Bilateral bartholin's gland abscesses in a 4-year-old girl with vitamin a deficiency: a case report.

BACKGROUND: A Bartholin's gland abscess is one of the most common infections in women of reproductive age. Although Bartholin's gland abscesses have been reported in prepubertal children, they are rarer in prepubertal children than in adults. Herein, we report a case of bilateral Bartholin's gland abscesses in a 4-year-old girl with vitamin A deficiency. CASE PRESENTATION: A 4-year-old girl diagnosed with autism spectrum disorder was admitted to the hospital for close examination and treatment because of persistent fever and malaise. The child was a marked fussy eater and was diagnosed with corneal ulceration and night blindness secondary to vitamin A deficiency. Both of the patient's labia were swollen, and a diagnosis of a bilateral Bartholin's gland abscess was made using computed tomography. Incisional drainage was performed under general anesthesia. The patient's postoperative course was uneventful, and she was discharged from the hospital on day 8 after the surgery. During hospitalization, attempts were made to correct the vitamin deficiency by adding nutritional supplements to the diet. Three months after the surgery, no recurrence of abscesses was noted. CONCLUSIONS: Decreased immunocompetence and mucosal barrier function due to vitamin A deficiency is thought to be the underlying cause of Bartholin's gland abscesses. Although prepubertal Bartholin's gland abscesses have been reported, they are rare. To the best of our knowledge, no reports of bilateral Bartholin's gland abscesses potentially caused by vitamin A deficiency have been reported. When prepubertal girls present with Bartholin's gland abscesses, the presence of immunodeficiency due to vitamin or trace element deficiency should also be considered.

Effects of intracordal trafermin injection on mutational voice disorder.

INTRODUCTION: Mutational voice disorder is the inability of the voice to adjust to the changes in the larynx during puberty, resulting in the speaking fundamental frequency failing to decrease. Standard treatments for mutational voice disorder are voice therapy and thyroplasty. However, voice therapy takes time to show its effects, and thyroplasty is highly invasive. Herein, we present a case of mutational voice disorder successfully treated with intracordal trafermin injection. CASE SUMMARY: A 31-year-old male patient was diagnosed with mutational voice disorder and offered standard treatment, but he requested a less invasive treatment with early effects. We performed intracordal trafermin injection with his consent. Two months after the procedure, the speaking fundamental frequency decreased from 155.5 Hz to 93.0 Hz, and the voice handicap index decreased from 14 to 2. DISCUSSION: This case suggests that intracordal trafermin injection is an effective treatment option for mutational voice disorder. Furthermore, compared with the standard treatment methods, it is less invasive and provides effects shortly with only one injection.

Changes in vital signs during adrenaline administration for hemostasis in intracordal injection: an observational study with a hypothetical design of endotracheal adrenaline administration in cardiopulmonary arrest.

BACKGROUND: The background is that intravenous adrenaline administration is recommended for advanced cardiovascular life support in adults and endotracheal administration is given low priority. The reason is that the optimal dose of adrenaline in endotracheal administration is unknown, and it is ethically difficult to design studies of endotracheal adrenaline administration with non-cardiopulmonary arrest. We otolaryngologists think so because we administered adrenaline to the vocal folds for hemostasis after intracordal injection under local anesthesia, but have had few cases of vital changes. We hypothesized that examining vital signs before and after adrenaline administration for hemostasis would help determine the optimal dose of endotracheal adrenaline. METHODS: We retrospectively examined the medical records of 79 patients who visited our hospital from January 2018 to December 2020 and received adrenaline in the vocal folds and trachea for hemostasis by intracordal injection under local anesthesia to investigate changes in heart rate and systolic blood pressure before and after the injection. RESULTS: The mean heart rates before and after injection were 83.96 ± 18.51 (standard deviation) beats per minute (bpm) and 81.50 ± 15.38 (standard deviation) bpm, respectively. The mean systolic blood pressure before and after the injection were 138.13 ± 25.33 (standard deviation) mmHg and 135.72 ± 22.19 (standard deviation) mmHg, respectively. Heart rate and systolic blood pressure had P-values of 0.136, and 0.450, respectively, indicating no significant differences. CONCLUSIONS: Although this study was an observational, changes in vital signs were investigated assuming endotracheal adrenaline administration. The current recommended dose of adrenaline in endotracheal administration with cardiopulmonary arrest may not be effective. In some cases of cardiopulmonary arrest, intravenous and intraosseous routes of adrenaline administration may be difficult and the opportunity for resuscitation may be missed. Therefore, it is desirable to have many options for adrenaline administration. Therefore, if the optimal dose and efficacy of endotracheal adrenaline administration can be clarified, early adrenaline administration will be possible, which will improve return of spontaneous circulation (ROSC) and survival discharge rates.

One Year Outcomes and Longitudinal Changes in Voice Improvement With Single High Dose Intracordal Trafermin Injections for Age-Related Vocal Fold Atrophy.

OBJECTIVE: Although intracordal trafermin injection has been performed in the treatment of age-related vocal fold atrophy, the effects of single high dose trafermin injections are unknown. In this study, we examined the 1 year outcomes and longitudinal changes in voice improvement with single high dose intracordal trafermin injections. STUDY DESIGN: Retrospective study with approval by our Ethics Committee. METHODS: The medical records of 34 patients who underwent single high dose (50ug per side) intracordal trafermin injections under local anesthesia for vocal fold atrophy were retrospectively reviewed at 1 month pre-injection and 1 month, 6 months and 1 year post injection. RESULTS: Maximum phonation time (MPT), pitch range (PR), Japanese version of voice handicap index (VHI), grade of GRBAS evaluation, and jitter% improved significantly at 1-year post-injection compared to 1-month pre-injection. MPT and PR improved as early as 1-month post-injection and continued to improve most at 1-year post-injection. VHI showed negative progression from 6-months to 1-year post-injection, during which time the speaking fundamental frequency (SFF) changed to the high pitch in men. CONCLUSIONS: Single high dose intracordal trafermin injections can be expected to improve voice in the early post-injection period and to maintain its effect for 1 year. SFF may play a role in worsening VHI in men. LEVEL OF EVIDENCE: level 4.

Changes in serum basic fibroblast growth factor concentration following intracordal injection.

Objective: Although many studies have reported improvements in voice outcomes with intracordal trafermin injection, there is a lack of data documenting its changes in serum basic fibroblast growth factor (bFGF) blood concentration. This study examined whether serum bFGF concentrations change after intracordal trafermin injection. Methods: This retrospective study was conducted at Tokyo Voice Center. We investigated serum bFGF concentrations before and after injection in 40 patients who underwent intracordal trafermin injection. There were 26 males and 14 females, with an age ranging from 13 to 88 years (average 53.25 years). They were diagnosed with paralysis (15 patients), atrophy (15 patients), sulcus (8 patients), and others (2 patients: scar and functional), presenting with severe hoarseness that interfered with daily life. Results: The mean pre- and post-injective serum bFGF concentration of the 40 patients was 6.689 and 4.658 pg/mL, respectively. The difference in mean serum bFGF concentration between pre- and post-injective was -2.031 pg/mL. The Pearson correlation coefficient was calculated to evaluate the correlation between dosage of trafermin and post-injective serum bFGF concentration, and a moderate correlation was found at r = 0.52. Generalized linear model regression analysis was performed for the purpose of adjusting for confounding among variables. The only variable that showed a statistically predominant association with post-injective serum bFGF concentrations was the dosage of trafermin, with an estimated regression coefficient of 0.048. Conclusion: In this study, the dosage of trafermin we injected and post-injective serum bFGF concentrations were dose-dependent but the amount of changes in the serum bFGF concentration was negligible within the physiological range. Therefore, as with subcutaneous and wound administration, intracordal trafermin injections may be safe. Level of Evidence: Level IV.

Evaluation of Safety After Intracordal Basic Fibroblast Growth Factor Injection.

OBJECTIVES: Although there are many reports of voice improvement with intracordal trafermin (a basic fibroblast growth factor) injections under local anesthesia, few papers have documented the safety of trafermin. Therefore, we aimed to investigate whether trafermin is safer than control drugs (triamcinolone acetonide) early after intracordal injection under local anesthesia. METHODS: We conducted a retrospective review from the medical records of patients who underwent intracordal injection with trafermin and triamcinolone acetonide under local anesthesia at our institution. Early postinjective complications were defined as changes in vital signs and chief complaints early after intracordal injection. RESULTS: A total of 699 and 297 patients underwent intracordal injection under local anesthesia with trafermin and triamcinolone acetonide, respectively. Of these, 227 and 130 patients had early postinjective complications with trafermin and triamcinolone acetonide, retrospectively. The most common complications occurring with trafermin was increased blood pressure in 39 cases (5.58%): 17 cases (2.43%) of blood pressure increase of ≥20 mm Hg. Other complications included pharyngeal discomfort in 37 (5.29%), lightheadedness in 33 (4.72%), and phlegm discharge in 29 (4.15%). Triamcinolone acetonide caused pharyngeal discomfort in 28 patients (9.43%), phlegm discharge in 17 patients (5.72%), lightheadedness in 12 patients (4.04%), sore throat in 11 patients (3.70%), increased blood pressure in 10 patients (3.37%): 7 cases (2.36%) of blood pressure increase of ≥20 mm Hg, and dizziness in seven patients (2.36%). Statistical analysis of the complications between trafermin and triamcinolone acetonide showed no significant differences. CONCLUSIONS: The proportion of early postinjective complications from intracordal injection of trafermin is no significant difference in that of triamcinolone acetonide. The results suggest that the early postinjective complications are not due to the drug action of trafermin, but rather to complications from the intracordal injection procedures. Intracordal trafermin injection may be safe in the short term.

Age-dependent treatment effect of vocal fold steroid injection for benign vocal fold lesions.

Objective: Benign vocal fold lesions (BVFLs) cause voice disorders and impair social life. Recently, office-based vocal fold steroid injection (VFSI) has gained attention as a minimally invasive treatment for BVFLs. This study aimed to analyze the age-dependent treatment effect of VFSI and to clarify the indications for treatment. Methods: In this retrospective cohort study, a total of 83 patients with BVFLs were treated with a similar regimen of VFSI. Three or four months after the injection, age-dependent phonological functions were evaluated. The differences between pre- and post-treatment findings were analyzed using the Wilcoxon matched-pair signed-rank test, and the correlation between patient age and improvement rates were determined by Pearson's correlation coefficient. Results: Improvement in voice handicap index (VHI), which was the primary endpoint, was observed. Subjective and objective voice quality measurements also showed significant improvements. Subgroup analyses revealed that there was no age-related difference in the improvement of voice quality and that there was no improvement in aerodynamic effect in patients over 45 years of age. Conclusion: This study clarified the age-dependent treatment effect of VFSI and provided the important suggestion of establishing indication criteria for BVFLs. The study results provided clarity on the indication criteria of VFSI and served as an important indicator for tailoring treatment to patients' needs. Level of Evidence: 4.

Intracordal injection therapy for vocal fold scarring: Steroid versus basic fibroblast growth factor.

Objectives: Vocal fold scarring is caused by replacement of vocal fold mucosa with fibrous tissue due to repeated inflammation or trauma. It can lead to severe dysphonia. It is currently treated conservatively and with phonosurgery and intracordal injections. Intracordal injection of steroid or basic fibroblast growth factor (bFGF) has been recently found to be useful for treating vocal fold scarring that does not respond to voice therapy. Methods: This retrospective study involved the administration of steroid injection and bFGF injection bilaterally under local anesthesia in 16 patients each. Laboratory measurements of voice parameters were performed before and 3-6 months after injection. Results: In the steroid injection group, the Voice Handicap Index (VHI) score significantly improved from 57.1 to 40.5, total Grade, Roughness, Breathiness, Asthenia, Strain (tGRBAS) score significantly improved from 4.2 to 2.6, and mean speech fundamental frequency (SFF) increased from 192.5 to 211.4 dB, but there was no improvement in maximum phonation time (MPT) and mean airflow rate (MFR). In the bFGF injection group, significant improvements in the VHI score (from 53.3 to 35.7), MPT (from 16.9 to 21.8 s) and MFR (from 314.6 to 210.5 ml/s) were seen; however, the tGRBAS score did not improve. In addition, the SFF significantly decreased from 178.1 to 160.5 Hz. Conclusion: These results suggest that both steroid and bFGF injections are effective for treating vocal fold scarring, with steroids improving voice quality and bFGF improving glottic closure, thereby contributing to improvements in VHI scores. Level of Evidence: 4.

Long-term results and safety of fibroblast growth factor injection for unilateral vocal fold paralysis.

Objectives: Treatments for unilateral vocal fold paralysis (UVFP) include conservative voice rehabilitation, vocal fold injection, and laryngeal framework surgery. We proposed basic fibroblast growth factor (bFGF) injection as a potential novel treatment for UVFP and have reported the short-term results. In this study, we present the long-term results and safety of vocal fold bFGF injection as a treatment for UVFP. Methods: This retrospective study included 42 patients (25 males and 17 females) with UVFP who were administered a local injection of bFGF. The injection regimen involved injecting FGF (0.5 µg/ml in 0.5 ml per side) into the bilateral vocal folds using a 23-gauge injection needle. Phonological outcomes were evaluated 6 months and 12 months after the injection. Results: Overall, 26 patients received a single injection of bFGF, six patients received an additional injection, and 10 patients received the additional framework surgery. Maximum phonation time, mean flow rate, pitch range, jitter and shimmer percentages, the total GRBAS (grade, roughness, breathiness, asthenia, strain) score, and voice handicap index scores improved significantly in the long term. In patients who received the additional injection or framework surgery, the effects of bFGF injection were temporary, but did not interfere with the performance of the framework surgery. Conclusion: In total, 42 patients who underwent vocal fold bFGF injections were reviewed. The bFGF injections were effective and safe in the long-term results for UVFP in the selected cases. Some patients with severe symptoms benefited from the additional framework surgery but not the additional bFGF injection.

Effect of intracordal injection under local anesthesia on vital signs in high-risk patients.

OBJECTIVE: Intracordal injection under local anesthesia is widely performed; however, few studies show hemodynamic changes in the heart rate, blood oxygen saturation, and blood pressure during intracordal injection under local anesthesia. This study examined changes in vital signs (heart rate, blood oxygen saturation, systolic blood pressure, diastolic blood pressure) during intracordal injection under local anesthesia among high-risk patients and investigated whether intracordal injection under local anesthesia could be safely conducted. METHODS: A retrospective chart review was adopted as the research design. We investigated the changes in vital signs (heart rate, blood oxygen saturation, blood pressure) before and after intracordal injection with basic fibroblast growth factor (bFGF) preparations under local anesthesia in 46 patients who visited our institution and developed unilateral vocal cord paralysis after a thoracic aortic aneurysm, thoracic aortic dissection surgery, thyroid disease, esophageal disease, idiopathic disease, etc. RESULTS: The average operation time for the high-risk group was 3.67 minutes, with the shortest operating time being 2 minutes and the maximum operating time being 13 minutes. The average operation time for the control group was 3.73 minutes, with the shortest operating time being 1 minute and the maximum operating time being 9 minutes. Results before and after intracordal injection with bFGF preparations under local anesthesia for heart rate, blood oxygen saturation, systolic blood pressure, and diastolic blood pressure had P-values of 0.324, 0.394, 0.215, and 0.508, respectively, in the high-risk group, and no significant differences were found. Conversely, heart rate, blood oxygen saturation, systolic blood pressure, and diastolic blood pressure had P-values of 0.057, 0.232, 0.265, and 0.091, respectively, in the control group, and no significant differences were found. CONCLUSION: Intracordal injection under local anesthesia may be safe, even for patients who require blood pressure management after thoracic aortic disease surgery.

Comparison of therapeutic effects of steroid injection by benign vocal fold lesion type.

BACKGROUND: Benign vocal fold lesions (BVFLs) can cause voice changes, including reduced loudness and pitch range. In recent times, with progression in endoscopic technology, office-based vocal fold steroid injection (VFSI) has been used as an alternative therapy for BVFLs. AIMS/OBJECTIVES: In this study, we analyzed the efficacy and safety of VFSI to investigate the mechanism underlying its therapeutic effects and determine the conditions in which VFSI will be most effective. MATERIALS AND METHODS: In this retrospective cohort study, we included 40 condition-matched patients (8 patients per lesion) with chorditis, vocal nodules, vocal polyps, Reinke's edema (RE), or vocal scars who received similar regimens of steroid injection using a commercial preparation of triamcinolone acetonide. Their phonological outcomes were evaluated 2 or 3 months after the injection. RESULTS: Significant improvements were observed in Voice Handicap Index scores, results of laboratory voice evaluation, and voice quality measured using the Grade, Roughness, Breathiness, Asthenia, Strain scale in all participants. In subgroup analysis, VFSI was highly effective against chorditis and vocal nodules, but less effective against RE and vocal scars. CONCLUSIONS: Single-dose VFSI is valuable as an alternative to voice rehabilitation and laryngo-microsurgery, but higher concentrations or repeated injections are required for intractable lesions.

Microlaryngeal surgery in severely obese elite vocal performers.

This study showed that microlaryngeal surgery under general anesthesia is feasible for patients with severe obese elite vocal performers if proper simulations are conducted beforehand and the position of the patient and anesthesia is considered.

Mechanism for H2 diffusion in sII hydrates by molecular dynamics simulations.

Among the many different types of molecules that form clathrate hydrates, H2 is unique as it can easily diffuse into and out of clathrate cages, a process that involves the physical-chemical interactions between guest (H2) and host (water) molecules, and is unlike any other molecular system. The dynamic and nano-scale process of H2 diffusion into binary structure II hydrates, where the large cages are occupied by larger molecules, was studied using molecular dynamics simulation. As the H2 molecules diffused from one cage to another, two types of diffusion processes were observed: (i) when moving between a pair of large cages, the H2 molecules pass through the central part of the hexagonal rings; (ii) however, when the H2 molecules move from a large cage to a small one, it requires one of the pentagonal rings to partially break, as this allows the H2 molecule to pass through the widened space. While the diffusion of H2 molecules between large cages was found to occur more frequently, the presence of SF6 molecules in the large cages was found to inhibit diffusion. Therefore, in order to attain higher H2 storage capacities in binary hydrates, it is suggested that there is an optimal number of large cages that should be occupied by SF6 molecules.

Cage occupancies, lattice constants, and guest chemical potentials for structure II hydrogen clathrate hydrate from Gibbs ensemble Monte Carlo simulations.

In this paper, equilibrium properties of structure II hydrates of hydrogen were determined from Monte Carlo simulations in the isothermal-isobaric Gibbs ensemble. Water and hydrogen molecules are described by the TIP4P/Ice and Silvera-Goldman models, respectively. The use of the Gibbs ensemble has many key advantages for the simulation of hydrates. By the separation of hydrogen vapor and hydrate phases into their own domains, coupled with transfer moves of hydrogen molecules between domains, cage occupancies were determined. Furthermore, the choice of this ensemble also allows equilibrium lattice constants and guest molecule chemical potentials to be straightforwardly estimated. Results for hydrogen mass fractions indicate reasonable agreement with prior simulation data and theoretical models, while detailed analysis of cage occupancy distributions and neighboring cage pair occupancy combinations gives valuable insight into the behavior of this hydrate at the inter-cage scale. These results will aid in the construction of theoretical models, for which knowledge of the occupancy of neighboring cages is of great importance. In support of previous experimental and theoretical works, we also find evidence of double occupancy of a few small cages inside of the hydrate stability zone, albeit at very high pressures; approximately 0.1% of small cages are doubly occupied at 300 MPa, for temperatures of 225 K and 250 K.

Reactivation of immune responses against Mycobacterium tuberculosis by boosting with the CpG oligomer in aged mice primarily vaccinated with Mycobacterium bovis BCG.

BACKGROUND: Mycobacterium bovis bacillus Calmette Guérin (BCG) vaccine, which has been inoculated to more than one billion people world-wide, has significant effect in preventing tuberculous meningitis and miliary tuberculosis (TB) in neonate and early childhood. However, BCG fails to adequately protect against pulmonary TB and reactivation of latent infections in adults. To overcome this problem, adequate booster is urgently desired in adult who received prior BCG vaccination, and appropriate animal models that substitute human cases would be highly valuable for further experimentation. FINDINGS: The booster effect of the synthesized CpG oligomer (Oligo-B) on aged mice which had been primarily vaccinated with BCG at the age of 4-week old. The specific Th1 type reaction, production of interferon-γ, in response to TB antigens, purified protein derivatives (PPD) and protection against challenge with Mycobacterium tuberculosis (MTB) H37Rv decreased with increasing age and were not observed in 89-week old mice. In order to rejuvenate the Th1 type response against PPD and protection activity against MTB infection, Oligo-B, which is known to augment Th1 responses, was administered as a booster to 81-90-week old mice (late 50's in human equivalent) vaccinated with BCG at 4-week old. The boosting with Oligo-B increased the number of CD4+ CD44high CD62Lhigh, central memory type T cell. Furthermore, the Oligo-B boosting rejuvenated the ability of mice to protect against infection with MTB H37Rv. CONCLUSIONS: Th1-adjuvant CpG oligo DNA, such as Oligo-B, may be a promising booster when coupled with BCG priming.

Antitubercular activity of disulfiram, an antialcoholism drug, against multidrug- and extensively drug-resistant Mycobacterium tuberculosis isolates.

The antimycobacterial activities of disulfiram (DSF) and diethyldithiocarbamate (DDC) against multidrug- and extensively drug-resistant tuberculosis (MDR/XDR-TB) clinical isolates were evaluated in vitro. Both DSF and DDC exhibited potent antitubercular activities against 42 clinical isolates of M. tuberculosis, including MDR/XDR-TB strains. Moreover, DSF showed remarkable bactericidal activity ex vivo and in vivo. Therefore, DSF might be a drug repurposed for the treatment of MDR/XDR-TB.

Synthesis and evaluation of anti-tubercular activity of new dithiocarbamate sugar derivatives.

The present study was undertaken to optimize the anti-tubercular activity of 2-acetamido-2-deoxy-ß-D-glucopyranosyl N,N-dimethyldithiocarbamate (OCT313, Glc-NAc-DMDC), a lead compound previously reported by us. Structural modifications of OCT313 included the replacements of the DMDC group at C-1 by pyrrolidine dithiocarbamate (PDTC) and the acetyl group at C-2 by either propyl, butyl, benzyl or oleic acid groups. The antimycobacterial activities of these derivatives were evaluated against Mycobacterium tuberculosis (MTB). Glc-NAc-pyrrolidine dithiocarbamate (OCT313HK, Glc-NAc-PDTC) exhibited the most potent anti-tubercular activity with the minimal inhibitory concentration (MIC) of 6.25-12.5 µg/ml. The antibacterial activity of OCT313HK was highly specific to MTB and Mycobacterium bovis BCG, but not against Mycobacterium avium, Mycobacterium smegmatis, Staphylococcus aureus or Escherichia coli. Importantly, OCT313HK was also effective against MTB clinical isolates, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Interestingly, OCT313HK was exerted the primary bactericidal activity, and it was also exhibited the bacteriolytic activity at high concentrations. We next investigated whether the mycobacterial monooxygenase EthA, a common activator of thiocarbamide-containing anti-tubercular drugs, also activated OCT313HK. Contrary to our expectations, the anti-tubercular activity of dithiocarbamate sugar derivatives and dithiocarbamates were not dependent on ethA expression, in contrast to thiocarbamide-containing drugs. Overall, this study presents OCT313HK as a novel and potent compound against MTB, particularly promising to overcome drug resistance.

Histochemical analysis of renal dysplasia with ureteral atresia.

Unilateral small kidney with ureteral obstruction was discovered in a 74-year-old female cadaver during an anatomical dissection course. In order to elucidate the histogenesis of renal dysplasia, we carried out histochemical and immunohistochemical analyses. On macroscopic view, the kidney was approximately 3 cm in length, 2 cm in width and weighed only 9 g. Although the ureter ran from the renal hilus to the bladder, its width was under 2 mm. The renal parenchyma was extremely thin and there was a large congested vein in the renal sinus. On microscopic examination of the kidney, we observed that numerous developing renal tubules had cytokeratin-positive epithelia, most of which were surrounded by concentric fibrosis. However, we could not detect any structures resembling the collecting duct, renal tubules, renal pelvis, or glomeruli. The concentric mesencymal fibrous tissue surrounding the immature renal tubules contained the smooth muscles that were positive for h-caldesmon. Serial sections of the ureter revealed several small and discontinuous lacunae lined by cuboidal and transitional epithelium, which did not constitute a patent lumen through the bladder. This case is a rare case of renal dysplasia with defect in recanalization of the ureteral bud during the early developmental stage.