Hybrid de novo and haplotype-resolved genome assembly of Vechur cattle - elucidating genetic variation.

Cattle contribute to the nutritional needs and economy of a place. The performance and fitness of cattle depend on the response and adaptation to local climatic conditions. Genomic and genetic studies are important for advancing cattle breeding, and availability of relevant reference genomes is essential. In the present study, the genome of a Vechur calf was sequenced on both short-read Illumina and long-read Nanopore sequencing platforms. The hybrid de novo assembly approach was deployed to obtain an average contig length of 1.97 Mbp and an N50 of 4.94 Mbp. By using a short-read genome sequence of the corresponding sire and dam, a haplotype-resolved genome was also assembled. In comparison to the taurine reference genome, we found 28,982 autosomal structural variants and 16,926,990 SNVs, with 883,544 SNVs homozygous in the trio samples. Many of these SNPs have been reported to be associated with various QTLs including growth, milk yield, and milk fat content, which are crucial determinants of cattle production. Furthermore, population genotype data analysis indicated that the present sample belongs to an Indian cattle breed forming a unique cluster of Bos indicus. Subsequent FST analysis revealed differentiation of the Vechur cattle genome at multiple loci, especially those regions related to whole body growth and cell division, especially IGF1, HMGA2, RRM2, and CD68 loci, suggesting a possible role of these genes in its small stature and better disease resistance capabilities in comparison with the local crossbreeds. This provides an opportunity to select and engineer cattle breeds optimized for local conditions.

Successful treatment of cytomegalovirus associated hemophagocytic lymphohistiocytosis with the interleukin 1 inhibitor - anakinra.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, frequently under-recognized condition associated with multi-organ failure and very high mortality. A 44-year-old woman was admitted with a 4-day history of fever, headache, delirium, and dyspnea. She progressed rapidly to type 1 respiratory failure and required intubation and mechanical ventilation. Laboratory tests showed pancytopenia, abnormal liver enzyme levels, elevated triglyceride level, and elevated ferritin level. Bone marrow biopsy showed features of HLH. Computed tomography scan showed bilateral consolidation. Bronchoalveolar lavage was positive for cytomegalovirus. She was treated with ganciclovir, methylprednisolone, broad spectrum antibiotics, and cytomegalovirus hyperimmunoglobulin without clinical response. Given the poor prognosis and reports of success in pediatric HLH, anakinra 100 µg subcutaneously daily was commenced. There was rapid defervescence, resolution of delirium, and improvement in gas exchange, leading to complete recovery. This case illustrates successful treatment of HLH associated with cytomegalovirus pneumonitis with the interleukin 1 inhibitor anakinra.

Influence of circulating levels of fibrinogen and perioperative coagulation parameters on predicting postoperative blood loss in cardiac surgery: a prospective observational study.

BACKGROUND: Fibrinogen, the major clotting protein in blood plasma, plays key roles in blood coagulation and thrombosis. In this prospective cohort study, we measured patient's fibrinogen levels and common coagulation parameters before and after cardiopulmonary bypass (CPB) and examined their relationships with postoperative blood loss. STUDY DESIGN: Patients undergoing cardiac surgery with CPB who did not have pre-existing coagulopathy were eligible. Standard blood and coagulation testing were performed before and after CPB. The association of these variables with postoperative blood loss (estimated blood loss from CPB) was assessed with Spearman's ranked correlation and multivariable linear regression models. RESULTS: Two hundred and fifty patients were enrolled in the study. The median blood loss was 780 mL (range 320-2340 mL). Variables independently associated with increasing blood loss were lower post-CPB platelet counts (p<0.001), lower postoperative fibrinogen levels (p<0.001), and larger percent decrease in fibrinogen levels (p<0.05). There was no correlation between preoperative fibrinogen levels and preoperative coagulation tests with postoperative bleeding. The only significant independent predictors of transfusion in a logistic regression model were postoperative fibrinogen concentration. CONCLUSION: Postoperative fibrinogen, the larger percent decrease in fibrinogen, and postoperative platelet levels are markers of bleeding and blood transfusion requirements after CPB than preoperative standard screening tests. Postoperative fibrinogen had the best predictive value of all tests of postoperative blood loss.

Use of recombinant activated Factor VII for refractory after lung transplant bleeding as an effective strategy to restrict blood transfusion and associated complications.

BACKGROUND: Recombinant activated factor VIIa (rFVIIa) has been increasingly used to stop massive bleeding after cardiothoracic surgical procedures. However, the risk : benefit profile of such a potent hemostatic agent remains unclear in the postsurgical patient, and the cost benefit is even less clear. In patients after lung transplantation, volume of blood transfused is of major concern, and all attempts are made to minimize large blood transfusions in this cohort. We report our experience with rFVIIa in patients with refractory bleeding after lung transplant surgery. STUDY DESIGN AND METHODS: All lung transplant patients who underwent single- or double-lung transplantation who received rFVIIa in the 5-year period, from January 2005 to June 2011, were included. A total of 15 patients were identified from a total of 95 lung transplant cases operated during this study period. Patient demographics, intra- and postoperative records were reviewed to assess the efficacy and safety of rFVIIa treatment. RESULTS: Patients with major bleeding treated with rFVIIa showed improved hemostasis with rapid normalization of coagulation variables. rFVIIa treatment was not associated with an increase in mechanical ventilation time, length of intensive care unit stay, or hospital stay compared to other lung transplant patients. In addition, the use of rFVIIa was associated with reduction in transfusion requirements of red blood cells, fresh-frozen plasma, and platelets (all p < 0.001). No definite thromboembolic-related event was recorded in our cohort. CONCLUSIONS: These data demonstrate that rFVIIa was associated with reduced blood loss, improvement of coagulation variables, and decreased need for transfusions. This reduction in losses led to a reduced requirement for blood transfusion, which may translate to a decrease in transfusion-related complications. Further investigation is needed to determine rFVIIa's safety and its efficacy in improving postoperative morbidity and mortality specifically in the field of post-lung transplantation surgery.

Impact of blood product transfusion on short and long-term survival after cardiac surgery: more evidence.

BACKGROUND: Despite the proven benefits in hemorrhagic shock, blood transfusions have been linked to increased morbidity and mortality. The short-term adverse effects of blood transfusion in cardiac surgical patients are well documented but there are very few studies that adequately assess the long-term survival. This study was undertaken to evaluate the effects of transfusion on both short-term and long-term survival after cardiac surgery. METHODS: Data from 5,342 patients who underwent a cardiac surgical procedure from January 2002 to December 2005 at our institution were reviewed. The effect of transfusion of packed red blood cells (PRBC) and other blood products was tested in a 2-level approach of transfusion (any) versus no transfusion, and also a 4-level approach of transfusion (PRBC, other blood products, and both blood and blood products) versus no transfusion. Long-term survival data of these patients were obtained. Cox proportional hazard models, Kaplan-Meier survival plots, and hazard functions were used to compare the groups. RESULTS: A total of 3,013 of the 5,342 study patients (56.4%) received transfusion during or within 72 hours of their cardiac surgery. Median time to death was significantly lower for patients who received transfusions; 1.15 years for PRC and 0.83 years for any transfusion, compared with 4.68 years in the non-transfused group. The overall 30-day mortality was 1.7%, but in patients who received transfusions (3.6%) was significantly higher than the non-transfused group (0.3%, p<0.001). The 1-year mortality (overall 3.9%) in the transfused group (7.3%, p<0.001) was also significantly higher than that in the non-transfused group (1.3%). The 5-year mortality rate in the transfused group was more than double that in the non-transfused group (16% vs 7%). After correction for comorbidities and other factors, transfusion was still associated with a 66% increase in mortality. CONCLUSIONS: This study suggests that blood or blood product transfusion during or after cardiac surgery is associated with increased short-term and long-term mortality. It reinforces the need for prospective randomized controlled studies for evaluation of restrictive transfusion triggers and objective clinical indicators for transfusion in the cardiac surgical patient population.

Foreign body aspiration pneumonia in an intravenous drug user.

Heroin use is associated with several well described respiratory complications, including noncardiogenic pulmonary edema, aspiration pneumonitis, acute respiratory distress syndrome,pneumonia, lung abscess, septic pulmonary emboli, and atelectasis. We describe an interesting case of a young female patient, an intravenous heroin user who presented with progressive dyspnea, hypoxia, and left lung consolidation.

Negative pressure pulmonary edema revisited: Pathophysiology and review of management.

Negative pressure pulmonary edema (NPPE) is a dangerous and potentially fatal condition with a multifactorial pathogenesis. Frequently, NPPE is a manifestation of upper airway obstruction, the large negative intrathoracic pressure generated by forced inspiration against an obstructed airway is thought to be the principal mechanism involved. This negative pressure leads to an increase in pulmonary vascular volume and pulmonary capillary transmural pressure, creating a risk of disruption of the alveolar-capillary membrane. The early detection of the signs of this syndrome is vital to the treatment and to patient outcome. The purpose of this review is to highlight the available literature on NPPE, while probing the pathophysiological mechanisms relevant in both the development of this condition and that involved in its resolution.

To transfuse, or not to transfuse: that is the question.

Transfusion practice, like medical practice in its entirety, has evolved rapidly over the past few decades. Recent research on clinical outcomes has examined the impact of blood transfusion on critically ill patients, patients with trauma, those undergoing cardiac surgery, those experiencing acute coronary syndromes, oncology patients and others. Evidence is mounting of adverse outcomes associated with blood transfusion in a wide variety of clinical contexts. Here, we highlight the deficit in the current literature guiding transfusion practice, and call for an Australasian study to fill this deficit.