An Innovative Approach for Precise Identification of the Lowest Unoccupied Molecular Orbital Using the Parametric Equation of Motion.

The lowest unoccupied molecular orbital (LUMO) plays a crucial role in quantum chemistry, but current quantum chemistry calculations fail to provide useful virtual orbitals, making it challenging to explore various processes such as photochemical reactions, electron attachment, reduction, or excitation processes. The LUMO obtained from the self-consistent field (SCF) solution can not be relied upon and needs to be identified as they are often present among the continuum states having almost similar energies. The nuclear charge stabilization method has been proven useful in identifying LUMO. Herein, we have proposed the application of parametric equations of motion (PEM) in conjunction with nuclear charge stabilization method to identify the LUMO obtained from the SCF solution exhibiting stability with different basis sets including diffuse functions.

Nanoscale core-shell structure and recrystallization of swift heavy ion tracks in SrTiO3.

It is widely accepted that the interaction of swift heavy ions with many complex oxides is predominantly governed by the electronic energy loss that gives rise to nanoscale amorphous ion tracks along the penetration direction. The question of how electronic excitation and electron-phonon coupling affect the atomic system through defect production, recrystallization, and strain effects has not yet been fully clarified. To advance the knowledge of the atomic structure of ion tracks, we irradiated single crystalline SrTiO3 with 629 MeV Xe ions and performed comprehensive electron microscopy investigations complemented by molecular dynamics simulations. This study shows discontinuous ion-track formation along the ion penetration path, comprising an amorphous core and a surrounding few monolayer thick shell of strained/defective crystalline SrTiO3. Using machine-learning-aided analysis of atomic-scale images, we demonstrate the presence of 4-8% strain in the disordered region interfacing with the amorphous core in the initially formed ion tracks. Under constant exposure of the electron beam during imaging, the amorphous part of the ion tracks readily recrystallizes radially inwards from the crystalline-amorphous interface under the constant electron-beam irradiation during the imaging. Cation strain in the amorphous region is observed to be significantly recovered, while the oxygen sublattice remains strained even under the electron irradiation due to the present oxygen vacancies. The molecular dynamics simulations support this observation and suggest that local transient heating and annealing facilitate recrystallization process of the amorphous phase and drive Sr and Ti sublattices to rearrange. In contrast, the annealing of O atoms is difficult, thus leaving a remnant of oxygen vacancies and strain even after recrystallization. This work provides insights for creating and transforming novel interfaces and nanostructures for future functional applications.

International Society for Cell & Gene Therapy Stem Cell Engineering Committee report on the current state of hematopoietic stem and progenitor cell-based genomic therapies and the challenges faced.

Genetic manipulation of hematopoietic stem cells (HSCs) is being developed as a therapeutic strategy for several inherited disorders. This field is rapidly evolving with several novel tools and techniques being employed to achieve desired genetic changes. While commercial products are now available for sickle cell disease, transfusion-dependent ß-thalassemia, metachromatic leukodystrophy and adrenoleukodystrophy, several challenges remain in patient selection, HSC mobilization and collection, genetic manipulation of stem cells, conditioning, hematologic recovery and post-transplant complications, financial issues, equity of access and institutional and global preparedness. In this report, we explore the current state of development of these therapies and provide a comprehensive assessment of the challenges these therapies face as well as potential solutions.

Developmental delay can precede neurologic regression in early onset metachromatic leukodystrophy.

OBJECTIVE: Metachromatic leukodystrophy (MLD) is a rare neurodegenerative disorder. Emerging therapies are most effective in the presymptomatic phase, and thus defining this window is critical. We hypothesize that early development delay may precede developmental plateau. With the advent of presymptomatic screening platforms and transformative therapies, it is essential to define the onset of neurologic disease. METHODS: The specific ages of gain and loss of developmental milestones were captured from the medical records of individuals affected by MLD. Milestone acquisition was characterized as: on target (obtained before the age limit of 90th percentile plus 2 standard deviations compared to a normative dataset), delayed (obtained after 90th percentile plus 2 standard deviations), or plateau (skills never gained). Regression was defined as the age at which skills were lost. LI-MLD was defined by age at onset before 2.5 years. RESULTS: Across an international cohort, 351 subjects were included (n = 194 LI-MLD subcohort). The median age at presentation of the LI-MLD cohort was 1.4 years (25th-75th %ile: 1.0-1.5). Within the LI-MLD cohort, 75/194 (39%) had developmental delay (or plateau) prior to MLD clinical presentation. Among the LI-MLD cohort with a minimum of 1.5 years of follow-up (n = 187), 73 (39.0%) subjects never attained independent ambulation. Within LI-MLD + delay subcohort, the median time between first missed milestone target to MLD decline was 0.60 years (maximum distance from delay to onset: 1.9 years). INTERPRETATION: Early developmental delay precedes regression in a subset of children affected by LI-MLD, defining the onset of neurologic dysfunction earlier than previously appreciated. The use of realworld data prior to diagnosis revealed an early deviation from typical development. Close monitoring for early developmental delay in presymptomatic individuals may help in earlier diagnosis with important consequences for treatment decisions.

Biosynthesis of silver nanoparticle from flower extract of Dillenia indica and its efficacy as antibacterial and antioxidant.

Dillenia indica is a medicinal tree of the Dilleniaceae and its flower extract was used for the synthesis of silver nanoparticle (AgNPs). The optimal conditions for AgNPs synthesis were as such: 2 mM AgNO3, pH 4.5 and 48-h reaction time. The characteristic band of AgNPs was observed at the wavelength of 435 nm by UV-visible spectroscopic study. Fourier-transform infrared (FTIR) analysis depicted the involvement of several functional groups of plant extracts in the synthesis of AgNPs. Nanoparticles were mostly spherical shaped and uniformly distributed, when observation was made by Transmission electron microscopy (TEM). Energy Dispersive X-Ray (EDX) showed absorption peak approximately at 3 keV thus confirmed the presence of silver metal in AgNP. X-ray diffraction (XRD) investigation and selected area electron diffraction (SAED) patterns showed the crystalline nature of the AgNPs. Dynamic light scattering (DLS) analysis exhibited average size of the nanoparticles as 50.17 nm with a polydispersity index (PDI) value of 0.298. The zeta potential of nanoparticles was observed as -24.9 mV. To assess antibacterial activity, both AgNPs alone or its combination with the antibiotic were tried against six pathogenic bacteria. The combination of AgNPs with antibiotic was maximum effective against Shigella boydii (16.07 ± 0.35) and Klebsiella pneumoniae (15.03 ± 0.20). AgNPs alone showed maximum inhibition for both Gram-positive bacteria: methicillin-resistant Staphylococcus aureus (19.97 ± 0.20 mm) and Enterococcus faecium (19.80 ± 0.15 mm). Maximum inhibition of Enterobactor cloacae and Pseudomonas aeruginosa was observed by antibiotic taken alone. Evaluation through 2,2-diphenyl-1-picrylhydrazyl (DPPH) and DNA nicking assays demonstrated the antioxidant capabilities of the nanoparticles.

Unveiling perceptions regarding post mastectomy breast reconstruction: A questionnaire-based survey of patients from central India.

INTRODUCTION: Post mastectomy breast reconstruction uptake remains low in the developing countries. We examined patient perspectives about it in a cohort of Indian breast cancer patients. METHODS: This prospective study was conducted at a tertiary care center in central India. All post mastectomy patients for breast cancer were interviewed via a survey questionnaire to assess their perspective regarding post mastectomy breast reconstruction. RESULTS: None of the 192 patients underwent immediate or delayed reconstruction by the end of 24 months follow-up. Age, education level, occupation and marital status did not affect the uptake of post mastectomy breast reconstruction. The most common patient-reported reasons for not having reconstruction were the desire to avoid additional surgery and the belief that it was not important (80% for each). System related factors such as additional cost of surgery and additional length of stay were reported to be important by 55% and 65% patients respectively. CONCLUSION: Our survey of 192 post mastectomy breast cancer patients showed that none opted for post mastectomy reconstruction, suggesting significant barriers to it. Understanding and addressing these barriers are crucial to ensuring comprehensive care for these breast cancer patients.

Nanoparticles as a Tool for Alleviating Plant Stress: Mechanisms, Implications, and Challenges.

Plants, being sessile, are continuously exposed to varietal environmental stressors, which consequently induce various bio-physiological changes in plants that hinder their growth and development. Oxidative stress is one of the undesirable consequences in plants triggered due to imbalance in their antioxidant defense system. Biochemical studies suggest that nanoparticles are known to affect the antioxidant system, photosynthesis, and DNA expression in plants. In addition, they are known to boost the capacity of antioxidant systems, thereby contributing to the tolerance of plants to oxidative stress. This review study attempts to present the overview of the role of nanoparticles in plant growth and development, especially emphasizing their role as antioxidants. Furthermore, the review delves into the intricate connections between nanoparticles and plant signaling pathways, highlighting their influence on gene expression and stress-responsive mechanisms. Finally, the implications of nanoparticle-assisted antioxidant strategies in sustainable agriculture, considering their potential to enhance crop yield, stress tolerance, and overall plant resilience, are discussed.

The Effect of Pneumoperitoneum on the Ankle-brachial Index of the Patients Undergoing Laparoscopic Cholecystectomy: An Observational Study.

Background: Improvement in the perioperative care has led to increased use of minimally invasive surgeries. Multiple physiological changes during minimally invasive surgeries are attributed to the creation of pneumoperitoneum. Materials and Methods: One hundred and nine patients who underwent laparoscopic cholecystectomy at a tertiary care hospital in north India meeting the inclusion and exclusion criteria were enrolled. Results: Out of the total 109 patients, 13 were males and 96 females (M:F = 1:7.3), the mean basal metabolic rate was 28.95 kg/m2. The mean systolic and diastolic blood pressure of the upper limb were 134.33 + 17.545 and 80.69 + 11.59 respectively. The mean systolic and diastolic blood pressure in lower limb (LL) were 142.32 + 21.552 and 79.44 + 11.94, respectively. Significant rise in the SBP was noticed in LL at the time of creation of Pneumoperitoneum and after changing the position for surgery (P < 0.05). The diastolic pressure in the LL rises significantly in the LL after creation of pneumoperitoneum, at induction, after reverse Trendelenburg position and extubation (P < 0.05). The mean arterial pressure increased significantly in the LL after the creation of pneumoperitoneum and persisted till the extubation (P < 0.05). A significant rise of ankle-brachial index (ABI) was observed in the patients after the creation of pneumoperitoneum and it remained significant till 15 min into surgery (P < 0.05). There was no correlation of ABI with weight and age of the patients on Pearson correlation. Conclusion: There is rise in ABI of the patients undergoing laparoscopic cholecystectomy at the time of creation of pneumoperitoneum, after Trendelenburg position and 15 min into surgery.

Tissue-free liquid biopsies combining genomic and methylation signals for minimal residual disease detection in patients with early colorectal cancer from the UK TRACC Part B study.

PURPOSE: Absence of post-operative circulating tumour DNA (ctDNA) identifies resected colorectal cancer (CRC) patients with low recurrence risk for adjuvant chemotherapy (ACT) de-escalation. We present the largest resected CRC cohort to date with tissue-free minimal residual disease (MRD) detection. DESIGN: TRACC included stage I-III resectable CRC patients. Prospective longitudinal plasma collection for ctDNA occurred pre- and post-surgery, post-ACT, every 3m for year 1 and every 6m in years 2 and 3 with imaging annually. The Guardant Reveal assay evaluated genomic and methylation signals. The primary endpoint was 2yr recurrence free survival (RFS) by post-operative ctDNA detection. (NCT04050345) Results: Between December 2016 and August 2022, 1203 were patients enrolled. Plasma samples (n=997) from 214 patients were analysed. 143 patients were evaluable for the primary endpoint; 92 (64.3%) colon, 51 (35.7%) rectal; 2 (1.4%) stage I, 64 (44.8%) stage II, 77 (53.8%) stage III. Median follow-up was 30.3m (95% CI: 29.5-31.3). 2yr RFS was 91.1% in patients with ctDNA not detected post-operatively and 50.4% in those with ctDNA detected (HR 6.5 [2.96-14.5] p<0.0001). Landmark negative predictive value (NPV) was 91.2% (95% CI 83.9-95.9). Longitudinal sensitivity and specificity were 62.1% (95% CI 42.2-79.3) and 85.9% (95% CI 78.9-91.3) respectively. Median lead-time from ctDNA detection to radiological recurrence was 7.3m (IQR 3.3-12.5; n=9). CONCLUSIONS: Tissue-free MRD detection with longitudinal sampling predicts recurrence in stage I-III CRC without need for tissue sequencing. NPV is high supporting ACT de-escalation in patients with ctDNA not detected post-operatively, now being investigated in the UK TRACC Part C study.

Medial Scapular Body (MSB) Goutallier Classification - MRI based reliability and validity of evaluation of the Goutallier classification for grading fatty infiltration of the rotator cuff.

INTRODUCTION: The degree of atrophy and fatty infiltration of rotator cuff muscle belly is a key predictor for cuff repairability. Traditionally, Goutallier grading of fatty infiltration is assessed at sagittal scapular Y-view. Massive rotator cuff tears are associated with tendon retraction and medial retraction of cuff musculature, resulting in medialization of the muscle bulk. Thus, standard Y-view can misrepresent the region of interest and may misguide clinicians when assessing repairability. It is hypothesized that by assessing the muscle belly with multiple medial sagittal MRI sections at medial scapular body, the Medial Scapular Body - Goutallier Classification (MSB-GC) will improve reliability and repeatability giving a more representative approximation to the degree of fatty infiltration, as compared with original Y-view. METHODS: Fatty infiltration of the rotator cuff muscles were classified based on the Goutallier grade (0 to 4) at three defined sections section 1: original Y-view; section 2: level of suprascapular notch; section 3: three cm medial to suprascapular notch on MRI scans. Six sub-specialist fellowship trained shoulder surgeons, and three musculoskeletal radiologists independently evaluated deidentified MRI scans of included patients. RESULTS: Out of 80 scans, 78% (n=62) were massive cuff tears involving supraspinatus, infraspinatus and subscapularis tendon. Inter-observer reliability (consistency between observers) for Goutallier grade was excellent for all three predefined sections (range:0.87-0.95). Intra-observer reliability (repeatability) for Goutallier grade was excellent for all three sections and four rotator cuff muscles (range:0.83-0.97). There was a moderate to strong positive correlation of Goutallier grades between sections 1 and 3 and between sections 2 and 3 and these were statistically significant (p<0.001). There was a reduction in the severity of fatty infiltration on the Goutallier classification from sections 1 to 3 across all muscles. 42.5% of both supraspinatus and infraspinatus were downgraded by one, 20% of supraspinatus and 3.8% of infraspinatus were downgraded by 2 and 2.5% of supraspinatus were downgraded by 3. CONCLUSION: This study found that applying the Goutallier classification to more medial MRI sections (MSB-GC) resulted in assignment of lower grades for all rotator cuff muscles. Additionally, this method demonstrated excellent test-retest reliability and repeatability. Inclusion of a more medial view or whole scapula on MRI, especially in advanced levels of tear retraction, could be more reliable and representative for assessment of the degree of fatty infiltration within the muscle bulk that could help predict tear repairability and therefore improve clinical decision-making which should be studied further in clinical studies.

Quality Improvement in Neonatal Care: Successful Adoption of the Eat, Sleep, Console Protocol in a Rural Hospital Setting.

Introduction: The United States faces a growing burden of neonatal opioid withdrawal syndrome in rural hospitals. Traditional treatments often extend hospital stays and medication use. The Eat, Sleep, and Console (ESC) approach offers a new management strategy but is challenging in resource-limited settings. This study aimed to apply ESC in rural hospitals to reduce neonatal intensive care unit admissions, decrease length of stay (LOS) to under 7 days, and lower medication use by more than 80% within a year. Methods: Our quality improvement initiative at rural hospitals implemented a multimodal approach for in utero opioid-exposed infants, involving staff education, electronic medical record updates, and nonpharmacological care strategies. Data from January 2020 to December 2023 assessed treatment impact, including pharmacotherapy need and hospital stay lengths, using statistical process control for analysis. Results: After ESC implementation, the percentage of opioid-exposed infants receiving pharmacological treatment significantly decreased from 60.7% to 7.9%. The average LOS was reduced from 14.5 days to 5.25 days. These improvements persisted for 24 months, with no readmissions within 30 days of discharge. This approach also reduced hospital charges by over $5 million, demonstrating its clinical and financial effectiveness. Conclusions: The multidisciplinary approach successfully implemented ESC in a resource-limited setting, significantly reducing both the LOS and medication exposure for opioid-exposed infants while also saving significant healthcare costs. This successful model has been adopted by at least four regional rural hospitals, thus broadening the program's impact.

Efficacy of the omental roll-up technique in pancreaticojejunostomy to prevent postoperative pancreatic fistula after pancreaticoduodenectomy.

Backgrounds/Aims: Pancreaticoduodenectomy (PD) is being performed more frequently. A pancreaticojejunostomy (PJ) leak is the major determinant of patient outcomes. An omental flap around PJ might improve postoperative outcomes. Methods: A prospective randomized controlled trial was planned at PGIMER, Chandigarh. Fifty-eight patients meeting the criteria were included in the study. Group A underwent PD with omental roll-up and group B underwent standard PD. Results: The mean age of patients in group A was 57.1 ± 14.3 years and 51.2 ± 10.7 in group B. Jaundice (p = 0.667), abdominal pain (p = 0.69), and co-morbidities were equal among the groups. The body mass index of patients in group B was higher at 24.3 ± 5.4 kg/m2 (p = 0.03). The common bile duct diameter (12.6 ± 5.3 mm vs. 17.2 ± 10.3 mm, p = 0.13) and the pancreatic duct diameter (4.06 ± 2.01 mm vs. 4.60 ± 2.43 mm, p = 0.91) were comparable. The intraoperative blood loss (mL) was significantly higher in group B (233.33 ± 9.57 vs. 343.33 ± 177.14, p = 0.04). Drain fluid amylase levels on postoperative day (POD) 1 (p = 0.97) and POD3 (p = 0.92) were comparable. The rate of postoperative pancreatic fistula (POPF) grade A (p ≥ 0.99) and grade B (p = 0.54) were comparable. The mean postoperative length of stay among was similar (p = 0.89). Conclusions: An omental wrap can be performed without increase in complexity of the procedure. However, its utility in preventing POPFs and morbidity remains unclear.

Targeting VEGF-mediated blood-brain barrier disruption in advanced cerebral leukodystrophy.

The earliest clinical manifestation of cerebral adrenoleukodystrophy (CALD) is adrenal insufficiency (AI) characterized by elevations in ACTH and loss of cortisol. We showed high (though physiologically achievable) levels of ACTH increases endothelial permeability, increases anisotropy, and increases VEGF secretion. An ACBD1 knockout endothelial cell line had increased sensitivity to ACTH and VEGF. Inhibition of VEGF via application of anti-VEGF (bevacizumab) improved permeability. Six boys with advanced CALD were treated with bevacizumab combined with dexamethasone and ruxolitinib as immune suppressants. Most boys had decreases in gadolinium enhancement on MRI indicating improvement in endothelial function, though all boys continued to progress symptomatically.

Direct conversion of lignin-rich black liquor to activated carbon for supercapacitor electrodes.

The escalating industrialization trend underscores the imperative for sustainable waste management practices. The present investigation explores a sustainable methodology for managing the waste generated from the kraft process by directly converting it into activated carbon (BLAC) through a cost-effective hydrothermal-assisted activation method. The research involved a comparative analysis of BLAC with acid-washed black liquor lignin-derived activated carbon (ABLAC) and commercial lignin-derived activated carbon (SALAC). The analysis revealed that BLAC possesses a well-developed micro and mesoporous structure, yielding a significantly higher surface area of 2277.2 m2/g as compared to ABLAC (1260 m2/g) and SALAC (1558.4 m2/g). The presence of inherent alkali in the black liquor is the main factor influencing the surface area of the BLAC. Furthermore, it demonstrated impressive electrochemical performance, showing a specific capacitance value of 871.4 F/g at 1 A/g current density, positioning it as a formidable electrode material for supercapacitor applications. The proposed direct conversion strategy will eliminate the need for high-temperature pre­carbonization and additional lignin extraction, reducing chemical usage and presenting a greener approach.

Risk factors predicting need for the pediatric intensive care unit (PICU) post-hematopoietic cell transplant, PICU utilization, and outcomes following HCT: a single center retrospective analysis.

Hematopoietic cell transplant (HCT) is a curative treatment for multiple malignant and non-malignant disorders. While morbidity and mortality have decreased significantly over the years, some patients still require management in the pediatric intensive care unit (PICU) during their HCT course for additional respiratory, cardiovascular, and/or renal support. We retrospectively reviewed pediatric patients (0-18 years) who underwent HCT from January 2015-December 2020 at our institution to determine risk factors for PICU care and evaluate PICU utilization and outcomes. We also assessed pulmonary function testing (PFT) data to determine if differences were noted between PICU and non-PICU patients as well as potential evolution of pulmonary dysfunction over time. Risk factors of needing PICU care were lower age, lower weight, having an underlying inborn error of metabolism, and receiving busulfan-based conditioning. Nearly half of PICU encounters involved use of each of respiratory support types including high-flow nasal cannula, non-invasive positive pressure ventilation, and mechanical ventilation. Approximately one-fifth of PICU encounters involved renal replacement therapy. Pulmonary function test results largely did not differ between PICU and non-PICU patients at any timepoint aside from individuals who required PICU care having lower DLCO scores at one-year post-HCT. Future directions include consideration of combining our data with other centers for a multi-center retrospective analysis with the goal of gathering and reporting additional multi-center data to work toward continuing to decrease morbidity and mortality for patients undergoing HCT.

Evaluation of factors that act as barriers in conducting academic trials - An investigator's perception.

Background: Academic trials are essential in investigating health research questions relevant to the society. Only a few leading research institutions in India have been engaged in academic trials. Thus, there is a need to understand what factors dampen the spirit of the academician in conducting academic clinical trials. Aims and Objectives: The aim of the study is to evaluate the investigator's perception of obstacles to carrying out academic trials and to identify factors that will motivate investigators in conducting academic trials. Materials and Methods: We conducted a prospective observational study in a tertiary care hospital for 6 months. Faculty members working in academic institutes were selected. A structured questionnaire was designed for the study and administered using google forms. Responses were taken on a Likert scale. Validity and reliability assessments were carried out. Mann-Whitney test was applied to assess differences between demographic groups. P <0.05 was considered significant. Results: Most of the participants rated applying for research grants (76%), obtaining funding for the study and making arrangements for compensation for trial-related events (75%) as extremely challenging. We found that the degree of challenge is significantly lower in the faculty members who conducted clinical trials in the past as against those who did not (P = 0.00069). We also found that the degree of challenge is significantly higher in the faculty members with <10 years of experience than those with >10 years of experience (P = 0.00001). Conclusion: Thus, to conclude the challenges faced by investigators were at multiple levels, most common being applying for research grants and making arrangements for the funds for payment towards participation or study-related injury. Faculty members with exposure to conducting clinical trials and with experience of more than 10 years had perceived a reduced degree of challenges.

Impact of environmental temperature on the survival outcomes of breast cancer: A SEER-based study.

BACKGROUND: Experimental evidence in tumor-bearing mouse models shows that exposure to cool, that is, sub-thermoneutral environmental temperature is associated with a higher tumor growth rate and an immunosuppressive tumor immune microenvironment than seen at thermoneutral temperatures. However, the translational significance of these findings in humans is unclear. We hypothesized that breast cancer patients living in warmer climates will have better survival outcomes than patients living in colder climates. METHODS: A retrospective population-based analysis was conducted on 270,496 stage I-III breast cancer patients, who were retrieved from the Surveillance, Epidemiology and End Results (SEER) over the period from 1996 to 2017. The average annual temperature (AAT) was calculated based on city level data from the National Centers for Environmental Information. RESULTS: A total of 270, 496 patients were analyzed. Temperature as assessed in quartiles. After adjusting for potential confounders, patients who lived in the 3rd and 4th quartile temperature regions with AAT 56.7-62.5°F (3rd quartile) and > 62.5°F (4th quartile) had a 7% increase in the OS compared to patients living at AAT < 48.5°F (1st quartile) (HR 0.93, 95% CI 0.90-0.95 and HR 0.93, 95% CI 0.91-0.96, respectively). For DSS, When comparing AAT quartiles, patients living with AAT in the range of 56.7-62.5°F and > 62.5°F demonstrated a 7% increase each in DSS after adjustment (HR 0.93, 95% CI 0.90-0.96 and HR 0.93, 95% CI 0.90-0.96). CONCLUSIONS: Higher environmental temperatures are associated with significantly better OS and DSS in breast cancer patients. Future research is warranted to confirm this observation using large datasets to elucidate the underlying mechanisms and investigate novel therapeutic strategies to minimize this geographic disparity in clinical outcomes.

Development and validation of a preliminary multivariable diagnostic model for identifying unusual infections in hospitalized patients.

Diagnostic delay leads to poor outcomes in infections, and it occurs more often when the causative agent is unusual. Delays are attributable to failing to consider such diagnoses in a timely fashion. Using routinely collected electronic health record (EHR) data, we built a preliminary multivariable diagnostic model for early identification of unusual fungal infections and tuberculosis in hospitalized patients. We conducted a two-gate case-control study. Cases encompassed adult patients admitted to 19 Mayo Clinic enterprise hospitals between January 2010 and March 2023 diagnosed with blastomycosis, cryptococcosis, histoplasmosis, mucormycosis, pneumocystosis, or tuberculosis. Control groups were drawn from all admitted patients (random controls) and those with community-acquired infections (ID-controls). Development and validation datasets were created using randomization for dividing cases and controls (7:3), with a secondary validation using ID-controls. A logistic regression model was constructed using baseline and laboratory variables, with the unusual infections of interest outcome. The derivation dataset comprised 1043 cases and 7000 random controls, while the 451 cases were compared to 3000 random controls and 1990 ID-controls for validation. Within the derivation dataset, the model achieved an area under the curve (AUC) of 0.88 (95% confidence interval [CI]: 0.87-0.89) with a good calibration accuracy (Hosmer-Lemeshow P = 0.623). Comparable performance was observed in the primary (AUC = 0.88; 95% CI: 0.86-0.9) and secondary validation datasets (AUC = 0.84; 95% CI: 0.82-0.86). In this multicenter study, an EHR-based preliminary diagnostic model accurately identified five unusual fungal infections and tuberculosis in hospitalized patients. With further validation, this model could help decrease time to diagnosis.

The Use of Glenoid Structural Allografts for Glenoid Bone Defects in Reverse Shoulder Arthroplasty.

Background: The use of reverse shoulder arthroplasty as a primary and revision implant is increasing. Advances in implant design and preoperative surgical planning allow the management of complex glenoid defects. As the demand for treating severe bone loss increases, custom allograft composites are needed to match the premorbid anatomy. Baseplate composite structural allografts are used in patients with eccentric and centric defects to restore the glenoid joint line. Preserving bone stock is important in younger patients where a revision surgery is expected. The aim of this article is to present the assessment, planning, and indications of femoral head allografting for bony defects of the glenoid. Methods: The preoperative surgical planning and the surgical technique to execute the plan with a baseplate composite graft are detailed. The preliminary clinical and radiological results of 29 shoulders which have undergone this graft planning and surgical technique are discussed. Clinical outcomes included visual analogue score of pain (VAS), American Shoulder and Elbow Surgeons score (ASES), Constant-Murley score (CS), satisfaction before and after operation, and active range of motion. Radiological outcomes included graft healing and presence of osteolysis or loosening. Results: The use of composite grafts in this series has shown excellent clinical outcomes, with an overall graft complication rate in complex bone loss cases of 8%. Conclusion: Femoral head structural allografting is a valid and viable surgical option for glenoid bone defects in reverse shoulder arthroplasty.

En bloc resection followed by gluteal advancement flap for sacral Ewing's sarcoma: A novel technique.

Ewing's sarcoma is a rare and highly aggressive bone tumor primarily affecting children and adolescents. It commonly presents in the pelvic and axial skeleton, with sacral involvement posing unique challenges due to its intricate anatomical location. This report details the case of an 18-year-old male with sacral Ewing's sarcoma, emphasizing the diagnostic, surgical, and reconstructive aspects of management. The patient presented with lower back pain, lower limb weakness, and urinary incontinence, which prompted an extensive diagnostic evaluation. Magnetic resonance imaging and computed tomography scans revealed a large lytic mass extending from the S2 vertebra to the coccyx invading the presacral space. Biopsy confirmed the diagnosis of Ewing's sarcoma, characterized by the EWS-FLI1 type 1 translocation. A multidisciplinary team comprising neurosurgeons, colorectal surgeons, and plastic surgeons was formulated. En bloc resection of the tumor, lumbopelvic fixation, and soft-tissue reconstruction using bilateral gluteus maximus advancement flaps were successfully performed. The procedure aimed to address both the oncological and functional aspects of the patient's condition. Chemotherapy and radiotherapy were administered as adjuvant therapies. At 2-year follow-up, the patient was ambulating independently with no residual tumor on imaging. This case highlights the complex nature of sacral Ewing's sarcoma and underscores the importance of a multidisciplinary approach. The described surgical technique, including the innovative use of gluteus maximus advancement flaps for soft-tissue reconstruction, contributes to reducing wound complications and promoting successful patient outcomes. The presented approach serves as a valuable addition to the armamentarium of treatment options for this challenging malignancy.