A systematic review and meta-analysis of neoadjuvant imatinib use in locally advanced and metastatic gastrointestinal stromal tumors.

BACKGROUND: Several doubts remain regarding the optimal use of neoadjuvant imatinib in gastrointestinal stromal tumors (GISTs), such as ideal treatment duration, patient selection, and long-term survival outcomes. This manuscript provides a comprehensive review on neoadjuvant imatinib treatment outcomes and facilitate evidence-based decision-making for the use of imatinib therapy in GISTs. METHODS: Four databases (PubMed, EMBASE, Scopus, and Cochrane Library) were searched from inception to September 9, 2023. Meta-analyses of proportions were performed for the outcomes of R0 resection, disease responses, and 1-year, 3-year, and 5-year overall survival (OS) as well as 1-year, 3-year, and 5-year disease free survival (DFS). Sensitivity analyses in the form of leave-one-out analyses, meta-regression, and subgroup analyses were performed for outcomes with substantial statistical heterogeneity. RESULTS: The search yielded 1254 articles, and 36 studies were included in our analysis. Meta-analysis of proportions revealed that 1-year, 3-year, and 5-year OS was 100%, 94%, and 88%, while 1-year, 3-year and 5-year DFS was 99%, 89%, and 79%, respectively. An R0 resection rate of 89% and a disease response rate of 67% was achieved after a mean duration of treatment of 8.41 ± 0.367 months. KIT exon 9 mutation was significantly associated with poorer 5-year DFS. CONCLUSION: This study quantified key outcomes for neoadjuvant imatinib in locally advanced and metastatic or recurrent GIST. Patients with gastric and rectal tumous stand to benefit from neoadjuvant imatinib with an optimal treatment duration of 8 months. Furthermore, the potential utility of mutational analysis in guiding treatment with neoadjuvant imatinib was demonstrated.

Factors affecting overall survival and disease-free survival after surgery for hepatocellular carcinoma: a nomogram-based prognostic model-a Western European multicenter study.

Few studies have assessed the clinical implications of the combination of different prognostic indicators for overall survival (OS) and disease-free survival (DFS) of resected hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic factors in HCC patients for OS and DFS outcomes and establish a nomogram-based prognostic model to predict the DFS of HCC. A multicenter, retrospective European study was conducted through the collection of data on 413 consecutive treated patients with a first diagnosis of HCC between January 2010 and December 2020. Univariate and multivariate Cox regression analyses were performed to identify all independent risk factors for OS and DFS outcomes. A nomogram prognostic staging model was subsequently established for DFS and its precision was verified internally by the concordance index (C-Index) and externally by calibration curves. For OS, multivariate Cox regression analysis indicated Child-Pugh B7 score (HR 4.29; 95% CI 1.74-10.55; p = 0.002) as an independent prognostic factor, along with Barcelona Clinic Liver Cancer (BCLC) stage ≥ B (HR 1.95; 95% CI 1.07-3.54; p = 0.029), microvascular invasion (MVI) (HR 2.54; 95% CI 1.38-4.67; p = 0.003), R1/R2 resection margin (HR 1.57; 95% CI 0.85-2.90; p = 0.015), and Clavien-Dindo Grade 3 or more (HR 2.73; 95% CI 1.44-5.18; p = 0.002). For DFS, multivariate Cox regression analysis indicated BCLC stage ≥ B (HR 2.15; 95% CI 1.34-3.44; p = 0.002) as an independent prognostic factor, along with multiple nodules (HR 2.04; 95% CI 1.25-3.32; p = 0.004), MVI (HR 1.81; 95% CI 1.19-2.75; p = 0.005), satellite nodules (HR 1.63; 95% CI 1.09-2.45; p = 0.018), and R1/R2 resection margin (HR 3.39; 95% CI 2.19-5.25; < 0.001). The C-Index of the nomogram, tailored based on the previous significant factors, showed good accuracy (0.70). Internal and external calibration curves for the probability of DFS rate showed optimal consistency and fit well between the nomogram-based prediction and actual observations. MVI and R1/R2 resection margins should be considered as significant OS and DFS predictors, while satellite nodules should be included as a significant DFS predictor. The nomogram-based prognostic model for DFS provides a more effective prognosis assessment for resected HCC patients, allowing for individualized treatment plans.

Surgery for liver metastases from primary breast cancer: A reconstructed individual patient data meta-analysis.

BACKGROUND: Currently, the outcomes of standard-of-care palliative treatment for BCLM remain poor. Recent literature has shown promising results of hepatic resection, however, not all studies concur. Given the lack of standardized international guidelines in this field, the aim of this study is to provide gold-standard evidence for breast cancer liver metastases (BCLM) through a reconstructed individual patient data meta-analysis approach. METHODS: Four databases were searched for articles comparing surgical and non-surgical treatment for BCLM. One-stage meta-analysis was performed using patient-level survival data reconstructed from Kaplan-Meier curves with plot digitizer software. Shared-frailty and stratified Cox models were fitted to compare survival endpoints. RESULTS: Four propensity-score matched (PSM) studies involving 205 surgical and 291 non-surgical patients for BCLM were included. There was a significant difference between both groups for overall survival (OS) (Hazard Ratio [HR] = 0.40, 95%CI 0.32-0.51). Sensitivity analyses for hormone receptor status of breast cancer (HR = 0.41, 95%CI 0.31-0.55) and type of resection performed (HR = 0.45, 95%CI 0.33-0.61) yielded HRs in favor of surgery. CONCLUSIONS: This meta-analysis concludes that surgery offers superior OS outcomes, compared to non-surgery, in a select group of patients. Future randomized controlled trials and PSM studies are warranted, using this study as a point of reference for similar parameters.

Different types of rotator cuff tear morphology do not affect post-repair clinical outcomes in large to massive tears.

OBJECTIVES: The primary aim of this current study is to evaluate the effects of rotator cuff tear morphology on clinical outcomes in large to massive tears, using a modified version of the existing classification system, with specific focus on tear symmetry and use of margin convergence. METHODS: Patients who underwent arthroscopic repair of large to massive, full thickness rotator cuff tears were retrospectively analysed. The tear pattern was classified at the time of surgery as Type IA, Type IB, Type IIA, and Type IIB according to tear symmetry and direction of maximum tear diameter, with Type I being symmetrical and Type II being asymmetrical. Type IA (U-shaped) had greater mediolateral (ML) than anteroposterior (AP) diameter while Type IB (crescent shaped) had greater AP than ML diameter. Type IIA tears have an anterior extension towards the rotator interval while IIB tears have a posterior extension into the infraspinatus, similar to AP L-shaped tears established in the literature. Type I tears were typically repaired from medial to lateral while Type II tears were repaired diagonally. All types were repaired using double row technique, with the addition of margin convergence for Types IA and IIB, which had larger tears in the medial and lateral directions. Primary outcome measures were Oxford Shoulder Score, Constant Shoulder Score, University of California at Los Angeles Shoulder Score followed-up at 6, 12, and 24-months as well as retear rates at latest follow-up. RESULTS: In total, 109 patients were included in the study with a mean age of 65.5 â€‹± â€‹9.4. The prevalence of each tear morphologies from Type IA to IIB was 22.0 â€‹%, 34.9 â€‹%, 27.5 â€‹%, and 15.6 â€‹%, respectively. All four groups showed statistically significant improvement from pre-operative scores in all 3 outcome measures at 24 months (p â€‹< â€‹0.001 for all). No significant difference in primary outcome measures or retear rates was detected between all 4 groups. CONCLUSION: This study found that different types of cuff tear morphology, despite affecting surgical repair technique, does not influence clinical outcomes post-arthroscopic rotator cuff repair at mid-term follow-up. LEVEL OF EVIDENCE: Retrospective Cohort study, Level III.

Anatomic risk factors for arthroscopic Bankart repair failure: A case-control study comparing failure and non-failure groups in an Asian population.

Introduction: Post-arthroscopic Bankart repair failure/re-dislocation rates are influenced by several risk factors, including anatomic defects. There is limited evidence on the role of anatomic defects, especially for Hill-Sachs size in on-track lesions. This study aimed to assess glenoid bone loss, Hill-Sachs lesion and labral tear size and evaluate their contribution to post-operative instability after a primary repair. Material and methods: Across 169 patients with on-track Bankart lesions who underwent primary arthroscopic Bankart repair from 2010 to 2015, this study matched 14 failure with 14 non-failure cases based on age/gender. Patient demographics, pre-operative radiological parameters (including size of glenoid bone loss and Hill-Sachs lesion) and labral tear size were compared between the failure and non-failure groups. Result: All patients were male with a mean age of 21.01 ± 4.97. Significantly greater glenoid bone loss (p = 0.024) and labral tear size (p = 0.039) were found in the failure group. However, there was no significant difference in mean volume of Hill-Sachs lesion between the two groups (p = 0.739). Conclusion: Extensive glenoid bone loss and labral tears are risk factors for post-arthroscopic Bankart failure. However, the size of Hill-Sachs lesion is not a risk factor for failure, in a specific group of on-track Hill-Sachs lesions. Level of evidence: Retrospective Study, Level IV.

Non-selective NSAIDs do not increase retear rates post-arthroscopic rotator cuff repair: A meta-analysis.

BACKGROUND: Arthroscopic rotator cuff repairs (RCRs) are known to be associated with substantial pain and post-operative pain management is critical in overall patients' outcomes. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used oral medications and can reduce opioid usage. However, controversies arise due to its postulated effect on postoperative tendon healing. As the evidence of safety and efficacy of NSAIDs remains unclear, this study aims to investigate the effect of NSAIDs on retear rates and clinical outcomes. METHODS: A systematic search of four databases (PubMed, EMBASE, Scopus, and Cochrane Library) was conducted, identifying studies that compared cohorts with post-RCR NSAIDs use versus control groups without NSAID use. Meta-analysis was conducted for retear rate as well as pain and functional outcomes (Visual Analogue Scale and American Shoulder and Elbow Surgeons Shoulder score). Subgroup analysis was conducted for retear rates to determine the overall treatment effect of including selective COX-2 inhibitors. RESULTS: Six studies were included in the meta-analysis. The total baseline cohort size was 916, with 443 (48.3%) patients in the NSAID group and 473 (51.6%) patients in the control group. There were no statistically significant differences in the baseline characteristics between the two groups. Meta-analysis between the two groups showed that there were no statistically significant differences in retear rates (p â€‹= â€‹0.70), early and late post-operative Visual Analogue Scale score (p â€‹= â€‹0.10 and p â€‹= â€‹0.10, respectively) and latest American Shoulder and Elbow Surgeons Shoulder score (p â€‹= â€‹0.31). However, subgroup analysis of retear rates revealed a statistically significant difference between the subgroup including COX-2 selective inhibitor versus non-selective COX inhibitor (p â€‹< â€‹0.01). CONCLUSION: NSAID use in post-arthroscopic RCR pain relief does not increase retear rates and can provide similar clinical outcomes compared to a non-NSAID regimen. LEVEL OF EVIDENCE: Meta-analysis, level of evidence, 4.

Early cement augmentation may be a good treatment option for pain relief for osteoporotic compression fractures: a systematic review and meta-analysis.

PURPOSE: The incidence of osteoporotic compression fractures (VCFs) have been rising over the past decades. Presently, vertebral cement augmentation procedures such as balloon kyphoplasty and vertebroplasty are common treatments allowing pain relief and functional recovery. However, there is controversy on whether different timeframes for cement augmentation affects clinical outcomes. Hence, this study aimed to compare pain relief and complication rates between early versus late cement augmentation. METHODS: A comprehensive systematic review of PubMed, EMBASE, Scopus and Cochrane Library was conducted, identifying studies that compared early versus late cement augmentation for VCFs. As the definitions of "early" and "late" phases across studies are heterogenous, we established the cut-off between early and late phase as intervals to accommodate as many studies as possible for analysis. We conducted two separate analyses with different cut-off intervals and included studies that reported interventions within these respective time intervals. In analysis 1, we included studies which grouped patients into "early" and "late" group based on a cut-off time frame of 2-4 weeks. On the other hand, in analysis 2, we included studies which grouped patients into "early" and "late" groups based on a cut-off time frame of 6-8 weeks. Meta-analysis was conducted via random-effect models, comparing outcomes of interest between early and late groups. RESULTS: Eleven studies were included. The total cohort size was 712 and 775 patients in analysis 1 and 2 respectively. Mean follow-up was 12.9 ± 3.7 months and 11 ± 0.6 months respectively. VAS change at final follow-up was significantly greater in the early group for both analyses. (MD = - 0.66, p = 0.01; and MD = - 1.18, p < 0.005 respectively). There was no significant difference in post-operative absolute VAS score, number of cement leakage, number of adjacent compression fractures and local kyphotic angle, for both analyses. Patients in both groups experienced reductions in VAS score that exceeded the minimum clinically important difference. CONCLUSION: Both early and late timeframes for cement augmentation offered significant improvement in pain relief, with similar post-operative absolute pain score, kyphotic angle, cement leakage and adjacent vertebral fractures. Early surgery may offer substantial pain relief in patients presenting with pain as early as < 2-4 weeks of VCFs.

Surgery for liver metastases from primary melanoma: a systematic review and meta-analysis.

BACKGROUND: Historically , liver metastases due to melanoma have been associated with dismal prognosis. Moreover, the actual survival benefit from the treatment of melanoma liver metastases is still controversial. Hence, this study aims to evaluate the difference in surgical versus non-surgical options for melanoma liver metastases. METHODS: Four databases (PubMed, EMBASE, Scopus, and Cochrane Library) were searched from inception to July 17, 2022. Studies were included if they compared outcomes between surgical and non-surgical treatment for patients with liver metastases from resectable melanoma. Meta-analyses were performed for the outcomes of 1-year, 2-year, 3-year and 5-year OS. Sensitivity analyses were performed for outcomes with substantial statistical heterogeneity. To account for possible moderators that might contribute to statistical heterogeneity, univariate meta-regression with mixed-effects models and subgroup analyses were conducted for the outcome of 2-year OS. RESULTS: The search yielded 6610 articles; 13 studies were included in our analysis. Meta-analyses showed that survival outcomes were in favour of patients undergoing surgery as compared to non-surgery: 1-year OS (HR = 0.29, 95%CI 0.19-0.44, p < 0.00001), 2-year OS (HR = 0.19, 95%CI 0.09-0.38, p < 0.00001), 3-year OS (HR = 0.07, 95%CI 0.03-0.19, p < 0.00001) and 5-year OS (HR = 0.07, 95%CI 0.02-0.22, p < 0.00001). All included studies were of high quality. There was moderate-to-high statistical heterogeneity. Findings were robust to sensitivity analyses. Subgroup analyses and univariate meta-regression revealed neoadjuvant therapy and age as statistically significant subgroup and moderator respectively. CONCLUSIONS: This study suggests that surgical treatment of melanoma liver metastases could offer better OS outcomes compared with non-surgical treatment.

Selective bundle versus complete anterior-cruciate ligament reconstruction: A systematic review and meta-analysis.

Purpose: Selective bundle reconstruction (SLB) refers to preservation of the intact bundle and reconstruction of the ruptured bundle in a partial tear while complete ACL reconstruction involves the removal of all remnant tissue and reconstruction of one or both bundles. As the evidence for SLB versus complete ACL reconstruction remains unclear, this study aimed to compare the two techniques. This study's hypothesis was that SLB reconstruction allows better function and stability compared to complete ACL reconstruction. Methods: A systematic search of PubMed, EMBASE, Scopus and Cochrane Library was conducted, identifying studies that compared SLB ('selective' group) versus complete ('complete' group) ACL reconstruction. Meta-analysis was conducted for post-operative functional scores, stability outcomes and complications as well as pre-operative to post-operative change. Results: Eleven studies were included in the meta-analysis, with 1107 patients and a pooled mean follow-up of 29.5 months. Post-operatively, the Selective group had significantly reduced anterior laxity, shown by a lower mean arthrometry side-to-side difference (p<0.01). Analysis of change results showed that the Selective group had a lower mean improvement in arthrometry side-to-side difference as well (p<0.01). No significant difference was shown for all other post-operative outcomes. Conclusion: This study provides valuable insight to the management of partial tears. It has demonstrated that the preservation of the intact bundle offers stability and function that is as good as complete reconstruction and that SLB is a potentially viable option in the management of partial tears. Level of evidence: Meta-analysis; Level of evidence, 4.

300 GHz wave generation based on a Kerr microresonator frequency comb stabilized to a low noise microwave reference.

In this Letter, we experimentally demonstrate low noise 300 GHz wave generation based on a Kerr microresonator frequency comb operating in the soliton regime. The spectral purity of a 10 GHz GPS-disciplined dielectric resonant oscillator is transferred to the 300 GHz repetition rate frequency of the soliton comb through an optoelectronic phase-locked loop. Two adjacent comb lines beat on a uni-traveling carrier photodiode emitting the 300 GHz millimeter-wave signal into a waveguide. In an out-of-loop measurement, we measure the 300 GHz power spectral density of phase noise to be -88dBc/Hz, -105dBc/Hz at 10 kHz, and 1 MHz Fourier frequency, respectively. Phase-locking error instability reaches 2×10-15 at 1 s averaging time. Such a system provides a promising path to the realization of compact, low power consumption millimeter-wave oscillators with low noise performance for out-of-the-laboratory applications.

Rotational State Microwave Mixing for Laser Cooling of Complex Diatomic Molecules.

We demonstrate the mixing of rotational states in the ground electronic state using microwave radiation to enhance optical cycling in the molecule yttrium (II) monoxide (YO). This mixing technique is used in conjunction with a frequency modulated and chirped continuous wave laser to slow longitudinally a cryogenic buffer-gas beam of YO. We generate a flux of YO below 10 m/s, directly loadable into a three-dimensional magneto-optical trap. This technique opens the door for laser cooling of diatomic molecules with more complex loss channels due to intermediate states.

2D Magneto-optical trapping of diatomic molecules.

We demonstrate one- and two-dimensional transverse laser cooling and magneto-optical trapping of the polar molecule yttrium (II) oxide (YO). In a 1D magneto-optical trap (MOT), we characterize the magneto-optical trapping force and decrease the transverse temperature by an order of magnitude, from 25 to 2 mK, limited by interaction time. In a 2D MOT, we enhance the intensity of the YO beam and reduce the transverse temperature in both transverse directions. The approach demonstrated here can be applied to many molecular species and can also be extended to 3D.

Evaporative cooling of the dipolar hydroxyl radical.

Atomic physics was revolutionized by the development of forced evaporative cooling, which led directly to the observation of Bose-Einstein condensation, quantum-degenerate Fermi gases and ultracold optical lattice simulations of condensed-matter phenomena. More recently, substantial progress has been made in the production of cold molecular gases. Their permanent electric dipole moment is expected to generate systems with varied and controllable phases, dynamics and chemistry. However, although advances have been made in both direct cooling and cold-association techniques, evaporative cooling has not been achieved so far. This is due to unfavourable ratios of elastic to inelastic scattering and impractically slow thermalization rates in the available trapped species. Here we report the observation of microwave-forced evaporative cooling of neutral hydroxyl (OH(•)) molecules loaded from a Stark-decelerated beam into an extremely high-gradient magnetic quadrupole trap. We demonstrate cooling by at least one order of magnitude in temperature, and a corresponding increase in phase-space density by three orders of magnitude, limited only by the low-temperature sensitivity of our spectroscopic thermometry technique. With evaporative cooling and a sufficiently large initial population, much colder temperatures are possible; even a quantum-degenerate gas of this dipolar radical (or anything else it can sympathetically cool) may be within reach.

Cold heteromolecular dipolar collisions.

Cold molecules promise to reveal a rich set of novel collision dynamics in the low-energy regime. By combining for the first time the techniques of Stark deceleration, magnetic trapping, and cryogenic buffer gas cooling, we present the first experimental observation of cold collisions between two different species of state-selected neutral polar molecules. This has enabled an absolute measurement of the total trap loss cross sections between OH and ND(3) at a mean collision energy of 3.6 cm(-1) (5 K). Due to the dipolar interaction, the total cross section increases upon application of an external polarizing electric field. Cross sections computed from ab initio potential energy surfaces are in agreement with the measured value at zero external electric field. The theory presented here represents the first such analysis of collisions between a (2)Π radical and a closed-shell polyatomic molecule.

Molecular beam collisions with a magnetically trapped target.

Cold, neutral hydroxyl radicals are Stark decelerated and efficiently loaded into a permanent magnetic trap. The OH molecules are trapped in the rovibrational ground state at a density of approximately 10;{6} cm;{-3} and temperature of 70 mK. Collision studies between the trapped OH sample and supersonic beams of atomic He and molecular D2 determine absolute collision cross sections. The He-OH and D2-OH center-of-mass collision energies are tuned from 60 cm;{-1} to 230 cm;{-1} and 145 cm;{-1} to 510 cm;{-1}, respectively, yielding evidence of quantum threshold scattering and resonant energy transfer between colliding particles.