Effects of SLC34A3 or SLC34A1 variants on calcium and phosphorus homeostasis.

BACKGROUND: Variants in SLC34A1 and SLC34A2 genes, which encode co-transporters NaPi2a and NaPi2c, respectively, can lead to hypophosphatemia due to renal phosphate loss. This condition results in hypercalcitriolemia and hypercalciuria, leading to formation of kidney stones and nephrocalcinosis. Phenotype is highly variable. Management includes hyperhydration, dietary modifications, and/or phosphate supplementation. Thiazides and azoles may be used, but randomized studies are needed to confirm their clinical efficacy. METHODS: We conducted a retrospective study in the pediatric nephrology unit at Grenoble University Hospital from January 2010 to December 2023. The study aimed to describe clinical and biological symptoms of patients with confirmed SLC34A1 and SLC34A3 gene variants and their outcomes. RESULTS: A total of 11 patients (9 females) from 6 different families had variants in the SLC34A1 (5 patients) and SLC34A3 (6 patients) genes. Median age at diagnosis was 72 [1-108] months. Average follow-up duration was 8.1 ± 4.5 years. Presenting symptom was nephrocalcinosis (4 cases), followed by renal colic (3 cases). At diagnosis, 90% of patients had hypercalciuria and 45% had hypercalcitriolemia. Management included hyperhydration and dietary advice. All patients showed favorable outcomes with normal growth and school attendance. One patient with an SLC34A3 variant showed regression of nephrocalcinosis. Kidney function remained normal. CONCLUSION: Clinical and biological manifestations of SLC34 gene variants are highly variable, even among siblings; therefore, management must be personalized. Hygienic and dietary measures (such as hyperhydration, a low sodium diet, and age-appropriate calcium intake) result in favorable outcomes in most cases. Use of azoles (e.g., fluconazole) appears to be a promising therapeutic option.

Smile dynamics: A comparative study of Fijians and NZ Europeans.

BACKGROUND: The Fijian 'Bula Smile' is often described as the world's friendliest; however, its description remains anecdotal. OBJECTIVE: This study aimed to describe and compare the dynamics of Fijians' smiles with those of New Zealand Europeans. METHODS: An observational study was conducted on two ethnic groups, Fijians (FJ; N = 23) and New Zealand Europeans (NZ; N = 23), age- and gender-matched. All participants were asked to watch amusing videos, and their reactions were video recorded. The videos were analysed by software to assess the frequency, duration, intensity and genuineness of smiling episodes. Based on the Facial Action Coding System, Action Unit 6 (AU6-cheek raiser), Action Unit 12 (AU12-lip corner puller) and Action Unit 25 (AU25-lips apart) were assessed. Data were analysed by generalised linear models after adjusting for personality traits. RESULTS: Fijians smiled longer than New Zealand Europeans (+19.9%; p = .027). Mean intensity of AU6 (+1.0; 95%CIs = 0.6-1.5; p < .001), AU12 (+0.5; 95%CIs = 0.1-0.9; p = .008) and AU25 (+22.3%; 95%CIs = 7.3%-37.3%; p = .005) were significantly higher in FJ group than the NZ group. CONCLUSION: Smiling features of Fijians and New Zealanders showed objective differences, the most distinctive being a higher activation of the Duchenne's marker (AU6) in the Fijian group, which is regarded as a sign of smile genuineness.

The effect of passive clear aligners on masticatory muscle activity in adults with different levels of oral parafunction.

BACKGROUND: There is limited knowledge of the possible side-effects of clear aligners on jaw function. OBJECTIVES: To determine the short-term effect of passive clear aligners (PCAs) on masticatory muscle activity (MMA), occlusal discomfort (OD) and temporomandibular disorder (TMD) symptoms in adults with different levels of self-reported oral parafunction. MATERIALS AND METHODS: Participants were screened for oral parafunctional behaviours using the oral behavioural checklist. Respondents in ≥85th and ≤15th percentiles were invited to participate and allocated to a high (HPF: N = 15) or low (lower parafunction [LPF]: N = 16) parafunction group. Participants underwent a TMD clinical examination; somatisation and somatosensory amplification were assessed by questionnaires; OD and stress were assessed by visual analogue scales. While wearing PCAs, awake-time MMA was assessed three times over 9 days using a wearable electromyography device, along with OD, stress and TMD symptoms. RESULTS: The wearing of PCAs was associated with a significant decrease in mean contraction episode amplitude in both groups (p = 0.003). OD levels increased and remained raised in all participants after insertion of the PCAs (p < 0.001), more so in the HPF group (p = 0.048). The HPF group had higher somatisation scores (p = 0.006) and reported more TMD symptoms at all time points (p ≤ 0.004). No significant changes in stress or TMD symptoms were found in either group during the study period. CONCLUSIONS: PCAs were associated with a decrease in MMA in all participants. HPF individuals had greater somatisation and reported greater discomfort when wearing PCAs than LPF individuals.

Malocclusion severity and smile features: Is there an association?

INTRODUCTION: This observational study investigated the relationship between malocclusion and smiling. METHODS: Adolescents and young adults (n = 72; aged 16-25 years) were identified according to their Dental Aesthetic Index (DAI) and allocated to 3 groups: (1) malocclusion group (n = 24; DAI ≥31), (2) retention group (n = 24; pretreatment DAI ≥31) with a prior malocclusion that had been corrected by orthodontic treatment, (3) control group with no-to-minor malocclusion (n = 24; DAI ≤25). Participants were requested to watch an amusing video. Based on the Facial Action Coding System, automated pattern recognition was used to detect smile episodes and assess their frequency, duration, genuineness, intensity, and extent of tooth show. Demographics, Big Five personality dimensions, and self-perceived smile esthetics-related quality of life were collected from all participants via questionnaires. Data were analyzed by mixed-model analysis and adjusted for possible confounders. RESULTS: Patients from the malocclusion and retention groups smiled significantly less than participants from the control group, with the duration of smiles and smiling time being around half those of control subjects. Smile genuineness, smile intensity, and teeth shown did not differ across groups. Personality traits did not differ significantly among the 3 groups, whereas the malocclusion group scored around 30% less for dental self-confidence than the other 2 groups. CONCLUSIONS: Patients with severe malocclusion tend to smile less, but the features of their smiles are similar to those without malocclusion. A lower propensity to smile in patients with a corrected malocclusion may persist after orthodontic treatment.

Immune responses following tocilizumab therapy to desensitize HLA-sensitized kidney transplant candidates.

Kidney transplant candidates (KTCs) who are HLA highly sensitized (calculated panel-reactive alloantibodies >95%) have poor access to deceased kidney transplantation. In this single-center prospective study, 13 highly sensitized desensitization-naïve KTCs received IV tocilizumab (8 mg/kg) every 4 weeks. We evaluated tolerability as well as immune responses, that is, T cell, B cell, T follicular helper (Tfh) subsets, blood cytokines (IL-6, soluble IL-6 receptor-sIL-6R-, IL-21), blood chemokines (CXCL10, CXCL13), and anti-HLA alloantibodies. Tocilizumab treatment was well-tolerated except in one patient who presented spondylodiscitis, raising a note of caution. Regarding immune parameters, there were no significant changes of percentages of lymphocyte subsets, that is, CD3+ , CD3+ /CD4+ , CD3+ /CD8+ T cells, and NK cells. This was also the case for Tfh cell subsets, B cells, mature B cells, plasma cells, pre-germinal center (GC) B cells, and post-GC B cells, whereas we observed a significant increase in naïve B cells (p = .02) and a significant decrease in plasmablasts (p = .046) over the tocilizumab treatment course. CXCL10, CXCL13, IL-21, total IgG, IgA, and IgM levels did not significantly change during tocilizumab therapy; conversely, there was a significant increase in IL-6 levels (p = .03) and a huge increase in sIL-6R (p = .00004). There was a marginal effect on anti-HLA alloantibodies (class I and class II). To conclude in highly sensitized KTCs, tocilizumab as a monotherapy limited B cell maturation; however, it had almost no effect on anti-HLA alloantibodies.

Automated detection of smiles as discrete episodes.

BACKGROUND: Patients seeking restorative and orthodontic treatment expect an improvement in their smiles and oral health-related quality of life. Nonetheless, the qualitative and quantitative characteristics of dynamic smiles are yet to be understood. OBJECTIVE: To develop, validate, and introduce open-access software for automated analysis of smiles in terms of their frequency, genuineness, duration, and intensity. MATERIALS AND METHODS: A software script was developed using the Facial Action Coding System (FACS) and artificial intelligence to assess activations of (1) cheek raiser, a marker of smile genuineness; (2) lip corner puller, a marker of smile intensity; and (3) perioral lip muscles, a marker of lips apart. Thirty study participants were asked to view a series of amusing videos. A full-face video was recorded using a webcam. The onset and cessation of smile episodes were identified by two examiners trained with FACS coding. A Receiver Operating Characteristic (ROC) curve was then used to assess detection accuracy and optimise thresholding. The videos of participants were then analysed off-line to automatedly assess the features of smiles. RESULTS: The area under the ROC curve for smile detection was 0.94, with a sensitivity of 82.9% and a specificity of 89.7%. The software correctly identified 90.0% of smile episodes. While watching the amusing videos, study participants smiled 1.6 (±0.8) times per minute. CONCLUSIONS: Features of smiles such as frequency, duration, genuineness, and intensity can be automatedly assessed with an acceptable level of accuracy. The software can be used to investigate the impact of oral conditions and their rehabilitation on smiles.

Fibrinogen reconstitution after therapeutic apheresis: Comparison of double-filtration plasmapheresis, plasma exchange, and immunoadsorption.

BACKGROUND: Fibrinogen reconstitution after therapeutic apheresis has been poorly studied. Apheresis modalities, for example, plasma exchange (PE), double-filtration plasmapheresis (DFPP), or selective immunoadsorption (IA), may have different impacts. METHODS: We retrospectively investigated therapeutic apheresis sessions performed at our center across four modalities (PE, DFPP, and IA with or without plasma filtration). Fibrinogen levels were assessed at the beginning and end of each apheresis session, and immediately before the subsequent session. We adjusted measurements on hematocrit values to account for hemoconcentration. RESULTS: Between January 10, 2016 and March 2, 2020, we included 90 patients for a total of 754 apheresis sessions (PE: 35; DFPP: 351; IA only: 109; IA + plasma filtration: 259). Each patient received a median of five sessions (1Q 3; 3Q 9); median plasma volume treated was 5.5 L (1Q 4.3 L; 3Q 7.0 L). Within a session, DFPP and PE induced a significantly greater depletion of fibrinogen than both IA modalities, even after adjustment for the treated plasma volume. Median fibrinogen reconstitution was 0.8 (0.4-1.2) g/L (median time between sessions: 38 hours). In multivariate analysis, fibrinogen reconstitution was significantly associated with intersession time (+0.66 g/L/log-hour P < .001), apheresis modality (ANOVA; P < .001), initial fibrinogen concentration (+0.15 g/L per gram of fibrinogen; P < .001), and the last fibrinogen concentration from the previous apheresis session (-0.14 g/L per gram of fibrinogen; P < .001). In a model that considered hemoconcentration, the results were unchanged. CONCLUSIONS: We demonstrate that fibrinogen reconstitution was highly variable between patients and apheresis sessions. Apheresis modalities had a significant impact on fibrinogen reconstitution, regardless of hemoconcentration.

How to improve clotting factors depletion in double-filtration plasmapheresis.

BACKGROUND: Double-filtration plasmapheresis (DFPP), a selective therapeutic apheresis, can deplete pathogenic antibodies/substances, but also important coagulation factors. AIM: To determine if the use of a separator filter with different characteristics (CascadefloEC-50 W) as compared to the reference filter (PlasmafloOP-08 W) is as efficient in terms of immunoglobulin loss, but can reduce coagulation factor losses and have similar tolerability. PATIENTS/METHODS: This is a single-center prospective study including 14 patients divided into two groups (7 each): that is, group1 = CascadefloEC-50 W and group2 = PlasmafloOP-08 W. We measured immunoglobulins, lipid profiles, blood-cell counts, hemostasis (prothrombin time, activated partial thromboplastin time), coagulation factors, and natural anticoagulants at before and after the first DFPP-session. RESULTS: In group 1, the loss of coagulation factors was significantly reduced as compared to group 2 for proteins with a molecular weight of >150 kDa: there was, respectively, an average decrease of 70% vs 31% for fibrinogen (P = 0.004), 66% vs 21% for factor V (P = 2.16e-07), 60% vs 32% for factor XI (P = 6.96e-06), 75% vs 17% for XIII-antigen (P = 0.0002), and 47% vs 0% for VWF-antigen(P = 0.02). The decrease in post-session IgG was, on average, 45% in group 1 and 50% in group 2 (P = 0.13). Those results remained significant even when adjusted to the treated-plasma volume and the pre-DFPP factor values. CONCLUSION: DFPP, using a CascadefloEC-50W as a first-filter, reduces efficiently IgGs similarly to PlasmafloOP-08W but spares clotting factors.

Treatment of refractory myasthenia gravis by double-filtration plasmapheresis and rituximab: A case series of nine patients and literature review.

INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disease mediated by circulating autoantibodies (anti-AchR, anti-MuSK, etc.). More than 20% of myasthenic patients are refractory to conventional treatments (plasma exchange, IVIg, steroids, azathioprine, mycophenolate mofetil). Rituximab (B-lymphocyte-depleting anti-CD20) and apheresis (double-filtration plasmapheresis [DFPP] and immunoadsorption [IA]) are interesting therapeutic alternatives. METHODS: This monocentric pilot study included nine refractory myasthenic patients (March 2018 to May 2020) treated by DFPP and/or IA associated with rituximab (375 mg/m2 ). Clinical responses were assessed using the Myasthenia Gravis Foundation of America (MGFA) score. RESULTS: Average age of patients was 53 ± 17 years. Gender ratio (M/F) was 3:6. The combination of apheresis and rituximab reduced median MGFA score from IV to II after 12 months of follow-up. Clinical improvement assessed by MGFA score was sustained in the long-term for all patients, during an average follow-up of 14 ± 9 months, allowing them to be self-sufficient and out sick-leave. The median number of apheresis sessions was 7 (5-30). The dose of prednisolone was reduced in two patients from 40 mg/d and 30 mg/d to 7.5 mg/d and 10 mg/d, respectively. It was stopped in a patient who was taking 30 mg/d. No infectious, bleeding, or thrombosis complications were noted. CONCLUSION: The combination of rituximab and DFPP was effective to treat refractory MG.

Comparison of three modalities of plasmapheresis on coagulation: Centrifugal, single-membrane filtration, and double-filtration plasmapheresis.

BACKGROUND: Plasmapheresis can deplete pathogenic antibodies and allow ABO- and/or HLA-incompatible transplantation. AIM: To determine the impacts of three modalities of plasmapheresis (centrifugal plasmapheresis [cTPE], single-filtration plasmapheresis [mTPE], double-filtration plasmapheresis [DFPP]) on hemostasis parameters and thrombin generation. MATERIALS/METHODS: Prospective, comparative study on 21 patients that received three modalities of plasmapheresis (7 patients/group). Hemostasis (prothrombin time [PT], activated partial thromboplastin time [aPTT], procoagulant factors and natural anticoagulants) were measured before and after the first plasmapheresis session. Thrombin generation was also assessed in platelet-poor plasma using an STA-Genesia (Stago) analyzer and Thromboscreen reagents (Stago) in 4-5 patients from each group. RESULTS: Both cTPE and mTPE resulted in high decreases in proteins, whatever their molecular weights. Median post/pre ratios were 0.27 to 0.55 for cTPE for most proteins (except FVIII [0.64] and VWF [0.57]). Median post/pre-ratios of mTPE were 0.28 to 0.56 for all proteins. DFPP decreased high-molecular-weight proteins (fibrinogen, FV, FVIII, FXI, VWF) and proteins strongly bound to large molecules (protein SandTFPI). Median post/pre ratios with cTPE and mTPE were similar to DFPP for fibrinogen and FXIII. Regarding thrombin generation, cTPE and mTPE did not significantly modify endogenous thrombin potential (ETP) and DFPP induced a slight decrease in ETP (median post/pre ratio at 0.73) in the absence of thrombomodulin. ETP inhibition by thrombomodulin was decreased for all procedures. CONCLUSIONS: DFPP depleted high molecular-weight proteins in contrast to cTPE and mTPE, which significantly decreased all proteins. Regarding thrombin generation, depletion of procoagulant factors was counterbalanced by a decrease in some natural anticoagulants whatever plasmapheresis method used; with all methods, fibrinogen and FXIII were highly depleted.

Treatment of antibody-mediated rejection with double-filtration plasmapheresis, low dose IVIg plus rituximab after kidney transplantation.

Antibody-mediated rejection (ABMR) at early or late post-transplantation remains challenging. We performed a single-center single-arm study where four cases of acute ABMR and nine cases of chronic active ABMR (defined by Banff classification) were treated with double-filtration plasmapheresis (two cycles of three consecutive daily sessions with a 4-day gap between). At the end of the third and sixth DFPP sessions, the patients received rituximab 375 mg/m2 . After a median follow-up of 1078 (61-1676) days, kidney-allograft survival was 50%. Before DFPP/rituximab therapy, the median donor-specific alloantibody (DSA) mean fluorescence intensity (MFI) was 9160 (4000-15 400); 45 days (D45) later it had significantly decreased to 7375 (215-18 100) (P = .018). In addition, at one-year (Y1) post-therapy, MFI had decreased further, that is, 4060 (400-7850) (P = .001). In two patients, DSA MFIs decreased and remained below 2000. The slope of estimated glomerular-filtration rate within the 6 months preceding intervention was -1.18 mL/min/month and remained unchanged at -1.29 mL/min/month within the year after intervention. Proteinuria remained unchanged. Baseline Banff scores on repeat allograft biopsies (post-therapy D45, Y1) did not show any improvement. Side-effects were mild to moderate. We conclude that the combined DFPP/rituximab significantly decreased DSAs in ABMR kidney-transplant recipients but did not improve renal function or renal histology at 1-year follow-up.

Isoagglutinin removal by plasma centrifugation or filtration (single or double): A prospective study in a single center.

INTRODUCTION: ABO-incompatible (ABOi) kidney transplantation, a well-established procedure, has good long-term results provided pretransplant desensitization that includes immunosuppression and apheresis. OBJECTIVE: To compare, within the first pretransplant apheresis session given to 29 ABOi kidney-transplant candidates, the effect on isoagglutinin titers (both IgG and IgM isotypes) of three modalities: centrifugation therapeutic plasmapheresis (cTP; n = 10), filtration TP (fTP; n = 9), and double-filtration plasmapheresis (DFPP; n = 10). RESULTS: The three groups were comparable according to baseline demographics. Treated plasma volumes were similar across the three groups, that is, 4111 ± 403 mL (cTP), 3861 ± 282 mL (fTP), and 3699 ± 820 mL (DFPP): that is, 54 ± 7, 53 ± 7, and 53 ± 10 mL/kg respectively. One session of centrifugation or filtration TP reduced IgG anti-A/anti-B isoagglutinin titer by ~4, whereas one DFPP session reduced it by ~2. One session of cTP reduced IgM anti-A isoagglutinin titer by a little less than 4, whereas fTP and DFPP sessions reduced it by ~3. There were no statistical differences across the three groups regarding isoagglutinin rebound (IgG and IgM). However, isoagglutinin IgG rebound was >4 dilutions for anti-B titers compared with ~2 dilutions for anti-A titers. The median decreases in IgG level were -3.9 g/L (DFPP), -5.9 g/L (cTP), and - 6.06 g/L (fTP) (p = ns). Median fibrinogen depletions were ~ 60% (fTP), 64% (DFPP), and 76% (cTP). CONCLUSIONS: Isoagglutinin depletions within the first apheresis session were similar across cTP, fTP, and DFPP: this was numerically lower for DFPP.

Associations among masticatory muscle activity, physical activity and self-reported oral behaviours in adult women.

OBJECTIVES: To examine the relationship between masticatory muscle activity (MMA), self-reported oral behaviours (OBs) and overall physical activity (PA) in adult women. MATERIALS AND METHODS: MMA and PA were assessed by a wearable electromyography (EMG) device and accelerometer respectively, worn over 2 non-consecutive days by 53 women (mean age 27.5 ± 6.4 years). Following the second recording day, self-reported OBs were assessed. MMA was assessed by the number, amplitude and duration of masseter contraction episodes. Masseter muscle EMG outcome measures were number of contraction episodes per hour (CEs/h) and the relative contraction time (RCT%). PA was assessed by time accumulated in moderate to vigorous physical activity (MVPA) and 10-min bouts of MVPA per hour. Data were analysed using mixed model analysis. RESULTS: MMA in free-living conditions consisted mostly of low-amplitude (<10% maximum voluntary clenching) and short-duration (<10 s) contraction episodes. Masseter CEs/h were not associated with self-reported levels of OB. Masseter CEs/h were positively associated with time accumulated in MVPA (F = 9.9; p = 0.002) and negatively associated with 10-min bouts of MVPA/h (F = 15.8; p <0.001). RCT% was not significantly associated with either. CONCLUSIONS: Objectively assessed MMA is not associated with self-reported OB in free-moving adult females. Moderate to vigorous exercise and physical inactivity are accompanied with an increase in the number of masseter muscle contractions and thus possibly tooth clenching activity. CLINICAL RELEVANCE: OB can be influenced by the type and extent of PA. Subjective assessment of MMA by questionnaire and/or interviews may be invalid.

Immunoadsorption for Recurrent Primary Focal Segmental Glomerulosclerosis on Kidney Allografts: A Single-Center Experience and Literature Review.

INTRODUCTION: Primary focal and segmental glomerulosclerosis (FSGS) frequently reoccurs on kidney transplants and may lead to premature allograft loss. There are no guidelines for treating FSGS recurrence on allografts; treatment is based on apheresis (plasma exchange plasmapheresis [PP], semi-specific immunoadsorption [IA] with reusable columns) plus rituximab. OBJECTIVE: We aimed to assess the efficacy of IA to treat recurrent FSGS. METHODS: We report on 7 patients with recurrent FSGS on kidney allograft (proteinuria ≥3 g/g of urinary creatinine or ≥3 g/day); they all received IA. Our primary objective was to reduce proteinuria by >50%. Patients' mean age was 45 ± 10 years. Postoperative immunosuppression relied on steroids, mycophenolate mofetil, tacrolimus, with an induction therapy of basiliximab or antithymocyte globulins. Prophylaxis to prevent FSGS recurrence was either rituximab alone (n = 3), rituximab plus either PP or IA (n = 3), or no treatment (n = 1). Mean follow-up was 20 ± 13 months. There was a median of 72 (14-101) IA sessions per patient, that is, a mean of 14 ± 1 sessions per IA column. RESULTS: At 12 months after starting IA, all patients had partial (n = 6) or complete (n = 1) remission, and allograft survival was 100%. The mean reduction in proteinuria within an IA session was 45 ± 15%. At last follow-up, 2 patients are in remission without IA, 3 patients are in partial remission that is IA dependent, and 2 patients lost their allograft due to FSGS recurrence. The most frequent adverse event was cytomegalovirus reactivation (n = 13), which subsided after valganciclovir therapy. CONCLUSIONS: We show that recurrence of FSGS can be controlled long term with IA plus rituximab. However, some patients remained dependent on IA.

Effect of immunoadsorption alone or combined with membrane filtration on hemostasis parameters.

INTRODUCTION: ABO- or HLA-incompatible kidney transplantation is possible thanks to pretransplant antibody-depletion achieved by extracorporeal-treatment modalities. These methods induce depletion of some plasma proteins and may also impact on proteins involved in hemostasis. METHODS: To determine the impact of one session of immunoadsorption (IA) alone or combined with membrane filtration (MF) on clotting factors and natural anticoagulants, we performed a prospective, observational study on 13 patients waiting for HLA-/ABO-incompatible kidney transplants. Plasma hemostasis parameters were measured before and immediately after a first session of IA alone in six patients and of IA + MF in seven patients. RESULTS: IA alone induced depletion of fibrinogen and factor XIII (FXIII) whereas IA + MF caused greater depletion of all high-molecular-weight hemostatic proteins (fibrinogen, FV, FVIII, FXI, FXIII, von-Willebrand factor [VWF]). After an IA session, median reductions were 30% for fibrinogen and 43% for FXIII compared to baseline values. After a session of IA + MF, median decreases were 70% for fibrinogen, 54% for FV, 56% for FVIII, 37% for FXI, 78% for FXIII, and 62% for VWF. Noticeably, levels of low-molecular-weight factors (<100 kDa) were far less decreased than high-molecular-weight proteins with IA + MF, except for protein S and the tissue factor pathway inhibitor, which are known to be partially physiologically bound to high-molecular-weight molecules. CONCLUSIONS: IA and IA + MF induced significant depletion of some proteins implicated in the hemostatic process; however, IA + MF resulted in stronger modifications to hemostasis parameters than IA alone. This may have potential clinical implications regarding bleeding risk, and particularly depletion of fibrinogen and FXIII.

Morphometric analysis of cervical vertebrae in relation to mandibular growth.

INTRODUCTION: Cervical vertebral maturation (CVM) methods have been criticized because of their subjective nature. The aims of this study were (1) to analyze the morphometric changes in the outline of the second to fourth cervical vertebrae with growth and (2) to test the validity of the CVM method for determining the mandibular growth peak. METHODS: Lateral cephalograms of 25 participants from ages 10 to 16 years were acquired from the Burlington Growth Study, and the CVM stage was qualitatively determined. Mandibular and cervical vertebral semilandmarks were then digitized, and point distribution models were used to describe the morphometric templates of the vertebrae in relation to chronologic age and the timing of peak mandibular growth. Mixed model analysis was used to determine the relationship between mandibular length, sex, CVM stage, and chronologic age. RESULTS: Morphometric changes of the second to fourth cervical vertebrae during growth were consistent with the CVM descriptions. However, mandibular length changes were not significantly associated with CVM stages after adjusting for chronologic age. Morphometric templates of vertebral shapes before and during the mandibular growth peak were similar, with changes detectable only after the growth peak had passed. Morphometric vertebral shape changes varied between the sexes. CONCLUSIONS: Morphometric changes of the cervical vertebrae and the CVM method could not accurately identify the mandibular growth peak.

Morphometric growth changes of the nasopharyngeal space in subjects with different vertical craniofacial features.

INTRODUCTION: The purpose of this study was to morphometrically investigate the growth pattern of the adenoids in growing subjects with hyperdivergent and hypodivergent vertical craniofacial features. METHODS: In this retrospective study, we used a longitudinal sample of lateral cephalometric radiographs of 28 hyperdivergent and 30 hypodivergent subjects from 4 to 13 years of age. The radiographs were obtained from the American Association of Orthodontists Foundation Craniofacial Growth Legacy Collection. Measurements were made using digital tracings of the lateral cephalograms and point distribution models. Mixed-model analyses were used for statistical analysis. RESULTS: The mean distance between the sphenoid bone and the posterior nasal spine increased up to 5.3 mm over a 9-year span (95% CI, 4.1-6.5 mm; P <0.001). Furthermore, the mean distance between the sphenoid bone and the posterior nasal spine differed significantly (P = 0.029) between facial types; it was consistently greater (1.8 mm; 95% CI, 0.2-3.3 mm) in the hyperdivergent group. The nasopharyngeal airway area showed a trend to increase with age up to 12-fold (P <0.001). A significant interaction (P = 0.004) was found between age and facial type. Assessment of the adenoid shapes showed greater convexities in the hyperdivergent group, which were observable from an earlier age and for a longer duration. CONCLUSIONS: Clear differences in the morphometric growth pattern of the adenoids were found between facial types. Evaluation of adenoid shapes showed more prominent convexities that lasted longer in the long facial types than in the short facial types.

Calcium-Free Dialysate Hemodialysis: A Simplified Approach.

Intermittent hemodialysis (HD) in high-bleeding-risk patients presents a challenge as circuit anticoagulation using heparin is contraindicated in such cases. Recently, the use of calcium-free citrate-containing dialysate with calcium supplementation emerged as a viable alternative to heparin-circuit anticoagulation. This is a retrospective, monocentric study to evaluate dialysis efficacy using calcium-free citrate-containing dialysate with calcium reinjection into the venous line in hemodialysis patients at risk of bleeding. A total of 53 patients were analyzed: 52 had a temporary contraindication to systemic anticoagulation (active bleeding or surgical intervention), and 1 chronic HD patient had prolonged bleeding time due to inoperable arteriovenous fistula stenosis. Only 7 out of 79 dialysis sessions performed were prematurely terminated (vascular access dysfunction). The median dialysis time was 240 min (range: 150-300). The chronic dialysis patient had 108 sessions with no premature termination. Frequent monitoring of ionized calcium was performed throughout the dialysis sessions: levels remained stable at T0 and T + 60 min (1.08 ± 0.08 mmol/L) and slightly increased at the end of the dialysis session (1.19 ± 0.13 mmol/L), remaining within normal limits. Target postfilter ionized calcium <0.4 mmol/L was achieved in all sessions (0.31 ± 0.07 mmol/L). There were no cases of symptomatic hypo-/hypercalcemia and no need for calcium infusion rate adjustment throughout the sessions. Hemodialysis with calcium-free citrate-containing dialysate and calcium reinjection into the venous line is efficient and safe in HD patients with contraindications to systemic anticoagulation.

Is There a Place for Apheresis in the Management of Idiopathic Membranous Nephropathy? A Report of Three Cases and Literature Review.

Membranous nephropathy constitutes approximately 20% of adult nephrotic syndrome cases. In approximately 80% of cases, membranous nephropathy is primary, mediated by IgG autoantibodies primarily targeting podocyte antigens (PLA2R, THSD7A, etc.). The treatment involves a combination of corticosteroids and cyclophosphamide or anti-CD20-based therapies, e.g., rituximab. In the event of significant proteinuria and in order to avoid the urinary elimination of rituximab, therapeutic apheresis, in particular semi-specific immunoadsorption, may be an option allowing for a reduction in proteinuria and autoantibodies before initiating treatment with rituximab. We present the preliminary experience of three patients treated with semi-specific immunoadsorption for primary membranous nephropathy between January 2021 and March 2023. Two patients were anti-PLA2R-autoantibody-positive and one was seronegative. The average age was 59 ± 17 years. Semi-specific immunoadsorption did not reduce albuminuria, but it, nevertheless, led to an increase in serum albumin, contributing to the regression of edema. It effectively eliminated anti-PLA2R autoantibodies in the two anti-PLA2R-positive patients. Consequently, apheresis may not induce a rapid reduction in proteinuria, but could contribute to a more accelerated remission when combined with the anti-CD20 treatment.