Dynamics of lidocaine in topical anesthesia for office-based laryngeal procedures: A pilot study.

OBJECTIVES: To study topical lidocaine for office-based laryngeal procedures recording onset, duration, and subjective experience of topical anesthesia. STUDY DESIGN: Nine healthy volunteers were anesthetized with 4 % lidocaine endoscopically. Laryngeal sensitivity prior to and during anesthesia was recorded until normal sensation returned measured by air-puff sensory testing. Subjective experience of the process was recorded. METHODS: Questionnaires regarding subjective experience were completed prior to, during, and after anesthesia. Laryngeal sensitivity via air-pulse trigger of the laryngeal adductor reflex (LAR) prior to and after 3 mL shower of 4 % lidocaine was recorded at 30 second intervals until the larynx was insensate with no LAR at 10 mmHg. Time to anesthesia was recorded and post-endoscopy questionnaire was given. Upon subjective change in sensation, sensitivity via air-pulse trigger of the LAR was recorded until baseline sensation returned. A post-anesthesia questionnaire recorded the subjective experience. RESULTS: Average time to full anesthesia was 110 s (±31.2). Subjective return of sensation was noted at 10 min (±2.5), however time to return to normal LAR was 22 min (±5.8). Based on three standard deviations, 99.7 % of the population will be anesthetized at 3.4 min, report subjective change at 18.2 min and regain full sensation at 40 min. CONCLUSIONS: Office-based laryngeal procedures should be performed at least 2 min following topical 4 % lidocaine with a window for manipulation of at least 16 min. Oral intake should be delayed for over 45 min to ensure complete return of sensation. The laryngeal shower of lidocaine is subjectively tolerated. LEVEL OF EVIDENCE: 2C Outcomes Research.

Long-Acting Cabotegravir Protects Macaques Against Repeated Penile Simian-Human Immunodeficiency Virus Exposures.

We used a novel penile simian-human immunodeficiency virus (SHIV) transmission model to investigate whether long-acting cabotegravir (CAB LA) prevents penile SHIV acquisition in macaques. Twenty-two macaques were exposed to SHIV via the foreskin and urethra once weekly for 12 weeks. Of these, 6 received human-equivalent doses of CAB LA, 6 received oral emtricitabine/tenofovir disoproxil fumarate, and 10 were untreated. The efficacy of CAB LA was high (94.4%; 95% confidence interval, 58.2%-99.3%) and similar to that seen with oral emtricitabine/tenofovir disoproxil fumarate (94.0%; 55.1%-99.2%). The high efficacy of CAB LA in the penile transmission model supports extending the clinical advancement of CAB LA preexposure prophylaxis to heterosexual men.

Novel fatty acyl apoE mimetic peptides have increased potency to reduce plasma cholesterol in mice and macaques.

Ac-hE18A-NH2 is a dual-domain apoE mimetic peptide that possesses the putative receptor binding domain from apoE (LRKLRKRLLR, denoted hE; residues 141-150) covalently attached to lipid-associating peptide 18A. Like apoE, Ac-hE18A-NH2 reduces plasma cholesterol in animal models and exhibits anti-inflammatory properties independent of its cholesterol-reducing effect. Ac-hE18A-NH2 has already undergone phase I clinical trials as a lipid-lowering agent. To explore the therapeutic potential more, we designed and synthesized new analogues by linking ɑ-aminohexanoic acid, octanoic acid, or myristic acid to LRRLRRRLLR-18A-NH2 ([R]hE18A-NH2) and examined the cholesterol-lowering potency in animals. The modified peptides effectively reduced plasma cholesterol in apoE-null mice fed standard chow or a Western diet; the myristyl analogue was the most effective. A single administration of the myristyl analogue reduced plasma total and LDL cholesterol in a dose-dependent manner in hypercholesterolemic cynomolgus macaques for up to 1 week despite the continuation of a cholesterol-supplemented diet. The myristyl peptide (7.4 mg/kg) reduced total and LDL cholesterol at 24 h by 64% and 74%, respectively; plasma HDL levels were modestly reduced and returned to baseline by day 7. These new analogues should exhibit enhanced potency at lower doses than Ac-hE18A-NH2, which may make them attractive therapeutic candidates for clinical trials.

Immediate Implant Placement of a Single Central Incisor Using a CAD/CAM Crown-Root Form Technique: Provisional to Final Restoration.

OBJECTIVE: Preserving soft and hard tissues after extraction and implant placement is crucial for anterior esthetics. This technique will show how the information gathered from a cone-beam computed tomography (CBCT) scan of the maxillary left central incisor and an intra-oral digital impression can be merged to fabricate a CAD/CAM crown-root matrix to be used as an immediate provisional restoration that mimics the natural anatomy. CLINICAL CONSIDERATIONS: Due to trauma, a left central incisor appeared to be fractured and was scheduled for extraction and implant placement. The crown-root configuration captured by the CBCT scan was merged with the digital files from an intra-oral digital impression. A CAD/CAM crown-root matrix was fabricated. Because the matrix shell was fabricated with the exact anatomy of the natural tooth, it replicated the position and three dimensional anatomy of the soft and hard tissue. It was connected to the implant with a customized provisional abutment. A digital impression of a coded healing abutment was made to fabricate the final implant abutment and final restoration. Throughout the treatment time and 36 months after completion, the thickness of tissue, emergence profile, and adjacent papilla was analyzed by clinical evaluation and photography and seemed to be maintained. CONCLUSION: The use of a pre-operative intra-oral digital scan of the clinical crown-root architecture and the CBCT scan of the bone/root anatomy, can be used together to fabricate a CAD/CAM crown-root form provisional matrix. This digital design helps in the preservation of the 3D tissue topography, as well as the final restoration. CLINICAL SIGNIFICANCE: The preservation of soft and hard tissue after extraction and implant placement has always been paramount for ideal anterior implant esthetics. Using the information from digital files from CBCT scans and intra-oral scans may help the clinician identify critical anatomical features that can be replicated in the provisional and final CAD/CAM restoration. (J Esthet Restor Dent 29:13-21, 2017).

Analysis of putative mucosal SHIV susceptibility factors during repeated DMPA treatments in pigtail macaques.

BACKGROUND: Depot-medroxyprogesterone acetate (DMPA) has been associated in some studies with increased HIV susceptibility in women. We used a pigtail macaque model to document the effects of repeated DMPA treatments and their potential contribution to increased SHIV susceptibility. METHODS: Nine pigtails were administered 2.5, 1.5, or 0.5 mg/kg DMPA in study weeks one and four. Menstrual cycling, vaginal epithelial thickness, and other SHIV susceptibility factors were monitored for a mean of 24 study weeks. RESULTS: All DMPA treatments suppressed menstrual cycling and increased vaginal pH. The vaginal epithelium thinned naturally during baseline menstrual cycles (from mean of 351 to 161 µm in late-luteal phase). Following DMPA, the non-nucleated layer was temporarily absent. Two weeks post-second DMPA injection, mean epithelial thickness was 53, 45, and 167 µm for the descending doses, respectively. CONCLUSIONS: All animals showed temporal vaginal epithelial thinning with loss of the non-nucleated layer, and vaginal pH changes post-DMPA injections.

Anti-inflammatory and cholesterol-reducing properties of apolipoprotein mimetics: a review.

Reduced levels of HDL cholesterol (HDL-C) are a strong independent predictor of coronary artery disease (CAD) risk. The major anti-atherogenic function of HDL is to mediate reverse cholesterol transport. This response is highly dependent on apoA-I and apoE, protein components of HDL. Randomized clinical trials have assessed effects of several classes of drugs on plasma cholesterol levels in CAD patients. Agents including cholestyramine, fibrates, niacin, and statins significantly lower LDL cholesterol (LDL-C) and induce modest increases in HDL-C, but tolerance issues and undesirable side effects are common. Additionally, residual risk may be present in patients with persistently low HDL-C and other complications despite a reduction in LDL-C. These observations have fueled interest in the development of new pharmacotherapies that positively impact circulating lipoproteins. The goal of this review is to discuss the therapeutic potential of synthetic apolipoprotein mimetic peptides. These include apoA-I mimetic peptides that have undergone initial clinical assessment. We also discuss newer apoE mimetics that mediate the clearance of atherogenic lipids from the circulation and possess anti-inflammatory properties. One of these (AEM-28) has recently been given orphan drug status and is undergoing clinical trials.

Pharmacokinetic and safety analyses of tenofovir and tenofovir-emtricitabine vaginal tablets in pigtailed macaques.

Vaginal rapidly disintegrating tablets (RDTs) containing tenofovir (TFV) or TFV and emtricitabine (FTC) were evaluated for safety and pharmacokinetics in pigtailed macaques. Two separate animal groups (n = 4) received TFV (10 mg) or TFV-FTC (10 mg each) RDTs, administered near the cervix. A third group (n = 4) received 1 ml TFV gel. Blood plasma, vaginal tissue biopsy specimens, and vaginal fluids were collected before and after product application at 0, 0.5, 1, 4, and 24 h. A disintegration time of <30 min following vaginal application of the RDTs was noted, with negligible effects on local inflammatory cytokines, vaginal pH, and microflora. TFV pharmacokinetics were generally similar for both RDTs and gel, with peak median concentrations in vaginal tissues and vaginal secretions being on the order of 10(4) to 10(5) ng/g (147 to 571 µM) and 10(6) ng/g (12 to 34 mM), respectively, at 1 to 4 h postdose. At 24 h, however, TFV vaginal tissue levels were more sustained after RDT dosing, with median TFV concentrations being approximately 1 log higher than those with gel dosing. FTC pharmacokinetics after combination RDT dosing were similar to those of TFV, with peak median vaginal tissue and fluid levels being on the order of 10(4) ng/g (374 µM) and 10(6) ng/g (32 mM), respectively, at 1 h postdose with levels in fluid remaining high at 24 h. RDTs are a promising alternative vaginal dosage form, delivering TFV and/or FTC at levels that would be considered inhibitory to simian-human immunodeficiency virus in the macaque vaginal microenvironment over a 24-h period.

Preclinical evaluation of the immunomodulatory lymphocyte trafficking drug FTY720 for HIV prevention in the female genital mucosa of macaques.

FTY720 has been shown to reduce inflammatory cytokines and immune cells in the genital mucosa of macaques. This pilot study examined the ability of FTY720 to inhibit HIV acquisition. Systemic treatment with FTY720 failed to prevent or delay vaginal SHIV transmission.

Evaluation of pigtail macaques as a model for the effects of copper intrauterine devices on HIV infection.

BACKGROUND: Long-acting, hormonal contraception may increase HIV risk. Copper intrauterine devices (IUDs) could serve as non-hormonal alternatives. We pilot a pigtail macaque model for evaluating HIV susceptibility factors during copper IUD use. METHODS: Frameless and flexible GyneFix(®) copper IUDs were surgically implanted into three SHIVSF 162p3 -positive macaques via hysterotomy and monitored for up to 4 months. Four macaques served as non-IUD controls. RESULTS: All animals retained the devices without complications. No consistent change in vaginal viral RNA or inflammatory cytokines was seen. Two animals had altered menstrual cycles and experienced marked thinning of vaginal epithelium after IUD insertion. Histological examination of uterine tissue at necropsy revealed endometrial ulceration and lymphocytic inflammation with glandular loss at sites of direct IUD contact. CONCLUSIONS: Although the need for insertion surgery could limit its usefulness, this model will allow studies on copper IUDs and SHIV shedding, disease progression, and HIV susceptibility factors.

Safety and Adverse Events of Medialization Thyroplasty: A Systematic Review.

INTRODUCTION: Unilateral vocal fold paralysis or paresis (UVFP) is a condition that causes significant morbidity due to dysphonia, dysphagia, and aspiration. Type I medialization thyroplasty (MT) is the current mainstay surgical treatment for UVFP. Though widely considered a safe procedure, concerns exist over possible airway complications which can lead to overnight observation. Herein, we report a systematic review of the safety and adverse events of MT to aid in determining the safety of same-day discharge. DATA SOURCES: PubMed and Embase databases. REVIEW METHODS: Our search identified studies investigating complications associated with MT. Articles were selected if published between January 1, 1989 and March 15, 2023. Abstracts were screened, and data were extracted from included studies. Only Type I MT procedures were included; case reports were excluded. Participant characteristics, intervention details, results, and adverse events were extracted. RESULTS: The database query identified 751 abstracts, of which 46 studies met eligibility criteria. A total of 2426 patients underwent MT. The most common implant was Silastic (n = 898, 37.0%) followed by Gore-Tex (n = 664, 27.4%). There were 254 (10.5%) total complications reported; 110 (4.5%) were considered major. The most common complication was nonobstructive hematoma (n = 59, 2.4%) followed by hemorrhage (n = 36, 1.5%). Implant extrusion (n = 24, 0.99%) or displacement (n = 15, 0.62%) occurred mostly in Silastic and Gore-Tex implants. Same-day discharge occurred with 429 patients and was not associated with adverse events. CONCLUSIONS: UVFP can be reliably improved by MT with a low risk of complications. Outpatient MT is a promising treatment with a favorable safety profile. Laryngoscope, 134:1994-2004, 2024.

Cationic peptide mR18L with lipid lowering properties inhibits LPS-induced systemic and liver inflammation in rats.

The cationic single domain peptide mR18L has demonstrated lipid-lowering and anti-atherogenic properties in different dyslipidemic mouse models. Lipopolysaccharide (LPS)-mediated inflammation is considered as one of the potential triggers for atherosclerosis. Here, we evaluated anti-inflammatory effects of mR18L peptide against LPS-mediated inflammation. First, we tested the efficacy and tolerance of 1, 2.5 and 5mg/kg mR18L in normolipidemic rats stimulated with 5mg/kg LPS. LPS and then mR18L were injected in different intraperitoneal regions. By 2h post LPS, mR18L inhibited LPS-mediated plasma TNF-α elevation at all doses, with the effect being stronger for 2.5mg/kg (P<0.05 vs. 1mg/kg, non-significant vs. 5mg/kg). In a similar model, 2.5mg/kg mR18L reduced LPS-mediated inflammation in the liver, as assessed by microscopic examination of liver sections and measurements of iNOS expression in the liver tissue. In plasma, 2.5mg/kg mR18L decreased levels of TNF-α and IL-6, decreased endotoxin activity and enhanced HDL binding to LPS. In another similar experiment, mR18L administered 1h post LPS, prevented elevation of plasma triglycerides by 6h post LPS and increased plasma activity of anti-oxidant enzyme paraoxonase 1, along with noted trends in reducing plasma levels of endotoxin and IL-6. Surface plasmon resonance study revealed that mR18L readily binds LPS. We conclude that mR18L exerts anti-endotoxin activity at least in part due to direct LPS-binding and LPS-neutralizing effects. We suggest that anti-endotoxin activity of mR18L is an important anti-inflammatory property, which may increase anti-atherogenic potential of this promising orally active lipid-lowering peptide.

Deletion of specific immune-modulatory genes from modified vaccinia virus Ankara-based HIV vaccines engenders improved immunogenicity in rhesus macaques.

Modified vaccinia virus Ankara (MVA) is a safe, attenuated orthopoxvirus that is being developed as a vaccine vector but has demonstrated limited immunogenicity in several early-phase clinical trials. Our objective was to rationally improve the immunogenicity of MVA-based HIV/AIDS vaccines via the targeted deletion of specific poxvirus immune-modulatory genes. Vaccines expressing codon-optimized HIV subtype C consensus Env and Gag antigens were generated from MVA vector backbones that (i) harbor simultaneous deletions of four viral immune-modulatory genes, encoding an interleukin-18 (IL-18) binding protein, an IL-1ß receptor, a dominant negative Toll/IL-1 signaling adapter, and CC-chemokine binding protein (MVAΔ4-HIV); (ii) harbor a deletion of an additional (fifth) viral gene, encoding uracil-DNA glycosylase (MVAΔ5-HIV); or (iii) represent the parental MVA backbone as a control (MVA-HIV). We performed head-to-head comparisons of the cellular and humoral immune responses that were elicited by these vectors during homologous prime-boost immunization regimens utilizing either high-dose (2 × 10(8) PFU) or low-dose (1 × 10(7) PFU) intramuscular immunization of rhesus macaques. At all time points, a majority of the HIV-specific T cell responses, elicited by all vectors, were directed against Env, rather than Gag, determinants, as previously observed with other vector systems. Both modified vectors elicited up to 6-fold-higher frequencies of HIV-specific CD8 and CD4 T cell responses and up to 25-fold-higher titers of Env (gp120)-specific binding (nonneutralizing) antibody responses that were relatively transient in nature. While the correlates of protection against HIV infection remain incompletely defined, our results indicate that the rational deletion of specific genes from MVA vectors can positively alter their cellular and humoral immunogenicity profiles in nonhuman primates.

Viral CTL escape mutants are generated in lymph nodes and subsequently become fixed in plasma and rectal mucosa during acute SIV infection of macaques.

SIV(mac239) infection of rhesus macaques (RMs) results in AIDS despite the generation of a strong antiviral cytotoxic T lymphocyte (CTL) response, possibly due to the emergence of viral escape mutants that prevent recognition of infected cells by CTLs. To determine the anatomic origin of these SIV mutants, we longitudinally assessed the presence of CTL escape variants in two MamuA*01-restricted immunodominant epitopes (Tat-SL8 and Gag-CM9) in the plasma, PBMCs, lymph nodes (LN), and rectal biopsies (RB) of fifteen SIV(mac239)-infected RMs. As expected, Gag-CM9 did not exhibit signs of escape before day 84 post infection. In contrast, Tat-SL8 escape mutants were apparent in all tissues by day 14 post infection. Interestingly LNs and plasma exhibited the highest level of escape at day 14 and day 28 post infection, respectively, with the rate of escape in the RB remaining lower throughout the acute infection. The possibility that CTL escape occurs in LNs before RBs is confirmed by the observation that the specific mutants found at high frequency in LNs at day 14 post infection became dominant at day 28 post infection in plasma, PBMC, and RB. Finally, the frequency of escape mutants in plasma at day 28 post infection correlated strongly with the level Tat-SL8-specific CD8 T cells in the LN and PBMC at day 14 post infection. These results indicate that LNs represent the primary source of CTL escape mutants during the acute phase of SIV(mac239) infection, suggesting that LNs are the main anatomic sites of virus replication and/or the tissues in which CTL pressure is most effective in selecting SIV escape variants.

A Novel Grading System for Supraglottic Stenosis Based on Morphology and Functional Status.

OBJECTIVE: Currently, no classification system exists to grade the severity of supraglottic stenosis. The aim of this investigation was to (1) develop a novel grading system for supraglottic stenosis that can both enhance communication between providers and relay information about patient functional status and (2) determine the reliability of the grading system. METHODS: A retrospective analysis of patients with supraglottic stenosis at three institutions from 2010-2021 was conducted. After demographic data were collected, two focus group meetings of five laryngologists were held to develop a grading system based on functional status and morphology of stenosis seen on laryngoscopy. Three laryngologists then used the grading system to rate 20 case examples of supraglottic stenosis. Quadratic-weighted kappa coefficients were calculated to assess inter-rater and intra-rater reliabilities of the novel grading system. RESULTS: Twenty-eight patients were included. Epiglottic and arytenoid fixation were morphological features associated with worse functional outcomes such as requiring a G-tube or a tracheostomy, respectively. Inter-rater reliability was substantial to almost perfect (Kw = 0.79-0.81) and intra-rater reliability was almost perfect for all raters (0.88-1.0) when using the novel grading system. CONCLUSION: A grading system for supraglottic stenosis has been proposed with strong inter-rater and intra-rater reliabilities. The proposed system has the advantage of being descriptive of both patient functionality and morphology of the stenosis. LEVEL OF EVIDENCE: 3-According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines, this non-randomized retrospective cohort study is classified as level 3 evidence Laryngoscope, 133:1442-1447, 2023.

Treatments for Age-related Vocal Atrophy: A Systematic Review.

OBJECTIVE: Age-related vocal atrophy (ARVA) can dramatically affect voice, communication, and quality of life. The objectives of this systematic review were to (1) determine whether treatments for ARVA were superior to controls (2) compare the relative efficacy of procedural and behavioral treatments (3) review the various types of outcome measures, and (4) evaluate the quality of studies. REVIEW METHODS: The literature was searched using strategies designed by a medical librarian (2/18/21, updated 3/9/22). Studies investigating treatments for bilateral vocal atrophy were included. Studies involving unilateral atrophy, presbyphonia (without endoscopic findings), or an absent comparator group were excluded. The Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist was used to guide this study. RESULTS: After applying the inclusion/exclusion criteria, 8 articles remained, including 4 randomized trials and 4 cohort studies, and a narrative synthesis was performed. Surgical and behavioral treatments for ARVA appeared to be superior to control groups, based on specific outcome measures. However, the superiority of these treatments over controls was not uniformly observed across multiple outcome measures. When comparing different treatments, superiority could not be established based on the quality and completeness of the studies included in the systematic review. Outcome measures also varied between individual studies. Finally, the risk of bias was analyzed and scored. Consistent point deductions among reviewed studies were noted. CONCLUSIONS: When comparing treatments for ARVA. Surgery and voice therapy were both superior to control groups based on specific outcome measures from different domains. Superiority of one treatment could not be established. LEVEL OF EVIDENCE: N/A Laryngoscope, 133:2846-2855, 2023.

Broadly neutralizing antibody-mediated protection against simian-HIV infection among macaques with vaginal sexually transmitted infections.

OBJECTIVE: Sexually transmitted infections (STIs) increase mucosal HIV infection risk and have the potential to reduce preexposure prophylaxis efficacy. Clinical trials of a broadly neutralizing antibody (bNAb) provided proof-of-concept that passive immunization against HIV can be efficacious in people. We sought to evaluate preclinically the protective efficacy of passive bNAb immunization against simian-human immunodeficiency virus (SHIV) infection in the context of concurrent vaginal STIs. DESIGN: Using a macaque model of combined ulcerative and nonulcerative vaginal STIs caused by Treponema pallidum , Chlamydia trachomatis , and Trichomonas vaginalis , we determined the protection that passively administered bNAb 10-1074 conferred against repeated vaginal SHIV challenges and compared correlates of protection to contemporaneous and historical controls without STIs. METHODS: Plasma viremia was monitored via RT-qPCR assay. Concentrations of 10-1074 were determined longitudinally in plasma samples via TZM-bl pseudovirus neutralization assay. RESULTS: Among macaques with vaginal STIs, a single subcutaneous injection of 10-1074 durably protected against vaginal SHIV acquisition, as compared with untreated controls. Interestingly, the median plasma concentration of 10-1074 at the time of SHIV breakthrough among macaques with STIs was significantly higher (10-fold) than that previously observed among 10-1074-treated macaques in the absence of STIs. CONCLUSION: Passive immunization with 10-1074 conferred significant protection against repeated vaginal SHIV challenges among macaques harboring vaginal STIs. However, our findings suggest that higher bNAb concentrations may be required for prophylaxis when STIs are present. Our findings potentially impact dose selection for the clinical development of bNAbs and highlight the importance of additional preclinical efficacy testing in STI models.

Sidedness of interfacial arginine residues and anti-atherogenicity of apolipoprotein A-I mimetic peptides.

To test the hypothesis that sidedness of interfacial arginine (Arg) in apoA-I mimetic peptides, similar to that observed in apoA-I (Bashtovyy, D. et al. 2011. Sequence conservation of apolipoprotein A-I affords novel insights into HDL structure-function. J. Lipid Res. 52: 435-450.), may be important for biological activity, we compared properties of 4F and analogs, [K4,¹5>R]4F and [K9,¹³>R]4F, with Lys>Arg substitutions on the right and left side, respectively, of the 4F amphipathic helix. Intraperitoneal administration of these peptides into female apoE null mice (n = 13 in each group) reduced en face lesions significantly compared with controls; 4F and [K4,¹5>R]4F were equally effective whereas [K9,¹³>R]4F was less effective. Turnover experiments indicated that [K4,¹5>R]4F reached the highest, whereas [K9,¹³>R]4F had the lowest, plasma peak levels with a similar half life as the [K4,¹5>R]4F analog. The half life of 4F was two times longer than the other two peptides. The order in their abilities to associate with HDL in human plasma, generation of apoA-I particles with pre-ß mobility from isolated HDL, lipid associating ability, and sensitivity of lipid complexes to trypsin digestion was: 4F>[K4,¹5,>R]4F>[K9,¹³>R]4F. These studies support our hypothesis that the sidedness of interfacial Arg residues in the polar face of apoA-I mimetics results in differential biological properties.

Vaccine-induced T cells provide partial protection against high-dose rectal SIVmac239 challenge of rhesus macaques.

Despite enormous efforts by the scientific community, an effective HIV vaccine remains elusive. To further address to what degree T cells in absence of antibodies may protect against simian immunodeficiency virus (SIV) disease progression, rhesus macaques were vaccinated intramuscularly with a chimpanzee-derived Ad vector (AdC) serotype 6 and then boosted intramuscularly with a serologically distinct AdC vector of serotype 7 both expressing Gag of SIVmac239. Animals were subsequently boosted intramuscularly with a modified vaccinia Ankara (MVA) virus expressing Gag and Tat of the homologous SIV before mucosal challenge with a high dose of SIVmac239 given rectally. Whereas vaccinated animals showed only a modest reduction of viral loads, their overall survival was improved, in association with a substantial protection from the loss of CD4(+) T cells. In addition, the two vaccinated Mamu-A*01(+) macaques controlled viral loads to levels below detection within weeks after challenge. These data strongly suggest that T cells, while unable to affect SIV acquisition upon high-dose rectal infection, can reduce disease progression. Induction of potent T-cell responses should thus remain a component of our efforts to develop an efficacious vaccine to HIV-1.

The dual-zone therapeutic concept of managing immediate implant placement and provisional restoration in anterior extraction sockets.

Improvements in implant designs have helped advance successful immediate anterior implant placement into fresh extraction sockets. Clinical techniques described in this case enable practitioners to achieve predictable esthetic success using a method that limits the amount of buccal contour change of the extraction site ridge and potentially enhances the thickness of the peri-implant soft tissues coronal to the implant-abutment interface. This approach involves atraumatic tooth removal without flap elevation, and placing a bone graft into the residual gap around an immediate fresh-socket anterior implant with a screw-retained provisional restoration acting as a prosthetic socket seal device.

Assessing the Clinical Utility of the Early Postoperative Pharyngogram in Hypopharyngeal Surgery for Dysphagia.

OBJECTIVES/HYPOTHESIS: To evaluate the clinical utility of postoperative contrast x-ray pharyngograms (XRP) for detecting pharyngoesophageal leaks following hypopharyngeal dysphagia surgery. STUDY DESIGN: Retrospective cohort study. METHODS: Medical records were reviewed of patients undergoing endoscopic (E-) or open (O-) Zenker's diverticulectomy (-ZD) with cricopharyngeal myotomy (-CPM) and CPM alone from 2008 to 2020 at one academic institution. Exclusion criteria were patients who were fed enterally or underwent repair of epiphrenic diverticula or O-CPM during laryngectomy. XRP clinical indication, impact on clinical care, and factors associated with use patterns were examined using descriptive statistics and logistic regression (LR). RESULTS: Of 152 subjects, 52% underwent O-ZD, 30% O-CPM, 15% E-ZD, and 3% E-CPM. An XRP was ordered for 65% of subjects, mostly routinely (94%). Among the four clinically apparent leaks observed in this cohort, early postoperative XRP confirmed one. It did not identify any clinically silent leaks. In univariate LR, undergoing XRP was associated with increasing day of diet advancement (odds ratio [OR] 4.7, 95% confidence interval [CI] 2.5-10.5) and hospital stay duration (OR 3.2, 95% CI 2.1-5.2), as well as surgeon specialty of otolaryngology compared to general surgery (OR 12.8, 95% CI 4.8-40.8) and procedure sub-type (O-CPM: OR 0.03, 95% CI 0.002-0.16). In multivariate LR, the following variables were significantly associated with XRP use: hospital stay (OR 1.7; 95% CI 1.1-3.0), otolaryngology (OR 105; 95% CI 15.4-2193), O-CPM (OR 0.03; 95% CI 0.002-0.16), and E-CPM (OR 0.04, 95% CI 0.002-0.60). CONCLUSIONS: Prospective, multi-institutional studies are needed to confirm the low clinical utility we observed of early, postoperative XRP following hypopharyngeal surgery for dysphagia. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:272-277, 2022.