Assessing the clinical efficacy of low-volume therapeutic plasma exchange in achieving recovery from acute liver failure induced by yellow phosphorous poisoning.

BACKGROUND: Acute liver failure (ALF) following yellow phosphorous (YP) ingestion is similar to acetaminophen-induced ALF and it has become a public concern in our region. This study assessed low volume therapeutic plasma exchange (LV-TPE) efficacy in improving the transplant free survival in YP poisoning. METHODS: Adult patients with toxicology reports of YP and ALF requiring critical care were included in the study. LV-TPE was planned for three consecutive days and three more if required. Performed 1.3 to 1.5 plasma volume replacing with 0.9% normal saline, 5% human albumin solution, and fresh frozen plasma based on ASFA 2019 criteria. MELD score, laboratory parameters, LV-TPE details were captured. The study end point was clinical outcome of the patients. RESULTS: Among 36 patients, 19 underwent LV-TPE and 17 opted out of LV-TPE and they were included as a control arm. The MELD score was 32.64 ± 8.05 and 37.83 ± 9.37 in both groups. There were 13 survivors in LV-TPE group leading to a 68.42% reduction in mortality. The coagulation and biochemical parameters showed a significant percentage change after LV-TPE. Refractory shock, delay in initiating procedure and acidosis were independent predictors of mortality. CONCLUSION: A well-timed LV-TPE improves the survival of patients with ALF due to YP poisoning.

Oxylipins in Breast Implant Associated Systemic Symptoms.

BACKGROUND: A subset of women with breast implants have reported a myriad of nonspecific systemic symptoms collectively termed systemic symptoms associated with breast implants (SSBI). SSBI symptoms are similar to manifestations associated with autoimmune and connective tissue disorders Breast tissue is rich in adipose cells, comprised of lipids. Insertion of an implant creates an oxidative environment leading to lipid oxidation. Oxylipins can influence immune responses and inflammatory processes. OBJECTIVES: This study explores the abundance of a spectrum of oxylipins in the peri-prosthetic tissue surrounding the breast implant. Since oxylipins are immunogenic, we sought to determine if they are associated with the SSBI subjects. We have also attempted to determine if the common manifestations exhibited by such subjects have any association with oxylipin abundance. METHODS: The study included 120 subjects divided in three cohorts. Forty-six subjects with breast implants exhibiting manifestation associated with SSBI, 29 in control cohort I subjects with breast implants not exhibiting manifestation associated with SSBI (non-SSBI) and 45 in control cohort II subjects without implants (normal tissue) were analyzed. Lipid extraction and oxylipin quantification was performed using LCMS. LC-MS/MS targeted analysis from the breast adipose tissue was performed. RESULTS: Of the fifteen oxylipins analyzed, four exhibited increased abundance in the SSBI cohort compared to the non-SSBI and normal cohorts. CONCLUSIONS: The study documents the association of the oxylipins with each manifestation reported by the subject. This study provides an objective assessment on the subjective questionnaire highlighting which symptoms could be more relevant than the others.

Role of Thromboelastogram in monitoring the activation of the coagulation pathway and assessing the associated risk factors for hypercoagulable state in transfusion dependent thalassemia patients.

BACKGROUND: Thromboembolic events are rare but one of the fatal complications in thalassemia. Assessment of the hypercoagulable state is not done regularly, and we have assessed the utility of Thromboelastography (TEG) for monitoring the activation of the coagulation pathway in patients with thalassemia. METHODOLOGY: A prospective single-center cohort study was conducted in a tertiary care set-up. Transfusion Dependent Thalassemia patients registered with the pediatric unit were screened for hypercoagulability using TEG during six months of the study period and followed up for three years for the development of thromboembolic events. Patient demographics, history of splenectomy, Serum ferritin levels and annual red cell transfusion requirement (mL/kg/year) were assessed. TEG parameters used were R time, K time, alpha angle, Maximum amplitude, Clot index, and Lysis 30. The thrombin generation test (V Curve) obtained from the first-degree derivate of the TEG velocity curve was also used for analysis. RESULTS: A total of 34 patients were recruited during the six months study period with an average age of 10.6 years ( ± 5.47). The average pre-transfusion hemoglobin level and the volume of packed red cells received were 7.24 g/dL and 152.82 mL/kg/year respectively. The TEG tracing was suggestive of a hypercoagulable state in 58.82% of patients. The mean values of angle (70.74), MA (64.16), CI (2.65) and TG (774.43) in TDT patients compared to age matched reference range (62.81, 57.99, 0.8, 577.83 respectively) was suggestive of prothrombotic changes. Annual blood transfusion requirement was negatively correlated with hypercoagulable status (-0.344, CI= -0.68 to 0.08). One out of 34 patients developed corona radiata infarct (with annual blood requirement; 112.7 mL/kg/Year). The risk to develop a hypercoagulable state appeared to be higher when the volume of RBCs transfused was less than 154 mL/kg/Year. CONCLUSION: TDT patients are at risk of developing thromboembolism, and screening with TEG may be useful to identify those at high risk.

Unveiling the masked native blood group following thalidomide therapy in a thalassemia patient: A 5 WHY analysis approach.

Blood grouping discrepancy in patients with hematological disorders can occur due to red cell sensitization following transfusion, transplantation, and pregnancy or pre-analytical errors. Prompt initiation of root cause analysis is vital to avoid complications of wrong blood transfusion. We present an unusual case of Rh mismatched grouping report of 24 year old female thalassemia patient being managed in our hospital since 2015. Her current type and screen were observed as O Rh D negative with negative antibody screen while the historical blood group was O Rh D positive. The pre-analytical errors were ruled out and blood grouping performed from fresh sample also demonstrated as O Rh D negative despite antigen enhancement techniques and had no recent transfusion history. We sought to reason out the possibilities for discordant Rh grouping report, historical and present group through "Funnel based problem solving 5 WHY analysis" approach. The review of the past clinical history revealed that the patient had undergone Rh mismatch bone marrow transplant (Rh D positive donor and Rh D negative recipient) at 5 years of age which soon resulted in graft failure. Yet, she continued to receive Rh D positive blood thereafter with no development of anti-D which explains the historical blood group. Recently the patient was started on thalidomide, the Hb F inducer drug, which helped in maintaining her hemoglobin level between 9 and 10 g/dl without transfusion support for two months. This allowed unmasking of native Rh D negative blood and the review of clinical history played a significant role in resolution of grouping discrepancy.

A Tropical Kiss by a Malabar Pit Viper.

Snakebite in India is often attributed to the "big 4," for which polyvalent anti-snake venom is effective. Also significant and less known is the burden of other venomous snakes, one of which is Trimeresurus malabaricus. We report a bite to the face of a tree climber by Trimeresurus malabaricus in the Western Ghats of India, which caused severe local envenomation in the form of facial edema and systemic signs of envenomation, including coagulopathy and hypotension. We discuss the role of thromboelastogram, infrared thermography, and routine diagnostics in this case, which led to the administration of Indian-made polyvalent anti-snake venom. The patient recovered and was discharged without any clinically evident physiological or physical dysfunction.

Experiential learnings from the Nipah virus outbreaks in Kerala towards containment of infectious public health emergencies in India.

Nipah virus (NiV) outbreak occurred in Kozhikode district, Kerala, India in 2018 with a case fatality rate of 91% (21/23). In 2019, a single case with full recovery occurred in Ernakulam district. We described the response and control measures by the Indian Council of Medical Research and Kerala State Government for the 2019 NiV outbreak. The establishment of Point of Care assays and monoclonal antibodies administration facility for early diagnosis, response and treatment, intensified contact tracing activities, bio-risk management and hospital infection control training of healthcare workers contributed to effective control and containment of NiV outbreak in Ernakulam.

Deletion in the A4GALT Gene Associated with Rare "P null" Phenotype: The First Report from India.

BACKGROUND: The present report illustrates a case with rare "P null" phenotype due to a large deletion in chromosome 22q13.2 and with clinically significant anti-PP1Pk antibody. Patient blood management in such cases is challenging. CASE REPORT: The transfusion center supporting the tertiary care referral center in the southern part of India received a blood sample from a trauma case for pre-transfusion testing. An antibody to a high-frequency blood group antigen was initially suspected. Following extensive immune-hematological workup, the patient was diagnosed to have naturally occurring anti-PP1Pk antibody and a rare "P null" phenotype. The genomic DNA of the patient was analyzed by exome sequencing followed by Sanger's sequencing. Molecular diagnostics revealed a large 21-bp deletion in chromosome 22q13.2 which encodes the A4GALT gene, resulting in truncation of seven amino acids I245-251P and resulted in rare "P null" phenotype. Patient blood management strategies were adopted to manage the patient conservatively without blood transfusion. CONCLUSION: A large deletion in chromosome 22q13.2 had resulted in a rare "P null" phenotype in the present case. The patient was a victim of a road traffic accident, required emergency hospitalization, as well as surgical intervention, and his plasma had antibodies to high-frequency antigens. A rare donor registry plays a major role in providing transfusion support to such cases.

The disappearance of blood group antigens: A clue to the clinical diagnosis of leukemia.

A 54-year-old male patient was admitted with low-grade intermittent fever not associated with chills. The cell grouping of the patient sample showed O Rh D positive and serum grouping as B, with a discrepancy to be resolved. Series of immunohematological workup was performed to rule out the discrepancy. Reviewing the past proxy history revealed that the patient blood group was B Rh D positive. Bone marrow aspirate showed hypercellularity with increased myelopoiesis and markedly suppressed megakaryopoiesis giving an impression of acute myeloid leukemia and was confirmed by flow cytometry. Based on the current results and past history the blood group of the patient was confirmed to be B Rh D positive with loss of B and H antigens expression on the red cell surface due to underlying leukemia. Correlating the lab results with the clinical details and the case history is an important step in resolving blood grouping discrepancy.

Thrombotic microangiopathy in hematotoxic snakebites and its impact on the prognosis: an entity often overlooked.

Snakebite associated thrombotic microangiopathy (TMA) is a spectrum of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury (AKI). We carried out this study to find out the prevalence of TMA in hematotoxic snake envenomation and to analyze its impact on the clinical outcome of patients. Retrospective data were collected from the medical records, hospital and lab information system after institutional ethics committee approval. Hematotoxic snake bite patients were categorized into Group 1 (with TMA) and Group 2 (without TMA). Chi square test, Mann-Whitney 'U' test and Odd's ratio (OR) were used for statistical analysis. Out of 331 snakebite cases admitted, 202 (64.33%) were hematotoxic envenomation with a mean age of 42.26 ± 15.61. Majority were males with a male to female ratio of 2.01:1. Lower limb was the most common site of bite (59.9%). The prevalence of coagulopathy, TMA and AKI observed was 56.4, 18.8 and 37.6% respectively. AKI had a significant risk of undergoing hemodialysis when it was associated with TMA (r = 0.635, OR = 19.3182, P < 0.0001). Higher number of patients in Group 1 received more blood products (r = 0.406, OR = 8.525, P < 0.0001). Prolonged hospital stay (17.25 ± 12.23 vs. 8.86 ± 7.18 days, P < 0.0001) and higher complication rates were (33.33% vs. 11.4%, P < 0.0048) observed in patients with TMA. Snakebite associated TMA has a significant impact on the prognosis and understanding the pathophysiology of this entity will help to formulate guidelines.

Role of therapeutic plasma exchange in snake bite associated thrombotic microangiopathy-A case report with review of literature.

Post snake bite renal failure due to thrombotic microangiopathy (TMA) is often overlooked and not considered as a separate entity while managing the patient. This case report highlights the efficacy of Therapeutic Plasma Exchange in managing the post envenomation TMA. Anti-snake venom was administered following severe hematotoxic envenomation, but later on developed acute kidney injury and hence hemodialysis was done for 2 days without much improvement. On third day of bite, diagnosis of TMA was made from microangiopathic hemolytic picture in peripheral blood smear, thrombocytopenia and renal failure. Therapeutic plasma exchange with human albumin solution was started on a daily basis and after 3 cycles, patient's condition improved as shown by the laboratory parameters. Though this entity is not well defined, the supporting evidence is found in few reports of published literature. Hence, we propose plasma exchange as an adjunctive therapeutic option in post snake TMA.

Evaluating patient blood management practices using PBM metrics in a tertiary care center.

BACKGROUND: PBM metrics play a crucial role in assessing and monitoring the effectiveness of PBM programs in healthcare settings. The present study aimed to assess the indicators to achieve effective enforcement of PBM at a tertiary care referral hospital. SUBJECTS AND METHOD: A prospective observational study was conducted on patients admitted for elective surgery at a tertiary care referral centre. PBM metrics were developed and assessed for various parameters, including documentation, patient evaluation, blood ordering schedule, and appropriateness. Experts in transfusion medicine and haematology checked content validity. Eleven different parameters were analysed, and a score was assigned based on the performance. The outcome was categorized as poor, satisfactory, or good. RESULTS: The study included 612 patients meeting the inclusion criteria and recruited from Orthopaedics, General Surgery, OBG, Urology, and ENT departments. All departments completed pre-operative anaemia tests, with General Surgery and Orthopaedics conducting the most red cell transfusions. During the study, all of the blood units were used, and there was no waste. The C/T ratio was greater in the Departments of General Surgery, Urology, and Otorhinolaryngology. Pre-operative anaemia was found in 44.12% of patients, 44 patients had red cell transfusions, with 65% getting single-unit PRBC transfusions. All departments received a PBM score between 17-19, showing adequate PBM but with room for improvement. CONCLUSION: The current study utilized Patient Blood Management (PBM) metrics to critically assess the existing practices and identify the key gaps and areas for improvement in a tertiary care centre.

S.O.S. - Save our supplies: Understanding reasons to tackle the challenge of wasted returned blood products.

OBJECTIVES: To evaluate the return of blood components across different hospital areas, reasons for the same and suggest preventive strategies which might reduce out of controlled temperature storage (CTS) blood logistics and wastage. MATERIAL AND METHODS: A retrospective audit was carried out in the department of Transfusion Medicine from January 2019 to December 2022. Data related to returned blood components was compiled using departmental records and blood centre software entries. RESULTS: A total of 218 instances of returned components were noted and the total number of components returned were 442 (0.4% of all issued components) (38.4% (170) packed red blood cells, 16.2% (72) single donor cryoprecipitate concentrate, 19.6% (87) platelet concentrate and 25.5% (113) fresh frozen plasma). Components were returned back within 30 mins in only 27% (59/218) of all instances . Wards followed by high dependency units/intensive care units were noted to have the highest number of instances (86 (39.4%) and 69 (31.6%) respectively) with emergency department having the least,comprising 19 instances (8.7%). 77.9% (170/218) instances were observed for routine transfusion requests and 44.5% (97/218) of all instances could have been prevented by an appropriate clinical status assessment of the patient. CONCLUSION: Stakeholders such as clinicians, transfusion laboratory professional and nursing staff must take consolidated efforts to eliminate wastage of blood components. Instances of returned blood components can be targeted by the hospital quality team as a quality improvement project.

The Lymphedematous Limb as a Donor Site for Breast Fat Grafting.

Breast cancer-related lymphedema results in chronic upper limb swelling with subcutaneous deposition of fluid and fibroadipose tissue. Morbidity includes psychosocial distress, infection, and difficulty using the extremity. Operative management includes excisional procedures such as suction-assisted lipectomy to reduce abnormal subcutaneous fibroadipose tissue to improve limb volume. Patients who have had postmastectomy breast reconstruction often benefit from fat grafting. This report introduces the concept of fat grafting the breast using the lymphedematous arm as a donor site. This technique improves the volume of the limb by removing the excess subcutaneous adipose, and at the same time reconstructs the breast without adding a donor site not related to the breast cancer-related lymphedema.

Topical tissue nanotransfection of Prox1 is effective in the prophylactic management of lymphedema.

Lymphedema is chronic limb swelling resulting from lymphatic dysfunction. There is no cure for the disease. Clinically, a preventive surgical approach called immediate lymphatic reconstruction (ILR) has gained traction. Experimental gene-based therapeutic approaches (e.g., using viral vectors) have had limited translational applicability. Tissue nanotransfection (TNT) technology uses a direct, transcutaneous nonviral vector, gene delivery using a chip with nanochannel poration in response to a rapid (<100 ms) focused electric field. The purpose of this study was to experimentally prevent lymphedema using focal delivery of a specific gene Prox1 (a master regulator of lymphangiogenesis). TNT was applied to the previously optimized lymphedematous mice tail (day 0) directly at the surgical site with genetic cargo loaded into the TNT reservoir: group I (sham) was given pCMV6 (expression vector backbone alone) and group II was treated with pCMV6-Prox1. Group II mice had decreased tail volume (47.8%) compared to sham and greater lymphatic clearance on lymphangiography. Immunohistochemistry showed greater lymphatic vessel density and RNA sequencing exhibited reduced inflammatory markers in group II compared to group I. Prox1 prophylactically delivered using TNT to the surgical site on the day of injury decreased the manifestations of lymphedema in the murine tail model compared to control.

Quantification of Lymphangiogenesis in the Murine Lymphedema Tail Model Using Intravital Microscopy.

Background: Lymphedema is chronic limb swelling resulting from lymphatic dysfunction. It affects an estimated five million Americans. There is no cure for this disease. Assessing lymphatic growth is essential in developing novel therapeutics. Intravital microscopy (IVM) is a powerful imaging tool for investigating various biological processes in live animals. Tissue nanotransfection technology (TNT) facilitates a direct, transcutaneous nonviral vector gene delivery using a chip with nanochannel poration in a rapid (<100 ms) focused electric field. TNT was used in this study to deliver the genetic cargo in the murine tail lymphedema to assess the lymphangiogenesis. The purpose of this study is to experimentally evaluate the applicability of IVM to visualize and quantify lymphatics in the live mice model. Methods and Results: The murine tail model of lymphedema was utilized. TNT was applied to the murine tail (day 0) directly at the surgical site with genetic cargo loaded into the TNT reservoir: TNTpCMV6 group receives pCMV6 (expression vector backbone alone) (n = 6); TNTProx1 group receives pCMV6-Prox1 (n = 6). Lymphatic vessels (fluorescein isothiocyanate [FITC]-dextran stained) and lymphatic branch points (indicating lymphangiogenesis) were analyzed with the confocal/multiphoton microscope. The experimental group TNTProx1 exhibited reduced postsurgical tail lymphedema and increased lymphatic distribution compared to TNTpCMV6 group. More lymphatic branching points (>3-fold) were observed at the TNT site in TNTProx1 group. Conclusions: This study demonstrates a novel, powerful imaging tool for investigating lymphatic vessels in live murine tail model of lymphedema. IVM can be utilized for functional assessment of lymphatics and visualization of lymphangiogenesis following gene-based therapy.

Seroprevalence of Streptococcal Inhibitor of Complement (SIC) suggests association of streptococcal infection with chronic kidney disease.

BACKGROUND: Group A streptococcus (GAS) is an etiological agent for the immune mediated sequela post streptococcal glomerulonephritis (PSGN). In some populations PSGN is recognized as a risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). It was found that a significantly greater proportion of subjects with past history of PSGN than without the history exhibited seroreactions to streptococcal antigens called streptococcal inhibitor of complement (SIC) and to distantly related SIC (DRS). These antigens are expressed by major PSGN-associated GAS types. We therefore predicted that in populations such as India, which is endemic for streptococcal diseases and which has high prevalence of CKD and ESRD, greater proportions of CKD and ESRD patients exhibit seroreaction to SIC and DRS than healthy controls. METHODS: To test this we conducted a SIC and DRS seroprevalence study in subjects from Mumbai area. We recruited 100 CKD, 70 ESRD and 70 healthy individuals. RESULTS: Nineteen and 35.7% of CKD and ESRD subjects respectively were SIC antibody-positive, whereas only 7% of healthy cohort was seropositive to SIC. Furthermore, significantly greater proportion of the ESRD patients than the CKD patients is seropositive to SIC (p=0.02; odds ratio 2.37). No association was found between the renal diseases and DRS-antibody-positivity. CONCLUSIONS: Past infection with SIC-positive GAS is a risk factor for CKD and ESRD in Mumbai population. Furthermore, SIC seropositivity is predictive of poor prognosis of CKD patients.

A survey on insight of blood donors during COVID pandemic in Southern India.

INTRODUCTION: Knowledge, Attitude and Practices (KAP) surveys prove beneficial to the transfusion services by providing an insight into the donors and, thus, aiding in mobilizing and retaining voluntary blood donors. We aim to study the knowledge, attitude and practices of donors towards blood donation in a pandemic setting. METHODS: A cross-sectional observational study to assess the knowledge, attitude and practices of blood donors was conducted between June to and October 2020. Non-parametric tests (Mann - Whitney U and Kruskal - Wallis) were performed to evaluate the relation of knowledge, attitude and practices overall scores with age group, gender and history of blood donations (first vs. repeat). The Chi-Square test/Fisher's Exact test was used to evaluate the differences in the distribution of Knowledge, Attitude and Practices items within the groups. RESULTS: A total of 403 of 2,748 individuals who came for whole blood donation participated in the study. The mean age of the study population was 31.1years (SD ± 8.4 range: 18 - 58), with 75% of the donors donating for the first time. The fear of acquiring COVID-19 infection was perceived as a major reason for the eligible population not to donate. The overall knowledge, attitude and practice score among the donors was satisfactory, being 76.14%, with a significant association with age. The overall positive attitude and practices scores of blood donors were 85.48% and 78.04%, respectively. CONCLUSION: The KAP scores were satisfactory among the donors. Timely communication of the precautionary measures at blood centers to contain the spread of the COVID-19 infection and effective counseling would help in motivating and retaining blood donors.

A case report and review of literature on the role of automated red cell exchange in managing sickle cell crisis in India.

Red cell exchanges (RCE) help in the treatment of complications of sickle cell anemia (SCA) by reducing the viscosity of blood and improving the oxygen-carrying capacity. We present a case of sickle cell crisis (SCC) managed with automated RCE and also reviewed the literature to assess the utilization and clinical efficiency of this therapy in India. A 19-year-old gentleman diagnosed with SCA presented with acute chest syndrome. Hemoglobin (Hb) was 8.8 g%, hematocrit (HCT) was 24%, and HbS was 90%. As there was worsening of symptoms with conventional management, the patient underwent two procedures of automated RCE. The clinical condition of the patient was improved, HbS was reduced to 16% and HCT was remained at 21% postprocedure. Articles on automated RCE in SCA conducted in India were reviewed and four articles were analyzed based on the search strategy. All the included articles concluded automated RCE as an effective procedure for complications of SCA. Common indication in India was SCA patients undergoing surgery as a prophylactic measure. Automated RCEs are promising as an acute treatment for indicated sickle cell complications. This therapy is underutilized in the Indian scenario, especially in patients with SCC.

Biofilm-derived oxylipin 10-HOME-mediated immune response in women with breast implants.

This study investigates a mechanistic link of bacterial biofilm-mediated host-pathogen interaction leading to immunological complications associated with breast implant illness (BII). Over 10 million women worldwide have breast implants. In recent years, women have described a constellation of immunological symptoms believed to be related to their breast implants. We report that periprosthetic breast tissue of participants with symptoms associated with BII had increased abundance of biofilm and biofilm-derived oxylipin 10-HOME compared with participants with implants who are without symptoms (non-BII) and participants without implants. S. epidermidis biofilm was observed to be higher in the BII group compared with the non-BII group and the normal tissue group. Oxylipin 10-HOME was found to be immunogenically capable of polarizing naive CD4+ T cells with a resulting Th1 subtype in vitro and in vivo. Consistently, an abundance of CD4+Th1 subtype was observed in the periprosthetic breast tissue and blood of people in the BII group. Mice injected with 10-HOME also had increased Th1 subtype in their blood, akin to patients with BII, and demonstrated fatigue-like symptoms. The identification of an oxylipin-mediated mechanism of immune activation induced by local bacterial biofilm provides insight into the possible pathogenesis of the implant-associated immune symptoms of BII.

Illustration: Thromboelastography - A useful tool to monitor COVID-19-associated coagulopathy.

COVID 19 is caused by Severe Acute Respiratory Syndrome Corona Virus-2 which results in wide range of manifestations. Systemic hypercoagulation is a typical feature of COVID-19. We present a case of COVID-19 in whom TEG was performed on admission and hypercoagulability was diagnosed and hence patient was started on Enoxaparin sodium 6000 IU twice daily. TEG was repeated after 5 days which showed normal coagulation status and the patient was discharged without any thrombotic complications.