Optimizing antifungal prophylaxis in allogeneic stem cell transplantation: A cohort study of two different approaches.

BACKGROUND: Limited consensus exists on the optimal use of antifungal agents to prevent invasive fungal infection in the early post allogeneic hematopoietic stem cell transplant (alloHCT) period, particularly when patients cannot tolerate oral medication administration. METHODS: We undertook a retrospective observational cohort study to assess the tolerability, efficacy, and cost of a new antifungal prophylaxis pathway at a major tertiary alloHCT centre. Patients aged ≥16 years who underwent alloHCT between February 2018 and October 2019 (cohort 1) or between April 2020 and November 2021 (cohort 2) were included. In both cohorts, first line prophylactic therapy was oral posaconazole. The second line drugs where oral therapy was unable to be administered were intravenous voriconazole (cohort 1) versus intravenous posaconazole (cohort 2). RESULTS: There were 142 patients enrolled in the study, 71 in each cohort. The proportion of patients remaining on first-line prophylaxis or progressing to second-, third-, and fourth-line options was 22.5%, 39.4%, 29.6%, and 8.5% in cohort 1 and 39.4%, 59.2%, 1.4%, and 0% in cohort 2, respectively. The frequency of neuropsychiatric adverse events was significantly higher in cohort 1 compared to cohort 2 (49.3% vs. 19.8%, p = .0004). Occurrence of proven and probable fungal infections was not significantly different between cohorts. Antifungal drug expenditure was $359 935 (AUD) more in cohort 1 ($830 486 AUD) compared to cohort 2 ($477 149 AUD). CONCLUSION: The antifungal prophylaxis pathway used in cohort 2 resulted in reduced antifungal-associated adverse effects, less patients requiring progression to 3rd and 4th line prophylaxis and reduced antifungal drug costs.

Role of procalcitonin in diagnosis of community acquired pneumonia in Children.

BACKGROUND: The role of serum Procalcitonin (PCT) in adults in diagnosis of Community acquired pneumonia (CAP) is well established, however, role in pediatric CAP remains controversial. OBJECTIVES: The objective of this study was to investigate the utility of serum procalcitonin in differentiating bacterial community-acquired lower respiratory tract infection from non-bacterial respiratory infection in children; radiologically confirmed pneumonia was used as the reference. In addition, we assessed the utility of adding the PCT assay to the clinical criteria for diagnosis of pneumonia. STUDY DESIGN: Subanalysis of a larger prospective,multicentriccohort study. PARTICIPANTS: Children, 2 months to 59 months of age, attending paediatric OPD of 5 urban tertiary care hospitals, suffering from acute respiratory infection (ARI). INTERVENTION: Detailed clinical history and examination findings of enrolled children were recorded on predesigned case record form. Samples for PCT were obtained at admission and were measured centrally at the end of the study except for one site using VIDAS® B.R.A.H.M.S PCT kit (Biomerieux SA, France). OUTCOMES: Sensitivity and specificity of procalcitonin for diagnosis of radiologically confirmed pneumonia. RESULTS: Serum Procalcitonin was measured in 370 patients; median (IQR) age of these children being 12 (7, 22) months, 235 (63.5%) were boys. The median (IQR) serum procalcitonin concentration was 0.1(0.05, 0.4) ng/mL.Sensitivity and specificity of raised PCT (> 0.5 ng/mL) for pneumonia as per any CXR abnormalities were 29.7% and87.5%,(P < 0.001) respectively. Raised PCT was also significantly associated with consolidation (34.5%,79.2%,P < 0.02)and pleural effusion(54.6%,79%,P < 001). Adding PCT to the existing clinical criteria of WHO did not improve the sensitivity for diagnosis of pneumonia. PCT was significantly higher in children with severe pneumonia. CONCLUSION: Positive PCT (> 0.5 ng/mL) is significantly associated with radiographic pneumonia but not with pneumonia based on WHO criteria.However, it can act as a surrogate marker for severe pneumonia.

Respiratory Viruses Cause Late Morbidity in Recipients of Hematopoietic Stem Cell Transplantation.

Common respiratory viral infections (CRVIs) frequently complicate hematopoietic stem cell transplantation (HSCT). We conducted a retrospective, single-center, observational cohort study to determine the incidence of CRVI in patients who received an allogeneic (allo) or autologous (auto) HSCT at the Royal Adelaide Hospital between 2009 and 2017. The median follow-up was 8.9 and 4.5 years for auto- and allo-HSCT recipients, respectively. There were 149 CRVI episodes in 74 patients, with rhinovirus being the most commonly isolated virus (n = 81, 47%). The majority of CRVIs (113/149, 75.8%) occurred more than 100 days post-HSCT and 67% were diagnosed in the outpatient setting. There was evidence of lower respiratory tract infection (LRTI) in 45.6% (68/149) of CRVIs. On multivariate logistic regression analysis, coviral infections and cytomegalovirus viremia were independent risk factors for progression of CRVI to LRTI. Ten (6.7%) CRVI episodes resulted in admission to intensive care for ventilatory support and 8 (5.4%) patients died within 30 days of CRVI diagnosis. In our study, 10.4% of HSCT recipients experienced a CRVI post-transplant, primarily causing late morbidity and potentially mortality. Prevention with strict infection control practices, vaccination, and patient education is essential.

The burden of immune-mediated refractoriness to platelet transfusions in myelodysplastic syndromes.

Up to 65% of patients with myelodysplastic syndromes (MDS) have thrombocytopenia and require platelet (PLT) transfusion. The current standard of practice is to provide random- or single-donor PLT transfusion and manage PLT refractoriness (PLT-R) if and when it develops. This study assessed the prevalence and risk factors for immune-mediated PLT-R in patients in the South Australian (SA) MDS Registry. STUDY DESIGN AND METHODS: A retrospective analysis of MDS patients enrolled in the SA-MDS registry was performed. HLA data was analyzed from January 2003 to 30 June 2017 to ensure minimum follow-up of 2 years. RESULTS: During the study period, 341 of 681 (50%) MDS patients required at least one PLT transfusion, with 29 of 341 (9%) of all PLT transfusion patients requiring HLA-matched PLT transfusion for PLT-R. Of these 29 patients, 70% were females treated with disease-modifying therapies suggesting that these patients are at high risk of HLA alloimmunization. CONCLUSIONS: Immune-mediated PLT-R is common in MDS and can be expensive and difficult to manage once it occurs. Therefore, PLT transfusion practices should be optimized, especially for female MDS patients planned for disease-modifying therapies. This can help save time and streamline management, especially in the provision of PLT products for these patients, where the consequences of alloimmunization and PLT-R can be severe.

Efficacy of GC Gold Label 9 and GC Miracle Mix® Restorations using Atraumatic Restorative Treatment (ART) in Rural Settings: A Randomized Controlled Trial.

Objectives: This study compared the longevity of high strength posterior glass ionomer and metal-reinforced glass ionomer using ART in rural settings within an 18-month observation period. Study Design: A nonblinded parallel design randomized controlled trial was conducted among children who attended dental outreach programs in a rural area of Southern India. Atraumatic Restorative Treatment (ART) was performed in 92 permanent posterior teeth with either high strength posterior glass ionomer or metal-reinforced glass ionomer restorations. The allocation ratio was 1:1. Restorations were evaluated at 1, 6, 12 and 18 months after placement. Results: The success rate of metal-reinforced glass ionomer restorations was 100%, 95.4%, 90.4% and 87.2% as compared to high strength posterior glass ionomer whose success rates were 100%, 93%, 85% and 61.8% at the four follow ups respectively. There was a statistically significant difference between the success rate of the two materials at the end of 18 months with the metal-reinforced glass ionomer restorations having a higher success rate (p=0.015). Conclusions : Although the clinical performance of both materials were largely similar, the metal-reinforced glass ionomer restorations had a higher success rate than the conventional GIC at the end of 18 months of follow-up.

Prosthetic treatment need and associated life course determinants in partially edentulous adults of age 18-35 years in Udupi taluk: A cross-sectional study.

AIM: The aims of this study were to assess the prevalence of use and need for dental prostheses and to associate need with the life course determinants in young adults of age 18-35 years in Udupi taluk, Karnataka, India. MATERIALS AND METHODS: It was a cross-sectional survey conducted on a total of 580 individuals those attended dental screening camps organized at random locations. A self-administered questionnaire was administered to participants to assess their life course determinants such as socioeconomic, behavioral, and psychological circumstances followed by an oral examination to assess their prosthetic status (WHO, 1997). Bivariate analysis followed by multivariate logistic regression analysis was carried out to determine the adjusted odds ratios (ORs) with 95% confidence interval (CI) for independent variables and the outcome. RESULTS: The need and use of dental prostheses was observed in 38% and 2.2% of young adults, respectively. Adjusted multivariable analysis revealed that life course determinants such as parental rearing style (OR = 7.66 [95% CI: 3.88-15.14]) and interaction between expenditure at 10 years of age and economic hardships at 10 years of age (OR = 9.63 [95% CI: 3.12-29.72] and OR = 6.43 [95% CI: 1.89-21.88]) were significantly associated with the need for prostheses. CONCLUSION: The need for dental prostheses in the young adults can be related to socioeconomic and psychosocial circumstances during childhood, and thus the concept of life course approach has been highlighted.

Red cell alloimmunization is associated with development of autoantibodies and increased red cell transfusion requirements in myelodysplastic syndrome.

Up to 90% of patients with a myelodysplastic syndrome require red blood cell transfusion; nevertheless, comprehensive data on red cell alloimmunization in such patients are limited. This study evaluates the incidence and clinical impact of red cell alloimmunization in a large cohort of patients with myelodysplastic syndrome registered in the statewide South Australian-MDS registry. The median age of the 817 patients studied was 73 years, and 66% were male. The cumulative incidence of alloimmunization was 11%. Disease-modifying therapy was associated with a lower risk of alloimmunization while alloimmunization was significantly higher in patients with a revised International Prognostic Scoring System classification of Very Low, Low or Intermediate risk compared to those with a High or Very High risk (P=0.03). Alloantibodies were most commonly directed against antigens in the Rh (54%) and Kell (24%) systems. Multiple alloantibodies were present in 49% of alloimmunized patients. Although 73% of alloimmunized patients developed alloantibodies during the period in which they received their first 20 red cell units, the total number of units transfused was significantly higher in alloimmunized patients than in non-alloimmunized patients (90±100 versus 30±52; P<0.0001). In individual patients, red cell transfusion intensity increased significantly following alloimmunization (2.8±1.3 versus 4.1±2.0; P<0.0001). A significantly higher proportion of alloimmunized patients than non-alloimmunized patients had detectable autoantibodies (65% versus 18%; P<0.0001) and the majority of autoantibodies were detected within a short period of alloimmunization. In conclusion, this study characterizes alloimmunization in a large cohort of patients with myelodysplastic syndrome and demonstrates a signficant increase in red cell transfusion requirements following alloimmunization, most probably due to development of additional alloantibodies and autoantibodies, resulting in subclinical/clinical hemolysis. Strategies to mitigate alloimmunization risk are critical for optimizing red cell transfusion support.

Dynamic assessment of RBC-transfusion dependency improves the prognostic value of the revised-IPSS in MDS patients.

RBC-transfusion dependency (RBC-TD) is an independent prognostic factor for poor overall survival (OS) in the WHO classification-based prognostic scoring system (WPSS) for MDS patients. However, WPSS did not include cytopenia, whereas revised International Prognostic Scoring System (IPSS-R) did not include RBC-TD. Thus, neither of these prognostic scoring systems incorporates both cytopenia and RBC-TD. We aimed to test whether RBC-TD adds prognostic value to the IPSS-R. We analyzed MDS patients not treated with disease-modifying therapy, and enrolled in SA-MDS Registry (derivation cohort; n = 295) and Dusseldorf registry (Germany; validation cohort; n = 113) using time-dependent Cox proportional regression and serial landmark analyses. In the derivation cohort, RBC-TD patients had inferior OS compared to RBC transfusion-independent (RBC-TI) patients (P < 0.0001) at 6- (18 vs. 64 months), 12- (24 vs. 71 months), and 24-months (40 vs. 87 months). In a Cox proportional regression analysis, RBC-TD was an independent adverse prognostic marker in addition to age, sex, and IPSS-R variables (P < 0.0001). A prognostic index (PI) was derived using these Cox-proportional regression model variables. In the validation cohort, this PI classified patients into four prognostic groups with significantly different OS (P < 0.001) as in the derivation cohort. In conclusion, multivariate analysis by Cox proportional hazards regression and serial landmark analyses clearly demonstrates that development of RBC-TD at any time during the course of MDS is associated with poor OS, independent of IPSS-R. This study demonstrates that dynamic assessment of RBC-TD provides additional prognostic value to IPSS-R and should be included in treatment decision algorithms for MDS patients.

Hemorrhagic Pseudocyst (Polyst) and True Hemorrhagic Cyst of the Vocal Fold.

OBJECTIVES: Though hemorrhagic vocal fold polyps are a common entity, hemorrhagic vocal fold cysts have not been previously described. In our study, we have evaluated patients who were diagnosed on stroboscopy with "hemorrhagic" cysts. METHODS: This 18-month retrospective study has received institutional ethics clearance. Using the database of our voice clinic, 14 patients diagnosed with hemorrhagic cysts by stroboscopy were reviewed. Age, sex, chief complaints, symptom duration, videostroboscopy findings, surgical details, and histopathology were noted. RESULTS: Out of a total 14 patients, 12 were males with a mean age of presentation of 41 years. The duration of hoarseness ranged from 2-24 months. Videostroboscopy revealed a markedly decreased amplitude of the mucosal waves over a well-delineated ovoid or spheroid hemorrhagic lesion, which seemed tethered down by overlying vocal fold epithelium. All patients had operative findings of a well-encapsulated hemorrhagic lesion in the superficial lamina propria with anterior and posterior fibrotic bands. Histopathology of 13 patients was similar and revealed a hemorrhagic polypoidal lesion. A pseudo-capsule could be identified occasionally. These lesions seemed to be hemorrhagic pseudocysts, named "polyst" by us. In one male patient, the histopathology revealed a true vocal fold cyst (type C Koren) with hemorrhage. CONCLUSIONS: A hemorrhagic pseudocyst (polyst) of the vocal fold has stroboscopic and surgical findings resembling a true vocal fold cyst with hemorrhage; however, histologically it resembles a hemorrhagic polyp. A true hemorrhagic cyst however is typically a type C Koren cyst with hemorrhage. Both these entities have not been previously described.

Age Assessment through Root Lengths of Mandibular Second and Third Permanent Molars Using Machine Learning and Artificial Neural Networks.

The present study explores the efficacy of Machine Learning and Artificial Neural Networks in age assessment using the root length of the second and third molar teeth. A dataset of 1000 panoramic radiographs with intact second and third molars ranging from 12 to 25 years was archived. The length of the mesial and distal roots was measured using ImageJ software. The dataset was classified in three ways based on the age distribution: 2-Class, 3-Class, and 5-Class. We used Support Vector Machine (SVM), Random Forest (RF), and Logistic Regression models to train, test, and analyze the root length measurements. The mesial root of the third molar on the right side was a good predictor of age. The SVM showed the highest accuracy of 86.4% for 2-class, 66% for 3-class, and 42.8% for 5-Class. The RF showed the highest accuracy of 47.6% for 5-Class. Overall the present study demonstrated that the Deep Learning model (fully connected model) performed better than the Machine Learning models, and the mesial root length of the right third molar was a good predictor of age. Additionally, a combination of different root lengths could be informative while building a Machine Learning model.

A Personalized Risk Model for Azacitidine Outcome in Myelodysplastic Syndrome and Other Myeloid Neoplasms Identified by Machine Learning Model Utilizing Real-World Data.

Azacitidine is an approved therapy for higher-risk myelodysplastic syndrome (MDS). However, only 30-40% patients respond to azacitidine, and the responses may take up to six cycles to become evident. Delayed responses and the myelosuppressive effects of azacitidine make it challenging to predict which patients will benefit. This is further compounded by a lack of uniform prognostic tools to identify patients at risk of early treatment failure. Hence, we performed a retrospective analysis of 273 consecutive azacytidine-treated patients. The median overall survival was 16.25 months with only 9% alive at 5 years. By using pre-treatment variables incorporated into a random forest machine learning model, we successfully identified those patients unlikely to benefit from azacytidine upfront (7.99 vs. 22.8 months, p < 0.0001). This model also identified those who required significantly more hospitalizations and transfusion support. Notably, it accurately predicted survival outcomes, outperforming the existing prognostic scoring system. By integrating somatic mutations, we further refined the model and identified three distinct risk groups with significant differences in survival (5.6 vs. 10.5 vs. 43.5 months, p < 0.0001). These real-world findings emphasize the urgent need for personalized prediction tools tailored to hypomethylating agents, reducing unnecessary complications and resource utilization in MDS treatment.

Factors predicting survival following alloSCT in patients with therapy-related AML and MDS: a multicenter study.

Therapy-related myeloid neoplasms (t-MN) are aggressive myeloid neoplasms. Factors predicting post-allogeneic stem cell transplant (alloSCT) survival are not well-known. We studied the prognostic utility of factors at: t-MN diagnosis, pre-alloSCT, and post-alloSCT. Primary endpoints were 3-year overall survival (OS), relapse incidence (RI), and non-relapse mortality (NRM). Post-alloSCT OS did not differ between t-MDS and t-AML (20.1 vs. 19.6 months, P = 1), though t-MDS had a significantly higher 3-year RI compared to t-AML (45.1% vs. 26.9%, P = 0.03). In t-MDS, the presence of monosomy 5 (HR 3.63, P = 0.006) or monosomy 17 (HR 11.81, P = 0.01) pre-alloSCT were associated with higher RI. Complex karyotype was the only factor adversely influencing survival at all the timepoints. The inclusion of genetic information yielded 2 risk-categories: high-risk defined by the presence of pathogenic variants (PV) in (TP53/BCOR/IDH1/GATA2/BCORL1) and standard-risk (remainder of the patients) with 3-year post-alloSCT OS of 0% and 64.6%, respectively (P = 0.001). We concluded that while alloSCT was curative in a subset of t-MN patients, outcomes remained poor, specifically in the high-risk category. t-MDS patients, especially those with persistent disease pre-alloSCT were at increased risk of relapse. Disease-related factors at t-MN diagnosis were the most prognostic of post-alloSCT survival; utility of factors available later in the course, was incremental.

Allogeneic hematopoietic stem cell transplant outcomes in adults with inherited myeloid malignancies.

There is increasing recognition that pathogenic germ line variants drive the development of hematopoietic cancers in many individuals. Currently, patients with hereditary hematologic malignancies (HHMs) receive similar standard therapies and hematopoietic stem cell transplant (HSCT) approaches as those with sporadic disease. We hypothesize that patients with myeloid malignancies and deleterious germ line predisposition variants have different posttransplant outcomes than those without such alleles. We studied 472 patients with myeloid neoplasms, of whom 26% had deleterious germ line variants and 34% underwent HSCT. Deleterious germ line variants in CHEK2 and DDX41 were most commonly seen in American and Australian cohorts, respectively. Patients with deleterious germ line DDX41 variants had a higher incidence of severe (stage 3-4) acute graft-versus-host disease (GVHD) (38%) than recipients with deleterious CHEK2 variants (0%), other HHM variants (12%), or patients without such germ line variants (9%) (P = .002). Importantly, the use of posttransplant cyclophosphamide reduced the risk of severe acute GVHD in patients receiving HSCT for deleterious germ line DDX41-associated myeloid neoplasms (0% vs 53%, P = .03). Based on these results, we advocate the use of posttransplant cyclophosphamide when individuals with deleterious germ line DDX41 variants undergo allogeneic HSCT for myeloid malignancies, even when transplantation has been performed using wild-type donors.

TP53 mutation variant allele frequency of ≥10% is associated with poor prognosis in therapy-related myeloid neoplasms.

Revised diagnostic criteria for myeloid neoplasms (MN) issued by the International Consensus Classification (ICC) and the World Health Organization (WHO) recommended major change pertaining to TP53-mutated (TP53mut) MN. However, these assertions have not been specifically examined in therapy-related myeloid neoplasm (t-MN), a subset enriched with TP53mut. We analyzed 488 t-MN patients for TP53mut. At least one TP53mut with variant allele frequency (VAF) ≥ 2% with or without loss of TP53 locus was noted in 182 (37.3%) patients and 88.2% of TP53mut t-MN had a VAF ≥10%. TP53mut t-MN with VAF ≥ 10% had a distinct clinical and biological profile compared to both TP53mut VAF < 10% and wild-type TP53 (TP53wt) cases. Notably, TP53mut VAF ≥ 10% had a significantly shorter survival compared to TP53wt (8.3 vs. 21.6 months; P < 0.001), while the survival of TP53mut VAF < 10% was comparable to TP53wt. Within TP53mut VAF ≥ 10% cohort, the inferior outcomes persisted irrespective of the single- or multi-hit status, co-mutation pattern, or treatments received. Finally, survival of TP53mut patients was poor across all the blast categories and MDS patients with >10% blasts had inferior survival compared to <5%. In summary, TP53mut VAF ≥10% signified a clinically and molecularly homogenous cohort regardless of the allelic status.

Effect of life course factors on dental fear among adult dental patients attending out-reach clinics in a rural area of Southern India.

Objectives: The aim of the study was to assess the effect of life course factors on dental fear among adult dental patients attending out-reach clinics in a rural area of South India. The objectives were to measure dental fear and changes in socio-economic status during the life course among the study population and to know whether social mobility reduced/increased dental fear. Methods: Dental fear scale and life course data were collected from 403 respondents. The improvement status of individual life course criteria was categorised into "less/minimal", "stable", or "upwardly mobile". Results: The odds of dental fear in the group showing less or minimal upward social mobility was two times that of the stable group [p = 0.022; 95% confidence interval (C.I): 1.104-3.598], whereas the odds of dental fear in the group showing more or good upward social mobility were 4.5 times that of the stable group [p = 0.001; 95% C.I: 1.928-10.515] when adjusted for covariates, that is, participant age, gender, and education and past history of dental avoidance. Conclusion: Social mobility was found to be a risk indicator for dental fear. Dental services may have been affected even with increased standards of living because of psychological factors such as dental fear.

Panel-based gene testing in myelodysplastic/myeloproliferative neoplasm overlap syndromes: Australasian Leukaemia and Lymphoma Group (ALLG) consensus statement.

This review aims to provide an expert consensus statement to address the role of gene-panel testing in the diagnosis, prognosis and management of adult myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes (MDS/MPN) in Australia. This consensus statement was developed by an expert group, actively involved in gene panel testing in the area of MDS/MPN in Australia. This work was led by the chairs of the MDS (A/Prof A. Enjeti) and MPN (A/Prof D. Ross) working parties of the Australasian Leukaemia and Lymphoma Group (ALLG). The authors were selected after an expression of interest process on the basis of active laboratory involvement in gene panel testing, a specific demonstrated interest in MDS/MPN and/or publication record in this field. The authors were then allocated sections for literature review to identify the specific genes of interest for each MDS/MPN entity. At least two authors reviewed each section and an overarching diagnostic algorithm was developed by a consensus amongst all authors.

Factors Affecting the Usage of Wearable Device Technology for Healthcare among Indian Adults: A Cross-Sectional Study.

BACKGROUND: Wearable device technology has recently been involved in the healthcare industry substantially. India is the world's third largest market for wearable devices and is projected to expand at a compound annual growth rate of ~26.33%. However, there is a paucity of literature analyzing the factors determining the acceptance of wearable healthcare device technology among low-middle-income countries. METHODS: This cross-sectional, web-based survey aims to analyze the perceptions affecting the adoption and usage of wearable devices among the Indian population aged 16 years and above. RESULTS: A total of 495 responses were obtained. In all, 50.3% were aged between 25-50 years and 51.3% belonged to the lower-income group. While 62.2% of the participants reported using wearable devices for managing their health, 29.3% were using them daily. technology and task fitness (TTF) showed a significant positive correlation with connectivity (r = 0.716), health care (r = 0.780), communication (r = 0.637), infotainment (r = 0.598), perceived usefulness (PU) (r = 0.792), and perceived ease of use (PEOU) (r = 0.800). Behavioral intention (BI) to use wearable devices positively correlated with PEOU (r = 0.644) and PU (r = 0.711). All factors affecting the use of wearable devices studied had higher mean scores among participants who were already using wearable devices. Male respondents had significantly higher mean scores for BI (p = 0.034) and PEOU (p = 0.009). Respondents older than 25 years of age had higher mean scores for BI (p = 0.027) and Infotainment (p = 0.032). CONCLUSIONS: This study found a significant correlation with the adoption and acceptance of wearable devices for healthcare management in the Indian context.