Tag: nevin manimala

Blood. 2023 Jun 23:blood.2022017643. doi: 10.1182/blood.2022017643. Online ahead of print.

ABSTRACT

T-cell large granular lymphocytic leukemia (T-LGLL) is a clonal proliferation of cytotoxic T-lymphocytes that can result in severe neutropenia, anemia, and bone marrow failure. Strong evidence from patients and mouse models demonstrate the critical role of interleukin-15 in T-LGLL pathogenesis. BNZ-1 is a pegylated peptide that selectively inhibits the binding of IL-15 and other gc cytokines to their cellular receptor complex, that has demonstrated efficacy in ex vivo T-LGLL cells and transgenic mice in pre-clinical studies. We conducted a phase I/II trial of BNZ-1 in patients with T-LGLL who had hematocytopenias (anemia or neutropenia) that required therapy. Clinical responses were assessed using hematologic parameters (improvement in hematocytopenias) based off response criteria from the ECOG 5998 T-LGLL trial. BNZ-1 demonstrated clinical partial responses in 20% of patients with T-LGLL with minimal toxicity and the maximum tolerated dose (MTD) was not reached. Further, T-LGLL leukemic cells showed significantly increased apoptosis in response to BNZ-1 treatment as early as day two, including in clinically non-responding patients, with changes that remained statistically different from baseline throughout treatment (p<0.005). We report first-in-human proof that T-LGLL leukemic cells are dependent on IL-15 and that intervention with IL-15 inhibition with BNZ-1 in T-LGLL patients shows therapeutic effects, which carries important implications for the understanding of the pathogenesis of this disease. Clinical Trial # NCT03239392.

PMID:37352612 | DOI:10.1182/blood.2022017643

Biochem Biophys Res Commun. 2023 Jun 14;672:137-144. doi: 10.1016/j.bbrc.2023.06.012. Online ahead of print.

ABSTRACT

The functional connectivity patterns of the brain during resting state are closely related to an individual’s cognition, emotion, behavior, and social interactions, making it an important research method to measure personality traits in an unbiased way, replacing traditional paper-and-pencil tests. However, due to the dynamic nature of the brain, whether the changes in functional connectivity caused by age can stably map onto personality traits has not been previously investigated. This study focuses on whether network features that are significantly related to personality traits can effectively distinguish subjects with different personality traits, and whether these network features vary across different periods of adulthood. The study included 343 healthy adult participants, divided into early adulthood and middle adulthood groups according to the age threshold of 35. Resting-state functional magnetic resonance imaging (fMRI) and the Big Five personality questionnaire were collected. we investigated the relationship between personality traits and intrinsic whole-brain functional connectome. We then used support vector machine (SVM) to evaluate the performance of personality network features in distinguishing subjects with high and low scores in the early-adulthood sample, and cross-validated in the mid-adulthood sample. Additionally, edge-based analysis (NBS) was used to explore the stability of personality networks across the two age samples. Our results show that the network features corresponding to openness personality trait are stable and can effectively differentiate subjects with different scores in both age samples. Furthermore, this study found that these network features vary to some extent across different periods of adulthood. These findings provide new evidence and insights into the application of resting-state functional connectivity patterns in measuring personality traits and help us better understand the dynamic characteristics of the human brain.

PMID:37352602 | DOI:10.1016/j.bbrc.2023.06.012

Int J Pediatr Otorhinolaryngol. 2023 Jun 15;171:111636. doi: 10.1016/j.ijporl.2023.111636. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare surgical outcomes for children with peritonsillar abscess (PTA) who are taken to the operating room (OR) for incision and drainage (I&D) or quinsy tonsillectomy.

METHODS: This is a multicenter retrospective study of pediatric patients who underwent I&D of a PTA between 2012 and 2017 included in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. Patient demographics, comorbidities, and 30-day postoperative events (reoperation, readmission, and complications) were assessed.

RESULTS: 777 patients were identified (mean age of 10.7 years, 54% female). 656 (84%) were admitted through the emergency department, and 395 (51%) met criteria for systemic inflammatory response syndrome or sepsis. Fifty-two (6.7%) had a quinsy tonsillectomy done at the time of incision and drainage. For quinsy tonsillectomy versus I&D alone, there was no statistically significant difference in length of stay (LOS) (1.9 v. 1.7 days, p = .523), readmission (17 v. 0, p = .265) or return to the OR (18 v. 1, p = .810). Patients younger than 5 years had a longer LOS (p < .001) while females (p = .003) and patients between 12 and 17 years of age (p = 0.021) were more likely to be readmitted. Of 725 patients treated with I&D alone, 10 (1.4%) patients required a repeat I&D and 6 (0.83%) went on to have an interval quinsy tonsillectomy.

CONCLUSIONS: Outcomes of I&D and quinsy tonsillectomy for pediatric PTA in the operating room are the same. If tonsillectomy is indicated in the case of recurrent tonsillitis or PTA, a quinsy tonsillectomy is a good option.

PMID:37352593 | DOI:10.1016/j.ijporl.2023.111636

Int J Pediatr Otorhinolaryngol. 2023 Jun 17;171:111632. doi: 10.1016/j.ijporl.2023.111632. Online ahead of print.

ABSTRACT

OBJECTIVES: Supraglottoplasty (SGP) for severe laryngomalacia (LM) in children with medical comorbidities has been associated with high risk of surgical failure and increased need of postoperative pediatric intensive care unit (PICU) intervention, but evidence for this is ambiguous. The objective was to evaluate surgical outcome and risk of need for PICU-intervention following SGP for severe LM in comorbid patients.

METHODS: Retrospective observational study of 116 patients treated with SGP for severe LM between 2000 and 2021 at a tertial referral pediatric airway surgery center Karolinska University Hospital. Medical records were reviewed and patient data regarding surgical timing, type of SGP procedure, PICU-intervention, complications, and outcomes were recorded. Patients were defined as non-comorbid vs high-risk comorbid (HRC) based on a coexisting comorbidity for risk of surgical failure and postoperative PICU-intervention. Surgical failure was defined as need of revision surgery, tracheostomy or assisted ventilation (continuous positive airway pressure and bilevel positive airway pressure). PICU intervention was defined as need of postoperative assisted ventilation or intubation. Statistical comparisons were performed with outcome of SGP on children with LM and no comorbidities.

RESULTS: 41/116 patients included had a HRC associated with an increased risk of PICU-intervention and surgical failure. 75/116 patients were defined as non-comorbid. The overall surgical success in the study population was 89.7% (104/116), 94.7% in the non HRC group vs 80.5% in the HRC-group. 5/41 HRC patients and 1/75 non-comorbid patients needed SGP revision in which 5/6 was successful. There was no significantly increased need for postoperative PICU intervention in HRC patients.

CONCLUSION: SGP for severe LM patients with high-risk comorbidities performed in a tertiary setting had an overall good result and low risk of PICU-intervention. Revision SGP was more common in HRC patients but had a good outcome. Multidisciplinary experience in perioperative care of comorbid patients may be of key importance for outcome and children with high-risk comorbidities should thus not be withheld the possible benefit of SGP without assessment at a tertiary pediatric airway center.

PMID:37352590 | DOI:10.1016/j.ijporl.2023.111632

Am J Emerg Med. 2023 Jun 7;71:74-80. doi: 10.1016/j.ajem.2023.06.002. Online ahead of print.

ABSTRACT

BACKGROUND: Emergency department (ED) visits can be divided into urgent and non-urgent. A delay in seeking medical help, especially in urgent cases, can lead to fatal consequences, along with a higher rate of complications and morbidity. Coronavirus disease 2019 (COVID-19) pandemic spread led to restrictions and eventually quarantines. We investigated the impact of the COVID-19 spread and quarantine on ED visits rates comparing to parallel periods in preceding years (2013-2019). In addition, we compared this decrease to holidays and weekends, times in which a decrease in ED visits is seen.

METHODS: This was a descriptive retrospective study. Causes of ED referrals were divided into urgent and non-urgent, then into different subcategories including infectious, cardiac, etc. RESULTS: For the spring COVID-192020 quarantine period, a 56.3% decrease of mean ED visits per day was seen, as compared to preceding years (55.7% and 98.9% respectively). This decrease was also statistically evident when comparing the urgent and non-urgent causes separately and for all sub-categories. This pattern of decrease also showed statistical evidence of fewer ED visits during holidays for most comparisons, in which lower ED visit rates are expected. Significantly lower rates of ED visits were demonstrated during the COVID-19 quarantine period, as compared to preceding years and main holidays and weekends, a decrease that was also demonstrated for urgent life-threatening causes.

CONCLUSION: Our findings can be used to inform a wide range of stakeholders, including regional planners, historians, sociologists, and international healthcare organizations. Healthcare providers should understand the reasons for this ED visit decline pattern, attempt to address patients’ concerns, and increase awareness regarding alarming symptoms in urgent medical situations.

PMID:37352578 | DOI:10.1016/j.ajem.2023.06.002

Melanoma Res. 2023 Jun 21. doi: 10.1097/CMR.0000000000000906. Online ahead of print.

ABSTRACT

CDKN2A pathogenic variants are well known to be associated with cutaneous melanoma and noncutaneous tumors (NCTs). Herein, we investigated the temporal correlation between the first cutaneous melanoma and NCT both in CDKN2A mutation carriers (MUT) and in wild-type melanoma patients, a poorly explored issue to date. Two hundred forty-five cutaneous melanoma patients were genotyped for the CDKN2A gene and divided into 51 MUT and 189 wild-type; the remaining five variant carriers were excluded from the analyses. MUT developed a significantly higher number of cutaneous melanoma than wild-type, while 13.7% in both genotyped groups received a diagnosis of at least one malignant NCT, without statistically significant differences. The onset of the first cutaneous melanoma preceded that of the first malignant or benign NCT in both MUT and wild-type patients by an average of 4.5 and 3.02 years, respectively. Considering only malignant tumors, the diagnosis of melanoma preceded that of the first NCT on an average of 8 and 4.34 years, in MUT and wild-type patients respectively. We emphasize the relevance to adopt a global vision for the primary and secondary surveillance of patients affected by cutaneous melanoma, not only limited to high-risk for multiple primary skin cancers but also to NCT that may develop several years after the diagnosis of the first cutaneous melanoma.

PMID:37352544 | DOI:10.1097/CMR.0000000000000906

P R Health Sci J. 2023 Jun;42(2):158-163.

ABSTRACT

OBJECTIVE: To assess the contraceptive methods used by sexually active Hispanic women living in Puerto Rico.

METHODS: From October 2016 through February 2018, 518 patients completed a self-administered questionnaire. The inclusion criteria were being over the age of 21 and having visited San Juan City Hospital or University District Hospital. The results were analyzed using descriptive statistics and a 2-sample t test, where P < .05 was considered significant.

RESULTS: A total of 518 participants completed the questionnaire. Of the 518, 413 (81.0%) reported having used at least 1 form of contraception; 252 (49.4%) used OCPs, 305 (60.8%) used male condoms, 92 (33.8%) used the rhythm method, 83 (30.6%) undergone female sterilization, 98 (19.9%) used the withdrawal method, 92 (18.9%%) used an implant, 67 (13.5%) received progesterone injections, 41 (8.3%) used female condoms, 13 (4.9%) had partners who undergone male sterilization, 20 (4.1%) used the transdermal patch, 16 (3.2%) used a vaginal ring, and 26 (5.3%) used an intrauterine device.

CONCLUSION: Of the 518 women, 24.2% used LARC, representing an increase in the usage by this population; this increase is likely linked to LARC’s being easily accessible and free of charge. Public health interventions should be developed to increase knowledge about sexual health, educate about the effectiveness of different contraceptive methods and the prevention of sexually transmitted diseases, and reduce both the barriers to acquiring contraception and, thereby, the number of unintended pregnancies in this population.

PMID:37352539

P R Health Sci J. 2023 Jun;42(2):127-131.

ABSTRACT

OBJECTIVE: The visit-to-visit variability (VVV) of blood pressure (BP) has been recognized as a risk factor for cardiovascular events and chronic kidney disease (CKD). The objective of this study is to valuate the association between the VVV of BP and changes in estimated glomerular filtration rate (eGFR) in elderly CKD patients at different stages of renal function.

MATERIALS AND METHODS: For 60 months, we analyzed the medical records of 105 patients with and without diabetes and hypertension. Systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) were examined. A multivariable linear regression model was used to analyze the correlation between eGFR and the VVV of BP.

RESULTS: No differences were demonstrated between the groups in the clinical characteristics. Mean SBP and DBP were not significant between the groups, and we observed no decrease in renal function. A significant negative correlation between PP and eGFR was observed in the total CKD population with a P of .010 (95% CI: -0.20, -0.03) and a correlation coefficient of -0.11.

CONCLUSION: Our study shows no statistical significances in terms of the VVVs of BP in any of the geriatric groups, with no significant decreases in renal function. However, we observed a significant negative correlation between PP and eGFR. We demonstrated that if a VVV of BP does not occur, there is no decrease in eGFR.

PMID:37352534

P R Health Sci J. 2023 Jun;42(2):121-126.

ABSTRACT

OBJECTIVE: The aim of this study was to determine the prevalence of severely increased albuminuria and the percentage of patients with the indication for canagliflozin in the type 2 diabetes population with chronic kidney disease (CKD) and low socioeconomic status in the San Juan City Hospital.

METHODS: This cross-sectional study examined the electronic records of 129 Hispanic type 2 diabetes patients. CKD in this population was defined according to the most recent nephrology and endocrinology guidelines. Albuminuria was diagnosed with two positive urine albumin/creatinine ratio results within 3-6 months. Data was obtained from July 2017 to January 2020 and analyzed utilizing descriptive statistics and correlations.

RESULTS: The prevalence of moderately and severely increased albuminuria in patients with type 2 diabetes and CKD were 51.2% and 18.6% respectively. The number of patients with type 2 diabetes who filled the FDA indication for canagliflozin were 16.3%. The prevalence of hypertension, coronary artery disease (CAD) and heart failure (HF) was 61.2%, 15.5% and 10.1% respectively. Between albuminuria severity and decreased renal function, a tendency was observed although not statistically significant (r = -0.14, 95% CI: -0.31, 0.03; P = 0.109). While evaluating association between albuminuria groups and CAD, there was a noticeable tendency close to reaching statistical significance (P = 0.060).

CONCLUSION: There is a scarcity of studies regarding the prevalence of severely increased albuminuria in type 2 diabetics with CKD and this study contributes to the literature. On analysis of associations, statistical significance not reached likely due to small sample size.

PMID:37352533

Clin Nucl Med. 2023 Jun 23. doi: 10.1097/RLU.0000000000004745. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to compare oral and IV administrations of 18F-NaF PET/CT for detection of suspicious bone metastatic lesions of breast and prostate cancers.

PATIENTS AND METHODS: Thirty-six patients with breast (n = 23) or prostate (n = 13) cancers and high risk for bone metastases were prospectively evaluated. All patients underwent 2 PET/CT studies after IV and oral 18F-NaF administration within a 2 to 23 days interval between them. The maximum SUVs from the same suspicious lesions (≤5 index lesions per patient) in both studies were measured. The target-to-background ratio (TBR), defined as the relation between the lesion maximum SUV and the whole skeletal mean SUV, was calculated for each lesion. The TBRs in the same lesion calculated using the 2 administration routes were compared. The agreements between 2 physicians in the definition of the number of lesions in both studies were also assessed using weighted κ.

RESULTS: One hundred thirty-four pairs of lesions were analyzed. There was no significant statistical difference between the median TBRs (P = 0.212) for IV (10.33) and oral (10.85). Excellent intraobserver agreement was observed between IV and oral routes: weighted κ of 1.0 (95% confidence interval, 0.92-1.0) and 0.92 (95% confidence interval, 0.81-0.99) for physicians 1 and 2, respectively. The interobserver coefficients were 0.82 and 0.87 for “oral versus oral” and “IV versus IV,” respectively.

CONCLUSIONS: 18F-NaF PET/CT studies using oral and IV routes present comparable performance; thus, it is possible to use oral route in patients with difficult venous access.

PMID:37351903 | DOI:10.1097/RLU.0000000000004745