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Objective: To explore the speech outcomes of adult patients with repaired cleft palate through subjective perception evaluation and objective acoustic analysis, and to compare the differences in pronunciation characteristics between speakers with complete velopharyngeal closure (VPC) and velopharyngeal insufficiency (VPI) patients., Participants and Intervention: Subjective evaluation indicators included speech intelligibility, nasality and consonant missing rate, for objective acoustic analysis, we used speech sample normalization and objective acoustic parameters included normalized vowel formants, voice onset time and the analysis of 3-dimensional spectrogram and spectrum, were carried out on speech samples produced by 3 groups of speakers: (a) speakers with velopharyngeal competence after palatorrhaphy (n=38); (b) speakers with velopharyngeal incompetence after palatorrhaphy (n=70), (c) adult patients with cleft palate (n=65) and (d) typical speakers (n=30)., Results: There was a highly negative correlation between VPC grade and speech intelligibility (ρ=-0.933), and a highly positive correlation between VPC and nasality (ρ=0.813). In subjective evaluation, the speech level of VPI patients was significantly lower than that of VPC patients and normal adults. Although the nasality and consonant loss rate of VPC patients were significantly higher than that of normal adults, the speech intelligibility of VPC patients was not significantly different from that of normal adults. In acoustic analysis, patients with VPI still performed poorly compared with patients with VPC., Conclusions: The speech function of adult cleft palate patients is affected by abnormal palatal structure and bad pronunciation habits. In subjective evaluation, there was no significant difference in speech level between VPC patients and normal adults, whereas there was significant difference between VPI patients and normal adults. The acoustic parameters were different between the 2 groups after cleft palate repair. The condition of palatopharyngeal closure after cleft palate can affect the patient's speech., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Introduction: Tension-type headache (TTH) refers to a type of functionalism disease, which is commonly characterized by recurrent headaches of mild to moderate intensity, bilateral location, pressing or tightening quality, and no aggravation by routine physical activity. Has significantly impacts on people's work and life. Ear acupuncture as a traditional Chinese therapy, showing several advantages (e.g., safety, economy, and less side effects), has been extensively used to treat TTH. However, its curative effect is supported by limited evidence. Accordingly, the present study aims to comprehensively assess the reliability of ear acupuncture in TTH., Methods and Analysis: The study will conduct a systematic review and meta-analysis. Seven databases, including the Embase, Cochrane Library, Pubmed, SinoMed, CNKI, VIP, and Wanfang Data, will be searched using predefined search terms to identify relevant studies. The primary outcomes will be the pain intensity, the pain frequency and the impact of headache. The methodological quality of the included studies will be assessed with a previously established checklist. The Cochrane Collaboration's bias risk tool will be used for assessing the bias of included RCTs. Stata 17.0 software is used for meta-analysis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To explore the speech outcomes of adult patients through subjective perception evaluation and objective acoustic analysis, and to compare the differences in pronunciation characteristics between speakers with adult patients with unrepaired cleft palate and their non-cleft peers., Participants and Intervention: Subjective evaluation indicators included speech intelligibility, nasality, and consonant missing rate, whereas objective acoustic parameters included normalized vowel formants, voice onset time, and the analysis of three-dimensional spectrogram and spectrum, were carried out on speech samples produced by 2 groups of speakers: (a) speakers with unrepaired cleft palate ( n = 65, mean age = 25.1 years) and (b) typical speakers ( n = 30, mean age = 23.7 years)., Results: Compared with typical speakers, individuals with unrepaired cleft palate exhibited a lower speech intelligibility with higher nasality and consonant missing rate, the missing rate is highest for the 6 consonants syllables The acoustic parameters are mainly manifested as differences in vowel formants and voice onset time., Conclusions: The results revealed important acoustical differences between adult patients with unrepaired cleft palate and typical speakers. The trend of spectral deviation may have contributed to the difficulty in producing pressure vowels and aspirated consonants in individuals with speech disorders related to cleft palate., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Competing Interests: The authors have no conflicts of interest to disclose.

Objective: By measuring velopharyngeal structure and evaluating speech intelligibility, to explore and observe the association between velopharyngeal anatomy and speech outcomes in these patients., Methods: Thirty-one adult patients with velopharyngeal insufficiency after the primary palatoplasty aged 18 to 35 years (mean 22.03 years) were enrolled as the study group. The patients had significant hypernasality and audible nasal emission. The degree of velopharyngeal closure assessed by electronic nasopharyngeal fiberoptic endoscopy was grade III. Cephalometric analysis was performed on lateral cephalograms to measure velopharyngeal structure, including hard palate length (ANS-PNS), velar length (PNS-U), pharyngeal depth (PNS-PPW), and oropharyngeal airway space (U-MPW). Their speech intelligibility was evaluated through the Mandarin Chinese speech intelligibility test, and each speech sample was examined by 2 speech and language pathologists. The results were assessed with the SPSS 23.0 software package, and regression analysis was used to examine the relationship between velopharyngeal structure and speech outcomes., Results: A significant negative correlation was confirmed between speech intelligibility and pharyngeal depth. Pharyngeal depth also showed a linear relationship with speech intelligibility, and there was no significant correlation between speech intelligibility and other measures (hard palate length, velar length, oropharyngeal airway space)., Conclusions: In the velopharyngeal anatomy, only pharyngeal depth was associated with speech intelligibility in adult patients with severe velopharyngeal insufficiency, this is consistent with our clinical observation. It suggests that appropriate reduction of pharyngeal depth during palatopharyngoplasty may have a good effect on the speech recovery in patients with cleft palate and patients with velopharyngeal insufficiency after palatorrhaphy., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Objectives: Patient safety climate is associated with patient outcomes in hospitals around the world. A better understanding of how safety climate varies within and across hospitals will help identify improvement opportunities. We examined variations in safety climate by work area and job category in Chinese hospitals., Methods: We administered the Chinese Hospital Survey on Patient Safety Climate in 2011 to workers in 6 hospitals in China, with completed surveys from 1464 (86% response). We calculated the percent positive response for survey items and dimensions among hospitals and compared this across work areas and job categories using general linear models., Results: Overall, 68% of responses suggested the presence of a positive safety climate. The percent positive responses were highest for organizational learning (86.1%) and unit management support for safety (84.5%) and lowest for staffing (30.6%) and error reporting (44.5%). Workers in surgical units, intensive care units, operating rooms, and emergency departments were slightly more negative regarding overall safety climate than those in medical and ancillary units. Physicians reported worse perceptions than nurses or other hospital workers on all dimensions except for unit management support for safety and communication and peer support., Conclusions: The perceived problem with staffing in Chinese hospitals was consistent with other studies. The lack of positive responses for error reporting may indicate a lack of awareness of the importance of learning from and reporting minor events and near misses. Variations within and across hospitals in safety climate suggest that improvement interventions should be tailored to individual units and professional groups., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study compared the speech outcomes of adult velopharyngeal insufficiency patients and adult cleft palate (ACP) patients, and explored whether there was any difference in the phonological level of these 2 types of patients., Methods: Perceptual evaluation was used to assess speech intelligibility, hypernasality and compensatory articulation in 89 adult patients with velopharyngeal insufficiency and 35 adult patients with unrepaired cleft palate. Each group was divided into complete cleft palate and incomplete cleft palate (including submucous cleft palate). The phonological differences were compared between the 2 groups of patients and 2 types of cleft palate., Results: The mean speech intelligibility was 43.04% in velopharyngeal insufficiency group and 32.87% in ACP group. There was a significant difference in speech intelligibility between the 2 groups by T test, t = 2.916 (P < 0.01), speech intelligibility between 2 types of cleft palate was no significant difference. Also, there was a significant difference between the 2 groups in the constitution of hypernasality degree by Chi-Square test, x2 = 31.650 (P < 0.01), compensatory articulation were present in 74.3% ACP patients (26/35) and 47.2% velopharyngeal insufficiency patients (42/89), x2 = 7.446 (P < 0.01), there was a significant difference in incidence of compensatory articulation between the 2 groups., Conclusions: Adult patients with unpaired cleft palate present an even worse speech intelligibility and hypernasality degree than velopharyngeal insufficiency patients after cleft palate repair, regardless of the cleft type. Additionally, patients in ACP group have a higher incidence of compensatory articulation than that in incomplete cleft palate group. In sequenced treatments of cleft lip and palate, evaluation and treatment of speech disorders cannot be ignored., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 by Mutaz B. Habal, MD.)

Rationale: Primary retroperitoneal germ cell tumors are uncommon and especially rare in female patients. However, this type should be included in the differential diagnosis of retroperitoneal tumors that may metastasize from the gonads and be a primary tumor., Patient Concerns: An abdominal mass was detected in a 38-year-old woman during physical examination, which was accompanied by left renal obstructive hydrops. She was admitted to our institution for further investigation. The patient had no obvious clinical symptoms, and the levels of serum tumor markers did not signifificantly increase. Abdominal noncontrast enhanced and contrast-enhanced computed tomography revealed a retroperitoneal neoplasm that invaded the left ureter, thereby causing left hydronephrosis., Diagnoses: Imaging examination characterized the tumor as malignant based on its invasion in the left ureter. Histopathology and immunohistochemistry confifirmed the resected tumor as a dysgerminoma. The primary gonad-derived germ cell tumor was not found in the pelvis; therefore, the patient was fifinally diagnosed with primary retroperitoneal germ cell tumor., Interventions: Preoperative examination was completed, and the retroperitoneal mass was resected., Outcomes: During the short-term follow-up, no tumor recurrence was detected., Lessons: Primary retroperitoneal seminoma should be included in the differential diagnosis of primary retroperitoneal tumors in female patients. The primary retroperitoneal seminoma/anaplastic tumor has an obvious occupying effect and can easily invade the surrounding structures. However, surgical resection of such tumors is an optional treatment strategy.

This article reports a clinical case of a boy who underwent an avulsion of the upper right central incisor at 8 years old. The avulsed tooth was kept in the socket for 11 years after replantation. The clinical and radiographic findings after 14 years revealed a complete root resorption, but alveolar bone volume is adequate for future implantation from the recent tomography scans view, even in labial area where alveolar bone morphology is poor.

Background: We conducted a multicenter study to evaluate mapping and ablation of ventricular fibrillation (VF) substrates or VF triggers in early repolarization syndromes (ERS) or J-wave syndrome (JWS)., Methods: We studied 52 patients with ERS (4 women; median age, 35 years) with recurrent VF episodes. Body surface electrocardiographic imaging and endocardial and epicardial electroanatomical mapping of both ventricles were performed during sinus rhythm and VF for localization of triggers, substrates, and drivers. Ablations were performed on VF substrates, defined as areas that had late depolarization abnormalities characterized by low-voltage fractionated late potentials, and VF triggers., Results: Fifty-one of the 52 patients had detailed mapping that revealed 2 phenotypes: group 1 had late depolarization abnormalities predominantly at the right ventricular (RV) epicardium (n=40), and group 2 had no depolarization abnormalities (n=11). Group 1 can be subcategorized into 2 groups: Group 1A included 33 patients with ERS with Brugada electrocardiographic pattern, and group 1B included 7 patients with ERS without Brugada electrocardiographic pattern. Late depolarization areas colocalize with VF driver areas. The anterior RV outflow tract/RV epicardium and the RV inferior epicardium are the major substrate sites for group 1. The Purkinje network is the leading underlying VF trigger in group 2 that had no substrates. Ablations were performed in 43 patients: 31 and 5 group 1 patients had only VF substrate ablation and VF substrates plus VF trigger, respectively (mean, 1.4±0.6 sessions); 6 group 2 patients and 1 patient without group classification had only Purkinje VF trigger ablation (mean, 1.2±0.4 sessions). Ablations were successful in reducing VF recurrences ( P <0.0001). After follow-up of 31±26 months, 39 (91%) had no VF recurrences., Conclusions: There are 2 phenotypes of ERS/J-wave syndrome: one with late depolarization abnormality as the underlying mechanism of high-amplitude J-wave elevation that predominantly resides in the RV outflow tract and RV inferolateral epicardium, serving as an excellent target for ablation, and the other with pure ERS devoid of VF substrates but with VF triggers that are associated with Purkinje sites. Ablation is effective in treating symptomatic patients with ERS/J-wave syndrome with frequent VF episodes.

Median cleft of lower lip and mandible is a rare congenital craniofacial malformation and has been described as isolated clinical reports. Fewer than 100 cases have been reported in the world literature so far, and the first case was reported by French scholar Monroe in 1819. The authors report a patient with median complete cleft of the lower lip and mandible which we made a special repair surgery for him, surgical effect satisfied with the restoration of appearance and function ideal. Therefore, the appropriate period and method of surgical management are very important.

Rationale: Hyperpigmentation is a common skin disease. However, there are few reported cases of Grave's disease with diffuse hyperpigmentation. We hereby described a rare case with diffuse hyperpigmentation induced by Grave's disease., Patient Concerns: A 42-year-old Chinese woman with accumulated general pigmentation of skin was admitted to our hospital in October 2017. On examination, hyperpigmentation was observed throughout the whole body, especially on the extremities and the face., Diagnoses: The patient has elevated levels of serum free thyroxine (FT4), free triiodothyronine (FT3), reduced levels of thyroid-stimulating hormone (TSH) and positive anti-TSH receptor antibody (TRAb). She presented with grade I goiter and a diffusely increased thyroid uptake to 18.5% in thyroid scan. Histopathological examination demonstrated melanin pigmentation in the pigmented skin area. The patient was diagnosed with hyperpigmentation induced by Grave's disease., Interventions: The patient was treated with oral methimazole (15 mg/day) for thyroid dysfunction and beta blocker for symptom control., Outcomes: After a period of treatment with methimazole and beta blocker, symptoms of hyperthyroidism ameliorated and hyperpigmentation abated., Lessons: Our studies proposed that in this case the diffuse hyperpigmentation in Grave's disease was caused by elevated adrenocorticotropic hormone (ACTH) as well as anti- TSH receptor stimulating antibody instead of enhanced capillary fragility. Other potential mechanisms for skin pigmentation in hyperthyroidism still need further exploration.

This study, a subgroup analysis of the data from the Organization Program of DiabEtes INsulIN ManaGement study, aimed to compare the efficacy and safety profiles of acarbose and metformin used in combination with premixed insulin.This analysis included 80 and 192 patients taking only 1 oral antidiabetic drug, classified into acarbose (treated with acarbose + insulin) and metformin groups (treated with metformin + insulin), respectively. The efficacy and safety data were analyzed for within- and between-group differences. The clinical trial registry number was NCT01338376.The percentage of patients who achieved target hemoglobin A1c (HbA1c) <7% in the acarbose and metformin groups were 38.75% and 30.73%, respectively, after a 16-week treatment. The average HbA1c levels in the acarbose and metformin groups were comparable at baseline and decreased significantly in both groups at the end of the study. All 7 blood glucose decreased significantly in both groups at endpoint compared with that at baseline. Insulin consumption was higher in the metformin group in terms of total daily amount and units/kg body weight. Incidences of hypoglycemia were similar in both groups. Body weight changed significantly in both groups from baseline to endpoint, but with no significant difference between the groups. Mean scores of Morisky Medication Adherence Scale improved in both groups at endpoint.Combination of insulin with acarbose or metformin could improve glycemic control in patients with type 2 diabetes mellitus. Acarbose and metformin were found to be comparable in terms of efficacy, weight gain, and incidence of hypoglycemia.

Background: Although sinoatrial node (SAN) dysfunction is a hallmark of human heart failure (HF), the underlying mechanisms remain poorly understood. We aimed to examine the role of adenosine in SAN dysfunction and tachy-brady arrhythmias in chronic HF., Methods and Results: We applied multiple approaches to characterize SAN structure, SAN function, and adenosine A1 receptor expression in control (n=17) and 4-month tachypacing-induced chronic HF (n=18) dogs. Novel intramural optical mapping of coronary-perfused right atrial preparations revealed that adenosine (10 μmol/L) markedly prolonged postpacing SAN conduction time in HF by 206 ± 99 milliseconds (versus 66 ± 21 milliseconds in controls; P=0.02). Adenosine induced SAN intranodal conduction block or microreentry in 6 of 8 dogs with HF versus 0 of 7 controls (P=0.007). Adenosine-induced SAN conduction abnormalities and automaticity depression caused postpacing atrial pauses in HF versus control dogs (17.1 ± 28.9 versus 1.5 ± 1.3 seconds; P<0.001). Furthermore, 10 μmol/L adenosine shortened atrial repolarization and led to pacing-induced atrial fibrillation in 6 of 7 HF versus 0 of 7 control dogs (P=0.002). Adenosine-induced SAN dysfunction and atrial fibrillation were abolished or prevented by adenosine A1 receptor antagonists (50 μmol/L theophylline/1 μmol/L 8-cyclopentyl-1,3-dipropylxanthine). Adenosine A1 receptor protein expression was significantly upregulated during HF in the SAN (by 47 ± 19%) and surrounding atrial myocardium (by 90 ± 40%). Interstitial fibrosis was significantly increased within the SAN in HF versus control dogs (38 ± 4% versus 23 ± 4%; P<0.001)., Conclusions: In chronic HF, adenosine A1 receptor upregulation in SAN pacemaker and atrial cardiomyocytes may increase cardiac sensitivity to adenosine. This effect may exacerbate conduction abnormalities in the structurally impaired SAN, leading to SAN dysfunction, and potentiate atrial repolarization shortening, thereby facilitating atrial fibrillation. Atrial fibrillation may further depress SAN function and lead to tachy-brady arrhythmias in HF., (© 2014 American Heart Association, Inc.)

Background: Several arrhythmogenic mechanisms have been inferred from animal heart failure models. However, the translation of these hypotheses is difficult because of the lack of functional human data. We aimed to investigate the electrophysiological substrate for arrhythmia in human end-stage nonischemic cardiomyopathy., Methods and Results: We optically mapped the coronary-perfused left ventricular wedge preparations from human hearts with end-stage nonischemic cardiomyopathy (heart failure, n=10) and nonfailing hearts (NF, n=10). Molecular remodeling was studied with immunostaining, Western blotting, and histological analyses. Heart failure produced heterogeneous prolongation of action potential duration resulting in the decrease of transmural action potential duration dispersion (64 ± 12 ms versus 129 ± 15 ms in NF, P<0.005). In the failing hearts, transmural activation was significantly slowed from the endocardium (39 ± 3 cm/s versus 49 ± 2 cm/s in NF, P=0.008) to the epicardium (28 ± 3 cm/s versus 40 ± 2 cm/s in NF, P=0.008). Conduction slowing was likely due to connexin 43 (Cx43) downregulation, decreased colocalization of Cx43 with N-cadherin (40 ± 2% versus 52 ± 5% in NF, P=0.02), and an altered distribution of phosphorylated Cx43 isoforms by the upregulation of the dephosphorylated Cx43 in both the subendocardium and subepicardium layers. Failing hearts further demonstrated spatially discordant conduction velocity alternans which resulted in nonuniform propagation discontinuities and wave breaks conditioned by strands of increased interstitial fibrosis (fibrous tissue content in heart failure 16.4 ± 7.7 versus 9.9 ± 1.4% in NF, P=0.02)., Conclusions: Conduction disorder resulting from the anisotropic downregulation of Cx43 expression, the reduction of Cx43 phosphorylation, and increased fibrosis is likely to be a critical component of arrhythmogenic substrate in patients with nonischemic cardiomyopathy.

Rationale: Transmural dispersion of repolarization has been shown to play a role in the genesis of ventricular tachycardia and fibrillation in different animal models of heart failure (HF). Heterogeneous changes of repolarization within the midmyocardial population of ventricular cells have been considered an important contributor to the HF phenotype. However, there is limited electrophysiological data from the human heart., Objective: To study electrophysiological remodeling of transmural repolarization in the failing and nonfailing human hearts., Methods and Results: We optically mapped the action potential duration (APD) in the coronary-perfused scar-free posterior-lateral left ventricular free wall wedge preparations from failing (n=5) and nonfailing (n=5) human hearts. During slow pacing (S1S1=2000 ms), in the nonfailing hearts we observed significant transmural APD gradient: subepicardial, midmyocardial, and subendocardial APD80 were 383+/-21, 455+/-20, and 494+/-22 ms, respectively. In 60% of nonfailing hearts (3 of 5), we found midmyocardial islands of cells that presented a distinctly long APD (537+/-40 ms) and a steep local APD gradient (27+/-7 ms/mm) compared with the neighboring myocardium. HF resulted in prolongation of APD80: 477+/-22 ms, 495+/-29 ms, and 506+/-35 ms for the subepi-, mid-, and subendocardium, respectively, while reducing transmural APD80 difference from 111+/-13 to 29+/-6 ms (P<0.005) and presence of any prominent local APD gradient. In HF, immunostaining revealed a significant reduction of connexin43 expression on the subepicardium., Conclusions: We present for the first time direct experimental evidence of a transmural APD gradient in the human heart. HF results in the heterogeneous prolongation of APD, which significantly reduces the transmural and local APD gradients.

Background: Cardiac hypertrophy is a major risk factor for arrhythmias and sudden cardiac death. However, the underlying signaling mechanisms involved in the induction of arrhythmia and electrophysiological remodeling in cardiac hypertrophy are unclear., Methods and Results: Using an inducible gene-switch approach, we achieved tissue-specific and temporally regulated induction of a well-established hypertrophic pathway, the Ras-Raf-mitogen-activated protein kinases pathway, in adult mouse heart. On Ras activation, the transgenic animal developed ventricular hypertrophy and arrhythmias. The development of ventricular arrhythmias was temporally correlated with electrophysiological remodeling in isolated ventricular myocytes, including action potential prolongation, increased sodium-calcium exchanger activity, reduced outward potassium currents, sarcoplasmic reticulum Ca2+ defects, and loss of protein kinase A-dependent phospholamban phosphorylation. From genome-wide expression profiling, we discovered a selective induction of G alpha inhibiting subunit 1 (Gi alpha1) expression in the Ras transgenic heart. Treatment of transgenic animals with the Gi/o inhibitor pertussis toxin normalized the phospholamban phosphorylation by protein kinase A, reversed the action potential prolongation, and significantly reduced the frequency of cardiac arrhythmias in Ras transgenic animals., Conclusions: These data suggest that selective induction of G alpha inhibiting subunit 1 expression and activity is a novel downstream event in hypertrophic signaling that may be a critical factor leading to cellular electrophysiological remodeling and cardiac arrhythmias in hypertrophic cardiomyopathy.

The purpose of this study was to compare the prevalence of Helicobacter pylori (HP) seropositivity among gastroenterology nurses and technicians with that of the general population. Nurses attending the 1996 Indiana Society of Gastroenterology Nurses and Associates Spring and Fall Education Courses were asked to complete a checklist regarding employment, current symptoms, and use of universal precautions, and to have 3 ml blood drawn. These 138 blood specimens as well as 112 serum samples from generally age- and sex-matched blood donors (representing the general population) underwent qualitative HP antibody testing. Results showed that the prevalence of seropositivity for immunoglobulin G (IgG) antibody for HP among the gastroenterology nurses and technicians was 19 of 138 (13.8%), which was less than that of the blood donor control group, whose seropositivity was 20 of 112 (17.9%). However, this difference failed to reach statistical significance. Seropositivity tended to increase with age, but there was no association between clinical symptomatology and seropositivity. Likewise, there was no difference in seropositivity between nurses assisting with endoscopic procedures for more than 10 years and those assisting for less than 10 years. Although the differences were not significant, these findings refute those of an earlier study in which the researchers found 122 gastroendoscopists and endoscopy nurses significantly more likely to be positive for HP antibodies. Therefore, the findings reported here provide important information.

The authors describe a case of bilateral acute necrotizing retinitis caused by Aspergillus fumigatus in an immunocompromised host. The patient rapidly lose useful vision and expired from progressive systemic disease while on parenteral amphotericin B. Postmortem aqueous cultures were negative whereas vitreous cultures were positive. Light and electron microscopy demonstrated marked choroidal and retinal vascular occlusion by fungi and thrombi, hyphae extending through vessel walls and the internal limiting membrane of the retina, fungi accumulating in tissue spaces, hyphae on the iris surface, and necrosis of the retina. In view of the extensive vascular occlusion present in this disease, early diagnostic vitrectomy plus intravitreal amphotericin B is recommended to deliver adequate drug levels to infected sites.