Magnetic resonance imaging and clinical features of Mayer-Rokitansky-Küster-Hauser syndrome: A 10-year review from a dedicated specialist centre.

OBJECTIVE: To correlate the clinical history with imaging findings of women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. DESIGN: Retrospective cohort study. SETTING: A UK IOTA and ESGO-certified tertiary referral centre for disorders of reproductive development. POPULATION: All patients with a diagnosis of MRKH and who had undergone an MRI pelvis between 1 January 2011 and 31 April 2021 were included. METHODS: MRI images were analysed by specialist gynaecological radiologists. Clinical data was extracted from an electronic patient record system. Statistical analysis was computed in R (version 4.1.2), R base stats package and ggstatsplot (v0.5.0). MAIN OUTCOME MEASURES: Clinical history and predefined imaging features. RESULTS: One hundred and thirty-four patients were included. Median age at MRI was 18 years (10-64 years). Half (48.2%) of women presenting had a history of pain, most often abdominal (84.6%) or vaginal (9.2%). Remnants were identified in 91.8% of women (n = 123). 4.5% of women had imaging features of endometriosis (n = 6). Women with a functional remnants were significantly more likely to experience pain (p < 0.001). Pain history was not strongly associated with ectopic ovarian position. Common gynaecological pathology such as endometriosis, ovarian cysts and fibroids were also identified. CONCLUSIONS: We identify that majority of women with MRKH will have uterine remnants with a connecting fibrous band, and an ectopic ovarian position 44.0% of cases. Abdominal pain was significantly associated with functional remnants on MRI. Further work is required to identify how other gynaecological pathology impacts women with MRKH.

Machine learning and radiomics for segmentation and classification of adnexal masses on ultrasound.

Ultrasound-based models exist to support the classification of adnexal masses but are subjective and rely upon ultrasound expertise. We aimed to develop an end-to-end machine learning (ML) model capable of automating the classification of adnexal masses. In this retrospective study, transvaginal ultrasound scan images with linked diagnoses (ultrasound subjective assessment or histology) were extracted and segmented from Imperial College Healthcare, UK (ICH development dataset; n = 577 masses; 1444 images) and Morgagni-Pierantoni Hospital, Italy (MPH external dataset; n = 184 masses; 476 images). A segmentation and classification model was developed using convolutional neural networks and traditional radiomics features. Dice surface coefficient (DICE) was used to measure segmentation performance and area under the ROC curve (AUC), F1-score and recall for classification performance. The ICH and MPH datasets had a median age of 45 (IQR 35-60) and 48 (IQR 38-57) years old and consisted of 23.1% and 31.5% malignant cases, respectively. The best segmentation model achieved a DICE score of 0.85 ± 0.01, 0.88 ± 0.01 and 0.85 ± 0.01 in the ICH training, ICH validation and MPH test sets. The best classification model achieved a recall of 1.00 and F1-score of 0.88 (AUC:0.93), 0.94 (AUC:0.89) and 0.83 (AUC:0.90) in the ICH training, ICH validation and MPH test sets, respectively. We have developed an end-to-end radiomics-based model capable of adnexal mass segmentation and classification, with a comparable predictive performance (AUC 0.90) to the published performance of expert subjective assessment (gold standard), and current risk models. Further prospective evaluation of the classification performance of this ML model against existing methods is required.

In vitro analysis of anti-HPA-1a dependent platelet phagocytosis and its inhibition using a new whole blood phagocytosis assay (WHOPPA).

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a serious bleeding condition mostly caused by the reaction between maternal anti-HPA-1a antibodies and fetal platelets. This reaction leads to Fc-dependent platelet phagocytosis. Although several serological methods have been developed to identify maternal antibodies, a reliable laboratory parameter as a prognostic tool for FNAIT severity is still lacking. In this study, we developed whole blood platelet phagocytosis assay (WHOPPA), a flow cytometry-based phagocytosis assay that uses a pH-sensitive fluorescent dye (pHrodo-SE) to analyze anti-HPA-1a-dependent platelet phagocytosis in whole blood. WHOPPA revealed a high phagocytosis rate for the anti-HPA-1a opsonized platelets by monocytes but not by neutrophils. Analysis of different monocyte populations showed that all monocyte subsets, including classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocytes, were able to engulf opsonized platelets. A unique monocyte subset, termed shifted monocytes (CD14+CD16-), showed the highest phagocytosis rate and was detected after platelet engulfment. FcγR inhibition tests revealed that except for FcγRIIa, FcγRI and FcγRIII on monocytes were responsible for the phagocytosis of anti-HPA-1a opsonized platelets. Analysis of anti-HPA-1a antibodies from FNAIT cases (n = 7) showed the phagocytosis of HPA-1aa but not of HPA-1bb platelets by monocytes. The phagocytosis rate was highly correlated with bound antibodies measured by flow cytometry (p < 0001; r = 0.9214) and MAIPA assay (p < 0.001; r = 0.7692). The phagocytosis rates were equal for type I and II anti-HPA-1a antibodies recognizing the plexin-semaphoring-integrin (PSI) domain and PSI/epidermal growth factor 1 domain of ß3 integrin, respectively. By contrast, type III anti-HPA-1a antibodies reacting with αvß3 integrin did not induce platelet phagocytosis. Furthermore, effector-silenced mAbs against HPA-1a inhibited the phagocytosis of anti-HPA-1a opsonized platelets. In conclusion, WHOPPA is a reliable in vitro platelet phagocytosis assay that mimics the phagocytosis of anti-HPA-1a opsonized platelets in whole blood. This assay allows to prove platelet phagocytosis ex vivo and evaluate the inhibitory capacity of different inhibitors as therapeutically strategies for the prevention of fetal thrombocytopenia in FNAIT in the future.

Fetal and neonatal alloimmune thrombocytopenia: No evidence of systemic inflammation as a modulator of disease severity. Could placental inflammation be key?

In fetal/neonatal alloimmune thrombocytopenia (FNAIT), maternal alloantibodies against paternal human platelet antigens (HPA) cross the placenta and lead to platelet destruction. The extent of thrombocytopenia varies among neonates, and inflammation may constitute an important trigger. A set of stable inflammatory markers was measured in serum samples from neonates with low platelet counts, of which n = 50 were diagnosed with FNAIT due to anti-HPA-1a antibodies and n = 50 were thrombocytopenic without detectable maternal HPA antibodies. Concentrations of C-reactive protein, soluble CD14, procalcitonin, and sFlt-1 did not differ between the two cohorts. There was no correlation between C-reactive protein or soluble CD14 and the platelet count, but a negative correlation between procalcitonin concentrations and the neonatal platelet count in both cohorts. sFlt-1 concentration and the platelet count were correlated in FNAIT cases exclusively. None of the inflammatory markers was statistically different between cases with and without intracranial haemorrhage. We were unable to identify systemic inflammation as a relevant factor for thrombocytopenia in FNAIT. The antiangiogenic enzyme sFlt-1, released by the placenta, did correlate with the platelet count in FNAIT cases. Our findings may give rise to the hypothesis that placental inflammation rather than systemic inflammation modulates disease severity in FNAIT.

Automated Light Transmission Aggregometry with and without Platelet Poor Plasma Reference: A Method Comparison.

Background Light transmission aggregometry (LTA) is considered the gold standard for the evaluation of platelet function but is labor-intensive and involves numerous manual steps. Automation may contribute to standardization. Here, we evaluate the performance characteristics of a new automated instrument, Thrombomate XRA (TXRA), and compare it against a manual instrument (PAP-8). Materials and Methods Leftover blood samples from blood donors or patients were tested in parallel with identical reagents and in identical concentrations both manually using PAP-8 and automated on the TXRA. In addition to precision and method comparison, an additional evaluation was performed on the TXRA against "virtual" platelet-poor plasma (VPPP) based on artificial intelligence. The main focus was on comparing the maximum aggregation (MA%) values. Results Precision for MA% ranged from 1.4 to 4.6% on TXRA for all reagents. Normal ranges for 100 healthy blood donors on both instruments were in a similar range for all reagents, with a tendency to slightly higher values with TXRA. Most agonists resulted in normally distributed MA%. Comparing 47 patient samples on both devices showed a good correlation for both slope and MA% with some differences in individual samples with epinephrine and TRAP. Correlation between the TXRA measurement against PPP and "virtual" PPP demonstrated excellent correlation. Reaction signatures of both devices were very similar. Conclusion TXRA provides reproducible LTA results that correlate with an established manual method when tested against PPP or VPPP. Its ability to perform LTA only from platelet-rich plasma without requiring autologous PPP simplifies LTA. TXRA is an important step not only for further standardizing LTA but also for a more widespread use of this important method.

ABO Incompatibility between the Mother and Fetus Does Not Protect against Anti-Human Platelet Antigen-1a Immunization by Pregnancy.

(1) Background: ABO blood group incompatibility between the mother and fetus protects against anti-D immunization by pregnancy. The possible role of ABO incompatibility in protecting against anti-human platelet antigen-1a immunization is unclear. (2) Methods: This study retrospectively screened 817 families (mother-father-neonate trios) of suspected fetal and neonatal alloimmune thrombocytopenia for inclusion. ABO genotypes were determined in 118 mother-child pairs with confirmed alloimmune thrombocytopenia due to anti-HPA-1a antibodies, and 522 mother-child pairs served as the control group. The expression of blood group antigen A on platelets was determined in 199 consecutive newborns by flow cytometry and compared with adult controls. (3) Results: ABO incompatibility between mother and fetus did not protect against anti-human platelet antigen-1a immunization by pregnancy. ABO blood groups of mothers and/or fetuses were not associated with the severity of fetal and neonatal alloimmune thrombocytopenia. The expression pattern of blood group A antigens on the platelets of newborns mirrored that of adults, albeit on a lower level. Blood group A antigen was detected on a subpopulation of neonatal platelets, and some newborns revealed high platelet expression of A determinants on all platelets (type II high-expressers). (4) Conclusion: The lack of a protective effect of ABO incompatibility between mother and fetus against anti-human platelet antigen-1a immunization by pregnancy may indicate that fetal platelets are not the cellular source by which the mother is immunized.

Long-Term Outcomes after Vaccine-Induced Thrombotic Thrombocytopenia.

Vaccine-induced thrombotic thrombocytopenia (VITT), or thrombosis with thrombocytopenia syndrome (TTS), is a rare but serious complication of adenovirus-based vaccines against severe respiratory syndrome coronavirus 2 (SARS-CoV-2). Observation of long-term outcomes is important to guide treatment of affected patients. This single-center consecutive cohort study included all patients diagnosed based on (1) vaccination 4 to 21 days before symptom onset, (2) signs or symptoms of venous or arterial thrombosis, (3) thrombocytopenia < 150/nL, (4) positive anti-platelet factor 4 (PF4) antibody, and (5) elevated D-Dimer > 4 times the upper limit of normal. Nine patients were enrolled. Acute management consisted of parenteral anticoagulants, corticosteroids, intravenous immunoglobulin (IVIG), and/or eculizumab. Eculizumab was successfully used in two patients with recurrent thromboembolic events after IVIG. Direct oral anticoagulants were given after hospital discharge. Median follow-up duration was 300 days (range 153 to 380). All patients survived the acute phase of the disease and were discharged from hospital. One patient died from long-term neurological sequelae of cerebral venous sinus thrombosis 335 days after diagnosis. Eight out of nine patients were alive at last follow-up, and seven had fully recovered. Anti-PF4 antibodies remained detectable for at least 12 weeks after diagnosis, and D-Dimer remained elevated in some patients despite oral anticoagulation. No recurrent thromboembolic events, other signs of VITT relapse, or bleeding complications occurred after discharge. In conclusion, VITT appears to be a highly prothrombotic condition. IVIG is not always successful, and eculizumab may be considered a rescue agent. Long-term management with direct oral anticoagulants appears to be safe and effective.

Anti-human platelet antigen-5b antibodies and fetal and neonatal alloimmune thrombocytopenia; incidental association or cause and effect?

Most cases of fetal and neonatal thrombocytopenia (FNAIT) are caused by maternal anti-human platelet antigen-1a antibodies (anti-HPA-1a). Anti-HPA-5b antibodies are the second most common antibodies in suspected FNAIT cases. Given the high prevalence of anti-HPA-5b antibodies in pregnant women delivering healthy newborns, the association with FNAIT may be coincidental. This review of the literature related to FNAIT using the MEDLINE database was conducted according to PRISMA guidelines. A retrospective analysis of a single-centre cohort of 817 suspected FNAIT cases was conducted. The pooled prevalence of anti-HPA-5b antibodies in unselected pregnant women of European descent was 1.96% (n = 3113), compared with 3.4% (n = 5003) in women with suspected FNAIT. We found weak evidence that a small proportion of pregnant women presenting with anti-HPA-5b antibodies will give birth to a newborn with mild thrombocytopenia. The neonatal platelet counts were not different between suspected FNAIT cases (n = 817) with and without maternal anti-HPA-5b antibodies. The prevalence of maternal anti-HPA-5b antibodies was not different between neonates with intracranial haemorrhage and healthy controls. The current experimental and epidemiological evidence does not support the hypothesis that anti-HPA-5b antibodies cause severe thrombocytopenia or bleeding complications in the fetus or newborn.

Evaluating the Usefulness and Acceptability of a Revision-Purposed 'Specialties' Webinar for Educating UK-Based Fifth and Final Year Medical Students During the COVID-19 Pandemic: Is This the Future of Medical Education?

BACKGROUND: To assess whether an online course is a useful method of learning for medical students revising for specialty examinations in the context of social distancing restrictions during the COVID-19 pandemic. METHODS: A free, one-day webinar was offered to fifth and final year medical students with an examination-based approach. Teaching was delivered by trainees in Psychiatry, Obstetrics and Gynaecology and Paediatrics (the 'specialties'). An online, questionnaire-based cross-sectional study was conducted to assess usefulness and acceptability of the webinar by enrolled students, who were invited to complete the research questionnaire. Student responses pertaining to knowledge, confidence and interest, pre- and post-webinar, were collected and analysed. RESULTS: A total of 247 students attended the webinar, with a 98.4% response rate to the questionnaire. Ninety-one percent of students agreed that webinars offer flexibility and convenience. About 55.1% felt that the pandemic had impacted their ability to learn new information. About 92.7% felt that the webinar was useful. Matched data showed an increase in participants' knowledge (p = <0.001) and confidence (p < 0.001). CONCLUSION: Online learning provides a useful, accessible and safe method of providing medical education in the context of the global pandemic. Webinars adopting a lecture-based, examination-style approach improved students' perceived confidence and knowledge.

Combined Administration of Fibrinogen and Factor XIII Concentrate Does Not Improve Dilutional Coagulopathy Superiorly Than Sole Fibrinogen Therapy: Results of an In-Vitro Thrombelastographic Study.

The early administration of fibrinogen has gained wide acceptance for the treatment of major hemorrhage, whereas the substitution of coagulation factor XIII (FXIII) is only supported by a low level of evidence. This study aimed to answer the question of whether a combined therapy of fibrinogen/FXIII substitution performs superiorly to sole fibrinogen administration in the treatment of dilutional coagulopathy. An in-vitro model of massive transfusion was used to compare the effect of combined fibrinogen/FXIII administration to that of sole fibrinogen therapy for the treatment of dilutional coagulopathy. For this purpose, the blood of red blood cell concentrates, fresh frozen plasma, and platelet concentrates were reconstituted in a ratio of 4:4:1, and then diluted with gelatin by 20% and 40%, respectively. Clot formation and stability were analyzed by thrombelastography. Both sole fibrinogen therapy (equivalent to 50 mg/kg) and the combined administration of fibrinogen (equivalent to 50 mg/kg) and FXIII (equivalent to 75 International Units (IU)/kg) increased fibrinogen-dependent mean clot firmness independently of the degree of dilution (20% dilution: 7 (6.3-7.8) mm; 20% dilution fibrinogen: 13.5 (13-17.3) mm; 20% dilution fibrinogen/FXIII: 16.5 (15.3-18.8) mm; 40% dilution: 3 (2-3.8) mm; 40% dilution fibrinogen: 8 (7-11.3) mm; 40% dilution fibrinogen/FXIII: 10 (8.3-11.8) mm; all p < 0.01). However, no differences were identified between the two treatment arms. Compared to fibrinogen therapy, no beneficial effect of the combined administration of fibrinogen and FXIII for the treatment of dilutional coagulopathy was detected in this in-vitro massive transfusion model. The result was independent of the degree of dilution.

PF4-Dependent Immunoassays in Patients with Vaccine-Induced Immune Thrombotic Thrombocytopenia: Results of an Interlaboratory Comparison.

BACKGROUND: Coronavirus disease 2019 vaccine ChAdOx1 nCov-19 may rarely lead to vaccine-induced thrombotic thrombocytopenia (VITT). Antibody-mediated, platelet factor 4 (PF4)-dependent platelet activation appears to resemble a key mechanism in VITT, partially comparable to heparin-induced thrombocytopenia. The use of PF4/heparin immunoassays has been proposed as part of a diagnostic approach, but their sensitivity has not been established. METHODS: Sera from 12 well-defined VITT patients were first studied by two different laboratories in functional assays. Sera where then used for an interlaboratory comparison, in which five different PF4/heparin immunoassays were used by four laboratories. RESULTS: Results for functional testing were highly concordant. VITT antibodies were also reliably detected by PF4/heparin enzyme-linked immunosorbent assays (ELISAs) (92-100%). In contrast, only 25% of VITT antibodies were reactive in a particle gel immunoassay (PaGIA), and 8% in a lateral flow assay (LFA). An automated chemiluminescence immunoassay (CLIA) was negative for all sera tested (0%). CONCLUSION: It seems feasible to establish functional antibody testing for the confirmation of VITT. For the initial screening of suspected VITT cases, PaGIA, LFA, and CLIA are useless when applied as single tests. Only ELISA-based PF4/heparin immunoassays are sensitive enough to be incorporated in the diagnostic workup. However, a combination of a positive ELISA and a negative CLIA may be useful to identify VITT antibodies in the absence of confirmatory functional assays.

Incidental diagnosis of leukocyte adhesion deficiency type II following ABO typing.

Individuals with the Bombay phenotype (Oh) in the ABO blood group system do not express the H, A, and B antigens but have no clinical symptoms. Bombay phenotype with clinical symptoms has been described in leukocyte adhesion deficiency type II (LAD II), a fucosylation disorder caused by mutations in SLC35C1. Only few LAD II patients have been described so far. Here we describe an additional patient, a 22-year old male, born to unrelated parents, presenting with inflammatory skin disease, periodontitis, growth, and mental retardation, admitted to the department of dentistry for treatment under general anesthesia. Pre-operative routine investigations revealed the presence of the Bombay phenotype (Oh). Genomic sequencing identified two novel triplet deletions of the SLC35C1 gene. Functional investigations confirmed the diagnosis of LAD II. Therapy with oral fucose led to the disappearance of the chronic skin infections and improvements in behavior and attention span.

Maternal antibodies against paternal class I human leukocyte antigens are not associated with foetal and neonatal alloimmune thrombocytopenia.

The causative role of maternal, anti-human leukocyte antigen (anti-HLA) class I antibodies in foetal and neonatal alloimmune thrombocytopenia (FNAIT) remains controversial. Furthermore, in FNAIT cases caused by anti-human platelet antigen-1a (anti-HPA-1a) antibodies, the possible additive effect of maternal anti-HLA class I antibodies on outcomes is unclear. Among 817 mother-father-neonate trios of suspected FNAIT, we assessed the possible association of maternal anti-HLA class I antibodies with neonatal platelet count, and the incidence of FNAIT caused by anti-HPA-1a antibodies. In 144 FNAIT cases caused by anti-HPA-1a antibodies, we investigated the possible association of maternal anti-HLA class I antibodies with neonatal platelet count, birth weight, and the incidence of intracranial haemorrhage (n = 16). Maternal anti-HLA class I antibodies were not associated with neonatal platelet count in suspected cases of FNAIT. There was no significant interaction between the presence of anti-HLA class I antibodies and anti-HPA-1a antibodies. In FNAIT cases caused by anti-HPA-1a antibodies, there was no association between the presence of anti-HLA class I antibodies and neonatal platelet count, birth weight, or occurrence of intracranial haemorrhage. This study's findings do not support the concept that maternal anti-HLA class I antibodies represent a risk factor of FNAIT or disease severity.

Training health workers to prevent and manage post-partum haemorrhage (PPH).

Post-partum haemorrhage (PPH) is the second greatest direct cause of maternal death in the United Kingdom, and rates of PPH continue to increase despite advances in clinical care. Training workers to manage PPH involves improvement of technical and non-technical skills in the context of a multidisciplinary team (MDT). Management of PPH should begin in the antenatal period, with identification of high-risk women and referral for multispecialty input. Training for the acute management of PPH should involve all members of the labour ward team and beyond, including haematology and non-clinical staff. Simulation-based training, didactic teaching and hybrid obstetric emergency courses are current options for training workers. Non-technical skills should also be taught, including specific training on communication, leadership, situational awareness and team-working skills. Improving management of obstetric emergencies requires thorough antenatal and intra-partum risk assessment, optimising knowledge and non-technical skills of individual members of the team, improving collaboration of the MDT, better simulation training and adjusting local infrastructure.

Glycoprotein V is a relevant immune target in patients with immune thrombocytopenia.

Platelet autoantibody-induced platelet clearance represents a major pathomechanism in immune thrombocytopenia (ITP). There is growing evidence for clinical differences between anti-glycoprotein IIb/IIIa and anti-glycoprotein Ib/IX mediated ITP. Glycoprotein V is a well characterized target antigen in Varicella-associated and drug-induced thrombocytopenia. We conducted a systematic study assessing the prevalence and functional capacity of autoantibodies against glycoprotein V. A total of 1140 patients were included. In one-third of patients, platelet-bound autoantibodies against glycoproteins Ib/IX, IIb/IIIa, or V were detected in a monoclonal antibody immobilization of platelet antigen assay; platelet-bound autoantiglycoprotein V was present in the majority of samples (222 out of 343, 64.7%). Investigation of patient sera revealed the presence of free autoantibodies against glycoprotein V in 13.5% of these patients by an indirect monoclonal antibody immobilization of platelet antigen assay, but in 39.6% by surface plasmon resonance technology. These antibodies showed significantly lower avidity (association/dissociation ratio 0.32±0.13 vs 0.73±0.14; P<0.001). High- and low-avidity antibodies induced comparable amounts of platelet uptake in a phagocytosis assay using CD14+ positively-selected human macrophages [mean phagocytic index, 6.81 (range, 4.75-9.86) vs 6.01 (range, 5.00-6.98); P=0.954]. In a NOD/SCID mouse model, IgG prepared from both types of anti-glycoprotein V autoantibodies eliminated human platelets with no detectable difference between the groups from the murine circulation [mean platelet survival at 300 minutes, 40% (range, 27-55) vs 35% (16-46); P=0.025]. Our data establish glycoprotein V as a relevant immune target in immune thrombocytopenia. We would suggest that further studies including glycoprotein V will be required before ITP treatment can be tailored according to platelet autoantibody specificity.

Red blood cell alloimmunization in neonates and children up to 3 years of age.

BACKGROUND: An alloimmune response to red blood cell (RBC) transfusion in neonates is a rare event. Several guidelines recommend limited pretransfusion testing in neonates. The evidence for these recommendations is based on small studies with sample sizes of between 30 and 90 infants. STUDY DESIGN AND METHODS: We conducted a retrospective cohort study among consecutive patients who received transfusions at a single university medical center. All non-alloimmunized patients who had received their first RBC transfusion between 1994 and 2013 and who underwent at least one antibody screening follow-up visit between 7 and 365 days after transfusion were included. RESULTS: The incidence of alloimmunization in the control group of 17,084 adult patients age 45 years or older who had received a median of 5 RBC units (interquartile range, 2-12 RBC units) was 3.55% (n = 607 alloimmunized patients). After transfusion of 40 RBC units, the cumulative incidence of alloimmunization in adult controls was 10.24% (95% confidence interval, 7.71%-13.17%). In total, 1641 neonates and children up to age 3 years received a median of 4 RBC units (interquartile range, 2-7 RBC units) in a median of two RBC transfusion episodes (interquartile range, one to five RBC transfusion episodes). Two children developed anti-M and anti-E antibodies post-transfusion at the ages of 181 and 611 days, respectively. CONCLUSION: To our knowledge, this study presents the largest longitudinal cohort study of RBC alloimmunization in neonates. Antibodies against RBC antigens were not detected within the first 6 months of life. Repeat antibody screening and cross-matching during the first months of life can be safely omitted.

Current clinical evidence for the use of mesenchymal stem cells in articular cartilage repair.

INTRODUCTION: Articular cartilage is renowned for its poor intrinsic capacity for repair. Current treatments for osteoarthritis are limited in their ability to reliably restore the native articular cartilage structure and function. Mesenchymal stem cells (MSCs) present an attractive treatment option for articular cartilage repair, with a recent expansion of clinical trials investigating their use in patients. AREAS COVERED: This paper provides a current overview of the clinical evidence on the use of MSCs in articular cartilage repair. EXPERT OPINION: The article demonstrates robust clinical evidence that MSCs have significant potential for the regeneration of hyaline articular cartilage in patients. The majority of clinical trials to date have yielded significantly positive results with minimal adverse effects. However the clinical research is still in its infancy. The optimum MSC source, cell concentrations, implantation technique, scaffold, growth factors and rehabilitation protocol for clinical use are yet to be identified. A larger number of randomised control trials are required to objectively compare the clinical efficacy and long-term safety of the various techniques. As the clinical research continues to evolve and address these challenges, it is likely that MSCs may become integrated into routine clinical practice in the near future.

A bead-based assay in the work-up of suspected platelet alloimmunization.

BACKGROUND: Alloantibodies against human platelet antigens (HPAs) are of clinical significance in immune-mediated thrombocytopenia such as fetal/neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura, and platelet (PLT) transfusion refractoriness. The gold standard for the detection of these antibodies is the monoclonal antibody immobilization of PLT antigens (MAIPA) assay. Both requirement of typed donor PLT panels and technical expertise often restrict its use to reference laboratories. STUDY DESIGN AND METHODS: An easy-to-use, bead-based assay (BBA) has been introduced recently. In this study, we compared MAIPA and BBA test results for 126 serum samples from women who gave birth to a child with FNAIT including rare HPA specificities (n = 111) and from patients with PLT transfusion refractoriness (n = 15). RESULTS: For sera with defined allospecificities, the number of BBA false-negatives was 12 of 126, or 9.5%, and the number of BBA false-positives (i.e., detection of additional specificities) was two of 126, or 1.6%. BBA had major problems in detecting antibodies against HPA-3a (3/15 undetected = 20% failure rate) and HPA-3b (5/6 undetected = 83.3% failure rate), but performed well in detecting typical FNAIT- or PLT transfusion refractoriness-associated antibodies including HPA-1a (35/35 = 100%), HPA-1b (15/15 = 100%), HPA-5b (22/24 = 91.6%), and glycoprotein IV (6/6 = 100%). CONCLUSION: BBA might be a useful and time-saving tool in the initial laboratory work-up of suspected PLT alloimmunization when an appropriate algorithm ensures follow-up investigation of BBA-negative sera.