Clozapine levels and outcomes in Serbian patients with treatment-resistant psychotic disorders previously treated without measuring clozapine levels (CLOSER).

Clozapine remains the only pharmacological treatment option for treatment-resistant schizophrenia. Therapeutic drug monitoring (TDM) of clozapine is recommended, although evidence for the therapeutic range of 350-600 ng/ml is limited. In various countries including Serbia, TDM of clozapine is not routinely performed. This study evaluated the distribution of clozapine levels and their relationship with clinical outcomes in Serbian patients who had not undergone prior TDM. 140 Patients with treatment-resistant schizophrenia and schizo-affective disorder were enrolled. Clozapine levels were measured by dried blood spot (DBS) analysis. Side effects were evaluated by GASS-c, severity of symptoms and functional impairment with WHODAS, CGI-S and GAF. Of the patients, 51.2% had subtherapeutic levels, 24.8% were in the therapeutic window, and 24% had supratherapeutic levels. Clozapine levels showed no association with side effects and a weak positive association with symptom severity and functional impairment. No serious side effects were observed in patients with clozapine levels surpassing 1000 ng/ml (n = 8). Based on these findings, we propose that the upper limit of the therapeutic range should not be regarded as an absolute barrier, and guidelines should allow for a personalized approach when prescribing clozapine.

Labral repair, reconstruction, and augmentation improve postoperative outcomes in patients with irreparable or hypoplastic labra: A systematic review.

PURPOSE: To review the postoperative outcomes of arthroscopic surgical options in treating irreparable and hypoplastic labrum of the hip. METHODS: Three online databases (PubMed, MEDLINE, and EMBASE) were searched from database inception to June 27, 2023 to identify literature on treatment strategies for hypoplastic/irreparable acetabular labrum. Data pertaining to classification of irreparable tears or labral hypoplasia, indication for surgery, description of treatment, radiographic findings, and clinical outcomes were recorded and described. The methodological quality of included studies was assessed by the Methodological Index for Non-Randomized Studies (MINORS) criteria. RESULTS: Seven level IV case series, eleven level III retrospective cohort studies, and two level II prospective cohort studies comprising 1937 patients were included for analysis. Studies were divided into an irreparable labral group comprising 1002 patients and a hypoplastic labral group comprising 935 patients. Treatments included repair, augmentation, or reconstruction. In the irreparable group, 12 studies recorded improvement of modified Harris Hip Score (mHHS) with preoperative scores ranging from 50.3 to 67.3 and postoperative scores ranging from 76.2 to 95.0. The rate of conversion to total hip arthroplasty (THA) and rate of revision arthroscopy were 6.6% and 5.9%, respectively across all studies. In the hypoplastic group, two studies that focused on repair noted no statistical difference in mHHS for repair in hypoplastic labrum vs repair in non-hypoplastic labrum. One study showed that there was a difference in post-operative mHHS for labral repair for hypoplastic vs non-hypoplastic labrum, with repair in non-hypoplastic labrum showing superior mHHS (p â€‹< â€‹0.001). CONCLUSION: The findings of this review suggest that treatment of irreparable labra with reconstruction or augmentation results in improved patient-reported outcome measures (PROMs). For the hypoplastic labrum, primary repair also results in improvement in PROMs. Future studies focusing on the hypoplastic labra alone with an appropriate control group, rather than irreparable labral tears, are needed to properly assess patient outcomes and guide surgical indications.

Lateral extra-articular tenodesis may be more cost-effective than independent anterolateral ligament reconstruction: A systematic review and economic analysis.

IMPORTANCE: Anterolateral augmentation during primary anterior cruciate ligament (ACL) reconstruction (ACLR) may lower rates of ACL graft failure. However, differences in costs between two techniques, lateral extra-articular tenodesis (LET) and anterolateral ligament reconstruction (ALLR), are unclear. OBJECTIVE: To perform a systematic review and subsequent cost-effectiveness analysis comparing LET versus ALLR in the setting of primary ACLR. The hypothesis was that LET is more cost-effective than ALLR. EVIDENCE REVIEW: A systematic review was conducted on studies in which patients underwent primary ACLR with a concomitant LET or ALLR with minimum 24 months follow-up published between January 2013 and July 2023. Primary outcomes included ACL graft failure rates and Knee Injury and Osteoarthritis Outcome Survey-Quality of Life (KOOS-QoL) subscale scores, which were used to determine health utilities measured by quality-adjusted life years (QALYs) gained. A decision tree model with one-way and two-way sensitivity analyses compared the cost of primary ACLR with a concomitant LET, independent autograft ALLR, or independent allograft ALLR. Costs were estimated using a combination of QALYs, institution prices, literature references, and a survey sent to 49 internationally recognized high-volume knee surgeons. FINDINGS: A total of 2505 knees undergoing primary ACLR with concomitant LET (n=1162) or ALLR (n=1343) were identified from 22 studies. There were 77 total ACL graft failures with comparable failure rates between patients receiving LET versus ALLR (2.9% vs. 3.2%, P=0.690). The average QALYs gained was slightly higher for those who received LET (0.77) compared to ALLR (0.75). Survey results revealed a 5 minute longer median self-reported operative time for ALLR (20 â€‹min) than LET (15 â€‹min). The estimated costs for LET, autograft ALLR, and allograft ALLR were $1,015, $1,295, and $3,068, respectively. CONCLUSIONS AND RELEVANCE: Anterolateral augmentation during primary ACLR with LET is more cost-effective than independent autograft and allograft ALLR given the lower costs and comparable clinical outcomes. Surgeons may utilize this information when determining the optimal approach to anterolateral augmentation during primary ACLR, although differences in preferred technique and health care systems may influence operative efficiency and material costs. LEVEL OF EVIDENCE: Systematic review; Level of evidence, IV.

Any Time, Any Place, Any Way, Any Pace: Markets, EdTech, and the spaces of schooling.

For decades investors have sought to find ways of profiting off the billions of public dollars spent annually on systems of public schooling across the world. This interest has coincided with the growing marketization of systems of public schooling, especially in the United States, as well as the increased use of educational technologies (or EdTech). This study examines the implications of the growing use of profit-driven educational technologies for the politics and spatial practices of schooling. Specifically, it examines past experiences with market-oriented EdTech systems in Oregon and Michigan to highlight how the combination of market systems of governance and profit-driven EdTech practices depend on the deconstruction of links between schools, communities, and students in order to roll out aspatial and apolitical educational practices that maximize profits. The placeless vision for education embedded in profit-driven EdTech helps promote the reproduction of dominant orders and stifles place-based struggles over educational justice.

Decreased posterior tibial slope is a risk factor for primary posterior cruciate ligament rupture and posterior cruciate ligament reconstruction failure: A systematic review.

PURPOSE: To determine bony knee morphological factors associated with primary posterior cruciate ligament (PCL) rupture or PCL graft failure after PCL reconstruction. METHODS: Three databases, namely MEDLINE, PubMed and EMBASE, were searched on 30th May 2023. The authors adhered to the PRISMA and R-AMSTAR guidelines as well as the Cochrane Handbook for Systematic Reviews of Interventions. Data such as receiver operating characteristic curve parameters, as well as p-values for comparisons of values between patients with PCL pathology and control patients, were recorded. RESULTS: Nine studies comprising 1054 patients were included. Four studies reported that patients with PCL injury had flatter medial posterior tibial slopes (MTS) than controls, with mean values of 4.3 (range: 3.0-7.0) and 6.5 (range: 5.0-9.2) degrees, respectively. Two studies reported an MTS cutoff value ranging below 3.90-3.93° being a significant risk factor for primary PCL rupture or PCL graft failure. Two studies reported that shallow medial tibial depths were associated with primary PCL rupture, with mean values of 2.1 (range: 2.0-2.2) and 2.6 (range: 2.4-2.7) mm in PCL injury and control groups, respectively. Stenotic intercondylar notches and femoral condylar width were not consistently associated with PCL injuries. CONCLUSION: Decreased MTS is associated with primary PCL rupture and graft failure after PCL reconstruction with values below 3.93° being considered as a significant risk factor. Less common risk factors include shallow medial tibial depth, while femoral condylar width and parameters with regards to the intercondylar notch, such as notch width, notch width index and intercondylar notch volume, demonstrated conflicting associations with primary or secondary PCL injuries. LEVEL OF EVIDENCE: Level III.

Editorial Commentary: Standardized Evaluation of Cartilage Damage and Restoration in Hip Arthroscopy Requires Consideration of Clinical, Imaging, and Patient-Reported Outcomes.

Articular cartilage lesions of the acetabulum may result in significant pain and dysfunction for patients with treatment options consisting of either microfracture or various forms of cartilage restoration procedures. A systematic review of 529 patients demonstrated similar, if not lower, reoperation rates and patient-reported outcomes in patients receiving cartilage restoration procedures compared with microfracture. The primary outcomes examined in this review were reoperation rates and patient-reported outcomes with no clear mention of radiographic outcomes and no clearly defined indications as to who would benefit from a cartilage-based procedure. This raises the question as to whether there should be a consensus-based and standardized criteria established and standardized among the hip preservation expert community to evaluate the success of these cartilage restoration procedures from an imaging standpoint. These criteria can also be incorporated into a composite evaluation that combines clinical, imaging, and patient-reported outcomes to determine optimal patient candidacy for cartilage procedures as well. This would be a very useful steppingstone for much-needed future Level I randomized studies or prospective, registry-based data on this topic.

Walking the talk for dementia: A unique immersive, embodied, and multi-experiential initiative.

Coping with dementia requires an integrated approach encompassing personal, health, research, and community domains. Here we describe "Walking the Talk for Dementia," an immersive initiative aimed at empowering people with dementia, enhancing dementia understanding, and inspiring collaborations. This initiative involved 300 participants from 25 nationalities, including people with dementia, care partners, clinicians, policymakers, researchers, and advocates for a 4-day, 40 km walk through the Camino de Santiago de Compostela, Spain. A 2-day symposium after the journey provided novel transdisciplinary and horizontal structures, deconstructing traditional hierarchies. The innovation of this initiative lies in its ability to merge a physical experience with knowledge exchange for diversifying individuals' understanding of dementia. It showcases the transformative potential of an immersive, embodied, and multi-experiential approach to address the complexities of dementia collaboratively. The initiative offers a scalable model to enhance understanding, decrease stigma, and promote more comprehensive and empathetic dementia care and research.

Editorial Commentary: Borderline Hip Dysplasia Combined With Increased Anteversion and Ligamentum Teres Disruption Is a Recipe for Hip Microinstability.

The ligamentum teres (LT) is known to play a role as a secondary stabilizer of the hip joint. LT tears can be associated with hip instability. In patients with borderline developmental dysplasia of the hip (BDDH), the correlation between LT tears and microinstability is even more pronounced because of the increased mechanical stress placed on the ligament. This relationship may lead certain surgeons to consider new indications for LT reconstructions. However, caution is warranted regarding the potential role of LT reconstruction in these patients, particularly since the primary deficiency in BDDH is bony undercoverage. Addressing this bony undercoverage should be a primary consideration that may be supplemented with other procedures, which may include addressing soft-tissue injuries around the hip such as LT tears. This is especially the case in those patients with persistent symptoms after management of labral tears or LT disruption.

Family Constellation therapy: A nascent approach for working with non-local consciousness in a therapeutic container.

Family Constellations are an emerging therapeutic approach for working with local and non-local consciousness. First developed by German psychoanalyst Bert Hellinger, and now practiced by thousands of licensed and un-licensed facilitators globally, Family Constellations are a transpersonal and systemically oriented therapeutic process. Their aim is to address a focus client's emotional, behavioral, relational, or somatic issues by uncovering and resolving transgenerational entanglements within their family system. The author expands on the proposal of symbiogenesis as a mediator of local and non-local consciousness to query whether applying the Observer Effect to inherited trauma may influence epigenetic marks. An expanded perspective on consciousness, life, death, and quantum fields may provide a more comprehensive framework to address therapeutic interventions for common emotional and behavioral disorders. Innovative features of Family Constellations are its phenomenological orientation, reference to family system entanglements, and potential for symptom relief through cellular mediation of ancestral memory. Family Constellations utilize techniques called representative perception and tuning-in to identify and release ancestral traumas. These are akin to remote viewing and mediumship. While the scientific basis for Family Constellations is speculative, the text references research on the quantum theory of consciousness, mediumship and remote viewing as potential supporting evidence. Four case studies are presented.

Return-to-Sport Rates After Hip Arthroscopy for Femoroacetabular Impingement Syndrome in Flexibility Sports Athletes: A Systematic Review.

CONTEXT: Femoroacetabular impingement syndrome (FAIS) is a common cause of hip pain in young adults. Flexibility athletes represent an interesting subset due to the extreme range of motion requirements of their sport. OBJECTIVE: The objective of this review was to provide a summary of the outcomes of hip arthroscopy for FAIS in patients who participate in flexibility sports. DATA SOURCES: Three online databases (Medline, Embase, and PubMed) were searched from database inception (1946, 1974, and 1966, respectively) to January 10, 2023. STUDY SELECTION: Studies were screened for literature addressing surgical outcomes for flexibility athletes undergoing hip arthroscopy for FAIS. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 4. DATA EXTRACTION: Various patient-reported outcomes that evaluated the efficacy of hip arthroscopy in this patient population were abstracted and presented in descriptive and analytical format. Abstraction was performed by 2 reviewers. RESULTS: Overall, a total of 8 Level 3 or 4 studies and 295 patients (312 hips) were included in this review. The pooled standardized mean differences for the Visual Analog Scale for pain score, Modified Harris Hip Score, Hip Outcome Score - Activity of Daily Living scale, and Hip Outcome Score - Sport-Specific Subscale all demonstrated significant improvement after undergoing arthroscopy for FAIS between 12 and 116 months (N = 175, -1.97, 95% CI -2.5 to -1.4, P < 0.01, I2 = 76%; N = 211, 1.82, 95% CI 1.49 to 2.16, P < 0.01, I2 = 52%; N = 164, 1.75, 95% CI 1.42 to 2.05, P < 0.01, I2 = 28%; N = 211, 1.71, 95% CI 1.38 to 2.04, P < 0.01, I2 = 52%, respectively). Across 289 patients, 75.6% to 98% returned to sport at a similar or higher level than presurgery. CONCLUSION: This review demonstrates a trend of improvement in patient-reported pain, function, quality of life, and return to sport at a minimum of 12 months among flexibility athletes after hip arthroscopy to treat FAIS.

Enhanced recovery after surgery protocols following emergency intra-abdominal surgery: a systematic review and meta-analysis.

PURPOSE: The aim of this systematic review and meta-analysis was to evaluate whether Enhanced Recovery After Surgery (ERAS) protocols for patients undergoing emergency intra-abdominal surgery improve postoperative outcomes as compared to conventional care. METHODS: MEDLINE, EMBASE, WoS, CENTRAL, and Pubmed were searched from inception to December 2022. Articles were eligible if they were randomized controlled trials (RCT) or non-randomized studies comparing ERAS protocols to conventional care for patients undergoing emergency intra-abdominal surgery. The outcomes included postoperative length of stay (LOS), postoperative morbidity, prolonged postoperative ileus (PPOI), and readmission. An inverse variance random effects meta-analysis was performed. A risk of bias was assessed with Cochrane tools. Certainty of evidence was assessed with GRADE. RESULTS: After screening 1018 citations, 20 studies with 1615 patients in ERAS programs and 1933 patients receiving conventional care were included. There was a reduction in postoperative LOS in the ERAS group for patients undergoing upper gastrointestinal (GI) surgery (MD3.35, 95% CI 2.52-4.17, p < 0.00001) and lower GI surgery (MD2.80, 95% CI 2.62-2.99, p < 0.00001). There was a reduction in postoperative morbidity in the ERAS group for patients undergoing upper GI surgery (RR0.56, 95% CI 0.30-1.02, p = 0.06) and lower GI surgery (RR 0.66, 95%CI 0.52-0.85, p = 0.001). In the upper and lower GI subgroup, there were nonsignificant reductions in PPOI in the ERAS groups (RR0.59, 95% CI 0.30-1.17, p = 0.13; RR0.49, 95% CI 0.21-1.14, p = 0.10). There was a nonsignificant increased risk of readmission in the ERAS group (RR1.60, 95% CI 0.57-4.50, p = 0.50). CONCLUSION: There is low-to-very-low certainty evidence supporting the use ERAS protocols for patients undergoing emergency intra-abdominal surgery. The currently available data are limited by imprecision.

Risk of clozapine-associated agranulocytosis and mandatory white blood cell monitoring: Can the regulations be relaxed?

After the introduction of clozapine eight Finnish patients died after developing agranulocytosis. Clozapine was withdrawn from the market and only reintroduced with strict mandatory white blood cell monitoring as long as treatment lasts and thresholds at which clozapine must be discontinued definitively. The fear of agranulocytosis and the need for intensive blood monitoring is the single most important barrier for prescribers and patients alike and leads to underprescription of the only effective and approved medication for treatment-resistant schizophrenia. We summarize evidence that the risk of agranulocytosis is smaller than perceived at the time of reintroduction, is concentrated in the first 18 weeks of treatment, is not greater than with other antipsychotics thereafter and that frequent blood monitoring has not demonstrably decreased the rate of agranulocytosis. Therefore we propose 1) mandatory monitoring of the absolute neutrophil count (ANC) exclusively during the first 18 weeks of clozapine treatment, 2) that thereafter the prescriber and the well-informed patient decide together about further monitoring frequency, 3) that clozapine treatment must be stopped if the ANC falls below 1.0 × 109/L. Continuation of clozapine or a rechallenge are possible if prescriber and patient determine that the benefits outweigh the risks. 4) National registries which control the haematologic monitoring are unnecessary and do not help to reduce clozapine-induced agranulocytosis. They should at least be restricted to the first 18 weeks of clozapine use.

Population-based affective-disorder-related biomedical/biophysical multi-hyper-morbidity across the lifespan: A 16-year population study.

BACKGROUND: There are few if any life-span population-based studies of psychiatric disorder-associated biomedical and biophysical disorders and diseases (morbidity). AIM: To scope the present state of research regarding the biomedical and biophysical morbidity associated with affective and mental disorder in epidemiological samples, and to examine the life-span relationship between affective disorders and biomedical/biophysical disorders to illustrate a novel approach employing the odds ratio to represent the intensity of biomedical and biophysical morbidity associated in time in a population. METHODS: A repeatable systematic literature search of PubMed was represented in summary. Additionally, a regional population-based dataset was constructed and analyzed to represent the age- and sex-specific diagnoses (International Classification of Diseases Version 9, ICD-9) for those with and without affective disorder. The analysis presents a novel index of the relative age-specific frequency of life-span biomedical and biophysical diagnoses associated with affective disorder. RESULTS: The volume of biomedical and biophysical morbidity associated with mental disorder literature has increased, yet few studies measure comprehensive temporal hyper-morbidity (over-representation of diseases over time, either before or after the index diagnostic event) in populations. Further, there have been only a few population-based studies examining the morbidity associated with affective disorder and only one that examines the full diagnostic range of lifespan morbidity. Substantial differences arose between males and females with more females than males having greater frequencies of diagnoses. The age-specific distributions of the maximum proportional diagnosis frequency ratios for each sex illustrate the greatest diagnosis-specific differences when comparing the biomedical and biophysical diagnoses of those with and without affective disorder when the same diagnosis was represented in each grouping at the same age. CONCLUSION: Clinical research needs to focus on more than one or two comorbid biomedical or biophysical disorders at a time. Comprehensive population-based examination of the lifespan biomedical and biophysical multi-morbidity associated with affective disorder has the potential to directly inform clinical practice. Representing the proportional ratios of age-specific frequency of diagnoses for the full range of ICD-9 diagnoses is a novel analytical model. Diagnostic frequency appears a viable representation of a given disease state, such as affective disorder. Fortunately, the WPA has developed a global education section to better understand the biomedical and biophysical morbidity associated with all psychiatric disorders. This has been identified by the WPA as the psychiatric practice challenge of the 21st century.

Evidence-based treatment of Achilles tendon rupture.

The treatment of Achilles tendon rupture has recently seen a shift toward non-operative management, as supported by the literature, yet many surgeons continue to treat these injuries operatively. The evidence clearly supports non-operative management of these injuries except for Achilles insertional tears and for certain patient groups, such as athletic patients, for whom further research is warranted. This nonadherence to evidence-based treatment may be explained by patient preference, surgeon subspecialty, surgeon era of practice or other variables. Further research to understand the reasons behind this nonadherence would help to promote conformity in the surgical community across all specialties and adherence to evidence-based approaches.

Though five-strand hamstring autografts demonstrate greater graft diameter, postoperative outcomes are equivocal to four-strand hamstring autograft preparations: a systematic review and meta-analysis of level I and II studies.

PURPOSE: To compare graft dimensions, functional outcomes, and failure rates following anterior cruciate ligament reconstruction (ACLR) with either five-strand or four-strand hamstring autograft options. METHODS: Three databases (MEDLINE, PubMed, and EMBASE) were searched from inception to 22 April 2023 for level I and II studies comparing five- and four-strand hamstring autografts in ACLR. The authors adhered to the PRISMA and R-AMSTAR guidelines as well as the Cochrane Handbook for Systematic Reviews of Interventions. Data on demographics, surgical details and rehabilitation, graft diameter, patient-reported outcome measures (PROMs), and rates of positive Lachman test, positive pivot shift test, and graft rupture were extracted. PROMs included Knee Osteoarthritis and Outcome Score (KOOS) subscales, Lysholm, and International Knee Documentation Committee (IKDC). RESULTS: One randomized controlled trial (RCT) and four prospective cohort studies with 572 patients were included. Graft diameters were larger in the five-strand group with a mean difference of 0.93 mm (95% CI 0.61 to 1.25, p < 0.001, I2 = 66%). The five-strand group reported statistically higher KOOS ADL subscale and Lysholm scores with a mean difference of 4.85 (95% CI 0.14 to 9.56, p = 0.04, I2 = 19%) and 3.01 (95% CI 0.48 to 5.53, p = 0.02, I2 = 0%), respectively. There were no differences in KOOS symptoms, pain, quality of life, or sports subscales, or IKDC scores. There were no differences in rates of positive Lachman test, positive pivot shift test, or graft rupture with pooled odds ratios of 0.62 (95% CI 0.13 to 2.91, n.s., I2 = 80%), 0.94 (95% CI 0.51 to 1.75, n.s., I2 = 31%), and 2.13 (95% CI 0.38 to 12.06, n.s., I2 = 0%), respectively. CONCLUSIONS: Although five-stranded hamstring autografts had significantly larger graft diameters compared to four-stranded grafts with a mean difference of 0.93 mm, similar graft rupture rates and clinical laxity assessments were identified following ACLR. While some PROMs were statistically superior in the five-stranded hamstring groups, the threshold for the minimal clinical important difference was not reached indicating similar clinical outcomes overall. LEVEL OF EVIDENCE: Level II.

Surgical techniques for medial Patellofemoral ligament reconstruction: a systematic review and meta-analysis of level I and II studies.

PURPOSE: To determine the most optimal surgical technique for medial patellofemoral ligament reconstruction (MPFLR). METHODS: Three databases MEDLINE, PubMed, and EMBASE were searched from inception to December 13th, 2022, for level I or II studies comparing MPFLR techniques. The authors adhered to the PRISMA and R-AMSTAR guidelines as well as the Cochrane Handbook for Systematic Reviews of Interventions. Data on patient-reported outcome measures were recorded. Quality assessment was carried out using the MINORS and Cochrane Risk of Bias assessment tools. Certainty of evidence was carried out with the GRADE assessment tool. RESULTS: Ten studies comprising 723 patients (723 knees) were included in this review. The weighted mean difference in Kujala, Lysholm, and IKDC scores comparing single- and double-tunnel patellar drilling techniques was 2.66 (95% CI -1.05-6.37, p = 0.16, I2 = 0%) with moderate certainty, 0.78 (95% CI -9.02-10.58, p = 0.88, I2 = 87%) with low certainty, and 1.71 (95% CI -2.43-5.86, p = 0.42, I2 = 0%) with low certainty, respectively. Double-suture anchor patellar fixation demonstrated greater Kujala scores than transpatellar fixation (87.1 ± 2.8 vs 84.0 ± 3.8, p < 0.001) with moderate certainty. Y-shaped graft patellar fixation demonstrated superior Kujala scores to C-shaped graft patellar fixation (95.9 ± 4.7 vs 91.3 ± 9.7, p = 0.001) with moderate certainty. Augmentation of femoral fixation with polyester sutures demonstrated superior Kujala scores (97.8 ± 6.4. vs 88.0 ± 6.3, p < 0.005) with low certainty. Four-stranded grafts demonstrated greater Kujala scores than two-stranded grafts (93.5 ± 2.6 vs 91.6 ± 3.5, p = 0.01) with low certainty. CONCLUSION: The optimal MPFLR surgical technique is likely to utilize a four-stranded graft using either endobutton, double-suture anchor, or transosseous suture patellar fixation with polyester suture augmented interference screw femoral fixation. Orthopedic surgeons can consider employing such a technique to improve patient outcomes by conferring greater graft stability, strength, and function. Level of evidence Level II.

Technology-assisted anterior cruciate ligament reconstruction improves tunnel placement but leads to no change in clinical outcomes: a systematic review and meta-analysis.

PURPOSE: To investigate the effect of technology-assisted Anterior Cruciate Ligament Reconstruction (ACLR) on post-operative clinical outcomes and tunnel placement compared to conventional arthroscopic ACLR. METHODS: CENTRAL, MEDLINE, and Embase were searched from January 2000 to November 17, 2022. Articles were included if there was intraoperative use of computer-assisted navigation, robotics, diagnostic imaging, computer simulations, or 3D printing (3DP). Two reviewers searched, screened, and evaluated the included studies for data quality. Data were abstracted using descriptive statistics and pooled using relative risk ratios (RR) or mean differences (MD), both with 95% confidence intervals (CI), where appropriate. RESULTS: Eleven studies were included with total 775 patients and majority male participants (70.7%). Ages ranged from 14 to 54 years (391 patients) and follow-up ranged from 12 to 60 months (775 patients). Subjective International Knee Documentation Committee (IKDC) scores increased in the technology-assisted surgery group (473 patients; P = 0.02; MD 1.97, 95% CI 0.27 to 3.66). There was no difference in objective IKDC scores (447 patients; RR 1.02, 95% CI 0.98 to 1.06), Lysholm scores (199 patients; MD 1.14, 95% CI - 1.03 to 3.30) or negative pivot-shift tests (278 patients; RR 1.07, 95% CI 0.97 to 1.18) between the two groups. When using technology-assisted surgery, 6 (351 patients) of 8 (451 patients) studies reported more accurate femoral tunnel placement and 6 (321 patients) of 10 (561 patients) studies reported more accurate tibial tunnel placement in at least one measure. One study (209 patients) demonstrated a significant increase in cost associated with use of computer-assisted navigation (mean 1158€) versus conventional surgery (mean 704€). Of the two studies using 3DP templates, production costs ranging from $10 to $42 USD were cited. There was no difference in adverse events between the two groups. CONCLUSION: Clinical outcomes do not differ between technology-assisted surgery and conventional surgery. Computer-assisted navigation is more expensive and time consuming while 3DP is inexpensive and does not lead to greater operating times. ACLR tunnels can be more accurately located in radiologically ideal places by using technology, but anatomic placement is still undetermined because of variability and inaccuracy of the evaluation systems utilized. LEVEL OF EVIDENCE: Level III.

Clozapine prescription rates in Southeast Europe: A cross-sectional study.

Introduction: International reports indicate that clozapine is under prescribed. Yet, this has not been explored in Southeast European (SEE) countries. This cross-sectional study investigates clozapine prescription rates in a sample of 401 outpatients with psychosis from Bosnia and Herzegovina, Kosovo by United Nations resolution, North Macedonia, Montenegro and Serbia. Methods: Descriptive analysis was used to explore clozapine prescription rates; daily antipsychotic dosage was calculated and converted into olanzapine equivalents. Patients receiving clozapine were compared to those not receiving clozapine; next those that were on clozapine monotherapy were compared to those who were on clozapine polytherapy regime. Results: It was showed that clozapine was prescribed to 37.7% of patients (with cross-country variation: from 25% in North Macedonia to 43.8% in Montenegro), with average dose of 130.7 mg/daily. The majority of patients on clozapine (70.5%) were prescribed at least one more antipsychotic (the most frequent combination was with haloperidol). Discussion: Our findings suggested that clozapine prescription rate in SEE outpatients is higher than in Western Europe. The average dose is significantly below the optimal therapeutic dosage recommended by clinical guidelines, and clozapine polytherapy is common. This might indicate that clozapine is prescribed mainly for its sedative effect rather than antipsychotic. We hope that this finding will be taken up by relevant stakeholders to address this non-evidence-based practice.

Staging Prostate Cancer with 68Ga-PSMA-11 PET/CT in the Elderly: Is Preimaging Biopsy Imperative?

Although prostate-specific membrane antigen (PSMA) PET/CT has been shown valuable for staging biopsy-proven [B(+)] high-risk prostate cancer, elderly patients are occasionally referred for PSMA PET/CT without a preimaging confirming biopsy [B(-)]. The current study evaluated the rate, clinical characteristics, and PET-based stage of elderly B(-) patients and explored whether biopsy status affects therapeutic approach. Methods: One hundred consecutive patients at least 80 y old who underwent staging 68Ga-PSMA-11 PET/CT were included. For each patient, we documented whether preimaging biopsy was performed, the clinical parameters, the PET-based staging parameters, and the primary therapy received. Results: Thirty-four (34%) of the elderly patients included in the study had no preimaging biopsy. Compared with B(+) patients, B(-) patients were older (median age, 87 vs. 82 y; P < 0.01), with worse performance status (P < 0.01) and higher prostate-specific antigen (PSA) levels (median, 57 vs. 15.4 ng/mL; P < 0.01). On 68Ga-PSMA-11 PET/CT, all B(-) patients had avid disease, with trends toward higher rates of bone metastases (47.1% vs. 28.8%) and overall advanced disease (50% vs. 33.3%) than in B(+) patients. Among patients with localized (n = 36) or locally advanced (n = 25) disease, B(-) patients were less commonly referred than B(+) patients for definitive therapies (P < 0.01). However, higher age, Eastern Cooperative Oncology Group performance status, and PSA were other probable factors determining their therapeutic approach. Among 39 patients with advanced disease, 38 received hormonal therapy irrespective of their biopsy status. Among B(-) patients with advanced disease who were referred for hormonal therapy, 12 of 13 with follow-up data showed a biochemical or imaging-based response. Conclusion: Real-life experience with 68Ga-PSMA-11 PET/CT indicates that around one third of elderly patients are referred for imaging without a preimaging confirming biopsy. These patients are likely to be older, with a worse clinical status and higher PSA levels. Advanced disease might be more likely to be identified on their 68Ga-PSMA-11 PET/CT images, and if it is, their biopsy status does not preclude them from receiving hormonal therapy.

PET radiotracers for whole-body in vivo molecular imaging of prostatic neuroendocrine malignancies.

Prostatic neuroendocrine malignancies represent a spectrum of diseases. Treatment-induced neuroendocrine differentiation (tiNED) in hormonally treated adenocarcinoma has been the subject of a large amount of recent research. However, the identification of neuroendocrine features in treatment-naïve prostatic tumor raises a differential diagnosis between prostatic adenocarcinoma with de novo neuroendocrine differentiation (dNED) versus one of the primary prostatic neuroendocrine tumors (P-NETs) and carcinomas (P-NECs). While [18F]FDG is being used as the main PET radiotracer in oncologic imaging and reflects cellular glucose metabolism, other molecules labeled with positron-emitting isotopes, mainly somatostatin-analogues labeled with 68Ga and prostate-specific membrane antigen (PSMA)-ligands labeled with either 18F or 68Ga, are now routinely used in departments of nuclear medicine and molecular imaging, and may be advantageous in imaging prostatic neuroendocrine malignancies. Still, the selection of the preferred PET radiotracer in such cases might be challenging. In the current review, we summarize and discuss published data on these different entities from clinical, biological, and molecular imaging standpoints. Specifically, we review the roles that [18F]FDG, radiolabeled somatostatin-analogues, and radiolabeled PSMA-ligands play in these entities in order to provide the reader with practical recommendations regarding the preferred PET radiotracers for imaging each entity. In cases of tiNED, we conclude that PSMA expression may be low and that [18F]FDG or radiolabeled somatostatin-analogues should be preferred for imaging. In cases of prostatic adenocarcinoma with dNED, we present data that support the superiority of radiolabeled PSMA-ligands. In cases of primary neuroendocrine malignancies, the use of [18F]FDG for imaging high-grade P-NECs and radiolabeled somatostatin-analogues for imaging well-differentiated P-NETs is recommended. KEY POINTS: • The preferred PET radiotracer for imaging prostatic neuroendocrine malignancies depends on the specific clinical scenario and pathologic data. • When neuroendocrine features result from hormonal therapy for prostate cancer, PET-CT should be performed with [18F]FDG or radiolabeled somatostatin-analogue rather than with radiolabeled PSMA-ligand. • When neuroendocrine features are evident in newly diagnosed prostate cancer, differentiating adenocarcinoma from primary neuroendocrine malignancy is challenging but crucial for selection of PET radiotracer and for clinical management.