Relationship between circulating FSH levels and body composition and bone health in patients with prostate cancer who undergo androgen deprivation therapy: The BLADE study.

Background: Among its extragonadal effects, follicle-stimulating hormone (FSH) has an impact on body composition and bone metabolism. Since androgen deprivation therapy (ADT) has a profound impact on circulating FSH concentrations, this hormone could potentially be implicated in the changes of fat body mass (FBM), lean body mass (LBM), and bone fragility induced by ADT. The objective of this study is to correlate FSH serum levels with body composition parameters, bone mineral density (BMD), and bone turnover markers at baseline conditions and after 12 months of ADT. Methods: Twenty-nine consecutive non-metastatic prostate cancer (PC) patients were enrolled from 2017 to 2019 in a phase IV study. All patients underwent administration of the luteinizing hormone-releasing hormone antagonist degarelix. FBM, LBM, and BMD were evaluated by dual-energy x-ray absorptiometry at baseline and after 12 months of ADT. FSH, alkaline phosphatase, and C-terminal telopeptide of type I collagen were assessed at baseline and after 6 and 12 months. For outcome measurements and statistical analysis, t-test or sign test and Pearson or Spearman tests for continuous variables were used when indicated. Results: At baseline conditions, a weak, non-significant, direct relationship was found between FSH serum levels and FBM at arms (r = 0.36) and legs (r = 0.33). Conversely, a stronger correlation was observed between FSH and total FBM (r = 0.52, p = 0.006), fat mass at arms (r = 0.54, p = 0.004), and fat mass at trunk (r = 0.45, p = 0.018) assessed after 12 months. On the other hand, an inverse relationship between serum FSH and appendicular lean mass index/FBM ratio was observed (r = -0.64, p = 0.001). This is an ancillary study of a prospective trial and this is the main limitation. Conclusions: FSH serum levels after ADT could have an impact on body composition, in particular on FBM. Therefore, FSH could be a promising marker to monitor the risk of sarcopenic obesity and to guide the clinicians in the tailored evaluation of body composition in PC patients undergoing ADT. Funding: This research was partially funded by Ferring Pharmaceuticals. The funder had no role in design and conduct of the study, collection, management, analysis, and interpretation of the data and in preparation, review, or approval of the manuscript. Clinical trial number: clinicalTrials.gov NCT03202381, EudraCT Number 2016-004210-10.

Treatments given to cancer patients can cause negative side effects. For example, a treatment known as androgen deprivation therapy ­ which is used to reduce male sex hormone levels in prostate cancer patients ­ can lead to increased body fat percentage and decreased bone density. These adverse effects can have further negative impacts on patient health, such as increasing the risk of cardiovascular disease and fractures from falls from standing height or less, respectively. Understanding how androgen deprivation therapy contributes to these negative side effects may help clinicians better manage care and outcomes for patients with prostate cancer. Follicle stimulating hormone (or FSH for short) has roles in male and female reproduction but has also been linked to changes in body composition. For example, elevated FSH levels are associated with higher total fat body mass in post-menopausal women. While androgen deprivation therapy is known to alter FSH blood levels, the impact of this change in prostate cancer patients was not well understood. To investigate the effect of androgen deprivation therapy on FSH levels and body composition, Bergamini et al. used X-ray technology to measure total fat body mass in prostate cancer patients before and after undergoing 12 months of androgen deprivation therapy. The findings showed that patient FSH blood levels significantly decreased after 12 months of treatment. Higher FSH blood levels strongly correlated with increased total fat body mass after 12 months of treatment. The findings of this clinical trial suggest that FSH blood levels impact the body composition of patients undergoing androgen deprivation therapy. As a result, FSH blood levels may be a suitable biomarker for identifying patients that are more likely to develop obesity and are therefore at greater risk of complications such as cardiovascular disease.

Pathological Complete Response to Pembrolizumab plus Axitinib Combination following Serious Immune-Related Adverse Events in an Advanced Renal Cell Carcinoma Patient with a History of Rheumatoid Arthritis.

Immune checkpoint inhibitors (ICIs)-based combinations have improved survival outcomes of advanced renal cell carcinoma (RCC) patients and are currently recommended as first-line treatment options. Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD) of unknown etiology characterized by a chronic inflammatory process involving joints and extra-articular organs. Patients with AD are usually excluded from large randomized clinical trials investigating immunotherapeutic drugs. Therefore, little is known about clinical outcomes of patients with a history of RA treated with ICIs in real-world practice. In the present study, we report the clinical outcome of an advanced RCC patient with a history of RA treated with pembrolizumab in combination with axitinib. The patient experienced serious immune-related adverse events (irAEs) and achieved pathological complete response following only one ICI administration. Our case report shows that ICI-based combinations can be administered efficaciously in advanced RCC patients with a history of AD. However, a close monitoring of these patients is required, given the risk of irAEs and clinical exacerbations of symptoms associated with the preexisting AD. Moreover, prospective clinical data are needed to assess the hypothesis of a correlation between the onset of irAEs and AD flares and responses and survival outcomes to ICIs.

Role of Body Composition in the Prediction of Skeletal Fragility Induced by Hormone Deprivation Therapies in Cancer Patients.

PURPOSE OF REVIEW: This review paper is intended to show that changes in body composition are key in the pathogenesis of bone fragility amongst patients with breast and prostate cancer receiving hormone deprivation therapies (HDTs) and that the mechanism is based on the development of alterations in bone quality rather than in bone quantity. RECENT FINDINGS: Preclinical and clinical data suggest a tight connection amongst bone, adipose and muscular tissues by means of several soluble mediators, potentially leading to (1) bone resorption and bone quality deterioration in sarcopenic obese subjects, (2) bone mineral deposition in healthy trained subjects. Cancer patients treated with HDTs frequently fall into the first condition, named osteosarcopenic obesity. Current clinical guidelines for the prevention of treatment-induced osteoporosis focus on bone mineral density (BMD) as a main predictive factor for fracture risk; however, the pathophysiology underlying HDT-induced bone fragility differs from that of primary and postmenopausal osteoporosis, suggesting a prevalent role for bone quality alterations. Focusing on available data from clinical trials, in our review we suggest osteosarcopenic obesity as a common target for the prevention and treatment of HDTs-related metabolic and skeletal complications, beyond a BMD-centred approach.

The Customized Alveolar Ridge-Splitting (CARS) Technique Combined with Guided Bone Regeneration or Sinus Elevation Augmentation in Maxillary Deficient Ridges.

Various techniques have been proposed to regenerate deficient ridges after tooth removal, including guided bone regeneration, block grafting, distraction osteogenesis, and ridge splitting. However, these procedures are technique-sensitive and often present complications which prevent reconstruction of the deficient ridge and implant placement. In an atrophic anterior or posterior maxilla, these techniques often fail to produce satisfactory long-term outcomes due to the poor bone quality, pneumatization of the maxillary sinus, and the highly cosmetic patient demands. The customized alveolar ridge-splitting (CARS) technique was introduced to improve outcomes and minimize the risk of complications. The synergistic combination of this technique with another augmentation procedure-including lateral window sinus augmentation and guided bone regeneration-allows implant placement into ridges with deficient bone volume both vertically and horizontally. This study presents two case reports that were successfully treated with the CARS technique and additional augmentation techniques to treat severely atrophic ridges in the anterior and posterior maxilla.

Gonadal Function in Male Patients With Metastatic Renal Cell Cancer Treated With Sunitinib.

BACKGROUND/AIM: Single-agent tyrosine kinase inhibitors are still prescribed as first-line treatment to a relevant subgroup of patients with metastatic renal cell carcinoma (mRCC). These agents are known to cause disfunction of many endocrine glands (e.g., thyroid). In this two-step trial, we aimed to assess gonadal function among male patients with mRCC treated with sunitinib. PATIENTS AND METHODS: We enrolled a first cross-sectional cohort of pre-treated (>6 months) patients and a subsequent cohort of treatment-naïve patients who were prospectively followed-up. All patients were screened for hypogonadism and received a Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire at study entry and after 6 months of therapy. Patients who were candidates for testosterone replacement therapy (TRT) also received a FACT-G questionnaire at baseline and 3 months after supplementation. RESULTS: Among the 30 enrolled patients, the prevalence of hypogonadism was found to be higher in those receiving sunitinib for a longer period (27.3% at baseline, 41.7% in the first 6 months, and 68.4% after 9 months of therapy). The testosterone level of patients correlated with quality of life (R=0.32). A total of six patients received TRT, with a significant improvement in their global quality of life after the first 3 months of treatment. CONCLUSION: An increasing prevalence of hypogonadism was seen among male patients who received long-term treatment with sunitinib. TRT was associated with relevant improvements in quality of life. These findings corroborate similar published observations and encourage the assessment of gonadal function in male patients with mRCC under treatment with sunitinib.

Clinical Considerations of Ehlers-Danlos Syndrome for Implant Dentistry: Two Case Reports.

Ehlers-Danlos Syndrome (EDS) is a group of congenital connective tissue disorders that commonly affect joints, muscles, soft tissue, and blood circulation in the affected population. Many oral manifestations are displayed in EDS patients that can include gingival recession, lack of attached gingiva, early severe periodontal disease, and dental caries. However, the literature is limited and oftentimes contradictory regarding dental implants in EDS patients. The aim of this study is to report two successful cases of implants placed in EDS patients, one treated with bone augmentation and both restored with prosthetic implant rehabilitations. Int J Periodontics Restorative Dent 2023;43:e81-e87. doi: 10.11607/prd.5842.

Ehlers-Danlos Syndrome in Prosthodontics, Periodontology, and Implant Dentistry: A Systematic Review of the Literature

Ehlers-Danlos Syndrome (EDS) is one of the most common congenital connective tissue disorders, affecting the synthesis and production of collagen cells. The medical implications for joints, muscles, soft tissue, and blood circulation have been documented in the literature. Many oral manifestations are displayed in EDS patients, including gingival recession, lack of attached gingiva, early severe periodontitis, and dental anomalies and dental caries. However, the literature is limited and oftentimes contradictory, and therefore provides no consensus for guidelines regarding prosthodontic, periodontal, and implant treatment of patients with EDS. Therefore, the aim of this systematic review was to analyze the pertinent literature regarding prosthodontics, periodontology, and implant dentistry in EDS patients.

A Population of TIM4+FOLR2+ Macrophages Localized in Tertiary Lymphoid Structures Correlates to an Active Immune Infiltrate Across Several Cancer Types.

TIM4 has previously been associated with antitumor immunity, yet the pattern of expression and the function of this receptor across human cancer tissues remain poorly explored. Here we combined extensive immunolabeling of human tissues with in silico analysis of pan-cancer transcriptomic data sets to explore the clinical significance of TIM4 expression. Our results unveil that TIM4 is expressed on a fraction of cavity macrophages (CATIM4+MΦ) of carcinoma patients. Moreover, we uncover a high expression of TIM4 on macrophages of the T-cell zone of the carcinoma-associated tertiary lymphoid structures (TLSTIM4+MΦ). In silico analysis of a pan-cancer data set revealed a positive correlation between TIM4 expression and markers of B cells, effector CD8+ T cells, and a 12-chemokine signature defining tertiary lymphoid structure. In addition, TLSTIM4+MΦ were enriched in cancers displaying microsatellite instability and high CD8+ T-cell infiltration, confirming their association with immune-reactive tumors. Both CATIM4+MΦ and TLSTIM4+MΦ express FOLR2, a marker of tissue-resident MΦ. However, CATIM4+MΦ had a higher expression of the immunosuppressive molecules TREM2, IL10, and TGFß as compared with TLSTIM4+MΦ. By analyzing a scRNA sequence data set of tumor-associated myeloid cells, we identified two TIM4+FOLR2+ clusters coherent with CATIM4+MΦ and TLSTIM4+MΦ. We defined specific gene signatures for each subset and found that the CATIM4+ MΦ signature was associated with worse patient survival. In contrast, TLSTIM4+MΦ gene signature positively correlates with a better prognosis. Together, these data illustrate that TIM4 marks two distinct macrophage populations with distinct phenotypes and tissue localization and that may have opposing roles in tumor immunity.

Case Report: 18F-PSMA PET/CT Scan in Castration Resistant Prostate Cancer With Aggressive Neuroendocrine Differentiation.

The development of a neuroendocrine phenotype as a mechanism of resistance to hormonal treatment is observed in up to 20% of advanced prostate cancer patients. High grade neuroendocrine prostate cancer (NEPC) is associated to poor prognosis and the therapeutic armamentarium is restricted to platinum-based chemotherapy. Prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) imaging has recently emerged as a potential new standard for the staging of prostate cancer and PSMA-based radioligand therapy (RLT) as a therapeutic option in advanced metastatic castration resistant prostate cancer (mCRPC). PSMA-based theranostic is not currently applied in the staging and treatment of NEPC since PSMA expression on neuroendocrine differentiated cells was shown to be lost. In this case series, we present 3 consecutive mCRPC patients with histologically proven high grade neuroendocrine differentiation who underwent PSMA-PET/CT and surprisingly showed high tracer uptake. This observation stimulates further research on the use of PSMA-based theranostic in the management of NEPC.

Maintenance of androgen deprivation therapy or testosterone supplementation in the management of castration-resistant prostate cancer: that is the question.

PURPOSE: Whether or not androgen receptor (AR) axis could still be targetable in castration resistant prostate cancer (CRPC) patients with disease progression to next generation hormonal agents (NGHAs) is a controversial issue. RESULTS: Serum testosterone in CRPC patients has a positive prognostic role and increasing testosterone levels after androgen deprivation therapy (ADT) withdrawal or testosterone supplementation, as part of a bipolar androgen therapy (BAT) strategy, has been shown to potentially restore sensitivity to previous lines of NGHAs. CONCLUSION: These data suggest that maintenance of ADT in CRPC patients receiving further lines of treatment, as recommended by current international guidelines, could be questionable. Conversely, testosterone supplementation aimed to re-sensitize CRPC to further hormonal manipulation is a strategy worth to be explored in future clinical trials.

Surgical Strategies Used to Successfully Re-implant an Implant that Failed Four Times at the Same Site: A Case Report.

Although implants have been shown to have high success rates, complications such as implant failure can occur. This presents a challenging dilemma for clinicians when attempting another implant placement in the failed site. The patient in this clinical case report presented with implant failure four times at the same site. This case report describes implant placement in a site where four failed implants were previously removed and evaluates the approach used to achieve a successful outcome.

Histologic Findings 8 Weeks After Customized Alveolar Ridge-Splitting Technique.

Different techniques have been introduced when replacement with an implant is planned after tooth extraction. The conventional approach consists of waiting 3 to 4 months before implant placement. However, many other options are available for implant placement, including immediate implant placement (IIP), IIP and immediate provisionalization (IIPIP), and early implant placement (EIP). When the ridge is deficient, guided bone regeneration (GBR) with simultaneous implant placement is often performed. However, this procedure has potential for postoperative complications and patient discomfort, as well as an extended treatment time. The recent introduction of the Customized Alveolar Ridge-Splitting (CARS) technique can help avoid many of these problems and treat atrophic ridges that will require two or three GBR surgeries. The purpose of this case report is to demonstrate the step-by-step surgical and restorative procedures for the CARS technique and present histologic data of the new bone generated utilizing this technique.

A New Concept of Safety Distance to Place Implants in the Area of the Inferior Alveolar Canal to Avoid Neurosensory Disturbance.

Inferior alveolar nerve (IAN) damage following implant placement is a severe complication that can compromise a patient's quality of life. Previous studies have suggested that a safety zone of 2 mm, if maintained, might avoid this problem. This retrospective study evaluates implants placed in closer proximity to the IAN without resulting in any postoperative neurologic complications and suggests a new concept of safety distance. A total of 60 consecutive patients receiving 101 mandibular implants < 2 mm from the IAN were included in this study. All enrolled patients had a CBCT scan done for radiologic assessment before implant placement and following final restoration. Measurements were obtained through cross-sectional views using Simplant software. In patients without neurologic disturbances, a mean distance of +0.75 mm was seen from the closest portion of the implant to the nerve bundle. In cases where a direct transection and/or compression of the nerve was not observed, the patients did not experience neurosensory disturbances.

Patient-Related Risk Factors for Maxillary Sinus Augmentation Procedures: A Systematic Literature Review.

The posterior maxilla has traditionally presented a challenge for successful placement of dental implants due to a combination of poor bone quality, ridge atrophy, and pneumatization of the sinus floor following tooth extraction. However, with the successful and predictable surgical outcomes reported in the literature, more clinicians and patients are choosing an implant-supported restoration in the edentulous posterior maxilla. Consequently, sinus elevation and augmentation have gained more popularity. Extensive research has been conducted on types of bone graft materials and implants, less-invasive techniques to perform sinus augmentation, and timing for implant placement for sinus grafting. Despite the predictability of the techniques and biomaterials employed in sinus grafting procedures, intra- and postoperative complications are common. Much of the current literature discusses the local risk factors related to sinus augmentation, with few studies focusing on the patient-related risk factors. The purpose of this review is to identify, evaluate, and discuss the possible management of patient-related risk factors to allow for more predictable maxillary sinus floor augmentation outcomes.

Are Cannabis and Electronic Cigarettes Risks for Early Sinus Lift Failures?

To achieve restorative success for esthetic cases a process is needed that can be reproduced repeatedly. As with any process there are critical steps that must be followed to ensure accurate and precise results. This article outlines a verification process of provisional restorations in order to obtain appropriate esthetics, phonetics, and function. Additionally, the article discusses how newly created contours can be transferred intraorally to the laboratory benchtop and then to the final restorations. Through the process of verification, the clinician can establish restorative predictability to enhance the restorative success of any esthetic case.

An Algorithmic Approach to Evaluation of an Ailing Implant.

With the incidence of failed and ailing dental implants increasing, the authors conducted research to evaluate and characterize all known criteria used in the assessment of implant health in the clinical setting. A review of articles found in electronic databases was performed. Once all parameters for implant assessment as supported by current literature were selected, implant assessment documents were created: a data acquisition form and a quantitative comprehensive evaluation. These documents provide the clinician an algorithm that yields a prognosis of survival for each implant. Diagnostic criteria were organized to offer a comprehensive assessment of risk factors related to implant health. Data acquisition prior to establishing the prognosis is necessary in accordance with the staging system developed. Parameters for diagnosis and staging include a thorough medical/social history of the patient, implant history, and clinical evaluation. The authors concluded that the establishment of parameters for comprehensive implant evaluation in the clinical setting is feasible. This assessment process enables an effective clinical approach to evaluate and treat ailing implants while facilitating a clinical diagnostic algorithm.

Limited Evidence Suggests Metformin Might Be Beneficial to Reduce Head and Neck Cancer Risk and Increase Overall Survival, While Any Benefit With Antiinflammatory Drugs Is Inconsistent.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Protective effects of metformin, statins, and antiinflammatory drugs on head and neck cancer: A systematic review. Saka Herrán C, Jané-Salas E, Devesa AE, López-López J. Oral Oncol 2018;85:68-81. SOURCE OF FUNDING: None. TYPE OF DESIGN: Systematic review with meta-analysis.

Anodised or turned dental implants?

Data sourcesAn electronic search without time or language restrictions was undertaken using several databases: PubMed/Medline, Web of Science and the Cochrane Oral Health Group Trials Register and ongoing clinical trials. Manual searches were performed in dental implant related journals and reference lists of identified studies, and relevant reviews were scanned for possible additional studies.Study selectionEligibility criteria included human clinical studies, either randomised or not, comparing implant failure rates, MBL and/or post-operative infection in any group of patients receiving turned (machined) and anodised-surface (TiUnite) implants, both from the same implant manufacturer.Data extraction and synthesisThe titles and abstracts of all reports identified through the electronic searches were read independently by the three authors. For studies appearing to meet the inclusion criteria, or for which there were insufficient data in the title and abstract to make a clear decision, the full report was obtained. Disagreements were resolved by discussion between the authors. Quality assessment of the studies was executed according to the Newcastle-Ottawa scale (NOS), which is a quality assessment tool used when observational studies are also included in systematic reviews.ResultsThirty-eight publications were included. The results suggest a risk ratio =2.82(95%CI, 1.95 - 4.06, P < 0.00001) for failure of turned implants when compared to anodised-surface implants. Sensitivity analyses showed similar results when only the studies inserting implants in maxillae or mandibles were pooled. There were no statistically significant effects of turned implants on the MBL (mean difference [MD]=0.02, (95%CI, 0.16 - 0.20; P = 0 82) in comparison to anodised implants. The results of a meta-regression considering the follow-up period as a covariate suggested an increase of the MD with the increase in the follow-up time (MD increase 0.012 mm year 1), however, without a statistical significance (P = 0.813). Due to lack of satisfactory information, meta-analysis for the outcome 'post-operative infection' was not performed.ConclusionsWithin the limitations of the existing investigations, the present study suggests that turned implants have a statistically higher probability to fail than anodised-surface implants, regardless of whether the implants were placed in maxilla or mandible. There were no statistically significant effects of turned implants on the MBL when compared with anodised implants. A comparison of post-operative infection between the implant types was not possible, due to lack of sufficient information. The reliability and validity of the data collected, the limitations of the quality assessment tool and the potential for biases and confounding factors are some of the shortcomings of the present study. The results have to be interpreted with caution due to the presence of several confounding factors in the included studies.

Are fibre posts associated with the occurrence of prosthetic complications?

Data sourcesThe Pubmed, Evidence-Based Dentistry, BMJ Clinical Evidence, EmbaseDynamed, and www.opengrey.eu databases and manual search of reference lists.Study selectionRandomised clinical trials (RCTs) were accepted if they had: participants with no periodontal disease and teeth restored with SCs or FDPs and compared fibre posts and other prosthetic systems and evaluated the prosthetic complications with a minimum observational period of 36 months.Data extraction and synthesisTitles and abstracts were evaluated independently by two reviewers, any disagreement was discussed with a third reviewer. The agreement for the two reviewers was 97%. The quality and the risk of bias of the studies included was assessed following the Cochrane Handbook considering the domains of randomisation, sample size, inclusion and exclusion criteria, follow-up achieved, blinding, withdrawing and groups' compatibility for quality assessment, and for the risk of bias the domains evaluated were allocation concealment, blinding of outcome assessor and follow-up.ResultsThe database search yielded 4,230 records; after duplications removal, 3,670 records were reviewed independently by the authors, and four articles were chosen to include in the systematic review.The most frequently reported failures in the available studies were as follows: fibre post debonding, loss of retention of single crowns and marginal gaps. Less frequently, chippings and fractures were recorded in SCs. No studies about complications related to FDPs were found.The failure rate ranged from 0 to 28.2%.ConclusionsA correlation between the failure rates of fibre posts and the type of prosthetic restoration (SCs or FDPs ) cannot be found. Further RCTs are required to achieve evidence-based conclusions, particularly about the use of fibre posts with FDPs.