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Clinical Lymphoma, Myeloma & Leukemia May 2024Talquetamab is a bispecific antibody targeting the multiple myeloma-associated antigen G protein-coupled receptor family C group 5 member D (GPRC5D). In the phase 1/2...
BACKGROUND
Talquetamab is a bispecific antibody targeting the multiple myeloma-associated antigen G protein-coupled receptor family C group 5 member D (GPRC5D). In the phase 1/2 MonumenTAL-1 trial (NCT03399799/NCT04634552), overall responses rates were > 71% in patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM). Due to the distribution of the target antigen, a unique pattern of GPRC5D-associated adverse events (AEs) was observed, together with T-cell redirection-associated AEs. Management strategies for talquetamab-associated AEs are described.
DISCUSSION
GPRC5D-associated AEs included dermatologic (rash, nonrash, and nail toxicities) and oral AEs (dysgeusia, dysphagia, and dry mouth). The incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were consistent with other T-cell redirection therapies. The incidence of high-grade infections was lower than observed with B-cell maturation antigen-targeting bispecific antibodies, with less frequent use of intravenous immunoglobulin required. GPRC5D-associated AEs were mostly low grade and led to few discontinuations. Skin toxicities were managed with emollients, topical corticosteroids, and oral corticosteroids (for high-grade, persistent, or AEs that progress). Nail toxicities were commonly managed with emollients. Based on investigator experience, dose modification may be effective for controlling oral events. Observation for potential weight changes is required. Infections were managed per standard of care. CRS and ICANS were effectively managed, consistent with other trials of T-cell redirection therapies.
CONCLUSION
Although talquetamab had a distinct safety profile, AEs were considered clinically manageable and mostly low grade. With appropriate education and support, health care practitioners can ensure patients with RRMM maintain quality of life and treatment adherence.
PubMed: 38871558
DOI: 10.1016/j.clml.2024.05.003 -
Alternative Therapies in Health and... Jun 2024Hyponatremia is one of the main types of complications of primary nephrotic syndrome in children, which can cause significant damage to the patient's nervous system and...
OBJECTIVE
Hyponatremia is one of the main types of complications of primary nephrotic syndrome in children, which can cause significant damage to the patient's nervous system and can lead to death or shock if not intervened early. In addition, patients are relatively young and often need to pay attention to the nursing cooperation of various key points in order to achieve ideal clinical treatment effects. To analyze the key points of nursing cooperation and the implementation effects of primary nephrotic syndrome in children complicated with hyponatremia.
METHODS
A retrospective analysis of 100 children with primary nephrotic syndrome complicated with hyponatremia admitted to our Hospital from January 2018 to November 2022 was conducted as the study objects. They were divided into a control and observation groups, with 50 cases each. Among them, the control group received routine nursing, while the observation group paid attention to various key points of nursing cooperation. This includes paying close attention to changes in plasma osmotic pressure, blood sodium, and electrocardiogram indicators, being alert to the above situations, and taking appropriate treatment measures in a timely manner; nursing staff need to guide family members to cooperate in alleviating clinical related symptoms, guide family members to avoid giving children irritating foods, and control the intake of sodium chloride. Guide parents to adjust their clothing and keep their skin dry and clean. Guide parents to provide psychological support for children and other key points of nursing cooperation. After different nursing measures were taken for the two groups, the scores of Quality of Life Core Questionnaire Scale related to patients after nursing, renal functions after nursing, and coagulation function indicators after nursing of the two groups were evaluated. Simultaneously compare the nursing efficacy, incidence of adverse reactions, and overall satisfaction rate of their family members between the two groups.
RESULTS
The scores of the core questionnaire scale of quality of life after nursing (physical function, emotional function, cognitive function, social function), coagulation function indexes after nursing (prothrombin time, activated partial thromboplastin), nursing efficacy, and the total satisfaction rate of patients' families were compared between the two groups. The observation group was higher than the control group (P < .05). The renal function indexes after nursing (serum creatinine, urea nitrogen, α1-microglobulin, 24h urine protein quantitative) and the incidence of adverse reactions (gastrointestinal discomfort, hypoglycemia, abnormal liver function) were compared between the two groups. The observation group was lower than the control group (P < .05).
CONCLUSION
As an auxiliary treatment intervention measure, the clinical effects obtained from the practice of nursing cooperation of each key point and the support of family members provide important strategic guidance for the selection of nursing strategies for children with primary nephrotic syndrome and hyponatremia. Such potential improvements have greatly promoted the improvement of the quality and efficiency of the entire department of pediatric nephrology and nursing, and are worthy of clinical promotion. That is, the focus of nursing cooperation should pay attention to the key points of nursing cooperation for children with primary nephrotic syndrome and hyponatremia to improve the quality of life of patients. Future studies can explore the universality of the application effect of relevant nursing points in other children.
PubMed: 38870508
DOI: No ID Found -
Journal of Applied Physiology... Jun 2024The purpose of this study was to investigate which climate/heat indices perform best in predicting heat-induced loss of physical work capacity (PWC-loss). Integrating...
The purpose of this study was to investigate which climate/heat indices perform best in predicting heat-induced loss of physical work capacity (PWC-loss). Integrating data from earlier studies, data from 982 exposures (75 conditions) exercising at a fixed cardiovascular load of 130b.min, in varying temperatures (15-50°C), humidities (20-80%), solar radiation (0-800W.m), wind (0.2-3.5m.s) and two clothing levels, were used to model the predictive power of ambient temperature, Universal Thermal Climate Index (UTCI), Wet Bulb Globe Temperature (WBGT), Modified Equivalent Temperature (mPET), Heat Index, Apparent Temperature (AT), and Wet Bulb Temperature () for the calculation of PWC-loss, skin temperature () and core-to-skin temperature gradient, and Thermal perception( TSV) in the heat. R, RMSD and Akaike stats were used indicating model performance. Indices not including wind/radiation in their calculation (, Heat Index, AT, ) struggled to provide consistent predictions across variables. For PWC-loss and TSV, UTCI and WBGT had the highest predictive power. For , and core-to-skin temperature gradient, the physiological models UTCI and mPET worked best in semi-nude conditions, but clothed, AT, WBGT and UTCI worked best. For all index predictions, , vapor pressure and were shown to be the worst heat strain predictors. While UTCI and WBGT had similar model performance using the full dataset, WBGT did not work appropriately in windy, hot-dry, conditions where WBGT predicted lower strain due to wind, whereas the empirical data, UTCI and mPET indicated that wind in fact increased the overall level of thermal strain. The findings of the current study highlight the advantages of using a physiological model-based index like UTCI when evaluating heat stress in dynamic thermal environments.
PubMed: 38867664
DOI: 10.1152/japplphysiol.00613.2023 -
Transdermal microarrayed electroporation for enhanced cancer immunotherapy based on DNA vaccination.Proceedings of the National Academy of... Jun 2024Despite the tremendous clinical potential of nucleic acid-based vaccines, their efficacy to induce therapeutic immune response has been limited by the lack of efficient...
Despite the tremendous clinical potential of nucleic acid-based vaccines, their efficacy to induce therapeutic immune response has been limited by the lack of efficient local gene delivery techniques in the human body. In this study, we develop a hydrogel-based organic electronic device (μEPO) for both transdermal delivery of nucleic acids and in vivo microarrayed cell electroporation, which is specifically oriented toward one-step transfection of DNAs in subcutaneous antigen-presenting cells (APCs) for cancer immunotherapy. The μEPO device contains an array of microneedle-shaped electrodes with pre-encapsulated dry DNAs. Upon a pressurized contact with skin tissue, the electrodes are rehydrated, electrically triggered to release DNAs, and then electroporate nearby cells, which can achieve in vivo transfection of more than 50% of the cells in the epidermal and upper dermal layer. As a proof-of-concept, the μEPO technique is employed to facilitate transdermal delivery of neoantigen genes to activate antigen-specific immune response for enhanced cancer immunotherapy based on a DNA vaccination strategy. In an ovalbumin (OVA) cancer vaccine model, we show that high-efficiency transdermal transfection of APCs with OVA-DNAs induces robust cellular and humoral immune responses, including antigen presentation and generation of IFN-γ cytotoxic T lymphocytes with a more than 10-fold dose sparing over existing intramuscular injection (IM) approach, and effectively inhibits tumor growth in rodent animals.
Topics: Animals; Vaccines, DNA; Electroporation; Mice; Immunotherapy; Administration, Cutaneous; Neoplasms; Cancer Vaccines; Ovalbumin; Antigen-Presenting Cells; Female; Mice, Inbred C57BL; Humans; Vaccination
PubMed: 38865265
DOI: 10.1073/pnas.2322264121 -
Kansas Journal of Medicine 2024
PubMed: 38859991
DOI: 10.17161/kjm.vol17.22020 -
The British Journal of Dermatology Jun 2024
PubMed: 38857924
DOI: 10.1093/bjd/ljae248 -
Cureus May 2024Anhidrotic ectodermal dysplasia (AED), or Christ-Siemens-Touraine syndrome, is an X-linked recessive dermatosis. Rare in incidence, it affects 1 in 100,000 births,...
Anhidrotic ectodermal dysplasia (AED), or Christ-Siemens-Touraine syndrome, is an X-linked recessive dermatosis. Rare in incidence, it affects 1 in 100,000 births, mostly boys. Through this observation, we detail the clinical signs that led us to suspect the diagnosis, how this pathology was confirmed, and the therapeutic management we carried out. We present a case of a 10-month-old boy presenting with altered manifestations affecting almost all the ectodermal structures like skin, hair, nails, teeth, sebaceous glands, sweat glands, and tear glands. He also had complete anodontia and a dry mouth. A multidisciplinary treatment was given to the patient with the collaboration of various health professionals. Although Christ-Siemens-Touraine syndrome is a rare condition, it is vital to recognize it early to improve care and prognosis for these patients, while mitigating the psychological impact of the condition on both children and parents.
PubMed: 38854225
DOI: 10.7759/cureus.60022 -
Respiratory Medicine 2024Salbutamol is a cornerstone for relieving acute asthma symptoms, typically administered through a pressurized metered-dose inhaler (pMDI). Dry powder inhalers (DPIs)... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Salbutamol is a cornerstone for relieving acute asthma symptoms, typically administered through a pressurized metered-dose inhaler (pMDI). Dry powder inhalers (DPIs) offer an alternative, but concerns exist whether DPIs provide an effective relief during an obstructive event.
OBJECTIVE
We aimed to show non-inferiority of Salbutamol Easyhaler DPI compared to pMDI with spacer in treating methacholine-induced bronchoconstriction. Applicability of Budesonide-formoterol Easyhaler DPI as a reliever was also assessed.
METHODS
This was a randomized, parallel-group trial in subjects sent to methacholine challenge (MC) test for asthma diagnostics. Participants with at least 20 % decrease in forced expiratory volume in 1 s (FEV) were randomized to receive Salbutamol Easyhaler (2 × 200 μg), Ventoline Evohaler with spacer (4 × 100 μg) or Budesonide-formoterol Easyhaler (2 × 160/4.5 μg) as a reliever. The treatment was repeated if FEV did not recover to at least -10 % of baseline.
RESULTS
180 participants (69 % females, mean age 46 yrs [range 18-80], FEV%pred 89.5 [62-142] %) completed the trial. Salbutamol Easyhaler was non-inferior to pMDI with spacer in acute relief of bronchoconstriction showing a -0.083 (95 % LCL -0.146) L FEV difference after the first dose and -0.032 (-0.071) L after the last dose. The differences in FEV between Budesonide-formoterol Easyhaler and Salbutamol pMDI with spacer were -0.163 (-0.225) L after the first and -0.092 (-0.131) L after the last dose.
CONCLUSION
The study confirms non-inferiority of Salbutamol Easyhaler to Ventoline Evohaler with spacer in relieving acute bronchoconstriction, making Easyhaler a sustainable and safe reliever for MC test and supports its use during asthma attacks.
Topics: Humans; Methacholine Chloride; Female; Bronchoconstriction; Male; Adult; Asthma; Middle Aged; Albuterol; Dry Powder Inhalers; Forced Expiratory Volume; Bronchodilator Agents; Young Adult; Administration, Inhalation; Metered Dose Inhalers; Adolescent; Bronchial Provocation Tests; Treatment Outcome; Aged; Inhalation Spacers; Budesonide, Formoterol Fumarate Drug Combination
PubMed: 38851404
DOI: 10.1016/j.rmed.2024.107693 -
Archives of Dermatological Research Jun 2024The objective was to study a large, international, ethnically diverse population of patients with atopic dermatitis (AD) to support the creation of patient-centric...
The objective was to study a large, international, ethnically diverse population of patients with atopic dermatitis (AD) to support the creation of patient-centric recommendations for AD management. Qualitative data were generated from 45-min, 1:1 telephone interviews conducted across 15 countries in each patient's native language. Interviews explored the impact of AD on patients' lives, patients' most important symptoms, treatment expectations, and treatment decision-making. Participants were also questioned on their current knowledge of AD scoring systems and what was most important to include in these tools. In total, 88 adult patients (≥ 18 years old) receiving treatment for AD were recruited through a market research database, clinician referrals, and local advertising. All patients were screened to ensure a balanced and diverse sample in terms of age, gender, educational level, employment status, geographic location, and AD severity. Patients involved in market research or activities supporting advocacy groups within the previous 6 months or affiliated with or employed by pharmaceutical companies were excluded. AD had a substantial impact on patients' lives. Itch, skin redness, and dry/flaky skin were the most frequently reported symptoms, with > 75% of patients experiencing these symptoms every 1-3 days. Mental health issues were common and resulted in the greatest negative impact on patients' daily lives. Patients perceived clinicians to underestimate the burden of their AD. Patients had little awareness of AD scoring systems and indicated a preference for these to be more clearly incorporated in clinical practice. For an ideal scoring system, patients favored using a combination of patient-reported and clinician-reported outcomes to reflect disease burden and ensure consistency across all settings. This global study generated diverse patient perspectives on the disease burden of AD, their expectations of treatment, and their views on AD scoring methods. These data provide evidence to support the development of patient-centric recommendations for AD management.
Topics: Humans; Dermatitis, Atopic; Female; Male; Adult; Middle Aged; Qualitative Research; Patient Reported Outcome Measures; Severity of Illness Index; Cost of Illness; Young Adult; Quality of Life; Aged; Adolescent
PubMed: 38850461
DOI: 10.1007/s00403-024-03130-w -
Military Medicine Jun 2024Operating room fires can have devastating consequences and as such must be prevented. There exists a paucity of literature requiring further elucidation regarding...
INTRODUCTION
Operating room fires can have devastating consequences and as such must be prevented. There exists a paucity of literature requiring further elucidation regarding manufacturer recommendations of a predefined waiting period prior to patient draping after using alcohol-based surgical antiseptics, in order to reduce the risk of operating room fires.
METHODS
This was further investigated by exposing two common alcohol-based surgical antiseptics to electrosurgery and open flames at various power settings and time intervals in an ex vivo porcine model. The simulated surgical site was prepped following manufacturer recommendations and exposed to monopolar electrosurgery at low and high power, using both PURE CUT and COAGULATION modes, and open flame, at 15-s increments after application.
RESULTS
While using PURE CUT mode at both low and high power, no ignition was observed on hairless surgical sites prepped with ChloraPrep® at any time point. However, use of COAGULATION mode at both low and high powers resulted in ignition consistently out to 1-min post-application. Additionally, if the prepped area subjectively appeared wet, especially with pooling of the antiseptic, both COAGULATION mode and open flame caused ignition. Dry time was found to be about 59 s for both prep solutions. It was also observed that the amount of pressure directly correlated with the amount of prep dispersed and increased dry times.
CONCLUSION
In conclusion, our data suggest an average dry time of less than 1-min, with ignition only observed when the antiseptic was visibly wet. Ignition did not occur on hairless skin with electrocautery on CUT mode using ChloraPrep at any time point. Additionally, ignition on hair-bearing skin was not observed past 3 min, with current manufacturer recommendations stating 1 h wait time for hair-bearing skin. Arbitrarily waiting a specific predetermined dry time until patient draping, as recommended by the manufacturers, may be unnecessary and lead to hours' worth of time wasted each year. Ongoing research will further investigate the utility of drying the antiseptic after application and its affect on not only preventing ignition but also antimicrobial efficacy.
PubMed: 38850224
DOI: 10.1093/milmed/usae300