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Shewanella is a genus of Gram-negative marine bacteria with some species associated with human and shellfish illnesses. This study evaluated the abundance of Shewanella species in oysters and seawater from the Chesapeake and Maryland Coastal Bays at four sites between 2019 and 2021. Physicochemical parameters such as temperature, salinity, dissolved oxygen, turbidity, pH, chlorophyll-a, rainfall within the last 48 h, total dissolved solids, and atmospheric pressure were also recorded to evaluate if there was a correlation between environmental parameters and the level of Shewanella. The highest total Shewanella counts were 1.8 × 107 CFU/g in oysters and 4.0 × 102 CFU/mL in seawater. 16S rRNA sequencing was performed on 1,344 representative isolates of which 890 (713 oyster, 177 seawater) were confirmed as Shewanella within 16 species. The top four species isolated from oysters and seawater were S. khirikhana a known shrimp pathogen (49%), S. marisflavi (19%), S. loihica (11%), and S. algae (8%). Testing for alpha and beta hemolysis were performed on all confirmed Shewanella isolates. Beta hemolysis was observed in 405 (46%) of the isolates of which 313 were in oysters and 92 in seawater. In oysters, beta-hemolysis was most prevalent in S. khirikhana (233 of 344 isolates, 68%), while in seawater 64 of 92 isolates (70%) were beta-hemolytic strains. Beta-hemolysis suggests that these could be potentially pathogenic strains. Correlations were performed between physicochemical attributes of the seawater and Shewanella counts. Only seawater temperature and dissolved oxygen correlated with Shewanella counts (r = 0.45 and − 0.41), respectively. No correlations were observed between the physicochemical parameters and Shewanella abundances in oysters. Results suggest that virulent strains of Shewanella may be present in oysters and seawater from the Chesapeake and Maryland Coastal Bays, perhaps as a consequence of rising seawater temperatures. [ABSTRACT FROM AUTHOR]

Abstract Background Hemolytic disease of the fetus and newborn (HDFN) is a condition due to maternal blood group antibodies targeting antigens in fetal red blood cells, with significant prenatal/perinatal morbidity and mortality. Severe HDFN cases are often associated with alloimmunization against Rhesus D (RhD) or Kell antigens. Information about HDFN epidemiology and treatment in Latin American countries is limited. This review aims to identify and synthesize the available evidence on the epidemiology and management of HDFN in this region. Methods In July 2023, EMBASE, PubMed, LILACS, and other databases were searched for articles reporting epidemiology, treatment, prenatal and perinatal outcomes, and patient journey of HDFN cases in Latin American countries. A snowball search of cross-references and gray literature complemented the initial search. Publications in English, Spanish, and Portuguese were reviewed. Data were extracted using a defined template and charted in tables. Results We reviewed five guidelines and 19 observational studies from Brazil, Chile, Mexico, Argentina, Colombia, Panamá, Paraguay, and Peru. HDFN due to Rh alloimmunization ranged from 0.5 to 5 per 1000 live births, and anti-D remains the most frequent alloantibody type for severe HDFN. The perinatal mortality rate of HDFN is approximately 1.3–1.6 per 100,000 live births, and fetal deaths can reach 30% among patients treated with intrauterine transfusions. Up to 47% of alloimmunized pregnancies were referred to reference centers only during the third trimester. About 60% of eligible pregnancies received anti-D IgG prophylaxis. Conclusions Although estimates in LATAM countries are scarce and lack standardized measures, we observed that the incidence, morbidity, and mortality of HDFN in this region are problematic. RhD alloimmunization was reported in approximately up to 70% of severe HDFN cases, despite anti D HDFN being largely preventable.

Phytochemicals and metabolites make Moringa oleifera (MO) a very nutritious vegetable tree with therapeutic properties. MO leaves contain phytochemicals that have anticarcinogenic, antidiabetic, antioxidant, and antibacterial abilities. This study investigates the antibacterial, antioxidant, total phenolic, total flavonoid , and hemolytic and antimicrobial activities of MO leaf (MoLe) extracts grown indigenously in Pakistan. Phytochemical study utilizing qualitative chemical tests revealed the presence of key phytochemical components such as alkaloids, saponins, flavonoids, tannins, coumarins, quinones, and terpenoids in organic solvents. Antioxidant (SOD, POD, and CAT) activities in the MoLe aqueous extract vary dose‐dependently. Acetic acid extract endured the highest total phenolic content (TPC) and total flavonoid content (TFC), followed by n‐hexane, chloroform, and butanol solvents. The current investigation suggests that all extracts have the ability, to varying extents, to function as radical scavengers because of the presence of polyphenolics. 2,2‐Diphenyl‐1‐picrylhydrazyl (DPPH) activity was observed to be significantly varied in all solvents, with the highest activity observed in acetic acid, methanol, and n‐butanol. Maximum ZOI (mm) in Streptococcus pneumoniae (13 ± 1.24) and Staphylococcus aureus (17 ± 1.26) was marked by an aqueous solvent; likewise, Escherichia coli (13 ± 1.24) and Pseudomonas aeruginosa (15 ± 1.69) showed maximum ZOI by acetic acid and methanol, respectively. Additionally, the acetic acid extract showed significant inhibitory activity (ZOI, mm) against fungal pathogens Aspergillus fumigatus (22 ± 1.24), A. flavus (24 ± 1.24). Maximum hemolytic was documented by aqueous (0.51 ± 0.001) followed by acetic acid (0.38 + 0.003), whereas minimum one was exhibited by n‐hexane (0.3 ± 0.002). Overall, the results indicated that MoLe is an excellent selection for elevated antioxidants, DPPH activity, and biological control of bacterial and fungal pathogens. [ABSTRACT FROM AUTHOR]

Background: Hemolytic disease of the fetus and newborn (HDFN) is a condition due to maternal blood group antibodies targeting antigens in fetal red blood cells, with significant prenatal/perinatal morbidity and mortality. Severe HDFN cases are often associated with alloimmunization against Rhesus D (RhD) or Kell antigens. Information about HDFN epidemiology and treatment in Latin American countries is limited. This review aims to identify and synthesize the available evidence on the epidemiology and management of HDFN in this region. Methods: In July 2023, EMBASE, PubMed, LILACS, and other databases were searched for articles reporting epidemiology, treatment, prenatal and perinatal outcomes, and patient journey of HDFN cases in Latin American countries. A snowball search of cross-references and gray literature complemented the initial search. Publications in English, Spanish, and Portuguese were reviewed. Data were extracted using a defined template and charted in tables. Results: We reviewed five guidelines and 19 observational studies from Brazil, Chile, Mexico, Argentina, Colombia, Panamá, Paraguay, and Peru. HDFN due to Rh alloimmunization ranged from 0.5 to 5 per 1000 live births, and anti-D remains the most frequent alloantibody type for severe HDFN. The perinatal mortality rate of HDFN is approximately 1.3–1.6 per 100,000 live births, and fetal deaths can reach 30% among patients treated with intrauterine transfusions. Up to 47% of alloimmunized pregnancies were referred to reference centers only during the third trimester. About 60% of eligible pregnancies received anti-D IgG prophylaxis. Conclusions: Although estimates in LATAM countries are scarce and lack standardized measures, we observed that the incidence, morbidity, and mortality of HDFN in this region are problematic. RhD alloimmunization was reported in approximately up to 70% of severe HDFN cases, despite anti D HDFN being largely preventable. [ABSTRACT FROM AUTHOR]

Real-world studies of pyruvate kinase (PK) deficiency and estimates of mortality are lacking. This retrospective observational study aimed to identify patients with PK deficiency and compare their overall survival (OS) to that of a matched cohort without PK deficiency. Patients with ≥1 diagnosis code related to PK deficiency were selected from the US Veterans Health Administration (VHA) database (01/1995–07/2019); patients with a physician-documented diagnosis were included (PK deficiency cohort; index: date of first diagnosis code related to PK deficiency). Patients in the PK deficiency cohort were matched 1:5 to patients from the general VHA population (non-PK deficiency cohort; index: random visit date during match's index year). OS from index was compared between the two cohorts. Eighteen patients in the PK deficiency cohort were matched to 90 individuals in the non-PK deficiency cohort (both cohorts: mean age 57 years, 94% males; median follow-up 6.0 and 8.0 years, respectively). At follow-up, patients in the non-PK deficiency cohort had significantly longer OS than the PK deficiency cohort (median OS: 17.1 vs. 10.9 years; hazard ratio: 2.3; p = 0.0306). During their first-year post-index, 75% and 40% of the PK deficiency cohort had laboratory-confirmed anemia and iron overload, respectively. Among patients who died, cause of death was highly heterogeneous. These results highlight the increased risk of mortality and substantial clinical burden among patients with PK deficiency. While the intrinsic characteristics of the VHA database may limit the generalizability of the results, this is the first real-world study to characterize mortality in patients with PK deficiency. [ABSTRACT FROM AUTHOR]

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Durio kutejensis, commonly known as Lai durian, has a unique characteristics of a creamy texture and a combination of sweet and bitter tastes. This study aimed to isolate and screen yeast from fruits as a potential probiotic agent. The tests consisted of tolerance to bile salt and gastric acid at pH 2, antibacterial activity against Listeria monocytogenes and Salmonella enteriditis, and hemolytic activity on blood agar medium. The results showed that 40 yeasts isolated from Lai durian fruit and 34 of these isolates grew on YMA medium. The two isolates showed high significance in the probiotic tests. These two isolates were able to grow on bile salt up to a concentration of 2% and gastric acid for up to 6 h, with survival rates of 99.06% and 100%, respectively. Two isolates were identified as Pichia kudriavzevii UNJCC Y-137 and Candida tropicalis UN-JCC Y-140 Therefore, these two yeast isolates can be used as potential probiotic agents. [ABSTRACT FROM AUTHOR]

In Serbia, Babesia gibsoni in dogs is less common than Babesia canis. Although two clinical cases were reported a decade ago, no additional clinical reports have since been published. Recently, a co-infection of B. gibsoni and B. canis was documented in Austria following a dog's trip to Serbia. The objectives of this study were to present comprehensive clinicopathological results of two clinical cases of B. gibsoni monoinfection in dogs in Serbia. Two male dogs: an 11-year-old Shih Tzu, and a 2-yearold Pit Bull Terrier, presented with clinical signs related to babesiosis with a history of biting by another dog. Both dogs had regenerative anemia, thrombocytopenia, and monocytosis while Shih Tzu had immune-mediated hemolytic anemia (IMHA). B. gibsoni mono-infection was confirmed by PCR testing. Both dogs were treated with a single dose of imidocarb-dipropionate, and a combination of metronidazole, clindamycin, and doxycycline (MCD protocol). The Shih Tzu also received prednisolone for three weeks. Following the MCD protocol, the Pitt Bull recovered, although thrombocytopenia persisted for nine months. In contrast, Shih Tzu's clinical condition worsened. The prednisolone treatment was discontinued, and azithromycin and atovaquone were introduced, leading to recovery after another three weeks of treatment. Long-term clinical and PCR monitoring revealed that the Pit Bull Terrier exhibited a more favorable response and a lower frequency of relapses compared to Shih Tzu. The findings suggest that B. gibsoni has become a clinically significant pathogen in Serbia. The MCD protocol appears effective for treating acute B. gibsoni infection in dogs, but further investigation is required to evaluate its efficacy in eliminating the parasite. [ABSTRACT FROM AUTHOR]

The current study aims to ascertain the chemical composition and biological activities of thyme leaves essential oil (TEO), with an emphasis on its in silico molecular docking studies targeting the antibacterial properties of its constituents. TEO was extracted from dried leaves using a standardized procedure, with a yield of 0.75%. The chemical constituents of TEO were identified using Gas Chromatography-Mass Spectrometry (GC-MS). The primary compounds detected included carvacrol, o-acetyl thymol, α-pinene, and spathulenol. Subsequently, the antioxidant activity of the isolated oil was measured, and the results showed that the total phenolic contents (TPC) was 4.69 ± 0.17 GAE mg/100 g, the total flavonoid contents (TFC) was 1.45 ± 0.04 CE mg/100 g, the ferric reducing antioxidant potential (FRAP) ranged from 0.07-0.81, and the DPPH radical scavenging activity was 42.88-86.94%. TEO exhibited notable antibacterial activity against certain strains of Staphylococcus aureus and Escherichia coli. The molecular docking studies were then conducted to further investigate the interaction of TEO's potent metabolites with key bacterial enzymes, identifying spathulenol and caryophyllene as the best-interacting ligands. Hemolytic activity tests of TEO indicated negligible cytotoxic effects. These findings support that TEO holds great potential for the development of functional food and nutra-pharmaceuticals. [ABSTRACT FROM AUTHOR]

Shewanella is a genus of Gram-negative marine bacteria with some species associated with human and shellfish illnesses. This study evaluated the abundance of Shewanella species in oysters and seawater from the Chesapeake and Maryland Coastal Bays at four sites between 2019 and 2021. Physicochemical parameters such as temperature, salinity, dissolved oxygen, turbidity, pH, chlorophyll-a, rainfall within the last 48 h, total dissolved solids, and atmospheric pressure were also recorded to evaluate if there was a correlation between environmental parameters and the level of Shewanella. The highest total Shewanella counts were 1.8 × 107 CFU/g in oysters and 4.0 × 102 CFU/mL in seawater. 16S rRNA sequencing was performed on 1,344 representative isolates of which 890 (713 oyster, 177 seawater) were confirmed as Shewanella within 16 species. The top four species isolated from oysters and seawater were S. khirikhana a known shrimp pathogen (49%), S. marisflavi (19%), S. loihica (11%), and S. algae (8%). Testing for alpha and beta hemolysis were performed on all confirmed Shewanella isolates. Beta hemolysis was observed in 405 (46%) of the isolates of which 313 were in oysters and 92 in seawater. In oysters, beta-hemolysis was most prevalent in S. khirikhana (233 of 344 isolates, 68%), while in seawater 64 of 92 isolates (70%) were beta-hemolytic strains. Beta-hemolysis suggests that these could be potentially pathogenic strains. Correlations were performed between physicochemical attributes of the seawater and Shewanella counts. Only seawater temperature and dissolved oxygen correlated with Shewanella counts (r = 0.45 and − 0.41), respectively. No correlations were observed between the physicochemical parameters and Shewanella abundances in oysters. Results suggest that virulent strains of Shewanella may be present in oysters and seawater from the Chesapeake and Maryland Coastal Bays, perhaps as a consequence of rising seawater temperatures.

Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia often overlooked as a potential etiology of hemolysis and is challenging to diagnose because of the complicated testing methods required. We performed a systematic review of all reported cases to better assess the clinical, immunohematologic, and therapeutic characteristics of PCH. We systematically analyzed PubMed, Medline, and EMBASE to identify all cases of PCH confirmed by Donath-Landsteiner (DL) testing. Three authors independently screened articles for inclusion, and systematically extracted epidemiologic, clinical, laboratory, treatment, and outcomes data. Discrepancies were adjudicated by a fourth author. We identified 230 cases, with median presentation hemoglobin of 6.5 g/dL and nadir of 5.5 g/dL. The most common direct antiglobulin test (DAT) result was the presence of complement and absence of immunoglobulin G (IgG) bound to red blood cells, although other findings were observed in one-third of cases. DL antibody class and specificity were reported for 71 patients, of which 83.1% were IgG anti-P. The use of corticosteroids is common, although we found no significant difference in the length of hospitalization for patients with and without steroid therapy. Recent reports have highlighted the use of complement inhibitors. Among patients with follow-up, 99% (213 of 216) were alive at the time of reporting. To our knowledge, this represents the largest compilation of PCH cases to date. We discovered that contemporary PCH most commonly occurs in children with a preceding viral infection, corticosteroid use is frequent (but potentially ineffective), and DAT results are more disparate than traditionally reported.

Background and objective: Autoimmune hemolytic anemia (AIHA) is a rare but important cause of morbidity in pediatric hematology patients. Given its rarity, there is little high‐quality evidence on which to base the investigation and management of pediatric AIHA. This scoping review aims to summarize the current evidence and highlight key gaps to inform future studies. Methods: This review searched MEDLINE and the Cochrane CENTRAL Trials Register from 2000 to November 03, 2023. Experimental and observational studies reporting AIHA diagnostic criteria, laboratory workup, or treatment/management in populations with at least 20% of patients ≤18 years were included. Results: Forty‐three studies were included, with no randomized controlled trials identified. AIHA diagnostic criteria, diagnostic tests, and treatments were highly variable. First‐line treatment approaches include corticosteroids, intravenous immunoglobulin, or both. Approaches to AIHA resistance to first‐line therapy were widely variable between studies, but most commonly included rituximab and/or cyclosporine. Conclusions: We identify a heterogenous group of observational studies into this complex, immune‐mediated disorder. Standardized definitions and classifications are needed to guide collaborative efforts needed to study this rare disease. The work done by the CEREVANCE group provides an important paradigm for future studies. [ABSTRACT FROM AUTHOR]

Following the advent of direct-acting antivirals (DAAs), the treatment of hepatitis C virus (HCV) infection is now rarely challenging. However, data are still limited concerning DAA use in patients affected by glucose-6-phosphate dehydrogenase deficiency (G6PDd). Based on these considerations, the goal of this study was to evaluate the effectiveness and safety of DAAs in this subpopulation. A retrospective multicenter observational study (2015–2023) was conducted on all 2754 consecutive HCV-positive patients treated with first- and second-generation all-oral DAAs, and with a G6PDd diagnosis confirmed by quantitative testing (n = 38). At the treating clinician's discretion, an enhanced clinical and laboratory follow-up was performed, generally on a monthly basis both during treatment and up to six months after the end of it. Concerning hematochemical parameters, no significant differences were found between any considered time point. In all cases, no treatment-related adverse events were reported, and virologic response rates were as expected without G6PDd. In conclusion, in a large experience which, to the best of our knowledge, is unprecedented in the literature, the treatment of HCV hepatitis with nearly all available DAAs in patients with G6PDd as a comorbidity—a common occurrence in countries such as Italy—proved to be highly effective and safe. [ABSTRACT FROM AUTHOR]

We report a case of severe anemia in a patient with recurrence of ovarian cancer who underwent comprehensive treatment with the immune checkpoint inhibitor (ICI) Tislelizumab combined with the paclitaxel + carboplatin (TC) regimen. The patient's medical history and additional diagnostic tests led to the consideration of autoimmune hemolytic anemia. Following a blood transfusion, administration of high -dose corticosteroids and immunoglobulin, and consistent oral cyclosporine soft capsule maintenance therapy for over 2 months, the individual's hemoglobin concentration gradually increased to 110 g/L. Subsequent monitoring over a 3-month period indicated sustained stability in the hemoglobin levels. In patients receiving ICI therapy combined with cytotoxic chemotherapy or radiotherapy, severe hematological adverse reactions attributed to ICI are very rare among immune-related events. Early diagnosis is challenging, as these reactions can easily be confused with bone marrow suppression caused by radiotherapy and chemotherapy. The earlier use of corticosteroids, the better the treatment outcome and prognosis of adverse reactions caused by ICI. Therefore, when combining clinical anti-tumor therapy with ICI in patients, it is important to pay attention to adverse reactions in the hematologic system and promptly identify them. [ABSTRACT FROM AUTHOR]

In this work, we sought to validate the use of Euphorbia calyptrata (L.), a Saharan and Mediterranean medicinal plant, in traditional pharmacopeia. GC‐MS/MS identified volatile compounds of potential therapeutic interest. Antioxidant tests were performed using β‐carotene decolorization, DPPH radical scavenging, FRAP, beta‐carotene bleaching, and TAC. The antimicrobial activity was evaluated on solid and liquid media for bacterial and fungal strains to determine the zone of inhibition and the minimum growth concentration (MIC) of the microbes tested. The hemolytic activity of these essential oils was assessed on red blood cells isolated from rat blood. Phytochemical characterization of the terpenic compounds by GC‐MS/MS revealed 31 compounds, with alpha‐Pinene dominating (35.96 %). The antioxidant power of the essential oils tested revealed an IC50 of 67.28 μg/mL (DPPH), EC50 of 80.25.08±1.42 μg/mL (FRAP), 94.83±2.11 μg/mL (beta carotene) and 985.07±0.70 μg/mL (TAC). Evaluating solid media's antibacterial and antifungal properties revealed a zone of inhibition between 10.28 mm and 25.80 mm and 31.48 and 34.21 mm, respectively. On liquid media, the MIC ranged from 10.27 μg/mL to 24.91 μg/mL for bacterial strains and from 9.32 μg/mL to 19.08 μg/mL for fungal strains. In molecular docking analysis, the compounds naphthalene, shogunal, and manol oxide showed the greatest activity against NADPH oxidase, with Glide G scores of −5.294, −5.218 and −5.161 kcal/mol, respectively. For antibacterial activity against E. coli beta‐ketoacyl‐[acyl carrier protein] synthase, the most potent molecules were cis‐Calamenene, alpha.‐Muurolene and Terpineol, with Glide G‐scores of −6.804, −6.424 and −6.313 kcal/mol, respectively. Hemolytic activity revealed a final inhibition of 9.42±0.33 % for a 100 μg/mL concentration. The essential oils tested have good antioxidant, antimicrobial, and hemolytic properties thanks to their rich phytochemical composition, and molecular docking analysis confirmed their biological potency. [ABSTRACT FROM AUTHOR]

Nanobiotechnology is the study of small biological structures ranging in size of 1-100nm. Zinc oxide (ZnO) is a versatile inorganic molecule having strong antimicrobial, disinfecting and drying properties, useful in production of medicines. ZnO nanoparticles (ZnO-NPs) are metallic nano-particles with high catalytic, biological and UV-blockage properties. Aim of this study is to synthesize cost-effective and eco-friendly ZnO-NPs by using zinc-acetate-dihydrate and Lallemantia royleana seed-extract as reducing, stabilizing and capping agent. Biosynthesized ZnO-NPs were characterized by various analytical techniques. The characteristic peak of ZnO-NPs was measured at ∼382nm. FT-IR analysis revealed polysaccharide nature of L. royleana-extract and their functional group's interaction with ZnO-NPs responsible for reduction and stabilization. SEM and XRD results revealed hexagonal-wurtzite structure of ZnO-NPs with average size of 18.26 nm. These ZnO-NPs possess strong anti-hemolytic and catalytic potentials. Our study showed that ZnO-NPs degrade organic pollutants effectively and can be useful for the purification of industrial effluents in future. [ABSTRACT FROM AUTHOR]

Sitosterolemia is a rare autosomal recessive disease that lead to an increase in the intestinal absorption and decreased biliary excretion plant sterols. It is caused by mutations in ABCG5 and ABCG8 genes, encoring sterolin‐1 and sterolin‐2 protein. The main clinical manifestations are xanthomas, premature atherosclerosis, arthralgia and, of note, hematological alterations. As in many other systemic diseases, hematological manifestations may be the only notable finding, for this reason we want to highlight the importance of multidisciplinary work and raise awareness of this rare disease that can lead to serious consequences if not treated prematurely. Here we present a case of this disease as well as its entire diagnostic process developed from a simple analytical alteration. [ABSTRACT FROM AUTHOR]

This study investigates the bioactivity profile of wood-rotting fungal species Daedaleopsis confragosa (Bolton) J. Schröt. 1888, focusing on its antioxidant, cytotoxic, and genotoxic activities and enzyme modulation properties with respect to its possible application in terms of enhancing women's reproductive health. Two types of extracts, including those based on EtOH extraction (DC) and hydrodistillation (DCHD), were investigated. The results indicate that the radical scavenging capacity against the DPPH radical and reduction potential were stronger in the DC extracts owing to the higher total phenolic content (TPC) and total flavonoid content (TFC) (25.30 ± 1.05 mg GAE/g d.w. and 2.84 ± 0.85 mg QE/g d.w., respectively). The same trend was observed in the protein phosphatase-1 (PP1) activity and in the genotoxic activity against the δ virus since only the DC extract exhibited DNA disintegration regarding a dilution of 1:100. Conversely, the DCHD extract exhibited increased hemolytic and cytotoxic effects (339.39% and IC50 = 27.76 ± 0.89 μg/mL—72 h incubation, respectively), along with greater inhibition of the AChE enzyme (IC50 = 3.11 ± 0.45 mg/mL) and hemolytic activity. These results suggest that terpenoids and steroids may be responsible for the observed activity in DCHD as these compounds could potentially be extracted following the HD procedure. This comprehensive bioactivity profiling offers valuable insights into the potential therapeutic applications of D. confragosa from Serbia and underscores the importance of further investigations for harnessing its pharmacological potential. [ABSTRACT FROM AUTHOR]

Patients with relapsed warm antibody autoimmune hemolytic anemia (wAIHA) have limited treatment options. Fostamatinib is a potent, orally administered spleen tyrosine kinase inhibitor approved in the United States and Europe for the treatment of adults with chronic immune thrombocytopenia (ITP). This phase 2 study evaluated the response to fostamatinib, administered at 150 mg BID orally with or without food in adults with wAIHA and active hemolysis with hemoglobin (Hgb) 10 g/dL with an increase of ≥2 g/dL from baseline by week 24 without rescue therapy or red blood cell transfusion. Eleven of 24 (46%) patients achieved the primary endpoint. Increases in median Hgb were detected at week 2 and sustained over time. Median lactate dehydrogenase levels and reticulocyte counts generally declined over time with little change in median haptoglobin levels. The most common adverse events (AEs) were diarrhea (42%), fatigue (42%), hypertension (27%), dizziness (27%), and insomnia (23%). AEs were manageable and consistent with the fostamatinib safety database of over 3900 patients across multiple diseases (rheumatoid arthritis, B-cell lymphoma, COVID-19, and ITP). No new safety signals were detected. Fostamatinib may be a promising therapeutic option for wAIHA. A randomized, double-blind, phase 3 study is nearing completion.

ObjectivesTo expand the number of conditions and interventions explored for their associations with thrombosis in the veterinary literature and to provide the basis for prescribing recommendations.DesignA population exposure comparison outcome format was used to represent patient, exposure, comparison, and outcome. Population Exposure Comparison Outcome questions were distributed to worksheet authors who performed comprehensive searches, summarized the evidence, and created guideline recommendations that were reviewed by domain chairs. The revised guidelines then underwent the Delphi survey process to reach consensus on the final guidelines. Diseases evaluated in this iteration included heartworm disease (dogs and cats), immune-mediated hemolytic anemia (cats), protein-losing nephropathy (cats), protein-losing enteropathy (dogs and cats), sepsis (cats), hyperadrenocorticism (cats), liver disease (dogs), congenital portosystemic shunts (dogs and cats) and the following interventions: IV catheters (dogs and cats), arterial catheters (dogs and cats), vascular access ports (dogs and cats), extracorporeal circuits (dogs and cats) and transvenous pacemakers (dogs and cats).ResultsOf the diseases evaluated in this iteration, a high risk for thrombosis was defined as heartworm disease or protein-losing enteropathy. Low risk for thrombosis was defined as dogs with liver disease, cats with immune-mediated hemolytic anemia, protein-losing nephropathy, sepsis, or hyperadrenocorticism.ConclusionsAssociations with thrombosis are outlined for various conditions and interventions and provide the basis for management recommendations. Numerous knowledge gaps were identified that represent opportunities for future studies.

Background and aim: Malaria is a global health issue causing substantial morbidity and mortality. Screening of various traditionally important medicinal plants is a key source for the discovery of new antimalarials. We evaluated the antimalarial and antioxidant activities, and performed detailed phytochemical analyses of Toona ciliata MJ Roem aqueous methanolic leaf extract (TcMLE). Experimental procedures: In vitro antiplasmodial studies in Plasmodium falciparum (Pf) 3D7 and PfCam3.IR539T strains were performed by [3H]-hypoxanthine uptake assays. In vitro cytotoxicity in HeLa and HEK293T cell lines was evaluated using MTT assays. Hemolysis assay was performed using RBCs. Phytochemical analysis by GC-MS and in vitro antioxidant studies by DPPH and ABTS assays were performed. In vivo antimalarial studies in Pb-infected mice were carried out using Rane's test and Peters' 4-day test. Results and conclusions: TcMLE showed significant in vitro antioxidant activity and had phytochemicals reported for antimalarial activity. In vitro studies showed prominent antiplasmodial activity against Pf3D7 strain (IC50 ∼22 μg/ml) and PfCam3. IR539Tstrain (IC50 value ∼43 μg/ml). In vitro cytotoxicity studies, in vitro hemolytic assays, and in vivo acute toxicity studies further suggested that TcMLE is nontoxic. In vivo antimalarial studies using Rane's test showed a significant decrease in parasitemia by ∼70% at 1200 mg/kg doses and delayed the mortality of mice by ∼10–14 days. Peters' 4-day test also showed a similar pattern. The present study demonstrated the antimalarial potential of TcMLE. These findings deliver a platform for further studies to identify the active components of TcMLE and discover new antimalarials.

S eeds of Peganum harmala L. have been traditionally used in Algerian medicine. This study investigates whether the antioxidant, antihemolytic, and anti-inflammatory activities of Peganum harmala extracts (PHE) are attributed to polyphenolic compounds, which are abundant in methanol, chloroform, and ethyl acetate extracts. Extraction and fractionation of polyphenols involved solvents with different polarities, resulting in a crude extract (CrE), a chloroform extract (CHE), and an ethyl acetate extract (EAE). The antioxidant potential of CrE and its fractions was assessed using the ferrothiocyanate (FTC) and thiobarbituric acid (TBA) assays. The inhibition of mice erythrocyte hemolysis was evaluated for methanol, chloroform, and ethyl acetate extracts in the presence of the oxidant (AAPH). PMA-induced mouse ear edema was used as an in vivo model for inflammation. The FTC assay demonstrated the strong antioxidant effect of CrE (87.64 ± 0.003%). EAE showed potent antioxidant activity with low MDA absorption levels. Assessment of antihemolytic effects against AAPH-induced oxidative hemolysis revealed significant protective effects of CrE and EAE, with EAE showing the most pronounced effect. In the in vivo model, CrE (100 mg/kg) exhibited substantial anti-inflammatory activity, inhibiting the ear edema. Computational analyses using molecular docking simulations showed that chlorogenic acid, hesperetin, and rutin have promising potential as inhibitors of COX-2 protein, which is a key component in inflammatory pathways. This study highlights the potent antioxidant properties of P. harmala, particularly in CrE, and its anti-inflammatory effects. The bioactive compounds, such as chlorogenic acid, hesperetin, and rutin, exhibit potential as antiinflammatory agents. P. harmala could be a valuable natural source for potential medical applications, suggesting the need for further exploration in medical treatments. [ABSTRACT FROM AUTHOR]

The anti-lung cancer properties of the plant Medicago orbicularis have not been explored yet. Therefore, we identified its phytochemical composition and investigated the antioxidant, anti-hemolytic, and anti-cancerous properties of extracts of this plant in A549 human lung adenocarcinoma cells. The results show that all parts of M. orbicularis (stems, leaves, and fruits) exhibit remarkable hemolytic activities and modest antioxidant capacity. In addition, all extracts showed a dose-dependent anti-cancerous cytotoxic activity against A549 cells, with fruit extracts being the most potent. This cytotoxic effect could be related, at least partly, to the induction of apoptosis, where M. orbicularis fruit extracts reduced the ratio of anti-apoptotic BCL-2/pro-apoptotic BAX, thereby promoting cellular death. Furthermore, the use of M. orbicularis, in combination with a conventional chemotherapeutic agent, cisplatin, was assessed. Indeed, the combination of cisplatin and M. orbicularis fruit extracts was more cytotoxic and induced more aggregation of A549 cells than either treatment alone. GC-MS analysis and total polyphenol and flavonoid content determination indicated that M. orbicularis is rich in compounds that have anti-cancerous effects. We propose M. orbicularis as a potential source of anti-cancerous agents to manage the progression of lung cancer and its resistance to therapy. [ABSTRACT FROM AUTHOR]

Origanum grosii (L.) and Thymus pallidus (L.) are medicinal plants recognized for their uses in traditional medicine. In this context, the aim of this article is to highlight the results of a phytochemical analysis (HPLC), with particular emphasis on the antioxidant (DPPH, TAC, and FRAP), analgesic, anti-inflammatory, haemagglutinin-test-related, and hemolytic activities of the total extracts of these plants. Phytochemical analysis via HPLC revealed that licoflavone C (30%) is the main compound in Origanum grosii, while hesperidin (43%) is found in T. pallidus. Evaluation of the antioxidant capacity of Origanum grosii and Thymus pallidus using the DPPH, TAC, and FRAP methods revealed an IC50 of the order of 0.085 mg/mL and 0.146 mg/mL, an EC50 of the order of 0.167 mg/mL and 0.185 mg/mL, and a total antioxidant capacity of between 750 mg EQ/g and 900 mg EQ/g, respectively. Analgesic evaluations revealed writhes inhibition of the order of 97.83% for O. grosii and 90% for T. pallidus. In addition, both plant extracts showed limited hemolytic activity, not exceeding 30% at a concentration of 100 mg/mL. Evaluation of the anti-inflammatory potential showed edema inhibition of the order of 94% (800 mg/kg) for O. grosii and 86% (800 mg/kg) for T. pallidus. These results highlight the potential applications of these extracts in pharmacological research. [ABSTRACT FROM AUTHOR]

A series of novel immunoadjuvant QS-21 analogs were synthesized, and their effects on the in vitro hemolysis of red blood cells were evaluated using QS-21 as a control and hemolytic properties as an index. Our results show that all the QS-21 analogs had lower hemolytic effects than QS-21, and their concentrations exhibited a certain quantitative effect relationship with the hemolysis rate. Notably, saponin compounds L1–L8 produced minimal hemolysis and showed lower hemolytic effects, warranting further investigation. [ABSTRACT FROM AUTHOR]

The study of wasp venoms has captured attention due to the presence of a wide variety of active compounds, revealing a diverse array of biological effects. Among these compounds, certain antimicrobial peptides (AMPs) such as mastoparans and chemotactic peptides have emerged as significant players, characterized by their unique amphipathic short linear alpha-helical structure. These peptides exhibit not only antibiotic properties but also a range of other biological activities, which are related to their ability to interact with biological membranes to varying degrees. This review article aims to provide updated insights into the structure/function relationships of AMPs derived from wasp venoms, linking this knowledge to the potential development of innovative treatments against infections.

Autoimmune hemolytic anemia (IMHA) is one of the leading causes of anemia in dogs and cats. This type of anemia can occur in animals of all ages, but is more common in young and middle-aged adult dogs and cats. In secondary IMHA, a trigger is often suspected because of a temporal association with the administration of certain drugs or a preexisting disease, but establishing a causal link is frequently difficult. While both forms of IMHA affect dogs and cats, the primary form is more common in dogs and the secondary form is more common in cats. [ABSTRACT FROM AUTHOR]

Microparticles or microvesicles (MPs/MVs) are sub-cellular vesicles with a growing number of known biological functions. Microvesicles from a variety of parent cells within the vascular system increase in numerous pathological states. Red blood cell-derived MVs (RMVs) are relatively less studied than other types of circulating MVs despite red blood cells (RBCs) being the most abundant intravascular cell. This may be in part due the echoes of past misconceptions that RBCs were merely floating anucleate bags of hemoglobin rather than dynamic and responsive cells. The initial aim of this study was to maximize the concentration of RMVs derived from various blood or blood products by focusing on the optimal isolation conditions without creating more MVs from artificial manipulation. We found that allowing RBCs to sediment overnight resulted in a continuum in size of RBC membrane-containing fragments or vesicles extending beyond the 1 µm size limit suggested by many as the maximal size of an MV. Additionally, dilution and centrifugation factors were studied that altered the resultant MV population concentration. The heterogeneous size of RMVs was confirmed in mice models of hemolytic anemia. This methodological finding establishes a new paradigm in that it blurs the line between RBC, fragment, and RMV as well as suggests that the concentration of circulating RMVs may be widely underestimated given that centrifugation removes the majority of such RBC-derived membrane-containing particles.

Mango seed kernels (MSKs) have been reported to show antioxidant, antibacterial, and anti‐inflammatory properties. This study explores the influence of different optimized extraction systems on the extraction of MSK. The effects on gallic acid (GA) content, total phenolic content (TPC), total flavonoid content (TFC), antioxidant, antimicrobial, and hemolytic activity of MSK extracts from different extraction systems (65.45% ethanol‐ultrasound assisted extraction [UAE], 62% ethanol‐incubator shaker, 19.4% ethanol‐UAE, and 100% water‐UAE) were assessed. Based on the results, a nonsignificant difference in phenolic (p = 0.222), flavonoids (p = 0.058), antioxidant (p = 0.165), and antimicrobial activity (p = 0.193) against Staphylococcus aureus whereas a significant difference (p < 0.0001) in hemolytic, GA content, and antimicrobial activity against Clostridium perfringens was observed. Among different extraction systems, aqueous extraction showed significantly lower hemolytic (1.09%) and higher GA content (4.72 mg/g) and comparable results in all other experiments; yield (32.40%), TPC (58.79 mg/g), TFC (2.16 mg/g), and antioxidant (73.19%). Hence, it has been concluded that aqueous extraction system could be considered a sustainable extraction system for practical applications. Practical Application: Aqueous extraction system could be a sustainable option for extraction of mango seed kernel for practical applications as it is readily available, cheap, nonflammable, and nontoxic. [ABSTRACT FROM AUTHOR]

Probiotic bacteria play an important role in fish growth and health in aquaculture, especially in fish rearing in inland waters. This study aimed to identify bacteria from the digestive tract of milkfish (Chanos chanos Forskal) and investigate their potential as probiotic candidates. Bacteria were isolated from the digestive tract of milkfish and identified using PCR technique and 16S rRNA gene sequencing. The probiotic potency was determined using amylolytic assay, synergistic activity, hemolytic activity, and antagonistic activity. The results showed that there were several types of bacteria found in the digestive tract of milkfish. One of these bacteria could produce an amylase enzyme with an amylolytic index of 5.16, identified as Bacillus paramycoides. This bacteria also synergized with other bacteria and did not have hemolytic activity on blood agar media. The results of the antagonistic test based on the well-diffused method against Aeromonas hydrophila showed that B. paramycoides did not produce an inhibition zone around the bacterial wells. The molecular identification found that the bacterial species was B. paramycoides B2.1. These results suggested that Bacillus paramycoides B2.1, which is found in the digestive tract of milkfish, can be used as a probiotic candidate for fish feed indicated by several probiotic tests that have been carried out. [ABSTRACT FROM AUTHOR]

Ultrashort cationic lipopeptides (USCLs) and quaternary ammonium salts constitute two groups of cationic surfactants with high antimicrobial activity. This study aimed to investigate the influence of quaternization of the amino group of the lysine side chain in USCLs on their antimicrobial, hemolytic and cytotoxic activities. To do this, two series of lipopeptides were synthesized, USLCs and their quaternized analogues containing trimethylated lysine residues — qUSCLs (quaternized ultrashort cationic lipopeptides). Quaternization was performed on a resin during a standard solid-phase peptide synthesis with CH3I as the methylating agent. According to our knowledge, this is the first study presenting on-resin peptide quaternization. The lipopeptides were tested for their antibacterial and antifungal activities against the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella aerogenes) bacteria and Candida glabrata yeast-like fungus. Most of the compounds proved to be active antimicrobial agents with enhanced activity against Gram-positive strains and fungi and a lower against Gram-negative species. In addition, the antimicrobial activity of lipopeptides was increasing with an increase in hydrophobicity but qUSCLs exhibited usually a poorer antimicrobial activity than their parent molecules. Furthermore, the toxicity against red blood cells and human keratinocytes was assessed. It's worth emphasizing that qUSCLs were less toxic than the parent molecules of comparative hydrophobicity. The results of the study proved that qUSCLs can offer a higher selectivity to pathogens over human cells than that of USCLs. Last but not least, quaternization of the peptides could increase their solubility and therefore their bioavailability and utility. [ABSTRACT FROM AUTHOR]

Objective: Rare disease. Background: RASopathies involve mutations in genes that encode proteins participating in the RAS-mitogen-activated protein kinase pathway and are a collection of multisystem disorders that clinically overlap. Variants in the SHOC2 gene have been reported in Noonan-like syndrome, which include distinct facial features, short stature, congenital cardiac defects, developmental delays, bleeding disorders, and loose anagen hair. This report is of a 7-yearold girl with the c.4A>G (p.Ser2Gly) variant of the SHOC2 gene, consistent with Noonan-like syndrome, with loose anagen hair, presenting with thrombotic thrombocytopenic purpura and autoimmune hemolytic anemia. Case Report: The child had a medical history of 7 hospitalizations at our institution. At the age of 2 months, she underwent surgical correction for ventricular and atrial septal defects. At the age of 2 years, tonsil and adenoid removal surgery was performed, followed by surgery for otitis media at age 5 years. At 7 years, she was hospitalized for the simultaneous occurrence of thrombotic thrombocytopenic purpura and autoimmune hemolytic anemia. The patient displayed short stature and mild intellectual disability. Notable facial features included sparse hair, mild frontal bossing, and low-set ears. Antinuclear antibody levels demonstrated a significant gradual shift. Through trio whole-exome sequencing, a c.4A>G (p.Ser2Gly) variation in the SHOC2 gene was identified. Conclusions: Given the clinical information and genetic testing results, the patient's condition appeared to closely be a type of RASopathy. This report has highlighted the importance of physical, developmental, and genetic testing in children presenting with dysmorphism, developmental delay, and hematological abnormalities. [ABSTRACT FROM AUTHOR]

Autoimmune haemolytic anaemia is a rare disease of the immune system characterized by haemolysis of patient’s own red blood cells caused by autoantibodies and/or activated components of the complement. Depending on the underlying disease, autoimmune haemolytic anaemia can be primary or secondary, and according to the serological characteristics of autoantibodies, it is divided into warm, cold and mixed. The diagnosis of the disease is made on the basis of a positive result of a direct antiglobulin test, anaemia and the presence of laboratory parameters for haemolysis. In very rare cases, direct antiglobulin test negative-autoimmune haemolytic anaemias are possible. For the proper treatment, in addition to precise immunohaematological diagnostics to distinguish between certain types of autoimmune haemolytic anaemia, the diagnosis of the underlying diseases is required. Corticosteroids, and in severe cases, rituximab are usually used to treat warm autoimmune haemolytic anaemia. In cold autoimmune haemolytic anaemia warming up a patient is important and avoiding exposure to cold temperatures is recommended, but in severe cases administration of rituximab, with or without bendamustine is required. In refractory cases of paroxysmal cold haemoglobinuria rituximab is used with immunosuppressive drugs. Corticosteroids with early administration of rituximab are recommended for the treatment of mixed autoimmune haemolytic anaemia. In the treatment of symptomatic anaemia blood transfusion is applied, and for the treatment of life-threatened patient it is possible to apply intravenous immunoglobulins, plasmapheresis and in rare cases of reticulocytopenia also erythropoietin. New drugs that are offered in clinical trials are promising for the treatment of severe forms of autoimmune haemolytic anaemias, such as complement-mediated autoimmune haemolytic anaemias or refractory forms of cold autoimmune haemolytic anaemias. For monitoring the therapeutic effect of autoimmune haemolytic anaemias, it is important to know the criteria which define the response to therapy and the outcome of the disease. The aim of this review paper is to present the current knowledge in the diagnostics and treatment of autoimmune haemolytic anaemias, and monitoring the therapeutic effect in autoimmune haemolytic anaemias.

Huimin Zhang,1 Jiaxin Cao,1 Zhien He,2,3 Xianchun Zong,1 Baolin Sun2,3 1College of Life Science and Technology, Mudanjiang Normal University, Mudanjiang, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital, University of Science and Technology of China, Hefei, People’s Republic of China; 3School of Life Science and Medicine, University of Science and Technology of China, Hefei, People’s Republic of ChinaCorrespondence: Baolin Sun, Email sunb@ustc.edu.cnPurpose: This study aimed to investigate the molecular characteristics, antimicrobial resistance and hemolytic phenotype of Staphylococcus aureus isolated from Anhui, China.Results: From August 2021 to January 2022, 214 S. aureus isolates were collected from the Anhui Provincial Hospital. This study identified 117 methicillin-resistant S. aureus and 97 methicillin-sensitive S. aureus isolates, and the detection rate of methicillin-resistant isolates was 1.8-fold higher than the average isolates reported in China (53.9% vs 30.5%). S. aureus isolates share identity at five or more of the seven MLST-based housekeeping loci, referred to as the clonal complex (CC). Forty ST types were found in 214 clinical S. aureus isolates, with the most extensive distribution of ST59 and ST6697 typing numbers and higher CC5 detection rates than any other clonal group. (The ST typing is the result of the MLST typing website query.) To detect the virulence of ST types of S. aureus, hemolysis experiments were performed on 214 clinical isolates, and it was concluded that ST59 had a relatively robust hemolytic capacity.Conclusion: Anhui S. aureus isolates have unique molecular and antibiotic resistance profiles. The antibiotic resistance profile may be related to the random use of antibiotics.Keywords: Staphylococcus aureus, epidemiological analysis, multilocus sequence typing, phenotype, hemolytic

Abstract Background Thrombotic thrombocytopenic purpura (TTP) considers a rare cause of ischemic stroke (IS). We reported a case of a newly diagnosed patient with acquired immune-mediated TTP (iTTP), in whom two IS events developed during 48 h. Case presentation A 59-year-old diabetic male was presented to the hospital 24 h after symptoms onset, including left hemiparesis, dysarthria, and decreased consciousness. A brain CT scan was performed with the suspicion of acute IS, indicating infarct lesions in the right middle cerebral artery (MCA) territory. The patient was not eligible for thrombolytic therapy due to admission delay. Over the next 24 h, the patient’s neurological condition deteriorated, and the second brain CT scan showed new ischemic lesions in the left MCA territory. Initial laboratory evaluation indicated thrombocytopenia without evidence of anemia. However, in the following days, thrombocytopenia progressed, and microangiopathic hemolytic anemia (MAHA) developed. The ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity and inhibitors assay confirmed the diagnosis of iTTP. The patient underwent plasma exchange activity and inhibitors assay confirmed the diagnosis of iTTP. The patient underwent and pulse IV methylprednisolone. Rituximab was also added due to the refractory course of the disease. After a prolonged hospital course, he had considerable neurologic recovery and was discharged. Conclusions Clinicians should consider two points. First, TTP should be considered in any patient presenting with IS and having thrombocytopenia or anemia without other symptoms of TTP. Second, worsening the patient's condition during hospitalization may indicate a new stroke and should be investigated immediately.

Key Clinical Massage: Autoimmune hemolytic anemia (AIHA) is a rare disease that is divided into primary and secondary types. In patients with AIHA we should consider mediastinal tumors as a serious cause. If such teratoma was found surgical removal of it is in order. Autoimmune hemolytic anemia (AIHA) is a rare disease that is divided into primary and secondary types. The secondary type usually appears as a complication to some diseases such as chronic inflammatory diseases, systemic lupus erythematosus (SLE), and malignancies. A 26 years‐old female with a chief complaint of weakness, fatigue, and exertional dyspnea is diagnosed with AIHA. Initially, medical steroid treatment appeared to be successful and the anemia improved, however, by weaning steroid dosage the disease relapsed. Eventually, surgical resection of the mediastinal teratoma lead to the hemolysis being treated successfully. In patients with AIHA we should consider mediastinal tumors as a serious cause. If such teratoma was found surgical removal of it is in order. [ABSTRACT FROM AUTHOR]

Thrombotic microangiopathy (TMA) is related to a histological lesion in arterioles and capillaries, characterized by thickening and inflammation of the vascular wall, detachment of endothelial cells, enlargement of the subendothelial space with accumulation of proteins and cell lysis material, and the presence of platelet thrombi that occlude the vascular lumen. There are two clinical entities with primary thrombotic microangiopathy lesions: thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Thrombotic thrombocytopenic purpura is related to a deficit or dysfunction of disintegrin and metalloproteinase activity, which splits the bond of von Willebrand factor, a protein involved in the clotting process. Clinically it is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and increased serum lactate dehydrogenase. On contrast, the hemolytic uremic syndrome is defined by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, and can be classified as typical and atypical. The typical hemolytic uremic syndrome is associated with the prodrome of diarrhea after infection with Shiga toxin-producing Escherichia coli, while atypical HUS is associated with abnormalities in the alternative complement pathway, Streptococcus pneumoniae infections, systemic lupus erythematosus, disorders of the cobalamin C metabolism, among others. [ABSTRACT FROM AUTHOR]

The present protocol will compare haemoglobin electrophoresis with sickling test, evaluating sensitivity, specificity, positive predicted value and negative predicted value of haemolytic anaemia patients. Haemoglobin electrophoresis is the confirmation test for sickle cell anaemia. Sickle cell anaemia is a type of haemolytic anaemia where red blood cells (RBC)’s biconcave form does not enable the best possible respiratory exchange. In haemolytic anaemia, EDTA is used to examine the peripheral smear stained with Giemsa stain. Peripheral smear shows polychromatic neutrophils, nucleated RBCs (Red blood cell) and fragmented RBCs. In haemolytic anaemia, patients have decreased haemoglobin (Hb) levels. In sickle cell disease (SCD), anaemia is brought about by a change in the DNA sequence of cells in the Hb beta-globin chain. Screening of the sickling test is done by using sodium metabisulfite to assess the shape of cells. Confirmation test of Hb electrophoresis on cellulose acetate paper uses band detection. This study will aim to evaluate the sensitivity and specificity of Hb electrophoresis with the sickling test utilizing quantifiable investigation. The effectiveness of sensitivity and specificity, positive and negative predicted values, and overall course of action for the two techniques, Hb electrophoresis and sickling test, will be collected. This research will also give an overview of existing haemolytic anaemia literature.

Immune checkpoint inhibitors (ICPis) are a novel class of immunotherapeutic agents that have revolutionized the treatment of cancer; however, these drugs can also cause a unique spectrum of autoimmune toxicity. Autoimmune hemolytic anemia (AIHA) is a rare, but often severe, complication of ICPis. We identified 14 patients from nine institutions across the United States who developed ICPi-AIHA. The median interval from ICPi initiation to development of AIHA was 55 days (interquartile range [IQR], 22-110 days). Results from the direct antiglobulin test (DAT) were available for 13 of 14 patients: 8 patients (62%) had a positive DAT and 5 (38%) had a negative DAT. The median pretreatment and nadir hemoglobin concentrations were 11.8 g/dL (IQR, 10.2-12.9 g/dL) and 6.3 g/dL (IQR, 6.1-8.0 g/dL), respectively. Four patients (29%) had a preexisting lymphoproliferative disorder, and two (14%) had a positive DAT prior to initiation of ICPi therapy. All patients were treated with glucocorticoids, with three requiring additional immunosuppressive therapy. Complete and partial recoveries of hemoglobin were achieved in 12 (86%) and 2 (14%) patients, respectively. Seven patients (50%) were rechallenged with ICPis, and one (14%) developed recurrent AIHA. Clinical and laboratory features of ICPi-AIHA were similar in DAT positive and negative patients. ICPi-AIHA shares many clinical features with primary AIHA; however, a unique aspect of ICPi-AIHA is a high incidence of DAT negativity. Glucocorticoids are an effective first-line treatment in the majority of patients with ICPi-AIHA, and most patients who are rechallenged with an ICPi do not appear to develop recurrence of AIHA.

Schiff bases (S1–S8) were prepared by the reaction of 4-aminophenylacetic acid/5-aminoisophthalic acid with benzaldehyde/acetophenone/benzophenone/anthraquinone in ethanol. The sodium salts (NaS1–NaS8) of the Schiff bases were reacted further with triphenyltin(IV) chloride in methanol for 4 h to produce the organotin derivatives (C1–C8). The structures of the synthesized products (S1–S8 and C1–C8) were verified by elemental analysis, FT-IR analysis, 1H NMR spectroscopy, and thermogravimetry. Elemental analysis (CHN) data agreed well with the chemical composition of compounds. FT-IR spectroscopy demonstrated the isobidentate coordination mode of the carboxylate moiety and a trigonal bipyramidal geometry of Sn(IV) in the solid state of complexes. Proton NMR spectra displayed the signals of the Schiff base skeleton as well as the triphenyltin(IV) moieties in the complexes C1–C8 in their anticipated regions. The thermogravimetric analysis has shown a good agreement between the observed percentages of the evolved contents and residues and the theoretically calculated values. The Schiff bases have shown higher thermal stabilities as compared to their organotin(IV) derivatives, owing to stronger hydrogen bonding in the former case. The complexes exhibited higher antibacterial potential as compared to their free ligand precursors against the tested bacteria (Bacillus subtilis and Escherichia coli). The biological activities were dependent upon the structures of investigated products, nature of incorporated ligand and type (gram-positive or gram-negative) of the bacterial strains. The compounds were also tested for their in vitro hemolytic effects on human red blood cells while using PBS as a negative control (0% lysis) and triton X-100 as a positive control (100% lysis). Cytotoxicity values lie in the range of 1.5–7.9%, which is an acceptable range and renders the safe medicinal uses of all the synthesized products. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course. Background: Sickle cell disease (SCD) is an autosomal recessive hereditary condition characterized by chronic hemolytic anemia and painful vaso-occlusive episodes. Homozygous sickle cell patients are at increased risk of morbidity and mortality from malaria. Autoimmune hemolytic anemia (AIHA) secondary to, or in the setting of, malarial infection is rare. In our case, the concurrence of Plasmodium falciparum malarial parasitemia and AIHA led to severe hemolytic anemia with an extensive packed red blood cell transfusion requirement. The patient's underlying SCD also contributed to the severity of the anemia and persistence of the malarial infection. Case Report: We report the case of a 29-year-old woman in the second trimester of pregnancy, with a history of SCD, who presented with severe anemia beyond her typical baseline in the setting of P. falciparum malaria. Hemolysis markers, including lactate dehydrogenase and bilirubin, were elevated. Direct Coombs testing was positive for IgG and C3 antibodies. Treatment with antimalarial agents and steroids led to clinical improvement and eventual clearance of the parasitemia. Conclusions: Our patient's clinical course was most compatible with P. falciparum malaria-induced AIHA. Although she received a short course of steroids, it was treatment and clearance of the parasitemia that led to resolution of the hemolysis and a return to baseline hemoglobin levels. While the exact mechanism of AIHA in malaria is not well characterized, several unique mechanisms have been proposed and should be considered in cases of P. falciparum malaria manifesting with particularly severe hemolytic anemia. [ABSTRACT FROM AUTHOR]

Objective: Rare disease. Background: Glutathione synthetase deficiency (GSD) is a rare autosomal recessive disorder caused by glutathione synthetase (GSS) gene variants that occur in 1 in 1 million individuals. The severe form of GSD is characterized by hemolytic anemia, metabolic acidosis with 5-oxoprolinuria, progressive neurological symptoms, and recurrent bacterial infections. This case report presents a male Japanese infant with severe hemolytic anemia and metabolic acidosis at birth caused by GSD, who developed progressive neurological symptoms on follow-up. Case Report: A Japanese male term infant developed severe hemolytic anemia and metabolic acidosis in the early neonatal period. We suspected GSD based on his symptoms and a high 5-oxoproline urine concentration. We began correcting his metabolic acidosis and administering vitamins C and E supplements. The patient required blood transfusion twice during the acute phase for hemolytic anemia. After age 1 month, he maintained good control of metabolic acidosis and hemolytic anemia. A definitive diagnosis of GSD was made based on high concentrations of 5-oxoproline in urine, low concentrations of glutathione and GSS activity in erythrocytes, and genetic testing. Several episodes of febrile convulsions were started at age 11 months, but none occurred after 2 years. At the last follow-up at age 25 months, metabolic acidosis and hemolytic anemia were well controlled, but he had mild neurodevelopmental delay. Conclusions: This case report shows that GSD can present with severe hemolytic anemia and metabolic acidosis at birth, and manifest with subsequent neurological impairment despite early diagnosis and treatment. Therefore, a careful long-term follow-up that includes neurological evaluation is essential for patients with GSD. [ABSTRACT FROM AUTHOR]

The anti-lung cancer properties of the plant Medicago orbicularis have not been explored yet. Therefore, we identified its phytochemical composition and investigated the antioxidant, anti-hemolytic, and anti-cancerous properties of extracts of this plant in A549 human lung adenocarcinoma cells. The results show that all parts of M. orbicularis (stems, leaves, and fruits) exhibit remarkable hemolytic activities and modest antioxidant capacity. In addition, all extracts showed a dose-dependent anti-cancerous cytotoxic activity against A549 cells, with fruit extracts being the most potent. This cytotoxic effect could be related, at least partly, to the induction of apoptosis, where M. orbicularis fruit extracts reduced the ratio of anti-apoptotic BCL-2/pro-apoptotic BAX, thereby promoting cellular death. Furthermore, the use of M. orbicularis, in combination with a conventional chemotherapeutic agent, cisplatin, was assessed. Indeed, the combination of cisplatin and M. orbicularis fruit extracts was more cytotoxic and induced more aggregation of A549 cells than either treatment alone. GC-MS analysis and total polyphenol and flavonoid content determination indicated that M. orbicularis is rich in compounds that have anti-cancerous effects. We propose M. orbicularis as a potential source of anti-cancerous agents to manage the progression of lung cancer and its resistance to therapy.

A series of novel immunoadjuvant QS-21 analogs were synthesized, and their effects on the in vitro hemolysis of red blood cells were evaluated using QS-21 as a control and hemolytic properties as an index. Our results show that all the QS-21 analogs had lower hemolytic effects than QS-21, and their concentrations exhibited a certain quantitative effect relationship with the hemolysis rate. Notably, saponin compounds L1–L8 produced minimal hemolysis and showed lower hemolytic effects, warranting further investigation.

Multiple myeloma is defined as the neoplastic proliferation of plasma cells resulting in a monoclonal gammopathy. The classic presentation of a patient is someone who presents with bone pain, osteopenia, or new onset fractures. We present a case of multiple myeloma presenting as Evan's syndrome (ES). Evan's syndrome is autoimmune hemolytic anaemia with autoimmune thrombocytopenia. A 44-year-old female was referred from her primary physician to the hospital as laboratory testing revealed haemoglobin of 5 gm/dL. The patient reported a two-month history of fatigue and a sixty-pound weight loss. Laboratory results demonstrated autoimmune hemolytic anaemia, C3 positivity, elevated immunoglobulin (Ig)G, elevated lactate dehydrogenase (LDH), low haptoglobin, elevated reticulocyte count, elevated RDW-CV (red blood cell distribution width-corpuscular volume), positive direct Coombs test, thrombocytopenia, and proteinuria, all of which led to an underlying ES. The patient was started on intravenous steroids followed by oral steroids. A flow cytometry, serum protein electrophoresis, and cytogenetics were obtained. A bone marrow biopsy revealed multiple myeloma and she was started on Bortezomib treatment. We present the fifth reported case of Evan's syndrome and multiple myeloma.

BackgroundCold agglutinin disease is a rare disorder characterized by an autoimmune hemolytic anemia occurring at low temperatures. Physical examination findings, often limited to acrocyanosis, are combined with a thermal amplitude test to help establish the diagnosis. Thermal amplitude testing determines the highest temperature at which the cold agglutination will occur and is an important parameter in diagnosing cold agglutinin disease.Case presentationHere we describe a 57-year-old white man of German and Nicaraguan descent with known chronic cold agglutinin disease who presented to our ophthalmology clinic for evaluation of a cataract. During routine cataract surgery, the lowered temperature of the conjunctiva from intermittent flow of balanced salt solution at room temperature induced a cold agglutination reaction in conjunctival vessels easily visible under a surgical microscope.ConclusionsTo the best of our knowledge, this method of demonstrating cold agglutinin disease has not been described in the literature and could easily be performed utilizing an ordinary slit lamp. This method could be used as an alternative and rapid screening method for cold agglutinin disease.