Glanzmann thrombasthenia (GT) is an autosomal recessive disorder of platelet aggregation caused by quantitative or qualitative defects in integrins αIIb and β3. These integrins are encoded by the
and
...genes and form platelet glycoprotein (GP)IIb/IIIa, which acts as the principal platelet receptor for fibrinogen. Although there is variability in the clinical phenotype, most patients present with severe mucocutaneous bleeding at an early age. A classic pattern of abnormal platelet aggregation, platelet glycoprotein expression and molecular studies confirm the diagnosis. Management of bleeding is based on a combination of hemostatic agents including recombinant activated factor VII with or without platelet transfusions and antifibrinolytic agents. Refractory bleeding and platelet alloimmunization are common complications. In addition, pregnant patients pose unique management challenges. This review highlights clinical and molecular aspects in the approach to patients with GT, with particular emphasis on the significance of multidisciplinary care.
The broad use of next-generation sequencing and microarray platforms in research and clinical laboratories has led to an increasing appreciation of the role of germline mutations in genes involved in ...hematopoiesis and lineage differentiation that contribute to myeloid neoplasms. Despite implementation of the American College of Medical Genetics and Genomics and Association for Molecular Pathology 2015 guidelines for sequence variant interpretation, the number of variants deposited in ClinVar, a genomic repository of genotype and phenotype data, and classified as having uncertain significance or being discordantly classified among clinical laboratories remains elevated and contributes to indeterminate or inconsistent patient care. In 2018, the American Society of Hematology and the Clinical Genome Resource co-sponsored the Myeloid Malignancy Variant Curation Expert Panel to develop rules for classifying gene variants associated with germline predisposition to myeloid neoplasia. Herein, we demonstrate application of our rules developed for the
gene to variants in six examples to show how we would classify them within the proposed framework.
For centuries, the Indian outlook on medicines has had foundations in the exploration of her rich biodiversity. Today, natural product (NP) research delivers an ample chemical space for drug ...discovery for almost every pathological condition. However, endophytes have emerged as a pandora's box of therapeutic secondary metabolites to resolve ecological, sustainability, and cost concerns. Marine sources of endophytes have garnered attention in the pharmaceutical sector, exemplified by increased FDA-approved marine drugs. With chemotherapy being the most common treatment for cancer patients, the need for novel drugs is steeping high. Endophytes from marine sources present a diverse natural productome for anticancer leads, especially for resistant cancers. For the first time, this review highlights the sustainable biotechnological potential of marine endophytes from the 3000 km long Indian coastline, a biogeographic zone. We also discuss the new cell death mechanisms and targets for marine anticancer drugs, emphasizing endophytes isolated from the Indian coasts. The advances in the NP yield enhancement strategies and possible chemical modifications on the product to reduce the complexity and increase the specificity for higher therapeutic value, followed by the challenges and prospects, are also reviewed.
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•Rates of novel natural product discovery remain high from marine sources.•The Indian coasts harbour diverse endophytes offering bioactive natural productome.•Marine drugs that target new cell death mechanisms offer specific anticancer therapies.•Endophyte biotechnology enhances the natural product yield sustainably.•Structurally complex and non-specific drugs can be improved with nano-modifications.
Retrospective cohort.
To investigate the impact of meeting a patient's preoperative expectations for back or leg pain or the achievement of minimum clinically important difference (MCID) on patient ...satisfaction following lumbar fusion.
Few studies have compared if MCID achievement or meeting preoperative expectations for pain reduction affects patient satisfaction.
A surgical database was reviewed for eligible patients who underwent lumbar fusion. Patient satisfaction and Visual Analog Scale (VAS) for back and leg pain were the outcomes of interest. Meeting expectations was calculated as a difference of ≤0 between preoperative expectations and postoperative VAS scores. MCID achievement was calculated by comparing changes in VAS scores with established values. Meeting preoperative expectations or MCID achievement as predictors of patient satisfaction was evaluated using regression analysis.
A total of 134 patients were included in this study. Patients demonstrated significant improvements in VAS back and VAS leg (p<0.001). At 1 year, 56.4% of patients had their VAS back expectations met compared with 59.5% for VAS leg. Similarly, at 1 year, 77.3% and 71.3% of patients achieved MCID for VAS back and leg, respectively. Meeting expectations for VAS back was significantly associated with patient satisfaction at all postoperative timepoints; however, MCID achievement only demonstrated a significant association with patient satisfaction at 6 and 12 weeks (all, p≤0.024). Meeting VAS leg expectations and MCID achievement both demonstrated a significant association with patient satisfaction at all postoperative timepoints (all, p≤0.02). No differences between MCID achievement and meeting expectations as predictors of satisfaction were noted.
The majority of patients achieved MCID and had their back and leg pain expectations met by 1 year. Both measures were significant predictors of patient satisfaction and suggest that MCID achievement may act as a suitable substitute for patient satisfaction.
Purpose
As more patients undergo lumbar spine surgery, novel interventions may improve physical and mental health outcomes. Few studies summarize the benefit of cognitive behavioral therapy (CBT) ...among lumbar spine surgery patients. This study collects randomized control trial data to investigate the influence of CBT on patient reported outcomes among lumbar spine surgery patients.
Methods
Our study used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and a medical library expert assisted in searching PubMed/MEDLINE, Scopus, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PsycINFO, and Google Scholar. We calculated standardized mean differences (SMD) to evaluate the effect size of CBT versus control groups with a sensitivity analysis.
Results
Our meta-analysis included seven studies with a total of 531 patients. The majority of included studies evaluated lumbar fusion, with preoperative CBT performed by physiotherapists. The largest effects were observed for overall quality of life (SMD = 0.55 95% CI 0.05, 1.05,
p
< 0.001,
I
2
= 86.7%) and psychological outcomes (SMD = 0.61 95% CI 0.28, 0.94,
p
< 0.001,
I
2
= 89.7%) though disability and pain outcomes also favored CBT intervention. Included studies demonstrated low overall bias but large heterogeneity. Sensitivity analysis demonstrated negligible study design differences and revealed moderators including CBT session frequency and final follow-up duration (
p
< 0.001).
Conclusion
Compared to usual care or alternative therapy control arms, CBT delivered the most improvement with overall quality of life and psychological outcomes. Among appropriately selected patients, CBT could improve perioperative disability, pain, quality of life, and psychological health following lumbar spine surgery.
Purpose
To determine whether there is an association between preoperative 10-Item Patient Activation Measure (PAM-10) scores and clinical outcomes following MIS LD.
Methods
Patients undergoing a ...primary MIS LD were retrospectively reviewed and stratified according to their preoperative PAM-10 scores: “low PAM,” “moderate PAM,” and “high PAM.” Preoperative PAM score cohorts were tested for improvements in Oswestry Disability Index (ODI), 12-Item Short-Form Physical Component Score (SF-12 PCS), and Visual Analog Scale (VAS) back and leg pain using multivariate linear regression.
Results
Eighty-nine patients were included: 29 had a low PAM score, 32 had a moderate PAM score, and 28 had a high PAM score. Cohorts experienced similar preoperative VAS back pain, VAS leg pain, ODI, and SF-12 PCS. Patients with low PAM scores experienced a trend of higher pain scores throughout 6 months with VAS back pain being significant at 3 months and VAS leg pain being significant at 6-week and 3-month follow-up. Patients with lower PAM scores experienced a worse improvement in ODI at 6-week, 3-month, and 6-month timepoints. Lastly, patients with lower PAM scores demonstrated less improvement in SF-12 PCS at 3-month and 6-month follow-up.
Conclusions
Lower preoperative PAM scores were associated with worse improvement in clinical outcomes following MIS LD. Patients with lower PAM scores had diminished improvement in long-term patient-reported outcomes including ODI, SF-12, and VAS back and leg pain. Our investigation suggests that preoperative PAM assessments may be an effective tool to predict postoperative outcomes following MIS LD.
IntroductionMusculoskeletal (MSK) infections are prevalent in the pediatric population, with previous research highlighting the significant impact of socioeconomic status (SES) on treatment outcomes. ...However, the specific link in pediatric cohorts remains poorly understood. The Area Deprivation Index (ADI), a measure of neighborhood-level disadvantage, serves as a crucial marker for SES. This study aims to investigate how ADI influences disease characteristics, treatment delays, and outcomes in pediatric patients with MSK infections.MethodsA single-center retrospective cohort analysis was conducted using patient charts from a large urban pediatric hospital over six years from 2017 to 2022. Patients aged 0-18 years with diagnoses of osteomyelitis, septic arthritis, cellulitis, or pyomyositis were identified using the International Classification of Diseases - 10th Revision (ICD-10) codes. Data collection included demographics, disease characteristics, treatment delay intervals, and complications. Patient zip codes were obtained and entered into the Neighborhood Atlas® mapping website to determine their ADI. Patients were then stratified into four groups based on ADI scores: 1-10, 11-20, 21-40, and 41-100. Statistical analysis included the use of the Mann-Whitney U test for continuous data and the Chi-square/Fisher’s exact test for binary and categorical data comparisons among the ADI groups.ResultsA total of 121 patients were included. Categorization based on ADI revealed 25 (20.7%) patients in the 1-10 ADI percentile group, 36 (29.8%) in the 11-20 group, 38 (31.4%) in the 21-40 group, and 22 (18.2%) in the 41-100 group. There were no significant differences between ADI and patient demographics, disease characteristics, presentation delay interval, treatment received, and complications.ConclusionThe study demonstrates that there was no significant difference between ADI groups regarding demographics, disease characteristics, presentation delay interval, treatment received, and complications in pediatric populations. Despite the lack of evidence for differences in MSK infections attributable to ADI, this does not negate the potential existence of such a relationship.
Meeting patient expectations is believed to impact satisfaction scores; however, the influence of achieving a minimum clinically important difference (MCID) is scarcely reported. This study aims to ...evaluate meeting patient expectations or MCID achievement for pain and disability as predictors of patient satisfaction.
A retrospective review of single or multilevel lumbar fusion patients was performed. Patients with missing preoperative Oswestry Disability Index (ODI) expectation questionnaires were excluded. Preoperative expectations and postoperative satisfaction scores for visual analog scale (VAS) back, VAS leg, and ODI were collected. Meeting expectations was defined as scores less than or equal to preoperative expectations. Achievement of MCID was evaluated. Improvement of all outcomes and correlations with satisfaction scores were evaluated using the Student's t-test and Pearson coefficient. Achievement of MCID or meeting expectations as predictors of satisfaction were evaluated and compared using linear regression and Suest test.
The study included 144 patients. All outcomes significantly improved and demonstrated significant correlations with satisfaction scores (P < 0.001, all). Patients reported a mean expectation of 17.7 (ODI), 1.7 (VAS back), and 0.9 (VAS leg). The majority had their expectations met and achieved MCID. Meeting expectations and MCID achievement demonstrated significant associations with satisfaction scores for all outcomes and time points. Achievement of MCID was a stronger predictor of satisfaction for ODI and VAS back.
Meeting preoperative expectations and achievement of an MCID for pain and disability measures was significantly associated with satisfaction. Achievement of MCID may be a more consistent and suitable replacement as a predictor of satisfaction over meeting patient expectations.
Standardized variant curation is essential for clinical care recommendations for patients with inherited disorders. Clinical Genome Resource (ClinGen) variant curation expert panels are developing ...disease-associated gene specifications using the 2015 American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) guidelines to reduce curation discrepancies. The ClinGen Myeloid Malignancy Variant Curation Expert Panel (MM-VCEP) was created collaboratively between the American Society of Hematology and ClinGen to perform gene- and disease-specific modifications for inherited myeloid malignancies. The MM-VCEP began optimizing ACMG/AMP rules for RUNX1 because many germline variants have been described in patients with familial platelet disorder with a predisposition to acute myeloid leukemia, characterized by thrombocytopenia, platelet functional/ultrastructural defects, and a predisposition to hematologic malignancies. The 28 ACMG/AMP codes were tailored for RUNX1 variants by modifying gene/disease specifications, incorporating strength adjustments of existing rules, or both. Key specifications included calculation of minor allele frequency thresholds, formulating a semi-quantitative approach to counting multiple independent variant occurrences, identifying functional domains and mutational hotspots, establishing functional assay thresholds, and characterizing phenotype-specific guidelines. Preliminary rules were tested by using a pilot set of 52 variants; among these, 50 were previously classified as benign/likely benign, pathogenic/likely pathogenic, variant of unknown significance (VUS), or conflicting interpretations (CONF) in ClinVar. The application of RUNX1-specific criteria resulted in a reduction in CONF and VUS variants by 33%, emphasizing the benefit of gene-specific criteria and sharing internal laboratory data.
•The ClinGen MM-VCEP has specified RUNX1-specific curation rules to address gene function, gene-specific domains, and phenotypic criteria.•RUNX1-specific criteria resulted in a reduction in CONF and VUS variants by 33%, emphasizing the need for expert variant curation.
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