Hypercalcemia in Pregnancy Due to CYP24A1 Mutations: Case Report and Review of the Literature

Pathogenic mutations of CYP24A1 lead to an impaired catabolism of vitamin D metabolites and should be considered in the differential diagnosis of hypercalcemia with low parathyroid hormone concentrations. Diagnosis is based on a reduced 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D ratio and confirmed by genetic analyses. Pregnancy is associated with an upregulation of the active vitamin D hormone calcitriol and may thus particularly trigger hypercalcemia in affected patients. We present a case report and a narrative review of pregnant women with CYP24A1 mutations (13 women with 29 pregnancies) outlining the laboratory and clinical characteristics during pregnancy and postpartum and the applied treatment approaches. In general, pregnancy triggered hypercalcemia in the affected women and obstetric complications were frequently reported. Conclusions on drugs to treat hypercalcemia during pregnancy are extremely limited and do not show clear evidence of efficacy. Strictly avoiding vitamin D supplementation seems to be effective in preventing or reducing the degree of hypercalcemia. Our case of a 24-year-old woman who presented with hypercalcemia in the 24th gestational week delivered a healthy baby and hypercalcemia resolved while breastfeeding. Pathogenic mutations of CYP24A1 mutations are rare but should be considered in the context of vitamin D supplementation during pregnancy.     

Gallic Acid-Functionalized,TiO2-Based Nanomaterial—Preparation,Physicochemical and Biological Properties

Wound healing and skin tissue regeneration remain the most critical challenges faced by medical professionals. Titanium(IV) oxide-based materials were proposed as components of pharmaceutical formulations for the treatment of difficult-to-heal wounds and unsightly scarring. A gallic acid-functionalized TiO₂ nanomaterial (TiO₂-GA) was obtained using the self-assembly technique and characterized using the following methods: scanning electron microscopy (SEM), transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), X-ray powder diffraction (XRPD), infrared spectroscopy (IR), Raman spectroscopy and thermogravimetry (TG). Additionally, physicochemical and biological tests (DPPH assay, Microtox^® acute toxicity test, MTT assay) were performed to assess antioxidant properties as well as to determine the cytotoxicity of the novel material against eukaryotic (MRC-5 pd19 fibroblasts) and prokaryotic (Staphylococcus aureus, Escherichia coli, Candida albicans, Aliivibrio fischeri) cells. To determine the photocytotoxicity of the material, specific tests were carried out with and without exposure to visible light lamps (425 nm). Following the results, the TiO₂-GA material could be considered an additive to dressings and rinsing suspensions for the treatment of difficult-to-heal wounds that are at risk of bacterial infections.     

Treatment of Vitamin D Deficiency with Calcifediol: Efficacy and Safety Profile and Predictability of Efficacy

Calcifediol (25-OH-vitamin D3) is the prohormone of the vitamin D endocrine system. It is used to prevent and treat vitamin D deficiency. Calcifediol, as well as cholecalciferol (vitamin D3), is efficient and safe in the general population, although calcifediol has certain advantages over cholecalciferol, such as its rapid onset of action and greater potency. This review analyzed studies comparing the efficacy and safety of both calcifediol and cholecalciferol drugs in the short and long term (>6 months). Calcifediol was found to be more efficacious, with no increase in toxicity. We also assessed the predictability of both molecules. A 25OHD increase depends on the dose and frequency of calcifediol administration. In contrast, after cholecalciferol administration, 25OHD increase depends on more factors than dose and frequency of administration, also phenotypic aspects (such as obesity and malabsorption), and genotypic factors impacts in this increase.     

Post-stenting intravascular brachytherapy trials on hypercholesterolemic rabbits using 32P liquid sources: implications for prevention of in-stent restenosis

PURPOSE: Liquid sources of radiation delivered in angioplasty balloons may be a convenient self-centering device used for prevention of in-stent restenosis. To test the effectiveness of this method an intravascular brachytherapy study was performed using 32P liquid sources in an animal model. METHODS: The radial dose distribution around angioplasty balloons filled with solutions of Na 2H 32PO 4 was calibrated by thermoluminescence dosimetry. The animal experiments were performed in rabbits with induced hypercholesterolemia. The balloons containing 32P were introduced into iliac arteries immediately after stent implantation. Estimated 7-49 Gy doses required 30-100 min irradiations. Radiation effects were evaluated by comparing the thickness of various components of the artery wall. RESULTS: Doses of 7, 12, 16 or 49 Gy on the internal artery surface required 30-100 min of irradiation. The dose of 49 Gy at "zero" distance corresponding to 16 Gy at 1.0 mm from the balloon surface reduced hypertrophy in every layer of the arterial wall: in the intima the cross-sectional areas were 0.13 versus 0.91 mm 2, in the media were 0.5 versus 0.46 mm 2 and in the adventitia were 0.04 versus 0.3 mm 2 (p <0.05). A dose of 7 Gy at the balloon surface produced adverse irradiation effects: the intimal area of the artery was 2.087 versus 0.857 mm 2, the medial area was 0.59 versus 0.282 mm 2 and the adventitial area was 0.033 versus 0.209 mm 2 in treated and control arteries, respectively. CONCLUSION: Application of a 49 Gy irradiation dose to the internal arterial surface effectively prevented in-stent restenosis.     

Claudin-6 is a nonspecific marker for malignant rhabdoid and other pediatric tumors

Claudins are tight junction proteins with claudin-6 (CLDN6) expression mostly restricted to embryonic and fetal life. Previously reported gene expression microarray analysis showed an increased level of CLDN6 in atypical teratoid rhabdoid tumors (AT/RT) compared with other central nervous system (CNS) tumors and sarcomas. However, there exist conflicting data on expression of CLDN6 as assessed by immunohistochemistry in CNS tumors. We established membranous staining as a specific and reproducible method for evaluating CLDN6 expression based on fetal and adolescent controls. We then evaluated a large group (257) of pediatric tumors using tissue microarrays, including: 47 malignant rhabdoid tumors (MRTs), (31 AT/RTs and 16 non-CNS MRTs); 67 small, round, blue cell tumors (10 Wilms tumors, 10 embryonal rhabdomyosarcomas, 10 neuroblastomas (NBs), 10 synovial sarcomas (SSs), 9 hepatoblastomas (HBs), 9 alveolar rhabdomyosarcomas, and 9 Ewings sarcomas); and 143 CNS tumors (24 medulloblastomas, 21 pilocytic astrocytomas, 14 astrocytomas grade II/III, 13 gangliogliomas, 12 glioblastomas, 12 ependymal tumors, 11 choroid plexus tumors, 10 meningiomas, 8 dysembryoplastic neuroepithelial tumors, 8 oligodendrogliomas, 4 craniopharyngiomas, 2 germinomas, 2 primitive neuroectodermal tumors (PNET), and 2 central neurocytomas). CLDN6 expression was seen in 12 of 31 (39%) AT/RTs, 7 of 16 (44%) non-CNS MRTs, 5 of 10 (50%) Wilms tumors, 1 of 9 (11%) HBs, 2 of 2 (100%) germinomas, 1 of 2 (50%) CNS PNETs, 1 of 24 (4%) medulloblastomas, and 1 of 10 (10%) meningiomas. Ten of 11 (91%) choroid plexus tumors showed apical staining but no concentric membranous staining. Although CLDN6 is expressed in both AT/RTs and MRTs, it is not a specific biomarker as it is expressed in a variety of other pediatric CNS and soft tissue tumors.     

The characteristics of fractures in Polish adolescents aged 16–20 years

The aim of the study was to identify associations between fractures in childhood and family, anthropometric and lifestyle factors. Among 1,246 subjects aged 16.3–20.6 years (539 boys, 707 girls), based on a questionnaire, 869 were fracture-free while 377 (30.26%) had fractures. Of those reporting fractures, 146 reported multiple fractures (12% of studied population, 39% of all fractures). More boys had fractures than girls (35.6% vs 24.9%, p < 0.001). Fracture sites included: forearm (37%), fingers (23%) wrist (16%), ankle (14%), humerus (10%), tibia (8%) clavicle (7%) and femoral shaft / neck (3%). Among adolescents with multiple fractures, 52% also reported fractures in at least one family member, compared with 29% of those without a fracture history. Fractures in siblings and mothers (but not fathers) accounted for 44% of the liability in adolescents fractures. Subjects with multiple fractures reported more time at the computer than those without fractures and reported more time participating in team sports, and 18.6% avoided milk, whereas 12.4% of those without fractures reported milk-free diets. Using a logistic regression model, none of the lifestyle factors, except for computer use, were independently associated with fractures. Fractures, particularly multiple fractures, are common in childhood and adolescence. Familial clustering of fractures suggests shared genetic and environmental factors are responsible.     

Role of pelvic drain and timing of urethral catheter removal following RARP: a systematic review and meta-analysis

Objectives

To assess the clinical value of routine pelvic drain (PD) placement and early removal of urethral catheter (UC) in patients undergoing robot-assisted radical prostatectomy (RARP), as perioperative management such as the necessity of PD or optimal timing for UC removal remains highly variable.

Methods

Multiple databases were searched for articles published before March 2022 according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Studies were deemed eligible if they investigated the differential rate of postoperative complications between patients with/without routine PD placement and with/without early UC removal, defined as UC removal at 2–4 days after RARP.

Results

Overall, eight studies comprising 5112 patients were eligible for the analysis of PD placement, and six studies comprising 2598 patients were eligible for the analysis of UC removal. There were no differences in the rate of any complications (pooled odds ratio [OR] 0.89, 95% confidence interval [CI] 0.78–1.00), severe complications (Clavien–Dindo Grade ≥III; pooled OR 0.95, 95% CI 0.54–1.69), all and/or symptomatic lymphocele (pooled OR 0.82, 95% CI 0.50–1.33; and pooled OR 0.58, 95% CI 0.26–1.29, respectively) between patients with or without routine PD placement. Furthermore, avoiding PD placement decreased the rate of postoperative ileus (pooled OR 0.70, 95% CI 0.51–0.91). Early removal of UC resulted in an increased likelihood of urinary retention (OR 6.21, 95% CI 3.54–10.9) in retrospective, but not in prospective studies. There were no differences in anastomosis leakage and early continence rates between patients with or those without early removal of UC.

Conclusions

There is no benefit for routine PD placement after standard RARP in the published articles. Early removal of UC seems possible with the caveat of the increased risk of urinary retention, while the effect on medium-term continence is still unclear. These data may help guide the standardisation of postoperative procedures by avoiding unnecessary interventions, thereby reducing potential complications and associated costs.     

Evidence for the involvement of endothelial nitric oxide synthase from smooth muscle cells in the erectile function of the human corpus cavernosum

Nitric oxide (NO) is an important mediator in the relaxation of cavernosal smooth muscle. The present study examines the existence and location of the constitutive isoform eNOS (endothelial NO synthase) accompanying the already substantiated neurogenic NOS (nNOS) in the human corpus cavernosum of men with and without erectile dysfunction. Activities of NOS enzymes were examined in specimens of 11 potent and nine long-term impotent patients by means of light and electron microscopy using NADPH-diaphorase staining and immunohistochemical eNOS-specific, smooth muscle actin-specific and nNOS-specific markers. Cavernosal smooth muscle shows a distinct expression of eNOS. In contrast to the weaker expression of eNOS and nitrinergic innervation found in larger veins, the small intracavernosal helicine arteries express large quantities of eNOS and possess a dense nitrinergic innervation. Long-term impotent patients display a broad heterogeneity in eNOS expression and nitrinergic innervation while no overall correlation between NOS expression and erectile function was observed. The expression of eNOS indicates eNOS as a main source of NO alongside nNOS. The differentiated localization of eNOS supports at least a role of this isoform in vascular regulation. Received: 21 April 1997 / Accepted 11 November 1997