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1.
Article in English | MEDLINE | ID: mdl-38992415

ABSTRACT

BACKGROUND: Fractures of the acromion and spine can have a major impact on the outcome of reverse shoulder arthroplasty (RSA) with respect to pain, motion, and function. Reports on internal fixation for these fractures are isolated to small series or case reports with variable outcomes. The purpose of this study was to report on the outcome of open reduction and internal fixation (ORIF) of acromion or spine fractures encountered before or after RSA and describe our evolution of fixation techniques. METHODS: Between 2011 and 2023, 22 fractures or nonunions of the acromion or spine of the scapula underwent ORIF at a single institution and were followed for a minimum of 1 year. In 16 shoulders, fractures occurred after RSA, whereas 5 shoulders underwent ORIF prior to RSA. One shoulder had undergone prior failed ORIF elsewhere and revision ORIF was performed at our institution. There were 10 males and 12 females with a mean age of 67 (SD=15.1) years. Fixation strategies included single (n=11) and double plate fixation (n=11). Kruskal-Wallis one-way analyses of variance were used to analyze continuous variables and Chi-square tests employed for categorical variables. RESULTS: Of the 5 fractures treated with ORIF pre-RSA, 1 shoulder suffered an additional fracture medial to the hardware and 1 required additional bone grafting for incomplete union at the time of RSA. These 5 shoulders all underwent RSA uneventfully, but one fracture experienced late displacement of the scapular spine nonunion, leading to plate removal. Of the 16 post-RSA ORIF shoulders, radiographic union was confirmed in 14 and substantial residual inferior angulation identified in 3. New fractures occurred after ORIF in 5 shoulders. For patients who underwent ORIF after RSA, pain scores improved from a mean of 8 to 1.9 points, with more modest elevation gains (58.2° to 91.3° pre- and postoperatively, respectively). CONCLUSIONS: ORIF of acromion and scapular spine fractures or nonunions in the setting of RSA have the potential to lead to union. When these fractures and nonunions are encountered prior to RSA, ORIF allows for uneventful RSA implantation, but secondary displacement may occur. ORIF seems to lead to improvements in pain, but more modest improvements in motion and function. Our fixation strategy has evolved to (1) dual plating, (2) spanning the whole length of the spine with one of the plates, (3) use of hook features under the acromion or os trigonum if possible, and (4) liberal use of bone graft.

2.
Article in English | MEDLINE | ID: mdl-38852709

ABSTRACT

INTRODUCTION: Technological advancements in implant design and surgical technique have focused on diminishing complications and optimizing performance of reverse shoulder arthroplasty (RSA). Despite this, there remains a paucity of literature correlating prosthetic features and clinical outcomes. This investigation utilized a machine learning approach to evaluate the effect of select implant design features and patient-related factors on surgical complications after RSA. METHODS: Over a 16-year period (2004 - 2020), all primary RSA performed at a single institution for elective and traumatic indications with a minimum follow-up of 2 years were identified. Parameters related to implant design evaluated in this study included inlay vs onlay humeral bearing design, glenoid lateralization (medialized or lateralized), humeral lateralization (medialized, minimally lateralized, or lateralized), global lateralization (medialized, minimally lateralized, lateralized, highly lateralized, or very highly lateralized), stem to metallic bearing neck shaft angle (NSA), and polyethylene NSA. Machine learning models predicting surgical complications were constructed for each patient and Shapley additive explanation (SHAP) values were calculated to quantify feature importance. RESULTS: A total of 3,837 RSAs were identified, of which 472 (12.3%) experienced a surgical complication. Those experiencing a surgical complication were more likely to be current smokers (Odds ratio [OR] = 1.71; P = .003), have prior surgery (OR = 1.60; P < .001), have an underlying diagnosis of sequalae of instability (OR = 4.59; P < .001) or non-union (OR = 3.09; P < .001), and required longer OR times (98 vs. 86 minutes; P < .001). Notable implant design features at an increased odds for complications included an inlay humeral component (OR = 1.67; P < .001), medialized glenoid (OR = 1.43; P = .001), medialized humerus (OR = 1.48; P = .004), a minimally lateralized global construct (OR = 1.51; P < .001), and glenohumeral constructs consisting of a medialized glenoid and minimally lateralized humerus (OR = 1.59; P < .001), and a lateralized glenoid and medialized humerus (OR = 2.68; P < .001). Based on patient- and implant-specific features, the machine learning model predicted complications after RSA with an area under the receiver operating characteristic curve (AUC ROC) of 0.61. CONCLUSIONS: This study demonstrated that patient-specific risk factors had a more substantial effect than implant design configurations on the predictive ability of a machine learning model on surgical complications after RSA. However, certain implant features appeared to be associated with a higher odd of surgical complications.

3.
Expert Opin Ther Pat ; 34(8): 665-700, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38886185

ABSTRACT

INTRODUCTION: Cannabinoid receptor type 2 (CB2R), predominantly expressed in immune tissues, is believed to play a crucial role within the body's protective mechanisms. Its modulation holds immense therapeutic promise for addressing a wide spectrum of dysbiotic conditions, including cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, and autoimmune diseases, as well as lung disorders, cancer, and pain management. AREAS COVERED: This review is an account of patents from 2016 up to 2023 which describes novel CB2R ligands, therapeutic applications, synthesis, as well as formulations of CB2R modulators. EXPERT OPINION: The patents cover a vast, structurally diverse chemical space. The focus of CB2R ligand development has shifted from unselective dual-cannabinoid receptor type 1 (CB1R) and 2 agonists toward agonists with high selectivity over CB1R, particularly for indications associated with inflammation and tissue injury. Currently, there are at least eight CB2R agonists and one antagonist in active clinical development. A better understanding of the endocannabinoid system (ECS) and in particular of CB2R pharmacology is required to unlock the receptor's full therapeutic potential.


Subject(s)
Cannabinoid Receptor Agonists , Drug Development , Patents as Topic , Receptor, Cannabinoid, CB2 , Humans , Receptor, Cannabinoid, CB2/metabolism , Receptor, Cannabinoid, CB2/agonists , Receptor, Cannabinoid, CB2/antagonists & inhibitors , Animals , Ligands , Cannabinoid Receptor Agonists/pharmacology , Cannabinoid Receptor Antagonists/pharmacology
4.
Urology ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38908561

ABSTRACT

OBJECTIVE: Limited data exist on the frequency with which clinical progression during neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) impacts eligibility for a vaginal-sparing surgical approach or on the utility of interim imaging assessment. We sought to evaluate the incidence of clinical upstaging following NAC that would render a patient ineligible for a vaginal-sparing cystectomy. METHODS: Eighty-nine female patients with non-metastatic MIBC treated with NAC and radical cystectomy (RC) (2012-2023) were retrospectively reviewed. Tumor location(s) was determined from transurethral resection of bladder tumor operative reports. Pre- and post-NAC clinical staging was determined from imaging. Outcomes of interest included clinical upstaging and upstaging to vaginal invasion after NAC. RESULTS: 75/89 patients had pre- and post-NAC imaging. Fifty-five had no change in clinical staging, 6 patients were upstaged (4 cT2→cT3, 2 cT3→cT4), and 14 patients were downstaged (13 cT3→cT2, 1 cT4→cT2). Of the 75 patients with pre- and post-NAC imaging, 39 had trigone tumors. Of these, 28 had no change in clinical staging, 2 were upstaged (1 cT2→cT3, 1 cT3→cT4) and 9 were downstaged (8 cT3→cT2, 1 cT4→cT2). Overall, 6/75 (8%) of patients demonstrated clinical upstaging after NAC. 2/39 (5%) of patients with trigone tumors clinically progressed after NAC and both had vaginal invasion (pT4) on final pathology. CONCLUSION: Although clinical upstaging after NAC was infrequent, 5% of patients with trigonal MIBC were rendered ineligible for vaginal-sparing cystectomy following NAC due to progression. Interim imaging assessment may identify non-responders and preserve eligibility for vaginal-sparing RC.

5.
Org Lett ; 26(26): 5467-5471, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38913674

ABSTRACT

We report a hydrogen atom transfer-initiated cyclization/reduction cascade for the synthesis of primary amines from δ,ε- and ε,ζ-unsaturated nitriles. The HAT transformation employs Mn(acac)3 as a catalyst and utilizes air as an oxidant along with NaBH4 as a dual-purpose reductant toward the olefin and subsequently C═N. Aromatic and aliphatic nitriles incorporating mono-, di-, and trisubstituted olefins are substrates for the reaction. Starting materials bearing malonates are transformed into the corresponding bicyclic lactams, enabling the rapid buildup of structural complexity.

6.
Parasit Vectors ; 17(1): 279, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38943214

ABSTRACT

BACKGROUND: Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult and juvenile schistosome worms is urgently needed to improve praziquantel efficacy and delay the potential development of drug resistance. We assessed the efficacy and safety of single-dose praziquantel combined with single-dose artesunate plus sulfalene-pyrimethamine in the treatment of Kenyan children with schistosomiasis. METHODS: This was an open-label, randomised clinical trial involving 426 school-aged children (7-15 years old) diagnosed with Schistosoma mansoni (by Kato-Katz) or S. haematobium (by urine filtration). They were randomly assigned (1:1:1) to receive a single dose of praziquantel (40 mg/kg), a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate) or combination therapy using a single dose of praziquantel (40 mg/kg) combined with a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate). The primary outcome was cure and egg reduction rates at 6 weeks post-treatment in the available case population. Adverse events were assessed within 3 h after treatment. RESULTS: Of the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data were available for 348 (81.7%) children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and the egg reduction rates were 80.1%, 85.0%, and 88.4% for praziquantel, artesunate plus sulfalene-pyrimethamine, and combination therapy, respectively. For S. haematobium-infected children (n = 145), the corresponding cure rates were 81.4%, 71.1%, and 82.2%, and the egg reduction rates were 95.6%, 97.1%, and 97.7%, respectively. Seventy-one (16.7%) children reported mild-intensity adverse events. The drugs were well tolerated and no serious adverse events were reported. CONCLUSIONS: A single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not significantly improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes.


Subject(s)
Anthelmintics , Artemisinins , Artesunate , Drug Therapy, Combination , Praziquantel , Pyrimethamine , Schistosoma haematobium , Schistosoma mansoni , Schistosomiasis haematobia , Schistosomiasis mansoni , Humans , Child , Praziquantel/administration & dosage , Praziquantel/adverse effects , Praziquantel/therapeutic use , Pyrimethamine/administration & dosage , Pyrimethamine/therapeutic use , Pyrimethamine/adverse effects , Animals , Adolescent , Artesunate/administration & dosage , Artesunate/therapeutic use , Female , Male , Schistosomiasis mansoni/drug therapy , Schistosoma haematobium/drug effects , Schistosomiasis haematobia/drug therapy , Schistosoma mansoni/drug effects , Kenya , Artemisinins/administration & dosage , Artemisinins/therapeutic use , Artemisinins/adverse effects , Treatment Outcome , Anthelmintics/administration & dosage , Anthelmintics/adverse effects , Anthelmintics/therapeutic use , Sulfalene/administration & dosage , Sulfalene/therapeutic use , Sulfalene/adverse effects , Drug Combinations , Parasite Egg Count
7.
Clin Radiol ; 79(8): e1081-e1087, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38824041

ABSTRACT

AIMS: This study aims to assess the impact that delivering an introductory interventional radiology (IR) lecture series has on the knowledge and perception of the specialty among medical students in a resource-limited setting with, until recently, no IR presence. MATERIALS AND METHODS: An introductory four-hour lecture series in IR was delivered to third-year medical students in Tanzania. Prior to and following the lecture series, participants completed a 27-item paper-based survey assessing their knowledge and perception of the specialty. RESULTS: Out of a class of 213, the pre- and post-lecture survey was returned by 148 (69.5%) and 151 (70.9%) respondents, respectively. 94.5% of respondents indicated that they were aware of IR as a specialty. Among respondents, 97.3% expressed interest in having IR lectures integrated into their curriculum, compared to 29.0% that reported having any prior IR training. 27.3% believed their knowledge in IR compared to other specialties was either "good" or "excellent", which improved to 43.3% (p<0.001). Identification that IR physicians consult patients directly, have outpatient clinics, have inpatient beds, and do rounds improved from 55.4% to 81.1% (p<0.001), 49.7% to 60.3% (p=0.066), 48.3% to 66.7% (p=0.001), and 52.0% to 66.2% (p=0.013), respectively. CONCLUSION: By introducing short lectures on IR-relevant topics, knowledge and perception of IR improved among Tanzanian medical students. Early education and exposure to IR should be prioritized to promote the continued growth of the specialty in this setting.


Subject(s)
Curriculum , Radiology, Interventional , Students, Medical , Tanzania , Humans , Radiology, Interventional/education , Students, Medical/psychology , Female , Male , Surveys and Questionnaires , Adult , Education, Medical, Undergraduate/methods , Health Knowledge, Attitudes, Practice , Educational Measurement , Clinical Competence
8.
BJU Int ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38881297

ABSTRACT

OBJECTIVE: To investigate whether preoperative body morphometry analysis can identify patients at risk of parastomal hernia (PH), which is a common complication after radical cystectomy (RC). PATIENTS AND METHODS: All patients who underwent RC between 2010 and 2020 with available cross-sectional imaging preoperatively and at 1 and 2 years postoperatively were included. Skeletal muscle mass and total fat mass (FM) were determined from preoperative axial computed tomography images obtained at the level of the L3 vertebral body using Aquarius Intuition software. Sarcopenia and obesity were assigned based on consensus definitions of skeletal muscle index (SMI) and FM index (FMI). PH were graded using both the Moreno-Matias and European Hernia Society criteria. Binary logistic regression and recursive partitioning were used to identify patients at risk of PH. The Kaplan-Meier method with log-rank and Cox proportional hazards models included clinical and image-based parameters to identify predictors of PH-free survival. RESULTS: A total of 367 patients were included in the final analysis, with 159 (43%) developing a PH. When utilising binary logistic regression, high FMI (odds ratio [OR] 1.63, P < 0.001) and low SMI (OR 0.96, P = 0.039) were primary drivers of risk of PH. A simplified model that only relied upon FMI, SMI, and preoperative albumin improved the classification of patients at risk of PH. On Kaplan-Meier analysis, patients who were obese or obese and sarcopenic had significantly worse PH-free survival (P < 0.001). CONCLUSION: Body morphometry analysis identified FMI and SMI to be the most consistent predictors of PH after RC.

9.
J Am Chem Soc ; 146(27): 18187-18188, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38940660
10.
Curr Rev Musculoskelet Med ; 17(8): 313-320, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38833135

ABSTRACT

PURPOSE OF REVIEW: Management of meniscal injuries in the elite athlete is a difficult problem secondary to the high demands of athletic competition, the need for a timely return to sport, and the desire to maximize performance over time. The purpose of this review is to provide an up-to-date summary on the current literature and trends regarding the management of meniscus injuries with a special consideration for elite athletes. RECENT FINDINGS: Historically, partial meniscectomy has been the primary treatment option for meniscus injuries. However, in recent years there has been an increased emphasis on meniscus preservation due to the increased risk of cartilage degeneration over time. Moreover, while partial meniscectomy still provides a quicker return to sport (RTS), recent literature has demonstrated similar rates of RTS and return to pre-injury levels between partial meniscectomy and meniscus repair. In the setting of symptomatic meniscal deficiency, meniscus allograft transplantation has become an increasingly utilized salvage procedure with promising yet variable outcomes on the ability to withstand elite competition. Currently, there is no uniform approach to treating meniscal injuries in elite athletes. Therefore, an individualized approach is required with consideration of the meniscus tear type, location, concomitant injuries, athlete expectations, rehabilitation timeline, and desire to prevent or delay knee osteoarthritis. In athletes with anatomically repairable tears, meniscus repair should be performed given the ability to restore native anatomy, provide high rates of RTS, and mitigate long-term chondral damage. However, partial meniscectomy can be indicated for unrepairable tears.

11.
J Endod ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38796056

ABSTRACT

INTRODUCTION: To compare the stress produced on the walls of simulated canals by rotary instruments with varied tip and taper sizes. METHODS: Ninety isotropic transparent blocks, each containing a 60-degree curved canal, were distributed into 18 groups (n = 5) based on the instrument tip (sizes 10, 15, 20, 25, 30, and 35) and taper (sizes 0.02, 0.04, and 0.06). The blocks were fixed in a circular polariscope setup for dark field analysis. A digital camera was employed to capture the real-time birefringence patterns generated by each instrument. Digital image frames, corresponding to the instrument reaching the end of each canal third, were extracted and evaluated by 2 independent observers for the stress generation on canal walls. The data analysis employed a semi-quantitative scale ranging from 0 to 5. Cohen's Kappa coefficient test was used to determine the inter-observer agreement while the results were compared using Kruskal-Wallis test followed by an all-pairwise posthoc procedure (α = 5%). RESULTS: Inter-observer agreement was 0.95. A significant influence of the tip size on stress was observed across the coronal (P = .011), middle (P = .006), and apical (P = .026) thirds. In contrast, taper size did not affect the stress induced at the coronal (P = .509), middle (P = .958), or apical (P = .493) thirds. The variations in tip and taper sizes did not result in a significant stress differences among the thirds (P = .181). CONCLUSIONS: The stress significantly increased across all canal thirds with larger tip sizes of rotary instruments, whereas the taper sizes did not influence the stress when compared to the canal thirds.

12.
BMC Health Serv Res ; 24(1): 597, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38715044

ABSTRACT

BACKGROUND: Globally, a fifth of the children continue to face chronic undernutrition with a majority of them situated in the Low- and Middle-Income Countries (LMIC). The rising numbers are attributed to aggravating factors like limited nutrition knowledge, poor feeding practices, seasonal food insecurity, and diseases. Interventions targeting behaviour change may reduce the devastating nutrition situation of children in the LMICs. OBJECTIVE: For the co-design of a Behaviour Change Communication (BCC) intervention for young children in rural Kenya, we aimed to identify the experiences, barriers, facilitators, and preferences of caregivers and stakeholders regarding nutrition and health counselling. DESIGN: We employed a qualitative study design and used a semi-structured interview guide. The in-depth interviews were recorded, transcribed, and analysed using content analysis, facilitated by the software NVivo. SETTING: Health and Demographic Surveillance System (HDSS) area in Siaya County, rural Kenya. PARTICIPANTS: We interviewed 30 caregivers of children between 6 and 23 months of age and 29 local stakeholders with experience in implementing nutrition projects in Kenya. RESULTS: Nutrition and health counselling (NHC) was usually conducted in hospital settings with groups of mothers. Barriers to counselling were long queues and delays, long distances and high travel costs, the inapplicability of the counselling content, lack of spousal support, and a high domestic workload. Facilitators included the trust of caregivers in Community Health Volunteers (CHVs) and counselling services offered free of charge. Preferences comprised (1) delivering of counselling by CHVs, (2) offering individual and group counselling, (3) targeting male and female caregivers. CONCLUSION: There is a disconnect between the caregivers' preferences and the services currently offered. Among these families, a successful BCC strategy that employs nutrition and health counselling should apply a community-based communication channel through trusted CHVs, addressing male and female caregivers, and comprising group and individual sessions.


Subject(s)
Caregivers , Counseling , Qualitative Research , Rural Population , Humans , Kenya , Caregivers/psychology , Counseling/methods , Infant , Female , Male , Adult , Interviews as Topic
13.
Article in English | MEDLINE | ID: mdl-38759838

ABSTRACT

INTRODUCTION: In primary shoulder arthroplasty (SA), intravenous (IV) cefazolin has demonstrated lower rates of infectious complications when compared to IV vancomycin. However, previous analyses included SA cohorts with both complete and incomplete vancomycin administration. Therefore, it is currently unclear whether cefazolin still maintains a prophylactic advantage to vancomycin when it is appropriately indicated and sufficiently administered at the time of surgical incision. This study evaluated the comparative efficacy of cefazolin and complete vancomycin administration for surgical prophylaxis in primary shoulder arthroplasty with respect to infectious complications. METHODS: A retrospective cohort study was conducted utilizing a single institution total joint registry database, where all primary SA types (hemiarthroplasty, anatomic total shoulder arthroplasty, reverse shoulder arthroplasty) performed between 2000 to 2019 for elective and trauma indications using IV cefazolin or complete vancomycin administration as the primary antibiotic prophylaxis were identified. Vancomycin was primarily indicated for patients with a severe self-reported penicillin or cephalosporin allergy and/or MRSA colonization. Complete administration was defined as at least 30 minutes of antibiotic infusion prior to incision. All included SA had at least 2 years of clinical follow-up. Multivariable Cox proportional hazard regression was used to evaluate all-cause infectious complications including survival free of prosthetic joint infection (PJI). RESULTS: The final cohort included 7,177 primary SA, 6,879 (95.8%) received IV cefazolin and 298 (4.2%) received complete vancomycin administration. Infectious complications occurred in 120 (1.7%) SA leading to 81 (1.1%) infectious reoperations. Of the infectious complications 41 (0.6%) were superficial infections and 79 were (1.1%) PJIs. When categorized by administered antibiotics, there were no differences in rates of all infectious complications (1.6% vs. 2.3%; P = .352), superficial complications (0.5% vs. 1.3%; P = .071), PJI (1.1% vs. 1.0%; P = .874), or infectious reoperations (1.1% vs. 1.0%; P = .839). On multivariable analyses, complete vancomycin infusion demonstrated no difference in rates of infectious complications compared to cefazolin administration (hazard ratio [HR], 1.50 [95% confidence interval (CI), 0.70 to 3.25]; P = .297), even when other independent predictors of PJI (male sex, prior surgery, and Methicillin-resistant Staphylococcus aureus colonization) were considered. CONCLUSIONS: In comparison to cefazolin, complete administration of vancomycin (infusion to incision time greater than 30 minutes) as the primary prophylactic agent does not adversely increase the rates of infectious complications and PJI. Prophylaxis protocols should promote appropriate indications for the use of cefazolin or vancomycin, and when necessary, ensure complete administration of vancomycin to mitigate additional infectious risks after primary SA.

14.
ACS Cent Sci ; 10(5): 956-968, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38799662

ABSTRACT

We report a blueprint for the rational design of G protein coupled receptor (GPCR) ligands with a tailored functional response. The present study discloses the structure-based design of cannabinoid receptor type 2 (CB2R) selective inverse agonists (S)-1 and (R)-1, which were derived from privileged agonist HU-308 by introduction of a phenyl group at the gem-dimethylheptyl side chain. Epimer (R)-1 exhibits high affinity for CB2R with Kd = 39.1 nM and serves as a platform for the synthesis of a wide variety of probes. Notably, for the first time these fluorescent probes retain their inverse agonist functionality, high affinity, and selectivity for CB2R independent of linker and fluorophore substitution. Ligands (S)-1, (R)-1, and their derivatives act as inverse agonists in CB2R-mediated cAMP as well as G protein recruitment assays and do not trigger ß-arrestin-receptor association. Furthermore, no receptor activation was detected in live cell ERK1/2 phosphorylation and Ca2+-release assays. Confocal fluorescence imaging experiments with (R)-7 (Alexa488) and (R)-9 (Alexa647) probes employing BV-2 microglial cells visualized CB2R expressed at endogenous levels. Finally, molecular dynamics simulations corroborate the initial docking data in which inverse agonists restrict movement of toggle switch Trp2586.48 and thereby stabilize CB2R in its inactive state.

15.
Urol Oncol ; 42(8): 247.e11-247.e19, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38729867

ABSTRACT

OBJECTIVES: Most renal tumors merely displace nephrons while others can obliterate parenchyma in an invasive manner. Substantial parenchymal volume replacement (PVR) by renal cell carcinoma (RCC) may have oncologic implications; however, studies regarding PVR remain limited. Our objective was to evaluate the oncologic implications associated with PVR using improved methodology including more accurate and objective tools. PATIENTS/METHODS: A total of 1,222 patients with non-metastatic renal tumors managed with partial nephrectomy (PN) or radical nephrectomy (RN) at Cleveland Clinic (2011-2014) with necessary studies were retrospectively evaluated. Parenchymal volume analysis via semiautomated software was used to estimate split renal function and preoperative parenchymal volumes. Using the contralateral kidney as a control, %PVR was defined: (parenchymal volumecontralateral-parenchymal volumeipsilateral) normalized by parenchymal volumecontralateral x100%. PVR was determined preoperatively and not altered by management. Patients were grouped by degree of PVR: minimal (<5%, N = 566), modest (5%-25%, N = 414), and prominent (≥25%, N = 142). Kaplan-Meier was used to evaluate survival outcomes relative to degree of PVR. Multivariable Cox-regression models evaluated predictors of recurrence-free survival (RFS). RESULTS: Of 1,122 patients, 801 (71%) were selected for PN and 321 (29%) for RN. Overall, median tumor size was 3.1 cm and 6.8 cm for PN and RN, respectively, and median follow-up was 8.6 years. Median %PVR was 15% (IQR = 6%-29%) for patients selected for RN and negligible for those selected for PN. %PVR correlated inversely with preoperative ipsilateral GFR (r = -0.49, P < 0.01) and directly with advanced pathologic stage, high tumor grade, clear cell histology, and sarcomatoid features (all P < 0.01). PVR≥25% associated with shortened recurrence-free, cancer-specific, and overall survival (all P < 0.01). Male sex, ≥pT3a, tumor grade 4, positive surgical margins, and PVR≥25% independently associated with reduced RFS (all P < 0.02). CONCLUSIONS: Obliteration of normal parenchyma by RCC substantially impacts preoperative renal function and patient selection. Our data suggests that increased PVR is primarily driven by aggressive tumor characteristics and independently associates with reduced RFS, although further studies will be needed to substantiate our findings.


Subject(s)
Kidney Neoplasms , Nephrectomy , Humans , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Male , Female , Middle Aged , Retrospective Studies , Nephrectomy/methods , Aged , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/pathology , Kidney/pathology , Kidney/physiopathology , Kidney/surgery
16.
Support Care Cancer ; 32(4): 271, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38581472

ABSTRACT

PURPOSE: In this work, we aimed to describe the strategy of the weekly SARS-CoV-2 RT-PCR surveillance program that was implemented in our bone marrow transplantation (BMT) unit. METHODS: Our unit performed SARS-CoV-2 RT-PCR before admission and then weekly during hospitalization even if the patient was asymptomatic. From May 2021 to May 2022, we collected data from all patients that were admitted in the BMT unit to perform transplantation. The total of SARS-CoV-2 RT-PCR performed and the positive rate were described. RESULTS: During the study period, 65 patients were admitted for HSCT. A total of 414 SARS-CoV-2 RT-PCR were performed. Two cases were detected (positivity rate, 0.48%). After the positive test, both patients were isolated outside the BMT unit. CONCLUSION: We postulate that diagnosing these patients and isolating them outside the transplantation unit may have prevented secondary symptomatic cases.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , SARS-CoV-2 , Bone Marrow Transplantation , Brazil/epidemiology , COVID-19 Testing , Clinical Laboratory Techniques , Hospitals, Teaching
17.
J Vasc Interv Radiol ; 35(7): 1049-1056, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38513756

ABSTRACT

PURPOSE: To evaluate the growth and quality of an interventional radiology (IR) training model designed for resource-constrained settings and implemented in Tanzania as well as its overall potential to increase access to minimally invasive procedures across the region. MATERIALS AND METHODS: IR training in Tanzania began in October 2018 through monthly deployment of visiting teaching teams for hands-on training combined with in-person and remote lectures. A competency-based 2-year Master of Science in IR curriculum was inaugurated at the nation's main teaching hospital in October 2019, with the first 2 classes graduating in 2021 and 2022. Procedural data, demographics, and clinical outcomes were collected and analyzed throughout the duration of this program. RESULTS: From October 2018 to July 2022, 1,595 procedures were performed in Tanzania: 1,236 nonvascular and 359 vascular, all with local fellows as primary interventional radiologists. Of these, 97.2% were technically successful, 95.2% were without adverse events, and 28.9% were performed independently by Tanzanian fellows and faculty with no difference in adverse event and technical success rates (P = .63 and P = .90, respectively), irrespective of procedural class. Ten IR physicians graduated from this program during the study period, followed by another 3 per year going forward. Partner training programs in Uganda and Rwanda mirroring this model commenced in 2023 and 2024, respectively. CONCLUSIONS: The reported training model offers a practical and effective solution to meet many of the challenges associated with the lack of access to IR in sub-Saharan Africa.


Subject(s)
Curriculum , Education, Medical, Graduate , Radiography, Interventional , Radiology, Interventional , Humans , Radiology, Interventional/education , Tanzania , Female , Male , Clinical Competence , Program Evaluation , Time Factors , Middle Aged , Adult , Radiologists/education , Developing Countries , Program Development
18.
Am J Trop Med Hyg ; 110(4): 677-680, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38460198

ABSTRACT

Unlike praziquantel, artemisinin derivatives are effective against juvenile schistosome worms. We assessed the efficacy and safety of a single oral dose of artesunate plus sulfalene-pyrimethamine versus praziquantel in the treatment of Schistosoma mansoni. Seventy-three schoolchildren (aged 9-15 years) with confirmed S. mansoni infection in Rarieda, western Kenya, were randomly assigned to receive either a single oral dose of artesunate plus sulfalene-pyrimethamine (n = 39) or a single dose of praziquantel (n = 34). The cure and egg reduction rates at 4 weeks posttreatment were 69.4% (25/36) versus 80.6% (25/31) (P = 0.297) and 99.1% versus 97.5% (P = 0.607) in the artesunate plus sulfalene-pyrimethamine group versus praziquantel group, respectively. Fourteen children developed adverse events, and there were no serious adverse events. A single oral dose of artesunate plus sulfalene-pyrimethamine has efficacy comparable to that of praziquantel in the treatment of S. mansoni, but these results should be confirmed in larger randomized controlled trials.


Subject(s)
Anthelmintics , Artemisinins , Schistosomiasis mansoni , Sulfalene , Adolescent , Animals , Child , Humans , Anthelmintics/therapeutic use , Artemisinins/adverse effects , Artesunate/therapeutic use , Drug Therapy, Combination , East African People , Kenya , Praziquantel/adverse effects , Pyrimethamine/therapeutic use , Schistosoma mansoni , Schistosomiasis mansoni/drug therapy , Sulfalene/pharmacology , Sulfalene/therapeutic use , Treatment Outcome
19.
J Am Chem Soc ; 146(14): 9519-9525, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38547006

ABSTRACT

We report convenient syntheses of aryl azocyclopropeniums and a study of their photochemical properties. Incorporation of the smallest arene leads to pronounced redshift of the π-π* absorbance band, compared to azobenzenes. Photoisomerization under purple or green light irradiation affords Z- or E-isomers in ratios up to 94% Z or 90% E, and the switches proved stable over multiple irradiation cycles. Thermal half-lives of metastable Z-isomers range from minutes to hours in acetonitrile and water. These properties together with the concise, versatile syntheses render aryl azocyclopropeniums exciting additions to the tool kit of readily available molecular photoswitches for wide ranging applications.

20.
Orthop Traumatol Surg Res ; : 103873, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38556209

ABSTRACT

BACKGROUND: Reverse shoulder arthroplasty (RSA) with concurrent latissimus dorsi transfer (LDT) is a potential treatment option for restoration of external rotation (ER). Biomechanical studies have emphasized the importance of the insertion site location for achieving optimal outcomes. In this systematic review and meta-analysis, we aimed to describe what insertion sites for LDT are utilized during concomitant RSA and their associated clinical outcomes. METHODS: A systematic review and meta-analysis were performed per PRISMA guidelines. We queried PubMed/MEDLINE, Embase, Web of Science, and Cochrane databases to identify articles reporting on patients who received RSA with LDT to restore ER and specified the site of tendon transfer insertion on the humerus. We first describe reported insertion sites in the literature. Secondarily, we present preoperative and postoperative range of motion and Constant score for different insertion sites as well as reported complications. RESULTS: Sixteen studies, analyzed as 19 separate cohorts (by insertion site and tendon-transfer), reporting on 264 RSAs with LDT (weighted mean age 66 years, follow-up 39 months, 61% female) were evaluated. Of these, 143 (54%) included a concomitant teres major transfer (LDT/TMT) and 121 (46%) were LDT-only. Fourteen cohorts (14/19, 74%) reported insertion at the posterolateral aspect of the greater tuberosity, four cohorts (4/19, 21%) reported insertion site at the lateral bicipital groove, and one cohort (1/19, 5%) reported separate LDT and TMT with insertion of the TMT to the posterolateral aspect of the greater tuberosity and LDT to the lateral bicipital groove. Meta-analysis revealed no differences in range of motion or Constant score based on humeral insertion site or whether the LDT was transferred alone or with TMT. Leading complications included dislocation, followed by infection and neuropraxia. No discernible correlation was observed between postoperative outcomes and the strategies employed for tendon transfer, prosthesis design, or subscapularis management. CONCLUSION: The posterolateral aspect of the greater tuberosity was the most-utilized insertion site for LDT performed with RSA. However, in the current clinical literature, LDT with or without concomitant TMT result in similar postoperative ROM and Constant score regardless of insertion site. Analysis of various proposed transfer sites reinforce the ability of LDT with RSA to restore both FE and ER in patients with preoperative active elevation and external rotation loss. Meta-analysis revealed significant improvements in range of motion and Constant score regardless of humeral insertion site or whether the LDT was transferred alone or with TMT, although future studies are needed to determine whether an ideal tendon transfer technique exists. LEVEL OF EVIDENCE: IV.

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