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In human leukocyte antigen (HLA)-mismatched allogeneic stem cell transplantation settings, donor-specific anti-HLA antibodies (DSAs) can independently lead to graft failure, including both primary graft rejection and primary poor graft function. Although several strategies, such as plasma exchange, intravenous immunoglobulin, rituximab, and bortezomib, have been used for DSA desensitization, the effectiveness of desensitization and transplantation outcomes in some patients remain unsatisfactory. In this review, we summarized recent research on the prevalence of anti-HLA antibodies and the underlying mechanism of DSAs in the pathogenesis of graft failure. We mainly focused on desensitization strategies for DSAs, especially novel methods that are being investigated in the preclinical stage and those with promising outcomes after preliminary clinical application. [ABSTRACT FROM AUTHOR]

Objectives Idiopathic inflammatory myopathies (IIMs) are heterogeneous diseases characterized by skeletal muscle inflammation associated with cutaneous, pulmonary and/or other visceral organ involvement. IVIG has been recommended as an adjunct therapy for IIM patients refractory to conventional therapy. However, IVIG has high resource needs and increased risk of adverse reactions. Subcutaneous immunoglobulin (SCIG) therapy has been used as an alternative to IVIG in primary immunodeficiencies and neuroinflammatory disorders. We assessed the satisfaction, patient preference and effectiveness in IIM patients who transitioned from IVIG to SCIG. Methods We retrospectively reviewed consecutive 20 patients with IIM who were transitioned from IVIG to SCIG therapy for >12 months. Patient preference between IVIG and SCIG was surveyed using a questionnaire previously used in studies of neuroinflammatory conditions. In addition, disease flares, changes in immunosuppression, cumulative prednisone doses and global disease activity were evaluated using the Myositis Intention to Treat Index (MITAX) 12 months pre- and post-SCIG initiation. Results Most patients (78.9%) preferred SCIG over IVIG and preferred home-based therapies to hospital-based therapies. There was no significant difference in global disease activity (MITAX 3.31 vs 3.02) or in cumulative steroid doses 12 months pre- or post-SCIG initiation. Three patients experienced disease flares, five escalated in immunosuppression, while four patients deescalated in immunosuppressive medications. Conclusions SCIG is preferred by most patients over IVIG without a substantial increased disease activity or need for additional CS. Future cost-effectiveness studies may provide an additional rationale for utilizing SCIG over IVIG for maintenance therapy for IIM. [ABSTRACT FROM AUTHOR]

The treatment landscape for relapsed/refractory B-cell lymphomas has evolved rapidly with the advent of immune cell-engaging therapies, including bispecific T-cell engagers (TCEs). In the past 2 years, the FDA has approved bispecific TCEs for the treatment of relapsed/refractory follicular lymphoma (mosunetuzumab-axgb [Lunsumio; Genentech, Inc] and epcoritamab-bysp [Epkinly; Genmab US, Inc]) and diffuse large B-cell lymphomas (epcoritamab and glofitamab-gxbm [Columvi; Genentech, Inc]). Additionally, odronextamab (Regeneron Pharmaceuticals, Inc), another bispecific T-cell-engaging antibody, is being investigated in both follicular and diffuse large B-cell lymphomas. These bispecific TCEs provide novel, non-chemotherapy-based treatment options for a historically difficult-to-treat relapsed/refractory B-cell lymphoma population. This article reviews the efficacy and safety data behind these treatments and highlights practical considerations for implementing these bispecific TCEs across various types of practice sites. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine how the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) inactivated vaccine antibody response and vitamin D levels in the older population are related. Materials and Methods: This study included people over the age of 60 who received their second dose of the SARS-CoV-2 inactivated vaccine after 28 days. Immunoglobulin G antibodies against SARS-CoV-2 spikes were measured; levels equal to or greater than 1 U/mL were classified as seropositive, and levels below 1 U/mL were classified as seronegative. Serum 25-hydroxyvitamin D levels were evaluated in the participants; levels below 30 nmol/L were classified as low, and levels above 30 nmol/L were classified as normal. Results: A total of 188 patients were included. A total of 152 people (80.9%) were found to be positive for the antibodies. The median [interquartile range (IQR)] age of the seropositive individuals was 71 (60-94) and the median (IQR) age of seronegative individuals was 72 (64-86) (p=0.272). While the vitamin D level was below 30 in 115 (75.6%) of the seropositive group, the vitamin D level was below 30 in 26 (70.9%) patients in the seronegative group (p=0.822). Conclusion: In this study, we examined the association between vitamin D levels and seroconversion rate after the second dose of SARS-CoV-2 inactivated vaccine. There were no differences between the seropositive and seronegative groups in terms of vitamin D levels. In another context, it was discovered that vitamin D level has no effect on antibody response. [ABSTRACT FROM AUTHOR]

Stiff-person syndrome (SPS) is a rare and complex neurologic disorder characterized by progressive muscle stiffness, painful spasms, and gait difficulties. In this report, we describe a case of SPS who presented with a relapse while on maintenance immunosuppressive treatment. In addition, we review the literature of 16 previously reported cases of SPS from India, highlighting the diverse clinical features, comorbidities, treatment response, and relapse. The occurrence of paraneoplastic SPS emphasizes the need for early recognition and diagnosis. [ABSTRACT FROM AUTHOR]

Objectives To understand the relative efficacy and safety of bimekizumab, a selective inhibitor of IL-17F in addition to IL-17A, vs other biologic and targeted synthetic DMARDs (b/tsDMARDs) for PsA using network meta-analysis (NMA). Methods A systematic literature review (most recent update conducted on 1 January 2023) identified randomized controlled trials (RCTs) of b/tsDMARDs in PsA. Bayesian NMAs were conducted for efficacy outcomes at Weeks 12–24 for b/tsDMARD-naïve and TNF inhibitor (TNFi)-experienced patients. Safety at Weeks 12–24 was analysed in a mixed population. Odds ratios (ORs) and differences of mean change with the associated 95% credible interval (CrI) were calculated for the best-fitting models, and the surface under the cumulative ranking curve (SUCRA) values were calculated to determine relative rank. Results The NMA included 41 RCTs for 22 b/tsDMARDs. For minimal disease activity (MDA), bimekizumab ranked 1st in b/tsDMARD-naïve patients and 2nd in TNFi-experienced patients. In b/tsDMARD-naïve patients, bimekizumab ranked 6th, 5th and 3rd for ACR response ACR20/50/70, respectively. In TNFi-experienced patients, bimekizumab ranked 1st, 2nd and 1st for ACR20/50/70, respectively. For Psoriasis Area and Severity Index 90/100, bimekizumab ranked 2nd and 1st in b/tsDMARD-naïve patients, respectively, and 1st and 2nd in TNFi-experienced patients, respectively. Bimekizumab was comparable to b/tsDMARDs for serious adverse events. Conclusion Bimekizumab ranked favourably among b/tsDMARDs for efficacy on joint, skin and MDA outcomes, and showed comparable safety, suggesting it may be a beneficial treatment option for patients with PsA. [ABSTRACT FROM AUTHOR]

Simple Summary: Bispecific antibodies (BsAbs) provide a new mode of targeting multiple myeloma (MM) plasma cells (PCs), basing their action on the activation and redirection of the T-cell compartment against neoplastic cells. Two BCMA-targeting (teclistamab and elranatamab) plus one GPRC5D-targeting (talquetamab) BsAbs are available for the management of heavily pretreated patients with relapsed/refractory (RR) MM. Novel strategies to augment potency, reduce toxicity, and improve management are under investigation. This review summarizes the clinical applications of BsAbs and discusses the current challenges of the treatment and opportunities for optimization. Bispecific antibodies (BsAbs) are artificially engineered antibodies that can bind simultaneously to the CD3 subunit within the T-cell receptor complex and an antigen on tumor cells, leading to T-cell activation and tumor cell killing. BsAbs against BCMA or GPRC5D have shown impressive clinical activity in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), with some agents having already received regulatory approval after the third (by the European Medicines Agency, EMA) or fourth (by the Food and Drug Administration, FDA) line of therapy; the results of early-phase clinical trials targeting FcRH5 are also promising. Overall, BsAbs as monotherapy correlated with an ORR that exceeded 60%, with a high CR rate ranging between 25% and 50% and a median PFS of around 1 year among patients with a median of 4–6 prior lines of therapy. The main toxicities include cytokine release syndrome, cytopenias, hypogammaglobulinemia, and infections; on-target off-tumor adverse events involving the skin, mucosa, hair, and nails may also occur with anti-GPRC5D BsAbs. Active research to increase their efficacy and improve their tolerance is still in progress, including combination therapies and application in earlier treatment lines and the development of novel agents. A better understanding of the mechanisms of resistance is a challenge and could lead to more personalized approaches. [ABSTRACT FROM AUTHOR]

The first successful heart transplant was carried out in 1979, and there are now approximately 200 transplants undertaken in the UK each year. Many medications are used to prevent rejection of the transplanted organ, but this needs to be balanced with the risk of complications of immunosuppression, such as infection, organ dysfunction, graft dysfunction and vasculopathy. Patients must be able to adhere to the complex and vast regimen of medications started post-transplant, and extensive monitoring is required to ensure the correct balance of rejection risk and adverse effects, depending on where the patient is in their postoperative journey. Immediately after the transplant is when the patient is at highest risk of rejecting their new heart. Guidance is available to recommend regimens to prevent rejection, but needs to be adapted to each patient, taking into consideration their clinical picture, together with comorbidities, drug interactions and organ dysfunction. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple myeloma (MM) represents the second most common hematological malignancy, but its diagnosis can be significantly delayed since symptoms are not specific and, mainly in the older population, alternate diagnoses can mimic MM. Bone marrow biopsy (evaluating the amount of proliferating myeloma cells) remains an essential procedure, but several imaging methods such as whole-body low-dose computed tomography, positron emission tomography or whole-body magnetic resonance have become crucial for the diagnosis and staging of MM, and are also taking on a prognostic role. MM is a clinically and biologically heterogeneous disease; therefore, with the aim to identify patients with different outcomes, some risk models such as ISS, R-ISS or R2-ISS have been proposed over time. However, the most recent attempts have been to establish individualized patient risk, integrating clinical, genomic and therapeutic data in order to personalize treatment and avoid overtreatment and toxicities. The outcome of multiple myeloma (MM) has significantly improved in the last few decades due to several factors such as new biological discoveries allowing to better stratify disease risk, development of more effective therapies and better management of side effects related to them. However, handling all these aspects requires an interdisciplinary approach involving multiple knowledge and collaboration of different specialists. The hematologist, faced with a patient with MM, must not only choose a treatment according to patient and disease characteristics but must also know when therapy needs to be started and how to monitor it during and after treatment. Moreover, he must deal not only with organ issues related to MM such as bone disease, renal failure or neurological disease but also with adverse events, often very serious, related to novel therapies, particularly new generation immunotherapies such as CAR T cell therapy and bispecific antibodies. In this review, we provide an overview on the newer MM diagnostic and monitoring strategies and on the main side effects of MM therapies, focusing on adverse events occurring during treatment with CAR T cells and bispecific antibodies. [ABSTRACT FROM AUTHOR]

Background: Stiff person syndrome (SPS) is a rare neuroimmunological disorder characterized by rigidity and painful spasm primarily affecting the truncal and paraspinal musculature due to autoimmune‐mediated neuronal hyperexcitability. Spinal cord stimulation (SCS) is an approved therapy for managing painful neuropathic conditions, including diabetic peripheral neuropathy and refractory angina pectoris. We describe the novel use of SCS for the treatment of spasm and rigidity in a 49‐year‐old man with seropositive stiff person syndrome (SPS). The patient was treated with intravenous immunoglobulin (IVIG) and oral medications over a 13‐month period with minimal improvement, prompting consideration of SCS. To our knowledge, this is the first report of the successful use of SCS in SPS with the demonstration of multifaceted clinical improvement. Methods: Following a successful temporary SCS trial, permanent implantation was performed. Spasm/stiffness (Distribution of Stiffness Index; Heightened Sensitivity Scale; Penn Spasm Frequency Scale, PSFS), disability (Oswestry Disability Index, ODI; Pain Disability Index, PDI), depression (Patient Health Questionnaire‐9, PHQ‐9), sleep (Pittsburgh Sleep Quality Index, PSQI), fatigue (Fatigue Severity Scale, FSS), pain (Numerical Pain Rating Scale, NPRS), quality of life (EuroQoL 5 Dimension 5 Level, EQ‐5D‐5L), and medication usage were assessed at baseline, 6‐month, and 10‐month postimplantation. Results: ODI, PHQ‐9, FSS, NPRS, PSQI, and EQ‐5D‐5L scores showed a notable change from baseline and surpassed the defined minimal clinically important difference (MCID) at 6‐month and 10‐month follow‐up. Oral medication dosages were reduced. Conclusions: The novel use of SCS therapy in seropositive SPS resulted in functional improvement and attenuation of symptoms. We present possible mechanisms by which SCS may produce clinical response in patients with SPS and aim to demonstrate proof‐of‐concept for a future comprehensive pilot study evaluating SCS‐mediated response in SPS. [ABSTRACT FROM AUTHOR]

Mosquito-borne diseases are a public health concern. Pharmacists are often a patient's first stop for health information and may be asked questions regarding transmission, symptoms, and treatment of mosquito borne viruses (MBVs). The objective of this paper is to review transmission, geographic location, symptoms, diagnosis and treatment of MBVs. We discuss the following viruses with cases in the US in recent years: Dengue, West Nile, Chikungunya, LaCrosse Encephalitis, Eastern Equine Encephalitis Virus, and Zika. Prevention, including vaccines, and the impact of climate change are also discussed. [ABSTRACT FROM AUTHOR]

Objective: Inborn errors of immunity (IEI), formerly known as primary immunodeficiencies, are a group of inherited diseases affecting different innate and adaptive immune system components. The most common finding in the heterogeneous group of patients with IEI is infections, which are associated with increased morbidity and mortality. This retrospective study aims to determine infections in a heterogeneous group of patients receiving immunoglobulin replacement therapy (IGRT). Methods: The medical records of the patients with IEI who received IGRT and were followed up in our clinic for the last five years were reviewed retrospectively. Results: In this study, including 45 patients diagnosed with IEI (55.6% male, average age 38.4±11.6 years), the most common subgroup was primary antibody deficiencies (40, 88.8%). The average age of diagnosis for patients was 26.8±14.8 years, with a median diagnostic delay of 6 years. Twenty (44.4%) of patients had bronchiectasis. All patients were receiving IGRT, with 82.2% using antimicrobial prophylaxis. Before diagnosis, the median annual number of infections was 4, which decreased to 1 post-treatment (p<0.001). Significant reductions in pneumonia and upper respiratory tract infection frequency were observed with IGRT compared to before the treatment (75.6% vs. 22.2%, p<0.001; 66.7% vs. 31.1%, p=0.003). Seventeen (37.8%) of patients were hospitalized due to infections during treatment. The rate of inactive influenza vaccination and the average body mass index (BMI) were significantly lower in patients with hospitalization than in those without hospitalization (20% vs 53.8%, p=0.034; 20.5 vs. 24.1 kg/m², p=0.019). Among those with bronchiectasis, the rate of pneumonia prior to diagnosis was significantly higher (95% vs. 60%, p=0.012). Lower BMI, the presence of bronchiectasis, and non-compliance with treatment were associated with more frequent infections under treatment. Conclusion: Many complications, especially infections, can be prevented by early diagnosis and treatment of IEI and increasing patient compliance with treatment. Therefore, increasing awareness of IEI both in society and among physicians from all specialties will enable patients to be diagnosed at an early stage and reduce hospitalization, mortality and morbidity. [ABSTRACT FROM AUTHOR]

Purpose: This study assessed the clinical and immunological outcomes of SARS-CoV-2-infected patients with risk factors for severe disease depending on their immunological status. Methods: In this retrospective study with single follow-up visit, clinical outcome and humoral immunity was monitored in SARS-CoV-2 infected patients at risk. The results were compared based on the patients' initial immunological status: unvaccinated (UV), patients who did not develop neutralizing antibodies after vaccination (vaccine non-responders, VNR), and patients who expressed neutralizing antibodies after vaccination (vaccine responders, VR). Patients who lacked neutralizing antibodies (VNR and UV) were treated with nMABs. Results: In total, 113 patients at risk of severe COVID-19 consented to participate in the study. VR and UV were not admitted to the hospital. During the observation period, UVs had the highest rate of SARS-CoV-2 re-infections. Three of 41 VNRs (7.3%) were hospitalized due to severe COVID-19, with two of them having undergone iatrogenic B-cell depletion. The humoral immune response after infection was significantly lower in the VNR group than in the VR group in terms of anti-N, anti-receptor-binding domain (RBD), anti-S antibody titers, and anti-S antibody avidity. In a sub-analysis of VNR, B cell-deficient non-responders had significantly lower levels of anti-N antibodies and anti-S avidity after infection than other VNRs. Conclusion: VNR, particularly B-cell-depleted VNR, remained at risk of hospitalization due to COVID-19. In the VR group, however, no clinical complications or severe disease were observed, despite not receiving nMAbs. Tailoring the administration of nMABs according to patient vaccination and immunological status may be advisable. [ABSTRACT FROM AUTHOR]

The article focuses on whooping cough (pertussis), detailing its history, transmission dynamics, diagnostic methods, complications, and the evolution of vaccination strategies. It highlights the resurgence of pertussis outbreaks, particularly affecting infants, and emphasizes the critical role of vaccination in controlling its spread, despite challenges such as vaccine hesitancy and waning immunity.

Activated phosphoinositide 3-kinase (PI3Kδ) Syndrome (APDS) is an inborn error of immunity (IEI) with a variable clinical presentation, characterized by infection susceptibility and immune dysregulation that may overlaps with other Primary Immune Regulatory Disorders (PIRDs). The rarity of the disease, its recent discovery, and the multiform /multifaced clinical presentation make it difficult to establish a correct diagnosis, especially at an early stage. As a result, the true prevalence of the pathology remains unknown. There is no treatment protocol for APDS, and drug therapy is primarily focused on treating symptoms. The most common therapies include immunoglobulin replacement therapy, antimicrobial prophylaxis, and immunosuppressive drugs. Hematopoietic stem cell transplantation (HSCT) has been used in some cases, but the risk-benefit balance remains unclear. With the upcoming introduction of specific medications, such as selective inhibitors for PI3Kδ, clinicians are shifting their attention towards target therapy. This review provides a comprehensive overview of APDS with a focus on diagnostic and treatments procedures available. This review may be useful in implementing strategies for a more efficient patients' management and therapeutic interventions. Main Text. [ABSTRACT FROM AUTHOR]

Aims: To find clinical and immunological signatures of the SARS‐CoV‐2 and the COVID‐19 pandemic on children newly diagnosed with type 1 diabetes (T1D). Methods: A single‐centre, retrospective, observational study comparing the clinical and immunological characteristics of children diagnosed with T1D the year before and during the first 2 years of the COVID‐19 pandemic. Data extracted from the medical records included clinical and demographic parameters, COVID‐19 PCR results and the presence of anti‐islet, thyroid and celiac‐related antibodies. Also obtained from the medical records was a family history of T1D, celiac disease and autoimmune thyroid disease in a first‐degree family member. Results: A total of 376 children were diagnosed with T1D during the study period. A total of 132 in the pre‐COVID era and 246 in the first 2 years of the pandemic. At diagnosis, the pH in children with DKA was lower, and HbA1c tended to be higher in the COVID‐19 group compared to the pre‐COVID‐19 group (7.30 [7.18, 7.35] vs 7.33 [7.19, 7.36], p = 0.046) and (110.9 [86.9, 129.5] vs 100 [80.3, 129.5], p = 0.067]) respectively. Multiple islet antibodies (IA) were significantly more common among patients in the pre‐COVID‐19 group compared to the COVID‐19 group (72% vs 61%, p = 0.032). Tissue transglutaminase antibodies were more common among children diagnosed in the COVID‐19 compared to the pre‐COVID group (16.6% vs 7.9%, p = 0.022). Conclusions: Our findings suggest that SARS‐CoV‐2 and the environmental alterations caused by the pandemic affected the clinical characteristics and the immunological profile of children diagnosed with T1D. It is, therefore, plausible that the virus plays a role in the autoimmune process causing T1D. [ABSTRACT FROM AUTHOR]

The complement is a crucial factor of the innate immune system. However, its activation can lead to various diseases, so it needs to be controlled. In mammals, surface-bound complement regulatory proteins safeguard cells from uncontrolled complement-mediated lysis. One of the human complement regulators is CD55, also known as the decay-accelerating factor (DAF), a single-chain, type I cell surface protein anchored to glycosylphosphatidylinositol (GPI). The genetic loss of the complement regulatory protein CD55 leads to a fatal illness known as CHAPLE disease. The complement and innate immunity become hyperactive in this disease, causing angiopathic thrombosis and protein-losing enteropathy. Patients with CHAPLE disease experience abdominal pain, nausea, vomiting, diarrhea, loss of appetite, weight loss, impaired growth, and swelling. This genetic condition has no known cure, and managing its symptoms can be challenging. Pozelimab, a human monoclonal immunoglobulin IgG4 antibody, is a drug that targets the terminal complement protein C5. The drug has a high affinity for both wild-type and variant human C5. Pozelimab has received designations such as fast track, orphan drug, and rare pediatric disease, making it a significant medical breakthrough. It is currently the only available treatment for this disease. In this review, we have summarized the preclinical and clinical data on pozelimab. [ABSTRACT FROM AUTHOR]

Objective: To explore the efficacy and safety of PD-1 antibody versus high-dose interferon in the adjuvant treatment of stage IIB-IIID melanoma patients after surgery. Methods: Clinical data of patients with stage IIB-IIID cutaneous and acral melanoma admitted into Nanjing Drum Tower Hospital, the affiliated hospital of Nanjing University Medical School between September 2013 and September 2022 were retrospectively collected. All patients received high-dose interferon (HDI) or PD-1 antibody as adjuvant therapy after surgery. Univariate survival analysis was performed and survival curves were plotted by the Kaplan-Meier method; Log-Rank method was used to analyze and assess whether the differences in RFS, DMFS, and OS between the groups were statistically significant, and prognostic factors were evaluated by univariate and multivariate Cox regression. Results: A total of 91 patients were enrolled in this study with a median follow-up of 31.0 months. The median RFS was 29.2 and 32.3 months in the HDI group and the PD-1 antibody group, respectively, and the difference was not statistically significant (HR=0.90, 95%CI [0.50, 1.64]; P=0.736). The median DMFS and the median OS in the HDI group were 36.0 and 109.2 months respectively, and neither was reached in the PD-1 antibody group (both P>0.05). The most common site of first distant metastasis in both groups was the lung, and there was no statistically significant difference in the incidence of distant metastasis at any site (P>0.05). By univariate Cox analysis, compared with PD-1, antibody HDI reduced the risk of distant metastasis in patients with BRAFV600E/K mutations (HR=10.03, 95% CI [1.10, 91.35]; P=0.041). Subgroup analyses showed that in patients with cutaneous and acral melanoma, the difference in RFS between the HDI group and the PD-1 antibody group was not statistically significant (both P>0.05). The incidence of adverse reactions in the HDI group and the PD-1 antibody group was 83.3% and 79.1%, respectively, most of which were grade 1 or 2. No deaths related to adverse reactions occurred in both groups. Conclusion: In this study, there was no statistically significant difference in clinical efficacy and safety between PD-1 antibody and HDI adjuvant therapy for malignant melanoma patients. Patients with BRAFV600E/K mutations may benefit more from HDI. Numerous prospective studies are needed to further explore the optimal adjuvant treatment options for melanoma patients in Asian populations. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive deterioration, functional impairments, and neuropsychiatric symptoms. Valiltramiprosate is a tramiprosate prodrug being investigated as a novel treatment for AD. The online databases PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched using the terms 'ALZ-801' or 'valiltramiprosate.' Alzheon press releases were reviewed for emerging clinical information. Valiltramiprosate is an oral, well-tolerated synthetic valine-conjugate prodrug of tramiprosate. Valiltramiprosate's active metabolite include tramiprosate and 3-sulfopropanoic acid. Proposed mechanism of action is multiligand binding to Aβ42 which stabilizes amyloid monomers to prevent peptide aggregation and oligomerization. Pharmacokinetic studies show 52% oral bioavailability, rapid absorption, approximately 40% brain-drug exposure, and near complete renal clearance. Compared to tramiprosate, valiltramiprosate extends plasma tramiprosate half-life and improves interindividual pharmacokinetic variability. Interim analyses from valiltramiprosate's phase II biomarker trial show: (1) significant reductions in plasma p-tau181 and related AD fluid biomarkers; (2) brain structure preservation and reduced hippocampal atrophy by MRI; and (3) improvements on cognitive assessments at multiple timepoints. Its phase III clinical trial in ApoE ε4 homozygotes is near completion. Valiltramiprosate's clinical trial data show early indications of efficacy with potential disease modifying effect in AD. [ABSTRACT FROM AUTHOR]

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Background: Some causes of first-line treatment failure for ITP are often closely related to infections. But parasitic infections are rarely mentioned and easily overlooked. The case is the first to describe a boy with immune thrombocytopenia associated with blastocystis hominis. Case presentation: The case involved a boy presenting with bleeding skin spots and ecchymosis and accompanied by intermittent epigastric pain and constipation. After a series of complete examinations, the platelet count was found to be decreased to 13 × 109/L and immune thrombocytopenia was diagnosed. After first-line treatment with gamma globulin and prednisolone, the thrombocytopenia remained unchanged. Blastocystis hominis was subsequently found in the patient's stool and then the treatment of metronidazole was provided. One week later, the patient's thrombocytopenia was completely relieved. He was followed up for six months and was found to have recovered well. Conclusions: The screening for potential predisposing factors is very important for immune thrombocytopenia patients with poor response to first-line treatment, and the best treatment strategy should include the management of potential diseases. [ABSTRACT FROM AUTHOR]

Background: Widespread vaccinations have significantly decreased the number of tetanus cases in developed countries. Today, most cases of tetanus affect the elderly and those with inadequate immunization in developed countries such as Japan. As vaccinations were believed to be nearly 100% effective in preventing tetanus, tetanus in young, immunized individuals were considered unlikely. However, unexpected tetanus infection has been reported in young adequately immunized individuals. Case: We herein describe a 20-year-old immunized female who visited our emergency department with trismus and painful muscle spasms that started after receiving a puncture wound to her right foot. A physical examination revealed an elevated body temperature (38°C), trismus, muscle spasms in her right leg and neck, and a puncture wound at the sole of her right foot. Following the development of dyspnea after admission to the intensive care unit, the patient was intubated and mechanically ventilated. She fully recovered after six days in intensive care. Conclusion: The present case serves as a stark reminder that tetanus may still occur in young, immunized individuals. Patients with a history of immunization may have a better prognosis than those with no immunizations. [ABSTRACT FROM AUTHOR]

Objective: A correlation between the intensity of S. aureus colonization and skin inflammation has been demonstrated. 30-60% of S. aureus bacteria in patients with atopic dermatitis (AD) generate exotoxins, specifically superantigen-like enterotoxins A-B-C-D and toxic shock syndrome toxin-1. This study aimed to determine the role of serum staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB)-specific IgE antibodies in children with AD. Materials and Methods: Forty-four children with AD, 30 with allergic respiratory disease (ARD) without AD, and 25 nonatopic healthy children were included in this study. AD cases were diagnosed according to Hanifin and Rajka criteria. The severity of AD was evaluated by the "Eczema Area and Severity Index". Serum total IgE (tIgE), SEA-specific IgE and SEB-specific IgE levels were analyzed in all children. Results: Serum tIgE levels were significantly elevated in children with ARD without AD compared to children with AD and healthy children (p=0.041). However, there was no significant difference in the levels and the rates of positive SEA-specific IgE and SEB-specific IgE for children with AD, children with ARD without AD, and healthy children. A significantly positive correlation was detected between the EASI scores and SEA-IgE levels in children with AD (p=0.002). Conclusion: Although the role of SEA in the pathogenesis of AD through IgE-mediated mechanisms is not fully known, the data in our study seems to provide support to the role of SEA on the severity of AD. To conclude, adding antistaphylococcal treatment to antiinflammatory therapy may be helpful in obtaining an effective clinical response in children with moderate to severe AD. [ABSTRACT FROM AUTHOR]

This case report expands the reported range of clinical presentations of CV2/CRMP5 antibody‐related syndromes with two novel findings (manic psychosis and psychogenic polydipsia). A systematic literature review highlights a potentially higher incidence of psychosis than previously reported, clinical features that should prompt antibody testing, and the potential for treatment response. [ABSTRACT FROM AUTHOR]

Simple Summary: Biomarker-guided therapies offer the possibility for targeted cancer therapies. For gastric cancer, HER2 plays a pivotal role. To date, with trastuzumab and trastuzumab-deruxtecan, two HER2-targeting options exist for the treatment of metastatic HER2-positive gastric cancer. However, these therapies rarely lead to long-lasting results as resistance mechanisms and heterogeneity limit their success. This review gives an overview of the current standard-of-care treatment of HER2-positive gastric cancer and new developments in the field. Despite a decreasing incidence in Western countries, gastric cancer is among the most common cancer subtypes globally and is associated with one of the highest tumor-related mortality rates. Biomarkers play an increasing role in the treatment against gastric cancer. HER2 was one of the first biomarkers that found its way into clinical practice. Since the ToGA trial, trastuzumab has been part of first-line palliative chemotherapy in metastatic or unresectable gastric cancer. HER2-targeting agents, such as the tyrosine kinase inhibitor lapatinib, the antibody drug conjugate (ADC) trastuzumab-emtansine or dual HER2 inhibition (pertuzumab and trastuzumab), have been investigated in the second-line setting but led to negative study results. More recently, the ADC trastuzumab-deruxtecan was authorized after the failure of trastuzumab-based treatment. However, further improvements in HER2-directed therapy are required as resistance mechanisms and HER2 heterogeneity limit the existing treatment options. This review aims to give an overview of the current standard-of-care HER2-directed therapy in gastric cancer, as well as its challenges and future developments. [ABSTRACT FROM AUTHOR]

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433. [ABSTRACT FROM AUTHOR]

Background While we strive to live with SARS-CoV-2, defining the immune response that leads to recovery rather than severe disease remains highly important. COVID-19 has been associated with inflammation and a profoundly suppressed immune response. Objective To study myeloid-derived suppressor cells (MDSCs), which are potent immunosuppressive cells, in SARS-CoV-2 infection. Results Patients with severe and critical COVID-19 showed higher frequencies of neutrophilic (PMN)–MDSCs than patients with moderate illness and control individuals (P =.005). Severe disease in individuals older and younger than 60 years was associated with distinct PMN-MDSC frequencies, being predominantly higher in patients of 60 years of age and younger (P =.004). However, both age groups showed comparable inflammatory markers. In our analysis for the prediction of poor outcome during hospitalization, MDSCs were not associated with increased risk of death. Still, patients older than 60 years of age (odds ratio [OR] = 5.625; P =.02) with preexisting medical conditions (OR = 2.818; P =.003) showed more severe disease and worse outcome. Among the immunological parameters, increased C-reactive protein (OR = 1.015; P =.04) and lymphopenia (OR = 5.958; P =.04) strongly identified patients with poor prognosis. Conclusion PMN-MDSCs are associated with disease severity in COVID-19; however, MDSC levels do not predict increased risk of death during hospitalization. [ABSTRACT FROM AUTHOR]

Introduction: Various factors, including viruses, are involved in developing liver cirrhosis. Although the association of human herpesvirus-8 (HHV-8) with liver cirrhosis remains poorly understood, a significant increase in the titer of antibodies against this virus has been observed in cirrhotic patients. The present study aimed to evaluate the frequency of HHV-8-immunoglobulin G (HHV-8 IgG) in Iranian patients with liver cirrhosis. Material & Methods: In this cross-sectional study, 30 healthy blood donors and 30 patients with liver cirrhosis related to hepatitis B (n=20) and hepatitis C (n=10) viruses from those waiting for liver transplantation were included. The serum seropositivity of HHV-8 IgG antibody was evaluated using the enzyme-linked immunosorbent assay (ELISA) technique. Results: The seropositivity of HHV-8 IgG antibodies in patients and healthy groups was 6.7% (2 patients) and 3.3% (1 case), respectively, which did not show a significant difference between the two groups (P=0.554). In addition, the infection was not significantly related to the age and gender of the patients (P>0.05). Discussion & Conclusion: Considering the low prevalence of HHV-8 infection in Iranian patients with liver cirrhosis, it can be concluded that HHV-8 may not be associated with the incidence and progression of liver cirrhosis. Therefore, HHV-8 monitoring will not raise the concern about the development or worsening of liver disorders. [ABSTRACT FROM AUTHOR]

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Prior to the advent of the HER2-targeted monoclonal antibody trastuzumab, HER2+ breast cancer (BC) was considered an aggressive disease with a poor prognosis. Over the past 25 years, innovations in molecular biology, pathology, and early therapeutics have transformed the treatment landscape. With the advent of multiple HER2-directed therapies, there have been immense improvements in oncological outcomes in both adjuvant and metastatic settings. Currently, 8 HER2-targeted therapies are approved by the Food and Drug Administration (FDA) for the treatment of early-stage and/or advanced/metastatic disease. Nonetheless, approximately 25% of patients develop recurrent disease or metastasis after HER2-targeted therapy and most patients with HER2+ metastatic breast cancer (MBC) die from their disease. Given the many mechanisms of resistance to HER2-directed therapy, there is a pressing need to further personalize care for patients with HER2+ MBC, by the identification of reliable predictive biomarkers, and the development of novel therapies and combination regimens to overcome therapeutic resistance. Of particular interest are established and novel antibody-drug conjugates, as well as other novel therapeutics and multifaceted approaches to harness the immune system (checkpoint inhibitors, bispecific antibodies, and vaccine therapy). Herein, we discuss standard-of-care treatment of HER2+ MBC, including the management of breast cancer brain metastases (BCBM). Furthermore, we highlight novel treatment approaches for HER2+ MBC, including endeavors to personalize therapy, and discuss ongoing controversies and challenges. [ABSTRACT FROM AUTHOR]

Simple Summary: Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in approximately 20% of breast cancer cases. This overexpression is correlated with a more aggressive form of the disease and predicts a less favorable prognosis. Historically, the standard treatment for patients with HER2-positive breast cancer has involved chemotherapy in combination with monoclonal antibodies that target the HER2 receptor, notably trastuzumab and pertuzumab. However, resistance to these drugs has been ubiquitous, presenting challenges in the management of the disease. Antibody–drug conjugates (ADCs) represent a promising therapeutic category for the treatment of breast cancer. Trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) are currently approved ADCs. These molecules have been pivotal, demonstrating superior clinical outcomes over previous conventional treatments in HER2-positive breast cancer (T-DM1, T-DXd) and HER2-Low (T-DXd). However, drug resistance remains an unresolved problem, and there is interest in developing better-tolerated and more effective therapeutics for breast cancer. This review focuses on the emergence of innovative HER2-targeted ADCs, including those currently undergoing investigation in clinical trials. Human epidermal growth factor receptor 2 (HER2) tyrosine kinase is overexpressed in 20% of breast cancers and associated with a less favorable prognosis compared to HER2-negative disease. Patients have traditionally been treated with a combination of chemotherapy and HER2-targeted monoclonal antibodies such as trastuzumab and pertuzumab. The HER2-targeted antibody–drug conjugates (ADCs) trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) represent a novel class of therapeutics in breast cancer. These drugs augment monoclonal antibodies with a cytotoxic payload, which is attached by a linker, forming the basic structure of an ADC. Novel combinations and sequential approaches are under investigation to overcome resistance to T-DM1 and T-DXd. Furthermore, the landscape of HER2-targeted therapy is rapidly advancing with the development of ADCs designed to attack cancer cells with greater precision and reduced toxicity. This review provides an updated summary of the current state of HER2-targeted ADCs as well as a detailed review of investigational agents on the horizon. Clinical trials are crucial in determining the optimal dosing regimens, understanding resistance mechanisms, and identifying patient populations that would derive the most benefit from these treatments. These novel ADCs are at the forefront of a new era in targeted cancer therapy, holding the potential to improve outcomes for patients with HER2-positive and HER2-Low breast cancer. [ABSTRACT FROM AUTHOR]

Little is known about deployment of SARS-CoV-2–neutralizing monoclonal antibodies (mab) in skilled nursing facilities (SNFs), a high-risk population for COVID-19–related complications. We assessed the utilization of mabs in SNFs and identified facility characteristics associated with effective use. Retrospective cohort study assessing the correlation of SNF characteristics with increasing mab use. United States SNFs participating in Project ECHO (Extensions for Community Health Outcomes). The primary outcome was percentage of total mabs per COVID-19 cases in SNFs. Facilities were divided into 3 groups based on the percentage of the administration of mabs per number of cases: 0%, >0% to 20%, >20%. Ordinal logistic regression was applied to assess whether facility characteristics—study group, state, location, type, size, rating at baseline, weekly average of residents vaccinated, weekly average of staff vaccinated, and total weeks short staffed—correlated with the primary outcome. A multivariable model was used to evaluate the independent effect of predictors. A total of 130 facilities were included. Between the weeks ending on May 30, 2021, and on May 29, 2022, mean mab use when accounting for the number of COVID-19 cases was 12.96% (±26.71%) and >50% of facilities administered 0 doses of mabs. Facility location was associated with mab use (P value.030), with micropolitan facilities having the highest percentage of facilities administering mabs (30.4% in >0% to 20%, and 39.1% in >20%, respectively). There was a nonsignificant trend toward increased mab use in facilities reporting fewer staffing shortages. When the multivariable ordinal logistic regression model was applied, location in a micropolitan vs metropolitan area was associated with higher odds [3.29 (1.30, 8.32), P value.012] of increasing percentage total mabs per cases. COVID-19 mabs were underutilized in a high-risk population for COVID-19 hospitalization and death. Understanding the barriers to effective distribution is critical in shaping pandemic preparedness efforts for the future. [ABSTRACT FROM AUTHOR]

Case presentation: A pregnant woman developed hepatitis due to a herpes simplex virus 2 primary infection with a severe systemic inflammatory response. Treatment with acyclovir and human immunoglobulin was given and both mother and baby survived. Purpose: We provide the first description of the inflammatory response associated with herpetic hepatitis in pregnancy. [ABSTRACT FROM AUTHOR]

Summary: Nivolumab can cause fatal myocarditis. We aimed to analyze the clinical characteristics of nivolumab-induced myocarditis and provide evidence for clinical diagnosis, treatment, and prevention. Studies involving nivolumab-induced myocarditis were identified in electronic databases from 2000 to 2023 for retrospective analysis. A total of 66 patients were included, with a median age of 68 years. The median onset time of myocarditis is 11.5 days. The main organs affected in persons presented with myocarditis are heart (100.0%) and skeletal muscle (22.7%). The main clinical manifestations are dyspnea (49.2%), fatigue (47.6%), and myalgias (25.4%). The levels of troponin, troponin T, troponin I, creatine kinase, creatine kinase myocardial band, creatine phosphokinase, C-reactive protein, brain natriuretic peptide, and N-terminal brain natriuretic peptide precursor were significantly increased. Histopathology often shows lymphocyte infiltration, myocardial necrosis, and fibrosis. Myocardial immunological parameters usually present positive. Cardiac imaging often suggests complete heart block, intraventricular conduction delay, arrhythmia, myocardial infarction, edema, left ventricular ejection fractions reduction, ventricular dysfunction, and other symptoms of myocarditis. Forty-two (63.6%) patients achieved remission within a median time of 8 days after discontinuation of nivolumab and treatment with systemic corticosteroids, immunoglobulins, plasmapheresis, and immunosuppressant. Thirty-five patients eventually died attributed to myocarditis (68.6%), cancer (20.0%), respiratory failure (5.7%), and other reasons (5.7%). Nivolumab-induced myocarditis should be comprehensively diagnosed based on clinical symptoms, histopathological manifestations, immunological parameters, and cardiac function imaging examinations. Nivolumab should be discontinued immediately, plasmapheresis and systemic corticosteroids combined with immunoglobulins or immunosuppressants may be an effective treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: With around 15 kD molecular weight, VHHs are considered the smallest antigen-binding fragments. Based on their unique properties, VHHs have broad application prospects such as bio-sensing, molecular imaging, drug delivery, disease treatments, and diagnosis. In this review, we discuss VHH applications for cancer treatments and diagnosis. Meanwhile, an overview of VHH-based agents in clinical trials is provided. The discovery of the distinctive structure of heavy chain-only antibodies in species belonging to the Camelidae family has elicited significant interest in their variable antigen binding domain (VHH) and gained attention for various applications, such as cancer diagnosis and treatment. This article presents an overview of the characteristics, advantages, and disadvantages of VHHs as compared to conventional antibodies, and their usage in diverse applications. The singular properties of VHHs are explained, and several strategies that can augment their utility are outlined. The preclinical studies illustrating the diagnostic and therapeutic efficacy of distinct VHHs in diverse formats against solid cancers are summarized, and an overview of the clinical trials assessing VHH-based agents in oncology is provided. These investigations demonstrate the enormous potential of VHHs for medical research and healthcare. [ABSTRACT FROM AUTHOR]

This Note explores the patent challenges facing antibody-based therapeutics, using a study of CAR (Chimeric Antigen Receptor) T cells. CAR T cells are a type of antibody-based therapeutic that use genetically modified T cells to target and eliminate cancer cells. CAR T cells have shown remarkable efficacy in clinical trials for lymphoma cancers, and the global market for these products was valued at US$1.7 billion in 2021. The Note focuses on Novartis' Kymriah, which is the only CD19 CAR T cell whose patent is owned by the parent company, among the four CD19 CAR T cells approved by the U.S. Food and Drug Administration. The Note examines how the recent decision by the U.S. Supreme Court in Amgen Inc. v. Sanofi may affect antibody-based therapeutics using Novartis' patent and its competitors as a case study. The Amgen Inc. v. Sanofi decision invalidated Amgen's patents for lack of enablement. This may create opportunities for competitors to design around antibody-based patents by making derivatives based around what is said to not be enabled in the patent. The Note also discusses the implications of Amgen Inc. v. Sanofi for the research and development incentives and litigation activities of biopharmaceutical companies, as well as for the patent system. The recent move by the Supreme Court to narrow enablement requirements for antibodybased therapeutics in Amgen Inc. v. Sanofi enhances the ability to invalidate antibody-based patents and allows for increased ability of competitors to patent derivatives of already patented antibody-based therapeutics. [ABSTRACT FROM AUTHOR]

We report 2 cases of pediatric ocular myasthenia gravis. The first case was a 7-year-old girl who presented with bilateral ophthalmoplegia and ptosis that correlated with the onset of upper respiratory symptoms. Neuroimaging and acetylcholine receptor antibody testing were unremarkable. The ice pack test was positive. Symptoms greatly improved with pyridostigmine, with full resolution of ophthalmoplegia achieved by 8-month follow-up. The second case was a 4-year-old girl who presented emergently with ptosis and bilateral ophthalmoplegia. Acetylcholine receptor antibodies testing was positive. The patient was started on pyridostigmine and intravenous immunoglobulin and is scheduled to follow-up with pediatric ophthalmology in the outpatient setting. [ABSTRACT FROM AUTHOR]

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a clinicoradiological syndrome first recognized during the influenza pandemic in Japanese population in the late twentieth century. 1 In this article, we presented a rare case report of AESD in a young child due to severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2) who presented with febrile status epilepticus, persistent encephalopathy, and had recurrence of seizures on day 4 of illness with characteristic magnetic resonance imaging findings and a relatively fair outcome [ABSTRACT FROM AUTHOR]

Working with patients with Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) requires a clear understanding of their current health status. In the scientific literature, there is not enough data on their quality of life with the different therapeutic regimens. No generic tools have been developed to assess functional indicators and health status. The aim of the study is to measure the health-related quality of life (physical, psychological and social functioning) in a Bulgarian population of patients with systemic vasculitis associated with ANCA undergoing treatment with rituximab using a common tool. Design - retrospective-prospective, observational, non- interventional, controlled study in two periods, in two rheumatology centers in Bulgaria. Treatment with rituximab leads to qualitative and quantitative improvement in all components of physical health, mental and social components. All measured parameters are within the normal range for the general population. Rituximab treatment of AAV is the best therapeutic alternative in current rheumatology practice. [ABSTRACT FROM AUTHOR]

Asthma is sustained by an underlying type 2 cytokines of T helper type 2 bias, resulting in airway inflammation, hyperresponsiveness, and obstruction. The potential benefit of immunotherapy with allergen can be used to prevent asthma related problems, but high level of risk in children is important. In children, for reduction of asthma progression risk with other atopic diseases (for example atopic dermatitis and allergic rhinitis), organized strategy is necessary. Nursing care and patients' family care have a strong effect on the future and control of allergic asthma attacks. These protocols also have a main effect on the efficacy of treatment and immunotherapy of asthma. This can introduce an effective network between clinicians, nurses, patients, and their families to control asthma. [ABSTRACT FROM AUTHOR]

Objective Immune-mediated necrotizing myopathies (IMNMs) are severe forms of myositis often associated with pathogenic anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies (aAbs). Efgartigimod is an engineered human IgG1 Fc fragment that antagonizes the neonatal Fc receptor (FcRn), thereby preventing recycling and promoting lysosomal degradation of IgG, including aAbs. We evaluated the therapeutic effects of IgG reduction by efgartigimod in a humanized murine model of IMNM. Methods Disease was induced in C5-deficient (C5def) or Rag2-deficient (Rag2–/–) mice receiving co-injections of anti-HMGCR+ IgG from an IMNM patient and human complement. C5def mice were treated in a preventive setting with s.c. injections of efgartigimod and Rag2–/– mice in a curative setting after disease was induced by anti-HMGCR+ IgG injections. Anti-HMGCR aAbs levels were monitored in mouse serum and muscle tissue. Histological analysis was performed on muscle sections. Muscle force was assessed by grip test or measurement of gastrocnemius strength upon electrostimulation. Results Administration of efgartigimod rapidly reduced total IgG levels, including the level of pathogenic anti-HMGCR aAbs, in both serum (P  < 0.0001) and muscle (P  < 0.001). In the preventive setting, efgartigimod prevented myofibre necrosis (P  < 0.05), thus precluding loss of muscle strength (P  < 0.05). In the therapeutic setting, efgartigimod prevented further necrosis and allowed muscle fibre regeneration (P  < 0.05). Hence, muscle strength returned to normal (P  < 0.01). Conclusion Efgartigimod reduces circulating IgG levels, including pathogenic anti-HMGCR+ IgG aAbs, in a humanized mouse model of IMNM, preventing further necrosis and allowing muscle fibre regeneration. These results support investigating the therapeutic efficacy of efgartigimod through a clinical trial in IMNM patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is a leading cause of death worldwide, accounting for nearly one in six deaths. The most common cancers are lung, breast, colon, rectum and prostate cancers. In recent years, antibodies against immune checkpoints have been rapidly developed. Compared to monoclonal antibodies, nanobodies have a much smaller size and subsequently have the ability to penetrate deeper into solid tissues, clear faster from the bloodstream and are easier to conjugate with specific carriers. Utilizing these characteristics, nanobodies have been widely used in cancer imaging and treatment. In this review, we focus on the up-to-date studies either in lab research or clinical trials. Monoclonal antibodies (mAbs) have exhibited substantial potential as targeted therapeutics in cancer treatment due to their precise antigen-binding specificity. Despite their success in tumor-targeted therapies, their effectiveness is hindered by their large size and limited tissue permeability. Camelid-derived single-domain antibodies, also known as nanobodies, represent the smallest naturally occurring antibody fragments. Nanobodies offer distinct advantages over traditional mAbs, including their smaller size, high stability, lower manufacturing costs, and deeper tissue penetration capabilities. They have demonstrated significant roles as both diagnostic and therapeutic tools in cancer research and are also considered as the next generation of antibody drugs. In this review, our objective is to provide readers with insights into the development and various applications of nanobodies in the field of cancer treatment, along with an exploration of the challenges and strategies for their prospective clinical trials. [ABSTRACT FROM AUTHOR]

Ocular flutter (OF) is a rare oculomotor syndrome. The most common etiologies are paraneoplastic, postinfectious and toxic-metabolic. However post-vaccinal etiology was rarely reported in OF. Here, we reported a post-vaccinal clinical syndrome characterized by OF-myoclonus and ataxia associated with oligoclonal bands (OCBs). A 60-year-old male who presented with dizziness, unsteady gait, involuntary movements, involuntary conjugate eye oscillations and extremity jerks that started 3 days after the second dose of mRNA BNT162b2 Covid-19 vaccine. Routine biochemical and serological analysis were within normal limits. No pathological finding was detected in brain MRI. Paraneoplastic and autoimmune encephalitis tests were unremarkable in cerebrospinal fluid (CSF). Oligoclonal band s were positive in CSF. This is the first description of the relationship between vaccines against SARS-CoV-2 and the clinical syndrome of OF, Myoclonus and Ataxia (OFMAS). Humoral immune mechanisms seem to play an important role in OFMAS. Presence of OCBs in CSF may also be associated with this condition. [ABSTRACT FROM AUTHOR]

Context.--Substantial variability between different antibody titration methods has been identified since the development and introduction of the uniform procedure in 2008. Objective.--To determine whether more recent methods or techniques decrease interlaboratory and intralaboratory variation measured using proficiency testing. Design.--Proficiency test data for antibody titration between 2014 and 2018 were obtained from the College of American Pathologists. Interlaboratory and intralaboratory variations were compared by analyzing the distribution of titer results by method and phase, comparing the results against the supplier's quality control titer, and by evaluating the distribution of paired titer results when each laboratory received a sample with the same titer twice. Results.--A total of 1337 laboratories participated in the antibody titer proficiency test during the study period. Only 54.1% (5874 of 10 852) of anti-D and 63.4% (3603 of 5680) of anti-A reported responses were within 1 titer of the supplier's intended result. Review of the agreement between laboratories of the same methodology found that 78.4% (3139 of 4004) for anti-A and 89.0% (9655 of 10 852) of laboratory responses for anti-D fell within 1 titer of the mode response. When provided with 2 consecutive samples of the same titer (anti-D titer: 16), 85% (367 of 434) of laboratories using the uniform procedure and 80% (458 of 576) using the other method reported a titer difference of 1 or less. Conclusions.--Despite advances, interlaboratory and intralaboratory variance for this assay remains high in comparison with the strong reliance on titer results in clinical practice. There needs to be a reevaluation of the role of this test in clinical decision-making. [ABSTRACT FROM AUTHOR]

Background: In recent years, breast cancer has become the most common cancer in the world, increasing women's health risks. Approximately 60% of breast cancers are categorized as human epidermal growth factor receptor 2 (HER2)-low tumors. Recently, antibody-drug conjugates have been found to have positive anticancer efficacy in patients with HER2-low breast cancer, but more studies are required to comprehend their clinical and molecular characteristics. Methods: In this study, we retrospectively analyzed the data of 165 early breast cancer patients with pT1-2N1M0 who had undergone the RecurIndex testing. To better understand HER2-low tumors, we investigated the RecurIndex genomic profiles, clinicopathologic features, and survival outcomes of breast cancers according to HER2 status. Results: First, there were significantly more hormone receptor (HR)-positive tumors, luminal-type tumors, and low Ki67 levels in the HER2-low than in the HER2-zero. Second, RI-LR (P =.0294) and RI-DR (P =.001) scores for HER2-low and HER2-zero were statistically significant. Third, within HER2-negative disease, HR-positive/HER2-low tumors showed highest ESR1, NFATC2IP, PTI1, ERBB2, and OBSL1 expressions. Fourth, results of the survival analysis showed that lower expression of HER2 was associated with improved relapse-free survival for HR-positive tumors, but not for HR-negative tumors. Conclusions: The present study highlights the unique features of HER2-low tumors in terms of their clinical characteristics as well as their gene expression profiles. HR status may influence the prognosis of patients with HER2-low expression, and patients with HR-positive/HER2-low expression may have a favorable outcome. In this study, the data of patients with early stage breast cancer who had undergone RecurIndex testing was analyzed. To better understand HER2-low tumors, genomic profiles, clinicopathologic features, and survival outcomes of breast cancers according to HER2 status were investigated. [ABSTRACT FROM AUTHOR]

Simple Summary: Small-cell lung cancer (SCLC) represents a highly aggressive form of lung cancer. Although SCLC initially responds to chemoimmunotherapy, it inevitably relapses. Antibody–drug conjugates (ADCs) have emerged as a promising treatment approach. ADCs consist of antibodies targeting specific tumor antigens, delivering cytotoxic drugs directly to cancer cells, and reducing side effects. In this review, we collected the available data regarding ADCs evaluated in SCLC. While some ADCs yielded negative results, others, such as those targeting B7-H3, SEZ6, CEACAM5, and TROP2 ADC, show promise. Further research is needed to determine ADCs' role in SCLC treatment. Small-cell lung cancer (SCLC) is a highly aggressive disease, accounting for about 15% of all lung cancer cases. Despite initial responses to chemoimmunotherapy, SCLC recurs and becomes resistant to treatment. Recently, antibody–drug conjugates (ADCs) have emerged as a promising therapeutic option for SCLC. ADCs consist of an antibody that specifically targets a tumor antigen linked to a cytotoxic drug. The antibody delivers the drug directly to the cancer cells, minimizing off-target toxicity and improving the therapeutic index. Several ADCs targeting different tumor antigens are currently being evaluated in clinical trials for SCLC. Despite the negative results of rovalpituzumab tesirine (Rova-T), other ADCs targeting different antigens, such as B7-H3, seizure-related homolog 6 (SEZ6), and CEACAM5, have also been investigated in clinical trials, including for SCLC, and their results suggest preliminary activity, either alone or in combination with other therapies. More recently, sacituzumab govitecan, an anti-TROP2 ADC, demonstrated promising activity in lung cancer, including SCLC. Furthermore, an anti-B7-H3 (CD276), ifinatamab deruxtecan (DS7300A), showed a high response rate and durable responses in heavily pretreated SCLC. Overall, ADCs represent an intriguing approach to treating SCLC, particularly in the relapsed or refractory setting. Further studies are needed to determine their efficacy and safety and the best location in the treatment algorithm for SCLC. In this review, we aim to collect and describe the results regarding the past, the present, and the future of ADCs in SCLC. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to investigate the association of neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR) with standard inflammation parameters, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), complement component C3, anti-double-stranded deoxyribonucleic acid (anti-dsDNA), anti-nucleosome and anti-C1q antibodies, and serum and urinary monocyte-chemoattractant protein-1 (MCP-1) with disease activity in patients with systemic lupus erythematosus (SLE). Results: This study included 160 patients (145 female and 15 male patients), hospitalized at the Rheumatology Department. A positive correlation between NLR and ESR (p < 0.01), anti-dsDNA antibodies (p < 0.05), and PLR (p < 0.001) was obtained, with a negative correlation with C3 (p < 0.005). PLR shows a positive correlation with ESR (p < 0.001), CRP (p < 0.005), anti-dsDNA antibodies (p < 0.001), anti-nucleosome antibodies (p < 0.05), and urine MCP-1 (p < 0.05), with a negative correlation with C3 (p < 0.005). Univariate analysis showed that all the examined laboratory parameters were independent predictors of disease activity (p < 0.001), while the method of standard multiple regression analysis revealed the most significant ESR and serum MCP-1 (p < 0.05). Conclusions: NLR and PLR, as inexpensive and accessible biomarkers, can help in routine clinical practice for the estimation of disease activity in SLE patients. [ABSTRACT FROM AUTHOR]

The article describes the case of a chronic smoker who presented with subacute onset, progressive weakness of all four limbs and developed difficulty in speaking and swallowing. Topics include the findings of physical and laboratory examinations which led to the diagnosis of polyarteritis nodosa (PAN), the atypical presentation of PAN along with some errors of omission which lead to delayed diagnosis, and patient outcome following treatment.

Graft-versus-host disease (GVHD) of central nervous system is an atypical and rare manifestation of chronic GVHD, presenting with a heterogeneous spectrum of signs and symptoms. Diagnosis of neurological manifestations of GVHD can be highly challenging and remain associated with dismal prognosis, significant morbidity, and reduced quality of life. In this report, we describe a 39-year-old woman developing neurological signs and symptoms 8 months after allogeneic HSCT magnetic resonance imaging showed multifocal hyperintense lesions involving the periventricular region and frontal subcortical white matter. There was no laboratory evidence of infective or malignant etiology, and the case was diagnosed as CNS-GVHD. The patient was treated with intravenous methylprednisolone pulse therapy and the clinical conditions gradually improved. After few months, patient symptoms progressed despite the addition of high-dose intravenous immunoglobulin, tacrolimus, and a new course of high dose steroids. To engage targeted therapy, the patient underwent brain biopsy that revealed a loss of myelin fibers, perivascular and diffuse infiltration of T cells, and macrophages associated with reactive gliosis, representing a demyelinating disease. We intensified treatment with cyclophosphamide and subsequently introduced ibrutinib as salvage strategy. Despite a magnetic resonance imaging showing great regression of the demyelinating lesions, patient's conditions deteriorated and she died 16 months after HSCT. CNS-GVHD is a rare complication of HSCT that is difficult to diagnose. Based on our experience, brain biopsy may represent a useful diagnostic tool when the clinical features of neurological symptoms are ambiguous or in patients without evidence of preceding chronic GVHD. [ABSTRACT FROM AUTHOR]