Short stature and dysmorphic features in Asian Indian siblings with DAAM2-associated steroid-resistant nephrotic syndrome: Expansion of the phenotypic spectrum or a blended phenotype?

Variants in more than 60 different genes, most of which code for podocyte-related proteins, have been found to be associated with monogenic forms of nephrotic syndrome (NS). Biallelic variants in DAAM2, a member of the formin family, were recently identified to cause autosomal recessive (AR) NS type 24 in four unrelated families with steroid-resistant nephrotic syndrome (SRNS). This case report represents only the fifth reported family of DAAM2-associated NS and the first from India, with two sibs who presented with a complex phenotype characterized by steroid-resistant nephrotic syndrome, short stature, dysmorphic facial features, deep-set toenails, myopia, increased thickness of the calvarium of the skull, and sloping ribs. Both sibs were found to have a homozygous likely pathogenic nonsense variant c.196C>T (p.Arg66Ter; NM_001201427.2) in exon 3 of the DAAM2 gene through whole exome sequencing. The dysmorphic features could possibly be part of the DAAM2-related phenotype which has hitherto not been reported or could represent a blended phenotype, with the extrarenal manifestations resulting from a yet to be identified coexisting genetic condition.

Common treatment strategies for calcium hydroxyapatite deposition disease: a cost-effectiveness analysis.

OBJECTIVE: To determine the cost-effectiveness of rotator cuff hydroxyapatite deposition disease (HADD) treatments. METHOD: A 1-year time horizon decision analytic model was created from the US healthcare system perspective for a 52-year-old female with shoulder HADD failing conservative management. The model evaluated the incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) of standard strategies, including conservative management, ultrasound-guided barbotage (UGB), high- and low-energy extracorporeal shock wave therapy (ECSW), and surgery. The primary effectiveness outcome was quality-adjusted life years (QALY). Costs were estimated in 2022 US dollars. The willingness-to-pay (WTP) threshold was $100,000. RESULTS: For the base case, UGB was the preferred strategy (0.9725 QALY, total cost, $2199.35, NMB, $95,048.45, and ICER, $33,992.99), with conservative management (0.9670 QALY, NMB $94,688.83) a reasonable alternative. High-energy ECSW (0.9837 QALY, NMB $94,805.72), though most effective, had an ICER of $121, 558.90, surpassing the WTP threshold. Surgery (0.9532 QALY, NMB $92,092.46) and low-energy ECSW (0.9287 QALY, NMB $87,881.20) were each dominated. Sensitivity analysis demonstrated that high-energy ECSW would become the favored strategy when its cost was < $2905.66, and conservative management was favored when the cost was < $990.34. Probabilistic sensitivity analysis supported the base case results, with UGB preferred in 43% of simulations, high-energy ECSW in 36%, conservative management in 20%, and low-energy ECSW and surgery in < 1%. CONCLUSION: UGB appears to be the most cost-effective strategy for patients with HADD, while surgery and low-energy ECSW are the least cost-effective. Conservative management may be considered a reasonable alternative treatment strategy in the appropriate clinical setting.

How effective is nephrectomy in curing hypertension in children with unilateral poorly functioning kidney? A systematic review.

PURPOSE: Some children with hypertension (HTN) have unilateral poorly functional kidney (PFK). This provides an opportunity for the clinician to cure the HTN by removal of the PFK, thereby avoiding the problems of long-term medication. However, there is sparse data in children regarding the effect of PFK nephrectomy on curing HTN. In this review, we analysed the etiology of PFK causing HTN and the effectiveness of nephrectomy in curing HTN in children. METHODS: We searched the databases to identify papers between January 2000 to December 2020 pertaining to children with PFK and HTN who underwent nephrectomy. Outcome analyzed was the resolution of HTN following nephrectomy. Duplicate publications, review articles and incomplete articles were excluded. Meta-analysis of heterogeneity was reported with I2statistics. Forest plot was constructed to compare the pooled prevalence of HTN resolution. RESULTS: Five articles with 88 patients were included. Majority (43%) of PFK were due to the unilateral atrophic kidney with or without vesicoureteral reflux (VUR); ureteropelvic junction obstruction and multicystic dysplastic kidney together accounted for 35% of cases and renovascular pathology for 22% of cases. With a follow-up of 1.5 to 3.3 years, nephrectomy was effective to cure HTN in 65.9% (95% CI 55-75%) children. CONCLUSIONS: In children with HTN and a unilateral PFK, nephrectomy cured the HTN in two-thirds of children. Unilateral atrophic kidney due to VUR was the most common cause of PFK. An increase in the utilisation of laparoscopy was observed in recent publications, hence laparoscopic nephrectomy may be considered a first choice of treatment in these children.

Insights and Opinions of Critical Care Healthcare Professionals in the Management of Carbapenem-resistant Enterobacteriaceae Cases and Antibiotic-Resistant Infections in the Intensive Care Unit Setting: A Survey-Based Approach.

INTRODUCTION: A survey-based approach to managing antibiotic-resistant infections in the intensive care unit (ICU) setting, with a focus on carbapenem-resistant Enterobacteriaceae (CRE) cases, was conducted. Among CRE, New Delhi metallo-ß-lactamase 1 (NDM-1) is a carbapenemase that is resistant to ß-lactam antibiotics and has a broader spectrum of antimicrobial resistance than other carbapenemase types. The article explains that healthcare-associated infections (HAIs) are a significant problem, particularly in low- and middle-income countries, and that carbapenem in combination with other antibiotics are the most potent class of antimicrobial agents effective in treating life-threatening bacterial infections, including those caused by resistant strains. AIM: The survey aimed to gather critical care healthcare professionals (HCPs') opinions on their current practices in managing infections acquired in the hospital and ICU settings, with a focus on CRE cases, specifically NDM-1 and other antibiotic-resistant infections. METHODS: Responses from critical care healthcare professionals, including online surveys and in-person interviews, to gain insights into the management of infections caused by multidrug-resistant bacteria. The findings related to the insights on the prevalence of bacterial flora, clinical experiences on efficacy and safety of meropenem sulbactam ethylenediaminetetraacetic acid (EDTA) (MSE) in CRE cases, and various combination therapies of antibiotics used to treat antibiotic-resistant infections in ICU setting were evaluated. RESULTS: Klebsiella pneumoniae bacteria were the most common bacteria in cultures, followed by Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. NDM-1 was the type of carbapenemase found in around 50% of CRE patients. MSE is among the most preferred antibiotics besides colistin, polymyxin B, and ceftazidime avibactum for CRE cases and specifically for NDM-1 cases due to its high rate of efficacy and safety. CONCLUSION: The article concludes with a discussion on the antibiotics used in response to CRE cases, reporting that critical care HCP considers MSE with high efficacy and safe antibiotic combination and was used as both monotherapy and in combination with other antibiotics. The survey highlights the need for exploring and better understanding the role of MSE in the management of CRE infections, especially in NDM-1.

Atrial Fibrillation (AFIB) in the ICU: Incidence, Risk Factors, and Outcomes: The International AFIB-ICU Cohort Study.

OBJECTIVES: To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF. DESIGN: Multicenter, prospective, inception cohort study. SETTING: Forty-four ICUs in 12 countries in four geographical regions. SUBJECTS: Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8-17.6), of which newly developed AF was 13.3% (11.5-15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16-23), magnesium 16% (13-20), potassium 15% (12-19), amiodarone 51% (47-55), beta-1 selective blockers 34% (30-38), calcium channel blockers 4% (2-6), digoxin 16% (12-19), and direct current cardioversion in 4% (2-6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95-1.99). CONCLUSIONS: In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.

The application of clinical registries in ophthalmic trauma-the International Globe and Adnexal Trauma Epidemiology Study (IGATES).

Ophthalmic trauma is a leading cause of preventable monocular blindness worldwide. The prevalence of ophthalmic trauma varies considerably based on geographic location, socio-economic status, age groups, occupation, and cultural practices such as firework celebrations. Clinical registries are known to be valuable in guiding the diagnosis, management, and prognostication of complex diseases. However, there is currently a lack of a centralized international data repository for ophthalmic trauma. We draw lessons from past and existing clinical registries related to ophthalmology and propose a new suitable international multicenter clinical registry for ophthalmic trauma: the International Globe and Adnexal Trauma Epidemiology Study (IGATES). IGATES is hosted on a secure web-based platform which exhibits user-friendly smart features, an integrated Ocular Trauma Score (OTS) prognosis calculator, efficient data collection points, and schematic graphical software. IGATES currently has 37 participating centers globally. The data collected through IGATES will be primarily used to develop a more robust and improved ophthalmic trauma prognostic classification system, the Ocular Trauma Score-2 (OTS-2), which builds on previous systems such as the Birmingham Eye Trauma Terminology System (BETTS) and Ocular Trauma Score (OTS). Furthermore, IGATES will act as a springboard for further research into the epidemiology, diagnosis, and management of ophthalmic trauma. Ultimately, IGATES serves to advance the field of ophthalmic trauma and improve the care that patients with ophthalmic trauma receive.

Corona, Acute Ischemic Stroke, Malignant Cerebral Edema, and Hemo-adsorption: A Case Report.

Background: COVID-19 infection can be associated with systemic hyperinflammation, hypercoagulable state, vasculitis, and cardiomyopathy leading to multiorgan failure. Use of extracorporeal blood purification has been shown to mitigate the cytokine storm, improving hemodynamic stability and pulmonary function. Case summary: We report a case of a young patient with malignant cerebral edema due to acute cerebrovascular accident, with COVID-19. He was taken up for life-saving decompression craniotomy amidst the cytokine storm and multiorgan failure, and was treated with steroids, antibiotics, and Cytosorb® therapy for the cytokine storm. IL-6 and PCT levels were reduced by 99.5 and 98.6%, respectively. Vasopressors were stopped on day 4 and successfully weaned off ventilator support by 2 weeks of tracheostomy. He was de-cannulated and discharged neurologically stable on day 32. Conclusion: Timely detection of COVID-19 and anti-inflammatory and hemo-adsorption measures may be helpful in modulating cytokine storm, thereby reducing morbidity and mortality. How to cite this article: Shah M, Kaidawala Z, Shah A, Desphande R. Corona, Acute Ischemic Stroke, Malignant Cerebral Edema, and Hemo-adsorption: A Case Report. Indian J Crit Care Med 2022;26(2):235-238.

A 30-day Survival and Safety of Percutaneous Tracheostomy in Moderate-to-severe COVID-19 Pneumonia Patients: A Single-center Experience.

Aims and objectives: In coronavirus disease-2019 (COVID-19) pneumonia, guidelines on timing and method of tracheostomy are evolving. The aim of the study was to analyze the outcomes of moderate-to-severe COVID-19 pneumonia patients who required tracheostomy and the safety with regard to the risk of transmission to the healthcare workers. Materials and methods: We retrospectively analyzed 30-day survival outcome of a total of 70 moderate-to-severe COVID-19 pneumonia patients on a ventilator, wherein tracheostomy was performed only in 28 (tracheostomy group), and the remaining were with endotracheal intubation beyond 7 days (non-tracheostomy group). Besides demographics, comorbidities and clinical data including 30-day survival and complications of tracheostomy were analyzed in both groups with respect to the timing of tracheostomy from the day of intubation. Healthcare workers were monitored for COVID-19 symptoms by carrying out periodical COVID tests. Results: The 30-day survival of the tracheostomy group was 75% as compared to 26.2% of the non-tracheostomy group. The majority of the patients (71.4%) had severe disease with PaO2/FiO2 (P/F ratio) <100. The first wave showed an 80% (4/5) while the second wave 100% (8/8) thirty days survival in the tracheostomy group performed before 13 days. All patients during the second wave underwent tracheostomy before 13 days with a median of 12th day from the day of intubation. These tracheostomies were performed percutaneously at the bedside, without any major complications and no transmission of disease to healthcare workers. Conclusion: Early percutaneous tracheostomy within 13 days of intubation demonstrated a good 30-day survival rate in severe COVID-19 pneumonia patients. How to cite this article: Shah M, Bhatuka N, Shalia K, Patel M. A 30-day Survival and Safety of Percutaneous Tracheostomy in Moderate-to-severe COVID-19 Pneumonia Patients: A Single-center Experience. Indian J Crit Care Med 2022;26(10):1120-1125.

"The Bitter Truth of Sugar"-Euglycemic Diabetic Ketoacidosis due to Sodium-glucose Cotransporter-2 Inhibitors: A Case Series.

Diabetic ketoacidosis (DKA) is an acute and major complication of diabetes mellitus (DM), both type I and type II. Biochemically, DKA consists of a triad of blood sugar levels greater than 250 mg/dL, ketonemia of greater than 3 mmol/L and/or significant ketonuria, and a blood pH less than 7.3 with an increased anion gap. Currently, the sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are widely used in management of type II diabetes. There have been several reports of an association between euglycemic diabetic ketoacidosis (EuDKA) and SGLT-2i agents. We present three different patients who were on SGLT-2i therapy who developed recurrent EuDKA postprocedure or sepsis. We believe that prolonged treatment (5-6 days) with intravenous (IV) insulin with glucose until resolution of glycosuria can be considered as an inexpensive marker of resolution of EuDKA. Moreover, the recommended duration for discontinuation of these drugs prior to elective procedures should be longer than 3 days. How to cite this article: Shah M, Pathrose E, Bhagwat NM, Chandy D. "The Bitter Truth of Sugar"-Euglycemic Diabetic Ketoacidosis due to Sodium-glucose Cotransporter-2 Inhibitors: A Case Series. Indian J Crit Care Med 2022;26(1):123-126.

Clinical Profile of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection Developing Pulmonary Barotrauma on Mechanical Ventilation.

Background: There is limited information on clinical profile and outcomes of patients on mechanical ventilation (MV) who developed pulmonary barotrauma (PBT) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients and methods: In a retrospective observational study, all SARS-CoV-2 pneumonia patients admitted from March 28, 2020, to August 31, 2020, at Sir HN Reliance Foundation Hospital and Research Center and Seven Hills Hospital (Reliance Facility), Mumbai, India, of 18 years and above on MV and developed PBT, were included. Results: A total of 14 SARS-CoV-2 patients of 45 on MV (31.0%) developed PBT of 1,029 hospitalized. All patients were male and divided as per admission into PaO2/FiO2 (P/F) ≤100 (median 80) and P/F >100 (median 222) group. Pneumothorax developed in seven and six cases of P/F ≤100 and P/F >100 groups, respectively. Three patients in each group developed subcutaneous emphysema, while four developed pneumomediastinum in P/F >100 group. Twelve patients (7, P/F ≤100, and 5, P/F >100) were on invasive, while two (P/F >100) were on noninvasive MV. The mean P/F on the day of PBT was reduced by 27.5 and 65.3%, while peak inspiratory pressure was elevated with a median of 36 and 28 cm H2O in P/F ≤100 and P/F >100 groups, respectively. The median highest tidal volume (420 mL), positive-end expiratory pressure (8 vs 6 cm H2O) on the day of PBT, and length of hospital stay (11 vs 25 days) did not differ between two groups. Survival was 28.6% (4/14). Conclusion: SARS-CoV-2 patients requiring MV with PBT had poor outcomes. Clinicians should be vigilant about the diagnosis of PBT. How to cite this article: Kargirwar KV, Rathod D, Kumar V, Patel M, Shah M, Choudhury H, et al. Clinical Profile of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection Developing Pulmonary Barotrauma on Mechanical Ventilation. Indian J Crit Care Med 2022;26(5):613-618.

Epidemiology and outcomes of open globe injuries: the international globe and adnexal trauma epidemiology study (IGATES).

PURPOSE: To detail the methodology for a novel ocular trauma registry and utilize the registry to determine the demographics, nature of injury, and associations of severe visual loss for open globe injuries (OGI). METHODS: Thirteen hospitals in 7 countries used International Globe and Adnexal Trauma Epidemiology Study (IGATES) platform. Patients presenting between April 2009 and 2020 with OGI (with or without) adnexal involvement or intraocular foreign body (IOFB) were included. RESULTS: Analyses of presenting and final VA, using "severe vision loss" (VA ≤ 6/60) and "no severe loss" (VA > 6/60), were performed. Four hundred fifty-four (64%) patients had VA < 6/60 at presentation and 327 (44.8%) at final follow-up, with a highly significant association between presenting and final VA (p < 0.0001). From the cohort of 746 patients, 37 were missing VA at presentation and 16 at follow-up and complete clinical data was available for 354 patients. The male to female ratio is 6:1, and mean age 36.0 ± 20.0 years old. Relative afferent pupillary defect (RAPD), zone III injury, IOFB, and eyelid injury at presentation were recorded in 50 (6.7%), 55 (7.8%), 97 (13%), and 87 (11.7%) patients, respectively, and were significantly associated with VA < 6/60 at follow-up. Older age, ≥ 61 years, was associated with 3.39 times (95% CI: 1.95-5.89) higher risk than ≤20-year-old patients (p < 0.0001) and males 0.424 times (95% CI: 0.27-0.70) lower risk than female (p = 0.0001) of severe vision loss (SVL). CONCLUSION: In OGIs from 13 hospitals, female gender, older age, zone III injury, eyelid injury, and IOFB were associated with higher risk of visual outcome of SVL.

Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia: The COVID STEROID 2 Randomized Trial.

Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.

Symptomatic lower urinary tract dysfunction in sacral agenesis: Potentially high risk?

INTRODUCTION: Sacral agenesis (SA) is a caudal regression anomaly that can cause neurogenic bladder but is not generally recognized as high risk. We studied the clinical presentation, upper urinary tract, bone and spine abnormalities, and urodynamic findings in patients with SA and compared them with related high-risk conditions, anorectal malformation (ARM), and cloacal malformation. MATERIALS AND METHODS: Patient records between May 2011 and December 2015 were identified and grouped into isolated SA without an overt anomaly (Group I), SA with overt caudal regression anomalies (Group II), and ARM or cloacal malformation without the SA (Group III). Distribution of clinical and urodynamic findings and factors associated with reduced eGFR were tested with rank sum test, t-test, and unadjusted odds (P < 0.05 significant) using R statistical program (version 3.1.3). RESULTS: Of 605 neurogenic bladder patients treated in the study period, 39 fulfilled the inclusion criteria. 12 were Group I, 5 Group II, and 22 Group III. Long-standing lower urinary symptoms were noted in all SA patients. Group I patients were older (14.5 years vs. 6 years and 5 years for II and III). Patients with SA (Group I and II) had poor compliance (6.7 ml/cmH2O, interquartile range [IQR] 4-13.6 ml/cmH2O), reduced age-adjusted bladder capacity (59%, IQR 22-85%), elevated end-fill pressure (22 cmH2O, IQR 11-28 cmH2O), hydronephrosis (88%), and reduction in eGFR (29%), all comparable to Group III. Most had Renshaw type II SA and tethered spinal cord rather than wedge-shaped termination. Limitations include small numbers and significant selection bias. CONCLUSIONS: Symptomatic neurogenic bladder due to SA may cause renal damage similar to ARM but often eludes diagnosis.

Pediatric ocular trauma score as a prognostic tool in the management of pediatric traumatic cataracts.

OBJECTIVE: To introduce and validate the pediatric ocular trauma score (POTS) - a mathematical model to predict visual outcome trauma in children with traumatic cataract METHODS: In this retrospective cohort study, medical records of consecutive children with traumatic cataracts aged 18 and below were retrieved and analysed. Data collected included age, gender, visual acuity, anterior segment and posterior segment findings, nature of surgery, treatment for amblyopia, follow-up, and final outcome was recorded on a precoded data information sheet. POTS was derived based on the ocular trauma score (OTS), adjusting for age of patient and location of the injury. Visual outcome was predicted using the OTS and the POTS and using receiver operating characteristic (ROC) curves. RESULTS: POTS predicted outcomes were more accurate compared to that of OTS (p = 0.014). CONCLUSION: POTS is a more sensitive and specific score with more accurate predicted outcomes compared to OTS, and is a viable tool to predict visual outcomes of pediatric ocular trauma with traumatic cataract.

A Randomized Controlled Trial of Two Distinct Shared Decision-Making Aids for Hip and Knee Osteoarthritis in an Ethnically Diverse Patient Population.

OBJECTIVES: To evaluate the use of decision aids for hip and knee osteoarthritis (OA) regarding the potential risks and benefits of different treatment options. METHODS: A prospective, randomized controlled trial was conducted of 147 patients with advanced hip or knee OA to compare the effect of two decision aids (booklet-only vs. booklet with DVD). RESULTS: Both decision aid programs were well received and demonstrated improvements in patient knowledge and willingness to participate in treatment decisions. The decision aids, however, had a marginal effect on patient willingness to participate in OA management, with an increase of 0.11 and 0.6 on a scale of 2 (P = 0.58) between groups. CONCLUSIONS: The decision aids were accepted for most patients and effective in improving patient knowledge and willingness to participate in the decision process. Nevertheless, the addition of a more expensive DVD to the booklet program did not improve patient acceptance or knowledge.

Atomic structure of the autosomal recessive hypercholesterolemia phosphotyrosine-binding domain in complex with the LDL-receptor tail.

Hypercholesterolemia, high serum cholesterol in the form of LDL, is a major risk factor for atherosclerosis. LDL is mostly degraded in the liver after its cellular internalization with the LDL receptor (LDLR). This clathrin-mediated endocytosis depends on the protein autosomal recessive hypercholesterolemia (ARH), which binds the LDLR cytoplasmic tail. Mutations in either the LDLR tail or in ARH lead to hypercholesterolemia and premature atherosclerosis. Despite the significance of this interaction for cholesterol homeostasis, no structure of either ARH or the LDLR tail is available to determine its molecular basis. We report the crystal structure at 1.37-Å resolution of the phosphotyrosine-binding (PTB) domain of ARH in complex with an LDLR tail peptide containing the FxNPxY(0) internalization signal. Surprisingly, ARH interacts with a longer portion of the tail than previously recognized, which extends to I(-7)xF(-5)xNPxY(0)QK(+2). The LDLR tail assumes a unique "Hook"-like structure with a double ß-turn conformation, which is accommodated in distinctive ARH structural determinants (i.e., an extended backbone hydrogen-bonding platform, three hydrophobic helical grooves, and a hydrophobic pocket for Y(0)). This unique complementarity differs significantly in related PTB proteins and may account for the unique physiological role of these partners in the hepatic uptake of cholesterol LDL. Moreover, the unusual hydrophobic pocket for Y(0) explains the distinctive ability of ARH to internalize proteins containing either FxNPxY(0) or FxNPxF(0) sequences. Biophysical measurements reveal how mutations associated with hypercholesterolemia destabilize ARH and its complex with LDLR and illuminate LDL internalization defects seen in patients.

The utility of plain radiographs in the initial evaluation of knee pain amongst sports medicine patients.

PURPOSE: To evaluate whether screening radiographs as part of the initial workup of knee pain impacts clinical decision-making in a sports medicine practice. METHODS: A questionnaire was completed by the attending orthopaedic surgeon following the initial office visit for 499 consecutive patients presenting to the sports medicine centre with a chief complaint of knee pain. The questionnaire documented patient age, duration of symptoms, location of knee pain, associated mechanical symptoms, history of trauma within the past 2 weeks, positive findings on plain radiographs, whether magnetic resonance imaging was ordered, and whether plain radiographs impacted the management decisions for the patient. Patients were excluded if they had prior X-rays, history of malignancy, ongoing pregnancy, constitutional symptoms as well as those patients with prior knee surgery or intra-articular infections. Statistical analyses were then performed to determine which factors were more likely do correspond with diagnostic radiographs. RESULTS: Overall, initial screening radiographs did not change management in 72 % of the patients assessed in the office. The mean age of patients in whom radiographs did change management was 57.9 years compared to 37.1 years in those patients where plain radiograph did not change management (p < 0.0001). Plain radiographs had no impact on clinical management in 97.3 % of patients younger than 40. In patients whom radiographs did change management, radiographs were more likely to influence management if patients were over age forty, had pain for over 6 months, had medial or diffuse pain, or had mechanical symptoms. A basic cost analysis revealed that the cost of a clinically useful radiographic series in a patient under 40 years of age was $7,600, in contrast to $413 for a useful series in patients above the age of 40. CONCLUSION: Data from the current study support the hypothesis that for the younger patient population, routine radiographic imaging as a screening tool may be of little clinical benefit. Factors supporting obtaining screening radiographs include age greater than 40, knee pain for greater than 6 months, the presence of medial or diffuse knee pain, and the presence of mechanical symptoms. LEVEL OF EVIDENCE: II.