The Use of Oral Amino-Bisphosphonates and Coronavirus Disease 2019 (COVID-19) Outcomes

The determinants of the susceptibility to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and severe coronavirus disease 2019 (COVID-19) manifestations are yet not fully understood. Amino-bisphosphonates (N-BPs) have anti-inflammatory properties and have been shown to reduce the incidence of lower respiratory infections, cardiovascular events, and cancer. We conducted a population-based retrospective observational cohort study with the primary objective of determining if oral N-BPs treatment can play a role in the susceptibility to development of severe COVID-19. Administrative International Classification of Diseases, Ninth Revision, Clinical ModificationI (ICD-9-CM) and anatomical-therapeutic chemical (ATC) code data, representative of Italian population (9% sample of the overall population), were analyzed. Oral N-BPs (mainly alendronate and risedronate) were included in the analysis, zoledronic acid was excluded because of the low number of patients at risk. Incidence of COVID-19 hospitalization was 12.32 (95% confidence interval [CI], 9.61–15.04) and 11.55 (95% CI, 8.91–14.20), of intensive care unit (ICU) utilization because of COVID-19 was 1.25 (95% CI, 0.38–2.11) and 1.42 (95% CI, 0.49–2.36), and of all-cause death was 4.06 (95% CI, 2.50–5.61) and 3.96 (95% CI, 2.41–5.51) for oral N-BPs users and nonusers, respectively. Sensitivity analyses that excluded patients with prevalent vertebral or hip fragility fractures and without concomitant glucocorticoid treatment yielded similar results. In conclusion, we found that the incidence of COVID-19 hospitalization, intensive care unit (ICU) utilization, and COVID-19 potentially related mortality were similar in N-BPs–treated and nontreated subjects. Similar results were found in N-BPs versus other anti-osteoporotic drugs. We provide real-life data on the safety of oral N-BPs in terms of severe COVID-19 risk on a population-based cohort. Our results do not support the hypothesis that oral N-BPs can prevent COVID-19 infection and/or severe COVID-19; however, they do not seem to increase the risk. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone,the murine model of X‐linked hypophosphatemia

X‐linked hypophosphatemia (XLH/HYP)—with renal phosphate wasting, hypophosphatemia, osteomalacia, and tooth abscesses—is caused by mutations in the zinc‐metallopeptidase PHEX gene (phosphate‐regulating gene with homologies to endopeptidase on the X chromosome). PHEX is highly expressed by mineralized tissue cells. Inactivating mutations in PHEX lead to distal renal effects (implying accumulation of a secreted, circulating phosphaturic factor) and accumulation in bone and teeth of mineralization‐inhibiting, acidic serine‐ and aspartate‐rich motif (ASARM)‐containing peptides, which are proteolytically derived from the mineral‐binding matrix proteins of the SIBLING family (small, integrin‐binding ligand N‐linked glycoproteins). Although the latter observation suggests a local, direct matrix effect for PHEX, its physiologically relevant substrate protein(s) have not been identified. Here, we investigated two SIBLING proteins containing the ASARM motif—osteopontin (OPN) and bone sialoprotein (BSP)—as potential substrates for PHEX. Using cleavage assays, gel electrophoresis, and mass spectrometry, we report that OPN is a full‐length protein substrate for PHEX. Degradation of OPN was essentially complete, including hydrolysis of the ASARM motif, resulting in only very small residual fragments. Western blotting of Hyp (the murine homolog of human XLH) mouse bone extracts having no PHEX activity clearly showed accumulation of an ～35 kDa OPN fragment that was not present in wild‐type mouse bone. Immunohistochemistry and immunogold labeling (electron microscopy) for OPN in Hyp bone likewise showed an accumulation of OPN and/or its fragments compared with normal wild‐type bone. Incubation of Hyp mouse bone extracts with PHEX resulted in the complete degradation of these fragments. In conclusion, these results identify full‐length OPN and its fragments as novel, physiologically relevant substrates for PHEX, suggesting that accumulation of mineralization‐inhibiting OPN fragments may contribute to the mineralization defect seen in the osteomalacic bone characteristic of XLH/HYP. © 2013 American Society for Bone and Mineral Research.     

Reconstruction of parietal bone defects with adiposederived mesenchymal stem cells. Experimental study

Purpose:This study assessed the regeneration potential of mesenchymal stem cells (MSC) from adipose tissue associated with platelet-rich plasma (PRP) in bone regeneration.Methods:Thirty Wistar rats (Rattus norvegicus albinos) were divided into five groups (according to the grafting material and time to euthanasia): (1) autograft - 14 days (control), (2) autograft - 28 days (control), (3) MSC + PRP - 14 days, (4) MSC + PRP + papaverine - 14 days and (5) MSC + PRP + papaverine - 28 days. After euthanasia, the graft was removed and histological slides were prepared. They were assessed by a blinded pathologist using a previously published histological scale as parameter.Results:There was some degree of neoformed bone trabeculae (NBT) in 93.3% of the samples, as well as osteoblastic activity (OA). The autograft groups (14 and 28 days) had higher levels in the formation of bone trabeculae. Nonparametric data were analyzed using the Wilcoxon-Mann-Whitney test and proved not to be statistically significant at p < 0.05.Conclusions:Experimental parietal bone reconstruction, combining MSC, PRP and papaverine presented regeneration in all groups with no significant difference among them.Key words: Bone Regeneration, Platelet-Rich Plasma, Tissue Engineering, Rats     

10‐Year Follow‐Up of Immediately Loaded Implants with TiUnite Porous Anodized Surface

Background: The immediate loading of implants with a porous anodized surface is a well‐described technique. Few data are however available on the long‐term outcomes. Purpose: The aim of this prospective study was to assess the 10‐year performance of TiUnite implants supporting fixed prostheses placed with an immediate loading approach in both postextractive and healed sites. Materials and Methods: All patients received a fixed provisional restoration supported by immediately loaded parallel design, self‐tapping implants with a porous anodized TiUnite surface, and an external‐hexagonal connection. Both healed and postextractive cases were included. Success and survival rate for restorations and implants, changes in marginal peri‐implant bone level, probing depth measurements, biological or technical complications, and any other adverse event were recorded at yearly follow‐up up to 10 years after surgery. Results: A total of 210 implants fulfilled the inclusion criteria and were consecutively placed in 59 patients. Forty‐seven (22.38%) implants were lost because of the recalled patient refused to attend the planned 10‐year follow‐up. Five over 210 (2.38%) implants were lost. At the final follow‐up, the accumulated mean marginal bone loss and probing depth were, respectively, 1.93 mm (SD 0.40) and 2.54 mm (SD 0.44) for the implants placed in healed sites (n = 84); 1.98 mm (SD 0.37) and 2.63 mm (SD 0.39) for the implants placed in postextractive sites (n = 74). The restorations examined achieved a cumulative 65.26% success rate and 97.96% survival rate. The implants placed in healed and postextractive sites, respectively, achieved a 98.05% and a 96.52% cumulative survival rate. Conclusions: Positive results in terms of bone maintenance in the long‐term perspective are to be expected using immediately loaded implants with a TiUnite porous anodized surface in both postextractive and healed sites when adequate levels of oral hygiene are kept.     

Extended axillary block (E. A. B.)

Key words  axillary - block     

Drainage of retro-parapharyngeal abscess: an additional indication for endoscopic sinus surgery

Deep neck abscesses are life-threatening conditions, in early stages preferably treated by intravenous antibiotic therapy; in advanced stages, surgical drainage is mandatory. We report two cases of retro-parapharyngeal abscess with prevalent retronasopharyngeal extension in two men aged 60 and 82, both of whom underwent transnasal endoscopic drainage. The main surgical steps were incision of the posterior pharyngeal mucosal wall, widening of the incision, drainage of purulent collection and careful dissection and removal of the necrotic tissue. The first patient, with an abscess associated with chronic otitis media and presenting hypoglossal nerve palsy, quickly recovered from pharyngodinia, otalgia and trismus. Twenty-six months after surgery, he is symptom-free, with hemitongue atrophy due to denervation as the only residual sign. The second patient, affected by skull base osteomyelitis secondary to malignant external otitis, after a first successful drainage, underwent a second endoscopic procedure for the reoccurrence of an abscess in the contralateral retroparapharyngeal space. Twelve months after the first surgery, the patient reported an improvement of symptoms, except for persistent dysphonia related to vagal nerve palsy. At follow-up MR, another abscess was detected in the left retro-parapharyngeal space. In selected cases of abscess, transnasal endoscopic drainage may be an effective alternative to external approaches. Minimal morbidity, the absence of cervical or palatal scars and a short hospitalization time can be considered as important advantages in comparison to external approaches. Patients with abscess secondary to skull base osteomyelitis require close imaging surveillance because of the difficulty of definitive control of the disease.     

Improved diagnostic effectiveness with a sequential diagnostic paradigm in idiopathic pediatric sensorineural hearing loss.

OBJECTIVES: To determine whether a stepwise diagnostic paradigm is more diagnostically efficient and cost-effective than a simultaneous testing approach in the evaluation of idiopathic pediatric sensorineural hearing loss (SNHL). DESIGN: Prospective prevalence study. SETTING: Tertiary referral children's hospital. PATIENTS: Consecutive children (n = 150) presenting with idiopathic SNHL in the last 2 years. INTERVENTIONS: All children were evaluated with full diagnostic evaluations including GJB2 screens, temporal bone computed tomography scans, and laboratory investigations. MAIN OUTCOME MEASURES: 1) Diagnostic yields of GJB2 screens, imaging, and laboratory results per SNHL category; 2) Cost analysis comparing a sequential versus a simultaneous testing approach. RESULTS: Overall, 12.0% of patients had biallelic mutations in the GJB2 gene, whereas 30% of patients had an abnormality on temporal bone scan. Laboratory testing did not reveal the SNHL etiology in any patient. While maintaining diagnostic accuracy, significant cost savings were inferred by using a sequential diagnostic algorithm. Our data show children with severe to profound SNHL should first be tested with a GJB2 screen, as opposed to those with milder SNHL, who should undergo imaging as the initial testing step. In patients with initially positive GJB2 or imaging screens, logistic regression analysis significantly predicted negative results on further testing. CONCLUSIONS: A stepwise diagnostic paradigm tailored to the level of the hearing loss in children with bilateral SNHL is more diagnostically efficient and cost effective than the more commonly used full, simultaneous testing approach. Laboratory investigation should not be routine but based on clinical history.