Microwave-induced one-pot synthesis of 3-imidazolyl indole clubbed 1,2,3-triazole hybrids as antiproliferative agents and density functional theory study.

Herein, we outline a highly efficient PEG-4000-mediated one-pot three-component reaction for the synthesis of 3-imidazolyl indole clubbed 1,2,3-triazole derivatives (5a-r) at up to 96% yield as antiproliferative agents. This three-component protocol offers the advantages of an environmentally benign reaction, excellent yield, quick response time, and operational simplicity triggered by the copper catalyst under microwave irradiation. All the synthesized compounds were tested for antiproliferative activity against six human solid tumor cell lines, that is, A549 and SW1573 (nonsmall cell lung), HBL100 and T-47D (breast), HeLa (cervix), and WiDr (colon). Among them, six compounds, 5g-j, 5m, and 5p, demonstrated effective antiproliferative action with GI50 values under 10 µM. Furthermore, density functional theory (DFT) calculations were performed for all the synthesized molecules through geometry optimizations, frontier molecular orbital approach, and molecular electrostatic potential (MESP). The theoretical DFT calculation was performed using the DFT/B3LYP/6-31+G (d,p) basis set. Moreover, the biological reactivity of all the representative synthesized molecules was compared with the theoretically calculated quantum chemical descriptors and MESP 3D plots. We also investigated the drug-likeness characteristic and absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction. In general, our approach enables environmentally friendly access to 3-imidazolyl indole clubbed 1,2,3-triazole derivatives as prospective antiproliferative agents.

Diversity-oriented synthesis of 1H-1,2,3-triazole tethered pyrazolo[5,1-b]quinazoline hybrids as antimicrobial agents.

A straightforward and high yielding synthetic approach is employed to synthesize the novel 1H-1,2,3-triazole tethered pyrazolo[5,1-b]quinazoline hybrids 7(a-t) as new antimicrobial agents with two pharmacophore in the effective two step synthesis. The first step is the four component one-pot synthesis of highly functionalized pyrazolo[5,1-b]quinazolines 5(a-j) catalysed by TBAB, with the advantages of an environmentally benign reaction, high yielding, quick reaction time, and operational simplicity. In the subsequent stage, CuSO4/NaAsc system was employed to synthesize the 1H-1,2,3-triazole tethered pyrazolo[1,5-b]quinazoline hybrids as 1H-1,2,3-triazoles are the structures of great diversity and importance in diverse therapeutics containing numerous biological activities. The antimicrobial activity of all the synthesized hybrid compounds have been preliminary tested using the broth dilution technique against two gram-positive and two gram-negative bacterial strains as well as two fungal strains. In comparison to standard drugs, the majority of compounds exhibited good to moderate activity. Among the all the compounds, 7a (MIC 18.54 µM) against Pseudomonas aeruginosa, 7j (MIC 89.76 µM) against Bacillus subtilis as well as Rhizopus oryzae and 7t (MIC 84.88 µM) against Aspergillus parasiticus have remarkable antimicrobial potency as compared to standard drug.

Ultrasound-promoted convenient and ionic liquid [BMIM]BF4 assisted green synthesis of diversely functionalized pyrazolo quinoline core via one-pot multicomponent reaction, DFT study and pharmacological evaluation.

An ultrasound-assisted green protocol for one-pot synthesis of a new series of pharmaceutically relevant pyrazolo quinoline derivatives (4a-t) were synthesized, characterized, and evaluated using DFT and biological activities. Pyrazolo quinoline derivatives (4a-t) were synthesized via a three-component tandem reaction of 1,3-dicarbonyl compound (1a-b), substituted aromatic aldehyde (2a-o), and 5-amino indazole (3a) in the presence of 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM]BF4 ionic liquid in ethanol at ambient conditions. The main purpose of the present work is selective functionalization of pyrazolo quinoline (4a-t) core excluding another potential parallel reaction under environmentally benign reaction conditions. The present protocol shows features such as amphiphilic behavior of ionic liquid during reaction transformation, and reusability of the [BMIM]BF4 ionic liquid under mild reaction condition. All newly derived compounds were evaluated for their in vitro anti-inflammatory and antioxidant activity. Among them, compound 4c showed encouraging antioxidant activity compared with standard antioxidant ascorbic acid, and compounds 4n and 4r displayed very good anti-inflammatory activity compared with a standard drug. In this study, a theoretical computational density functional study was also executed to perform the geometry optimizations, frontier molecular orbital approach, and molecular electrostatic potential (MESP). The DFT study was carried out with the basis set DFT/B3LYP/6-31+G (d, p) level of theory. The quantum chemical descriptors (QCDS) and MESP diagrams were plotted to examine the biological reactivities of representative pyrazolo quinolines (4a-t).

Fixed- vs. variable-angle humeral neck cut in anatomic total shoulder arthroplasty: a randomized controlled trial.

BACKGROUND: Variable neck-shaft angle (NSA) stemmed humeral components have been incorporated into certain implant designs to better re-create normal anatomy in total shoulder arthroplasty (TSA). The purpose of this study was to determine if premorbid glenohumeral joint anatomy is better restored with a fixed- vs. variable-NSA prosthesis. METHODS: A randomized controlled trial was performed including 50 patients with osteoarthritis indicated for primary anatomic TSA. Patients were randomized preoperatively to receive either a variable- (n = 26) or fixed-NSA (n = 24) prosthesis. Humeral neck cut in the variable-NSA group matched the patient's anatomic neck, with prosthetic NSA of 127.5°, 132.5°, and 137.5° available. Fixed-NSA cuts were made with an intramedullary guide of 132.5°. Preoperative and postoperative radiographs were evaluated for specific radiographic anatomic variables: NSA, head thickness, tuberosity-to-head height, head offset, articular arc, greater tuberosity offset, and center of rotation (COR). Postoperative radiographic criteria were compared between groups. RESULTS: No differences were found between groups in demographics or preoperative radiographic measures. When comparing average difference in preoperative and postoperative measurements in the fixed-NSA group, the humeral head offset from the humeral shaft axis significantly decreased by 1.4 mm (P = .046), and the COR moved superiorly (3.0 mm, P = .002) without significant medialization or lateralization. In the variable angle group, humeral head offset decreased but did not reach significance (1.2 mm, P = .091), and the COR also moved superiorly (2.9 mm, P < .001) without significant medialization or lateralization. All remaining radiographic parameters did not significantly change from pre- to postoperative imaging. In comparing the fixed- and variable-NSA groups' net change from the premorbid measurements, no significant differences were found in tuberosity-to-head height, head offset, or COR position in both the horizontal and vertical planes. CONCLUSIONS: Both fixed- and variable-NSA anatomic TSA humeral components demonstrate adequate restoration of premorbid anatomy radiographically.

What was the Prevalence of COVID-19 in Asymptomatic Patients Undergoing Orthopaedic Surgery in One Large United States City Mid-pandemic?

BACKGROUND: Many patients with coronavirus disease 2019 (COVID-19) are asymptomatic. The prevalence of COVID-19 in orthopaedic populations will vary depending on the time and place where the sampling is performed. The idea that asymptomatic carriers play a role is generalizable but has not been studied in large populations of patients undergoing elective orthopaedic surgery. We therefore evaluated this topic in one large, metropolitan city in a state that had the ninth-most infections in the United States at the time this study was completed (June 2020). This work was based on a screening and testing protocol that required all patients to be tested for COVID-19 preoperatively. QUESTIONS/PURPOSES: (1) What is the prevalence of asymptomatic COVID-19 infection in patients planning to undergo orthopaedic surgery in one major city, in order to provide other surgeons with a framework for assessing COVID-19 rates in their healthcare system? (2) How did patients with positive test results for COVID-19 differ in terms of age, sex, and orthopaedic conditions? (3) What proportion of patients had complications treated, and how many patients had a symptomatic COVID-19 infection within 30 days of surgery (recognizing that some may have been missed and so our estimates of event rates will necessarily underestimate the frequency of this event)? METHODS: All adult patients scheduled for surgery at four facilities (two tertiary care hospitals, one orthopaedic specialty hospital, and one ambulatory surgery center) at a single institution in the Philadelphia metropolitan area from April 27, 2020 to June 12, 2020 were included in this study. A total of 1295 patients were screened for symptoms, exposure, temperature, and oxygen saturation via a standardized protocol before surgical scheduling; 1.5% (19 of 1295) were excluded because they had COVID-19 symptoms, exposure, or recent travel based on the initial screening questionnaire, leaving 98.5% (1276 of 1295) who underwent testing for COVID-19 preoperatively. All 1276 patients who passed the initial screening test underwent nasopharyngeal swabbing for COVID-19 via reverse transcription polymerase chain reaction before surgery. The mean age at the time of testing was 56 ± 16 years, and 53% (672 of 1276) were men. Eighty-seven percent (1106), 8% (103), and 5% (67) were tested via the Roche, Abbott, and Cepheid assays, respectively. All patients undergoing elective surgery were tested via the Roche assay, while those undergoing nonelective surgery received either the Abbott or Cepheid assay, based on availability. Patients with positive test results undergoing elective surgery had their procedures rescheduled, while patients scheduled for nonelective surgery underwent surgery regardless of their test results. Additionally, we reviewed the records of all patients at 30 days postoperatively for emergency room visits, readmissions, and COVID-19-related complications via electronic medical records and surgeon-reported complications. However, we had no method for definitively determining how many patients had complications, emergency department visits, or readmissions outside our system, so our event rate estimates for these endpoints are necessarily best-case estimates. RESULTS: A total of 0.5% (7 of 1276) of the patients tested positive for COVID-19: five via the Roche assay and two via the Abbott assay. Patients with positive test results were younger than those with negative results (39 ± 12 years versus 56 ± 16 years; p = 0.01). With the numbers available, we found no difference in the proportion of patients with positive test results for COVID-19 based on subspecialty area (examining the lowest and highest point estimates, respectively, we observed: trauma surgery [3%; 2 of 68 patients] versus hip and knee [0.3%; 1 of 401 patients], OR 12 [95% CI 1-135]; p = 0.06). No patients with negative preoperative test results for COVID-19 developed a symptomatic COVID-19 infection within 30 days postoperatively. Within 30 days of surgery, 0.9% (11 of 1276) of the patients presented to the emergency room, and 1.3% (16 of 1276) were readmitted for non-COVID-19-related complications. None of the patients with positive test results for COVID-19 preoperatively experienced complications. However, because some were likely treated outside our healthcare system, the actual percentages may be higher. CONCLUSION: Because younger patients are more likely to be asymptomatic carriers of disease, surgeons should emphasize the importance of taking proper precautions to prevent virus exposure preoperatively. Because the rates of COVID-19 infection differ based on city and time, surgeons should monitor the local prevalence of disease to properly advise patients on the risk of COVID-19 exposure. Further investigation is required to assess the prevalence in the orthopaedic population in cities with larger COVID-19 burdens. LEVEL OF EVIDENCE: Level III, therapeutic study.

Incidence of peripheral nerve injury in revision total shoulder arthroplasty: an intraoperative nerve monitoring study.

BACKGROUND: The incidence of nerve injuries in revision total shoulder arthroplasty (TSA) is not well defined in the literature and may be higher than that in primary procedures, with 1 study reporting a complication rate of 50% for shoulder revisions. Given that continuous intraoperative nerve monitoring (IONM) can be an effective tool in diagnosing evolving neurologic dysfunction and preventing postoperative injuries, the purpose of this study was to report on IONM data and nerve injury rates in a series of revision TSAs. METHODS: A retrospective cohort review of consecutive patients who underwent revision TSA was performed from January 2016 to March 2020. Indications for revision included infection (n = 7); failed total arthroplasty and hemiarthroplasty secondary to pain, dysfunction, and/or loose components (n = 36); and periprosthetic fracture (n = 1). Of the shoulders, 32 underwent revision to a reverse TSA, 6 underwent revision to an anatomic TSA, and 6 underwent spacer placement. IONM data included transcranial electrical motor evoked potentials (MEPs), somatosensory evoked potentials, and free-run electromyography. The motor alert threshold was set at ≥80% signal attenuation in any peripheral nerve. Patients were screened for neurologic deficits immediately following surgery, prior to administration of an interscalene nerve block, and during the first 2 postoperative visits. Additional data collection included surgical indication, sex, laterality, age at surgery, procedure performed, body mass index, history of tobacco use, Charlson Comorbidity Index, medical history, and preoperative range of motion. RESULTS: A total of 44 shoulders in 38 patients were included, with a mean age of 63.2 years (standard deviation, 13.0 years). Of the procedures, 22.4% (n = 10) had an MEP alert, with 8 isolated to a single nerve (7 axillary and 1 radial) and 1 isolated to the axillary and musculocutaneous nerves. Only 1 patient experienced a major brachial plexus alert involving axillary, musculocutaneous, radial, ulnar, and median nerve MEP alerts, as well as ulnar and median nerve somatosensory evoked potential alerts. Age, sex, body mass index, Charlson Comorbidity Index, and preoperative range of motion were not found to be significantly different between cases in which an MEP alert occurred and cases with no MEP alerts. In the postoperative period, no minor or major nerve injuries were found whereas distal peripheral neuropathy developed in 4 patients (9.1%). CONCLUSION: Among 44 surgical procedures, no patients (0%) had a major or minor nerve injury postoperatively and 4 patients (9.1%) complained of distal peripheral neuropathy postoperatively. In this study, we have shown that through the use of IONM, the rate of minor and major nerve injuries can be minimized in revision shoulder arthroplasty.

Effect of perioperative acetaminophen on pain management in patients undergoing rotator cuff repair: a prospective randomized study.

BACKGROUND: Limiting opioid use in perioperative pain management is currently an important focus in orthopedic surgery. The ability of acetaminophen to reduce postoperative opioid consumption while providing acceptable pain management has not been thoroughly investigated in patients undergoing rotator cuff repair (RCR). METHODS: Patients undergoing primary arthroscopic RCR were prospectively randomized to 1 of 3 treatment groups: Group 1 (control) received both 5 mg of oxycodone every 6 hours as needed and 1000 mg of acetaminophen orally every 6 hours as needed after surgery and had the option to take either medication or both. Group 2 (control) received only 5 mg of oxycodone every 6 hours as needed without any additional acetaminophen after surgery. Group 3 received 1000 mg of acetaminophen orally every 6 hours for 1 day prior to and after surgery, which was subsequently decreased to administration every 8 hours during postoperative days 2-5. Group 3 patients were also allowed to take 5 mg of oxycodone every 6 hours as needed after surgery. All patients received interscalene blocks with liposomal bupivacaine (Exparel). Opioid use, pain scores, side effects, and overall satisfaction were assessed daily for the first week after surgery. RESULTS: A total of 57 patients (mean age, 57.8 ± 9.55 years) were included in this study. Baseline demographic characteristics including age, sex, and body mass index were similar between the groups (P > .05). Patients in group 3 took significantly fewer narcotics overall (P = .017) and took significantly fewer pills each day compared with group 2. Group 3 also reported significantly better overall pain control compared with the other groups (P = .040). There were no significant differences in overall patient satisfaction between the groups (P > .05). Additionally, there were no significant differences between groups regarding postoperative medication-associated side effects (P > .05). CONCLUSION: Perioperative acetaminophen represents an important component of multimodal analgesia in appropriately selected patients undergoing shoulder surgery. In this study, the use of perioperative acetaminophen significantly decreased opioid consumption and improved overall pain control after primary arthroscopic RCR.

Early repair of traumatic rotator cuff tears improves functional outcomes.

BACKGROUND: The impact of surgical timing on outcomes involving traumatic rotator cuff tears (RCTs) remains uncertain. The purpose of this study was to determine how functional outcomes are affected by surgical timing in traumatic RCTs. METHODS: We performed a retrospective review of patients with repair of traumatic full-thickness RCTs. Preoperative magnetic resonance imaging scans were evaluated by 2 blinded reviewers to measure RCT area and muscular atrophy. Functional outcomes were assessed via the American Shoulder and Elbow Surgeons (ASES) score, Single Assessment Numeric Evaluation (SANE) score, Simple Shoulder Test score, and visual analog scale (VAS) pain score. Patients were divided into 4 groups based on the time from injury to surgery: 0-2 months (group 1), 2-4 months (group 2), 4-6 months (group 3), and 6-12 months (group 4). Multivariate analysis was performed to assess the impact of surgical timing on functional outcomes. A subanalysis was performed to assess outcomes in patients who underwent surgery within 3 weeks of injury. RESULTS: The study included 206 patients (150 men and 56 women) with a mean age of 60.0 ± 9.7 years and a minimum of 24 months' clinical follow-up (mean, 35.5 months; range, 24-54.4 months). The average tear area was 8.4 ± 6.3 cm2 in group 1 (66 patients), 5.8 ± 5.1 cm2 in group 2 (76 patients), 5.1 ± 4.6 cm2 in group 3 (29 patients), and 3.7 ± 3.1 cm2 in group 4 (35 patients) (P < .001). There were significant differences between the 4 cohorts in the final postoperative ASES score (P = .030) and VAS pain score (P = .032). The multivariate regression demonstrated that patients who underwent surgery within 4 months of injury had estimated improvements of 10.3 points in the ASES score (P = .008), 1.8 points in the Simple Shoulder Test score (P = .001), 8.6 points in the SANE score (P = .033), and 0.93 points in the VAS pain score (P = .028) compared with patients who underwent surgery later. The subanalysis demonstrated that patients who underwent surgery within 3 weeks of injury (n = 13) had significantly better VAS (P = .003), ASES (P = .008), and SANE (P = .019) scores than patients who underwent surgery at between 3 weeks and 4 months after injury (n = 129). CONCLUSIONS: This study demonstrates that surgical repair of traumatic RCTs results in significant improvements in functional outcomes for all patients; however, patients who undergo surgery within 3 weeks can expect the best functional outcomes, with a drop in function in patients who undergo surgery >4 months after injury.

Three-dimensional measures of posterior bone loss and retroversion in Walch B2 glenoids predict the need for an augmented anatomic glenoid component.

HYPOTHESIS: The purpose of this study is to evaluate whether the amount of measured posterior bone loss on 2- and 3-dimensional (2D and 3D) imaging of Walch B2 glenoids can reliably predict the plan for an augmented anatomic glenoid component. METHODS: Patients with Walch B2 glenoids and preoperative computed tomography (CT) scans were retrospectively identified. 2D axial CT scans were reviewed and posterior bone loss was measured by 3 independent reviewers. Images were then formatted into BluePrint (Wright Medical) preoperative planning software. The same 3 reviewers again measured posterior bone loss on 3D imaging. Additionally, all cases were planned with BluePrint software. An augment was used when the following criteria were unable to be satisfied with standard implants: <10° retroversion, <10° superior inclination, ≥90% backside contact, <2 mm medial reaming, and ≤1 peg perforation. RESULTS: Forty-two patients were included in the final analysis with a mean age of 63.1 ± 6.3 years. As measured by BluePrint, the mean retroversion was 23° ± 7° (range = 9°-40°), the mean superior inclination was 5° ± 6° (range = -9° to 22°), and the mean posterior subluxation was 80% ± 17% (range = 41%-95%). The mean 2D bone loss measurements (3.5 ± 1.6 mm) were significantly lower than the mean 3D bone loss (4.0 ± 1.8 mm) measurements (P = .03). There was substantial agreement between reviewers on both 2D and 3D measurements with an interclass correlation of 0.815 (95% confidence interval [CI] 0.714-0.889, P < .001) and an interclass correlation of 0.802 (95% CI 0.683-0.884, P < .001), respectively. Augments were used in 73.8%, 63.4%, and 63.4% of cases by reviewers 1, 2, and 3, respectively, with moderate agreement with a Fleiss kappa of 0.592 (95% CI 0.416-0.769, P < .001). Augment size was moderately, positively correlated with the amount of bone loss on 3D imaging but not with 2D imaging. After multivariate logistic regression, both 3D bone loss and retroversion were found to be predictive for a plan to use an augment. CONCLUSION: Planning for a posterior augment in Walch B2 glenoids is better predicted with 3D imaging than with 2D imaging, as 2D imaging may underestimate posterior bone loss. Additionally, use of a larger augment size is moderately correlated with posterior bone loss on 3D imaging but not 2D imaging. Standard 2D imaging may be limited in cases of posterior bone loss, and 3D imaging may be beneficial for preoperative planning in Walch B2 glenoids.

Social media use by shoulder and elbow surgeons increases the number of ratings on physician review websites.

BACKGROUND: The use of physician review websites by patients is increasingly frequent. One potential way for shoulder and elbow surgeons to enhance their online reputation and attract patients is via social media, yet its impact is unknown. This study sought to analyze the effect of social media use on the number of online ratings and overall rating of shoulder and elbow surgeons. We secondarily studied variables affecting social media use. METHODS: The American Shoulder and Elbow Surgeons directory was probed to identify practicing surgeons. Surgeon evaluation data, including ratings, comments, and reviews, were compiled from 3 physician review websites (Google, Healthgrades, and Vitals). Google was queried to assess for a professional Facebook, Twitter, or Instagram account, as well as obtain information on surgeon training, practice location, and other demographic variables. RESULTS: A total of 646 surgeons met the inclusion criteria (93.8% male and 6.2% female surgeons). Overall, 37% had a professional social media account (Facebook, 23.1%; Twitter, 24.1%; and Instagram, 9.4%). Linear regression analysis showed that Facebook use correlated with an average increase of 48.6 in the number of ratings. No social media platform correlated with physician rating. The surgeons more likely to use social media were those who graduated residency in 2000 or later (40.8% vs. 29.2%), those who practiced in cities with higher populations (mean, 1188.9 vs. 708.4 [per 1000]), and those with more surgeons practicing in the same city (mean, 7.0 vs. 5.0). CONCLUSION: The majority of shoulder and elbow surgeons do not have a professional social media account. Those using this platform are younger and located in more populous cities with more competition. Having a professional social media profile was not correlated with ratings, but there was a positive association with the number of online ratings, and Facebook had the strongest association. Surgeon ratings are overwhelmingly positive with minimal variability; therefore, a high number of ratings confirms a surgeon's exceptional reputation. The residency graduation year, city population, and number of nearby surgeons affected ratings, although the absolute differences were minimal. For shoulder and elbow surgeons, a professional social media account correlates with an increase in the number of online physician ratings. Recent graduates practicing in competitive locations may feel increased pressure to leverage this in an attempt to build their practices.

Perioperative pain management for shoulder surgery: evolving techniques.

Improving management of postoperative pain following shoulder surgery is vital for optimizing patient outcomes, length of stay, and decreasing addiction to narcotic medications. Multimodal analgesia (ie, controlling pain via multiple different analgesic methods with differing mechanisms) is an ever-evolving approach to enhancing pain control perioperatively after shoulder surgery. With a variety of options for the shoulder surgeon to turn to, this article succinctly reviews the pros and cons of each approach and proposes a potential pain management algorithm.

Cutibacterium acnes: a threat to shoulder surgery or an orthopedic red herring?

Cutibacterium acnes is a lipophilic, anaerobic, gram-positive bacillus that mainly colonizes the pilosebaceous glands of human skin. It has been implicated as the leading cause of prosthetic joint infection (PJI) after shoulder arthroplasty. However, PJI caused by C acnes rarely manifests as overt clinical, laboratory, or imaging features. In fact, more than 40% of shoulders undergoing revision arthroplasty are likely to be culture positive. However, rates of infection following a positive culture can be as low as 5%. The purpose of this review was to put forth alternative explanations for this discordance between positive cultures and infection. We describe C acnes roles as a commensal, bystander, and/or contaminant organism; the role of cultures in diagnosis and other methods that may be more accurate; its existence in a shoulder microbiome; and the variable virulence of C acnes. C acnes is an important cause of shoulder PJI in some patients. However, there is a large body of literature that suggests other functions that need to be considered. Further research is needed to define the role of C acnes that is logically explained by all of the literature and not only some.

Meglumine-based Sustainable Three-component Deep Eutectic Solvent Applicable for the Synthesis of Pyrazolo[5,1-b]quinazoline-3-carboxylates as a Sensing Probe for Cu2+ Ions.

An unprecedented meglumine-based three-component deep eutectic solvent (3c-DES) (MegPAc) was synthesized using meglumine, p-toluenesulfonic acid (PTSA), and acetic acid as a renewable, and non-toxic solvent. The exploitation of the MegPAc as an eco-friendly reaction media to construct a selective and sensitive small organic molecular sensing probe, namely, pyrazolo[5,1-b]quinazoline-3-carboxylates (PQCs) was executed. Captivatingly, the MegPAc served the dual role of solvent and catalyst, and it delivered the title components with 69-94 % yields within 67-150 minutes. Furthermore, a UV-visible study unfolds the selective detection of Cu2+ ions with our synthetic probe 4 ba and resulted in hypsochromic shift due to electrostatic interactions. Additionally, 1H NMR titration study and density functional theory (DFT) calculations were performed to attest the binding mechanism of sensing probe 4 ba and Cu2+ ions. Worthy of mention, this protocol unveils the efficacy of meglumine-based 3c-DES for the first time as a bio-renewable system to synthesize the PQCs.

Humeral Head Avascular Necrosis: Pathophysiology, Work-up, and Treatment Options.

¼ Avascular necrosis (AVN) of the humeral head is the result of ischemic injury to the epiphyseal bone leading to humeral head collapse and arthritis.¼ Common causes include trauma, chronic corticosteroid use, or systemic disease processes, such as sickle cell disease, systemic lupus erythematosus, or alcohol abuse.¼ Nonoperative treatment consists of risk factor management, physical therapy, anti-inflammatory medications, and activity modification.¼ Surgical treatment options include arthroscopic debridement, core decompression, vascularized bone grafts, and shoulder arthroplasty.

Can Patients Accurately Recall their Preoperative Pain and Functional Scores Following Rotator Cuff Repair and Total Shoulder Arthroplasty?

Objectives: Accurate analysis of preoperative shoulder pain and function is important for understanding treatment efficacy and producing high-quality research. Oftentimes, preoperative patient-reported outcomes (PROs) are missing. Therefore the accuracy of recalled preoperative PROs may be important. We investigate the ability of patients who underwent rotator cuff repair (RCR) or shoulder arthroplasty (TSA) to recall their preoperative PROs. Methods: We identified 145 patients who underwent either RCR or TSA and had preoperative PROs. All patients completed the ASES, SANE, SST, and VAS surveys within 3 months prior to surgery. Patients were contacted between one and four years after surgery and asked to recall their baseline pain and shoulder function prior to surgery. The mean difference was calculated by determining the difference between the mean recalled score and the mean actual score. Intraobserver reliability analysis was performed, comparing recall and actual score for each using the 2-way mixed-effects intraclass correlation coefficient (ICC) model. The ICC values > 0.75 were considered excellent, values between 0.4 and 0.75 were considered moderate, and values of < 0.4 demonstrated a weak agreement. Results: For patients who underwent RCR, the mean differences between actual and recalled ASES, SANE, SST and VAS pain were 6.3 (P=0.004), 2.0 (P=0.155), -0.04 (P=0.625) and - 1.0 (P<0.001), respectively. In patients who underwent TSA, the mean differences between actual and recalled ASES, SANE, SST and VAS pain were 4.5 (P =0.038), -3.9 (P=0.262), -1.2 (P=0.001) and -1.5 (P<0.001), respectively. ASES, SST, and VAS show moderate reliability, and SANE reliability was weak in both RCR and TSA populations. Patients had a tendency to recall higher pain scores than actual preoperative pain scores. Conclusion: In patients who underwent RCR or TSA, there was too much variability between individual patient's ability to accurately recall preoperative pain and function to reliably use recall data for research purposes.

In silico and in vitro evaluation of newly synthesized pyrazolo-pyridine fused tetrazolo-pyrimidines derivatives as potential anticancer and antimicrobial agents.

Diversely functionalized pyrazolo-pyridine fused tetrazolo-pyrimidines 10aa-am and 10ba-bn were successfully synthesized via a catalyst-free synthetic protocol with moderate to very good yields. The compounds were evaluated for cytotoxicity against MCF-7 and HEK-293 cells using MTT assay. Among the tested compounds, 10ab (IC50- 23.83 µM) and 10ah (IC50- 23.30 µM) demonstrated the highest potency against MCF-7 cells, while 10bc (IC50- 14.46 µM) and 10bh (IC50- 2.53 µM) exhibited excellent cytotoxicity against HEK-293 cells. Additionally, antibacterial screening was performed against three Gram-negative bacteria (E. coli, P. aeruginosa, and S. enterica) and three Gram-positive bacteria (S. aureus, B. megaterium, and B. subtilis) using broth dilution method, while antifungal activity was assessed against three fungal strains (A. niger, Penicillium, and S. cerevisiae) using agar well diffusion method. In antimicrobial screening, the majority of the compounds demonstrated significant antibacterial efficacy compared to antifungal activity. We also conducted comprehensive computational studies, including DFT calculations, molecular docking and dynamics, and drug-likeness assessments. In the DFT study, compounds 10ac and 10bc displayed stable conformations, indicating their potential for higher therapeutic activity. Molecular docking analyses revealed compelling interactions, with compound 10ah demonstrating docking score -7.42 kcal/mol against catalytical domain PARP1 (PDB ID: 7KK4) and 10bh exhibiting a best docking score -10.77 kcal/mol against human corticotropin-releasing factor receptor 1 (PDB ID: 4Z9G). A 100 ns molecular dynamics (MD) simulation study of compounds 10ah and 10bh revealed the stable conformation and binding energy in a stimulating environment. In drug-likeness assessments, both the compounds 10ah and 10bh adhere all the established guidelines.Communicated by Ramaswamy H. Sarma.

Modified Weaver-Dunn Technique Using Transosseous Bone Tunnels and Coracoid Suture Augmentation.

INTRODUCTION: A modified Weaver-Dunn procedure for the management of acromioclavicular joint injuries that uses transosseous bone tunnels and coracoid suture augmentation is described with associated clinical results. METHODS: A retrospective review of 39 consecutive patients who underwent a primary mWD procedure by a single surgeon from January 2013 to July 2019 was conducted. Patient charts and radiographs were reviewed for clinical course, complications and management, and radiographic evaluation. Satisfaction, American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation, and Simple Shoulder Test scores were obtained. RESULTS: A total of 28 patients (72%) with a mean follow-up of 37.5 (12 to 84 months) and a mean age of 44.3 ± 15.1 years were included. Postoperative ASES, Simple Shoulder Test, Single Assessment Numeric Evaluation, and satisfaction scores were 90.6 ± 14.2, 11.1 ± 1.5, 87.3 ± 10.2, and 4.4 ± 1.2 (out of 5), respectively, with a significant improvement in ASES of 42.2 ± 21.8 points (P < 0.001). All patients had significant decrease in coracoclavicular distance (P < 0.001). Three patients (10.7%) had complications, with two (7.1%) requiring additional surgery. CONCLUSION: Excellent functional and radiographic outcomes can be achieved with this modified Weaver-Dunn technique. Complication and revision rates are comparable with those that are found in the literature. LEVEL OF EVIDENCE: Level IV, Retrospective cohort study.

Incidence, Risk Factors, Prevention, and Management of Peripheral Nerve Injuries Following Shoulder Arthroplasty.

In this article, the authors review the incidence and causes of iatrogenic peripheral nerve injuries following shoulder arthroplasty and provide preventative measures to decrease nerve injury rate and management options. They describe common direct and indirect causes of injury such as laceration and retractor use versus arm positioning and lengthening, respectively. Preventative measures include an understanding of anatomy and high-risk locations in the shoulder, minimizing extreme ranges of arm motion and utilization of intraoperative nerve monitoring. Lastly, the authors review diagnosis and management of neurologic symptoms including how and when to use electrodiagnostic studies, nerve grafts, transfers, or muscle/tendon transfers.

Outcomes Following Different Fixation Strategies of Neer Type IIB Distal Clavicle Fractures.

Background: Multiple surgical techniques for fixation of Neer type IIB distal clavicle fractures have been described without consensus on optimal treatment. The purpose of this study is to compare functional and radiographic results with surgical management of Neer type IIB distal clavicle fractures at a single institution. Methods: Sixty-three patients with acute Neer type IIB fractures treated operatively were evaluated. Patients with a minimum of two year follow up were included. Functional scores included American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), Simple Shoulder Test (SST), and Likert patient satisfaction (1 to 5). Radiographs were assessed for osseous union and coracoclavicular (CC) distance. Results: Thirty-eight patients met inclusion with a mean follow-up of 5.3 years. Patients were divided into five groups based on fixation technique: suture-only CC fixation (n=6), CC screw fixation only (n=3), open reduction internal fixation (ORIF) without CC fixation (n=8), hook plate fixation (n=4), and ORIF with suture CC reconstruction (n=17). Outcome scores for the entire cohort were 91.8 for ASES, 90.2 for SANE, and 10.8 for STT. Patients with hook plates had significantly lower SANE score (p=0.016), but no other significant differences in functional, satisfaction, or radiographic outcomes were found between groups. Sixteen patients (42.1%) required reoperation. Conclusion: Treatment of Neer type IIB fractures via suture- only fixation, plate-only fixation, or a combination of both demonstrated satisfactory mid to long term outcomes. While implant removal was more common in the CC screw and ORIF groups, no fixation technique proved functionally superior.

Meglumine-Promoted Eco-Compatible Pseudo-Three-Component Reaction for the Synthesis of 1,1-Dihomoarylmethane Scaffolds and Their Green Credentials.

A simple, straightforward, and energy-efficient greener route for the synthesis of a series of biologically interesting functionalized 1,1-dihomoarylmethane scaffolds has been developed in the presence of meglumine as an efficient and eco-friendly organo-catalyst via one-pot pseudo-three-component reaction at room temperature. Following this protocol, it is possible to synthesize 1,1-dihomoarylmethane scaffolds of an assortment of C-H activated acids such as dimedone, 1,3-cyclohexadione, 4-hydroxy-6-methyl-2-pyrone, 4-hydroxycoumarin, and 1-phenyl-3-methyl-pyrazolone. The salient features of the present green protocol are mild reaction conditions, good to excellent yields, operational simplicity, easy isolation of products, no cumbersome post treatment, high atom economy, and low E-factor. In addition, this chemistry portrays several green advantages including the reusability of reaction media and product scalability, which makes protocol sustainably efficient. Additionally, several control experiments such as protection of catalyst reactive site, D2O exchange, and 1H NMR studies revealed possible pathways for meglumine-promoted reactions. Inspired by the natural physiological environment of 1,1-dihomoarylmethane scaffolds, we reconnoitered the biological profile of our compounds and synthesized compounds that were promising for their antiproliferative and antibacterial activities.