Symptomatic androgen deficiency and sexual dysfunctions in male patients receiving alectinib for ALK-positive advanced nonsmall cell lung cancer.

BACKGROUND: It is reported that treatment with anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) induces hypogonadism both in male patients with ALK-positive cancer and in murine models. METHODS: In this study, three groups, including an experimental group of male patients with ALK-positive, advanced nonsmall cell lung cancer (ANSCLC) who were receiving alectinib (cohort A), a control group of female patients with ALK-positive ANSCLC who were receiving alectinib (cohort B), and a control group of male patients with ALK-negative ANSCLC (cohort C), prospectively underwent a full hormone assessment for androgen deficiency at 8 weeks after the start of treatment and in case of reported suspected symptoms. Patients with major sexual dysfunctions were referred to an endocrinologist. RESULTS: Ninety-five patients were consecutively enrolled onto the study. Among sixty-eight male patients, both median total testosterone levels (2.93 vs. 4.92 ng/ml; p = .0001) and free testosterone levels (0.11 vs. 0.17 pg/ml; p = .0002) were significantly lower in ALK-positive ANSCLC patients in cohort A compared with ALK-negative patients in cohort C; conversely, median FSH (10.32 vs. 17.52 mUI/ml; p = .0059) and LH levels (4.72 vs. 7.49 mUI/ml; p = .0131) were significantly higher in cohort C compared to cohort A. Median inhibin B levels were higher in ALK-positive male patients (74.3 vs. 44.24 pg/ml; p = .0038), but all patients had inhibin B values within the normal range. The percentage of male patients who had positive scores on the Androgen Deficiency in Aging Males (ADAM) questionnaire was 62% in cohort A and 26.8% in cohort C, including eight patients who reported at least one major symptom and were referred to Andrology Unit. No significant differences in the endocrine assessment were reported between cohorts A and B. CONCLUSIONS: Symptoms of androgen deficiency should be tracked in male patients with ALK-positive ANSCLC who are receiving alectinib, and testosterone replacement should be considered, as appropriate.

2023 ASCO genitourinary cancers symposium: focus on renal cell carcinoma.

This article describes the main acquisitions of renal cell carcinoma (RCC) management presented during the 2023 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium. In particular, the efficacy of adjuvant pembrolizumab in patients with resected renal cell carcinoma (RCC) at increased risk of recurrence was confirmed through a subgroup analysis. In the metastatic setting, the updated analysis of the CheckMate 9ER study confirmed the efficacy in terms of overall survival (OS) of the combination of nivolumab plus cabozantinib; of note, this survival advantage was clear in the subgroup of patients at poor IMDC prognosis, but not in favorable IMDC risk group patients. As concern the triplet therapy (i.e. nivolumab+ipilumumab+cabozantinib), the updated analysis of the COSMIC-313 study confirmed a significant PFS advantage in the subgroup of mRCC patients at intermediate IMDC risk, while the lack of benefit in the poor risk group supports the critical role of immunotherapy (but not of VEGFR-TKIs) in this poor prognosis subgroup of patients. Finally, the activity of cabozantinib as second-line therapy after progression to ICI-based combinations was prospectively assessed. This 2023 ASCO Genitourinary Cancer Symposium laid the foundations for further knowledge development necessary for an increasingly personalized management of mRCC.

Multiplex Proteomic Evaluation in Inborn Errors with Deregulated IgE Response.

(1) Background: Atopic dermatitis constitutes one of the most common inflammatory skin manifestations of the pediatric population. The onset of many inborn errors occurs early in life with an AD-like picture associated with a deregulated IgE response. The availability of proteomic tests for the simultaneous evaluation of hundreds of molecules allows for more precise diagnosis in these cases. (2) Methods: Comparative genomic hybridization microarray (Array-CGH) analysis and specific IgE evaluation by using allergenic microarray (ISAC) and microarray (ALEX2) systems were performed. (3) Results: Proteomic investigations that use multiplex methods have proven to be extremely useful to diagnose the sensitization profile in inborn errors with deregulated IgE synthesis. Four patients with rare diseases, such as recessive X-linked ichthyosis (RXLI, OMIM 308100), Comel-Netherton syndrome (NS, OMIM256500), monosomy 1p36 syndrome (OMIM: 607872), and a microduplication of Xp11.4 associated with extremely high levels of IgE: 7.710 kU/L, 5.300 kU/L, 1.826 kU/L, and 10.430 kU/L, respectively, were evaluated by micro- and macroarray multiplex methods. Polyreactivity to both environmental and food allergens was observed in all cases, including the first described case of association of X-chromosome microduplication and HIE. (4) Conclusions: Extensive use of proteomic diagnostics should be included among the procedures to be implemented in inborn errors with hyper-IgE.

Multimodality treatment in recurrent/metastatic squamous cell carcinoma of head and neck: current therapy, challenges, and future perspectives.

Squamous cell carcinoma of the head and neck is a complex group of diseases that presents a challenge to the clinician. The prognosis in the recurrent/metastatic disease is particularly dismal, with a median survival of approximately 12 months. Recently, the personalized and multimodal approach has increased prognosis by integrating locoregional strategies (salvage surgery and stereotactic radiotherapy) and systemic treatments (chemotherapy, immunotherapy, and target therapy). Malnutrition is a significant clinical problem that interferes with dose intensity, and thus, feeding supplementation is critical not only to increase the quality of life but also to improve overall survival. With this review, we want to emphasize the importance of the multidisciplinary approach, quality of life, and nutritional supportive care and to integrate the latest updates of predictive biomarkers for immunotherapy and future therapeutic strategies.

The role of immune profile in predicting outcomes in cancer patients treated with immunotherapy.

Background: Despite the efficacy of immunotherapy, only a small percentage of patients achieves a long-term benefit in terms of overall survival. The aim of this study was to define an immune profile predicting the response to immune checkpoint inhibitors (ICIs). Methods: Patients with advanced solid tumors, who underwent ICI treatment were enrolled in this prospective study. Blood samples were collected at the baseline. Thirteen soluble immune checkpoints, 3 soluble adhesion molecules, 5 chemokines and 11 cytokines were analyzed. The results were associated with oncological outcomes. Results: Regardless of tumor type, patients with values of sTIM3, IFNα, IFNγ, IL1ß, IL1α, IL12p70, MIP1ß, IL13, sCD28, sGITR, sPDL1, IL10 and TNFα below the median had longer overall survival (p<0.05). By using cluster analysis and grouping the patients according to the trend of the molecules, two clusters were found. Cluster A had a significantly higher mean progression free survival (Cluster A=11.9 months vs Cluster B=3.5 months, p<0.01), a higher percentage of disease stability (Cluster A=34.5% vs. Cluster B=0%, p<0.05) and a lower percentage of disease progression (Cluster A=55.2% vs. Cluster B = 94.4%, p=0.04). Conclusion: The combined evaluation of soluble molecules, rather than a single circulating factor, may be more suitable to represent the fitness of the immune system status in each patient and could allow to identify two different prognostic and predictive outcome profiles.

IgE Sensitization Profile in Patients with Netherton Syndrome.

BACKGROUND: Scant data are currently available on the allergen-specific immunoglobulin (Ig)E sensitization profile in primary immunodeficiencies with hyper IgE. Netherton syndrome (NS, OMIM 266500) is an extremely rare form of congenital ichthyosis characterized by congenital scaly erythroderma, hair abnormalities, and deregulated IgE reactivity associated with severe atopic manifestations. OBJECTIVE: The aim of this study was to evaluate the feasibility and reliability of a multiplex proteomic approach in the detection of specific IgE in NS. METHODS: Specific IgE was evaluated in 10 individuals with an established molecular diagnosis of NS using an allergenic molecules microarray (immuno-solid-phase allergen chip). RESULTS: Polireactivity to airway allergens, mainly house dust mites and olive tree pollen, and food allergens were observed in NS. Eighty per cent of patients were responsive to LTP or profilins. A clinical history suggestive of severe egg, milk, and fish allergy was confirmed by reactivity to the thermostable molecules Gal d 1, Bod 8, and parvalbumin Gad c 1, respectively. Latex reactivity was associated with Hev b 5 and 6 reactivity. Two distinct clusters of reactivity were observed after hierarchical analysis. Extremely high IgE levels (> 10,000 kU/L) do not affect the results obtained with microarrays. CONCLUSION: IgE multiplex evaluation allows (i) to profile IgE polyreactivity pictures, in the presence of LTP and profilin sensitization, (ii) to verify the clinical history of food allergy to milk, egg, and seafood, (iii) to confirm the allergic events associated with latex exposure, and (iv) to disclose the presence of preclinical sensitizations in patients affected by primary immunodeficiencies with hyper IgE, such as the NS.

Sequential healing of the elevated sinus floor with different size of antrostomy: a histomorphometric study in rabbits.

PURPOSE: To study the influence of the access window dimensions on the healing at the antrostomy and within the augmented maxillary sinus. MATERIAL AND METHODS: A maxillary sinus augmentation was performed in twenty-four albino New Zealand rabbits. Antrostomies of 3 × 6 mm (small) or 5 × 6 mm (large) in dimensions were randomly prepared in each animal. A collagenated cortico-cancellous porcine bone was used to fill the elevated region, and an equine collagen membrane was placed on the antrostomies. Three different groups were formed, based on the time of euthanasia, i.e., 2, 4, and 8 weeks from surgery. RESULTS: No relevant changes of the height of the augmented sinus were detected over time. Mineralized bone increased between 2 and 4 weeks of healing while remained stable between 4 and 8 weeks. The highest amounts of new bone were found close to the sinus bone walls. No antrostomies were found healed with an even layer of corticalized bone, while large amounts of connective tissue were occupying the antrostomy in both groups. CONCLUSION: Antrostomies of different dimensions resulted in similar outcome in bone formation both in the antrostomy regions and within the elevated sinus.

Effects of a collagen membrane positioned between augmentation material and the sinus mucosa in the elevation of the maxillary sinus floor. An experimental study in sheep.

OBJECTIVE: To assess the influence of a collagen membrane placed subjacent to a pristine sinus mucosa on the healing outcome of a sinus floor elevation procedure. MATERIALS AND METHODS: Eight Pelibuey sheep (Cubano rojo) underwent sinus floor elevation on both sides of the maxilla. At a randomly selected side (test), a collagen membrane was placed subjacent to the sinus mucosa, while the contralateral side (control) was left without the placement of a membrane. Deproteinized bovine bone mineral (DBBM) was used to fill the space created. A collagen membrane was placed bilaterally to cover the access osteotomy. After 4 months, biopsies were harvested and ground sections prepared. Morphometric analysis was performed in four different regions, three within the elevated area and one at the site of the osteotomy. RESULTS: The total percentages of mineralized new bone within the elevated area were 29.4 ± 16.2% and 30.9 ± 9.2% and of marrow spaces 44.0 ± 23.0% and 45.6 ± 14.1%, at the Non-membrane and at the Membrane sites, respectively. A low content of connective tissue within the elevated area was noticed. A higher content of connective tissue was found in the osteotomy region, however. Remnants of DBBM granules were found at a percentage of 17-19%. No statistically significant differences were observed between test and control sites. CONCLUSION: The application of a collagen membrane subjacent to the Schneiderian mucosa in a sinus floor elevation procedure did not influence the healing outcomes at all.

Sequential healing of the elevated sinus floor after applying autologous bone grafting: an experimental study in minipigs.

AIM: To describe the sequential healing after elevation of the maxillary sinus mucosa applying the lateral access technique with the use of autogenous bone grafting without membrane to occlude the osteotomy access. MATERIAL AND METHODS: Immediately after the elevation of the maxillary sinus Schneiderian membrane, applying the lateral access technique in 10 minipigs, autologous bone was harvested from the lateral aspect of the mandibular molar region and ground into particles with a bone mill. The space under the Schneiderian membrane was filled with this graft. No membranes were placed onto the access osteotomy. The healing was evaluated after 15, 30, 90 and 180 days. Paraffin sections were prepared and analyzed histologically. RESULTS: After 15 days of healing, the elevated area was mainly filled with provisional matrix, newly formed bone and some remnants of bone chips, and appeared reduced in volume compared with that at the time of surgery. After 30 days of healing, further shrinkage of the height of the elevated space was found, with similar percentages of the different tissue components. After 90 and 180 days, the area underneath the Schneiderian membrane appeared reduced in volume and condensed toward the base of the sinus. The bone tissues appeared to be more mature, both for the mineralized and the non-mineralized portions, while connective tissue occupied 20% of the space, most likely related to the lack of the use of a membrane occluding the access at the time of surgery. CONCLUSIONS: Suboptimal healing outcomes with respect to augmentation of the space under the sinus floor membrane were documented when autologous bone chips were used as a filler and no membrane was applied to cover the access.

Sequential healing of open extraction sockets. An experimental study in monkeys.

AIM: To describe the sequential healing of open extraction sockets at which no attempts to obtain a primary closure of the coronal access to the alveolus have been made. MATERIAL AND METHODS: The third mandibular premolar was extracted bilaterally in 12 monkeys, and no sutures were applied to close the wound. The healing after 4, 10, 20, 30, 90 and 180 days was morphometrically studied. RESULTS: After 4 days of healing, a blood clot mainly occupied the extraction sockets, with the presence of an inflammatory cells' infiltrate. A void was confined in the central zones of the coronal and middle regions, in continuity with the entrance of the alveoli. At 10 days, the alveolus was occupied by a provisional matrix, with new bone formation lining the socket bony walls. At 20 days, the amount of woven bone was sensibly increasing. At 30 days, the alveolar socket was mainly occupied by mineralized immature bone at different stages of healing. At 90 and 180 days, the amount of mineralized bone decreased and substituted by trabecular bone and bone marrow. Bundle bone decreased from 95.5% at 4 days to 7.6% at 180 days, of the whole length of the inner alveolar surface. CONCLUSIONS: Modeling processes start from the lateral and apical walls of the alveolus, leading to the closure of the socket with newly formed bone within a month from extraction. Remodeling processes will follow the previous stages, resulting in trabecular and bone marrow formation and in a corticalization of the socket access.

Use of a titanium device in lateral sinus floor elevation: an experimental study in monkeys.

AIM: To evaluate the effect of a space-maintaining device fixed to the lateral wall of the maxillary sinus after the elevation of the sinus mucosa on bone filling of the sinus cavity. MATERIAL AND METHODS: Immediately after the elevation of the maxillary sinus Schneiderian membrane accomplished through lateral antrostomy in four monkeys, a titanium device was affixed to the lateral sinus wall protruding into the sinus cavity to maintain the mucosa elevated without the use of grafting material. The healing of the tissue around the implants was evaluated after 3 and 6 months. Ground sections were prepared and analyzed histologically. RESULTS: The void under the elevated sinus membrane, originally filled with the blood clot, was reduced after 3 as well as after 6 months of healing of about 56% and 40.5%, respectively. In seven out of eight cases, the devices had perforated the sinus mucosa. The formation of mineralized bone and bone marrow amounted to about 42% and 69% after 3 and 6 months, respectively. The connective tissue represented about 53% and 23% of the newly formed tissue after 3 and 6 months, respectively. CONCLUSIONS: New bone formation was found below the devices. However, shrinkage of the newly formed tissue was observed both after 3 and 6 months of healing. Hence, the space-maintaining function of the devices used in the present study has to be questioned.

Healing outcomes at implants installed in grafted sites: an experimental study in dogs.

AIM: To evaluate the integration of implants installed using a surgical guide in augmented sites with autologous bone or deproteinized bovine bone mineral (DBBM) blocks, concomitantly with a collagen membrane. MATERIAL AND METHODS: Mandibular molars were extracted bilaterally in six Labrador dogs, the buccal bony wall was removed, and a box-shaped defect was created. After 3 months, flaps were elevated, a bony graft was harvested from the ascending ramus, and secured to the lateral wall of the defect by means of screws. In the left mandibular side, a DBBM block was fixed into the defect. A resorbable membrane was applied at both sides, and the flaps were sutured. After 3 months, flaps were elevated, and a customized device was used as surgical guide to prepare the recipient sites in the interface between grafts and parent bone. One implant was installed in each side of the mandible. After 3 months, biopsies were harvested, and ground sections were prepared for histologic evaluation. RESULTS: One autologous bone block graft was lost before implant installation. The width of the alveolar crest at the test sites (DBBM) was 5.4 ± 1.2 mm before, 9.4 ± 1.2 mm immediately after grafting, and 9.3 ± 1 mm at implant installation. At the control sites (autologous bone), the corresponding values were: 5.2 ± 1, 9 ± 1.2, and 8.7 ± 0.9 mm, respectively. All implants installed were available for histologic evaluation (n = 5). The autologous bone grafts, rich in vessels and cells, were integrated in the parent bone, and only little non-vital bone was found. The BIC% was 56.7 ± 15.6% and 54.2 ± 13.2% at the buccal and lingual aspects, respectively. At the test sites, the DBBM appeared to be embedded into connective tissue, and very little newly formed bone was encountered within the grafts. The BIC% was 5.8 ± 12.3% and 51.3 ± 14.2% at the buccal and lingual aspects, respectively. CONCLUSIONS: Autologous bone blocks used to augment the alveolar bony crest horizontally allowed the complete osseointegration of implants installed after 3 months of healing. However, similar blocks of DBBM did not promote osseointegration, although the installed implants were stable owing to the osseointegration in the sites of the parent bone.

Effect of mismatching abutments on implants with wider platforms--an experimental study in dogs.

AIM: To evaluate the effect of mismatching abutments on implants with a wider platform on the peri-implant hard tissue remodeling and the soft tissue dimensions. MATERIAL AND METHODS: Mandibular premolars and first molars of six Labrador dogs were extracted bilaterally. After 3 months of healing, one tapered implant was installed on each side of the mandibular molar region with the implant shoulder placed at the level of the buccal alveolar bony crest. On the right side of the mandible, an abutment of reduced diameter in relation to the platform of the implant was used, creating a mismatch of 0.85 mm (test), whereas an abutment of the same diameter of the implant platform was affixed in the left side of the mandible (control). The flaps were sutured to allow a non-submerged healing. After 4 months, the animals were sacrificed and ground sections were obtained for histometric assessment. RESULTS: All implants were completely osseo-integrated. Bone levels were superior at the test than at the control sites. However, statistically significant differences were found only at the buccal and proximal aspects. The soft tissue vertical dimension was higher at the control compared with the test sites. However, statistically significant differences were demonstrated only at the buccal aspects. CONCLUSIONS: A mismatch of 0.85 mm between the implant and the abutment yielded more coronal levels of bone-to-implant contact and a reduced height of the peri-implant soft tissue (biologic width), especially at the buccal aspect, if the implant shoulder was placed flush with the level of the buccal alveolar bony crest.

Lack of influence of the Schneiderian membrane in forming new bone apical to implants simultaneously installed with sinus floor elevation: an experimental study in monkeys.

AIM: To describe the early healing processes around the implants installed after elevation of the sinus mucosa applying the lateral access technique without the use of grafting material. MATERIAL AND METHODS: Immediately after the elevation of the maxillary sinus Schneiderian membrane by the lateral approach in eight monkeys, implants were installed without the use of grafting material. The healing of the tissue around the implants was evaluated after 4, 10, 20 and 30 days. Ground sections were prepared and analyzed histologically. RESULTS: After 4 days of healing, the formation of coagulum and provisional matrix was documented within the elevated area. At 10-day interval, sprouts of woven bone were in continuity with the parent bone, and partly in contact with the implant surface at the base of the augmented area. While bone-to-implant contact increased after 20 and 30 days, the area underneath the Schneiderian membrane appeared reduced in volume and condensed toward the apex of the implants. The sinus mucosa was to some extent collapsed onto the implant surface and on the newly formed bone. CONCLUSIONS: The void initially occupied by the coagulum after sinus membrane elevation shrank substantially during the observation period. A lack of influence of the Schneiderian membrane in bone formation apical to implants was documented in the early phase of healing.

Efeito da plataforma Switching sobre os tecidos peri-implantares: estudo experimental em cães / Effect of plataform Switching on peri-implant tissues: an experimental study in dogs

Objetivo: Avaliar a influência da plataforma Switching sobre a remodelação dos tecidos peri-implantares. Material e métodos: Em 6 cães labradores, foram extraídos os pré-molares e primeiro molares inferiores bilateralmente. Após 3 meses de cicatrização, na região correpondente ao 1º molar, foi instalado um implante cônico em cada lado da mandíbula, com o ombro do mesmo posicionado ao nível da crista óssea alveolar vestibular. No lado direito da mandíbula, foi utilizado um pilar de diâmetro reduzido em relação à plataforma do implante, criando uma incompatibilidade de 0,85 milímetros (grupo teste), enquanto no lado esquerdo selecionou-se um pilar do mesmo diâmetro da plataforma do implante (grupo controle). Os retalhos foram suturados permitindo a cicatrização não-submersa. Após 4 meses, os animais foram eutanasiados para obtenção dos cortes histológicos para avaliação histométrica. Resultados: Todos os implantes apresentaram-se completamente osseointegrados. No grupo teste foram observados que os níveis ósseos apresentaram-se superiores ao grupo controle. No entanto, a diferença estatisticamente significativa foi encontrada apenas na região vestibular e na região proximal. A dimensão vertical dos tecidos moles foi maior no grupo controle em comparação ao grupo teste. No entanto, foi encontrada diferença estatisticamente significativa apenas na vestibular. Conclusões: O presente estudo demonstrou diferenças nas dimensões dos tecidos duros e moles peri-implantares (vestibular e proximal) como resultado da incompatibilidade do implante / pilar de 0,85 milímetros, quando o ombro do implante foi posicionado ao nível da crista óssea vestibular...

Aim: to evaluate the effect of platform switching on the peri-implant tissue remodeling. Material & methods: Mandibular premolars and first molars of 6 Labrador dogs were extracted bilaterally. After 3 months of healing, 1 tapered implant was installed on each side of the mandibular molar region with the implant shoulder placed at the level of the alveolar buccal bony crest. On the right side of the mandible, an abutment of reduced diameter in relation to the platform of the implant was used creating a mismatch of 0.85mm (test), while an abutment of the same diameter of the implant platform was affixed in the left side of the mandible (control). The flaps were sutured to allow a non-submerged healing. After 4 months, the animals were sacrificed and ground sections were obtained for histometric assessment. Results: All implants were completely osseointegrated. Bone levels were superior at the test than at the control sites. However, statistically significant differences were found only at the buccal and proximal aspects. The soft tissue vertical dimension was higher at the control compared to the test sites. However, statistically significant differences were demonstrated only or at the buccal aspects. Conclusions: The present study demonstrated differences in peri-implant (buccal and proximal) hard and soft tissue dimensions as a result of an implant/abutment mismatch of 0.85mm, when the implant shoulder was placed at the level of the buccal bony crest

Efeito da plataforma Switching sobre os tecidos peri-implantares: estudo experimental em cães / Effect of plataform Switching on peri-implant tissues: an experimental study in dogs

Objetivo: Avaliar a influência da plataforma Switching sobre a remodelação dos tecidos peri-implantares. Material e métodos: Em 6 cães labradores, foram extraídos os pré-molares e primeiro molares inferiores bilateralmente. Após 3 meses de cicatrização, na região correpondente ao 1º molar, foi instalado um implante cônico em cada lado da mandíbula, com o ombro do mesmo posicionado ao nível da crista óssea alveolar vestibular. No lado direito da mandíbula, foi utilizado um pilar de diâmetro reduzido em relação à plataforma do implante, criando uma incompatibilidade de 0,85 milímetros (grupo teste), enquanto no lado esquerdo selecionou-se um pilar do mesmo diâmetro da plataforma do implante (grupo controle). Os retalhos foram suturados permitindo a cicatrização não-submersa. Após 4 meses, os animais foram eutanasiados para obtenção dos cortes histológicos para avaliação histométrica. Resultados: Todos os implantes apresentaram-se completamente osseointegrados. No grupo teste foram observados que os níveis ósseos apresentaram-se superiores ao grupo controle. No entanto, a diferença estatisticamente significativa foi encontrada apenas na região vestibular e na região proximal. A dimensão vertical dos tecidos moles foi maior no grupo controle em comparação ao grupo teste. No entanto, foi encontrada diferença estatisticamente significativa apenas na vestibular. Conclusões: O presente estudo demonstrou diferenças nas dimensões dos tecidos duros e moles peri-implantares (vestibular e proximal) como resultado da incompatibilidade do implante / pilar de 0,85 milímetros, quando o ombro do implante foi posicionado ao nível da crista óssea vestibular.

Aim: to evaluate the effect of platform switching on the peri-implant tissue remodeling. Material & methods: Mandibular premolars and first molars of 6 Labrador dogs were extracted bilaterally. After 3 months of healing, 1 tapered implant was installed on each side of the mandibular molar region with the implant shoulder placed at the level of the alveolar buccal bony crest. On the right side of the mandible, an abutment of reduced diameter in relation to the platform of the implant was used creating a mismatch of 0.85mm (test), while an abutment of the same diameter of the implant platform was affixed in the left side of the mandible (control). The flaps were sutured to allow a non-submerged healing. After 4 months, the animals were sacrificed and ground sections were obtained for histometric assessment. Results: All implants were completely osseointegrated. Bone levels were superior at the test than at the control sites. However, statistically significant differences were found only at the buccal and proximal aspects. The soft tissue vertical dimension was higher at the control compared to the test sites. However, statistically significant differences were demonstrated only or at the buccal aspects. Conclusions: The present study demonstrated differences in peri-implant (buccal and proximal) hard and soft tissue dimensions as a result of an implant/abutment mismatch of 0.85mm, when the implant shoulder was placed at the level of the buccal bony crest.

Early healing after elevation of the maxillary sinus floor applying a lateral access: a histological study in monkeys.

AIM: To describe the early healing within the void obtained after the elevation of the sinus mucosa and simultaneous implant installation without the use of any grafting material in monkeys. MATERIAL AND METHODS: Implants were installed simultaneously with the elevation of the maxillary sinus using the lateral approach in eight monkeys without the use of grafting material. The healing after 4, 10, 20 and 30 days was evaluated in the area distal to the implants. Paraffin sections were prepared and analyzed using qualitative histological methods. RESULTS: The healing process was initiated by the formation of a coagulum and followed by a provisional matrix and woven bone. Subsequently, a parallel-fiber bone replaced woven bone. The dimension of the elevated area shrank during the healing process. Sprouts of woven bone, present to a moderate extent after 4 days, were more numerous after 10 and 20 days. Newly formed bone originated from the sinus walls and septa, while there was no evidence of participation of the Schneiderian membrane in this process. After 30 days, the window access appeared to be closed by a layer of newly formed trabecular bone. CONCLUSIONS: The coagulum that filled the void distal to the implant after simultaneous elevation of the sinus floor gave rise to newly formed bone. However, the void occupied by the coagulum shrank substantially. The Schneiderian membrane did not provide a basis for new bone formation in the early phase of healing.