Cureus. 2023 Jul 23;15(7):e42315. doi: 10.7759/cureus.42315. eCollection 2023 Jul.

ABSTRACT

Nivolumab is an immune checkpoint inhibitor used in the treatment of several types of cancer. Among the adverse effects of this drug, immune-mediated colitis (IMC) has been described. However, in contrast to other checkpoint inhibitors, such as ipilimumab, drug-induced colitis due to nivolumab is not commonly reported. We report the case of a 59-year-old male who had undergone surgical resection for gastroesophageal junction adenocarcinoma, had been on nivolumab during the past five months, and presented with worsening diarrhea. Colonoscopy demonstrated local edema and mild colitis in a region of the colonic mucosa located 30 cm distal to the ileocecal valve. Biopsies revealed acute moderate colitis. The patient responded well to loperamide and dietary modifications. Although nivolumab rarely causes IMC, this occurrence requires proper management in order to avoid further complications.

PMID:37614260 | PMC:PMC10442715 | DOI:10.7759/cureus.42315

J Clin Neuromuscul Dis. 2023 Sep 1;25(1):11-17. doi: 10.1097/CND.0000000000000439.

ABSTRACT

OBJECTIVES: Plasmapheresis (PLEX) and intravenous immunoglobulin (IVIg) are commonly used to treat autoimmune neuromuscular disorders, including myasthenia gravis, acute inflammatory demyelinating polyradiculoneuropathy, chronic inflammatory demyelinating polyradiculoneuropathy, and other autoimmune neurological disorders. The side effect profiles of these therapies vary, and concern has been raised regarding the safety of PLEX in the elderly population. In this study, we have examined the pattern of PLEX and IVIg use for autoimmune neurological disorders at a single facility and in a national database, focusing on the complications in elderly patients.

METHODS: We performed a retrospective chart review of adult patients at our institution receiving PLEX or IVIg for any autoimmune neuromuscular or neuro-immunological disease. Next, we analyzed the National Inpatient Sample database to confirm the trend in IVIg and PLEX use from 2012 to 2018 for a set of neuromuscular and neuro-immunological primary diagnoses.

RESULTS: IVIg was overall favored over PLEX. The adverse effects were similar among elderly patients (age ≥65 years) compared with younger patients (<65 years) in our institution, even after adequate matching of patients based on age, sex, and medical history. We examined the National Inpatient Sample dataset and noted increasingly higher frequency of IVIg use, consistent with the findings from our institution or facility.

CONCLUSIONS: Both PLEX and IVIg are safe therapeutic choices in adult patients with autoimmune neuromuscular disorders and other neuro-immunological diseases and can be safely administered in the appropriate clinical setting.

PMID:37611265 | DOI:10.1097/CND.0000000000000439

PLoS One. 2023 Aug 23;18(8):e0289825. doi: 10.1371/journal.pone.0289825. eCollection 2023.

ABSTRACT

INTRODUCTION: Drug-related problems (DRPs) are common in clinical practice and occur at all stages of the medication process. The major factor contributing to DRPs is prescription, although patients' poor adherence to treatment is also a significant factor. This study evaluated type 2 diabetes outpatients in a hospital in Vietnam for drug-related problems (DRPs) and related variables.

METHODS: A cross-sectional descriptive study was conducted on 495 outpatients who met the criteria and 157 people agreed to participate in the interview. Medication order review and medication adherence review were used to identify DRPs. The types of DRP were based on the Pharmaceutical Care Network Europe (PCNE) categories version 9.0. The identification and assessment DRPs were carried out by clinical pharmacists and get agreed upon by physicians who had not directly prescribed patients who participated in the study.

RESULTS: A total of 762 DRPs were identified via prescribing review process, the average number of DRP on each prescription was 1.54±1.07, while 412 DRPs were determined through patient interviewing. The most frequent DRPs were "ADR (Adverse Drug Reaction) occurring" (68.8%). The main causes were "patient is unable to understand instructions properly" or "patient is not properly instructed", "patient stores insulin inappropriately", "patient decides to use unnecessary drugs" and "patient intentionally uses/takes less drug than prescribed or does not take the drug at all for whatever reason" which accounted for 65.0%, 41.4%, 38.2%, and 28.7%, respectively. From the prescribing review, the most observed DRPs were "Inappropriate drug according to guidelines/formulary" and "No or incomplete drug treatment in spite of existing indication", accounting for 45.0% and 42.9%, respectively. There was a significant association between age (OR 3.38, 95% CI: 1.01-11.30), duration of diabetes (OR 3.61, 95%CI: 1.11-11.74), presence of comorbidity (OR 5.31, 95%CI: 1.97-14.30), polypharmacy (OR: 2.95, 95%CI: 1.01-8.72) and DRPs. In patients, poor knowledge of antidiabetic agents was the main reason to lack adherence and occurring ADR (OR 2.73, 95%CI: 1.32-5.66, p = 0.007 and OR 2.49, 95%CI: 1.54-4.03, p = 0.001 respectively).

CONCLUSION: DRPs occurred in the prescribing stage and relating to patient's behavior of drug administration was high. Clear identification of DRPs and the associated factors are essential for building the intervention process to improve effectiveness and safety in the treatment of type 2 diabetes mellitus patients.

PMID:37611036 | PMC:PMC10446199 | DOI:10.1371/journal.pone.0289825

Rev Med Suisse. 2023 Aug 23;19(838):1508-1512. doi: 10.53738/REVMED.2023.19.838.1508.

ABSTRACT

This article proposes 10 points considered essential on the ethics associated with the practice of psychotherapy assisted by psychedelics (PAP) : 1) respect of the legal framework (LStup) of the use of psychotropic drugs ; 2) adequately manage psychedelics (storage, production and safety) ; 3) announce adverse effects to the competent authority ; 4) guarantee a psychotherapeutic follow-up ; 5) guarantee the safety of the patients during the treatment ; 6) establish indications on the basis of scientific evidence ; 7) do not confuse personal recreational use and strict medical use ; 8) avoid proselytizing or bad medical practices ; 9) do not to consider the personal consumption of psychedelics as a competency in care and 10) ensure that access to care is equitable and reasonable.

PMID:37610195 | DOI:10.53738/REVMED.2023.19.838.1508

Cochrane Database Syst Rev. 2023 Aug 23;8:CD011570. doi: 10.1002/14651858.CD011570.pub2.

ABSTRACT

BACKGROUND: Anorexia nervosa is a psychological condition characterised by self-starvation and fear or wait gain or other body image disturbance. The first line of treatment is specific psychological therapy; however, there is no consensus on best practice for treating people who develop severe and enduring anorexia nervosa (SEAN). Notably, there is no universal definition of SEAN.

OBJECTIVES: To evaluate the benefits and harms of specific psychological therapies for severe and enduring anorexia nervosa compared with other specific therapies, non-specific therapies, no treatment/waiting list, antidepressant medication, dietary counselling alone, or treatment as usual.

SEARCH METHODS: We used standard, extensive Cochrane search methods. The last search date was 22 July 2022.

SELECTION CRITERIA: We included parallel randomised controlled trials (RCTs) of people (any age) with anorexia nervosa of at least three years' duration. Eligible experimental interventions were any specific psychological therapy for improved physical and psychological health in anorexia nervosa, conducted in any treatment setting with no restrictions in terms of number of sessions, modality, or duration of therapy. Eligible comparator interventions included any other specific psychological therapy for anorexia nervosa, non-specific psychological therapy for mental health disorders, no treatment or waiting list, antipsychotic treatment (with or without psychological therapy), antidepressant treatment (with or without psychological therapy), dietary counselling, and treatment as usual as defined by the individual trials.

DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were clinical improvement (weight restoration to within the normal weight range for participant sample) and treatment non-completion. Results were presented using the GRADE appraisal tool.

MAIN RESULTS: We found two eligible studies, but only one study provided usable data. This was a parallel-group RCT of 63 adults with SEAN who had an illness duration of at least seven years. The trial compared outpatient cognitive behaviour therapy for SEAN (CBT-SEAN) with specialist supportive clinical management for SEAN (SSCM-SE) over eight months. It is unclear if there is any difference between the effect of CBT-SEAN versus SSCM-SE on clinical improvement at 12 months (risk ratio (RR) 1.42, 95% confidence interval (CI) 0.66 to 3.05) or treatment non-completion (RR 1.72, 95% CI 0.45 to 6.59). There were no reported data on adverse effects. The trial was at high risk of performance and detection bias. We rated the GRADE level of evidence as very low-certainty for both primary outcomes, downgrading for imprecision and risk of bias concerns.

AUTHORS' CONCLUSIONS: This review reports evidence from one trial that evaluated CBT-SEAN versus SSCM-SE. There was very low-certainty evidence of little or no difference in clinical improvement and treatment non-completion between the two therapies. There is a need for larger high-quality trials to determine the benefits of specific psychological therapies for people with SEAN. These should take into account the duration of illness as well as participants' previous experience with evidence-based psychological therapy for anorexia nervosa.

PMID:37610143 | DOI:10.1002/14651858.CD011570.pub2

Med Sci Monit. 2023 Aug 23;29:e939858. doi: 10.12659/MSM.939858.

ABSTRACT

BACKGROUND Patients experience severe pain in early postoperative rehabilitation after total knee arthroplasty (TKA). This study aimed to compare the effect of femoral nerve block with different concentrations of chloroprocaine on postoperative rehabilitation in patients with TKA. MATERIAL AND METHODS Ninety patients who only received unilateral TKA were randomly and equally divided into C1 (1% chloroprocaine 0.2 ml/kg), C2 (2% chloroprocaine 0.2 ml/kg), or NS (0.9% sodium chloride solution 0.2 ml/kg) groups. The patients received rehabilitation 3 times a day on days 3-6 after surgery, and femoral nerve block was performed with corresponding solution 10 min before each training session. We recorded the maximum knee flexion angles (MKFA) and maximum knee extension angles (MKEA) during active exercise on day 7 after surgery, as well as the incidence of MKFA ³100°, American knee society (AKS) scores, and postoperative rehabilitation satisfaction. Adverse effects after administration in each group were also recorded. RESULTS Compared with group NS, patients in group C1 and C2 had larger MKFA during active exercise on day 7 after TKA, and had better rehabilitation satisfaction (P<0.05). MKEA, the incidence of MKFA ≥100°, and AKS scores showed no significant differences in the 3 groups. There were more patients with decline of muscle strength in group C2 (P<0.05), and no other adverse reactions were recorded. CONCLUSIONS Chloroprocaine for femoral nerve block can be safely used in rehabilitation after TKA and to improve the knee flexion angle in the early postoperative period. Because they may have fewer adverse effects, 1% chloroprocaine 0.2 ml/kg may be preferred.

PMID:37608539 | DOI:10.12659/MSM.939858

Drug Ther Bull. 2023 Aug 23:dtb-2023-000045. doi: 10.1136/dtb.2023.000045. Online ahead of print.

NO ABSTRACT

PMID:37612130 | DOI:10.1136/dtb.2023.000045

Eur J Hosp Pharm. 2023 Sep;30(5):e26. doi: 10.1136/ejhpharm-2022-003417. Epub 2022 Sep 2.

ABSTRACT

Anthracyclines are associated with cardiotoxic manifestations that are mainly dose-dependent, with onset varying from a few days to many years after stopping treatment. Frequent monitoring for toxic manifestations, early detection, cessation of anthracycline use and appropriate treatment is the key to preventing morbidity and mortality. Complete heart block with doxorubicin use in Hodgkin's lymphoma is rarely reported, and is a severe toxic manifestation necessitating withdrawal or changing of regimen to etoposide + bleomycin + vinblastine + dacarbazine (EBVD), as in this case.

PMID:37611964 | DOI:10.1136/ejhpharm-2022-003417

Methods Mol Biol. 2023;2967:159-171. doi: 10.1007/978-1-0716-3358-8_13.

ABSTRACT

As a powerful tool, polymerase chain reaction (PCR) has been indispensable and widely used in a large array of applications. In practice, many factors may affect the overall performance of a PCR. One such factor is the stability of intramolecular secondary structure formed within single-stranded template. The higher the stability of such a structure, the more likely it will have adverse effects on PCR performance. Traditionally, chemical reagents believed to reduce the stability of nucleic acid secondary structures, such as DMSO and betaine, have been used to mitigate their adverse effects on PCR performance. However, these reagents have apparent downsides including increasing replication error rate, inhibiting polymerase activity, and being ineffective against secondary structures of very high stabilities. Disruptors, a new class of oligonucleotide reagents, do not exhibit such downsides. They are specifically designed to target intramolecular secondary structures only without any effect on the replication of other regions of the template. Their effective concentration range for improving PCR performance is well tolerated by PCR. And they are very effective in improving PCR performance on templates that are notoriously difficult to amplify by PCR even in the presence of DMSO or betaine, e.g., the inverted terminal repeat of adeno-associated virus (AAV-ITR). In this chapter, the application of disruptors in PCR is described with AAV-ITR as the example template.

PMID:37608110 | DOI:10.1007/978-1-0716-3358-8_13

PLoS One. 2023 Aug 22;18(8):e0277718. doi: 10.1371/journal.pone.0277718. eCollection 2023.

ABSTRACT

Riluzole is the only treatment known to improve survival in patients with Amyotrophic Lateral Sclerosis (ALS). However, oral riluzole efficacy is modest at best, further it is known to have large inter-individual variability of serum concentration and clearance, is formulated as an oral drug in a patient population plagued with dysphagia, and has known systemic side-effects like asthenia (limiting patient compliance) and elevated liver enzymes. In this context, we postulated that continuous intrathecal (IT) infusion of low doses of riluzole could provide consistent elevations of the drug spinal cord (SC) concentrations at or above those achieved with oral dosing, without increasing the risk for adverse events associated with systemic drug exposure or off-target side effects in the brain. We developed a formulation of riluzole for IT delivery and conducted our studies in purpose-bred hound dogs. Our non-GLP studies revealed that IT infusion alone was able to increase SC concentrations above those provided by oral administration, without increasing plasma concentrations. We then conducted two GLP studies that combined IT infusion with oral administration at human equivalent dose, to evaluate SC and brain concentrations of riluzole along with assessments of safety and tolerability. In the 6-week study, the highest IT dose (0.2 mg/hr) was well tolerated by the animals and increased SC concentrations above those achieved with oral riluzole alone, without increasing brain concentrations. In the 6-month study, the highest dose tested (0.4 mg/hr) was not tolerated and yielded SC significantly above those achieved in all previous studies. Our data show the feasibility and safety profile of continuous IT riluzole delivery to the spinal cord, without concurrent elevated liver enzymes, and minimal brain concentrations creating another potential therapeutic route of delivery to be used in isolation or in combination with other therapeutics."

PMID:37607205 | PMC:PMC10443869 | DOI:10.1371/journal.pone.0277718

Cochrane Database Syst Rev. 2023 Aug 22;8:CD013127. doi: 10.1002/14651858.CD013127.pub2.

ABSTRACT

BACKGROUND: The prevalence of mental health problems is high, and they have a wide-ranging and deleterious effect on many sectors in society. As well as the impact on individuals and families, mental health problems in the workplace negatively affect productivity. One of the factors that may exacerbate the impact of mental health problems is a lack of 'mental health literacy' in the general population. This has been defined as 'knowledge and beliefs about mental disorders, which aid their recognition, management, or prevention'. Mental Health First Aid (MHFA) is a brief training programme developed in Australia in 2000; its aim is to improve mental health literacy and teach mental health first aid strategies. The course has been adapted for various contexts, but essentially covers the symptoms of various mental health disorders, along with associated mental health crisis situations. The programmes also teach trainees how to provide immediate help to people experiencing mental health difficulties, as well as how to signpost to professional services. It is theorised that improved knowledge will encourage the trainees to provide support, and encourage people to actively seek help, thereby leading to improvements in mental health. This review focuses on the effects of MHFA on the mental health and mental well-being of individuals and communities in which MHFA training has been provided. We also examine the impact on mental health literacy. This information is essential for decision-makers considering the role of MHFA training in their organisations.

OBJECTIVES: To examine mental health and well-being, mental health service usage, and adverse effects of MHFA training on individuals in the communities in which MHFA training is delivered.

SEARCH METHODS: We developed a sensitive search strategy to identify randomised controlled trials (RCTs) of MHFA training. This approach used bibliographic databases searching, using a search strategy developed for Ovid MEDLINE (1946 -), and translated across to Ovid Embase (1974 -), Ovid PsycINFO (1967 -), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Common Mental Disorders Group's Specialised Register (CCMDCTR). We also searched online clinical trial registries (ClinicalTrials.gov and WHO ICTRP), grey literature and reference lists of included studies, and contacted researchers in the field to identify additional and ongoing studies. Searches are current to 13th June 2023.

SELECTION CRITERIA: We included RCTs and cluster-RCTs comparing any type of MHFA-trademarked course to no intervention, active or attention control (such as first aid courses), waiting list control, or alternative mental health literacy interventions. Participants were individuals in the communities in which MHFA training is delivered and MHFA trainees. Primary outcomes included mental health and well-being of individuals, mental health service usage and adverse effects of MHFA training. Secondary outcomes related to individuals, MHFA trainees, and communities or organisations in which MHFA training has been delivered DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We analysed categorical outcomes as risk ratios (RRs) and odds ratios (ORs), and continuous outcomes as mean differences (MDs) or standardised mean differences (SMDs), with 95% confidence intervals (CIs). We pooled data using a random-effects model. Two review authors independently assessed the key results using the Risk of Bias 2 tool and applied the GRADE criteria to assess the certainty of evidence MAIN RESULTS: Twenty-one studies involving a total of 22,604 participants were included in the review. Fifteen studies compared MHFA training with no intervention/waiting list, two studies compared MHFA training with an alternative mental health literacy intervention, and four studies compared MHFA training with an active or an attention control intervention. Our primary time point was between six and 12 months. When MHFA training was compared with no intervention, it may have little to no effect on the mental health of individuals at six to 12 months, but the evidence is very uncertain (OR 0.88, 95% CI 0.61 to 1.28; 3 studies; 3939 participants). We judged all the results that contributed to this outcome as being at high risk of bias. No study measured mental health service usage at six to 12 months. We did not find published data on adverse effects. Only one study with usable data compared MHFA training with an alternative mental health literacy intervention. The study did not measure outcomes in individuals in the community. It also did not measure outcomes at our primary time point of six to 12 months. Four studies with usable data compared MHFA training to an active or attention control. None of the studies measured outcomes at our primary time point of six to 12 months.

AUTHORS' CONCLUSIONS: We cannot draw conclusions about the effects of MHFA training on our primary outcomes due to the lack of good quality evidence. This is the case whether it is compared to no intervention, to an alternative mental health literacy intervention, or to an active control. Studies are at high risk of bias and often not sufficiently large to be able to detect differences.

PMID:37606172 | DOI:10.1002/14651858.CD013127.pub2

Pak J Pharm Sci. 2023 Jul;36(4(Special)):1291-1296.

ABSTRACT

The serious adverse effects, such as nephrotoxicity, limit the clinical utility of anticancer doxorubicin (DOX) drug. Cichorium endivia L. is reputed to show antioxidive effectiveness. The present investigation was conducted to explore the nephroprotective potential of crude methanol extract of Cichorium endivia (CECE) pretreatment against DOX-induced nephrotoxicity. Randomly, twenty male Wistar rats were assigned into four groups: Control (no-treatment), DOX group (15mg/kg, i.p, once), DOX + CECE (100mg/kg) and DOX + CECE (200mg/kg). All experiments were performed for 15 consecutive days except for DOX, was delivered once on day twelve. Samples of kidney and serum were collected one day after the last treatment for further assays. Pretreatment with CECE significantly protected the kidney function from DOX toxicity. Urea and creatinine levels were reduced in the serum. Furthermore, CECE administration decreased the damage in the renal histological structure. Restoration of the renal corpuscle and tubules structures was more manifested in a high dose (200mg/kg) of CECE. In summary, these findings demonstrate the nephroprotective effect of CECE pretreatment in DOX-treated rats.

PMID:37606018

Stem Cell Res Ther. 2023 Aug 21;14(1):210. doi: 10.1186/s13287-023-03440-2.

ABSTRACT

INTRODUCTION: Treatments for AGA have yet to produce satisfactory outcomes and may cause intolerable side effects. Recent studies have reported that adipose tissue-derived stem cell conditioned media (ADSC-CM) could induce hair growth and regeneration.

OBJECTIVE: To investigate the efficacy of ADSC-CM combined with minoxidil for hair regeneration therapy in male AGA.

METHODS: This study lasted for 6 weeks. Subjects were divided into two groups: concentrated and non-concentrated ADSC-CM. Scalp was divided vertically in half before intradermal injection was administered from the frontal region of the scalp toward the vertex with a 30G needle, spaced about 1 cm apart. Treatment side received 2 ml of ADSC-CM; the other side was given 2 ml of NaCl 0.9% as placebo. Patients applied 5% minoxidil twice daily post-injection. Improvements were assessed using photographs and trichoscan every 2 weeks.

RESULTS: Hair count, hair density, and mean thickness increased significantly on both sides after 6 weeks, while vellus rate decreased proportionally with the increase of terminal rate. No statistically significant differences between treatment groups were found. Minimum side effects were reported, and subjects were satisfied with the results.

CONCLUSION: Combination of ADSC-CM and minoxidil could be a potential agent for hair regrowth. Follow-up research with extensive populations, longer duration, and different study design may be required to confirm the exact mechanisms of ADSC-CM on hair growth.

TRIAL REGISTRATION: Clinicaltrials.gov, NCT05296863. Registered 25 March 2022-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05296863 .

PMID:37605227 | DOI:10.1186/s13287-023-03440-2

Drugs Aging. 2023 Sep;40(9):857-868. doi: 10.1007/s40266-023-01055-z. Epub 2023 Aug 21.

ABSTRACT

BACKGROUND: Polypharmacy, particularly among older adults, is gaining recognition as an important risk to health. The harmful effects on health arise from disease-drug and drug-drug interactions, the cumulative burden of side effects from multiple medications and the burden to the patient. Single-disease clinical guidelines fail to consider the complex reality of optimising treatments for patients with multiple morbidities and medications. Efforts have been made to develop and implement interventions to reduce the risk of harmful effects, with some promising results. However, the theoretical basis (or pre-clinical work) that informed the development of these efforts, although likely undertaken, is unclear, difficult to find or inadequately described in publications. It is critical in interpreting effects and achieving effectiveness to understand the theoretical basis for such interventions.

OBJECTIVE: Our objective is to outline the theoretical underpinnings of the development of a new polypharmacy intervention: the Team Approach to Polypharmacy Evaluation and Reduction (TAPER).

METHODS: We examined deprescribing barriers at patient, provider, and system levels and mapped them to the chronic care model to understand the behavioural change requirements for a model to address polypharmacy.

RESULTS: Using the chronic care model framework for understanding the barriers, we developed a model for addressing polypharmacy.

CONCLUSIONS: We discuss how TAPER maps to address the specific patient-level, provider-level, and system-level barriers to deprescribing and aligns with three commonly used models and frameworks in medicine (the chronic care model, minimally disruptive medicine, the cumulative complexity model). We also describe how TAPER maps onto primary care principles, ultimately providing a description of the development of TAPER and a conceptualisation of the potential mechanisms by which TAPER reduces polypharmacy and its associated harms.

PMID:37603255 | DOI:10.1007/s40266-023-01055-z

Sci Rep. 2023 Aug 21;13(1):13624. doi: 10.1038/s41598-023-40094-9.

ABSTRACT

Chemotherapy is one of the main treatment options for cancer, but it is usually accompanied with negative side effects. The classical drugs combination with synergistic adjuvants can be the solution to this problem, allowing reducing therapeutic dose. Elucidating the mechanism of adjuvant action is of key importance for the selection of the optimal agent. Here we examine the system drug-adjuvant to explain the observed effect in practice. We used the first line drug cisplatin. Morpholinium and 4-methylpiperazinium 4,5-dichloro isothiazol-3-carboxylates were selected as adjuvants. The study of the cisplatin-adjuvant system was carried out by quantum chemical modeling using DFT. It turned out that adjuvants form conjugates with cisplatin that lead to the relocation of frontier molecular orbitals as well as increase of conjugate's dipole moment. It resulted in change of the interaction character with DNA and increase of the bioactivity of the system. The data obtained are the basis for expanding the studies to include other drugs and adjuvants. Oncologists will have opportunity to use "classical" chemotherapy drugs in combination with synergists for those patients who have not been previously recommended to such a treatment because of pronounced toxic side effects.

PMID:37604841 | PMC:PMC10442360 | DOI:10.1038/s41598-023-40094-9

J Immunother Cancer. 2023 Aug;11(8):e007236. doi: 10.1136/jitc-2023-007236.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors have revolutionized cancer treatment. However, they are associated with a unique spectrum of side effects, called immune-related adverse events (irAEs), which can cause significant morbidity and quickly progress to severe or life-threatening events if not treated promptly. Identifying predictive biomarkers for irAEs before immunotherapy initiation is therefore a critical area of research. Polymorphisms within the T-cell receptor beta (TCRB) variable (TRBV) gene have been implicated in autoimmune disease and may be mechanistically linked to irAEs. However, the repetitive nature of the TCRB locus and incomplete genome assembly has hampered the evaluation of TRBV polymorphisms in the past.

PATIENTS AND METHODS: We used a novel method for long-amplicon next generation sequencing of rearranged TCRB chains from peripheral blood total RNA to evaluate the link between TRBV polymorphisms and irAEs in patients treated with immunotherapy for cancer. We employed multiplex PCR to create amplicons spanning the three beta chain complementarity-determining regions (CDR) regions to enable detection of polymorphism within the germline-encoded framework and CDR1 and CDR2 regions in addition to CDR3 profiling. Resultant amplicons were sequenced via the Ion Torrent and TRBV allele profiles constructed for each individual was correlated with irAE annotations to identify haplotypes associated with severe irAEs (≥ grade 3).

RESULTS: Our study included 81 patients who had irAEs when treated with immunotherapy for cancer. By using principal component analysis of the 81 TRBV allele profiles followed by k-means clustering, we identified six major TRBV haplotypes. Strikingly, we found that one-third of this cohort possessed a TRBV allele haplotype that appeared to be protective against severe irAEs.

CONCLUSION: The data suggest that long-amplicon TCRB repertoire sequencing can potentially identify TRBV haplotype groups that correlate with the risk of severe irAEs. Germline-encoded TRBV polymorphisms may serve as a predictive biomarker of severe irAEs.

PMID:37604642 | DOI:10.1136/jitc-2023-007236

JAMA Netw Open. 2023 Aug 1;6(8):e2329074. doi: 10.1001/jamanetworkopen.2023.29074.

NO ABSTRACT

PMID:37603336 | DOI:10.1001/jamanetworkopen.2023.29074

Med Oncol. 2023 Aug 21;40(9):273. doi: 10.1007/s12032-023-02151-1.

ABSTRACT

Conventional chemotherapy has significant limitations for colorectal cancer (CRC) treatment, especially those who have developed metastatic recurrence CRC. A growing number of studies have investigated the potential use of monoclonal antibodies (mAbs) for CRC therapy. mAbs showing clinical benefits for CRC, making the treatment more selective with lower side effects without significant immunogenicity. In addition, recent advancements in antibody engineering strategies and the development of bifunctional or even trifunctional drugs have helped to overcome heterogeneity as the main challenge in cancer treatment. The current review discusses advances in applying mAbs for CRC therapy alone, combined, or with small molecules.

PMID:37603117 | DOI:10.1007/s12032-023-02151-1

Psychopharmacol Bull. 2023 Aug 11;53(3):61-65.

ABSTRACT

Cannabis is a widely used illicit substance that is historically consumed via smoking, but alternative methods of cannabis consumption have been growing in popularity over the past several decades. One such modality is vaporization, which can appeal specifically to adolescent consumers given these pen devices' ease of concealment, lack of characteristic odor, and marketability. Cannabis products designed for vaping often have higher concentrations of the psychoactive component of cannabis, tetrahydrocannabinol (THC), when compared with traditional cannabis leaf smoking. This can increase the intensity of cannabis-related effects such as analgesia, relaxation, appetite stimulation, and reduced nausea and emesis, but also potentially increases the risk for adverse effects such as dysphoria, and more severely, cannabis-induced psychosis (CIP). Here, we present the case of an adolescent female who was brought after school to our emergency department presenting with symptoms of acute psychosis. Her subsequent workup was effectively normal apart from a urine drug screen positive for THC, which the patient confirmed was due to use of a cannabis pen prior to leaving school that day. This prompted the diagnosis of CIP, which was self-limited and resolved without significant intervention. We use this case to provide the symptomatology and treatment of CIP secondary to cannabis pen use, as well as more broadly discuss the potential implications of cannabis vaping on adolescent neurodevelopment, substance use, and psychiatric comorbidities.

PMID:37601084 | PMC:PMC10434310

Front Immunol. 2023 Aug 3;14:1230893. doi: 10.3389/fimmu.2023.1230893. eCollection 2023.

ABSTRACT

Immunotherapy has developed rapidly in solid tumors, especially in the areas of blocking inhibitory immune checkpoints and adoptive T-cell transfer for immune regulation. Many patients benefit from immunotherapy. However, the response rate of immunotherapy in the overall population are relatively low, which depends on the characteristics of the tumor and individualized patient differences. Moreover, the occurrence of drug resistance and adverse reactions largely limit the development of immunotherapy. Recently, the emergence of nanodrug delivery systems (NDDS) seems to improve the efficacy of immunotherapy by encapsulating drug carriers in nanoparticles to precisely reach the tumor site with high stability and biocompatibility, prolonging the drug cycle of action and greatly reducing the occurrence of toxic side effects. In this paper, we mainly review the advantages of NDDS and the mechanisms that enhance conventional immunotherapy in solid tumors, and summarize the recent advances in NDDS-based therapeutic strategies, which will provide valuable ideas for the development of novel tumor immunotherapy regimen.

PMID:37600822 | PMC:PMC10435760 | DOI:10.3389/fimmu.2023.1230893