Perils and Problems in Bispecific T-Cell Engager Antibodies.

Bispecific antibodies (BsAbs) are promising immunotherapies for cancer treatment designed to engage both tumour and immune cells. However, their use is associated with potential toxicities, including cytokine release syndrome (CRS), neurotoxicity, and on-target, off-tumour toxicity. CRS, characterized by cytokine release, is the most common, potentially life-threatening toxicity. Neurotoxicity presents as neurological symptoms and on-target, off-tumour toxicity damages healthy cells. Incidence and severity vary based on BsAb type, dose, patient factors, and tumor characteristics. For this study, articles pertaining to BsAb toxicity were searched on PubMed. Moreover, the management involves early recognition, dose modification, supportive care, and, in severe cases, immunosuppressive therapy or treatment discontinuation. Clinicians must carefully assess risks and benefits, considering individual patient profiles. Close monitoring and multidisciplinary collaboration are crucial for effective BsAb therapy. All in all, while toxicity is a concern, with vigilant management, BsAbs remain a valuable cancer treatment option.

Behavioral Validation of Individualized Low-Intensity Transcranial Electrical Stimulation (tES) Protocols.

Large interindividual variability in the effects of low-intensity transcranial electrical stimulation (tES) considerably limits its potential for clinical applications. It has been recently proposed that individualizing stimulation dose by accounting for interindividual anatomic differences would reduce the variability in electric fields (E-fields) over the targeted cortical site and therefore produce more consistent behavioral outcomes. However, improvement in behavioral outcomes following individualized dose tES has never been compared with that of conventional fixed dose tES. In this study, we aimed to empirically evaluate the effect of individualized dose tES on behavior and further compare it with the effects of sham and fixed dose stimulations. We conducted a single-blinded, sham-controlled, repeated-measures study to examine the impact of transcranial direct current stimulation on motor learning and that of transcranial alternating current stimulation on the working memory of 42 healthy adult individuals. Each participant underwent three sessions of tES, receiving fixed dose, individualized dose, or sham stimulation over the targeted brain region for the entire behavioral task. Our results showed that the individualized dose reduced the variability in E-fields at the targeted cortical surfaces. However, there was no significant effect of tES on behavioral outcomes. We argue that although the stimulation dose and E-field intensity at the targeted cortical site are linearly correlated, the effect of E-fields on behavior seems to be more complex. Effective optimization of tES protocols warrants further research considering both neuroanatomical and functional aspects of behavior.

A Comparative Review of ICMR, WHO, and EMA Guidelines for Good Clinical Laboratory Practices.

With the advancement of clinical research and the increased burden on laboratory services, there is an unmet need for guidelines regarding proper laboratory functioning and reliable data generation. Several organizations from all over the world have published guidelines for these clinical and research laboratories. Good Clinical Laboratory Practices (GCLP) are stepwise procedures aimed at strengthening the quality of test results produced by all clinical laboratories engaged in human sample analysis. In this article, we attempt a comparison of the GCLP guidelines recently issued by the Indian Council of Medical Research with the guidelines released by the World Health Organization and the European Medicines Agency. Also, we have included and discussed several suggestions that, if included, will lead to the strengthening of the laboratory practices used for both research and patient care for overall improvement in the Indian healthcare system.

Dual energy CT angiography for lower extremity trauma: comparison with conventional CT.

PURPOSE: To determine if rapid switching dual-energy CT (rsDECT) provides improvements in vascular attenuation, subjective diagnostic quality, and detection of vascular injuries compared to conventional CT in trauma patients undergoing lower extremity CT angiography. MATERIALS AND METHODS: The IRB approved this HIPAA-compliant retrospective study. Informed consent was waived. Thirty-nine patients with acute lower extremity trauma including gunshot wounds (19 patients), falls (6 patients), motor vehicle accidents (5 patients), stab wounds (4 patients), pedestrian struck (2 patients), and unspecified trauma (3 patients) who underwent IV contrast-enhanced rsDECT angiography of the lower extremities on a rapid-kilovoltage-switching dual-energy CT scanner (Revolution CT, GE Healthcare) from 6/4/2019 to 1/14/2021 were studied. 7 patients were initially positive for vascular injury on conventional CT, while 32 patients were negative. Blended CT reconstructions simulating conventional 120 kVp single-energy CT, and rsDECT reconstructions (50 keV monoenergetic and iodine density maps) were reviewed. Region of interest contrast density measurements were recorded on conventional and 50 keV reconstructions at multiple levels from the distal aorta to the ankles and compared using Wilcoxon signed-rank tests. Vascular contrast density of 150 HU was used as a minimum cutoff for diagnostically adequate opacification. Images were interpreted by consensus for subjective image quality and presence of injury on both conventional and DECT reconstructions by two fellowship-trained abdominal radiologists blinded to clinical data, and compared using the paired McNemar test. RESULTS: Density measurement differences between conventional and rsDECT at every level of the bilateral lower extremities were statistically significant, with the average difference ranging from 304 Hounsfield units (HU) in the distal aorta to 121 HU at the ankles (p < 0.0001). Using a cutoff of 150 HU, 9.5% (93/976) and 3.1% of vascular segments (30/976) were considered non-diagnostic in the conventional and rsDECT groups, respectively, a reduction of 67.7% (p < 0.0001). Subjective image quality between conventional and rsDECT was not statistically significant, but there were 7 vascular segments out of a total of 976 segments across 3 different patients out of a total of 39 patients in which diagnostic quality was upgraded from non-diagnostic on conventional CT to diagnostic on rsDECT, all of which showed suboptimal bolus quality on conventional CT (unmeasurable in 4/7 and ranging from 56-146 HU in the remaining 3). Similarly, rate of injury detection was identical between conventional CT (15/39 patients) and DECT (15/39 patients). CONCLUSIONS: Vascular contrast density is statistically significantly higher with rsDECT compared to conventional CT, and subjective image quality was upgraded from non-diagnostic on conventional CT to diagnostic on rsDECT in 7 vascular segments across 3 patients. CLINICAL RELEVANCE: rsDECT provides greater vascular contrast density than conventional CT, with potential to salvage suboptimal examinations caused by poor contrast opacification.

IoT-Based Smart Health Monitoring System for COVID-19.

With the commencement of the COVID-19 pandemic, social distancing and quarantine are becoming essential practices in the world. IoT health monitoring systems prevent frequent visits to doctors and meetings between patients and medical professionals. However, many individuals require regular health monitoring and observation through medical staff. In this proposed work, we have taken advantage of the technology to make patients life easier for earlier diagnosis and treatment. A smart health monitoring system is being developed using Internet of Things (IoT) technology which is capable of monitoring blood pressure, heart rate, oxygen level, and temperature of a person. This system is helpful for rural areas or villages where nearby clinics can be in touch with city hospitals about their patient health conditions. However, if any changes occur in a patient's health based on standard values, then the IoT system will alert the physician or doctor accordingly. The maximum relative error (%ϵ r) in the measurement of heart rate, patient body temperature and SPO2 was found to be 2.89%, 3.03%, 1.05%, respectively, which was comparable to the commercials health monitoring system. This health monitoring system based on IoT helps out doctors to collect real-time data effortlessly. The availability of high-speed internet allows the system to monitor the parameters at regular intervals. Furthermore, the cloud platform allows data storage so that previous measurements could be retrieved in the near future. This system would help in identifying and early treatment of COVID-19 individual patients.

The Effect of Psychosocial Factors on Outcomes in Patients With Rotator Cuff Tears: A Systematic Review.

PURPOSE: To determine whether psychosocial factors affect patient-reported outcomes in individuals with rotator cuff tears or after rotator cuff repair. METHODS: A systematic review was conducted using a computerized search of the PubMed and Web of Science electronic databases in adherence with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. Articles were then evaluated based on inclusion and exclusion criteria. The Newcastle-Ottawa Scale was used to assess study quality and risk of bias. Because of study heterogeneity and varied levels of evidence, meta-analysis was not possible. RESULTS: Of 980 identified articles, 15 met the inclusion and exclusion criteria. In those reported, the visual analog scale correlation with distress scales ranged from -0.476 to 0.334, depending on outcome, with a trend toward increased pain in patients with distress. The depression subscale of the Hospital Anxiety and Depression Scale was negatively correlated with the American Shoulder and Elbow Surgeons score in 2 of 3 studies (-0.309 to 0.235). Six studies evaluated the presence of psychosocial factors and their correlation with patient-reported outcomes prior to surgery. These showed a significant correlation between rotator cuff pathology and psychological distress (i.e., depression or anxiety) as identified on standardized patient-reported outcome measures. Nine studies evaluated psychosocial factors either before and after surgery or only postoperatively. Of these 9 studies, 3 found no statistically significant differences in outcomes as related to psychosocial factors. In contrast, 6 of 9 reported an association between outcomes and psychosocial factors. Moreover, 2 of these 6 studies reported a direct relationship between patient expectations and outcomes, with 1 of these 2 studies finding that higher expectations improved baseline scores on the mental component summary of the Short Form 36 (r = 0.307). One study found significant differences in mental status in patients with rotator cuff tears based on age and sex. CONCLUSIONS: This review found that most studies support that psychosocial factors do significantly influence the level of disability and pain experienced by patients preoperatively; however, 3 of 9 studies showed significant improvements in postoperative pain and function even with significant psychosocial confounders. These studies, however, do support that there is a direct relation between patient expectations and outcomes in rotator cuff surgery. LEVEL OF EVIDENCE: Level IV, systematic review of Level I through IV studies.

Risk Factors for Elbow and Shoulder Injuries in Adolescent Baseball Players: A Systematic Review.

BACKGROUND: The incidence of shoulder and elbow injuries among adolescent baseball players is on the rise. These injuries may lead to surgery or retirement at a young age. PURPOSE: To identify independent risk factors for elbow and shoulder injuries in adolescent baseball players. A secondary aim was to determine whether the literature supports the Major League Baseball and USA Baseball Pitch Smart guidelines. STUDY DESIGN: Systematic review. METHODS: A systematic review was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines utilizing MEDLINE, SPORTDiscus, and Web of Science. Because of study heterogeneity, a quantitative synthesis was not performed. A qualitative review was performed on 19 independent risk factors for elbow and shoulder injuries in adolescent baseball players. Level of evidence was assigned per the Oxford Centre for Evidence-Based Medicine Working Group, and risk of bias was graded per the Newcastle-Ottawa Scale. RESULTS: Twenty-two articles met criteria for inclusion. Of the 19 independent variables that were analyzed, age, height, playing for multiple teams, pitch velocity, and arm fatigue were found to be independent risk factors for throwing arm injuries. Pitches per game appears to be a risk factor for shoulder injuries. Seven independent variables (innings pitched per game, showcase participation, games per year, training days per week, pitch type, shoulder external rotation, and shoulder total range of motion) do not appear to be significant risk factors. The data were inconclusive for the remaining 6 variables (weight, months of pitching per year, innings or pitches per year, catching, shoulder horizontal adduction, and glenohumeral internal rotation deficit). CONCLUSION: The results from this study demonstrate that age, height, playing for multiple teams, pitch velocity, and arm fatigue are clear risk factors for throwing arm injuries in adolescent baseball players. Pitches per game appears to be a risk factor for shoulder injuries. Other variables are either inconclusive or do not appear to be specific risk factors for injuries.

Surgical Trends in Articular Cartilage Injuries of the Knee, Analysis of the Truven Health MarketScan Commercial Claims Database from 2005-2014.

PURPOSE: To evaluate trends in procedures for the treatment of chondral injuries of the knee using the MarketScan database in the hope that further work can be performed to refine the indications for chondral intervention. METHODS: The MarketScan Research Database was searched using Current Procedure Terminology, 4th edition, codes to identify patients who underwent chondral procedures of the knee from 2005-2014. Combined procedures, including meniscal transplant or osteotomy, were also identified. Patients were characterized by gender, age group and year of initial procedure. A χ2 test was used to evaluate differences in surgical trends between individual patient groups delineated by age and gender. The Cochran-Armitage trend test was used to identify significant differences in surgical trends yearly. RESULTS: Of 148,373,254 unique patients, 520,934 patients underwent a total of 599,119 procedures. Arthroscopy with debridement/shaving of articular cartilage decreased in proportion from 75% of all procedures in 2005 to 51% of all procedures in 2014 (P < .0001). Open osteochondral allograft saw the greatest change during the study period; a higher number of females than males underwent condral procedures (P < .0001). Patients aged 45-54 underwent the most procedures (32.9% of all procedures). A total of 483 patients underwent chondral procedures in conjunction with meniscal transplant with variable incidence during the study period. A total of 1,418 patients underwent chondral procedures in conjunction with osteotomy; cumulative incidence decreased from 4.5 procedures per 1,000,000 patients/year in 2005 to 2.6 procedures per 1,000,000 patients/year in 2014 (P < .0001). CONCLUSIONS: Knee arthroscopy with debridement/shaving of articular cartilage remains the most common procedure performed. Although open allograft and autograft transplantation saw a sustained increase in incidence, the overall incidence of cartilage procedures, as well as those performed with osteotomies, declined. LEVEL OF EVIDENCE: Level IV, cross-sectional study.

Scurvy: a rare case in an adult.

A 69-year-old man presented with unilateral calf pain, swelling, and erythematous rash. He was initially treated with antibiotics for suspected cellulitis. A venous duplex ultrasound, performed to exclude deep venous thrombosis, revealed multiple heterogeneous hypoechoic foci of unknown etiology throughout the calf musculature. His condition did not improve with antibiotics, instead progressing to a necrotic ulcer along the medial malleolus. Clinical suspicion of vascular insufficiency or vasculitis prompted an extensive imaging work-up. CT and MRI revealed the intramuscular abnormalities observed on previous ultrasound represented foci of intramuscular hemorrhage. Marrow signal abnormality was also noted in the proximal tibia. A punch biopsy of the skin rash ultimately demonstrated distorted hair follicles with perifollicular inflammation and hemorrhage concerning for scurvy. The diagnosis was confirmed by low vitamin C levels and dietary history. A resurgence of scurvy has occurred in the pediatric population in recent years. However, this diagnosis remains uncommon in adults, with limited reports of the potential advanced imaging findings in the current literature.

Prevalence of Vitamin D Deficiency and Associated Risk Factors in the US Population (2011-2012).

Introduction 1,25-dihydroxyvitamin D3 (cholecalciferol), the hormonally active form of vitamin D3, is a lipid-soluble compound that plays a significant role in clinical medicine due to its potent effects on calcium homeostasis and bone metabolism. Since foods containing natural vitamin D are rare, the primary source of the compound remains its nonenzymatic dermal synthesis through exposure to ultraviolet rays in sunlight. Although uncommon in most developed countries, recent literature has demonstrated that subclinical vitamin D deficiency can exist in certain populations and plays a role in downstream clinical consequences, including cardiovascular disease, cancer, diabetes, osteoporosis, and fractures. This study aims to identify the prevalence and change in the pattern of vitamin D deficiency in subpopulations throughout the United States to provide a foundation for further clinical studies correlating the clinical outcomes to vitamin deficiency. Methods Data analyzed in this study were collected through National Health and Nutrition Examination Survey (NHANES), specifically from a population of 4962 participants, age ≥20 years, who were hospitalized between 2011 and 2012. This cohort was stratified to divide the population into patients that were vitamin D sufficient (>50 nmol/L) versus patients who were vitamin D deficient (50 nmol/L). The risk factors were compared between the subpopulations in 2005-2006 and 2011-2012. Conclusions The prevalence of vitamin D deficiency is greater in certain clinical subpopulations, and the presence of associated characteristics should raise the index of suspicion for the practicing clinician with regard to conditions associated with vitamin D deficiency, such as osteoporosis and osteomalacia. Further research investigating the pathophysiology of hypovitaminosis D and its clinical consequences can help better understand and prevent the development of associated comorbidities.

Recurrent Instability After Arthroscopic Bankart Reconstruction: A Systematic Review of Surgical Technical Factors.

PURPOSE: Recurrent instability remains of concern after arthroscopic Bankart reconstruction. We evaluated various technical factors including anchor design, anchor material, number of anchors used, and interval closure on risk of recurrent instability after arthroscopic Bankart reconstruction. METHODS: A systematic review of MEDLINE and Cochrane databases was conducted, following PRISMA guidelines. Extracted data were recorded on a standardized form. Methodological index for non-randomized studies (MINORS) and Newcastle-Ottawa Scale (NOS) were used to assess study quality and risk bias. Because of study heterogeneity and low levels of evidence, meta-analysis was not possible. Pooled weighted means were calculated and individual study evaluation and comparisons (qualitative analysis) were performed for systematic review. RESULTS: Of 2097 studies identified, 26 met criteria for systematic review. Pooled weighted means revealed 11.4% versus 15% recurrent instability with 3 or more suture anchors versus fewer than 3 anchors, 10.1% versus 7.8% with absorbable versus nonabsorbable suture anchors, respectively, and 8.0% versus 9.4% with knotless versus standard anchors, respectively. Interval closure did not qualitatively decrease recurrent instability or decrease range of motion. CONCLUSIONS: Our systematic review reveals that despite individual study, and previous systematic reviews pointing to the contrary, the composite contemporary published literature would support no difference in the risk of recurrent instability after arthroscopic Bankart reconstruction with rotator interval closure, differing numbers of anchors used for the repair, use of knotless versus standard anchors, or use of bioabsorbable versus nonabsorbable anchors. We recommend surgeons focus on factors that have been shown to modify the risk factors after arthroscopic Bankart reconstruction, such as patient selection. LEVEL OF EVIDENCE: Level IV, systematic review of Level III and IV studies.