Availability and utilization of endoscopic retrograde cholangiopancreatography at children's hospitals.

OBJECTIVES: No study has explored whether availability of endoscopic retrograde cholangiopancreatography (ERCP) is adequate and equitable across US children's hospitals. We hypothesized that ERCP availability and utilization differs by geography and patient factors. METHODS: Healthcare encounter data from 2009 to 2019 on children with pancreatic and biliary diseases from the Pediatric Health Information System were analyzed. ERCP availability was defined as treatment at a hospital that performed pediatric ERCP during the year of service. RESULTS: From 2009 to 2019, 37,946 children (88,420 encounters) had a potential pancreatic or biliary indication for ERCP; 7066 ERCPs were performed. The commonest pancreatic diagnoses leading to ERCP were chronic (47.2%) and acute pancreatitis (43.2%); biliary diagnoses were calculus (68.3%) and obstruction (14.8%). No ERCP was available for 25.0% of pancreatic encounters and 8.1% of biliary encounters. In multivariable analysis, children with public insurance, rural residence, or of Black race were less likely to have pancreatic ERCP availability; those with rural residence or Asian race were less likely to have biliary ERCP availability. Black children or those with public insurance were less likely to undergo pancreatic ERCP where available. Among encounters for calculus or obstruction, those of Black race or admitted to hospitals in the West were less likely to undergo ERCP when available. CONCLUSIONS: One-in-four children with pancreatic disorders and one-in-12 with biliary disorders may have limited access to ERCP. We identified racial and geographic disparities in availability and utilization of ERCP. Further studies are needed to understand these differences to ensure equitable care.

Index admission cholecystectomy for acute cholecystitis reduces 30-day readmission rates in pediatric patients.

BACKGROUND: Adult patients with cholecystitis who do not undergo cholecystectomy on index admission have worse outcomes, however, there is a paucity of data of the role of cholecystectomy during index hospitalization in the pediatric population. Our aim was to determine outcomes and readmission rates among pediatric patients with cholecystitis who underwent index cholecystectomy versus those who did not. METHODS: We performed a retrospective study of pediatric (< 18 years old) admitted with acute cholecystitis (AC) requiring hospitalization using the 2018 National Readmission Database (NRD). Exclusion criteria included age ≥ 18 years and death on index admission. Multivariable logistic regression was performed to identify factors associated with 30-day readmissions. RESULTS: We identified 550 unique index acute cholecystitis admissions. Mean age was 14.6 ± 3.0 years. Majority of patients were female (n = 372, 67.6%). Index cholecystectomy was performed in (n = 435, 79.1%) of cases. Thirty-day readmission rate was 2.8% in patients who underwent index cholecystectomy and 22.6% in those who did not (p < 0.001). On multivariable analysis, patients who did not undergo index cholecystectomy had higher odds of 30-day readmission than those who did not (OR 10.66, 95% CI 5.06-22.45, p < 0.001). Female patients also had higher odds of 30-day readmission compared to males (OR 3.37, 95% CI 1.31-8.69). CONCLUSIONS: Patients who did not undergo index cholecystectomy had over tenfold increase in odds of 30-day readmission. Further research is required to understand the barriers to index cholecystectomy despite society recommendations and clear clinical benefit.

Index admission cholecystectomy for biliary acute pancreatitis or choledocholithiasis reduces 30-day readmission rates in children.

BACKGROUND: Adult patients with biliary acute pancreatitis (BAP) or choledocholithiasis who do not undergo cholecystectomy on index admission have worse outcomes. Given the paucity of data on the impact of cholecystectomy during index hospitalization in children, we examined readmission rates among pediatric patients with BAP or choledocholithiasis who underwent index cholecystectomy versus those who did not. METHODS: Retrospective study of children (< 18 years old) admitted with BAP, without infection or necrosis (ICD-10 K85.10), or choledocholithiasis (K80.3x-K80.7x) using the 2018 National Readmission Database (NRD). Exclusion criteria were necrotizing pancreatitis with or without infected necrosis and death during index admission. Multivariable logistic regression was performed to identify factors associated with 30-day readmission. RESULTS: In 2018, 1122 children were admitted for index BAP (n = 377, 33.6%) or choledocholithiasis (n = 745, 66.4%). Mean age at admission was 13 (SD 4.2) years; most patients were female (n = 792, 70.6%). Index cholecystectomy was performed in 663 (59.1%) of cases. Thirty-day readmission rate was 10.9% in patients who underwent cholecystectomy during that index admission and 48.8% in those who did not (p < 0.001). In multivariable analysis, patients who underwent index cholecystectomy had lower odds of 30-day readmission than those who did not (OR 0.16, 95% CI 0.11-0.24, p < 0.001). CONCLUSIONS: Index cholecystectomy was performed in only 59% of pediatric patients admitted with BAP or choledocholithiasis but was associated with 84% decreased odds of readmission within 30 days. Current guidelines should be updated to reflect these findings, and future studies should evaluate barriers to index cholecystectomy.

Design, Synthesis of 3-(5-Substituted Phenyl-[1,3,4]oxadiazol-2-yl)-1H-indole and Its Microbial Activity.

Fischer indole synthesis of indole by using phenyl-hydrazine and acetaldehyde resulted 1H-Indole while phenyl-hydrazine reacted with malonaldehyde gives 1H-Indole-3-carbaldehyde. Also Vilsmeier-Haack formylation of 1H-Indole gives 1H-Indole-3-carbaldehyde. 1H-Indole-3-carbaldehyde were oxidized to form 1H-Indole-3-carboxylic acid. 1H-Indole reacted with excess of BuLi at -78 °C using dry ice also gives 1H-Indole-3-carboxylic acid. Obtained 1H-Indole-3-carboxylic acid was converted to ester and ester in to acid hydrazide. Finally 1H-Indole-3-carboxylic acid hydrazide reacted with substituted carboxylic acid gives microbial active indole substituted oxadiazoles. Synthesized compounds 9a-j showing promising in vitro anti microbial activities against S. aureus bacteria compared with Streptomycin. Compound 9a, 9f and 9g showing activities against E. coli compared with standards. Compound 9a and 9f are found potent active against B. subtilis compared with reference standard while compound 9a, 9c and 9j active against S. typhi.

Development and internal validation of clinical prediction models for outcomes of complicated intra-abdominal infection.

BACKGROUND: Complicated intra-abdominal infections (cIAIs) are associated with significant morbidity and mortality. The aim of this study was to describe the clinical characteristics of patients with cIAI in a multicentre study and to develop clinical prediction models (CPMs) to help identify patients at risk of mortality or relapse. METHODS: A multicentre observational study was conducted from August 2016 to February 2017 in the UK. Adult patients diagnosed with cIAI were included. Multivariable logistic regression was performed to develop CPMs for mortality and cIAI relapse. The c-statistic was used to test model discrimination. Model calibration was tested using calibration slopes and calibration in the large (CITL). The CPMs were then presented as point scoring systems and validated further. RESULTS: Overall, 417 patients from 31 surgical centres were included in the analysis. At 90 days after diagnosis, 17.3 per cent had a cIAI relapse and the mortality rate was 11.3 per cent. Predictors in the mortality model were age, cIAI aetiology, presence of a perforated viscus and source control procedure. Predictors of cIAI relapse included the presence of collections, outcome of initial management, and duration of antibiotic treatment. The c-statistic adjusted for model optimism was 0.79 (95 per cent c.i. 0.75 to 0.87) and 0.74 (0.73 to 0.85) for mortality and cIAI relapse CPMs. Adjusted calibration slopes were 0.88 (95 per cent c.i. 0.76 to 0.90) for the mortality model and 0.91 (0.88 to 0.94) for the relapse model; CITL was -0.19 (95 per cent c.i. -0.39 to -0.12) and - 0.01 (- 0.17 to -0.03) respectively. CONCLUSION: Relapse of infection and death after complicated intra-abdominal infections are common. Clinical prediction models were developed to identify patients at increased risk of relapse or death after treatment, these now require external validation.

Randomized controlled trial comparing the Franseen needle with the Fork-tip needle for EUS-guided fine-needle biopsy.

BACKGROUND AND AIMS: EUS-guided FNA primarily provides cytologic samples. EUS-guided fine-needle biopsy (FNB) with needles that provide histologic specimens may enhance diagnostic yield and facilitate accessory tissue staining. Several different needle designs are currently available and design superiority is unknown. We designed a randomized controlled trial to compare 2 commonly used EUS-FNB needles in their ability to provide histologic tissue samples (primary endpoint) and to reach an accurate diagnosis (secondary endpoint). METHODS: A total of 150 lesions from 134 patients (November 2018 to June 2019) were randomized 1:1 between biopsy with a Franseen needle and a Fork-tip needle. The groups were compared regarding the quality of the tissue samples and diagnostic accuracy. RESULTS: Of 150 lesions, 75 were pancreatic and 75 were other solid lesions in and around the GI tract. There was no statistically significant difference between the Franseen needle and the Fork-tip needle in the yield of adequate histologic samples, 71 of 75 (94.7%) versus 72 of 75 (96%), (P = 1.00), an absolute difference of -1.3% (95% confidence interval [CI], -8.1% to 5.4%). The 2 groups were similar in the diagnostic accuracy of histologic analysis, 64 of 75 (85.3%) versus 68 of 75 (90.7%) (P = .45), absolute difference -5.4% (95% CI, -15.7% to 5%); and in the diagnostic accuracy of combined cytologic and histologic analysis, 65 of 75 (86.7%) versus 69 of 75 (92%) (P = .43), absolute difference -5.3% (95% CI, -15.2% to 4.5%). CONCLUSIONS: There was no significant difference in the performance of the Franseen needle versus the Fork-tip needle. Both needles achieved a high yield of histologic tissue samples and high diagnostic accuracy. (Clinical trial registration number: NCT03672032.).

Clinical Outcomes Following Therapeutic Endoscopic Retrograde Cholangiopancreatography in Children With Pancreas Divisum.

OBJECTIVES: Pancreas divisum (PD) is a risk factor in children for the development of acute pancreatitis. Endoscopic retrograde cholangiopancreatography (ERCP) with minor papilla endoscopic sphincterotomy (mPES) may be of clinical benefit, however, the clinical outcomes from endotherapy remain unclear. We sought to review the outcomes and safety of therapeutic ERCP in children with PD. METHODS: We performed a retrospective chart of children with PD who underwent an ERCP between February 2012 and December 2018. Pertinent patient, clinical and procedure information was collected including procedure-related adverse events. A follow-up questionnaire of the parent was conducted to determine the clinical impact from endotherapy. RESULTS: Fifty-eight ERCPs were performed in 27 patients (14 boys; mean age: 9.7 years, range 2-19) with PD. All patients underwent a successful mPES. A genetic variant was identified in 19/26 (73%) tested patients. Post-ERCP pancreatitis (PEP) was the only observed adverse event; 21% (12/58). Median follow-up interval from first ERCP intervention to questionnaire completion was 31.5 months (range: 4--72 months). Of the 20 questionnaire responders, 13 reported clinical improvement from endotherapy. CONCLUSIONS: The majority of children from our PD cohort possessed at least 1 genetic variant. Most questionnaire responders had a favorable response to endotherapy. PEP rate was comparable with that of prior reports in adult patients.

Engineered bioclimatic responses in ancient settlements: a case study.

The Mandya district of Karnataka, India, houses a unique Jain settlement constructed about 1000 years ago. Recent excavations by the Archaeological Survey of India (ASI) indicate a high degree of engineering skills among the builders of this settlement. Adapting to heat-stresses in a region where the Monsoons often failed was and is still a matter of concern. Ingenious methods were adopted to modulate bioclimatic responses to maintain thermal comfort indices. The Aretippurians used composite building fabrics which modulated heat transfer to the interiors. Indeed, the thermal transmittances for these composite fabrics were low to moderate for both the temple complexes as well as the dormitories; these were 0.27 Wm-1K-1 and 0.23 Wm-1K-1, respectively. A site visit revealed that a unique and engineered micro-climate was also made to prevail on this hilltop settlement housing several hundred Jain settlers. A granite skirted reservoir was indeed the pièce-de-résistance promoting hydraulic air-conditioning for eight months of the year around the premises with copious winds blowing over a large and exposed rain-fed reservoir. This fanned chilled air across the open plan temples, courtyards, and lived-in areas. This paper explores bioclimatic responses for around 120 residents to the prevailing indoor settings modulated by an engineered microclimate. This was possible because of the staggered layout, unique building forms, use of mixed building fabric, and carefully chosen glazing ratios which yielded salubrious settings. Clearly, this entailed a complex interplay between the intercepted solar insolation, structure-driven turbulence, and the transfer of heat across the original composite walls within and around the complex, requiring a systematic experimental as well as modelling study. The experimental part of the project involved the calculation of the thermal transmittivity across the walls made up of fired bricks, granite, and limestone, and the theoretical part involved the use of appropriate software to reconstruct air flow and heat distribution across floors, walls, and ceilings to proxy the original flow pattern yielding the comfortable PMV (predicted mean vote) and PET (physiological equivalent temperature) values within these premises. This exercise may well lead to further explorations on indoor comfort adaptations in tropical settings with the use of many edifying vernacular idioms in ancient settlements which prevail even in modern layouts.

EPCAM mutation update: Variants associated with congenital tufting enteropathy and Lynch syndrome.

The epithelial cell adhesion molecule gene (EPCAM, previously known as TACSTD1 or TROP1) encodes a membrane-bound protein that is localized to the basolateral membrane of epithelial cells and is overexpressed in some tumors. Biallelic mutations in EPCAM cause congenital tufting enteropathy (CTE), which is a rare chronic diarrheal disorder presenting in infancy. Monoallelic deletions of the 3' end of EPCAM that silence the downstream gene, MSH2, cause a form of Lynch syndrome, which is a cancer predisposition syndrome associated with loss of DNA mismatch repair. Here, we report 13 novel EPCAM mutations from 17 CTE patients from two separate centers, review EPCAM mutations associated with CTE and Lynch syndrome, and structurally model pathogenic missense mutations. Statistical analyses indicate that the c.499dupC (previously reported as c.498insC) frameshift mutation was associated with more severe treatment regimens and greater mortality in CTE, whereas the c.556-14A>G and c.491+1G>A splice site mutations were not correlated with treatments or outcomes significantly different than random simulation. These findings suggest that genotype-phenotype correlations may be useful in contributing to management decisions of CTE patients. Depending on the type and nature of EPCAM mutation, one of two unrelated diseases may occur, CTE or Lynch syndrome.

A homozygous mutation in TRIM36 causes autosomal recessive anencephaly in an Indian family.

Anencephaly (APH) is characterized by the absence of brain tissues and cranium. During primary neurulation stage of the embryo, the rostral part of the neural pore fails to close, leading to APH. APH shows a heterogeneous etiology, ranging from environmental to genetic causes. The autosomal recessive inheritance of APH has been reported in several populations. In this study, we employed whole-exome sequencing and identified a homozygous missense mutation c.1522C > A (p.Pro508Thr) in the TRIM36 gene as the cause of autosomal recessive APH in an Indian family. The TRIM36 gene is expressed in the developing brain, suggesting a role in neurogenesis. In silico analysis showed that proline at codon position 508 is highly conserved in 26 vertebrate species, and the mutation is predicted to affect the conformation of the B30.2/SPRY domain of TRIM36. Both in vitro and in vivo results showed that the mutation renders the TRIM36 protein less stable. TRIM36 is known to associate with microtubules. Transient expression of the mutant TRIM36 in HeLa and LN229 cells resulted in microtubule disruption, disorganized spindles, loosely arranged chromosomes, multiple spindles, abnormal cytokinesis, reduced cell proliferation and increased apoptosis as compared with cells transfected with its wild-type counterpart. The siRNA knock down of TRIM36 in HeLa and LN229 cells also led to reduced cell proliferation and increased apoptosis. We suggest that microtubule disruption and disorganized spindles mediated by mutant TRIM36 affect neural cell proliferation during neural tube formation, leading to APH.

Comparison of outcomes following intersphincteric resection vs low anterior resection for low rectal cancer: a systematic review.

BACKGROUND: Low Rectal Anterior Resection (LAR) is challenging when anal canal mucosa and/or internal sphincter are involved by very low tumors. In these cases, Intersphincteric resection (ISR) with the removal of the internal sphincter is designed to increase the distal margin of resection, thus preserving the external sphincter and pubo-rectalis muscle complex. Aim is to compare results after ISR with those of LAR, including subgroup analysis of open, laparoscopic and robotic ISR. METHODS: Studies published from January 1991 to January 2017 describing ISR and comparing results with LAR in adults were included irrespective of the technique. Tumor and surgical characteristics, clinical, functional and oncological results were collected. RESULTS: 25 non-randomized studies were included. Postoperative mortality ranged between 0% and 2.3%. The hospital stay ranged from 5 days to 40 days, lower in robotic ISR group if compared with laparoscopic ISR. Patients avoiding permanent stoma with ISR accept a lower continence level as satisfactory. Furthermore, anorectal function after ISR often tends to improve. ISR and LAR presented not statistically significant differences. Oncological outcomes were not statistically different Morbidity, blood loss and need for blood transfusions were lower in the laparoscopic ISR if compared with open approach. CONCLUSIONS: Morbidity could more frequently affect open ISR if compared with laparoscopic ISR. Functional outcomes were influenced by neoadjuvant CRT, but not by the surgical approach of reconstruction, while were positively influenced by partial ISR with respect to total ISR.

Association of Environmental Factors, Prevalence of Asthma and Respiratory Morbidity in Mumbai: Need of a Public Health Policy.

OBJECTIVE: To study the association between environmental factors, prevalence of asthma and respiratory morbidity in relation to air quality levels in a mega city. To study modifiable environmental factors in people with diagnosed asthma and increased respiratory morbidity. METHODS: Cross sectional survey of population (N-3233) from 6 localities near air quality stations was done to study prevalence of asthma and respiratory morbidity (n-1006) followed by case control study of environmental factors by air sampling to study biological contamination. RESULTS: Univariate analysis was performed to study effect of various risk factors. Respiratory morbidity was significantly high in areas with high SPM levels. Odd's ratio was 10.3 for wheezing, 9.16 for cough, and 12.6 for breathlessness. Presence of biological contamination of air [bacterial spores] was associated with respiratory morbidity with odds ratio of 2.2 in areas with open drainage system. Pigeon droppings were found to be the source of fungal spores and associated with respiratory symptoms with odds ratio of 1.8. CONCLUSIONS: Respiratory morbidity significantly rises in areas with high particulate matter levels and biological contamination of air. Identification of environmental risk factors in different localities will be useful for undertaking specific mitigation measures at local level as a public health measure.

Hemiarthroplasty of the elbow: the effect of implant size on joint congruency.

BACKGROUND: Distal humeral hemiarthroplasty is a treatment option for elbow joint disease that predominantly affects the distal humerus, including distal humerus fractures, nonunions, and avascular necrosis. The effect of hemiarthroplasty implants on joint contact has not been reported. The purpose of this in vitro study was to quantify the effects of hemiarthroplasty and implant size on ulnohumeral joint congruency. METHODS: Five fresh frozen cadaveric upper extremities were mounted to a custom elbow testing system. Active and passive motion were performed in dependent, horizontal, varus, and valgus positions. A registration and interbone distance algorithm was used to quantify ulnohumeral joint congruency throughout elbow flexion. RESULTS: The optimally sized hemiarthroplasty implant demonstrated the greatest joint congruency with the ulna, followed by the oversized implant, then the undersized implant. Joint congruency was greater during active vs. passive flexion, indicating that the elbow joint is more reduced in active flexion than in passive flexion. CONCLUSION: This study demonstrates that undersized distal humeral hemiarthroplasty implants have the lowest joint congruency compared with an optimally sized or oversized implant.

An anthropometric study of the distal humerus.

BACKGROUND: The optimal articular shape for distal humeral hemiarthroplasty has not been defined because of a paucity of data quantifying the morphology of the normal distal humerus. This study defines the osseous anatomy and anatomic variability of the distal humerus using 3-dimensional imaging techniques. METHODS: Three-dimensional surface models were created from computed tomography scans obtained from 50 unpaired human cadaveric elbows. Geometric centers of the capitellum and the trochlear groove defined the anatomic flexion-extension axis. A coordinate system was created, and the distal humerus was sectioned into 100 slices along this axis. The C line was defined as the line of best fit connecting the geometric centers of each of the slices. RESULTS: The anatomic flexion-extension axis of the distal humerus was found to be an average of 1° ± 1° from the C line (range, 0°-3°) in the coronal plane and 2° ± 1° (range, 0°-7°) in the transverse plane. The average trochlear width was 22 ± 3 mm, and the average trochlear height was 18 ± 2 mm. The mean width of the capitellum was 17 ± 2 mm; the height was 23 ± 2 mm (P < .001). CONCLUSIONS: The difference in the capitellum width and height demonstrates that the capitellum is ellipsoid, not spherical. A data bank of humeral dimensions may be used for the development of future distal humeral hemiarthroplasty implants. A more anatomic implant may optimize kinematics and maximize contact area, thus minimizing contact stresses on the native ulna and radius.

Hemiarthroplasty of the elbow: the effect of implant size on kinematics and stability.

BACKGROUND: Distal humeral hemiarthroplasty is a treatment option for distal humeral fractures, nonunions, and avascular necrosis. The biomechanical effects, however, have not been reported. The purpose of this in vitro study was to quantify the effects of hemiarthroplasty and implant size on elbow joint kinematics. METHODS: Eight fresh-frozen cadaveric arms were mounted in an in vitro motion simulator. An electromagnetic tracking system quantified elbow kinematics. A custom distal humeral stem was implanted by use of navigation, and 3 humeral articular spools were evaluated: optimally sized, undersized, and oversized. Statistical analysis was performed with repeated-measures analysis of variance. RESULTS: Distal humeral hemiarthroplasty altered elbow kinematics, regardless of implant size. In the valgus position, the optimally sized implant resulted in a mean increase in valgus angulation of 3° ± 1° (P = .003) as compared with the osteotomy control. In the varus position, the optimal and undersized implants both resulted in significant increases in varus angulation: 3° ± 1° (P = .01) and 3° ± 1° (P = .001), respectively. The undersized implant had the greatest alteration in kinematics, whereas the oversized implant best reproduced native elbow kinematics. CONCLUSION: This study showed a small but significant alteration in elbow joint kinematics with placement of a distal humeral hemiarthroplasty implant, regardless of implant size. This could be due to errors in implant positioning and/or differences in the shape of the humeral implant relative to the native elbow. These changes in joint tracking may cause abnormal articular contact and loading, which may result in pain and cartilage degeneration over time.

A comparison of surgical delays in directly admitted versus transferred patients with hip fractures: opportunities for improvement?

BACKGROUND: The increasing incidence of hip fractures in our aging population challenges orthopedic surgeons and hospital administrators to effectively care for these patients. Many patients present to regional hospitals and are transferred to tertiary care centres for surgical management, resulting in long delays to surgery. Providing timely care may improve outcomes, as delay carries an increased risk of morbidity and mortality. METHODS: We retrospectively reviewed the cases of all patients with hip fractures treated in a single Level 1 trauma centre in Canada between 2005 and 2012. We compared quality indicators and outcomes between patients transferred from a peripheral hospital and those directly admitted to the trauma centre. RESULTS: Of the 1191 patients retrospectively reviewed, 890 met our inclusion criteria: 175 who were transferred and 715 admitted directly to the trauma centre. Transfer patients' median delay from admission to operation was 93 hours, whereas nontransfer patients waited 44 hours (p < 0.001). The delay predominantly occurred before transfer, as the patients had to wait for a bed to become available at the trauma centre. The median length of stay in hospital was 20 days for transfer patients compared with 13 days for nontransfer patients (p < 0.001). Regional policy changes enacted in 2011 decreased the median transfer delay from regional hospital to tertiary care centre from 47 to 27 hours (p = 0.005). CONCLUSION: Policy changes can have a significant impact on patient care. Prioritizing patients and expediting transfer will decrease overall mortality, reduce hospital stay and reduce the cost of hip fracture care.

CONTEXTE: L'incidence croissante des fractures de la hanche dans notre population vieillissante pose un défi aux chirurgiens orthopédistes et aux administrateurs hospitaliers qui souhaitent offrir des soins efficaces à ces patients. De nombreux patients se présentent dans des hôpitaux régionaux avant d'être transférés dans des centres de soins tertiaires pour y être opérés, ce qui retarde la chirurgie. Fournir les soins requis en temps voulu pourrait améliorer les résultats étant donné que tout retard s'accompagne d'un risque accru de morbidité et de mortalité. MÉTHODES: Nous avons effectué une revue rétrospective de tous les cas de fracture de la hanche traités dans un centre canadien de traumatologie de niveau 1 entre 2005 et 2012. Nous avons comparé les indicateurs de qualité et les résultats entre les patients transférés d'un hôpital régional et les patients admis directement au centre de traumatologie. RÉSULTATS: Parmi les 1191 cas analysés rétrospectivement, 890 répondaient à nos critères d'inclusion : 175 avaient été transférés et 715 avaient été admis directement au centre de traumatologie. Le délai médian entre l'admission et la chirurgie chez les patients transférés a été de 93 heures, alors que les patients non transférés ont attendu 44 heures (p < 0,001). Le délai est principalement survenu avant le transfert, car les patients devaient attendre qu'un lit se libère au centre de traumatologie. La durée médiane du séjour hospitalier a été de 20 jours pour les patients transférés, contre 13 jours pour les patients non transférés (p < 0,001). Les changements apportés à la politique régionale en 2011 ont abrégé de 47 à 27 heures (p = 0,005) le délai médian avant le transfert des hôpitaux régionaux vers le centre de soins tertiaires. CONCLUSION: Les changements de politiques peuvent avoir un impact significatif sur les soins aux patients. Prioriser les cas et accélérer les transferts réduiront la mortalité globale, abrégeront les séjours hospitaliers et réduiront les coûts associés au traitement des fractures de la hanche.

Factors affecting transfusion requirement after hip fracture: can we reduce the need for blood?

BACKGROUND: Hip fractures are common injuries that result in blood loss and frequently require the transfusion of blood products. We sought to identify risk factors leading to increased blood transfusion in patients presenting with hip fractures, especially those factors that are modifiable. METHODS: We retrospectively reviewed the cases of all patients who had fixation of their hip fractures between October 2005 and February 2010. The need for transfusion was correlated with potential risk factors, including age, sex, preoperative hemoglobin, fracture type, fixation method and more. RESULTS: A total of 835 patients had fixation of their hip fractures during the study period; 631 met the inclusion criteria and 249 of them (39.5%) were transfused. We found an association between need for blood transfusion and female sex (p = 0.018), lower preoperative hemoglobin (p < 0.001), fracture type (p < 0.001) and fixation method (p < 0.001). Compared with femoral neck fractures, there was a 2.37 times greater risk of blood transfusion in patients with intertrochanteric fractures (p < 0.001) and a 4.03 times greater risk in those with subtrochanteric fractures (p < 0.001). Dynamic hip screw (DHS) fixation decreased the risk of transfusion by about half compared with intramedullary nail or hemiarthroplasty. We found no association with age, delay to operation (p = 0.17) or duration of surgery (p = 0.30). CONCLUSION: The only modifiable risk factor identified was fixation method. When considering blood transfusion requirements in isolation, we suggest a potential benefit in using a DHS for intertrochanteric and femoral neck fractures amenable to DHS fixation.

CONTEXTE: La fracture de la hanche est un traumatisme fréquent, qui cause une perte sanguine et nécessite souvent la transfusion de produits sanguins. Nous avons tenté d'identifier les facteurs de risque associés à une hausse du nombre des transfusions sanguines chez des patients ayant subi une fracture de la hanche, en particulier les facteurs modifiables. MÉTHODES: Au cours d'une étude rétrospective, on a revu les cas de tous les patients chez qui on avait pratiqué une ostéosynthèse pour une fracture de la hanche survenue entre octobre 2005 et février 2010. La nécessité d'une transfusion sanguine a été associée à d'éventuels facteurs de risque, dont l'âge, le sexe, le taux d'hémoglobine préopératoire, le type de fracture, la technique d'ostéosynthèse, et d'autres facteurs encore. RÉSULTATS: Au total, 835 patients avaient subi une ostéosynthèse pour fracture de la hanche au cours de la période à l'étude; 631 satisfaisaient les critères d'inclusion à l'étude et parmi eux, 249 (39,5 %) ont reçu une transfusion sanguine. On a observé l'existence d'un lien entre la nécessité d'une transfusion sanguine et le sexe féminin (p = 0,018), une plus faible concentration d'hémoglobine préopératoire (p < 0,001), le type de fracture (p <0,001) et la technique d'ostéosynthèse (p < 0,001). Par rapport aux fractures du col fémoral, le risque de transfusion sanguine était 2,37 fois plus élevé chez les patients présentant une fracture intertrochantérienne (p < 0,001) et 4,03 fois plus élevé chez ceux présentant une fracture sous-trochantérienne (p <0,001). En utilisant une vis dynamique de hanche, le risque de transfusion sanguine a diminué d'environ 50 % par rapport à l'enclouage centromédullaire ou à l'hémiarthroplastie. Aucun lien n'a été observé avec l'âge, le délai de l'intervention chirurgicale (p = 0,17), ni avec sa durée (p = 0,30). CONCLUSION: La technique d'ostéosynthèse est l'unique facteur de risque modifiable ayant été identifié. Mais lorsqu'on évalue la nécessité d'une transfusion sanguine sans tenir compte des facteurs de risque, nos résultats semblent indiquer qu'on aurait avantage à utiliser une vis dynamique de hanche pour consolider les fractures intertrochantériennes et les fractures du col fémoral.

Empowering Family Glaucoma Risk Communication Using QR-Code-Mediated Online Intervention.

PURPOSE: Attempts at engaging relatives of glaucoma patients in education and screening have had limited success. This study explores the feasibility of an electronic intervention to facilitate direct yet reliable glaucoma risk communication between open-angle glaucoma patients (probands) and their first-degree relatives (FDRs). DESIGN: Prospective survey and assessment of intervention. PARTICIPANTS: Fifty adult probands, engaging 140 FDRs. METHODS: Phase I was an iterative process involving creating a customized website and Quick Response (QR)-code-based intervention designed with input from probands, FDRs of patients, community members, and researchers. In phase II, the intervention was deployed in a clinical setting; this involved recruiting probands who had a smartphone and were willing to use the QR-code to message their FDRs a standard message, including a website link about glaucoma risk in FDRs and the importance of getting examined. Follow-up interviews were conducted with probands 1 to 2 weeks after their clinic visit to assess the impact of the intervention. Demographic data, website analytics, and participant feedback were collected and analyzed. MAIN OUTCOME MEASURES: Increased awareness of glaucoma risk among FDRs and enhanced discussions. RESULTS: At the time of the first interview, probands reported that 70% of the FDRs were aware of the probands' glaucoma diagnosis, but only 26% had undergone glaucoma screening. Ninety percent of probands had no issues using the QR-codes. Website analytics recorded 73 visits from 51 distinct internet protocol addresses (IPs). After receiving the standard message, 95% of FDRs followed up with the probands, actively discussing glaucoma. Of the probands, 84% completed the follow-up interview 1 to 2 weeks after enrollment. Fifty-nine percent of the FDRs were reported to have scheduled screening appointments. The collected feedback revealed that 96% of probands found the intervention helpful, fostering glaucoma discussions with their FDRs and improving probands' comfort level in discussing health issues with FDRs from baseline (very comfortable: 88%, comfortable: 8%, neutral: 2%, and very uncomfortable: 2%) to the follow-up interview (very comfortable: 98% and comfortable: 2%). CONCLUSIONS: This innovative online method of communicating the risk of glaucoma to FDRs of probands prompted and increased the comfort level of familial discussions of glaucoma. More than half of FDRs reported making an appointment to get screened for glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Prominent tauopathy and intracellular ß-amyloid accumulation triggered by genetic deletion of cathepsin D: implications for Alzheimer disease pathogenesis.

BACKGROUND: Cathepsin D (CatD) is a lysosomal protease that degrades both the amyloid-ß protein (Aß) and the microtubule-associated protein, tau, which accumulate pathognomonically in Alzheimer disease (AD), but few studies have examined the role of CatD in the development of Aß pathology and tauopathy in vivo. METHODS: CatD knockout (KO) mice were crossed to human amyloid precursor protein (hAPP) transgenic mice, and amyloid burden was quantified by ELISA and immunohistochemistry (IHC). Tauopathy in CatD-KO mice, as initially suggested by Gallyas silver staining, was further characterized by extensive IHC and biochemical analyses. Controls included human tau transgenic mice (JNPL3) and another mouse model of a disease (Krabbe A) characterized by pronounced lysosomal dysfunction. Additional experiments examined the effects of CatD inhibition on tau catabolism in vitro and in cultured neuroblastoma cells with inducible expression of human tau. RESULTS: Deletion of CatD in hAPP transgenic mice triggers large increases in cerebral Aß, manifesting as intense, exclusively intracellular aggregates; extracellular Aß deposition, by contrast, is neither triggered by CatD deletion, nor affected in older, haploinsufficient mice. Unexpectedly, CatD-KO mice were found to develop prominent tauopathy by just ∼ 3 weeks of age, accumulating sarkosyl-insoluble, hyperphosphorylated tau exceeding the pathology present in aged JNPL3 mice. CatD-KO mice exhibit pronounced perinuclear Gallyas silver staining reminiscent of mature neurofibrillary tangles in human AD, together with widespread phospho-tau immunoreactivity. Striking increases in sarkosyl-insoluble phospho-tau (∼ 1250%) are present in CatD-KO mice but notably absent from Krabbe A mice collected at an identical antemortem interval. In vitro and in cultured cells, we show that tau catabolism is slowed by blockade of CatD proteolytic activity, including via competitive inhibition by Aß42. CONCLUSIONS: Our findings support a major role for CatD in the proteostasis of both Aß and tau in vivo. To our knowledge, the CatD-KO mouse line is the only model to develop detectable Aß accumulation and profound tauopathy in the absence of overexpression of hAPP or human tau with disease-associated mutations. Given that tauopathy emerges from disruption of CatD, which can itself be potently inhibited by Aß42, our findings suggest that impaired CatD activity may represent a key mechanism linking amyloid accumulation and tauopathy in AD.