Therapeutic role of plasma exchange in the management of stiff person syndrome: experience from a tertiary care centre.

INTRODUCTION: The stiff person syndrome (SPS) is a rare and disabling neurological disorder characterized by muscle stiffness, painful spasms and rigidity involving the proximal and axial limb muscles, with an estimated incidence of 1 case per million per year. The first line of treatment for symptomatic management includes gamma-aminobutyric acid (GABA)ergic agonists, benzodiazepines and baclofen. The therapeutic plasma exchange (TPE), alone or as an adjuvant to other forms of immunomodulation, has been used as a therapeutic option, particularly in refractory cases. METHODS: An observational study was performed to review SPS patient symptoms, comorbidities, electromyography (EMG) studies and treatment, identifying autoantibodies, therapeutic plasma exchange (TPE) procedural details and clinical response. MAIN RESULTS: Five patients (4 male and one female) were treated with TPE during the study period as adjuvant therapy. The average age was 47 years (range 34 - 61 years), and anti-glutamic acid decarboxylase 65-kilodalton isoform (anti-GAD65) antibodies were positive in 80 % (4/5) of the patient population. All patients received immunosuppressive drugs along with TPE. Four patients received TPE during the first admission and one received it during the third hospital admission. All patients showed good improvement immediately after TPE, but it was not a sustainable effect. CONCLUSION: TPE may be helpful as adjuvant therapy for SPS patients to provide relief from clinical symptoms.

Biomineralized fluorocanasite-reinforced biocomposite scaffolds demonstrate expedited osteointegration of critical-sized bone defects.

The development of patient-specific bone scaffolds that can expedite bone regeneration has been gaining increased attention, especially for critical-sized bone defects or fractures. Precise adaptation of the scaffold to the region of implantation and reduced surgery times are also crucial at clinical scales. To this end, bioactive fluorcanasite glass-ceramic microparticulates were incorporated within a biocompatible photocurable resin matrix following which the biocomposite resin precursor was 3D-printed with digital light processing method to develop the bone scaffold. The printing parameters were optimized based on spot curing investigation, particle size data, and UV-visible spectrophotometry. In vitro cell culture with MG-63 osteosarcoma cell lines and pH study within simulated body fluid demonstrated a noncytotoxic response of the scaffold samples. Further, the in vivo bone regeneration ability of the 3D-printed biocomposite bone scaffolds was investigated by implantation of the scaffold samples in the rabbit femur bone defect model. Enhanced angiogenesis, osteoblastic, and osteoclastic activities were observed at the bone-scaffold interface, while examining through fluorochrome labelling, histology, radiography, field emission scanning electron microscopy, and x-ray microcomputed tomography. Overall, the results demonstrated that the 3D-printed biocomposite bone scaffolds have promising potential for bone loss rehabilitation.

An overview of translational research in bone graft biomaterials.

Natural bone healing is often inadequate to treat fractures with critical size bone defects and massive bone loss. Immediate surgical interventions through bone grafts have been found to be essential on such occasions. Naturally harvested bone grafts, although are the preferred choice of the surgeons; they suffer from serious clinical limitations, including disease transmission, donor site morbidity, limited supply of graft etc. Synthetic bone grafts, on the other hand, offer a more clinically appealing approach to decode the pathways of bone repair through use of tissue engineered biomaterials. This article critically retrospects the translational research on various engineered biomaterials towards bringing transformative changes in orthopaedic healthcare. The first section of the article discusses about composition and ultrastructure of bone along with the global perspectives on statistical escalation of bone fracture surgeries requiring use of bone grafts. The next section reviews the types, benefits and challenges of various natural and synthetic bone grafts. An overview of clinically relevant biomaterials from traditionally used metallic, bioceramic, and biopolymeric biomaterials to new generation composites have been summarised. Finally, this narrative review concludes with the discussion on the emerging trends and future perspectives of the promising bone grafts.

Role of altered IL-33/ST2 immune axis in the immunobiology of Guillain-Barré syndrome.

BACKGROUND: The IL-33/ST2 immune axis plays crucial roles in infection and immunity. A dysregulated IL-33/ST2 axis can induce autoimmune reaction and inflammatory responses. Guillain-Barré syndrome (GBS) is an acute peripheral neuropathy, mostly caused by post-infection autoimmunity. The role of IL-33/ST2 axis is not known in GBS. This study aimed to explore the role of IL-33/ST2 axis in GBS. METHODS: Three single nucleotide polymorphisms (SNPs) of Il33 gene (rs16924159, rs7044343, rs1342336) and three SNPs of Il1rl1 gene (rs10192157, rs1041973, rs10206753) coding for suppressor of tumorigenicity 2 (ST2) were genotyped in 179 GBS patients and 186 healthy controls by TaqMan Allelic Discrimination Assay. Plasma levels of IL-33 and sST2 were measured in a subset of GBS patients (n = 80) and healthy controls (n = 80) by ELISA. RESULTS: The frequencies of CC genotype of rs10192157 (p = 0.043) and TT genotype of rs10206753 (p = 0.036) SNPs of Il1rl1 gene differed significantly between GBS patients and healthy controls. Gene-gene interaction between Il33 and Il1rl1 genes also conferred significant risk for GBS. In addition, the plasma sST2 levels were significantly elevated in GBS patients compared to healthy subjects (24,934.31 ± 1.81 pg/ml vs. 12,518.97 ± 1.51 pg/ml, p < 0.001). Plasma sST2 levels showed a significant correlation with the disability scores at the peak of neurological deficit in GBS patients. CONCLUSIONS: The IL-33/ST2 axis is suggested to influence the immunopathogenesis of GBS. Genetic variants of Il1rl1 gene might serve as a risk determinant of GBS and plasma sST2 levels might emerge as a biomarker of severity of GBS, if replicated further by other studies.

Donor's Perspectives on Blood Donation During Covid-19 Pandemic.

Covid-19 pandemic had affected transfusion services including recruitment of donors and blood donation camps activities. The blood donors may have concerns, confusion, and misleading rumours about blood donation during pandemic. People's priorities for blood donation may shift because of a dearth of necessities. It is important to identify factors which prevent or motivate blood donors during pandemic. This study was designed to understand blood donors' knowledge, attitudes, and perceptions during the Covid-19 pandemic. A descriptive cross-sectional study to assess donor's knowledge, attitude, and perception regarding blood donation using self-administered 20 questions. The study duration was 4 months. A total 503 whole blood donors participated. The fear of infection and reduced blood donor motivation were observed to be the major deterrents of blood donation activity. Environment of blood donation area and travel to blood donation site were perceived two major sources of Covid-19 infection by participants. The top 3 motivational factor for blood donation were direct patient request to donate (30%), followed by family/ friends need and social media campaigns (26% each). Most donors (70.6%) were aware of importance of Covid-19 appropriate behaviour during current pandemic. The 67% donors felt that adequate Covid-19 preventive measures had been followed by the staff involved in blood collection. Based on the survey results, the inferences are that donors may harbour fear of infection and concerns for their safety, deterring blood donation. The direct appeal from a patient's relative to donate blood or a requirement in their family/friends and social media appeals emerge important factors to motivate donors. Travel facility arrangement may aide blood donation. Most of the donors are more than satisfied with the blood donation experience and are motivated to inform the transfusion services of any appearance of Covid-19 symptoms post donation. The donors were satisfied with the steps to reduce Covid-19 infection. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-021-01504-y.

Therapeutic apheresis and non-blood donor related apheresis current practices at various blood centres of healthcare organisations of India: A brief online survey.

OBJECTIVES: To determine the variability in therapeutic apheresis (TA) and non-blood donor related apheresis practices, and the extent of expertise and knowledge of blood centre staff. BACKGROUND: Apheresis activity that was earlier limited to therapeutic plasma exchange (TPE) and donor apheresis at few centres in India has seen remarkable surge involving many centres practising TA and non-blood donor related apheresis. The decentralised transfusion medicine practice in country has resulted in wide variability of knowledge and practice of TA. An online survey was conducted to achieve study objectives. STUDY DESIGN AND METHODS: A 22 questionnaire survey was sent to the 215 blood centres through e-mail link focussing on three aspects; basic information of the participating centres, details of TA procedures and education and training levels of the staff. RESULTS: Majority (71.9%) of centres were teaching institutions among analysed 57 centres. TPE (85.9%) and therapeutic cytapheresis (71.9%) were the most common TA procedures. The clinical haematology (68.4%) followed by neurology (64.9%) were the specialities utilising TA. The 64.9% centres used continuous flow cell separator and central venous access (52%) was preferred vascular access. A combination of normal saline, fresh frozen plasma and 5% albumin replacement fluid was first choice. Doctors involved in TA were trained in apheresis during their MD/DNB degree, but no structured training program existed for other category of staff. CONCLUSION: There was a wide variability in TA practice in India and a dedicated training program for all categories of staff was emphasised by majority of participants.

Case series of HbQ-India, a rare alpha globin variant in a referral laboratory setting in South India.

HbQ variants are rare alpha globin chain variants commonly found in Sindhi community. It results from a point mutation of α-1 globin gene at position 223 of the coding region of exon 64. It is inherited in an autosomal dominant fashion. HbQ-India is usually clinically silent in heterozygous state unless associated with other conditions like beta thalassemia, alpha thalassemia, HbE disease, or nutritional anemia. High performance liquid chromatography (HPLC) identifies HbQ-India with a prominent peak present just after the Sickle window. We present five cases of HbQ-India from a retrospective analysis of 6034 cases over a period of 3 years, a rarity in a referral setting of South India. Awareness of this entity is important for appropriate recognition to prevent clinically symptomatic hemoglobinopathies. This study also highlights the retention time (RT) and characteristic chromatographic HPLC pattern seen in HbQ-India.

Analysis of Donor Safety in High Yield Plateletpheresis Procedures: An Experience from Tertiary Care Hospital in South India.

The apheresis platelets are the preferred blood components for the thrombocytopenic hemato-oncology patients. The one of the important factors for post transfusion increment is the dose of the platelet product infused. The minimum platelet product yield is defined but the amount of maximum possible platelets collection from a single donor is not universally defined. There is lots of apprehension in our country for apheresis procedures harvesting more than a standard unit. This retrospective observational study was conducted to determine safety of high yield plateletapheresis collection among Indian donors This retrospective observational study was conducted for a period of 15 months including all consecutive plateletapheresis procedures. The informed consent had been obtained from all donors including high yield plateletapheresis (Yield ≥ 5 × 1011). The apheresis product was subjected to platelet count. The donor adverse reactions were recorded along with procedural details. Post procedure complete blood count was done for the donors who consented for post procedure blood sample draw A total 569 procedures were performed during this period including 174 high yield procedure. The 526 procedures were analyzed for adverse donor reactions. The 43 were excluded for adverse donor reaction analysis due to yield less than 3 × 1011 (n = 43). The adverse reactions rate between high yield procedures (18/174, 10.34%) and normal yield (20/352, 5.68%) were not statistically different (p = 0.052). The phlebotomy related complication (3.23%) followed by citrate toxicity (2.28%) were the two most common adverse reaction observed. The adverse reactions associated with high yield plateletapheresis procedures are comparable to normal yield procedures in term of overall adverse reactions observed and post procedural platelet counts. This can be beneficial to patients by providing products of greater yield.

Prevalence of risk factors for platelet transfusion refractoriness in multitransfused hemato-oncological patients at tertiary care center in North India.

BACKGROUND: This study was designed to determine the prevalence and assess the risk factors responsible for platelet transfusion refractoriness in hemato-oncological patients. MATERIALS AND METHODS: The study included 30 patients. Twelve were clinically diagnosed as aplastic anemia and the 18 were of acute myeloid leukemia. A prospective 3 months follow-up was planned to monitor the response of platelet transfusion therapy, based on their posttransfusion corrected count increment at 1(st) and 24(th) h. Based on the observations, patients were categorized into refractory and nonrefractory groups. Common nonimmunological causes such as fever, sepsis, bleeding, disseminated intravascular coagulation, chemotherapy, splenomegaly, ABO mismatch, and antithymocyte globulin therapy were monitored. Among the immunological causes, presence of antihuman leukocyte antigen (HLA) class I antibodies and platelet glycoprotein antibodies in patient's serum were monitored. RESULTS: During the study period, 17 (56.66%) patients did not show desired platelet count increment. Transfusion requirements of refractory group for both red cell and platelet product were significantly higher (P < 0.05) in comparison to nonrefractory group. Among immunological causes, anti HLA class I antibodies (P < 0.013), antihuman platelet antigen-5b antibodies (P < 0.033) were significantly associated with refractoriness. Among nonimmunological causes, bleeding (P < 0.019, odd ratio 8.7), fever (P < 0.08, odd ratio 5.2), and infection (P < 0.07, odd ratio 5.4) were found to associated with refractoriness. CONCLUSION: Platelet refractoriness should be suspected in multitransfused patients not showing expected increment in platelet counts and thoroughly investigated to frame further guidelines in order to ensure proper management of these kind of patients.

Anti-N antibody reacting at 37°C: An unusual occurrence interfering with routine testing: Two interesting cases.

Most anti-N antibodies are naturally occurring, IgM antibodies, and not active above 25°C and are not clinically significant but IgG anti- N has also been described. Immune anti-N resulting from multiple transfusions does occur & has been implicated as the cause of hemolytic transfusion reactions and mild hemolytic disease of fetus and newborn. Anti- N reacting at room temperature can be a cause for ABO blood group discrepancy.

Blocked D phenomenon and relevance of maternal serologic testing.

A blood requisition for double-volume exchange transfusion was received for a 2-day-old male child born to a 29-year-old multiparous female (P2002) referred to our institute having neonatal jaundice with encephalopathy; no maternal sample was received. the neonatal blood sample was typed as group A, D-, and the direct antiglobulin test (DAT) was strongly positive (4+) using the gel method. Mono-specific DAT showed the presence of IgG antibodies on neonatal red blood cells (RBCs). Acid elution and gentle heat elution (at 56°C) confirmed the presence of anti-D on neonatal RBCs. The baby received two exchange transfusions with group O, D-, packed RBCs compatible with his own serum. Later, on day 3, the neonate's mother was typed as group AB, D-, and her serum revealed the presence of alloanti-D, -C, and -S reactive in the anti-human globulin phase. The anti-D titer was 1024. this report highlights the "blocking" phenomenon caused by maternal anti-D in a case of hemolytic disease of fetus and newborn with a positive DAT.

Alloimmunization and autoimmunization in transfusion dependent thalassemia major patients: Study on 319 patients.

BACKGROUND: The development of anti-red blood cell antibodies (both allo-and autoantibodies) remains a major problem in thalassemia major patients. We studied the frequency of red blood cell (RBC) alloimmunization and autoimmunization among thalassemia patients who received regular transfusions at our center and analyzed the factors, which may be responsible for development of these antibodies. MATERIALS AND METHODS: The study was carried out on 319 multiply transfused patients with ß-thalassemia major registered with thalassemia clinic at our institute. Clinical and transfusion records of all the patients were examined for age of patients, age at initiation of transfusion therapy, total number of blood units transfused, transfusion interval, status of splenectomy or other interventions. Alloantibody screening and identification was done using three cell and 11 cell panel (Diapanel, Bio-rad, Switzerland) respectively. To detect autoantibodies, autocontrol was carried out using polyspecific coombs (IgG + C3d) gel cards. RESULTS: Eighteen patients out of total 319 patients (5.64%) developed alloantibodies and 90 (28.2%) developed autoantibodies. Nine out of 18 patients with alloantibodies also had autoantibodies. Age at first transfusion was significantly higher in alloimmunized than non-immunized patients (P = 0.042). Out of 23 alloantibodies, 52.17% belonged to Rh blood group system (Anti-E = 17%, Anti D = 13%, Anti-C = 13%, Anti-C(w) = 9%), 35% belonged to Kell blood group system, 9% of Kidd and 4% of Xg blood group system. CONCLUSION: Alloimmunization was detected in 5.64% of multitransfused thalassemia patients. Rh and Kell blood group system antibodies accounted for more than 80% of alloantibodies. This study re-emphasizes the need for RBC antigen typing before first transfusion and issue of antigen matched blood (at least for Rh and Kell antigen). Early institution of transfusion therapy after diagnosis is another means of decreasing alloimmunization.

Significance of serological monitoring in a Bombay Rh (D) negative phenotype pregnant woman: a case report.

A 32 year old Indian female was referred to our hospital at 32 weeks of gestation because of difficulty in blood group determination and further antenatal care. The results of cell and serum grouping of her blood sample were suggestive of Bombay (O(h)) Rh (D) negative phenotype. An indirect antiglobulin test (IAT) using a pool of red cells from two Bombay Rh (D) positive blood donors gave negative result using the tube as well as the gel technique (LISS-Coombs Card, BioRad, Switzerland), thus ruling out anti-D antibody in her serum. The anti-H titer was 16 (tube technique) and with dithiothreitol (DTT) treated patient's serum the antibody screening was negative suggestive of IgM type of anti-H antibodies. Within the patient's family, only one member (younger sister) was of O(h) phenotype and also was Rh (D) negative. The baby was born vaginally at 38+6 weeks of gestation and was non-hydropic with a packed cell volume (PCV) of 55%. The baby's blood group was AB Rh (D) negative and the cord blood direct antiglobulin test (DAT) was negative. Thus, a careful serological testing of O(h) phenotype antenatal women especially with Rh (D) negative phenotype is of utmost importance in determining the isoimmunization status.