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Purpose: To investigate the effect of delayed application of leukocyte-rich platelet-rich plasma (PRP) on rotator cuff repair results as assessed by outcome scores and imaging at one year.Methods: Patients with a symptomatic rotator cuff tear awaiting arthroscopic repair were approached to take part in the study. Final eligibility for the study was confirmed at the time of surgery. A total of 97 patients were randomized to an ultrasound guided injection of leukocyte-rich PRP or normal saline between 10 and 14 days postsurgery. A total of 87 patients completed clinical evaluation and underwent magnetic resonance imaging imaging at 1 year. Outcome scores included the American Shoulder and Elbow Score, Constant score, Western Ontario Rotator Cuff Index, and the Disabilities of the Arm, Shoulder and Hand Score. Structural integrity of the repair was assessed according to the Sugaya grading. Muscle fatty infiltration was assessed on magnetic resonance imaging using the Goutallier classification.Results: At 1 year postsurgery, there was no significant difference between the treatment groups on any of the patient-reported outcome measures or Constant score. On postoperative imaging analysis, there was no difference in the retear rates (Sugaya 4 and 5) between the groups (21% in control group vs 15.3% in PRP group). Fatty infiltration on postoperative imaging was found to be significantly higher in the normal saline group compared with the PRP group (Kendall's tau-b P = .032).Conclusions: The delayed application of PRP postrotator cuff repair did not improve function as measured by patient-reported outcome measures and Constant score at 1 year postoperatively.Level Of Evidence: Level II, prospective randomized therapeutic trial. [ABSTRACT FROM AUTHOR]

Objective: Pregnancy hypertension is a leading cause of maternal and perinatal mortality and morbidity. Between 34+0 and 36+6 weeks gestation, it is uncertain whether planned delivery could reduce maternal complications without serious neonatal consequences. In this individual participant data meta-analysis, we aimed to compare planned delivery to expectant management, focusing specifically on women with preeclampsia.Data Sources: We performed an electronic database search using a prespecified search strategy, including trials published between January 1, 2000 and December 18, 2021. We sought individual participant-level data from all eligible trials.Study Eligibility Criteria: We included women with singleton or multifetal pregnancies with preeclampsia from 34 weeks gestation onward.Methods: The primary maternal outcome was a composite of maternal mortality or morbidity. The primary perinatal outcome was a composite of perinatal mortality or morbidity. We analyzed all the available data for each prespecified outcome on an intention-to-treat basis. For primary individual patient data analyses, we used a 1-stage fixed effects model.Results: We included 1790 participants from 6 trials in our analysis. Planned delivery from 34 weeks gestation onward significantly reduced the risk of maternal morbidity (2.6% vs 4.4%; adjusted risk ratio, 0.59; 95% confidence interval, 0.36-0.98) compared with expectant management. The primary composite perinatal outcome was increased by planned delivery (20.9% vs 17.1%; adjusted risk ratio, 1.22; 95% confidence interval, 1.01-1.47), driven by short-term neonatal respiratory morbidity. However, infants in the expectant management group were more likely to be born small for gestational age (7.8% vs 10.6%; risk ratio, 0.74; 95% confidence interval, 0.55-0.99).Conclusion: Planned early delivery in women with late preterm preeclampsia provides clear maternal benefits and may reduce the risk of the infant being born small for gestational age, with a possible increase in short-term neonatal respiratory morbidity. The potential benefits and risks of prolonging a pregnancy complicated by preeclampsia should be discussed with women as part of a shared decision-making process. [ABSTRACT FROM AUTHOR]

Abstract: Revision anterior cruciate ligament (ACL) reconstruction is becoming more frequent, especially in specialized centers, because of the large numbers of primary ACL procedures performed. In 2-stage revisions, bone grafting of the tunnels may be undertaken if the primary position was inaccurate or if osteolysis has caused widening of the tunnels. This will allow the desired placement of the new tunnels without the risk of loss of structural integrity. It is technically difficult to deliver and impact bone graft into the femoral tunnel with the standard surgical and arthroscopic instruments. We describe a new technique for femoral and tibial tunnel impaction grafting in 2-stage ACL revisions, using the OATS grafting instruments (Osteochondral Autologous Transfer System; Arthrex, Naples, FL). The appropriately sized OATS harvester is chosen 1 mm larger than the tunnel size and is used to harvest bone graft from the iliac crest through a percutaneous approach. This provides a cylindrical graft, which is delivered to the femoral tunnel through the arthroscopic portal. The inside punch of the harvester is tapped and this allows delivery of the graft in a controlled manner and its impaction into the tunnel. The same is repeated for the tibial tunnel while providing support for the proximal end of the tunnel. [Copyright &y& Elsevier]

Pre-clinically, phosphoinositide 3-kinase (PI3K) inhibition radiosensitises tumours by increasing intrinsic radiosensitivity and by reducing tumour hypoxia. We assessed whether buparlisib, a class 1 PI3K inhibitor, can be safely combined with radiotherapy in patients with non-small cell lung carcinoma (NSCLC) and investigated its effect on tumour hypoxia. This was a 3 + 3 dose escalation and dose expansion phase I trial in patients with advanced NSCLC. Buparlisib dose levels were 50 mg, 80 mg and 100 mg once daily orally for 2 weeks, with palliative thoracic radiotherapy (20 Gy in 5 fractions) delivered during week 2. Tumour hypoxic volume (HV) was measured using 18F-fluoromisonidazole positron-emission tomography–computed tomography at baseline and following 1 week of buparlisib. Twenty-one patients were recruited with 9 patients evaluable for maximum tolerated dose (MTD) analysis. No dose-limiting toxicity was reported; therefore, 100 mg was declared the MTD, and 10 patients received this dose in the expansion phase. Ninety-four percent of treatment-related adverse events were ≤grade 2 with fatigue (67%), nausea (24%) and decreased appetite (19%) most common per patient. One serious adverse event (grade 3 hypoalbuminaemia) was possibly related to buparlisib. No unexpected radiotherapy toxicity was reported. Ten (67%) of 15 patients evaluable for imaging analysis were responders with 20% median reduction in HV at the MTD. This is the first clinical trial to combine a PI3K inhibitor with radiotherapy in NSCLC and investigate the effects of PI3K inhibition on tumour hypoxia. This combination was well tolerated and PI3K inhibition reduced hypoxia, warranting investigation into whether this novel class of radiosensitisers can improve radiotherapy outcomes. • Buparlisib, a phosphoinositide 3-kinase (PI3K) inhibitor, is safe when combined with thoracic radiotherapy. • PI3K inhibition resulted in a rapid reduction in tumour hypoxia in non–small cell lung carcinoma. • This study supports the development of PI3K inhibitors as novel radiosensitisers. [ABSTRACT FROM AUTHOR]

Purpose: Poly (ADP-ribose) polymerase (PARP) inhibitors have been shown to enhance the radiosensitivity of cancer cells in vitro in a replication-dependent manner. Their in vivo radiosensitizing effects have also been demonstrated in preclinical tumor models. However, whether PARP inhibition can enhance the response to radiation therapy in normal tissues has been largely neglected. We hypothesized that PARP inhibition might also potentiate the response of replicating normal tissues to radiation therapy. In this study, we examined the normal tissue response in mice treated with PARP inhibitors (BMN673 or AZD2281) in combination with thoracic irradiation.Methods and Materials: The antitumor effects of fractionated irradiation (5 Gy × 4) in combination with BMN673 were evaluated in nude mice bearing established Calu-6 human lung cancer xenografts. The normal tissue response was evaluated in C57BL6 mice that were treated with BMN673 or AZD2281 combined with fractionated irradiation, 5 Gy × 4, delivered to the whole thorax. Body weight and histology of the esophagus and skin in the field of irradiation were examined. The DNA damage response in the esophagus and skin was assessed by γH2AX immunohistochemistry.Results: While PARP inhibition enhanced irradiation-induced tumor growth inhibition in nude mice, it was also associated with significant body weight loss and increased damage to the esophagus and skin within the field of irradiation in C57BL6 mice. PARP inhibition compromised the repair of irradiation-induced DNA damage in the esophagus and skin.Conclusions: Although PARP inhibition enhanced the antitumor response to fractionated irradiation, it also enhanced the irradiation response in replicating normal tissues. Therefore, our study suggests that additional caution may be warranted in the clinical development of combination therapies using PARP inhibitors and radiation therapy, in particular where the field of irradiation includes the esophagus. [ABSTRACT FROM AUTHOR]