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1.
Nat Commun ; 15(1): 3994, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38734761

ABSTRACT

NADPH oxidase 5 (NOX5) catalyzes the production of superoxide free radicals and regulates physiological processes from sperm motility to cardiac rhythm. Overexpression of NOX5 leads to cancers, diabetes, and cardiovascular diseases. NOX5 is activated by intracellular calcium signaling, but the underlying molecular mechanism of which - in particular, how calcium triggers electron transfer from NADPH to FAD - is still unclear. Here we capture motions of full-length human NOX5 upon calcium binding using single-particle cryogenic electron microscopy (cryo-EM). By combining biochemistry, mutagenesis analyses, and molecular dynamics (MD) simulations, we decode the molecular basis of NOX5 activation and electron transfer. We find that calcium binding to the EF-hand domain increases NADPH dynamics, permitting electron transfer between NADPH and FAD and superoxide production. Our structural findings also uncover a zinc-binding motif that is important for NOX5 stability and enzymatic activity, revealing modulation mechanisms of reactive oxygen species (ROS) production.


Subject(s)
Calcium , NADPH Oxidase 5 , NADP , Humans , Binding Sites , Calcium/metabolism , Cryoelectron Microscopy , Electron Transport , Enzyme Activation , Flavin-Adenine Dinucleotide/metabolism , Molecular Dynamics Simulation , NADP/metabolism , NADPH Oxidase 5/metabolism , NADPH Oxidase 5/genetics , NADPH Oxidase 5/chemistry , Protein Binding , Reactive Oxygen Species/metabolism , Superoxides/metabolism , Zinc/metabolism
2.
bioRxiv ; 2024 May 11.
Article in English | MEDLINE | ID: mdl-38765983

ABSTRACT

Ribosomal RNA modifications in prokaryotes have been sporadically studied, but there is a lack of a comprehensive picture of modification sites across bacterial phylogeny. B. subtilis is a preeminent model organism for gram-positive bacteria, with a well-annotated and editable genome, convenient for fundamental studies and industrial use. Yet remarkably, there has been no complete characterization of its rRNA modification inventory. By expanding modern MS tools for the discovery of RNA modifications, we found a total of 25 modification sites in 16S and 23S rRNA of B. subtilis, including the chemical identity of the modified nucleosides and their precise sequence location. Furthermore, by perturbing large subunit biogenesis using depletion of an essential factor RbgA and measuring the completion of 23S modifications in the accumulated intermediate, we provide a first look at the order of modification steps during the late stages of assembly in B. subtilis. While our work expands the knowledge of bacterial rRNA modification patterns, adding B. subtilis to the list of fully annotated species after E. coli and T. thermophilus, in a broader context, it provides the experimental framework for discovery and functional profiling of rRNA modifications to ultimately elucidate their role in ribosome biogenesis and translation.

3.
NPJ Digit Med ; 7(1): 131, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38762669

ABSTRACT

Subjectivity and ambiguity of visual field classification limits the accuracy and reliability of glaucoma diagnosis, prognostication, and management decisions. Standardised rules for classifying glaucomatous visual field defects exist, but these are labour-intensive and therefore impractical for day-to-day clinical work. Here a web-application, Glaucoma Field Defect Classifier (GFDC), for automatic application of Hodapp-Parrish-Anderson, is presented and validated in a cross-sectional study. GFDC exhibits perfect accuracy in classifying mild, moderate, and severe glaucomatous field defects. GFDC may thereby improve the accuracy and fairness of clinical decision-making in glaucoma. The application and its source code are freely hosted online for clinicians and researchers to use with glaucoma patients.

4.
Prehosp Emerg Care ; : 1-4, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38687280

ABSTRACT

OBJECTIVE: The prehospital treatment for stable patients with atrial fibrillation with rapid ventricular response is rate-controlling agents such as calcium channel blockers, often diltiazem given as a bolus. At our agency we encourage the use of a bolus given via the infusion pump over two to four minutes immediately followed by a maintenance infusion, given concerns of recurrent tachycardia or hypotension secondary to rapid bolus administration. We examined if administering a bolus and infusion via an infusion pump shows better heart rate (HR) control at arrival to the emergency department (ED) compared with administration of a bolus only, while maintaining hemodynamic stability during transport. We also analyzed if a patient received a second bolus within 60 min of arrival to the ED. METHODS: We used a retrospective propensity-matched cohort of prehospital patients with atrial fibrillation for whom diltiazem was administered, from 1/1/2018 to 12/31/2021, in our system of 10 New Jersey paramedic units. We analyzed the age, gender, and initial HR and used it to match groups. We analyzed the mode and time of administration, dosage of the bolus, and presence of hypotension prehospitally. RESULTS: The matched groups contained 145 patients who received a prehospital diltiazem bolus only (BO) and 146 patients who received a diltiazem bolus and infusion (BI). There was no significant difference between the mean change in HR from initial paramedic arrival to ED arrival between the two groups (BO 38 vs. BI 34, p = 0.16). There was no significant difference in the need for a second bolus within the first 60 min of arrival to the ED (BO 9.7% vs. BI 11.6%, p = 0.30). Patients in the BO group were more likely to experience prehospital hypotension then in the BI group (BO 17.2% vs BI 8.2%, p = 0.01), despite receiving smaller initial bolus doses (BO 14.2 mg vs. BI 17.4 mg, p < 0.001). CONCLUSION: Our results show no significant differences in HR control or need for repeat bolus at the ED with the use of a diltiazem infusion following a diltiazem bolus. However, even when administering larger boluses, the use of an infusion pump resulted in less hypotension.

5.
PLOS Digit Health ; 3(4): e0000341, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38630683

ABSTRACT

Large language models (LLMs) underlie remarkable recent advanced in natural language processing, and they are beginning to be applied in clinical contexts. We aimed to evaluate the clinical potential of state-of-the-art LLMs in ophthalmology using a more robust benchmark than raw examination scores. We trialled GPT-3.5 and GPT-4 on 347 ophthalmology questions before GPT-3.5, GPT-4, PaLM 2, LLaMA, expert ophthalmologists, and doctors in training were trialled on a mock examination of 87 questions. Performance was analysed with respect to question subject and type (first order recall and higher order reasoning). Masked ophthalmologists graded the accuracy, relevance, and overall preference of GPT-3.5 and GPT-4 responses to the same questions. The performance of GPT-4 (69%) was superior to GPT-3.5 (48%), LLaMA (32%), and PaLM 2 (56%). GPT-4 compared favourably with expert ophthalmologists (median 76%, range 64-90%), ophthalmology trainees (median 59%, range 57-63%), and unspecialised junior doctors (median 43%, range 41-44%). Low agreement between LLMs and doctors reflected idiosyncratic differences in knowledge and reasoning with overall consistency across subjects and types (p>0.05). All ophthalmologists preferred GPT-4 responses over GPT-3.5 and rated the accuracy and relevance of GPT-4 as higher (p<0.05). LLMs are approaching expert-level knowledge and reasoning skills in ophthalmology. In view of the comparable or superior performance to trainee-grade ophthalmologists and unspecialised junior doctors, state-of-the-art LLMs such as GPT-4 may provide useful medical advice and assistance where access to expert ophthalmologists is limited. Clinical benchmarks provide useful assays of LLM capabilities in healthcare before clinical trials can be designed and conducted.

6.
Eye (Lond) ; 38(8): 1581-1585, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38341494

ABSTRACT

OBJECTIVE: FFA is a well-established investigation for the diagnosis of optic nerve abnormalities, requiring an intravenous cannula and extended imaging acquisition time. Cannulation can present a challenge in paediatric patients and whilst oral FFA has been used for decades, it has been limited by imaging technology and unconfirmed image acquisition timings. For years, we have used a modern ultra-widefield retinal camera, and established imaging time-points to demonstrate dynamic optic nerve head changes upon ingestion of fluorescein and collected a database of oFFA images for various presentations. METHODS: Using an established protocol, optic nerve colour images were obtained, followed by oral administration of fluorescein dye. The optic nerves are then imaged at established intervals. An interpretation of oFFA tutorial was delivered to consultant ophthalmologists and trainees. Subsequently, these groups were assessed using a series of fifteen cases with the sensitivity and specificity of the test determined. RESULTS: Our study presents a series of images and descriptions for common optic nerve abnormalities in paediatric populations. In the interpretation part of the study, overall sensitivity of 76.8% in the consultant group vs 63.3% in the combined consultant + trainees and specificity of 87.5% vs 68.4% in the combined group. CONCLUSIONS: This is the first study that describes characteristic features of several common, and serious, optic nerve abnormalities specifically for oFFA interpretation in a paediatric population. It also highlights the rapid accumulation of oFFA interpretation skills in non-specialist consultant and trainee ophthalmologists such as to obtain a high diagnostic accuracy with high sensitivity and specificity.


Subject(s)
Fluorescein Angiography , Optic Nerve Diseases , Humans , Child , Fluorescein Angiography/methods , Male , Female , Child, Preschool , Optic Nerve Diseases/diagnosis , Optic Nerve Diseases/diagnostic imaging , Fluorescein/administration & dosage , Administration, Oral , Adolescent , Infant , Optic Disk/diagnostic imaging , Sensitivity and Specificity , Fluorescent Dyes/administration & dosage , Optic Nerve/diagnostic imaging , Optic Nerve/abnormalities
7.
Chem Biodivers ; 20(7): e202300331, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37337355

ABSTRACT

BACKGROUND: A very high rate of resistance causes health-care-associated and community-acquired infections. E. coli is one of the nine pathogens of highest concern to most of the antibiotics and other class of antimicrobials. OBJECTIVE: The objective of the present study is to develop novel thiophene derivatives using 2D QSAR and in silico approach for E. coli resistance. METHODS: Substituted thiophene series reported by Nishu Singla et al., were taken for QSAR analysis. From the results, a set of 15 new compounds were designed. A complete in silico analysis has been done using PADEL, Autodock vina, Swiss ADME, Protox II software. RESULTS: The designed compounds obey the Lipinski's rule of five and were known to have excellent inhibitory action (pIC50 values -0.87 to -1.46) which is similar to the most active compound of the data set (pIC50 -0.69) taken for the study. The bioavailability score (0.65) with no toxicity representing that the designed compounds are suitable for oral administration. CONCLUSION: The designed compounds are inactive for mutagenicity and cytotoxicity and ADMET studies states that these molecules are likely to be orally bioavailable and could be easily transported, diffused, and absorbed. So, the designed compounds will definitely serve as a lead antibacterial agent for E. coli resistance.


Subject(s)
Anti-Infective Agents , Quantitative Structure-Activity Relationship , Lactams , Thiophenes/pharmacology , Escherichia coli , Drug Design , Anti-Infective Agents/pharmacology , Anti-Bacterial Agents/pharmacology , Molecular Docking Simulation
8.
Cureus ; 15(1): e34194, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36843733

ABSTRACT

BACKGROUND: A variety of surgical approaches (anterior vs. posterior vs. anterior and posterior) are available for Isthmic Spondylolisthesis (IS). The aim of our study was to analyze the pattern and 30-day outcomes in patients undergoing different surgical approaches for single-level IS. MATERIALS AND METHODS: National Surgical Quality Improvement Program (NSQIP) database was queried using the ICD-9/10 and CPT 4th edition, from 2012 to 2020. We included patients 18-65 years of age who underwent spine fusions for IS. Outcomes were a length of stay (LOS), discharge disposition, 30-day complications, hospital readmission, and complication rates. RESULTS: Of 1036 patients who underwent spine fusions for IS, 838 patients (80.8%) underwent posterior only, 115 patients (11.1%) underwent anterior-only fusions and the rest (8%) underwent combined anterior and posterior procedures. 60% of patients in the posterior-only cohort had at least one comorbidity compared to 54% of patients in anterior only and 55% of patients in the combined cohort. No statistically significant differences in terms of LOS (3 days each) and discharge to home (96% vs. 93% vs. 94%) were noted among the anterior-only, posterior-only and combined cohorts, p> 0.05. In terms of 30-day complication rates, combined procedures had slightly higher rates (13%) compared to anterior (10%) or posterior-only (9%) procedures. CONCLUSION: Posterior-only fusions were performed in 80% of patients with IS. No differences in terms of LOS, discharge disposition to home, 30-day complications, hospital readmission and reoperation rates were noted across the cohorts.

9.
Nucleic Acids Res ; 51(1): 463-474, 2023 01 11.
Article in English | MEDLINE | ID: mdl-36583344

ABSTRACT

DNA polymerase θ (Pol θ) plays an essential role in the microhomology-mediated end joining (MMEJ) pathway for repairing DNA double-strand breaks. However, the mechanisms by which Pol θ recognizes microhomologous DNA ends and performs low-fidelity DNA synthesis remain unclear. Here, we present cryo-electron microscope structures of the polymerase domain of Lates calcarifer Pol θ with long and short duplex DNA at up to 2.4 Šresolution. Interestingly, Pol θ binds to long and short DNA substrates similarly, with extensive interactions around the active site. Moreover, Pol θ shares a similar active site as high-fidelity A-family polymerases with its finger domain well-closed but differs in having hydrophilic residues surrounding the nascent base pair. Computational simulations and mutagenesis studies suggest that the unique insertion loops of Pol θ help to stabilize short DNA binding and assemble the active site for MMEJ repair. Taken together, our results illustrate the structural basis of Pol θ-mediated MMEJ.


Subject(s)
DNA End-Joining Repair , DNA-Directed DNA Polymerase , Perciformes , DNA Breaks, Double-Stranded , DNA-Directed DNA Polymerase/metabolism , Perciformes/classification , Perciformes/metabolism , DNA Polymerase theta
11.
iScience ; 25(12): 105528, 2022 Dec 22.
Article in English | MEDLINE | ID: mdl-36465100

ABSTRACT

Mutations and defects in nuclear lamins can cause major pathologies, including inflammation and inflammatory diseases. Yet, the underlying molecular mechanisms are not known. We now report that the pro-inflammatory activation of macrophages, as induced by LPS or pathogenic E. coli, reduces Lamin-A/C levels thereby augmenting pro-inflammatory gene expression and cytokine secretion. We show that the activation of bone-marrow-derived macrophages (BMDMs) causes the phosphorylation and degradation of Lamin-A/C, as mediated by CDK1 and Caspase-6, respectively, necessary for upregulating IFN-ß expression. Enhanced IFN-ß expression subsequently increases pro-inflammatory gene expression via the IFN-ß-STAT axis. Pro-inflammatory gene expression was also amplified in the complete absence of Lamin-A/C. Alternatively, pharmacological inhibition of either Lamin-A/C phosphorylation or degradation significantly downregulated pro-inflammatory gene expression, as did the targeting of IFN-ß-STAT pathway members, i.e. phospho-STAT1 and phospho-STAT3. As Lamin-A/C is a previously unappreciated regulator of the pro-inflammatory macrophage response, our findings suggest novel opportunities to treat inflammatory diseases.

12.
APL Bioeng ; 6(3): 031502, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36051106

ABSTRACT

Many inflammatory diseases that are responsible for a majority of deaths are still uncurable, in part as the underpinning pathomechanisms and how to combat them is still poorly understood. Tissue-resident macrophages play pivotal roles in the maintenance of tissue homeostasis, but if they gradually convert to proinflammatory phenotypes, or if blood-born proinflammatory macrophages persist long-term after activation, they contribute to chronic inflammation and fibrosis. While biochemical factors and how they regulate the inflammatory transcriptional response of macrophages have been at the forefront of research to identify targets for therapeutic interventions, evidence is increasing that physical factors also tune the macrophage phenotype. Recently, several mechanisms have emerged as to how physical factors impact the mechanobiology of macrophages, from the nuclear translocation of transcription factors to epigenetic modifications, perhaps even DNA methylation. Insight into the mechanobiology of macrophages and associated epigenetic modifications will deliver novel therapeutic options going forward, particularly in the context of increased inflammation with advancing age and age-related diseases. We review here how biophysical factors can co-regulate pro-inflammatory gene expression and epigenetic modifications and identify knowledge gaps that require urgent attention if this therapeutic potential is to be realized.

14.
Neurosurgery ; 91(1): 103-114, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35377352

ABSTRACT

BACKGROUND: Anxiety and depression are associated with suboptimal outcomes, higher complications, and cost of care after elective spine surgery. The effect of combined anxiety-depression and preoperative antidepressant treatment in spinal fusion patients is not known. OBJECTIVE: To study the burden of combined anxiety-depression and its impact on healthcare utilization and costs in patients undergoing spinal fusion and to study the prevalence and impact of antidepressant treatment preoperatively. METHODS: This is a retrospective cohort study from the IBM MarketScan Research Database (2000-2018). Patients were studied in 7 different "phenotypes" of anxiety and depression based on combination of diagnoses and treatment. Outcome measures included healthcare utilization and costs from 1 year preoperatively to 2 years postoperatively. Bivariate and multivariable analyses have been reported. RESULTS: We studied 75 087 patients with a median age of 57 years. Patients with combined anxiety-depression were associated with higher preoperative and postoperative healthcare utilization and costs, as compared with anxiety or depression alone. The presence of depression in patients with and without anxiety disorder was a risk factor for postoperative opioid use and 2-year reoperation rates, as compared with anxiety alone. Patients with anxiety and/or depression on antidepressants are associated with significantly higher healthcare costs and opioid use. The adjusted 2-year reoperation rate was not significantly different between treated and untreated cohorts. CONCLUSION: Spine surgeons should use appropriate measures/questionnaires to screen depressed patients for anxiety and vice versa because the presence of both adds significant risk of higher healthcare utilization and costs over patients with 1 diagnosis, especially anxiety alone.


Subject(s)
Spinal Diseases , Spinal Fusion , Analgesics, Opioid/therapeutic use , Antidepressive Agents/therapeutic use , Anxiety/epidemiology , Anxiety Disorders/drug therapy , Anxiety Disorders/epidemiology , Comorbidity , Depression/epidemiology , Humans , Phenotype , Retrospective Studies , Spinal Diseases/etiology , Spinal Fusion/adverse effects
15.
Clin Spine Surg ; : E636-E642, 2022 03 29.
Article in English | MEDLINE | ID: mdl-35344518

ABSTRACT

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim was to compare 90-day and 2-year reimbursements for ≥2-level anterior cervical discectomy and fusion (mACDF), anterior cervical corpectomy and fusion (ACCF), posterior laminectomy and fusion (LF) and laminoplasty (LP) done for degenerative cervical myelopathy (DCM). SUMMARY OF BACKGROUND DATA: In DCM pathologies where there exists a clinical equipoise in approach selection, a randomized controlled trial found that an anterior approach did not significantly improve patient-reported outcomes over posterior approaches. In the era of value and bundled payments initiatives, cost profile of various approaches will form an important consideration for decision making. MATERIALS AND METHODS: IBM MarketScan Research Database (2005-2018) was used to study beneficiaries (30-75 y) who underwent surgery (mACDF, ACCF, LF, LP) for DCM. Index hospital stay (operating room, surgeon, hospital services) and postdischarge inpatient, outpatient and prescription medication payments have been used to simulate 90-day and 2-year bundled payment amounts, along with their distribution for each procedure. RESULTS: A total of 10,834 patients with median age of 54 years were included. The median 90-day payment was $46,094 (interquartile range: $34,243-$65,841) for all procedures, with LF being the highest ($64,542) and LP the lowest ($37,867). Index hospital was 62.4% (operating room: 46.6) and surgeon payments were 17.5% of the average 90-day bundle. There was significant difference in the index, 90-day and 2-year reimbursements and their distribution among procedures. CONCLUSION: In a national cohort of patients undergoing surgery for DCM, LP had the lowest complication rate, and simulated bundled reimbursements at 90 days and 2 years postoperatively. The lowest quartile 90-day payment for LF was more expensive than median amounts for mACDF, ACCF, and LP. If surgeons encounter scenarios of clinical equipoise in practice, LP is likely to result in maximum value as it is on an average 70% less expensive than LF over 90 days.

16.
Nucleic Acids Res ; 50(19): 10801-10816, 2022 10 28.
Article in English | MEDLINE | ID: mdl-35141754

ABSTRACT

RbgA is an essential protein for the assembly of the 50S subunit in Bacillus subtilis. Depletion of RbgA leads to the accumulation of the 45S intermediate. A strain expressing a RbgA variant with reduced GTPase activity generates spontaneous suppressor mutations in uL6. Each suppressor strain accumulates a unique 44S intermediate. We reasoned that characterizing the structure of these mutant 44S intermediates may explain why RbgA is required to catalyze the folding of the 50S functional sites. We found that in the 44S particles, rRNA helices H42 and H97, near the binding site of uL6, adopt a flexible conformation and allow the central protuberance and functional sites in the mutant 44S particles to mature in any order. Instead, the wild-type 45S particles exhibit a stable H42-H97 interaction and their functional sites always mature last. The dependence on RbgA was also less pronounced in the 44S particles. We concluded that the binding of uL6 pauses the maturation of the functional sites, but the central protuberance continues to fold. RbgA exclusively binds intermediates with a formed central protuberance and licenses the folding of the functional sites. Through this mechanism, RbgA ensures that the functional sites of the 50S mature last.


Ribosomal subunits in bacteria assemble according to energy landscapes comprised of multiple parallel pathways. In this study, the authors identified a critical maturation step in the late assembly stages of the large 50S ribosomal subunit in bacteria. This step represents a merging point where all parallel assembly pathways of the ribosomal particles converge. At this critical step, the convergent assembly intermediate that accumulates in cells exists in a 'locked' state, and its maturation is paused. The RbgA protein acts on this critical step to 'unlock' the last maturation steps involving folding of the functional sites. Through this mechanism, RbgA ensures that the functional sites of the 50S mature last.


Subject(s)
Ribosomal Proteins , Ribosome Subunits, Large, Bacterial , Ribosome Subunits, Large, Bacterial/metabolism , Ribosomal Proteins/genetics , Bacillus subtilis/genetics , Bacillus subtilis/metabolism , RNA, Ribosomal/metabolism , GTP Phosphohydrolases/metabolism
17.
J Neurosurg Spine ; : 1-8, 2022 Jan 14.
Article in English | MEDLINE | ID: mdl-35171836

ABSTRACT

OBJECTIVE: In degenerative cervical myelopathy (DCM) pathologies in which there exists a clinical equipoise in approach selection, a randomized controlled trial found that an anterior approach did not significantly improve patient-reported outcomes compared with posterior approaches. In this era of value and bundled payment initiatives, the cost profiles of various surgical approaches will form an important consideration in decision-making. The objective of this study was to compare 90-day and 2-year reimbursements for ≥ 2-level (multilevel) anterior cervical discectomy and fusion (mACDF), anterior cervical corpectomy and fusion (ACCF), posterior cervical laminectomy and fusion (LF), and cervical laminoplasty (LP) performed for DCM. METHODS: The IBM MarketScan research database (2005-2018) was used to study beneficiaries 30-75 years old who underwent surgery using four approaches (mACDF, ACCF, LF, or LP) for DCM. Demographics, index surgery length of stay (LOS), complications, and discharge disposition were compared. Index admission (surgeon, hospital services, operating room) and postdischarge inpatient (readmission, revision surgery, inpatient rehabilitation), outpatient (imaging, emergency department, office visits, physical therapy), and medication-related payments were described. Ninety-day and 2-year bundled payment amounts were simulated for each procedure. All payments are reported as medians and interquartile ranges (IQRs; Q1-Q3) and were adjusted to 2018 US dollars. RESULTS: A total of 10,834 patients, with a median age of 54 years, were included. The median 90-day payment was $46,094 (IQR $34,243-$65,841) for all procedures, with LF being the highest ($64,542) and LP the lowest ($37,867). Index hospital payment was 62.4% (surgery/operating room 46.6%) and surgeon payments were 17.5% of the average 90-day bundle. There were significant differences in the index, 90-day, and 2-year reimbursements and their distribution among procedures. CONCLUSIONS: In a national cohort of patients undergoing surgery for DCM, LP had the lowest complication rate and simulated bundled reimbursements at 90 days and 2 years postoperatively. The lowest quartile 90-day payment for LF was more expensive than median amounts for mACDF, ACCF, and LP. If surgeons encounter scenarios of clinical equipoise in practice, LP is likely to result in maximum value because it is 70% less expensive on average than LF over 90 days.

18.
J Minim Access Surg ; 18(3): 401-407, 2022.
Article in English | MEDLINE | ID: mdl-35046167

ABSTRACT

Background: Thoracoscopic enucleation of oesophageal leiomyomas has been adopted by many centres. The procedure when performed in prone position gives good results. The long-term outcome has not been reported earlier. This single-centre study establishes the role of this particular technique. Methods: A retrospective analysis of a prospectively maintained hospital database was performed and after following the study criteria eleven cases of oesophageal submucosal tumours were included in the study. All patients underwent thoracoscopic enucleation in the prone position by a single surgeon. Peri-operative data were recorded and patients followed up for a mean period of 78 months (range = 24-120 months). Results: Thoracoscopic enucleation in prone position was done for all patients with no conversions to an open procedure. Two patients had a mucosal rent during dissection that was repaired. There was no post-operative morbidity greater than Clavien-Dindo Grade 2. Long-term follow-up is available for eight patients (73%) with no recurrence of disease or symptoms. Conclusion: Oesophageal submucosal tumours (predominantly leiomyomas) are benign neoplasms with an indolent biological behaviour and deserve a procedure that would serve the purpose of minimal post-operative morbidity coupled with excellent outcome. Thoracoscopic enucleation in the prone position provides a physiological benefit that translates into better peri-operative outcomes without compromising the long-term outcome and should be the preferred form of treatment for oesophageal submucosal tumours.

19.
Hip Int ; 32(1): 131-139, 2022 Jan.
Article in English | MEDLINE | ID: mdl-32538154

ABSTRACT

BACKGROUND: Discharge to an inpatient care facility (skilled-care or rehabilitation) has been shown to be associated with adverse outcomes following elective total joint arthroplasties. Current evidence with regard to hip fracture surgeries remains limited. METHODS: The 2015-2016 ACS-NSQIP database was used to query for patients undergoing total hip arthroplasty, hemiarthroplasty and open reduction internal fixation for hip fractures. A total of 15,655 patients undergoing hip fracture surgery were retrieved from the database. Inpatient facility discharge included discharges to skilled-care facilities and inpatient rehabilitation units. Multi-variate regression analysis was used to assess for differences in 30-day post-discharge outcomes between home-discharge versus inpatient care facility discharge, while adjusting for baseline differences between the 2 study populations. RESULTS: A total of 12,568 (80.3%) patients were discharged to an inpatient care facility. Discharge to an inpatient care facility was associated with higher odds of any complication (OR 2.03 [95% CI, 1.61-2.55]; p < 0.001), wound complications (OR 1.79 [95% CI, 1.10-2.91]; p = 0.019), cardiac complications (OR 4.49 [95% CI, 1.40-14.40]; p = 0.012), respiratory complication (OR 2.29 [95% CI, 1.39-3.77]; p = 0.001), stroke (OR 7.67 [95% CI, 1.05-56.29]; p = 0.045, urinary tract infections (OR 2.30 [95% CI, 1.52-3.48]; p < 0.001), unplanned re-operations (OR 1.37 [95% CI, 1.03-1.82]; p = 0.029) and readmissions (OR 1.38 [95% CI, 1.16-1.63]; p < 0.001) following discharge. CONCLUSION: Discharge to inpatient care facilities versus home following hip fracture surgery is associated with higher odds of post-discharge complications, re-operations and readmissions. These results stress the importance of careful patient selection prior to discharge to inpatient care facilities to minimise the risk of complications.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Fractures , Aftercare , Arthroplasty, Replacement, Hip/adverse effects , Hip Fractures/epidemiology , Hip Fractures/surgery , Humans , Incidence , Inpatients , Patient Discharge , Patient Readmission , Postoperative Complications/epidemiology , Risk Factors
20.
Hip Int ; 32(2): 239-245, 2022 Mar.
Article in English | MEDLINE | ID: mdl-32866054

ABSTRACT

INTRODUCTION: With limited evidence on national incidences of hip arthroscopy in the elderly population, the current study aims to investigate trends of primary hip arthroscopies being performed in the elderly population, using the US Medicare database, and determine risk factors for conversion to total hip arthroplasty (THA). METHODS: Medicare Standard Analytic Files were queried using CPT codes to retrieve records of primary hip arthroscopies done for degenerative pathology during 2005-2014. Overall and age-stratified trends in the incidence of hip arthroscopy over time were analysed. Kaplan Meier survival curves were used to assess the overall 2-year conversion rate to a THA. Cox regression analysis was implemented to study risk factors for conversion. RESULTS: 8100 primary hip arthroscopies for degenerative pathology were performed during 2005-2014. There was a 280% increase in overall incidence of arthroscopy. The most commonly performed arthroscopic procedure was for chondroplasty and/or resection of labrum, with 4712 (58.1%) procedures. Around 18.5% patients underwent arthroplasty within 2 years after primary arthroscopy. Following Cox regression an existing diagnosis of osteoarthritis, ages 65-69, ages 70-74, and arthroscopies done in the West were associated with higher risk of conversion to THA within 2 years. Undergoing a repeat arthroscopy was not significantly associated with a higher risk of conversion. CONCLUSIONS: Despite inconclusive clinical evidence, hip arthroscopies are being increasingly used in patients older than 65 in the Medicare population. We conclude that patients in the age bracket of 65-74 years and with a pre-existing diagnosis of osteoarthritis, arthroscopy should be approached with caution.


Subject(s)
Arthroplasty, Replacement, Hip , Aged , Arthroplasty, Replacement, Hip/methods , Arthroscopy/methods , Hip Joint/surgery , Humans , Kaplan-Meier Estimate , Medicare , Risk Factors , United States/epidemiology
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