Hamman Syndrome with a Rare Feature of Pneumorrhachis - An Unusual Complication of Polysubstance abuse and e-vaping.

Hamman syndrome is defined as dissection of air in mediastinum and skin fascia usually due to increased intrathoracic pressure. The air leak tends to make its way into pleural and pericardial layers; however, in rare instances air can also dissect into epidural spaces, regarded as pneumorrhachis. We present a case of a young male with a history of polysubstance abuse and e-vaping, who presented with symptoms of altered mental status. Given the concerning physical examination, a computed tomography of the chest was undertaken, which showed pneumothorax, pneumomediastinum and pneumorrhachis. The patient was closely monitored in the intensive care unit and improved after symptomatic management. The symptoms of pneumorrhachis depend on the volume and location of air in intracranial and intraspinal space. Although asymptomatic in our case, it is crucial for clinicians to be aware that pneumorrhachis with Hamman syndrome can potentially cause neurological deficits and cardiopulmonary arrest in severe cases due to increased intraspinal and intracranial hypertension, emphasising the need for close monitoring. LEARNING POINTS: Elevated intrathoracic pressure generated by deep inhalation of an aerosolised product is one of the triggers of air dissection in pleural, pericardial, and mediastinal regions. In rare instances, air can also translocate into intracranial and intraspinal spaces, which is referred to as pneumorrhachis.Mostly asymptomatic, pneumorrhachis has the potential to develop acute neurological deficits due to increased intracranial and intraspinal pressure, validating the need for acute monitoring.Most cases of pneumorrhachis are managed conservatively. However, severe cases warrant decompression or high concentrations of oxygen administration to facilitate air absorption.

Current Novel Targeted Therapeutic Strategies in Multiple Myeloma.

Multiple myeloma (MM) is a hematologic malignancy caused by the clonal expansion of immunoglobulin-producing plasma cells in the bone marrow and/or extramedullary sites. Common manifestations of MM include anemia, renal dysfunction, infection, bone pain, hypercalcemia, and fatigue. Despite numerous recent advancements in the MM treatment paradigm, current therapies demonstrate limited long-term effectiveness and eventual disease relapse remains exceedingly common. Myeloma cells often develop drug resistance through clonal evolution and alterations of cellular signaling pathways. Therefore, continued research of new targets in MM is crucial to circumvent cumulative drug resistance, overcome treatment-limiting toxicities, and improve outcomes in this incurable disease. This article provides a comprehensive overview of the landscape of novel treatments and emerging therapies for MM grouped by molecular target. Molecular targets outlined include BCMA, GPRC5D, FcRH5, CD38, SLAMF7, BCL-2, kinesin spindle protein, protein disulfide isomerase 1, peptidylprolyl isomerase A, Sec61 translocon, and cyclin-dependent kinase 6. Immunomodulatory drugs, NK cell therapy, and proteolysis-targeting chimera are described as well.

The Outcome of Aplastic Anaemia Associated with Terbinafine Therapy.

Onychomycosis (OM), a widespread fungus that affects the toenails and/or fingernails, causes a large amount of morbidity and is very frequent in the general population. The best treatment is systemic antifungals. Terbinafine is a potent antifungal drug that works by targeting the keratin and lipids found in fungi. In the United States, the prevalence of this nail ailment ranges from 2% to 14%; it is 5.5% globally. Here, we describe a case of aplastic anaemia linked to oral terbinafine use. Clinicians should be aware of this rare adverse effect and early discontinuation of the treatment is required to prevent significant morbidity and mortality. LEARNING POINTS: Aplastic anaemia is a rare side effect of terbinafine.Patients should be advised about this, and serial laboratory testing can be helpful for those who are on a long-term course of terbinafine.Early diagnosis and start of treatment can lead to a favourable outcome.

Independent predictors of mortality and 5-year trends in mortality and resource utilization in hospitalized patients with diffuse large B cell lymphoma.

Background: This retrospective study analyzed factors influencing all-cause inpatient mortality in 80,930 adult patients (2016-2020) with diffuse large B cell lymphoma using the National Inpatient Sample database. Methods: Utilizing ICD-10 codes, patients were identified, and statistical analysis was conducted using STATA. Fisher's exact and Student's t tests compared proportions and variables, multivariate logistic regression examined mortality predictors, and a 5-year longitudinal analysis identified mortality and resource utilization trends. Results: The inpatient mortality rate was found to be 6.56% with a mean age of 67.99 years. Several hospital- and patient-level factors including specific comorbidities such as congestive heart failure, atrial fibrillation, acute kidney injury, chronic obstructive pulmonary disease, liver failure, pancytopenia, tumor lysis syndrome, and severe protein-calorie malnutrition were independently associated with inpatient mortality. Hospitalization costs showed an increasing trend, impacting the overall population and survivors. Conclusion: These insights may refine risk assessment, treatment selection, and interventions.

The Effect of High Parity on the Occurrence of Anaemia in Pregnant Women.

OBJECTIVE: To compare high-para and low-para women with respect to haematological findings, determinants, and consequences secondary to anaemia. STUDY DESIGN: Descriptive cohort study. Place and Duration of the Study: Maternity and Child Hospital, Hail, Saudi Arabia and Specialist Care Hospital (private), Islamabad, Pakistan, from April 2022 to April 2023. METHODOLOGY: The study population comprised of pregnant women in the last trimester, with the exception of those women who had more than one fetus and history of haematological disease. Purposive non-probability sampling technique was adopted. Hospital data were retrieved retrospectively for the past obstetrical, contraception usage, and supplement history. Blood parameters, type of delivery, and maternofetal complications were noted down. For qualitative-variable and quantitative-variable comparisons, Chi-square test and t-test were applied, respectively. Significance level was kept at p ≤0.05. RESULTS: The frequency of severe anaemia in high-para was 52%. High parity and anaemia had a significant dose-response relationship (p <0.05). There was a significant difference (p <0.05) in blood parameters between high-para and low-para groups. Main determinants identified for anaemia were lack of intake of iron-rich food (36%) followed by inadequate intake of oral iron (25%). Preterm birth (68%) and post-partum haemorrhage (96%) were significantly associated (p <0.05) with high parity. There was a significantly high proportion (83%) of high-para women with more than 3 cesarean deliveries and admissions in ICU. CONCLUSION: High parity and anaemia had a significant dose-response relationship. High parity was the main determinant of maternal and fetal admissions in ICU. KEY WORDS: Parity, Comparison, Maternal anaemia, Haematological findings, Diet, Contraception, Cost-effective.

Autoimmune diabetes from pembrolizumab: A case report and review of literature.

BACKGROUND: Immunotherapy, specifically the use of checkpoint inhibitors such as pembrolizumab, has become an important tool in personalized cancer therapy. These inhibitors target proteins on T-cells that regulate the immune response against tumor cells. Pembrolizumab, which targets the programmed cell death 1 receptor on T-cells, has been approved for the treatment of metastatic melanoma and non-small cell lung cancer. However, it can also lead to immune-related side effects, including pneumonitis, colitis, thyroid abnormalities, and rare cases of type 1 diabetes. CASE SUMMARY: The case presented involves an adult patient in 30s with breast cancer who developed hyperglycemia after receiving pembrolizumab treatment. The patient was diagnosed with diabetic ketoacidosis and further investigations were performed to evaluate for new-onset type 1 diabetes. The patient had a history of hypothyroidism and a family history of breast cancer. Treatment for diabetic ketoacidosis was initiated, and the patient was discharged for close follow-up with an endocrinologist. CONCLUSION: This literature review highlights the occurrence of diabetic ketoacidosis and new-onset type 1 diabetes in patients receiving pembrolizumab treatment for different types of cancer. Overall, the article emphasizes the therapeutic benefits of immunotherapy in cancer treatment, particularly pembrolizumab, while also highlighting the potential side effect of immune-related diabetes that can occur in a small percentage of patients. Here we present a case where pembrolizumab lead to development of diabetes after a few cycles highlighting one of the rare yet a serious toxicity of the drug.

Calcitriol induced hypercalcemia - a rare phenomenon in lung cancer: A case report.

BACKGROUND: Calcitriol-induced hypercalcemia has been rarely reported in cases of lung cancer; however, it is frequently reported in cases of lymphoid malignancy and granulomatous disease. We present a rare case of hypercalcemia associated with squamous cell cancer of the lung with elevated calcitriol level. CASE SUMMARY: A 61-year-old Caucasian female with severe hypercalcemia of 15 mg/dL, which led to a new diagnosis of metastatic lung cancer. Since the parathyroid hormone-related peptide (PTHrP) level was minimally elevated at 2.1 pmol/L, we believe excessive calcitriol production by tumor cells was the underlying mechanism for hypercalcemia. Calcitriol was significantly elevated at 130 pg/mL with a low 25-hydroxyvitamin D level of 25.9 ng/mL and suppressed PTH level of 8 pg/mL. Corticosteroids are generally used to treat calcitriol-induced hypercalcemia, but we successfully treated our patient with bisphosphonate, highlighting the further utility of bisphosphonates in hypercalcemia treatment. CONCLUSION: We believe that the underlying cause of hypercalcemia, in this case of metastatic squamous cell lung carcinoma, was elevated calcitriol, which was likely produced by the tumor cells. In addition to PTHrP, calcitriol levels should be included in the workup for hypercalcemia in cases of lung cancer. However, the pathophysiology and prognostic significance of dysregulated calcitriol production in solid tumors remain unclear and warrant further research. Bisphosphonate may be used as a steroid-sparing therapy even in cases of calcitriol-induced hypercalcemia and warrants further investigation.

Impact of Concomitant Thrombotic Thrombocytopenic Purpura on COVID-19 Mortality and Morbidity: A Nationwide Inpatient Sample Analysis.

Utilizing the comprehensive Nationwide Inpatient Sample (NIS) database, we examined the impact of thrombotic thrombocytopenic purpura (TTP) on the outcomes of patients with coronavirus disease-19 (COVID-19), emphasizing the potential role of the ADAMTS13 enzyme in disease pathogenesis and evolution. We analyzed extensive data from the NIS database using STATA v.14.2 and accounted for potential confounders using multivariate regression analysis to uphold the validity and reliability of the study. Among 1 050 045 adult patients hospitalized with COVID-19, only 300 (0.03%) developed TTP. These patients were younger (mean age 57.47 vs 64.74, P < .01) and exhibited a higher prevalence of preexisting conditions, such as congestive heart failure (13.33% vs 16.82%, P value not provided) and end-stage renal disease (3.33% vs 3.69%, P value not provided). On multivariate regression analysis, COVID-19 patients with concomitant TTP demonstrated a significant increase in mortality (adjusted odds ratio [AOR] 3.99, P < .01), venous thromboembolism (AOR 3.33, P < .01), acute kidney injury (AOR 7.36, P < .01), gastrointestinal bleeding (AOR 10.75, P < .01), intensive care unit admission (AOR 14.42, P < .01), length of hospital stay (17.42 days, P < .01), and total hospitalization charges ($298 476, P < .01). Thrombotic thrombocytopenic purpura in COVID-19 patients elevates the risk of mortality and complications, likely driven by the thrombotic nature of TTP. Our data underline the potential significance of ADAMTS13 in COVID-19 and TTP pathophysiology, suggesting its possible role as a therapeutic target.

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) in an Elderly Female: A Rare Case.

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a rare hematologic malignancy derived from type 2 Dendritic cells (immature Plasmacytoid dendritic cells). It is an aggressive lymphoma and most commonly presents as nonpruritic cutaneous lesions. It can also involve the bone marrow, lymph nodes, or circulating peripheral blasts. Here we present a 61-year-old female with skin bruises all over her body for the last three months associated with fatigue, night sweats, and unintentional weight loss. Her initial diagnosis was Acute Myeloid Leukemia (AML), but later she was diagnosed with BPDCN on tumor biopsy consistent with CD56+ neoplasm. The patient was treated with cyclophosphamide with steroid bridge. She was follow-up every week for the disseminated intravascular coagulation panel and monitored for tumor lysis syndrome. The management of the BPDCN is still unclear due to the condition's rarity. tagraxofusp has been used for remission induction as it has a higher response rate with an acceptable toxicity profile than conventional chemotherapy. Allogeneic hematopoietic stem cell transplantation (HCT) is recommended in patients with the first remission. For patients with relapsed/refractory disease, tagraxofusp demonstrates a good overall response, followed by HCT.

Hemophagocytic Lymphohistiocytosis and Pancreatic Cancer: A Rare Association.

Introduction: Hemophagocytic lymphohistiocytosis (HLH) or hemophagocytic syndrome (HPS) is a life-threatening and relatively rare condition that usually presents as a multisystem febrile illness. It is associated with excessive activation of the immune system and hypercytokinemia, leading to an unregulated aggregation of macrophages and lymphocytes. Here, we present the first likely case of HLH with metastatic pancreatic carcinoma being the underlying etiology. Case: A 44-year-old male with past medical history significant for heart transplant for which he was on tacrolimus, End-Stage Renal Disease (ESRD) on hemodialysis, recently treated CMV viremia, and necrotizing pancreatitis presented to the emergency with complaints of chills, decreased appetite, worsening non-bloody emesis, and dull left upper quadrant abdominal pain with radiation to the back for four days. No shortness of breath, fever, diarrhea, or blood in the stool was reported. Vitals on admission were blood pressure of 90/61 mmHg, a heart rate of 110 beats per minute, temperature of 98.1 °F, and respiratory rate of 18 per minute. Physical exam was significant for scleral icterus, decreased bibasilar breath sounds, moderate abdominal tenderness in the left flank and left upper abdominal quadrant without any palpable mass, and 1+ bilateral pedal edema. The remainder of the physical examination was benign. Electrocardiogram (EKG) showed sinus tachycardia without any ischemic changes, and chest x-ray showed mild pulmonary edema. Initial blood workup revealed WBC at 8.3 k/uL, hemoglobin of 10.2 g/dL, platelet count of 90 k/uL, and BUN/creatinine of 45/5.8 (baseline 40/5.0). Cardiac workup showed an elevated high sensitivity troponin level of 2479 pg/mL and brain natriuretic peptide (BNP) of 600 (0-100 pg/mL). The hepatobiliary profile showed an aspartate transaminase (AST) level of 2645 U/L, an alanine transaminase (ALT) of 2935 U/L, alkaline phosphatase (ALP) of 106 U/L, and lipase of 61 U/L, with total and conjugated bilirubin of 3.5 mg/dL and 2.1 mg/dL, respectively. Transthoracic echocardiogram (TTE) showed reduced left ventricular size with hyperdynamic systolic function. Computerized tomography (CT) scan of the abdomen (Fig. 1) revealed numerous new pulmonary nodules, ring-enhancing lesions within the liver, hyperenhancement of the pancreas with walled-off necrosis, and splenomegaly. Microbiological work-up was positive for cytomegalovirus (CMV) serologies (IgM and IgG) but absent viral load on Polymerase Chain Reaction (PCR). The initial diagnosis was systemic inflammatory respiratory syndrome (SIRS), likely septic versus distributive in the setting of pancreatitis, demand mediated non-ST segment elevation myocardial infarction (NSTEMI), and shock liver. Tacrolimus was held, and the patient was started on broad-spectrum antibiotics including vancomycin and cefepime for sepsis of unknown origin along with vasopressors for hypotension, requiring admission to the medical intensive care unit. Blood and urine cultures were collected on admission which remained negative throughout the course of hospital. CA19-9 levels were found elevated at 5587 U/mL. Liver biopsy was consistent with poorly differentiated adenocarcinoma of pancreatic origin. Both Infectious Disease and Hematology were consulted due to broad differential diagnoses. Due to the patient's continued hemodynamic instability and nonresponsiveness to the antibiotics, HLH was suspected with supporting labs as follows: ferritin 55,740 ng/mL (22-322 ng/mL), triglycerides 177 mg/dL (30-150 mg/dL), and fibrinogen 244 mg/dL (173-454 mg/dL), thus conferring 70-80% probability of HPS based on H-score. Soluble IL-2 R levels came out at 19,188 pg/mL (ref range 175-858 pg/mL). The patient couldn't be started on HLH treatment due to initial concerns of underlying infection and the delay in results of soluble IL-2 Receptor (IL-2 R) levels. The infection as a possible etiology was ruled out due to negative blood and urine cultures and HLH was attributed to pancreatic cancer. A marrow biopsy couldn't be pursued as the patient died within a week of hospitalization. An autopsy was not performed as per family's request. Conclusion: HLH can occur secondary to solid cell malignancies including those from the pancreas and should be kept high in the differential in critically ill cancer patients who are nonresponsive to antibiotics. H-score has been reported to be a more sensitive tool compared to the HLH protocol, especially if used earlier during the presentation. Further research is needed to compare diagnostic efficacy for HLH protocol verses H-score especially in critically ill patients as they might benefit from steroid trial.

Predictors of Escalation to Intensive Care Unit Level of Care Among Admissions for Alcohol Withdrawal.

According to the 2019 National Survey on Drug Use and Health, 14.5 million people ages 12 and older had alcohol abuse disorder. Alcohol withdrawal syndrome (AWS) can be defined as a collection of physical symptoms experienced due to abrupt cessation of alcohol after long-term dependence. In instances where regular inpatient management fails to control AWS symptoms, patients are shifted to intensive care units (ICUs) for closer monitoring and prevention of life-threatening complications like withdrawal seizures and delirium tremens (DTs), labeled as severe alcohol withdrawal syndrome (SAWS). Although this represents a significant healthcare burden, minimal studies have been conducted to determine objective predictors. In this study, we aim to determine the effect of patient demographics, socio-economic status, biochemical parameters, and clinical factors on the need for escalation to ICU level of care among admissions for AWS. Our study showed that factors such as a history of DTs or alcohol-related seizures, the initial protocol of management, degree of reported alcohol usage, activation of rapid response teams, mean corpuscular value, alcohol level on admission, highest Clinical Institute Withdrawal Assessment Alcohol Revised (CIWA-Ar) scored during the hospital stay, and the total amount of sedatives used were significantly associated with escalation to ICU level of care. Clinicians must use these objective parameters to identify high-risk patients and intervene early. We encourage further studies to establish a scoring algorithm incorporating biochemical parameters to tailor management algorithms that might better suit high-risk patients.

Genome-Wide Mining of Selaginella moellendorffii for Hevein-like Lectins and Their Potential Molecular Mimicry with SARS-CoV-2 Spike Glycoprotein.

Multidisciplinary research efforts on potential COVID-19 vaccine and therapeutic candidates have increased since the pandemic outbreak of SARS-CoV-2 in 2019. This search has become imperative due to the increasing emergences and limited widely available medicines. The presence of bioactive anti-SARS-CoV-2 molecules was examined from various plant sources. Among them is a group of proteins called lectins that can bind carbohydrate moieties. In this article, we present ten novel, chitin-specific Hevein-like lectins that were derived from Selaginella moellendorffii v1.0's genome. The capacity of these lectin homologs to bind with the spike protein of SARS-CoV-2 was examined. Using the HDOCK server, 3D-modeled Hevein-domains were docked to the spike protein's receptor binding domain (RBD). The Smo446851, Smo125663, and Smo99732 interacted with Asn343-located complex N-glycan and RBD residues, respectively, with binding free energies of -17.5, -13.0, and -26.5 Kcal/mol. The molecular dynamics simulation using Desmond and the normal-state analyses via torsional coordinate association for the Smo99732-RBD complex using iMODS is characterized by overall higher stability and minimum deformity than the other lectin complexes. The three lectins interacting with carbohydrates were docked against five individual mutations that frequently occur in major SARS-CoV-2 variants. These were in the spike protein's receptor-binding motif (RBM), while Smo125663 and Smo99732 only interacted with the spike glycoprotein in a protein-protein manner. The precursors for the Hevein-like homologs underwent additional characterization, and their expressional profile in different tissues was studied. These in silico findings offered potential lectin candidates targeting key N-glycan sites crucial to the virus's virulence and infection.

Timing matters: An analysis of the relationship between red cell transfusion timing and hospitalization outcomes in sickle cell crisis patients using the National Inpatient Sample database.

Vaso-occlusive pain crisis is a debilitating complication of sickle cell disease (SCD) and it is the most common cause of hospitalization among these individuals. We studied the inpatient outcomes among patients admitted with sickle cell crisis based on the timing of red blood cell transfusion. In this retrospective study, we used the United States National Inpatient Sample (NIS) data for the year 2019, to identify adult patients hospitalized with the principal diagnosis of sickle cell crisis who received simple red blood cell transfusion during their hospitalization. Patients were divided into two groups. Those who received simple red cell transfusion within 24 hours of admission were classified as early transfusion. After adjusting for confounders, the mean adjusted length of stay for patients with early transfusion was significantly lower than those who received a late blood transfusion by 3.51 days (p-value < 0.001) along with a decrease in mean adjusted hospitalization charges and cost, by 25,487 and 4,505 United States Dollar (USD) respectively. The early red cell transfusion was also associated with a decrease in inpatient mortality, demonstrated by an adjusted odds ratio (aOR) of 0.19 (p-value 0.036), and a reduction in in-hospital sepsis, with an aOR of 0.28 (p-value < 0.001), however, no statistically significant difference was found between the two groups regarding acute respiratory failure requiring intubation, vasopressors requirement, acute kidney injury requiring dialysis and intensive care unit (ICU) admission. We recommend timely triage and reassessment to identify sickle cell crisis patients requiring blood transfusion. This intervention can notably affect the inpatient length of stay, resource utilization, and hospitalization outcomes.

Neurological Adverse Effects of Immune Checkpoint Inhibitors and Chimeric Antigen Receptor T-Cell Therapy.

Immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor (CAR) T-cell constitute recently approved novel therapies targeted to treat a wide number of malignancies. Both the treatments modulate the immune system and can cause a number of immune-related adverse events (irAEs), including polyendocrinopathies, gastrointestinal and neurological complications. This literature review focuses on the neurological side effects of these therapies as these are uncommon and alter the course of the treatment. Neurological complications involve the peripheral and central nervous system, including polyneuropathy, myositis, myasthenia gravis, demyelinating polyradiculopathy, myelitis, and encephalitis. If early recognized, the neurological complications can be treated effectively with steroids to reduce the potential of short-term and long-term complications. Therefore, early identification and treatment of irAEs are needed to optimize the outcomes associated with ICPI and CAR T-cell therapies.

Systemic AL amyloidosis: current approach and future direction.

Systemic Light chain (AL) amyloidosis is a monoclonal plasma cell proliferative disorder characterized by deposition of amyloidogenic monoclonal light chain fragments causing organ dysfunction. It is a fatal disease and if not diagnosed and treated early can lead to organ failure and potentially death. The renal system along with the cardiovascular system are the most common organs involved but other organs such as gut and liver can be involved as well. The initial evaluation of patients requires confirming the diagnosis with tissue biopsy and staining with Congo red followed by confirmatory typing with mass spectrometry of the Congo red positive tissue. Then establishing the extent of the organs involvement by various staging and biomarkers testing. The treatment options and the tolerability of therapy depend on the disease staging, frailty, and co-morbidities. The autologous hematopoietic cell transplantation (HCT) after high dose melphalan therapy is an effective strategy which is usually done after initial bortezomib induction therapy. Unfortunately, most systemic AL amyloidosis patients are not candidate for HCT due to frailty, old age, multi-organ involvement, renal and heart failure at the time of diagnosis. While it is widely accepted that the patients need to be treated until they achieve complete hematologic response, the maintenance therapy after HCT is not well established in AL amyloidosis. In this review, we report the literature on the latest treatment updates of AL amyloidosis and the ongoing clinical trials highlighting the future treatments.

Liquid biopsies and minimal residual disease in myeloid malignancies.

Minimal residual disease (MRD) assessment through blood component sampling by liquid biopsies (LBs) is increasingly being investigated in myeloid malignancies. Blood components then undergo molecular analysis by flow cytometry or sequencing techniques and can be used as a powerful tool for prognostic and predictive purposes in myeloid malignancies. There is evidence and more is evolving about the quantification and identification of cell-based and gene-based biomarkers in myeloid malignancies to monitor treatment response. MRD based acute myeloid leukemia protocol and clinical trials are currently incorporating LB testing and preliminary results are encouraging for potential widespread use in clinic in the near future. MRD monitoring using LBs are not standard in myelodysplastic syndrome (MDS) but this is an area of active investigation. In the future, LBs can replace more invasive techniques such as bone marrow biopsies. However, the routine clinical application of these markers continues to be an issue due to lack of standardization and limited number of studies investigating their specificities. Integrating artificial intelligence (AI) could help simplify the complex interpretation of molecular testing and reduce errors related to operator dependency. Though the field is rapidly evolving, the applicability of MRD testing using LB is mostly limited to research setting at this time due to the need for validation, regulatory approval, payer coverage, and cost issues. This review focuses on the types of biomarkers, most recent research exploring MRD and LB in myeloid malignancies, ongoing clinical trials, and the future of LB in the setting of AI.

Molecular evolutionary model based on phylogenetic and mutation analysis of SARS-CoV-2 spike protein sequences from Asian countries: A phylogenomic approach.

The lethal pathogenic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has caused the COVID-19 pandemic, posing serious risks to people. The clove-like spike (S) protein that distinguishes coronaviruses from other viruses is important for viral pathogenicity, evolution, and transmission. The investigation of the unique structural mutations of the SARS-CoV-2 spike protein among 34 Asian countries, as well as the resulting phylogenetic relationship, provided critical information in understanding the pathogenesis. This can be utilized for the discovery of possible treatments and vaccine development. The current study analyzed and depicted phylogenetic and evolutionary models useful for understanding SARS-CoV-2 human-human transmission dynamics in Asian regions with shared land borders. Further, integrated bioinformatics analysis was performed to predict the pathogenic potential and stability of 53 mutational positions among 34 coronavirus strains. Mutations at positions N969K, D614G and S884F have deleterious effects on protein function. These findings are crucial because the Asian mutations could potentially provide a vaccine candidate with co-protection against all SARS-CoV-2 strains. This region is vulnerable because of the high population density and the volume of domestic and international travel for business and tourism. These discoveries would also aid in the development of plans for governments and the general populace to implement all required biocontainment protocols common to all countries.

Role of Parity and Age in Cesarean Section Rate among Women: A Retrospective Cohort Study in Hail, Saudi Arabia.

In the context of the global increase in the rate of cesarean deliveries, with an associated higher morbidity and mortality, this study aimed to investigate the role of maternal age and parity in the cesarean section rate among women in the Hail Region of Saudi Arabia. This retrospective cohort study used data collected from the labor ward of the Maternity and Child Health Hospital, Hail, over a period of 8 months, forming a cohort of 500 women. Women were categorized into four different parity classes. The results revealed that there was no significant relationship between cesarean deliveries and maternal age (p-value, 0.07). There was no significant difference in the mode of delivery between the study's parity cohort group. A significant increase in cesarean deliveries was noticed among obese women with a BMI between 35-39.9 (52.14%). This increase was even greater among those with a BMI above 40 (63.83%). Fetal distress, malpresentation and abruptio placenta were the most significant indications for CS among all age groups (p-value 0.000, 0.021, and 0.048, respectively). Conclusions: The number of cesarean deliveries has no association with parity or age. However, there was a statistically significant association with BMI, a perineal tear after previous vaginal delivery, and a history of diabetes mellitus and gestational diabetes. The most reported reasons for CS were fetal distress, malpresentation, and abruptio placenta among all age groups.

Efficacy and Safety of Recombinant Thrombomodulin for the Prophylaxis of Veno-Occlusive Complication in Allogeneiccit Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

BACKGROUND: Hepatic veno-occlusive disease (VOD), also termed as sinusoidal obstruction syndrome (SOS), is a lethal complication after hematopoietic stem cell transplantation (HSCT). Various factors put patients undergoing allogeneic HSCT at an increased risk for VOD. Thrombomodulin (TM) is an important factor which has a wide range of effects, including anticoagulant, anti-inflammatory, angiogenic, and protective effect, on endothelial cells. It plays a role in preventing excessive coagulation and thrombosis by binding with thrombin and inhibiting the coagulation cascade. There are a limited number of options for the prevention of this fatal complication. Recombinant thrombomodulin (rTM), an endothelial anticoagulant co-factor, as prophylactic therapy might be able to prevent veno-occlusive complications after stem cell transplantation. METHODS: A literature search was performed on PubMed, Embase, and Web of Science. We used the following Mesh terms and Emtree terms, "Hepatic Veno-Occlusive Diseases" OR "Sinusoidal Obstruction" OR "Stem Cell Transplantations " AND "Thrombomodulin" from the inception of data up to April 1, 2021. The PICO (Patient/Population, Intervention, Comparison and Outcomes) framework was used for the literature search. RESULTS: For the VOD incidence after HSCTstem cell transplantation, the result was in favor of rTM with a risk ratio (RR) of 0.53 (I2 = 0%, 95% confidence interval [CI] = 0.32-0.89). The incidence of transplant-associated thrombotic microangiopathy (TA-TMA) after HSCT was reduced in rTM group. The RR for incidence of TA-TMA was 0.48 (I2 = 62%, 95% CI = 0.20-1.17) favoring rTM. The RR for incidence of graft-versus-host disease (GvHD) was also lower in rTM group, 0.48 (I2 = 64%, 95% CI = 0.32-0.72). CONCLUSION: In our meta-analysis, we evaluate the efficacy and safety of rTM in the prevention of SOS after HSCT. According to our results, rTM use led to a significant reduction in SOS episodes, TA-TMA, and GvHD after HSCT.