Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma.

BACKGROUND: Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease. METHODS: In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival. RESULTS: A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%). CONCLUSIONS: A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.).

The bone marrow is the primary site of thrombopoiesis.

ABSTRACT: Megakaryocytes (MKs) generate thousands of platelets over their lifespan. The roles of platelets in infection and inflammation has guided an interest to the study of extramedullary thrombopoiesis and therefore MKs have been increasingly reported within the spleen and lung. However, the relative abundance of MKs in these organs compared to the bone marrow and the scale of their contribution to the platelet pool in a steady state remain controversial. We investigated the relative abundance of MKs in the adult murine bone marrow, spleen, and lung using whole-mount light-sheet and quantitative histological imaging, flow cytometry, intravital imaging, and an assessment of single-cell RNA sequencing (scRNA-seq) repositories. Flow cytometry revealed significantly higher numbers of hematopoietic stem and progenitor cells and MKs in the murine bone marrow than in spleens or perfused lungs. Two-photon intravital and light-sheet microscopy, as well as quantitative histological imaging, confirmed these findings. Moreover, ex vivo cultured MKs from the bone marrow subjected to static or microfluidic platelet production assays had a higher capacity for proplatelet formation than MKs from other organs. Analysis of previously published murine and human scRNA-seq data sets revealed that only a marginal fraction of MK-like cells can be found within the lung and most likely only marginally contribute to platelet production in the steady state.

Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma.

BACKGROUND: In patients with newly diagnosed multiple myeloma, the effect of adding autologous stem-cell transplantation (ASCT) to triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, is unknown. METHODS: In this phase 3 trial, adults (18 to 65 years of age) with symptomatic myeloma received one cycle of RVD. We randomly assigned these patients, in a 1:1 ratio, to receive two additional RVD cycles plus stem-cell mobilization, followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Both groups received lenalidomide until disease progression, unacceptable side effects, or both. The primary end point was progression-free survival. RESULTS: Among 357 patients in the RVD-alone group and 365 in the transplantation group, at a median follow-up of 76.0 months, 328 events of disease progression or death occurred; the risk was 53% higher in the RVD-alone group than in the transplantation group (hazard ratio, 1.53; 95% confidence interval [CI], 1.23 to 1.91; P<0.001); median progression-free survival was 46.2 months and 67.5 months. The percentage of patients with a partial response or better was 95.0% in the RVD-alone group and 97.5% in the transplantation group (P = 0.55); 42.0% and 46.8%, respectively, had a complete response or better (P = 0.99). Treatment-related adverse events of grade 3 or higher occurred in 78.2% and 94.2%, respectively; 5-year survival was 79.2% and 80.7% (hazard ratio for death, 1.10; 95% CI, 0.73 to 1.65). CONCLUSIONS: Among adults with multiple myeloma, RVD plus ASCT was associated with longer progression-free survival than RVD alone. No overall survival benefit was observed. (Funded by the National Heart, Lung, and Blood Institute and others; DETERMINATION ClinicalTrials.gov number, NCT01208662.).

S100A8/A9 drives the formation of procoagulant platelets through GPIbα.

S100A8/A9, also known as "calprotectin" or "MRP8/14," is an alarmin primarily secreted by activated myeloid cells with antimicrobial, proinflammatory, and prothrombotic properties. Increased plasma levels of S100A8/A9 in thrombo-inflammatory diseases are associated with thrombotic complications. We assessed the presence of S100A8/A9 in the plasma and lung autopsies from patients with COVID-19 and investigated the molecular mechanism by which S100A8/A9 affects platelet function and thrombosis. S100A8/A9 plasma levels were increased in patients with COVID-19 and sustained high levels during hospitalization correlated with poor outcomes. Heterodimeric S100A8/A9 was mainly detected in neutrophils and deposited on the vessel wall in COVID-19 lung autopsies. Immobilization of S100A8/A9 with collagen accelerated the formation of a fibrin-rich network after perfusion of recalcified blood at venous shear. In vitro, platelets adhered and partially spread on S100A8/A9, leading to the formation of distinct populations of either P-selectin or phosphatidylserine (PS)-positive platelets. By using washed platelets, soluble S100A8/A9 induced PS exposure but failed to induce platelet aggregation, despite GPIIb/IIIa activation and alpha-granule secretion. We identified GPIbα as the receptor for S100A8/A9 on platelets inducing the formation of procoagulant platelets with a supporting role for CD36. The effect of S100A8/A9 on platelets was abolished by recombinant GPIbα ectodomain, platelets from a patient with Bernard-Soulier syndrome with GPIb-IX-V deficiency, and platelets from mice deficient in the extracellular domain of GPIbα. We identified the S100A8/A9-GPIbα axis as a novel targetable prothrombotic pathway inducing procoagulant platelets and fibrin formation, in particular in diseases associated with high levels of S100A8/A9, such as COVID-19.

Can my surgeon scope? Trends in endoscopy training volume and experience among general surgery residents in the United States: a nationwide analysis.

INTRODUCTION: Endoscopy is a major part of surgical training. Accreditation Council for Graduate Medical Education (ACGME) has set standards regarding the minimum volume of endoscopy cases required for graduation. However, there is paucity of high-quality data on the number of cases that most surgical graduates perform. METHODS: We conducted a retrospective analysis of operative case logs of all general surgery residents graduating from ACGME-accredited programs from 2010 to 2023. Data on mean number of endoscopy cases, including mean in each subcategory, were retrieved. Mann-Kendall trend test was used to investigate trends in endoscopy experience. RESULTS: Between 2010 and 2023, the mean overall endoscopy procedures per resident remained stable, with 129.5 in 2010 and 132.1 in 2023 (t = 0.429; p-value = 0.037). The majority of these cases were performed as surgeon junior (76.6% in 2010; 80.9% in 2023), while the remaining cases were logged as surgeon chief. The most substantial contribution to the overall volume was from flexible colonoscopy (mean: 64.1 in 2010 and 67.2 in 2023). The volume for colonoscopy remained fairly stable (t = 0.429; p-value = 0.036). This was followed by esophagogastroduodenoscopy (mean: 35.3 in 2010 and 35.5 in 2023), which saw a significant increase in volume (t = 0.890; p-value ≤ 0.001). There was a significant increase in the number of overall upper endoscopic procedures (t = 0.791; p-value ≤ 0.001), while lower endoscopic procedures did not change significantly (t = 0.319; p-value = 0.125). The procedural volume for endoscopic retrograde cholangiography, sigmoidoscopy, cystoscopy/ureteroscopy, laryngoscopy, and bronchoscopy decreased significantly (p-value < 0.05 for all). CONCLUSION: The overall endoscopy volume for general surgery residents has largely remained stable, with a minor increase in esophagogastroduodenoscopy and no change in colonoscopy. Future research should investigate whether simulation-based exercises can bridge the gap between procedural volume and learning curve requirements for endoscopy.

Tran slation , cultural adap tation an d psycho metric anal ysis of U rd u ver sion of Vic torian; institu te of sp or ts ass es sme nt: Achill es quest i onnaire fo r athletes with achilles tendinopathy.

OBJECTIVE: To translate, culturally adapt and psychometrically analyse the Urdu version of the Victorian Institute of Spor t Assessment-Achilles questionnaire. METHODS: The cross-sec tional study was conducted at the Pak istan Sports Board, Lahore, Pakistan, from June 17, 2021, to February 15, 2022, and comprised patients with Achilles tendinopathy in group A and healthy controls in group B. Beaton's guidelines for cultural adaptation and validation for self-repor ted measures were followed to translate and validate the Victorian Institute of Sport Assessment-Achilles questionnaire in Urdu language. Data was analysed using SPSS 23. RESULTS: Of the 180 subjects with mean age 28.06±5.95 years, 125(69.6%) were males. There were 130(72.2%) patients in group A and 50(27.8%) controls in group B. The overall mean score of the Victorian Institute of Sport Assessment- Achille s questionnaire was 55.99±25.43; group A 41.14±9.54 and group B 94.60±4.22. The Urdu version exhibited excellent internal consistency with Cronbach's alpha values 0.95, and excellent test-retest reliability (p<0.001). Absolute reliability was expressed by standard error of measurement 5.317 and minimal detectable change (6.38). Convergent validity demonstrated strong correlation with the physical domain (r=0.81) of the Urdu version of the World Health Organisation Quality of Life Brief Version. CONCLUSIONS: The Victorian Institute of Sport Assessment-Achilles questionnaire could be utilised for assessing severity of Achilles tendinopathy among Urdu-speaking population for clinical as well as research purposes.

Perioperative prophylactic corticosteroids for cardiac surgery in children: A systematic review and meta-analysis.

OBJECTIVE: Perioperative corticosteroids have been used for pediatric cardiac surgery for decades, but the underlying evidence is conflicting. We aimed to investigate the efficacy and safety of perioperative prophylactic corticosteroids in pediatric heart surgeries. METHODS: We searched electronic databases until March 2023 to retrieve all randomized controlled trials (RCTs) that administered perioperative prophylactic corticosteroids to children undergoing heart surgery. We used RevMan 5.4 to pool risk ratios (RRs) and mean differences (MDs). RESULTS: A total of 12 RCTs (2,209 patients) were included in our review. Corticosteroids administration was associated with a nonsignificant reduction in all-cause mortality (RR 0.62; 95% CI: 0.37-1.02, I2 = 0%; moderate certainty); however, it was associated with a lower duration of mechanical ventilation (MV) (MD -0.63 days; 95% CI: -1.16 to -0.09 days, I2 = 41%; high certainty). Corticosteroids did not affect the length of ICU and hospital stay but significantly reduced the incidence of postoperative low cardiac output syndrome (LCOS) (RR 0.76; 95% CI: 0.60-0.96, I2 = 0%; moderate certainty) and reoperation (RR 0.37; 95% CI: 0.19-0.74, I2 = 0%; moderate certainty). There was no increase in adverse events except a higher risk of hyperglycemia and postoperative insulin use. CONCLUSIONS: The use of perioperative corticosteroids in pediatric heart surgeries is associated with a trend toward reduced all-cause mortality without attaining statistical significance. Corticosteroids reduced MV duration, and probably decrease the incidence of LCOS, and reoperations. The choice of corticosteroid agent and dose is highly variable and further larger studies may help determine the ideal agent, dose, and patient population for this prophylactic therapy.

Basic human values drive food choice decision-making in different food environments of Kenya and Tanzania.

Increased access to a variety of foods in low-and-middle-income countries (LMICs) has led to greater autonomy in food choice decision-making. Autonomy allows individuals to make decisions through negotiation of considerations in ways that are consistent with basic values. The aim of this study was to identify and describe how basic human values drive food choice in two diverse populations with transitioning food environments living in the neighboring East African countries of Kenya and Tanzania. Secondary data analysis was carried out on focus group discussions conducted with men and women in Kenya (n = 28) and Tanzania (n = 28) as part of prior studies on food choice. A priori coding based on Schwartz's theory of basic human values was conducted, followed by a narrative comparative analysis, which included review by original principal investigators. Values of conservation (security, conformity, tradition), openness to change (self-directed thought and action, stimulation, indulgence), self-enhancement (achievement, power, face), and self-transcendence (benevolence-dependability and -caring) were prominent drivers of food choice in both settings. Participants described how values were negotiated and highlighted existing tensions. For example, the value of tradition was cited as important in both settings but changing food contexts (e.g., new foods, diverse neighborhoods) increased prioritization of values like stimulation, indulgence, and self-directed thought and action. The application of a basic values framework was useful for understanding food choice in both settings. A focused understanding of how values drive food choice decision-making in the context of changing food availability in LMICs is essential for the promotion of sustainable healthy diets.

From Protocol to Definitive Study-The State of Randomized Controlled Trial Evidence in Sports Medicine Research: A Systematic Review and Survey Study.

OBJECTIVE: To evaluate the progression, quality, and challenges associated with conducting and publishing randomized controlled trials (RCTs) in sports medicine. DESIGN: Systematic review and survey. SETTING: MEDLINE and Embase were searched for all publications before September 17, 2021. A targeted search of clinicaltrials.gov , BMC Musculoskeletal Disorders, PubMed, and Google Scholar were also conducted. The survey was administered to authors using REDCap. PARTICIPANTS: Where the systematic search revealed no corresponding published definitive trial, authors of the published pilots were surveyed. INTERVENTIONS: Survey assessing limitations to definitive trials. MAIN OUTCOME MEASURES: Protocol/method articles, pilot articles, and relevant clinical trial registry records with corresponding definitive trials were pooled. RESULTS: Our literature search yielded 27 006 studies; of which, we included 208 studies (60 (28.8%) pilot RCTs, 84 (40.4%) protocol/method articles, and 64 (30.8%) trial registry records). From these, 44 corresponding definitive RCTs were identified. Pilot study and definitive RCT methodological quality increased on average most significantly during the duration of this review (30.6% and 8.2%). Of the 176 authors surveyed, 59 (33.5%) responded; 24.6% (14/57) stated that they completed an unpublished definitive trial, while 52.6% (30/57) reported having one underway. CONCLUSIONS: The quality and number of RCT publications within the field of sports medicine has been increasing since 1999. The number of sports medicine-related protocol and pilot articles preceding a definitive trial publication showed a sharp increase over the past 10 years, although only 5 pilot studies have progressed to a definitive RCT.

Ex Vivo Antiplatelet and Thrombolytic Activity of Bioactive Fractions from the New-Fangled Stem Buds of Ficus religiosa L. with Simultaneous GC-MS Examination.

Different parts of Ficus religiosa are the common components of various traditional formulations for the treatment of several blood disorders. The new-fangled stem buds' powder was extracted with 80% ethanol and successively fractionated by chloroform and methanol. Chloroform and methanol fractions of Ficus religiosa (CFFR and MFFR) were tested for antiplatelet, antithrombotic, thrombolytic, and antioxidant activity in ex vivo mode. The MFFR was particularly investigated for GC-MS and toxicity. The antiplatelet activity of the CFFR, MFFR, and standard drug aspirin at 50 µg/mL was 54.32%, 86.61%, and 87.57%, and a significant delay in clot formation was noted. CFFR at different concentrations did not show a significant effect on the delay of clot formation, antiplatelet, and free radical scavenging activity. The most possible marker compounds for antiplatelet and antioxidant activity identified by GC-MS in the MFFR are salicylate derivatives aromatic compounds such as benzeneacetaldehyde (7), phenylmalonic acid (13), and Salicylic acid (14), as well as Benzamides derivatives such as carbobenzyloxy-dl-norvaline (17), 3-acetoxy-2(1H)-pyridone (16), and 3-benzylhexahydropyrrolo [1,2-a] pyrazine-1,4-dione (35). A toxicity study of MFFR did not show any physical indications of toxicity and mortality up to 1500 mg/kg body weight and nontoxic up to 1000 mg/kg, which is promising for the treatment of atherothrombotic diseases.

Clinical Presentation and Outcome of Multiple Rare Earth Magnet Ingestions in Children of Qatar. A Single-Center Experience.

INTRODUCTION: Rare earth magnets are powerful magnets that can have several negative effects if ingested. The goal of our study is to describe the result of multiple rare earth magnets ingested by children in Qatar. MATERIALS AND METHODS: This is observational research. We conducted a retrospective chart review and descriptive analysis of all cases of multiple rare earth magnetic ingestion that werepresented to the Emergency Department of Sidra Medicine between January 2018 and July 2022. We obtained an exemption for this study from our institutional review board (IRB). RESULTS: In our research, we identified 21 children having multiple rare earth magnetic ingestions. The predominant symptoms were abdominal pain and vomiting which were observed in 57% (n = 12) and 48% (n = 10) of the patients respectively. The most common sign was abdominal tenderness,observed in 14% (n = 3) of the patients. In our sample, 38% (n = 8) of the patients were managed conservatively whereas 62% (n = 13) needed intervention. In our study, 48% (n = 10) of the patients sustained complications. The frequent complications were intestinal perforation appreciated in 24% (n = 5) and intestinal perforation with fistula formation in 19% (n = 4) of the patients. The median age of these patients was two years while the median number of magnets ingested was six. The ingestions were unwitnessed, and the duration of ingestions was unknowninthemajorityofpatientswhoexperiencedcomplications (n = 8/10). CONCLUSION: If numerous rare earth magnetis ingested, children are in high danger of harm. It can be difficult to pinpoint the cases in younger children due to poor communication skills, especially if the intake is unreported. Although Qatar has established restrictions banning the import of rare earth magnets, there are reported cases of children with rare earth magnets ingestions.

An insight to rhizosphere bacterial community composition and structure of consecutive winter-initiated sugarcane ratoon crop in Southern China.

BACKGROUND: Ratooning in sugarcane is a crucial strategy for ensuring the long-term sustainability of the sugarcane industry. Knowledge gap relating to the interaction between rhizosphere microbiome and ratooning crop, particularly the impact of different sugarcane cultivars on the rhizosphere microbiome in consecutive ratooning, requires additional research. The response of two different sugarcane cultivars, viz ZZ-1 and ZZ-13, were evaluated in consecutive ratooning towards the rhizosphere microbial community and cane morphological characters. RESULTS: Significant changes in the rhizosphere microbiome were observed in the second ratooning over the years. Several important genera were observed in high abundance during the second ratooning, including Burkholderia, Sphingomonas, Bradyzhizobium, and Acidothermus. Cultivar ZZ-13 caused more alterations in the rhizosphere microbiome than ZZ-1, resulting in a more favorable rhizosphere environment for sugarcane growth. The genotypes also varied in terms of nutrients and enzyme activity over the years. There were significant differences between the genotypes and year for number of stalks and yield was significant for genotypes, years and genotype × year. CONCLUSION: This finding will help to understand thorough interactions between rhizosphere microorganisms and ratoon sugarcane and lay the foundation for promoting and maximizing yield as far as possible. In the future, this work can serve as guidance in sugarcane husbandry, mainly in Guangxi, China.

Atmospheric propagation of space-fractional Gaussian-beam waves in a FSO communication system.

We present a novel, self-consistent analytical model of Gaussian-beam propagation through the atmospheric turbulence by solving the paraxial wave equation in a fractional-dimension space of dimension D, in the range 2 < D ≤ 3, corresponding to the effective spatial dimension experienced by the beam under given turbulent conditions in a free space optical (FSO) communication system. The well-known refractive index structure parameter (C n2) has been mapped from D = 2.668 (C n2≈10-13, strong fluctuations) to D = 2.999 (C n2≈10-16, weak fluctuations) in our simple analytical model, whereas D = 3 corresponds to the ideal case of free-space propagation under zero turbulence. Finally, an optimization problem is developed to mitigate the effects of atmospheric turbulence, leading to efficient transceiver design for the FSO communication system to ensure the reliability of links under varying atmospheric turbulence.

Sorting nexin 24 is required for α-granule biogenesis and cargo delivery in megakaryocytes.

Germline defects affecting the DNA-binding domain of the transcription factor FLI1 are associated with a bleeding disorder that is characterized by the presence of large, fused α-granules in platelets. We investigated whether the genes showing abnormal expression in FLI1-deficient platelets could be involved in platelet α-granule biogenesis by undertaking transcriptome analysis of control platelets and platelets harboring a DNA-binding variant of FLI1. Our analysis identified 2,276 transcripts that were differentially expressed in FLI1-deficient platelets. Functional annotation clustering of the coding transcripts revealed significant enrichment for gene annotations relating to protein transport, and identified Sorting nexin 24 (SNX24) as a candidate for further investigation. Using an induced pluripotent stem cell-derived megakaryocyte model, SNX24 expression was found to be increased during the early stages of megakaryocyte differentiation and downregulated during proplatelet formation, indicating tight regulatory control during megakaryopoiesis. CRISPR-Cas9 mediated knockout (KO) of SNX24 led to decreased expression of immature megakaryocyte markers, CD41 and CD61, and increased expression of the mature megakaryocyte marker CD42b (P=0.0001), without affecting megakaryocyte polyploidisation, or proplatelet formation. Electron microscopic analysis revealed an increase in empty membrane-bound organelles in SNX24 KO megakaryocytes, a reduction in α-granules and an absence of immature and mature multivesicular bodies, consistent with a defect in the intermediate stage of α-granule maturation. Co-localization studies showed that SNX24 associates with each compartment of α-granule maturation. Reduced expression of CD62P and VWF was observed in SNX24 KO megakaryocytes. We conclude that SNX24 is required for α-granule biogenesis and intracellular trafficking of α-granule cargo within megakaryocytes.

Post-translational polymodification of ß1-tubulin regulates motor protein localisation in platelet production and function.

In specialised cells, the expression of specific tubulin isoforms and their subsequent post-translational modifications drive and coordinate unique morphologies and behaviours. The mechanisms by which ß1-tubulin, the platelet and megakaryocyte (MK) lineage restricted tubulin isoform, drives platelet production and function remains poorly understood. We investigated the roles of two key post-translational tubulin polymodifications (polyglutamylation and polyglycylation) on these processes using a cohort of thrombocytopenic patients, human induced pluripotent stem cell (iPSC) derived MKs, and healthy human donor platelets. We find distinct patterns of polymodification in MKs and platelets, mediated by the antagonistic activities of the cell specific expression of Tubulin Tyrosine Ligase Like (TTLLs) and Cytosolic Carboxypeptidase (CCP) enzymes. The resulting microtubule patterning spatially regulates motor proteins to drive proplatelet formation in megakaryocytes, and the cytoskeletal reorganisation required for thrombus formation. This work is the first to show a reversible system of polymodification by which different cell specific functions are achieved.

An infant with inconsolable crying.

Inconsolable crying in infants can be caused by as simple as infantile colic to wide variety of pathologies. A thorough history, physical examination followed by laboratory and radiologic evaluation can identify the cause of inconsolable crying. We present a case of infant who presented with inconsolable crying and after extensive workup no cause could ne identified. Eventually after consultation scorpion envenomation was considered. Antivenom was administered and the patient returned to normal. Patient did not exhibit any signs of somatic or cranial nerve dysfunction with inconsolable crying and tachycardia as the only manifestation of envenomation. In summary "Bites and stings can cause inconsolable crying".

A higher proportion of patients may reach the MCID with capsular closure in patients undergoing arthroscopic surgery for femoroacetabular impingement: a systematic review and meta-analysis.

PURPOSE: The purpose of this review is to provide a summary of the techniques and outcomes of various capsular management strategies in patients undergoing hip arthroscopy for femoroacetabular impingement (FAI). The information this review provides on capsular management strategies will provide surgeons with operative guidance and decision-making when managing patients with FAI lesions arthroscopically. METHODS: Three databases MEDLINE, EMBASE, and PubMed were searched from database inception to November 2nd 2021, for literature addressing capsular management of patients undergoing hip arthroscopy for FAI. All level I-IV data on capsular management strategy as well as postoperative functional outcomes were recorded. A meta-analysis was used to combine the mean postoperative functional outcomes using a random-effects model. RESULTS: Overall, there were a total of 36 studies and 4744 patients included in this review. The mean MINORS score was 10.7 (range 8-13) for non-comparative studies and 17.6 (range 15-20) for comparative studies. Three comparative studies in 1302 patients examining the proportion of patients reaching the MCID for the mHHS score in patients undergoing interportal capsulotomy with either capsular repair or no repair found that the capsular repair group had a higher odds ratio of reaching the MCID at 1.46 (95% CI 0.61-3.45, I2 = 67%, Fig. 2, Table 3); however, this difference was not significant with a p value of 0.39. When looking at only level 1 and 2 studies, four studies in 1308 patients reporting on the mHHS score in patients undergoing capsular closure regardless of capsulotomy type, found a pooled standardized mean difference in the mHHS score of 2.1 (95% CI 1.7-2.55, I2 = 70%, Fig. 3), while four studies in 402 patients reporting on the mHHS score in patients not undergoing capsular closure regardless of capsulotomy type found a pooled standardized mean difference in the mHHS score of 1.46 (95% CI 1.2-1.7, I2 = 30%, Fig. 4). CONCLUSION: This review may demonstrate improved postoperative outcomes in patients undergoing complete capsular closure regardless of capsulotomy type based on postoperative mHHS score. Furthermore, this review may suggest improved postoperative outcomes after closure of an interportal capsulotomy. There are limited published outcome data regarding T-type capsulotomy without closure. This review provides surgeons with operative guidance on capsular management strategies when treating patients with FAI lesions arthroscopically. LEVEL OF EVIDENCE: IV.

Clinical Presentation of Toddlers With New Intracranial Space-Occupying Lesions: A Case Series.

OBJECTIVE: Intracranial space occupying lesions (ICSOLs) like tumors and abscesses can be life-threatening conditions. It can be especially difficult to diagnose these conditions in toddlers. We aimed to describe symptoms and signs present in a sample of toddlers with ICSOLs. METHODS: We performed a retrospective chart review of 15 toddlers with intracranial tumors, abscesses, or infected cysts. We collected data on the presence of various signs and symptoms on presentation to the emergency department. RESULTS: Eight toddlers (53%) presented with vomiting. A change in behavior was the second most common symptom (6, 40%). Seven children (47%) had motor weakness, and 5 (33%) had ataxia. Eleven of the 12 children with tumors (92%) had documented abnormal neurologic signs on initial physical examination. CONCLUSIONS: Vomiting, a change in behavior, and an abnormal neurologic examination were common signs and symptoms in our sample of toddlers with ICSOLs. An accurate history and appropriate neurologic examination can help physicians make this challenging diagnosis in this age group.

Role of Epithelial-to-Mesenchymal Transition Markers in Different Stages of Endometriosis: Expression of the Snail, Slug, ZEB1, and Twist Genes.

Among various epithelial-to-mesenchymal transition (EMT)-related transcription factors (TFs), altered expression levels of Snail-1, Snail-2/Slug, Twist, and ZEB1 have shown a significant association in different cancers having a higher risk of metastasis. However, their role in the circulation of endometriosis patients is not well understood. Hence, the present study was designed to evaluate the crucial role of these TFs in defining the molecular pathogenesis for endometriosis progression and differentiation from control subjects. The qualitative and quantitative expression analysis of Snail-1, Snail-2/Slug, Twist, and ZEB1 were analyzed in peripheral blood samples of 75 different stages of endometriosis patients and compared with 50 control subjects. Total RNA was extracted and converted into complementary DNA (cDNA) for relative quantification of each gene transcript using SYBRGreen-based reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). The Livak method of relative quantification was used for calculating the fold change in each TF compared with endogenous control. All four selected TFs showed significantly upregulated expression levels in endometriosis patients compared with control subjects. A three-fold increase was observed for Snail-1 (p = 0.0001), and a two-fold increase was observed for Snail-2 (p = 0.01), Twist (p = 0.0002), and ZEB1 (p = 0.001) in stage III and IV compared with stage I and II of endometriosis patients. The present study revealed that EMT-related TFs play a crucial role in the pathogenesis and differentiating different stages of endometriosis patients through expression analysis of specific molecular cascades using non-invasive tools.

Topological data analysis quantifies biological nano-structure from single molecule localization microscopy.

MOTIVATION: Localization microscopy data is represented by a set of spatial coordinates, each corresponding to a single detection, that form a point cloud. This can be analyzed either by rendering an image from these coordinates, or by analyzing the point cloud directly. Analysis of this type has focused on clustering detections into distinct groups which produces measurements such as cluster area, but has limited capacity to quantify complex molecular organization and nano-structure. RESULTS: We present a segmentation protocol which, through the application of persistence-based clustering, is capable of probing densely packed structures which vary in scale. An increase in segmentation performance over state-of-the-art methods is demonstrated. Moreover we employ persistent homology to move beyond clustering, and quantify the topological structure within data. This provides new information about the preserved shapes formed by molecular architecture. Our methods are flexible and we demonstrate this by applying them to receptor clustering in platelets, nuclear pore components, endocytic proteins and microtubule networks. Both 2D and 3D implementations are provided within RSMLM, an R package for pointillist-based analysis and batch processing of localization microscopy data. AVAILABILITY AND IMPLEMENTATION: RSMLM has been released under the GNU General Public License v3.0 and is available at https://github.com/JeremyPike/RSMLM. Tutorials for this library implemented as Binder ready Jupyter notebooks are available at https://github.com/JeremyPike/RSMLM-tutorials. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.