients with haemophilic arthropathy. We detected several peaks predictive in mass with ferritin light (m/z 1608) and heavy chain (m/z 1345), alpha- (m/z 1071) and beta (m/z 1274) haemoglobin subunits, truncated coagulation factor VIII peptide (m/z 1502, 1176), beta- and gamma fibrinogen peptides (m/z 980, 1032, 1117 and 1683), and annexin A2 (m/z 1111, 1268, 1460, 2164). In addition, the distribution of these proteins in synovial tissue sections was demonstrated. MALDI IMS identified and mapped specific proteins in the synovial membrane of patients with haemophilic arthropathy known to be involved in the pathogenesis of other joint diseases. This technique is a powerful tool to analyse the distribution of proteins in synovial tissue sections.

A Staphylococcus aureus lipoteichoic acid (LTA) derived structural variant with two diacylglycerol residues.

Based on 1,2-O-isopropylidene-sn-glycerol five chiral building blocks containing differently modified glycerol residues were required for the synthesis of the target molecule 2. One of these building blocks is diacylglyceryl beta-gentiobioside carrying a phosphite residue at 6b-O position. Ligation of these five building blocks led to the desired glycerol phosphate backbone to which d-alanyl residues were attached, thus generating after O-deprotection the target molecule 2, a bisamphiphilic structural variant of Staphylococcus aureus LTA. This compound displayed higher potency in terms of cytokine release by human blood leukocytes than the monoamphiphilic variant LTA.

Glycosylphosphatidyl inositol-anchored proteins and fyn kinase assemble in noncaveolar plasma membrane microdomains defined by reggie-1 and -2.

Using confocal laser scanning and double immunogold electron microscopy, we demonstrate that reggie-1 and -2 are colocalized in < or =0.1-microm plasma membrane microdomains of neurons and astrocytes. In astrocytes, reggie-1 and -2 do not occur in caveolae but clearly outside these structures. Microscopy and coimmunoprecipitation show that reggie-1 and -2 are associated with fyn kinase and with the glycosylphosphatidyl inositol-anchored proteins Thy-1 and F3 that, when activated by antibody cross-linking, selectively copatch with reggie. Jurkat cells, after cross-linking of Thy-1 or GM1 (with the use of cholera toxin), exhibit substantial colocalization of reggie-1 and -2 with Thy-1, GM1, the T-cell receptor complex and fyn. This, and the accumulation of reggie proteins in detergent-resistant membrane fractions containing F3, Thy-1, and fyn imparts to reggie-1 and -2 properties of raft-associated proteins. It also suggests that reggie-1 and -2 participate in the formation of signal transduction centers. In addition, we find reggie-1 and -2 in endolysosomes. In Jurkat cells, reggie-1 and -2 together with fyn and Thy-1 increase in endolysosomes concurrent with a decrease at the plasma membrane. Thus, reggie-1 and -2 define raft-related microdomain signaling centers in neurons and T cells, and the protein complex involved in signaling becomes subject to degradation.

Molecular characterization of a conformational epitope of hen egg white lysozyme by differential chemical modification of immune complexes and mass spectrometric peptide mapping.

A new approach for the characterization of conformationally dependent epitope structures in protein antigens is described using differential chemical modification of immune complexes in combination with mass spectrometric peptide mapping analysis. Well-established methods for epitope characterization are frequently not applicable to conformationally dependent epitopes, and direct methods of structure analysis such as X-ray crystallography of immune complexes have been successful only in a few cases. Our approach combines tertiary structure-selective chemical modification of immune complexes with the molecular characterization of reaction products by mass spectrometric peptide mapping. The comparison of the modification pattern of free and antibody-bound antigen provides the identification of residues protected from modification by the antibody. These residues hence are characterized as part of the epitope structure. The well-characterized hen egg white lysozyme and a corresponding monoclonal IgM-type antibody were investigated as a model system. Specific modification reactions for arginine, lysine, and tyrosine residues were performed, and the modification sites in free and antibody-bound antigen were determined by mass spectrometric peptide mapping. The R14 residue and residues K13 and K96 in the antibody-bound lysozyme were found to be protected from modification, comprising a surface of spatially adjacent residues by folding of the native protein. In contrast, other K and R residues as well as Y20 and Y23 showed no significant shielding from modification in the immune complex. These results provided an estimation of the molecular epitope surface area of native lysozyme.

Treatment of chronic stomatitis of cats by local paramunization with PIND-ORF.

33 cats, suffering from chronic stomatitis, were treated with orally given paramunity inducer PIND-ORF (local paramunization). As a control 39 cats in the same practice were treated with other conventional methods. The reconvalescence rate (healing without rezidives) of experimental animals was 42%. From control animals only 13% reached this status. Oral paramunization with PIND-ORF is recommended as an alternative treatment for hitherto existing therapeutic measures against chronic stomatitis.

Behavioral characteristics and laboratory parameters in homo- and bisexual men in West Berlin: an evaluation of five years of testing and counselling on AIDS.

Sera of 1980 homo- and bisexual men who visited the Landesinstitut für Tropenmedizin Berlin (West) between April 1983 and December 1987 were tested for HIV antibodies; 24.3% were positive. Of HIV-antibody-positive men, 78.9% reported both active and passive anal intercourse, 58.8%, rectal enemas, and 53.3%, use of butyl nitrite. There was a sexual partner with known positive HIV-antibody status or AIDS in 33.9%, and in 32.4% there was a history of sexual activity in the USA. In the year before the test, 18.8% had had more than 50 partners. All these behavioral characteristics were found to be significantly correlated to HIV antibodies. We noted a substantial reduction of high-risk behavior from 1983 to 1987. The most important behavioral factor for HIV infection in 1983 and 1984 was sexual activity in the USA, and from 1984 to 1987, the numbers of lifetime partners. Persons infected with HIV were significantly more often carriers of antibodies against HAV, HBV, CMV, EBV, and syphilis. Prevalence of antibodies against HIV, HAV, HBV, and syphilis increased with age, duration of homosexual practice, and the number of partners. Overall crude prevalence rates of HIV antibodies, anti-HBc, anti-HAV, and antibodies to syphilis declined during the observation period. Clinical findings such as fever, oral lesions, and lymphadenopathy syndrome (LAS) were found to be highly indicative of HIV infection. Lower hemoglobin values, a reduced white cell count, and hyperimmunoglobulinemia were significantly more frequent in subjects with HIV antibodies.

HIV infection in intravenous drug abusers in Berlin: risk factors and time trends.

To investigate the epidemiology of HIV infection among intravenous drug abusers (IVDA) in Berlin (West), from October 1984 to October 1988, 741 heterosexual IVDA were recruited from facilities for drug treatment and counseling. In this group 22.8% were seropositive for antibodies against HIV, representing 21.1% of the females and 23.5% of the males. Seroprevalences of hepatitis B, hepatitis A, and lues were 67.7%, 40.1%, and 4.0%, respectively. Seropositivity for HIV antibodies correlated with positive seromarkers for hepatitis B and A, and with certain behavioral and social features such as sharing of injection equipment, imprisonment, and intravenous drug use in prison. The crude time trend of HIV seroprevalence shows an increase from 17.1% in those subjects who discontinued i.v. drug abuse in 1983 or earlier to 31.5% in 1985, and a decrease over the past 3 years to 14.1% in 1988. After adjusting for temporary changes in the study group, the estimated HIV seroprevalence odds show an almost steady increase and were significantly higher for those who were injecting drugs in 1987 and 1988 compared with those who stopped i.v. drug use before 1984. Thus IVDA with a persistent risk profile are at a still-increasing risk of acquiring HIV infection.

Time trends of HIV-I antibody prevalence in homosexual men.

1840 homosexual and bisexual men were tested for human immunodeficiency virus type I (HIV) infection at the Landesinstitut für Tropenmedizin, Berlin between April 1983 and December 1987. A total of 25.1% were seropositive for HIV, but the percentage was seemingly declining. During the study period we observed also a steady decrease in the prevalence of lymphadenopathy syndrome (LAS), antibodies to hepatitis B and syphilis, and high-risk sexual behaviour in the study population. By adjusting for these changes of population characteristics we assessed the odds of HIV infection which had more than doubled between 1983 and 1986 (prevalence odds ratio 2.43, 95% confidence interval 1.58 to 3.76). In 1987 the HIV prevalence odds showed a drop which, however, was not significant (p = 0.34) when compared with the odds in 1986. Methodological aspects of time trend estimation based on data of voluntary HIV testing are discussed.