For the monitoring of chimeric antigen receptor (CAR) T-cell therapies, antigen-based CAR detection methods are usually applied. However, for each target-antigen, a separate detection system is required. Furthermore, when monitored CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods produce false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment promise a universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19-targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel, the sensitivity was significantly lower compared to that for antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel, or Ide-cel, respectively. Cilta-cel (containing a monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but are not universally applicable.

We have developed and validated a highly specific, versatile antibody to the extracellular domain of human LGR5 (α-LGR5). α-LGR5 detects LGR5 overexpression in >90% of colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pre-B-ALL tumour cells and was used to generate an Antibody-Drug Conjugate (α-LGR5-ADC), Bispecific T-cell Engager (α-LGR5-BiTE) and Chimeric Antigen Receptor (α-LGR5-CAR). α-LGR5-ADC was the most effective modality for targeting LGR5+ cancer cells in vitro and demonstrated potent anti-tumour efficacy in a murine model of human NALM6 pre-B-ALL driving tumour attrition to less than 1% of control treatment. α-LGR5-BiTE treatment was less effective in the pre-B-ALL cancer model yet promoted a twofold reduction in tumour burden. α-LGR5-CAR-T cells also showed specific and potent LGR5+ cancer cell killing in vitro and effective tumour targeting with a fourfold decrease in pre-B-ALL tumour burden relative to controls. Taken together, we show that α-LGR5 can not only be used as a research tool and a biomarker but also provides a versatile building block for a highly effective immune therapeutic portfolio targeting a range of LGR5-expressing cancer cells.

We report a case of Vandammella animalimorsus in an adult female patient following a cat scratch/bite. Animal bite/scratches may lead to zoonotic transmission of bacteria that subsequently lead to infection. Wound management and antimicrobial therapy is often necessary. The organism was initially misidentified as Neisseria animaloris/zoodegmatis and highlights the difficulty of correctly identifying some bacteria in clinical microbiology laboratories.
Dogs and cats carry bacteria that are not carried in humans. Dog and cat bites or scratches may lead to these bacteria being spread to humans. This can lead to infection. These infections are usually treated by wound care and antibiotics. We describe a case of infection in a human with a bacteria from a cat following a cat bite/scratch to the patient\'s leg and discuss how the infection was diagnosed and treated.

Human cytomegalovirus is a ubiquitous herpesvirus that, while latent in most individuals, poses a great risk to immunocompromised patients. In contrast to directly acting traditional antiviral drugs, such as ganciclovir, we aim to emulate a physiological infection control using T cells. For this, we constructed several bispecific T-cell engager (BiTE) constructs targeting different viral glycoproteins of the murine cytomegalovirus and evaluated them in vitro for their efficacy. To isolate the target specific effect without viral immune evasion, we established stable reporter cell lines expressing the viral target glycoprotein B, and the glycoprotein complexes gN-gM and gH-gL, as well as nano-luciferase (nLuc). First, we evaluated binding capacities using flow cytometry and established killing assays, measuring nLuc-release upon cell lysis. All BiTE constructs proved to be functional mediators for T-cell recruitment and will allow a proof of concept for this treatment option. This might pave the way for strikingly safer immunosuppression in vulnerable patient groups.

UNASSIGNED: Breast reconstruction following mastectomy is a critical component of breast cancer treatment, aimed at improving patient quality of life. However, the management is fraught with potential complications, including skin necrosis and wound dehiscence, which can significantly impact clinical outcomes.
UNASSIGNED: We report a unique case of a patient, 5 years post-breast reconstruction following mastectomy and radiation therapy, who developed severe skin necrosis and wound dehiscence due to a brown recluse spider bite on the reconstructed breast. The complication necessitated the debridement of skin, removal of the implant, and further reconstruction with a latissimus flap.
UNASSIGNED: The case underscores the unusual etiology of spider bite-induced necrosis in breast reconstruction and highlights the challenges and strategic considerations in managing such complications. Upon presentation, the patient\'s affected breast area showed signs of extensive necrosis and wound dehiscence, directly attributed to the cytotoxic effects of the brown recluse spider\'s venom. The venom\'s pathophysiology involves a complex cascade, leading to local and systemic effects. The local effects, marked by dermonecrosis, com- promised skin integrity in this instance. Systemic effects, not observed in this patient but potentially severe, can include hemolysis, coagulopathy, and acute renal failure, highlighting the seriousness of brown recluse spider bites.
UNASSIGNED: In conclusion, this case illustrates the complexities of managing breast reconstruction post-mastectomy complications, particularly those caused by external factors such as brown recluse spider bites. It highlights the need for meticulous attention to unusual etiologies of necrosis and dehiscence, demonstrating the importance of adaptable surgical strategies and a thorough understanding of venom pathophysiology in ensuring successful patient outcomes.

There is a rich history of cancer treatments which provides a number of important lessons for present and future cancer therapies. We outline this history by looking in the past, reviewing the current landscape of cancer treatments, and by glancing at the potential future cancer therapies.

Metastatic castrate resistant prostate cancer (mCRPC) continues to have poor survival rates due to limited treatment options. Bi-specific T cell engagers (BiTEs) are a promising class of novel immunotherapies with demonstrated success in haematological malignancies and melanoma. BiTEs developed for tumour associated antigens in prostate cancer have entered clinical testing. These trials have been hampered by high rates of treatment related adverse events, minimal or transient anti-tumour efficacy and generation of high titres of anti-drug antibodies. This paper aims to analyse the challenges faced by the different BiTE therapy constructs and the mCRPC tumour microenvironment that result in therapeutic resistance and identify possible strategies to overcome these issues.

BACKGROUND: Dog bite injuries are a preventable yet common cause of animal related hospitalisation. Dog bites in metropolitan areas have been well characterised however there is limited information regarding dog bites in regional areas. This study sought to describe the demographics, clinical presentation and short-term outcomes of patients presenting with dog bite related injuries to Broome Regional Hospital (BRH).
METHODS: A retrospective cohort study examined all dog bite related injuries presenting to BRH Emergency Department (ED) between July 1st 2021 - June 30th 2023, with the terms \"dog\" AND \"bitten OR bite\" in ED triage note. Chart review was performed to extract demographics, clinical presentation and short-term outcomes of dog bite related injuries.
RESULTS: After exclusions, 207 patients were identified during the 2-year study period; approximately four dog-bites per week. Median age was 32 (IQR: 32, range 1-97 years old) with 46 % of patients being female. Residents of the Kimberley represented 78 % of presentations for dog bites. Dogs that belonged to or were known to patients were involved in 74 % of cases. The lower limb below the knee (42 %) was most commonly bitten, followed by the distal upper limb (30.5 %) and then face (13 %). Most patients presented on the same-day (67 %), were treated with antibiotics (79 %) and 83 % were discharged on the day of presentation. There were 43 (23 %) patients who required repair in the ED or operating theatre. Thirty-three patients were admitted to BRH. Seven patients required transfer for subspecialty tertiary level care.
CONCLUSIONS: Dog-bite trauma is common and consumes significant health resources associated with ED presentations, hospital admissions, theatre usage and transfer in severe cases. A multifaceted approach encompassing education, engineering, and enforcement is required to prevent dog bites.

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In the past decade, a lot of insight was gathered into the composition of the host and tumor factors that promote oncogenesis and treatment resistance. This in turn has led to the ingenious design of multiple new classes of drugs, which have now become the new standards of care in cancer therapy. These include novel antibody-drug conjugates, chimeric antigen receptor T cell therapies (CAR-T), and bispecific T cell engagers (BitTE). Certain host factors, such as the microbiome composition, are also emerging not only as biomarkers for the response and toxicity to anti-cancer therapies but also as potentially useful tools to modulate anti-tumor responses. The field is slowly moving away from one-size-fits-all treatment options to personalized treatments tailored to the host and tumor. This commentary aims to cover the basic concepts associated with these emerging therapies and the promises and challenges to fight cancer.