OBJECTIVE: To conceptualize a composite primary endpoint for parallel-group RCTs of exercise-based cardiac rehabilitation (CR) interventions and to explore its application and statistical efficiency.
METHODS: We conducted a statistical exploration of sample size requirements. We combined exercise capacity and physical activity for the composite endpoint (CE), both being directly related to reduced premature mortality in patients with cardiac diseases. Based on smallest detectable and minimal clinically important changes (change in exercise capacity of 15 W and change in physical activity of 10 min/day), the CE combines 2 dichotomous endpoints (achieved/not achieved). To examine statistical efficiency, we compared sample size requirements based on the CE to single endpoints using data from 2 completed CR trials.
METHODS: Cardiac rehabilitation phase III.
METHODS: Patients in cardiac rehabilitation.
METHODS: Not applicable.
METHODS: Exercise capacity (Pmax assessed by incremental cycle ergometry) and physical activity (daily minutes of moderate to vigorous physical activity assessed by accelerometry).
RESULTS: Expecting, for example, a 10% between-group difference and improvement in the clinical outcome, the CE would increase sample size by up to 21% or 61%, depending on the dataset. When expecting a 10% difference and designing an intervention with the aim of non-deterioration, the CE would allow to reduce the sample size by up to 55% or 70%.
CONCLUSIONS: Trialists may consider the utility of the CE for future studies in exercise-based CR to reduce sample size requirements. However, perhaps surprisingly at first, the CE could also lead to an increased sample size needed, depending on the observed baseline proportions in the trial population and the aim of the intervention.

BACKGROUND: Macular hole (MH) development following scleral buckling (SB) surgery for rhegmatogenous retinal detachment (RRD) repair is rare. This study presents both full-thickness MH (FTMH) and lamellar MH (LMH) cases following SB for the treatment of RRD.
METHODS: Clinical records of patients undergoing SB surgery for treatment of RRD at the Xi\'an People\'s Hospital (Xi\'an Fourth Hospital) from January 2016 to December 2021 were reviewed, and cases with postoperative MH were selected. Clinical features and follow-up data were summarised, and possible causes were analysed.
RESULTS: Among 483 identified cases (483 eyes), four eyes (three male patients, one female patient) had postoperative MH, with prevalence, mean age, and mean axial length of 0.83%, 43.5 ± 10.66 years, and 29.13 ± 3.80 mm, respectively. All patients did not undergo subretinal fluid (SRF) drainage. The mean time for detecting MH was 26 ± 15.5 days postoperatively. Macula-off RRD with high myopia and FTMH combined with retinal re-detachment were diagnosed in three patients. One patient had macula-on RRD with outer LMH. The average follow-up duration was 7.25 ± 1.5 months. The FTMH closed successfully after reoperation, while the outer LMH closed without intervention. Visual acuity insignificantly improved or slightly decreased in all patients.
CONCLUSIONS: Patients with high myopia combined with macula-off RRD might be more susceptible to FTMH, causing MH related retinal detachment. Additionally, LMH following SB was noted in patients with macula-on RRD. Therefore, we should raise awareness of MH following SB for RRD repair.

OBJECTIVE: The goal of this article was to introduce a new root coverage (RC) technique, the mixed-thickness tunnel access (MiTT) technique, which approaches a full-split design and intends to augment soft tissues coronal to the gingival margin. It was shown step-by-step, and the results were presented in a case series.
METHODS: Healthy individuals (non-diabetics) and non-smokers with gingival recession (GR) type 1 or 2 (RT1 or RT2) were included. After evaluation, prophylaxis was performed 14 days before the surgical procedure. During the surgical appointment, one or two vertical incision(s) on the mucosa (around 1-2 mm apical to the MGJ), lateral to the papilla base, was/were performed after anesthesia. Initially, there was a partial incision to detach the mucosa of the muscles (split design). It was permitted (but not mandatory) to perform intrasulcular incisions. Through the vertical incision, internally, subperiosteal access from the MGJ toward the gingival margin (coronally) was performed to create a full-thickness tunnel. Then, communication from the vertical incision with the gingival sulcus and the papilla base occurred, keeping the papilla tip intact. A connective tissue graft was harvested and inserted through the linear incision or intrasulcularly. There were interrupted sutures. An adjunctive material may be applied (e.g., Endogain). The root coverage was measured using a periodontal probe and considered fully covered when the gingival margin was 1 mm coronal to the cementum-enamel junction (CEJ).
RESULTS: Nine healthy individuals (seven females and two males) aged 19 and 43 were enrolled. They were treated following the MiTT steps. Four cases had a single GR; two patients had two teeth involved; and three others had three or four GR. There were seven cases of RT1 and two RT2. All RT1 cases achieved 100% RC, while the mean RC obtained for RT2 was around 80%.
CONCLUSIONS: The MiTT technique can be considered a more straightforward approach for minimally invasive surgical techniques, which is a feasible option to treat RC with a high success rate, predictability, and esthetic preservation. Therefore, there is a technical sensitivity to performing the full-split design procedure.

OBJECTIVE: The purpose of this case series was to describe the effect of autologous PRF membrane for corneal reconstruction surgery in dogs. PRF membranes made from two healthy dogs unrelated to the current case series were used for PRF histologic analyses.
METHODS: Seven dogs with complicated corneal ulcerations.
METHODS: A complete ophthalmic examination, hematology, and fibrinogen analysis were performed pre-surgery. A PRF clot was made from autologous blood in a serum tube after centrifugation in a horizontal Bio-PRF® Centrifuge at 700 × g for 8 min. The PRF clot was processed in a PRF-Box® into a PRF membrane. The PRF membrane was sutured to the corneal ulcer bed. Each dog had a follow-up at days 5-7, 12-14, and 30-40 post-surgery. A final long-term follow-up was performed as well.
RESULTS: A positive outcome with healing and a \"good\" quality PRF membrane was seen in six out of seven dogs. One dog had a fibrinogen level below normal range and the PRF membrane was of \"poor\" quality. This dog developed a descemetocele 13 days post-surgery and needed rescue surgery. Mean healing time for all dogs was 9 ± 5.5 days. Minimal scarring, corneal pigmentation, and vascularization were observed at the final long-term follow-up 288 ± 44 days post-surgery.
CONCLUSIONS: PRF membrane was successful as graft material for corneal ulceration reconstruction surgery. Low fibrinogen appeared to have negative effect on the quality of the PRF membrane, showing the importance for the surgeon to evaluate the quality of the PRF membrane prior to surgery.

Background: We have recently proposed an alternative strategy of free gingival graft (FGG) and connective tissue graft (CTG) using micronized-gingival connective tissues (MGCTs). The advantage of this strategy is that MGCTs from a small piece of maxillary tuberosity can regenerate the keratinized tissue band. However, safety and efficacy have not yet been established in patients. This clinical study was a pilot case series, and the objective was to assess the safety and the preliminary efficacy of MGCTs on peri-implant mucosa regeneration. Methods: This was a pilot interventional, single-center, first-in-human (FIH), open (no masking), uncontrolled, and single-assignment study. A total of 4 patients who needed peri-implant soft tissues reconstruction around dental implants received transplantation of atelocollagen-matrix with MGCTs micronized by the tissue disruptor technique. The duration of intervention was 4 weeks after surgery. Results: This first clinical study demonstrated that using MGCTs did not cause any irreversible adverse events, and it showed the preliminary efficacy for peri-implant soft tissues reconstruction in dental implant therapy. Conclusions: Though further studies are needed on an appropriate scale, as an alternative strategy of FGG or CTG, MGCTs might be promising for peri-implant mucosa reconstruction without requiring a high level of skills and morbidity to harvest graft tissues.

The objective of this study was to investigate the survival and biological and mechanical complications of one-piece and two-piece zirconia implants at five years of loading.
Consecutive patients receiving zirconia implants were studied, collecting data at five years of loading on their clinical history, peri-implant health status, mechanical complications, esthetic results, and patient related outcomes.
The study included 18 patients with 29 implants. The survival rate was 86% in implant-based analysis and 78% in patient-based analysis. There were no cases of peri-implantitis, but mucositis was present in 53% of implants. A mean of 4.1 ± 0.81 mm was obtained for probing depth and 1.6 ± 0.9 mm for crestal bone loss (radiographic assessment). There were no implant fractures. Major (10%) and minor (10%) prosthesis complications were observed. The esthetic outcome was moderate to almost perfect, with a high level of patient satisfaction. No significant association was found between survival rate and the presence of mucositis around one- or two-piece implants or any other study variable.
The survival rate is low for one- and two-piece zirconia implants. Both types of implants demonstrated a low mechanical complication rate. The incidence of periimplantitis is low but mucositis is present in 50%. Patient satisfaction related to esthetics and function is moderate to high. They represent a good option for patients requiring an alternative to titanium implants.
Zirconia implants appear to be an alternative to the titanium option and may be indicated for patients requiring \"metal-free\" restorations.

BACKGROUND: Emicizumab promotes effective haemostasis in people with haemophilia A (PwHA). It is indicated for routine prophylaxis of bleeding episodes in PwHA with or without factor (F)VIII inhibitors.
OBJECTIVE: To investigate the effect of emicizumab dose up-titration in PwHA with suboptimal bleeding control.
METHODS: Data from seven completed or ongoing phase III studies were pooled. Pharmacokinetics, pharmacodynamics and bleeding events were evaluated before and after dose up-titration. Adverse events (AEs) were compared between PwHA with and without dose up-titration.
RESULTS: Of 675 PwHA evaluable for the analysis, 24 (3.6%) had their maintenance dose up-titrated to 3 mg/kg once weekly (QW). Two participants had neutralising antibodies (nAbs) associated with decreased emicizumab exposure, and dose increase did not compensate for the effect of nAbs. In the other 22 participants, mean emicizumab steady-state trough concentrations increased from 44.0 to 86.2 μg/mL after up-titration. The median (interquartile range [IQR]) efficacy period prior to up-titration was 24.6 (24.0-32.0) weeks. The model-based annualised bleed rate for \'treated bleeds\' and \'all bleeds\' decreased by 70.2% and 72.9%, respectively, after a median (IQR) follow-up of 97.1 (48.4-123.3) weeks in the up-titration period. Incidences of injection-site reactions and serious AEs were higher in PwHA with up-titration; however, this was already observed in these participants before the dose up-titration. Overall, the safety profile appeared similar between PwHA with and without up-titration.
CONCLUSIONS: The dose up-titration to 3 mg/kg QW was well tolerated. Bleed control improved in most participants whose bleeding tendency was inadequately controlled during clinical trials.

UNASSIGNED: Microwave ablation (MWA) for hepatocellular carcinoma (HCC) under the hepatic dome is still clinically challenging. This retrospective control study set out to analyze the technical application and clinical benefits of cone beam computed tomography (CBCT)-guided MWA for HCC under the hepatic dome.
UNASSIGNED: The study analyzed 76 patients with 110 HCC lesions under the hepatic dome from April 2016 to January 2020. The patients were divided into two groups: (I) the CBCT group (n=31), in which iGuide navigation was used for the puncture, and (II) the conventional computed tomography (cCT) group (n=45), in which a navigation tool was not used for the puncture. The primary endpoints were technical success, puncture score, and the rates of complete ablation (CA), complications, and local tumor progression (LTP). The secondary endpoints were tumor-free survival (TFS) and overall survival (OS).
UNASSIGNED: In terms of the primary endpoints, the puncture score, occurrence of pleural effusion, and occurrence of right shoulder pain differed significantly between the CBCT group and the cCT group (2.8 vs. 2.2, P=0.002; 12.9% vs. 35.6%, P=0.03; 9.7% vs. 33.3%, P=0.03, respectively). However, the rates of technical success, CA, major complications, and LTP showed no significant differences between the two groups (100% vs. 100%, P>0.009; 0% vs. 0%, P>0.009; 95.6% vs. 89.2%, P=0.30; 4.5% vs. 4.6%, P=0.96, respectively). Regarding the secondary endpoints, the median TFS was 23.0 [95% confidence interval (CI): 19.5-26.5] vs. 22.0 (95% CI: 18.4-25.6) months (P=0.41) and the median OS was 31.0 (95% CI: 21.4-40.6) vs. 33.0 (95% CI: 27.9-38.2) months (P=0.95).
UNASSIGNED: Cone beam CT is a feasible and effective image guidance tool for MWA of HCC under the hepatic dome.

Many mental disorders (MD) share common etiology, fuelling debates about the specificity of clinical categories and whether the presence of specific risk factors (RF) can distinguish among them. The study of developmental language disorder (DLD), more specifically, has been further hindered by a lack of consensus regarding its definition. These limitations increase the risk of under-detection and lifelong consequences for affected children. This paper aims (1) to document which individual RF allow differentiating DLD from other MD and (2) to compare the cumulative RF between children with DLD versus other MD. This case-control design study used medical records of a psychiatric sample of 795 preschoolers (mean age 4:11, 75% boys). A logistic regression measured the predictive value of potential RF on DLD. Later first sentences, maternal immigration and family history of language delay were identified as significant in explaining 30% of the variance for DLD diagnosis. An ANCOVA revealed that children with DLD were exposed to a significantly higher number of RF than were children with other MD. Public health policies informed with the knowledge of specific RF associated with DLD, and their cumulative impact, could improve early detection and reduce the cascade of negative consequences associated with DLD.

The objective of this study was to evaluate the clinical and radiographic behavior of a novel triangular neck implant configuration in partially edentulous patients. Sixteen patients with a mean age of 58.3 years, were rehabilitated with 25 implants inserted in the healed sites of the maxilla and mandible; implant diameter was Ø3.3 and 3.9 mm. Clinical and radiographic measurements were first performed at prosthesis delivery that served as baseline; they were further evaluated after a mean period of 15.6 months. The interproximal peri-implant bone levels were the primary outcome; the mesial and distal data were recorded and a mean value was calculated. Secondary outcomes included peri-implant probing depth (PPD) and bleeding on probing (BoP). The paired t-test was used to compare the radiographic and clinical outcomes between baseline and follow-up. The mean bone levels at the mesial and distal aspects at baseline were 0.45 (0.47) and 0.57 (0.69), respectively; at follow-up they were 0.59 (0.42) and 0.78 (0.59), respectively. The differences were not statistically significant. Similarly, no significant differences were found for the clinical parameters. Within the limitations of the present study, it could be concluded that this new triangular neck bone level implant macro-design was used successfully to treat partially edentulous patients. Larger controlled clinical studies are warranted to confirm the present radiographic and clinical findings.