Impact of COVID-19 on clinical outcomes following total shoulder arthroplasty.

Background: The coronavirus (COVID-19) pandemic has introduced patient stressors and changes to perioperative protocols in total shoulder arthroplasty (TSA). The purpose of this study is to evaluate the short-term effects of the COVID-19 pandemic on various patient outcomes and satisfaction following elective TSA. Methods: A retrospective review was performed on 147 patients who underwent primary TSA at a single institution between June 2019 and December 2020. Patients were divided into 2 cohorts: pre-COVID (June 2019-March 2020; n = 74) and post-COVID (April 2020-December 2020; n = 73). No elective TSA were performed between 10 March 2020 and 23 April 2020 at our institution. Data were collected prospectively both pre- and postoperatively. Range of motion (ROM) testing included active abduction, internal rotation, and external rotation. Patient reported outcome measures (PROMs) included global shoulder function, Simple Shoulder Test, American Shoulder and Elbow Surgeons, Visual Analog Scale pain scoring systems, and patient satisfaction. ROM and PROMs were compared at preoperative, 3-month follow-up, and 12-month follow-up intervals. Operative time, length of stay (LOS), 90-day readmission, and 90-day reoperation were also compared. Results: There were no differences in baseline patient characteristics. The operative time, LOS, home discharge rate, readmission, and reoperation did not differ between groups. For both cohorts, the PROMs and ROM improved at each follow-up visit postoperatively. While preoperative abduction, internal rotation, and external rotation were significantly greater in the post-COVID group, all ROM measures were similar at 3-month and 12-month follow-up visits. There was no difference in pain, global function, Simple Shoulder Test, American Shoulder and Elbow Surgeons, or patient satisfaction between groups at all time intervals. Conclusions: Patients undergoing elective TSA amidst the COVID-19 pandemic demonstrate excellent PROMs, ROM, and high satisfaction up to 12-months postoperatively that are comparable to pre-pandemic standards. Operative time, LOS, discharge destination, as well as 90-day readmission and reoperation rates were not impacted by the pandemic. Patients can expect similar outcomes for TSA when comparing pre-COVID to post-COVID as the pandemic continues.

Pumpkin carving knife injuries: National incidence and trends of hand injury.

INTRODUCTION: Seasonal media reports often describe the dangers of pumpkin carving, yet little data exists regarding the actual incidence of hand injuries resulting from pumpkin carving. The purpose of this study is to describe, quantify, and trend ED encounters associated with pumpkin-related knife injuries. METHODS: The National Electronic Injury Surveillance System (NEISS) was queried for pumpkin-related knife injuries from 2012 to 2021. Patient demographic and injury data was collected and analyzed to describe trends in incidence, patient demographics, and injury patterns associated with an ED encounter for a pumpkin-related knife injury. RESULTS: There were an estimated 20,579 (95% CI: 17,738-23,420) pumpkin-related knife injuries from 2012 to 2021. The incidence of pumpkin-related knife injuries remained stable over time (R2 = 0.195, P = 0.201). Hand injuries comprised 87.6% of all injuries, with the thumb (33.5%) and index finger (25.0%) most commonly affected. Men and women were injured at similar rates (51.6% vs 48.4%). The most common demographic injured were 10 to 19-year olds (31.5%) followed by children <10-years old (19.5%). Women ages 10 to 19-years old were the most commonly injured subgroup (10.0% of all injuries). Most ED presentations occurred on Saturdays (16.5%) or Sundays (23.3%). The large majority occurred during the months of October (83.5%) followed by November (11.2%), with almost half of all cases (45.6%) occurring in the last week of October. Peak incidence of injury occurred on October 30th. CONCLUSION: Pumpkin-related knife injuries are a preventable cause of hand injury with predictably high-incidence in fall months. Additionally, our data suggests further precautions should be taken to prevent injury in pediatric patients. Understanding at-risk populations in addition to implementing public safety initiatives and education on safe pumpkin-carving techniques could prevent serious injuries in the future.

Increased Risk of Short-Term Complications and Venous Thromboembolism in Latarjet-Bristow Procedures Compared With Bankart Repairs.

PURPOSE: To (1) determine the rate of surgical complications and venous thromboembolism (VTE) in patients undergoing arthroscopic Bankart repair, open Bankart repair, or Latarjet-Bristow; and (2) assess potential risk factors for surgical complications and VTE in patients undergoing shoulder stabilization procedures. METHODS: The NSQIP database was used to identify patients undergoing isolated surgery for shoulder instability from 2005 to 2017. Demographic data were collected and compared. Logistic regression was used to assess the risk factors for developing a postoperative complication, and regression analyses were used to evaluate the odds of postoperative complications between types of surgery. RESULTS: We identified 7,233 patients for inclusion. Patients undergoing Latarjet-Bristow were more likely to be male and Black and to report current tobacco use. Overall, there was a low rate of surgical complications (0.4%) and VTE (0.2%). However, patients undergoing Latarjet-Bristow had nearly a 10-fold increase in the risk of surgical complications compared with an arthroscopic or open Bankart repair (1.9% versus 0.2%, P < .001), including deep surgical site infections, return to operating room within 30 days, and symptomatic VTE (deep venous thrombosis rate: arthroscopic Bankart repair, 0.1%; Latarjet-Bristow, 0.8%; P < .001). There were no differences in the odds of developing a surgical complication or VTE between patients undergoing arthroscopic or open Bankart repair. CONCLUSION: This study used a nationally representative, widely validated, peer-reviewed database to demonstrate that patients undergoing a Latarjet-Bristow procedure are at significantly higher risk for short-term postoperative complications, including deep surgical site infections, return to the operating room, and symptomatic VTE, than those undergoing Bankart repair. These findings should not discourage surgeons from proceeding with a coracoid transfer procedure when indicated for glenoid deficiencies, but should inform preoperative counseling and help guide perioperative care to optimize patient outcomes. LEVEL OF EVIDENCE: III, retrospective comparative trial.

Effects of the Obesity Epidemic on Total Hip and Knee Arthroplasty Demographics.

BACKGROUND: Higher body mass index (BMI) is a well-known risk factor for the development of hip and knee osteoarthritis and predicts total hip arthroplasty (THA) and total knee arthroplasty (TKA) at an earlier age. The purpose of this study is to document the nationwide trends in age and obesity in primary THA and TKA throughout the obesity epidemic. METHODS: A retrospective analysis of the National Inpatient Sample database was conducted on patients undergoing primary THA and TKA for primary OA between 2002 and 2017. Analysis of variance and chi-square tests were performed to examine changes in age and obesity percentage over time, respectively. Pearson correlations were used to assess the relationship between patient age, BMI, and year of surgery. RESULTS: A total of 688,371 THA and 1,556,651 TKA were identified over the sixteen-year period. Between 2002 and 2017, the proportion of obese patients increased for both THA (7.0% to 22.7%, P < .001) and TKA (10.7% to 30.4%, P < .001). Mean age significantly decreased for both THA (66.7 to 65.9 years, P < .001) and TKA (67.6 to 66.8 years; P < .001). Over time, BMI significantly increased (THA: r = 0.221 vs. TKA: r = 0.272) and patient age decreased (THA: r = -0.031 vs. TKA: r = -0.137) for both procedures (P < .001 for all). CONCLUSION: THA and TKA patients have become younger and increasingly more obese throughout the obesity epidemic, as obesity rates have tripled over this time period. The current investigation is the first to demonstrate significant trends in both age and obesity in the THA and TKA populations on a national level. LEVEL OF EVIDENCE: III.

Non-Orthopedic Encounters Increase Opioid Exposure in Joint Osteoarthritis: A Single-Institution Analysis.

BACKGROUND: There has been little-to-no evidence to support the use of opioid analgesia as a treatment modality for osteoarthritis (OA). Chronic opioid use has been associated with peri-operative and post-operative complications with joint reconstruction. The purpose of this study is to compare opioid-prescribing habits for OA between orthopedic and non-orthopedic physicians to identify encounters that increase opioid exposure. METHODS: A retrospective chart review was performed on opioid-naive adult patients with outpatient opioid prescriptions for OA at a single academic institution between 2013 and 2018. Patients with prior surgery or opioid prescriptions were excluded. Independent t-tests and analysis of variance were used to compare prescription characteristics among providers. RESULTS: A total of 9625 opioid prescriptions were identified. Non-orthopedic providers account for 92% of prescriptions vs 8% by orthopedic surgeons. The greatest number of prescriptions is written by Internal Medicine (37.1%) and Family Medicine physicians (36.0%). Non-orthopedic physicians prescribe a greater number of prescriptions per patient, dosages, and refills (P < .001 for all). Non-orthopedic encounters are associated with increased risk for prescription dosages ≥50 MME/d (odds ratio 5.81, 95% confidence interval 4.35-7.81, P < .001) and 90 MME/d (odds ratio 18.2, 95% confidence interval 4.43-35.70, P < .001). CONCLUSION: The majority of opioid prescriptions for OA are written by non-orthopedic providers, with higher prescription rates, dosages, and more refills than orthopedic surgeons. OA is a common condition that will benefit from multi-disciplinary awareness to minimize unnecessary opioid exposure and reduce potential complications with joint arthroplasty.

Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2: A Randomized Clinical Trial.

PURPOSE: To test the effects of an encapsulated cell-based delivery of a neuroprotective agent, ciliary neurotrophic factor (CNTF), on progression of macular telangiectasia type 2, a neurodegenerative disease with no proven effective therapy. DESIGN: Randomized sham-controlled clinical trial. PARTICIPANTS: Ninety-nine study eyes of 67 eligible participants were enrolled. METHODS: Single-masked randomized clinical trial of 24 months' duration conducted from May 2014 through April 2017 in 11 clinical centers of retinal specialists in the United States and Australia. Participants were randomized 1:1 to surgical implantation of intravitreal sustained delivery of human CNTF versus a sham procedure. MAIN OUTCOME MEASURES: The primary outcome was the difference in the area of neurodegeneration as measured in the area of the ellipsoid zone disruption (or photoreceptor loss) measured on spectral-domain (SD) OCT images at 24 months from baseline between the treated and untreated groups. Secondary outcomes included comparison of visual function changes between treatment groups. RESULTS: Among the 67 participants who were randomized (mean age, 62±8.9 years; 41 women [61%]; 58 white persons [86%]), 65 (97%) completed the study. Two participants (3 study eyes) died and 3 participants (4 eyes) were found ineligible. The eyes receiving sham treatment had 31% greater progression of neurodegeneration than the CNTF-treated eyes. The difference in mean area of photoreceptor loss was 0.05±0.03 mm2 (P = 0.04) at 24 months. Retinal sensitivity changes, measured using microperimetry, were correlated highly with the changes in the area of photoreceptor loss (r = 0.86; P < 0.0001). The mean retinal sensitivity loss of the sham group was 45% greater than that of the treated group (decrease, 15.81±8.93 dB; P = 0.07). Reading speed deteriorated in the sham group (-13.9 words per minute) with no loss in the treated group (P = 0.02). Serious adverse ocular effects were found in 2 of 51 persons (4%) in the sham group and 2 of 48 persons (4%) in the treated group. CONCLUSIONS: In participants with macular telangiectasia type 2, a surgical implant that released CNTF into the vitreous cavity, compared with a sham procedure, slowed the progression of retinal degeneration. Further research is needed to assess longer-term clinical outcomes and safety.

Sustained Benefit from ivacaftor demonstrated by combining clinical trial and cystic fibrosis patient registry data.

RATIONALE: In clinical trials, patients with cystic fibrosis and a G551D mutation who received ivacaftor experienced improvements in pulmonary and nutritional outcomes. However, whether these improvements reflect a change in disease trajectory cannot be determined without longer-term analyses with an appropriate comparator population. OBJECTIVES: To examine, over a 3-year period, whether ivacaftor therapy affects pulmonary function and nutritional measures in patients with CF with a G551D mutation compared with patients with CF who are homozygous for the F508del mutation. METHODS: A propensity score was used to match patients with CF greater than or equal to 6 years of age who have a G551D mutation and received ivacaftor in clinical trials for up to 144 weeks with data from patients in the U.S. Cystic Fibrosis Foundation Patient Registry who are homozygous for the F508del mutation. Matching was based on variables including age, sex, weight for age, height for age, body mass index for age, % predicted FEV1, and chronic therapies (dornase alfa, inhaled antibiotics, inhaled and oral corticosteroids). MEASUREMENTS AND MAIN RESULTS: By calculating the annual estimated rate of decline in lung function for G551D patients receiving ivacaftor and comparing it with the rate of decline in lung function for matched F508del control patients, we show that the rate of lung function decline in G551D ivacaftor-treated patients was slower by nearly half. Moreover, treatment with ivacaftor is shown to improve body mass index and weight-for-age z scores for G551D patients over the 3-year analysis period. CONCLUSIONS: These findings suggest that ivacaftor is a disease-modifying therapy for the treatment of cystic fibrosis.

Effect of intercalator substituent and nucleotide sequence on the stability of DNA- and RNA-naphthalimide complexes.

DNA intercalators are commonly used as anti-cancer and anti-tumor agents. As a result, it is imperative to understand how changes in intercalator structure affect binding affinity to DNA. Amonafide and mitonafide, two naphthalimide derivatives that are active against HeLa and KB cells in vitro, were previously shown to intercalate into DNA. Here, a systematic study was undertaken to change the 3-substituent on the aromatic intercalator 1,8-naphthalimide to determine how 11 different functional groups with a variety of physical and electronic properties affect binding of the naphthalimide to DNA and RNA duplexes of different sequence compositions and lengths. Wavelength scans, NMR titrations, and circular dichroism were used to investigate the binding mode of 1,8-naphthalimide derivatives to short synthetic DNA. Optical melting experiments were used to measure the change in melting temperature of the DNA and RNA duplexes due to intercalation, which ranged from 0 to 19.4°C. Thermal stabilities were affected by changing the substituent, and several patterns and idiosyncrasies were identified. By systematically varying the 3-substituent, the binding strength of the same derivative to various DNA and RNA duplexes was compared. The binding strength of different derivatives to the same DNA and RNA sequences was also compared. The results of these comparisons shed light on the complexities of site specificity and binding strength in DNA-intercalator complexes. For example, the consequences of adding a 5'-TpG-3' or 5'-GpT-3' step to a duplex is dependent on the sequence composition of the duplex. When added to a poly-AT duplex, naphthalimide binding was enhanced by 5.6-11.5°C, but when added to a poly-GC duplex, naphthalimide binding was diminished by 3.2-6.9°C.

Identification and functional validation of the novel antimalarial resistance locus PF10_0355 in Plasmodium falciparum.

The Plasmodium falciparum parasite's ability to adapt to environmental pressures, such as the human immune system and antimalarial drugs, makes malaria an enduring burden to public health. Understanding the genetic basis of these adaptations is critical to intervening successfully against malaria. To that end, we created a high-density genotyping array that assays over 17,000 single nucleotide polymorphisms (∼ 1 SNP/kb), and applied it to 57 culture-adapted parasites from three continents. We characterized genome-wide genetic diversity within and between populations and identified numerous loci with signals of natural selection, suggesting their role in recent adaptation. In addition, we performed a genome-wide association study (GWAS), searching for loci correlated with resistance to thirteen antimalarials; we detected both known and novel resistance loci, including a new halofantrine resistance locus, PF10_0355. Through functional testing we demonstrated that PF10_0355 overexpression decreases sensitivity to halofantrine, mefloquine, and lumefantrine, but not to structurally unrelated antimalarials, and that increased gene copy number mediates resistance. Our GWAS and follow-on functional validation demonstrate the potential of genome-wide studies to elucidate functionally important loci in the malaria parasite genome.

Long-Term Oral Steroid Use: A Unique Risk Factor in 4-Corner Fusion Compared With Other Wrist Salvage Operations.

INTRODUCTION: Salvage procedures such as proximal row carpectomy, 4-corner fusion, total wrist arthroplasty, and total wrist arthrodesis are commonly used at the end stages of wrist arthritis. These operations have high complication rates, and significant controversy exists regarding the selection of procedure. Long-term oral glucocorticoid therapy has previously been identified as a risk factor for complications in multiple orthopedic procedures. The purpose of this study is to investigate the effect long-term oral preoperative corticosteroid use has on complications after different salvage operations for wrist arthritis. METHODS: The National Surgical Quality Improvement Program database was queried to identify patients who underwent proximal row carpectomy, 4-corner fusion, total wrist arthroplasty, or total wrist fusion between 2005 and 2020. Patients were classified by steroid use. Univariate analysis and multivariate logistic regression were used to assess the risk of complications. RESULTS: A total of 1298 patients were identified. Overall, steroid use was found to be independently associated with a higher complication rate. On multivariate analysis of patients who underwent 4-corner fusion, steroid use was found to be associated with higher complication rate and surgical site infection rate. Steroid use was not associated with increased complications in patients who underwent proximal row carpectomy, total wrist arthroplasty, or total wrist fusion when examined individually. CONCLUSION: Long-term oral corticosteroid therapy was associated with an increased risk of postoperative infections in patients who underwent 4-corner fusion, which was not found in other wrist salvage operations.

National incidence and trends of bicycle injury.

Bicycle utilization continues to increase annually, and this trend was recently accelerated by the coronavirus disease of 2019 pandemic. There is limited epidemiologic data, however, regarding the prevalence and nature of bicycle-related injuries. Therefore, the purpose of this study is to characterize trends in bicycle-related injuries. The National Electronic Injury Surveillance System was queried for bicycle-related injuries from 2012 to 2021. Patient demographic and injury data were collected and analyzed to describe trends in incidence, patient demographics, and injury patterns associated with an emergency department encounter for a bicycle-related injury. There were an estimated 4,666,491 (95% confidence interval: 4,661,472-4,671,510) bicycle-related injuries from 2012 to 2021. The incidence of these injuries has significantly decreased over time (R = -0.983, R2 = 0.967, p < 0.001). However, the rate of injury in elderly patients increased over time. Injuries occurred most often during summer months (36%) and on weekend days (31.9%). Males and younger patients were more commonly injured. Head injuries were the most commonly affected body part among all age groups. Fractures were the most common injury type overall. Upper extremity injuries were more common than the lower extremity. Despite increased public bicycle utilization, there is a significant downtrend in bicycle-related injuries over the last decade. Injuries among elderly patients are becoming more common, who demonstrate a high rate of fracture and head injury. Fractures and head injuries were the most common injuries among all age groups, highlighting the importance of bicycle safety initiatives and helmet-wearing regardless of age.

Efferent duct toxicity with secondary testicular changes in rats following administration of a novel leukotriene A4 hydrolase inhibitor.

The efferent ducts represent an important site of toxicity in the male reproductive tract but are not routinely examined in toxicity studies. This article describes a primary efferent duct toxicity that resulted in secondary testicular changes in rats. Male rats were administered LTI-1, a leukotriene A4 hydrolase inhibitor, at doses up to 250 mg/kg/d for 3 month or 150 mg/kg/d for 6 month. At the highest dose levels, testicular changes were predominantly unilateral and characterized by diffuse dilation or atrophy of the seminiferous tubules. These testicular changes correlated with granulomatous inflammation in the corresponding efferent ducts, suggesting that the mechanism for the testicular changes involves obstruction and impaired fluid reabsorption in the efferent ducts. Subsequent buildup in fluid volume and back-pressure upstream of the blockage cause dilation of the seminiferous tubules, which, in its late stages, progress to tubular atrophy. There are important differences in efferent duct anatomy between rats and larger mammals, including humans, such that the latter are less susceptible to testicular injury by this mechanism. Because of the limited relevance of this rat-specific finding to humans, it is important to distinguish testicular changes secondary to efferent duct toxicity from primary drug-induced testicular toxicity.

Risk Factors for 30-Day Complications and Unplanned Reoperation Following Surgical Treatment of Distal Radius Fractures.

BACKGROUND: The purpose of this study was to identify demographic data, medical comorbidities, and perioperative factors that are associated with increased risk of overall surgical complications, wound complications, and reoperation within 30 days of open reduction and internal fixation (ORIF) of distal radius fractures. METHODS: All adult patients undergoing ORIF of distal radius fractures in the National Surgical Quality Improvement Program database between 2005 and 2020 were identified. Patients were excluded for secondary procedures, open/infected injuries, or inpatient surgical setting. Demographic data, medical comorbidities, and perioperative data were examined for each patient, and patients were grouped by the presence or absence of any surgical complication. Univariate analysis and multivariate logistic regression were used to identify risk factors. RESULTS: A total of 20 301 patients from between 2005 and 2020 met the inclusion criteria, of which 219 complications (1.1% of cases) were identified. Following multivariate analysis, independent risk factors found to be associated with surgical complications included male sex, smoking, heart failure, longer operative time, and American Society of Anesthesiologists (ASA) classification of 3 or higher. CONCLUSION: Male sex, smoking, heart failure, prolonged operative time, and ASA status of 3 or higher are associated with an increased risk of surgical complications following ORIF of distal radius fractures. These complications, with the exception of heart failure, were also associated with an increased risk of wound complications. Finally, male sex, nonwhite race, smoking, dialysis, prolonged operative time, and 3 or higher ASA class were associated with reoperations. Understanding these risk factors allows surgeons to better predict and prevent complications in high-risk populations.

Self-assembled monolayers of alkoxy-substituted octadehydrodibenzo[12]annulenes on a graphite surface: attempts at peri-benzopolyacene formation by on-surface polymerization.

Self-assembled monolayers of a series of tetraalkoxy-substituted octadehydrodibenzo[12]annulene (DBA) derivatives 1c-g possessing butadiyne linkages were studied at the 1,2,4-trichlorobenzene (TCB) or 1-phenyloctane/graphite interface by scanning tunneling microscopy (STM). The purpose of this research is not only to investigate the structural variation of two-dimensional (2D) monolayers, but also to assess a possibility for peri-benzopolyacene formation by two-dimensionally controlled polymerization on a surface. As a result, the formation of three structures, porous, linear, and lamella structures, were observed by changing the alkyl chain length and the solute concentration. The formation of multilayers of the lamella structure was often observed for all compounds. The selection of molecular networks is basically ascribed to intermolecular and molecule-substrate interactions per unit area and network density. The selective appearance of the linear structure of 1d is attributed to favorable epitaxial registry matching between the substrate lattice and the overlayer lattice. Even though the closest interatomic distance between the diacetylenic units of the DBAs in the lamella structure (approximately 0.6 nm) is slightly larger compared to the typical distances necessary for topochemical polymerization, the reactivity toward external stimuli (electronic-pulse irradiation from an STM tip and UV irradiation) was investigated. Unfortunately, no evidence for polymerization of the DBAs on the surface was observed. The present results indicate the necessity for further designing a suitable system for the on-surface construction of structurally novel conjugated polymers, which are otherwise difficult to prepare.

Protonation activates anion binding and alters binding selectivity in new inherently fluorescent 2,6-bis(2-anilinoethynyl)pyridine bisureas.

A new class of 2,6-bis(2-anilinoethynyl)pyridine-based bisureas forms 1 : 1 complexes with halides; protonation enhances binding by over one order of magnitude, alters the binding selectivity, and provides a colorimetric indication of anion binding.

Risk factors for rate of decline in forced expiratory volume in one second in children and adolescents with cystic fibrosis.

OBJECTIVES: To characterize the rate of decline of forced expiratory volume in 1 second (FEV(1)) in children and adolescents with cystic fibrosis and to identify and compare risk factors associated with FEV(1) decline. STUDY DESIGN: The rate of decline in FEV(1)% predicted over 3 to 6 years in 3 different age groups was determined. Risk factors for decline were identified and compared among and within age groups as a function of disease severity with repeated-measures, mixed-model regression. RESULTS: Mean (+/-SD) baseline FEV(1)% predicted was 88.4% +/- 20.5% for 6- to 8-year-olds (n = 1811), 85.3% +/- 20.8% for 9- to 12-year-olds (n = 1696), and 78.4% +/- 22.0% for 13- to 17-year-olds (n = 1359). Decline in FEV(1)% predicted/year was -1.12, -2.39, and -2.34, respectively. High baseline FEV(1) and persistent crackles were significant independent risk factors for decline across all age groups. Female sex, Pseudomonas aeruginosa infection, low weight-for-age, sputum, wheezing, sinusitis, pulmonary exacerbations treated with intravenous antibiotics, elevated liver test results, and pancreatic insufficiency were also identified as independent risk factors in some age groups. CONCLUSIONS: This study identifies risk factors for FEV(1) decline in children and adolescents with cystic fibrosis. Clinicians should not be reassured by high lung function, particularly in young children, because this factor, among others, is independently associated with steeper decline in FEV(1).

Carbon networks based on benzocyclynes. 6. synthesis of graphyne substructures via directed alkyne metathesis.

Intramolecular ring closing alkyne metathesis afforded the graphyne biscyclyne (3) in high macrocyclization yield and good overall yield. This methodology also furnished the tris[12]cyclyne 4, which contains the longest linear diphenylacetylene conjugation pathway for any graphyne substructure based on the tribenzo[12]cyclyne core.

Solid-State Examination of Conformationally Diverse Sulfonamide Receptors Based on Bis(2-anilinoethynyl)pyridine, -Bipyridine, and -Thiophene.

Utilizing an induced-fit model and taking advantage of rotatable acetylenic C(sp)-C(sp2) bonds, we disclose the synthesis and solid-state structures of a series of conformationally diverse bis-sulfonamide arylethynyl receptors using either pyridine, 2,2'-bipyridine, or thiophene as the core aryl group. Whereas the bipyridine and thiophene structures do not appear to bind guests in the solid state, the pyridine receptors form 2 + 2 dimers with water molecules, two halides, or one of each, depending on the protonation state of the pyridine nitrogen atom. Isolation of a related bis-sulfonimide derivative demonstrates the importance of the sulfonamide N-H hydrogen bonds in dimer formation. The pyridine receptors form monomeric structures with larger guests such as BF4- or HSO4-, where the sulfonamide arms rotate to the side opposite the pyridine N atom.

Pulmonary exacerbations in cystic fibrosis.

The clinical characteristics most relevant to the decision to treat for a pulmonary exacerbation with antibiotics in cystic fibrosis patients were determined. Variables including age, increased cough frequency and sputum production, new crackles and wheezing, asthma, symptomatic sinusitis, hemoptysis, decreased lung function, weight loss, and new acquisition of Pseudomonas aeruginosa were collected in a large prospective multicenter database (Epidemiologic Study of Cystic Fibrosis). During a 12-month baseline period, data from 11692 patients were compared with data collected during the subsequent 6-month study period. Because pulmonary function assessments were unavailable for patients <6 years of age, separate analyses were done for those <6 and >or=6 years of age. The outcome of interest was any antibiotic treatment in the 6-month study period reported as indicated for an exacerbation. Characteristics with the most discriminatory power were determined using stepwise multiple logistic regression. For patients <6 years of age, the strongest independent associations with treatment for a pulmonary exacerbation were new crackles, increased cough frequency, decline in weight, and increased sputum production. For those patients >or=6 years of age, the strongest independent associations were a relative decrease in percent predicted forced expired volume in 1 sec, increased cough frequency, new crackles, and hemoptysis. The presence of three or more of these key characteristics was strongly associated with the occurrence of a treated exacerbation. The reproducibility of the model over time was confirmed by application to a subsequent set of data. This model has potential for use as an outcome measure in clinical trials, and to assist in treatment decisions for individual patients.