Glucose Derivative Induced Vasculopathy in Children on Chronic Peritoneal Dialysis.

[Figure: see text].

De novo inflammatory bowel disease in children after solid organ transplantation / Szolidszerv-transzplantáció után kialakuló de novo gyulladásos bélbetegség gyermekkorban.

Összefoglaló. A gyulladásos bélbetegség (inflammatory bowel disease, IBD) incidenciája folyamatosan no, etiológiája egyelore ismeretlen. Kezelésében gyakran alkalmazunk immunszuppresszív, illetve immunmoduláns szereket. Egyes esetekben azonban szolidszerv-transzplantációt követoen, folyamatos immunszuppresszív kezelés mellett is megfigyelheto de novo IBD kialakulása. Célunk az volt, hogy Klinikánk beteganyagából összesítsük azon eseteket, amelyekben szolid szerv (máj, vese, tüdo) transzplantációját követoen de novo IBD alakult ki. A transzplantációt megelozoen szklerotizáló cholangitis miatt gondozott betegeket kizártuk. A Klinikánkon gondozott, szolid szerv transzplantációján (179 máj, 197 vese, 29 tüdo) átesett betegek közül 4 (2 máj- és 2 vesetranszplantált) gyermeknél alakult ki de novo IBD. A transzplantációhoz vezeto alapbetegségek biliaris atresia, polycystás vese és Denys-Drash-szindróma voltak. A transzplantációt követo immunszuppresszív terápia mind a 4 esetben tartalmazott szisztémásszteroid- és takrolimuszkezelést, emellett 3 esetben mikofenolát-mofetil (MMF)-terápiát is. A kivizsgálást indikáló fobb tünetek a haematochesia, hasmenés, fáradékonyság és fogyás voltak. A családi anamnézis 1 esetben volt pozitív. A de novo IBD diagnózisának felállítását követoen mind a 4 betegnél az addigi immunszuppressziós terápia módosításra került. Összességében elmondható, hogy a szolidszerv-transzplantációt követo de novo IBD kialakulása ritka, etiológiája tisztázatlan. Az irodalom felveti az alkalmazott immunszuppresszív szerek (takrolimusz és MMF), illetve infekciók etiológiai szerepét, de az is felmerül, hogy a de novo IBD olyan önálló entitás, mely elkülönül a klasszikus IBD kategóriáitól. Klinikai szempontból fontos a tünetek hátterében álló betegség tisztázása, hiszen a prezentációs tüneteknek megfelelo, a differenciáldiagnosztika során felmerülo egyéb betegségek terápiája meroben eltér. A megfelelo terápia hozzájárulhat a transzplantált betegek morbiditásának és mortalitásának csökkentéséhez. Orv Hetil. 2021; 162(18): 720-726. Summary. The incidence of inflammatory bowel disease (IBD) is increasing, however, the aetiology is still unknown. The therapy consists of immunosuppressants and immunomodulators. In some cases, despite the continuous immunosuppressant therapy, de novo IBD develops. Our aim was to evaluate patients diagnosed with de novo IBD after solid organ (liver, kidney, or lung) transplantation. Patients treated with sclerosing cholangitis prior to liver transplantation were excluded. 4 patients (two kidney and two liver transplants) were diagnosed with de novo IBD. The underlying diseases leading to transplantation were biliary atresia, polycystic kidney, and Denys-Drash syndrome. All patients received systemic steroid and tacrolimus treatment, and 3 patients (2 kidney and 1 liver transplant) also received mycophenolate mofetil (MMF). The main symptoms indicative of de novo IBD were haematochezia, diarrhoea, fatigue, and weight loss. Family history for IBD was positive in 1 case. Following the diagnosis of IBD, immunosuppressive therapy was modified. Overall, the development of de novo IBD following solid organ transplantation is quite rare, and its aetiology is unknown. According to the literature, immunosuppressants (tacrolimus and MMF) and infections play a role in the pathomechanism, but it seems that de novo IBD is a separate entity from the classical IBD categories. From a clinical point of view, it is important to elucidate the underlying disease of the symptoms, as the treatment of other diseases that arise during differential diagnosis according to the presentation symptoms is very different. Appropriate therapy can help reduce morbidity and mortality in transplant patients. Orv Hetil. 2021; 162(18): 720-726.

Neutral pH and low-glucose degradation product dialysis fluids induce major early alterations of the peritoneal membrane in children on peritoneal dialysis.

The effect of peritoneal dialysates with low-glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low-glucose degradation products. Follow-up biopsies were obtained from 24 children after a median peritoneal dialysis of 13 months. Prior to dialysis, mild parietal peritoneal inflammation, epithelial-mesenchymal transition and vasculopathy were present. After up to six and 12 months of peritoneal dialysis, blood microvessel density was 110 and 93% higher, endothelial surface area per peritoneal volume 137 and 95% greater, and submesothelial thickness 23 and 58% greater, respectively. Subsequent peritoneal changes were less pronounced. Mesothelial cell coverage was lower and vasculopathy advanced, whereas lymphatic vessel density was unchanged. Morphological changes were accompanied by early fibroblast activation, leukocyte and macrophage infiltration, diffuse podoplanin presence, epithelial mesenchymal transdifferentiation, and by increased proangiogenic and profibrotic cytokine abundance. These transformative changes were confirmed by intraindividual comparisons. Peritoneal microvascular density correlated with peritoneal small-molecular transport function by uni- and multivariate analysis. Thus, in children on peritoneal dialysis neutral pH dialysates containing low-glucose degradation products induce early peritoneal inflammation, fibroblast activation, epithelial-mesenchymal transition and marked angiogenesis, which determines the PD membrane transport function.

Reduced Microvascular Density in Omental Biopsies of Children with Chronic Kidney Disease.

BACKGROUND: Endothelial dysfunction is an early manifestation of cardiovascular disease (CVD) and consistently observed in patients with chronic kidney disease (CKD). We hypothesized that CKD is associated with systemic damage to the microcirculation, preceding macrovascular pathology. To assess the degree of "uremic microangiopathy", we have measured microvascular density in biopsies of the omentum of children with CKD. PATIENTS AND METHODS: Omental tissue was collected from 32 healthy children (0-18 years) undergoing elective abdominal surgery and from 23 age-matched cases with stage 5 CKD at the time of catheter insertion for initiation of peritoneal dialysis. Biopsies were analyzed by independent observers using either a manual or an automated imaging system for the assessment of microvascular density. Quantitative immunohistochemistry was performed for markers of autophagy and apoptosis, and for the abundance of the angiogenesis-regulating proteins VEGF-A, VEGF-R2, Angpt1 and Angpt2. RESULTS: Microvascular density was significantly reduced in uremic children compared to healthy controls, both by manual imaging with a digital microscope (median surface area 0.61% vs. 0.95%, p<0.0021 and by automated quantification (total microvascular surface area 0.89% vs. 1.17% p = 0.01). Density measured by manual imaging was significantly associated with age, height, weight and body surface area in CKD patients and healthy controls. In multivariate analysis, age and serum creatinine level were the only independent, significant predictors of microvascular density (r2 = 0.73). There was no immunohistochemical evidence for apoptosis or autophagy. Quantitative staining showed similar expression levels of the angiogenesis regulators VEGF-A, VEGF-receptor 2 and Angpt1 (p = 0.11), but Angpt2 was significantly lower in CKD children (p = 0.01). CONCLUSIONS: Microvascular density is profoundly reduced in omental biopsies of children with stage 5 CKD and associated with diminished Angpt2 signaling. Microvascular rarefaction could be an early systemic manifestation of CKD-induced cardiovascular disease.

Comparison of Interscalene Brachial Plexus Block Performed With and Without Steroids.

This prospective comparative clinical study was performed to evaluate the effect of triamcinolone when added to bupivacaine during brachial plexus blockade in patients undergoing shoulder surgery. Interscalene brachial plexus blocks were performed on 910 patients before shoulder surgery. Of the patients, 574 were randomly allocated to receive steroids added to the injected local anesthetic and 336 patients received local anesthetic without steroids. All patients were followed prospectively to evaluate the rate of successful anesthesia, duration of anesthesia, side effects of the block, adverse events, and persistent neurologic complications associated with interscalene brachial plexus block. Patients who received steroids had statistically longer pain relief than those who did not receive steroids (P<.001). No difference was found in adverse events, complications, or side effects. Compared with blocks performed without steroids, a statistically longer duration of block analgesia occurred with the addition of steroids to the local anesthetic solution during brachial plexus blockade. Rates of side effects, adverse events, and persistent neurologic complications were similar between the groups. [Orthopedics. 2016; 39(6):e1100-e1103.].

Quantitative Histomorphometry of the Healthy Peritoneum.

The peritoneum plays an essential role in preventing abdominal frictions and adhesions and can be utilized as a dialysis membrane. Its physiological ultrastructure, however, has not yet been studied systematically. 106 standardized peritoneal and 69 omental specimens were obtained from 107 patients (0.1-60 years) undergoing surgery for disease not affecting the peritoneum for automated quantitative histomorphometry and immunohistochemistry. The mesothelial cell layer morphology and protein expression pattern is similar across all age groups. Infants below one year have a thinner submesothelium; inflammation, profibrotic activity and mesothelial cell translocation is largely absent in all age groups. Peritoneal blood capillaries, lymphatics and nerve fibers locate in three distinct submesothelial layers. Blood vessel density and endothelial surface area follow a U-shaped curve with highest values in infants below one year and lowest values in children aged 7-12 years. Lymphatic vessel density is much lower, and again highest in infants. Omental blood capillary density correlates with parietal peritoneal findings, whereas only few lymphatic vessels are present. The healthy peritoneum exhibits major thus far unknown particularities, pertaining to functionally relevant structures, and subject to substantial changes with age. The reference ranges established here provide a framework for future histomorphometric analyses and peritoneal transport modeling approaches.

Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort.

BACKGROUND AND OBJECTIVES: Steroid-resistant nephrotic syndrome is a rare kidney disease involving either immune-mediated or genetic alterations of podocyte structure and function. The rare nature, heterogeneity, and slow evolution of the disorder are major obstacles to systematic genotype-phenotype, intervention, and outcome studies, hampering the development of evidence-based diagnostic and therapeutic concepts. To overcome these limitations, the PodoNet Consortium has created an international registry for congenital nephrotic syndrome and childhood-onset steroid-resistant nephrotic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Since August of 2009, clinical, biochemical, genetic, and histopathologic information was collected both retrospectively and prospectively from 1655 patients with childhood-onset steroid-resistant nephrotic syndrome, congenital nephrotic syndrome, or persistent subnephrotic proteinuria of likely genetic origin at 67 centers in 21 countries through an online portal. RESULTS: Steroid-resistant nephrotic syndrome manifested in the first 5 years of life in 64% of the patients. Congenital nephrotic syndrome accounted for 6% of all patients. Extrarenal abnormalities were reported in 17% of patients. The most common histopathologic diagnoses were FSGS (56%), minimal change nephropathy (21%), and mesangioproliferative GN (12%). Mutation screening was performed in 1174 patients, and a genetic disease cause was identified in 23.6% of the screened patients. Among 14 genes with reported mutations, abnormalities in NPHS2 (n=138), WT1 (n=48), and NPHS1 (n=41) were most commonly identified. The proportion of patients with a genetic disease cause decreased with increasing manifestation age: from 66% in congenital nephrotic syndrome to 15%-16% in schoolchildren and adolescents. Among various intensified immunosuppressive therapy protocols, calcineurin inhibitors and rituximab yielded consistently high response rates, with 40%-45% of patients achieving complete remission. Confirmation of a genetic diagnosis but not the histopathologic disease type was strongly predictive of intensified immunosuppressive therapy responsiveness. Post-transplant disease recurrence was noted in 25.8% of patients without compared with 4.5% (n=4) of patients with a genetic diagnosis. CONCLUSIONS: The PodoNet cohort may serve as a source of reference for future clinical and genetic research in this rare but significant kidney disease.

A prospective analysis of interscalene brachial plexus blocks performed under general anesthesia.

BACKGROUND: The purpose of this prospective study was to assess the safety and efficacy of interscalene brachial plexus block anesthesia when performed on patients who were anesthetized with a general anesthetic prior to the performance of the block. METHODS: Patients were assessed postoperatively through surveys, interviews, and physical examinations to document block success, duration of anesthesia, block side effects, and persistent neurological complications. Nine-hundred fifty-one patients were available for the analysis. RESULTS: The overall block success rate was 97% and the mean duration of anesthesia provided by the blocks was 23.9 hours. Immediate postoperative block side effects occurred in 16% (142 of 910), persistent neurological complications occurred in 4.4% (40 of 910) of patients, and long-term neurologic complications occurred in 0.8% (8 of 910). CONCLUSION: Our study results suggest that the rates of success and complications associated with the performance of interscalene block regional anesthesia performed after induction of general anesthesia are similar to the results demonstrated in prior studies in which brachial plexus block was performed on nonanesthetized patients. Although significant complications were not common, this procedure is not without risk and can result in long-term neurologic complications.

Frequency of various tear patterns in full-thickness tears of the rotator cuff.

PURPOSE: We define specific rotator cuff tear patterns, prospectively document their occurrences, and emphasize the importance of tear pattern recognition during arthroscopy. METHODS: We prospectively analyzed 193 full-thickness rotator cuff tears intraoperatively from a single surgeon's practice. We address specific tear patterns, tear size, tissue mobility, tissue quality, and chronicity. RESULTS: Most of the tears were able to be categorized into 6 morphologic patterns. Of the tears, 3% could not be categorized. Appreciation of various rotator cuff tear patterns guided the positioning of bone and tissue sutures to achieve accurate apposition of tendon fibers. Transverse tears were the smallest and most common tear pattern, whereas tongue-shaped and U-shaped tears were larger patterns of comparable size. U-shaped tears had more retraction and less mobility and were of poorer tissue quality. Transverse tears were easily repaired, whereas U-shaped tears could not be repaired in 38% of cases (5/13). CONCLUSIONS: The quality and mobility of rotator cuff tissue were correlated with tear pattern, size, retraction, and chronicity. We describe a comprehensive rotator cuff tear classification scheme that encompasses 97% of all tears. Tear type was correlated with tendon retraction, tear size, cuff mobility, and tissue quality. On the basis of this information, the surgeon can anticipate tear patterns, which may improve pattern recognition and facilitate anatomic repair. LEVEL OF EVIDENCE: Level IV, prognostic case series.

Urinary excretion of endothelin-1 (ET-1), transforming growth factor- beta1 (TGF- beta1) and vascular endothelial growth factor (VEGF165) in paediatric chronic kidney diseases: results of the ESCAPE trial.

UNLABELLED: The severity and dynamics of renal tissue damage in chronic kidney disease (CKD) may be reflected by the urinary excretion of vasoactive and growth factors released by the damaged kidney. Urinary excretion of ET-1, TGF-beta1 and VEGF(165) was evaluated in 303 children with CKD stage II-IV (GFR 48 +/- 22 ml/min/1.73 m(2)) and 81 age-matched healthy controls. Major renal disease groups were hypo-/dysplastic kidney disease (N = 183), obstructive uropathies (N = 47), glomerulopathies (N = 34), nephronophthisis (N = 19) and polycystic kidney disease (N = 20). RESULTS: The mean urinary excretion rates of each of the three putative biomarkers were significantly elevated in CKD patients compared to controls: 965 +/- 2042 vs 216 +/- 335 fmol/g creatinine for ET-1; 252 +/- 338 vs 155 +/- 158 ng/g for VEGF; 31.6 +/- 37.0 vs 10.9 +/- 9.8 ng/g for TGF-beta1 (each P < 0.0001). The excretion of ET-1 and TGF-beta1 was highest in patients with obstructive uropathies. In the patients, ET-1, TGF-beta1 and VEGF excretion rates were inversely correlated with age (r = -0.22, -0.32 and -0.17, all P < 0.005) and renal function (r = -0.21, -0.13 and -0.15; P < 0.001; < 0.05; < 0.01; respectively) VEGF and TGF-beta1 excretion rates were positively correlated both in patients and controls. CONCLUSIONS: Children with CKD exhibit significantly elevated urinary excretion of ET-1, TGF-beta1 and VEGF(165) in comparison to healthy children. Urinary excretion of these biomarkers was most enhanced in patients with obstructive uropathies. A positive correlation between urinary TGF-beta1 and VEGF(165) excretion, shown both in patients and healthy controls, indicates an interdependent nature of their generation.

A longitudinal study of patients with multidirectional instability of the shoulder with seven- to ten-year follow-up.

The purpose of our study was to evaluate the long-term outcomes of patients with multidirectional instability of the shoulder initially treated with rehabilitation exercises. Sixty-four patients were treated for atraumatic multidirectional instability of the shoulder between 1987 and 1990. Preliminary evaluation was performed 2 years after initiation of treatment, and final evaluation of the patients was performed at a mean of 8 years after initiation of treatment. At the preliminary evaluation, 5 patients were lost to follow-up. Of the remaining 59 patients, 20 had undergone surgical treatment for stabilization of their shoulder. Of the 39 nonsurgically treated patients, 19 continued to have significant pain, and 18 continued to have significant instability of their shoulder. Of the 59 patients, 28 subjectively rated their shoulder condition as better or much better after conservative treatment. At the final evaluation, 2 more patients were lost to follow-up, and 1 additional patient had had surgical treatment. Thus, of the 57 patients available for final follow-up, 36 had received nonsurgical care, and 21 had undergone surgical treatment. Of the 36 nonsurgically treated patients, 23 rated their shoulders as good or excellent with regard to pain, and 17 were good or excellent with regard to instability. By the modified Rowe grading scale, 5 of 36 patients had excellent results, and 12 had good results. The remaining 19 patients were rated as having poor results. Only 8 patients reported that their shoulders were free of all pain and instability. Overall, of the entire group of 57 patients evaluated between 7 and 10 years after initiation of care, 17 had a satisfactory outcome from nonsurgical management based on stability and Rowe scores, 23 had good or excellent results with regard to pain, and 20 subjectively rated their shoulders as good or excellent. This review revealed a relatively poor response to nonsurgical treatment of multidirectional instability in this population of young, athletic patients.

Measurement of baseline shoulder function in subjects receiving workers' compensation versus noncompensated subjects.

The purpose of this study was to ascertain whether a measurable difference existed in normative scores for the American Shoulder and Elbow Surgeons (ASES) questionnaire between subjects who had an active workers' compensation claim (WC) with no known shoulder injury and subjects without a compensation claim (non-WC). Subjects with non-shoulder-related orthopaedic injuries were recruited from a suburban orthopaedic sports medicine clinic and an urban occupational medicine clinic. They were asked to complete a composite questionnaire that consisted of demographic information and the ASES questionnaire. There were no significant differences in the ASES scores between subject groups. There were significant differences between subject groups with regard to work hours (P = .0001), work demands (P = .0001), and tobacco use (P = .0001). Subject group was also significantly associated with education level (P = .0001), marital status (P = .0001), work demands (P = .0001), gender (P = .0001), and sports participation (P = .0314). The ASES score was significantly affected by marital status (P = .0476), sports participation (P = .0008), and age (P = .0129).

The measurement of normative American Shoulder and Elbow Surgeons scores.

We determined baseline scores on the American Shoulder and Elbow Surgeons (ASES) questionnaire in individuals who had no known shoulder condition and evaluated related factors that could influence the score. A modified version of the questionnaire was completed by 343 patients from an outpatient orthopaedic center being seen for conditions unrelated to the shoulder. A separate group completed the questionnaire at two different times to assess its reliability. The mean ASES score was 92.2 +/- 14.5 points. The instrument was found to be very reliable (intraclass correlation coefficient = 0.96). Only the variables of shoulder status and sports participation entered the regression model to explain the variance in scores. Subjects aged 60 years or older exhibited decreased ability to lift above shoulder level and reach behind the back when compared with younger cohorts. Previous investigators have made the assumption that a normal preinjury ASES score is 100 points. This study raises questions about this assumption. This information can serve as a basis to compare normative scores with those of patients with active shoulder disease.

Surgical repair of complete proximal hamstring tendon rupture.

BACKGROUND: Complete proximal hamstring tendon rupture is a rare injury associated with significant functional loss. Nonoperative treatment has proven inadequate in returning patients to their previous activity level. PURPOSE: We wanted to describe the outcome of primary surgical repair of the proximal hamstring tendon avulsion. STUDY DESIGN: Retrospective cohort study. METHODS: Between 1994 and 1999, 11 patients (4 women and 7 men) with an average age of 41.5 years (range, 21 to 51) had a diagnosis of complete proximal hamstring tendon rupture based on mechanism of injury, physical examination, and radiographic assessment. All underwent a single operation followed by standard postoperative physical therapy. At the latest follow-up (average, 34 months), patients completed a questionnaire regarding such outcome parameters as pain, function, leg control, stiffness, return to activity, and overall satisfaction. RESULTS: Isokinetic muscle testing revealed an overall average of 91%return of hamstring muscle strength. Ten of 11 patients were satisfied with the result, and 7 of 9 athletically active patients were able to return to sport an average of 6 months (range, 3 to 10) after surgery. No difference between early and late repairs was identified in regard to functional outcome or return to sport. CONCLUSIONS: Satisfactory results can be achieved with both early and late hamstring tendon repairs in a majority of cases with surgical repair.