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Clinical Oral Implants Research Oct 2018To assess the impact of platelet-rich fibrin (PRF) on implant dentistry. The primary focused question was as follows: What are the clinical, histological, and...
OBJECTIVE
To assess the impact of platelet-rich fibrin (PRF) on implant dentistry. The primary focused question was as follows: What are the clinical, histological, and radiographic outcomes of PRF administration for bone regeneration and implant therapy?
METHOD
A systematic literature search comprised three databases: MEDLINE, EMBASE, and Cochrane followed by a hand search of relevant scientific journals. Human studies using PRF for bone regeneration and implant therapy were considered and articles published up to December 31, 2017 were included. Eligible studies were selected based on the inclusion criteria. Randomized controlled trials (RCT) and controlled clinical trials (CCT) were included.
RESULTS
In total, 5,963 titles were identified with the search terms and by hand search. A total of 12 randomized controlled trials (RCT) met the inclusion criteria and were chosen for data extraction. Included studies focused on alveolar ridge preservation after tooth extraction, osseointegration process, soft tissue management, bone augmentation, bone regeneration after sinus floor elevation and surgical peri-implantitis treatment. Overall, the risk of bias was moderate or unclear. Nine studies showed superior outcomes for PRF for any of the evaluated variables, such as ridge dimension, bone regeneration, osseointegration process, soft tissue healing. Three studies failed to show any beneficial effects of PRF. No meta-analysis could be performed due to the heterogeneity of study designs.
CONCLUSIONS
There is moderate evidence supporting the clinical benefit of PRF on ridge preservation and in the early phase of osseointegration. It remains unclear whether PRF can reduce pain and improve soft tissue healing. More research support is necessary to comment on the role of PRF to improve other implant therapy outcomes.
Topics: Alveolar Process; Bone Regeneration; Dental Implantation, Endosseous; Humans; Platelet-Rich Fibrin
PubMed: 30306698
DOI: 10.1111/clr.13275 -
Maedica Mar 2023Cadaveric dissection is a unique and unrivalled educational tool that allows students in medicine and associated life sciences to explore spatial three-dimensional...
Cadaveric dissection is a unique and unrivalled educational tool that allows students in medicine and associated life sciences to explore spatial three-dimensional anatomy, principles of structure and related function, and anatomical variations, including pathological alterations. Human tissue dissection enables researchers to comprehend the variety that exists in life that cannot be appreciated through the literature or artificial specimens. Using cadavers is the best way to simulate surgical and anatomical teaching. A cadaver has been shown to imitate surgical and anatomical training better than any other existing method. By the use of soft embalming approaches, cadavers have become more realistic and training-friendly. The main aim of this review is to describe various innovative and recent cadaver preservation techniques in detail, which can help anatomists to modify the techniques in their institute for gross anatomy teaching and surgical training or workshops to get a lifelike cadaver.
PubMed: 37266469
DOI: 10.26574/maedica.2023.18.1.127 -
Indian Heart Journal 2023To provide a pooled effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cardiovascular outcomes in patients with heart failure with preserved ejection... (Meta-Analysis)
Meta-Analysis
AIM
To provide a pooled effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cardiovascular outcomes in patients with heart failure with preserved ejection fraction (HFpEF: ≥50%) or/and mildly reduced EF (HFmrEF: 41-49%) regardless of baseline diabetes.
METHODS
We systemically searched PubMed/MEDLINE, Embase, Web of Science databases and clinical trial registries using appropriate keywords till August 28, 2022, to identify randomized controlled trials (RCTs) or post-hoc analysis of RCTs, reporting cardiovascular death (CVD) and/or urgent visits/hospitalization for heart failure(HHF) in patients with HFmrEF/HFpEF receiving SGLTi vs. placebo. Hazard ratios (HR) with 95% confidence intervals (CI) for outcomes were pooled together using generic inverse variance method with fixed-effects model.
RESULTS
We identified six RCTs, pooling data retrieved from 15,769 patients with HFmrEF/HFpEF. Pooled analysis showed that compared to placebo, SGLT2i use was significantly associated with improved CVD/HHF outcomes in HFmrEF/HFpEF (pooled HR 0.80, 95% CI: 0.74, 0.86, p < 0.001, I = 0%). When separately analyzed, benefits of SGLT2i remained significant across HFpEF (N = 8891, HR 0.79, 95% CI: 0.71, 0.87, p < 0.001, I = 0%) and HFmrEF (N = 4555, HR 0.77, 95% CI: 0.67, 0.89, p < 0.001, I = 40%). Consistent benefits were observed also in HFmrEF/HFpEF subgroup without baseline diabetes (N = 6507, HR 0.80, 95% CI: 0.70, 0.91, p < 0.001, I = 0%). Sensitivity analysis including the DELIVER and EMPEROR-Preserved trials found a trend towards significant beneficial effects on CV deaths with no heterogeneity (HR 0.90, 95% CI: 0.79, 1.02, p = 0.08, I = 0%).
CONCLUSIONS
This meta-analysis established the place of SGLT2i as a foundational therapy among patients with HF with preserved and mildly reduced EF regardless of diabetes.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Cause of Death; Prognosis; Risk Factors; Stroke Volume; Heart Failure; Diabetes Mellitus
PubMed: 36914068
DOI: 10.1016/j.ihj.2023.03.003 -
Journal of Assisted Reproduction and... Aug 2021To compare the effects of different endometrial preparation protocols for frozen-thawed embryo transfer (FET) cycles and present treatment hierarchy. (Meta-Analysis)
Meta-Analysis
PURPOSE
To compare the effects of different endometrial preparation protocols for frozen-thawed embryo transfer (FET) cycles and present treatment hierarchy.
METHODS
Systematic review with meta-analysis was performed by electronic searching of MEDLINE, the Cochrane Library, Embase, ClinicalTrials.gov and Google Scholar up to Dec 26, 2020. Randomised controlled trials (RCTs) or observational studies comparing 7 treatment options (natural cycle with or without human chorionic gonadotrophin trigger (mNC or tNC), artificial cycle with or without gonadotropin-releasing hormone agonist suppression (AC+GnRH or AC), aromatase inhibitor, clomiphene citrate, gonadotropin or follicle stimulating hormone) in FET cycles were included. Meta-analyses were performed within random effects models. Primary outcome was live birth presented as odds ratio (OR) with 95% confidence intervals (CIs).
RESULTS
Twenty-six RCTs and 113 cohort studies were included in the meta-analyses. In a network meta-analysis, AC ranked last in effectiveness, with lower live birth rates when compared with other endometrial preparation protocols. In pairwise meta-analyses of observational studies, AC was associated with significant lower live birth rates compared with tNC (OR 0.81, 0.70 to 0.93) and mNC (OR 0.85, 0.77 to 0.93). Women who achieved pregnancy after AC were at an increased risk of pregnancy-induced hypertension (OR 1.82, 1.37 to 2.38), postpartum haemorrhage (OR 2.08, 1.61 to 2.78) and very preterm birth (OR 2.08, 1.45 to 2.94) compared with those after tNC.
CONCLUSION
Natural cycle treatment has a higher chance of live birth and lower risks of PIH, PPH and VPTB than AC for endometrial preparation in women receiving FET cycles.
Topics: Birth Rate; Cryopreservation; Embryo Transfer; Endometrium; Female; Fertilization in Vitro; Humans; Live Birth; Network Meta-Analysis; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic
PubMed: 33829375
DOI: 10.1007/s10815-021-02125-0 -
Upsala Journal of Medical Sciences May 2020Recent evidence suggests that follicular development occurs in a wave-like model during the ovarian cycle, where up to three cohorts of follicles are recruited to...
DuoStim - a reproducible strategy to obtain more oocytes and competent embryos in a short time-frame aimed at fertility preservation and IVF purposes. A systematic review.
Recent evidence suggests that follicular development occurs in a wave-like model during the ovarian cycle, where up to three cohorts of follicles are recruited to complete folliculogenesis. This understanding overtakes the previous dogma stating that follicles grow only during the follicular phase of the menstrual cycle. Therefore, in fertilization (IVF), novel protocols regarding ovarian stimulation have been theorized based on the use of gonadotrophins to prompt the growth of antral follicles at any stage of the menstrual cycle. These unconventional protocols for ovarian stimulation aim at a more efficient management of poor-prognosis patients, otherwise exposed to conflicting outcomes after conventional approaches. DuoStim appears among these unconventional stimulation protocols as one of the most promising. It combines two consecutive stimulations in the follicular and luteal phases of the same ovarian cycle, aimed at increasing the number of oocytes retrieved and embryos produced in the short time-frame. This protocol has been suggested for the treatment of all conditions requiring a maximal and urgent exploitation of the ovarian reserve, such as oncological patients and poor responders at an advanced maternal age. At present, data from independent studies have outlined the consistency and reproducibility of this approach, which might also reduce the drop-out between consecutive failed IVF cycles in poor-prognosis patients. However, the protocol must be standardized, and more robust studies and cost-benefit analyses are needed to highlight the true clinical pros and cons deriving from DuoStim implementation in IVF.
Topics: Clinical Protocols; Fertility Preservation; Fertilization in Vitro; Humans; Outcome Assessment, Health Care; Ovulation Induction
PubMed: 32338123
DOI: 10.1080/03009734.2020.1734694 -
Machine perfusion preservation versus static cold storage for deceased donor kidney transplantation.The Cochrane Database of Systematic... Mar 2019Kidney transplantation is the optimal treatment for end-stage kidney disease. Retrieval, transport and transplant of kidney grafts causes ischaemia reperfusion injury.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Kidney transplantation is the optimal treatment for end-stage kidney disease. Retrieval, transport and transplant of kidney grafts causes ischaemia reperfusion injury. The current accepted standard is static cold storage (SCS) whereby the kidney is stored on ice after removal from the donor and then removed from the ice box at the time of implantation. However, technology is now available to perfuse or "pump" the kidney during the transport phase or at the recipient centre. This can be done at a variety of temperatures and using different perfusates. The effectiveness of treatment is manifest clinically as delayed graft function (DGF), whereby the kidney fails to produce urine immediately after transplant.
OBJECTIVES
To compare hypothermic machine perfusion (HMP) and (sub)normothermic machine perfusion (NMP) with standard SCS.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies to 18 October 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
All randomised controlled trials (RCTs) and quasi-RCTs comparing HMP/NMP versus SCS for deceased donor kidney transplantation were eligible for inclusion. All donor types were included (donor after circulatory (DCD) and brainstem death (DBD), standard and extended/expanded criteria donors). Both paired and unpaired studies were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
The results of the literature search were screened and a standard data extraction form was used to collect data. Both of these steps were performed by two independent authors. Dichotomous outcome results were expressed as risk ratio (RR) with 95% confidence intervals (CI). Continuous scales of measurement were expressed as a mean difference (MD). Random effects models were used for data analysis. The primary outcome was incidence of DGF. Secondary outcomes included: one-year graft survival, incidence of primary non-function (PNF), DGF duration, long term graft survival, economic implications, graft function, patient survival and incidence of acute rejection.
MAIN RESULTS
No studies reported on NMP, however one ongoing study was identified.Sixteen studies (2266 participants) comparing HMP with SCS were included; 15 studies could be meta-analysed. Fourteen studies reported on requirement for dialysis in the first week post-transplant (DGF incidence); there is high-certainty evidence that HMP reduces the risk of DGF when compared to SCS (RR 0.77; 95% CI 0.67 to 0.90; P = 0.0006). HMP reduces the risk of DGF in kidneys from DCD donors (7 studies, 772 participants: RR 0.75; 95% CI 0.64 to 0.87; P = 0.0002; high certainty evidence), as well as kidneys from DBD donors (4 studies, 971 participants: RR 0.78, 95% CI 0.65 to 0.93; P = 0.006; high certainty evidence). The number of perfusions required to prevent one episode of DGF (number needed to treat, NNT) was 7.26 and 13.60 in DCD and DBD kidneys respectively. Studies performed in the last decade all used the LifePort machine and confirmed that HMP reduces the incidence of DGF in the modern era (5 studies, 1355 participants: RR 0.77, 95% CI 0.66 to 0.91; P = 0.002; high certainty evidence). Reports of economic analysis suggest that HMP can lead to cost savings in both the North American and European settings.Two studies reported HMP also improves graft survival however we were not able to meta-analyse these results. A reduction in incidence of PNF could not be demonstrated. The effect of HMP on our other outcomes (incidence of acute rejection, patient survival, hospital stay, long-term graft function, duration of DGF) remains uncertain.
AUTHORS' CONCLUSIONS
HMP is superior to SCS in deceased donor kidney transplantation. This is true for both DBD and DCD kidneys, and remains true in the modern era (studies performed in the last decade). As kidneys from DCD donors have a higher overall DGF rate, fewer perfusions are needed to prevent one episode of DGF (7.26 versus 13.60 in DBD kidneys).Further studies looking solely at the impact of HMP on DGF incidence are not required. Follow-up reports detailing long-term graft survival from participants of the studies already included in this review would be an efficient way to generate further long-term graft survival data.Economic analysis, based on the results of this review, would help cement HMP as the standard preservation method in deceased donor kidney transplantation.RCTs investigating (sub)NMP are required.
Topics: Delayed Graft Function; Graft Rejection; Graft Survival; Humans; Incidence; Kidney; Kidney Transplantation; Organ Preservation; Perfusion; Randomized Controlled Trials as Topic; Refrigeration; Time Factors; Tissue Donors
PubMed: 30875082
DOI: 10.1002/14651858.CD011671.pub2 -
Fertility and Sterility Dec 2021To investigate the association between luteal serum progesterone levels and frozen embryo transfer (FET) outcomes. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the association between luteal serum progesterone levels and frozen embryo transfer (FET) outcomes.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Women undergoing FET.
INTERVENTION(S)
We conducted electronic searches of MEDLINE, PubMed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and grey literature (not widely available) from inception to March 2021 to identify cohort studies in which the serum luteal progesterone level was measured around the time of FET.
MAIN OUTCOME MEASURE(S)
Ongoing pregnancy or live birth rate, clinical pregnancy rate, and miscarriage rate.
RESULT(S)
Among the studies analyzing serum progesterone level thresholds <10 ng/mL, a higher serum progesterone level was associated with increased rates of ongoing pregnancy or live birth (relative risk [RR] 1.47, 95% confidence interval [CI] 1.28 to 1.70), higher chance of clinical pregnancy (RR 1.31, 95% CI 1.16 to 1.49), and lower risk of miscarriage (RR 0.62, 95% CI 0.50 to 0.77) in cycles using exclusively vaginal progesterone and blastocyst embryos. There was uncertainty about whether progesterone thresholds ≥10 ng/mL were associated with FET outcomes in sensitivity analyses including all studies, owing to high interstudy heterogeneity and wide CIs.
CONCLUSION(S)
Our findings indicate that there may be a minimum clinically important luteal serum concentration of progesterone required to ensure an optimal endocrine milieu during embryo implantation and early pregnancy after FET treatment. Future clinical trials are required to assess whether administering higher-dose luteal phase support improves outcomes in women with a low serum progesterone level at the time of FET.
PROSPERO NUMBER
CRD42019157071.
Topics: Cryopreservation; Embryo Transfer; Female; Humans; Live Birth; Luteal Phase; Pregnancy; Pregnancy Rate; Progesterone; Prospective Studies; Reproductive Techniques, Assisted; Retrospective Studies
PubMed: 34384594
DOI: 10.1016/j.fertnstert.2021.07.002 -
The Cochrane Database of Systematic... Apr 2021Alveolar bone changes following tooth extraction can compromise prosthodontic rehabilitation. Alveolar ridge preservation (ARP) has been proposed to limit these changes... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alveolar bone changes following tooth extraction can compromise prosthodontic rehabilitation. Alveolar ridge preservation (ARP) has been proposed to limit these changes and improve prosthodontic and aesthetic outcomes when implants are used. This is an update of the Cochrane Review first published in 2015.
OBJECTIVES
To assess the clinical effects of various materials and techniques for ARP after tooth extraction compared with extraction alone or other methods of ARP, or both, in patients requiring dental implant placement following healing of extraction sockets.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 19 March 2021), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2021, Issue 2), MEDLINE Ovid (1946 to 19 March 2021), Embase Ovid (1980 to 19 March 2021), Latin American and Caribbean Health Science Information database (1982 to 19 March 2021), Web of Science Conference Proceedings (1990 to 19 March 2021), Scopus (1966 to 19 March 2021), ProQuest Dissertations and Theses (1861 to 19 March 2021), and OpenGrey (to 19 March 2021). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. A number of journals were also handsearched.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) on the use of ARP techniques with at least six months of follow-up. Outcome measures were: changes in the bucco-lingual/palatal width of alveolar ridge, changes in the vertical height of the alveolar ridge, complications, the need for additional augmentation prior to implant placement, aesthetic outcomes, implant failure rates, peri-implant marginal bone level changes, changes in probing depths and clinical attachment levels at teeth adjacent to the extraction site, and complications of future prosthodontic rehabilitation.
DATA COLLECTION AND ANALYSIS
We selected trials, extracted data, and assessed risk of bias in duplicate. Corresponding authors were contacted to obtain missing information. We estimated mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes, with 95% confidence intervals (95% CI). We constructed 'Summary of findings' tables to present the main findings and assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 16 RCTs conducted worldwide involving a total of 524 extraction sites in 426 adult participants. We assessed four trials as at overall high risk of bias and the remaining trials at unclear risk of bias. Nine new trials were included in this update with six new trials in the category of comparing ARP to extraction alone and three new trials in the category of comparing different grafting materials. ARP versus extraction: from the seven trials comparing xenografts with extraction alone, there is very low-certainty evidence of a reduction in loss of alveolar ridge width (MD -1.18 mm, 95% CI -1.82 to -0.54; P = 0.0003; 6 studies, 184 participants, 201 extraction sites), and height (MD -1.35 mm, 95% CI -2.00 to -0.70; P < 0.0001; 6 studies, 184 participants, 201 extraction sites) in favour of xenografts, but we found no evidence of a significant difference for the need for additional augmentation (RR 0.68, 95% CI 0.29 to 1.62; P = 0.39; 4 studies, 154 participants, 156 extraction sites; very low-certainty evidence) or in implant failure rate (RR 1.00, 95% CI 0.07 to 14.90; 2 studies, 70 participants/extraction sites; very low-certainty evidence). From the one trial comparing alloplasts versus extraction, there is very low-certainty evidence of a reduction in loss of alveolar ridge height (MD -3.73 mm; 95% CI -4.05 to -3.41; 1 study, 15 participants, 60 extraction sites) in favour of alloplasts. This single trial did not report any other outcomes. Different grafting materials for ARP: three trials (87 participants/extraction sites) compared allograft versus xenograft, two trials (37 participants, 55 extraction sites) compared alloplast versus xenograft, one trial (20 participants/extraction sites) compared alloplast with and without membrane, one trial (18 participants, 36 extraction sites) compared allograft with and without synthetic cell-binding peptide P-15, and one trial (30 participants/extraction sites) compared alloplast with different particle sizes. The evidence was of very low certainty for most comparisons and insufficient to determine whether there are clinically significant differences between different ARP techniques based on changes in alveolar ridge width and height, the need for additional augmentation prior to implant placement, or implant failure. We found no trials which evaluated parameters relating to clinical attachment levels, specific aesthetic or prosthodontic outcomes for any of the comparisons. No serious adverse events were reported with most trials indicating that the procedure was uneventful. Among the complications reported were delayed healing with partial exposure of the buccal plate at suture removal, postoperative pain and swelling, moderate glazing, redness and oedema, membrane exposure and partial loss of grafting material, and fibrous adhesions at the cervical part of previously preserved sockets, for the comparisons xenografts versus extraction, allografts versus xenografts, alloplasts versus xenografts, and alloplasts with and without membrane.
AUTHORS' CONCLUSIONS
ARP techniques may minimise the overall changes in residual ridge height and width six months after extraction but the evidence is very uncertain. There is lack of evidence of any differences in the need for additional augmentation at the time of implant placement, implant failure, aesthetic outcomes, or any other clinical parameters due to lack of information or long-term data. There is no evidence of any clinically significant difference between different grafting materials and barriers used for ARP. Further long-term RCTs that follow CONSORT guidelines (www.consort-statement.org) are necessary.
Topics: Adult; Alveolar Process; Alveolar Ridge Augmentation; Bias; Biocompatible Materials; Bone Regeneration; Bone Remodeling; Confidence Intervals; Dental Implantation, Endosseous; Heterografts; Humans; Middle Aged; Organ Sparing Treatments; Randomized Controlled Trials as Topic; Time Factors; Tooth Extraction; Tooth Socket; Treatment Outcome
PubMed: 33899930
DOI: 10.1002/14651858.CD010176.pub3 -
Cancers Sep 2023Parenchymal-sparing approaches to pancreatectomy are technically challenging procedures but allow for preserving a normal pancreas and decreasing the rate of... (Review)
Review
BACKGROUND
Parenchymal-sparing approaches to pancreatectomy are technically challenging procedures but allow for preserving a normal pancreas and decreasing the rate of postoperative pancreatic insufficiency. The robotic platform is increasingly being used for these procedures. We sought to evaluate robotic parenchymal-sparing pancreatectomy and assess its complication profile and efficacy.
METHODS
This systematic review consisted of all studies on robotic parenchymal-sparing pancreatectomy (central pancreatectomy, duodenum-preserving partial pancreatic head resection, enucleation, and uncinate resection) published between January 2001 and December 2022 in PubMed and Embase.
RESULTS
A total of 23 studies were included in this review ( = 788). Robotic parenchymal-sparing pancreatectomy is being performed worldwide for benign or indolent pancreatic lesions. When compared to the open approach, robotic parenchymal-sparing pancreatectomies led to a longer average operative time, shorter length of stay, and higher estimated intraoperative blood loss. Postoperative pancreatic fistula is common, but severe complications requiring intervention are exceedingly rare. Long-term complications such as endocrine and exocrine insufficiency are nearly nonexistent.
CONCLUSIONS
Robotic parenchymal-sparing pancreatectomy appears to have a higher risk of postoperative pancreatic fistula but is rarely associated with severe or long-term complications. Careful patient selection is required to maximize benefits and minimize morbidity.
PubMed: 37686648
DOI: 10.3390/cancers15174369 -
Journal of Medicine and Life Mar 2022The aim of this study was to evaluate the clinical need and impact of socket preservation to protect the bone for future dental implant placement. Moreover, we aimed to... (Review)
Review
The aim of this study was to evaluate the clinical need and impact of socket preservation to protect the bone for future dental implant placement. Moreover, we aimed to list down various methods of socket preservation by going through randomized clinical trials. We searched PubMed, Google Scholar, and Cochrane databases for all relevant publications, where researchers compared various methods and tools for socket preservation. All eight randomized controlled trials mentioned several methods that are helpful in preserving bone levels both horizontally and vertically. The studies included in this systematic review demonstrate that each material has certain efficacy in preserving the socket after tooth extraction for future implant placement. Socket preservation methods and materials are effective in preparing patients for future prostheses.
Topics: Humans; Tooth Extraction; Tooth Socket
PubMed: 35450006
DOI: 10.25122/jml-2021-0308