Retrospective study in 1020 cases on the rate of surgical site infections after lacrimal surgery without prophylactic systemic antibiotics.

BACKGROUND/AIMS: Data regarding the effectiveness of prophylactic systemic antibiotics (PSA) in lacrimal surgery is scarce. Therefore, we determined the postoperative surgical site infection (SSI) rate in lacrimal surgery without PSA. METHODS: We retrospectively analysed files of patients who underwent external (extDCR) or endoscopic endonasal dacryocystorhinostomy (endoDCR). We excluded patients with incomplete data (n = 68), acute a priori infection with the need for antibiotics (n = 15) and PSA post-operatively for other reasons (n = 28). Indications for surgery were canalicular stenosis (n = 51, 18.6% endoDCR vs n = 131, 19.5% extDCR), nasolacrimal duct obstruction (n = 118, 43.2% endoDCR vs n = 480, 64.3% extDCR) and mucocele/chronic dacryocystitis (n = 52, 19.0% endoDCR vs n = 187, 25.0% extDCR). RESULTS: In this study, 1020 DCR surgeries were performed in 899 patients. Postoperative SSI was diagnosed in eight patients (0.8%); exclusively after extDCR (1.1% of all extDCR). No SSIs were found in endoDCR cases. The prevalence between SSI in extDCR versus endoDCR did not prove significant (n = 8/747 0.8% vs n = 0/273 0%, p = 0.13). All patients diagnosed with SSI were successfully treated with systemic oral antibiotics. CONCLUSION: The prevalence of SSI after DCR is low and was effectively treated with oral antibiotics. In our study, SSI occurred rarely after extDCR and was not observed after endoDCR. We conclude that lacrimal surgery is safe without the routine administration of PSA.

Aetiology of cerebrospinal fluid rhinorrhoea in a Dutch retrospective cohort from two tertiary referral centres.

BACKGROUND: Cerebrospinal fluid (CSF) rhinorrhoea has different aetiologies, with spontaneous leaks related to female gender and obesity. Limited data is available on patient characteristics and surgical outcomes across different aetiologies of CSF leaks in relatively non-obese populations. METHODS: Retrospective cohort study from two tertiary referral centres including adult patients that underwent surgical closure of a CSF leak, divided into four aetiologies: traumatic, iatrogenic, secondary to structural intracranial pathology (SIP), and spontaneous. Data included patient characteristics, presenting symptoms, preoperative radiologic findings, intracranial pressure (ICP) and surgical outcomes. RESULTS: 72 patients were included: 9 traumatic, 15 iatrogenic, 4 SIP and 44 spontaneous leaks. Primary surgical success was 79%, rising to 93% with reinterventions. Spontaneous leak cases displayed highest female proportion and BMI. A meningo(-encephalo)cele was present in 33 patients and was associated with surgical failure and previous meningitis. No significant differences were observed between different aetiologies regarding patient characteristics, presenting symptoms, or surgical success rates. CONCLUSIONS: Even in a relatively non-obese population, the majority of CSF leaks is spontaneous and associated with female gender and obesity. Otherwise, no differences exist across aetiologies regarding patient characteristics, presenting symptoms or surgical success.

Vision loss caused by immunoglobulin G4-related disease of the skull base complicated by a mucocele of the sphenoid sinus.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a fibro-inflammatory disorder and manifestation in de paranasal and sphenoid sinus is well recognized. In this patient, IgG4-RD presented in an unusual manner with vision loss due to mucocele formation in the sphenoid sinus. CASE DESCRIPTION: A 19-year-old man, with an unremarkable medical history, was referred with decreased vision in the left eye, headaches, and a sharp pain in the left orbit and ear. Compression of the left optic nerve due to a large mucocele caused papillary edema and emergency endoscopic marsupialization of the mucocele was performed. When the vision decreased again, a more extensive decompressing sphenoidotomy was performed. Histopathology showed IgG4-RD. Despite dexamethasone, the lesion expanded to the anterior skull base and the patient required repeat endoscopic surgery. After 3 months, a decrease in smell and vision warranted for a fourth extensive endoscopic decompressing surgery, complicated by a cerebrospinal fluid leak. Prednisone and later rituximab were commenced. Unfortunately, the patient reported a complete loss of vision after 4 months of rituximab due to increased mass effect on the optic nerve. An extensive combined craniofacial-endoscopic surgery was performed to remove the entire mucocele and to prevent further contralateral and intracranial progression. Methylprednisolone monthly was commenced to prevent further complications. DISCUSSION: This case illustrates that in therapy-resistant sino-orbital IgG4-RD, extensive surgery might be necessary at an earlier stage. It may even be the only option to prevent irreversible damage to the surrounding tissues. A multidisciplinary approach in the management of sino-orbital IgG4-RD is therefore warranted.

TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study.

In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10-10, OR 3.11, 95% CI 2.2-4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.

Steroid-resistant human inflammatory ILC2s are marked by CD45RO and elevated in type 2 respiratory diseases.

Group 2 innate lymphoid cells (ILC2s) orchestrate protective type 2 immunity and have been implicated in various immune disorders. In the mouse, circulatory inflammatory ILC2s (iILC2s) were identified as a major source of type 2 cytokines. The human equivalent of the iILC2 subset remains unknown. Here, we identify a human inflammatory ILC2 population that resides in inflamed mucosal tissue and is specifically marked by surface CD45RO expression. CD45RO+ ILC2s are derived from resting CD45RA+ ILC2s upon activation by epithelial alarmins such as IL-33 and TSLP, which is tightly linked to STAT5 activation and up-regulation of the IRF4/BATF transcription factors. Transcriptome analysis reveals marked similarities between human CD45RO+ ILC2s and mouse iILC2s. Frequencies of CD45RO+ inflammatory ILC2 are increased in inflamed mucosal tissue and in the circulation of patients with chronic rhinosinusitis or asthma, correlating with disease severity and resistance to corticosteroid therapy. CD45RA-to-CD45RO ILC2 conversion is suppressed by corticosteroids via induction of differentiation toward an immunomodulatory ILC2 phenotype characterized by low type 2 cytokine and high amphiregulin expression. Once converted, however, CD45RO+ ILC2s are resistant to corticosteroids, which is associated with metabolic reprogramming resulting in the activation of detoxification pathways. Our combined data identify CD45RO+ inflammatory ILC2s as a human analog of mouse iILC2s linked to severe type 2 inflammatory disease and therapy resistance.

Assessing hearing loss in older adults with a single question and person characteristics; Comparison with pure tone audiometry in the Rotterdam Study.

INTRODUCTION: Hearing loss (HL) is a frequent problem among the elderly and has been studied in many cohort studies. However, pure tone audiometry-the gold standard-is rather time-consuming and costly for large population-based studies. We have investigated if self-reported hearing loss, using a multiple choice question, can be used to assess HL in absence of pure tone audiometry. METHODS: This study was performed within 4,906 participants of the Rotterdam Study. The question (in Dutch) that was investigated was: 'Do you have any difficulty with your hearing (without hearing aids)?'. The answer options were: 'never', 'sometimes', 'often' and 'daily'. Mild hearing loss or worse was defined as PTA0.5-4(Pure Tone Average 0.5, 1, 2 & 4 kHz) ≥20dBHL and moderate HL or worse as ≥35dBHL. A univariable linear regression model was fitted with the PTA0.5-4 and the answer to the question. Subsequently, sex, age and education were added in a multivariable linear regression model. The ability of the question to classify HL, accounting for sex, age and education, was explored through logistic regression models creating prediction estimates, which were plotted in ROC curves. RESULTS: The variance explained (R2) by the univariable regression was 0.37, which increased substantially after adding age (R2 = 0.60). The addition of sex and educational level, however, did not alter the R2 (0.61). The ability of the question to classify hearing loss, reflected in the area under the curve (AUC), was 0.70 (95% CI 0.68, 0.71) for mild hearing loss or worse and 0.86 (95% CI 0.85, 0.87) for moderate hearing loss or worse. The AUC increased substantially when sex, education and age were taken into account (AUC mild HL: 0.73 (95%CI 0.71, 0.75); moderate HL 0.90 (95%CI 0.89, 0.91)). CONCLUSION: Self-reported hearing loss using a single question has a good ability to detect hearing loss in older adults, especially when age is accounted for. A single question cannot substitute audiometry, but it can assess hearing loss on a population level with reasonable accuracy.

Somatostatin Receptor Expression in GH-Secreting Pituitary Adenomas Treated with Long-Acting Somatostatin Analogues in Combination with Pegvisomant.

BACKGROUND: Growth hormone-secreting pituitary adenomas (somatotroph adenoma) predominantly express somatostatin receptors (SSTRs) subtypes 2 and 5. Higher SSTR2 expression on somatotroph adenomas results in a better response to somatostatin analogues (SSAs), which preferentially bind, but also downregulate, SSTR2. The effect of the combined treatment with SSAs and the GH receptor antagonist pegvisomant (PEGV) on SSTR expression in somatotroph adenomas is currently unknown. AIM OF THE STUDY: To assess SSTR2 and SSTR5 expression in three groups of somatotroph adenomas: drug-naive, treated with long-acting (LA) SSA monotherapy, or LA-SSA/PEGV combination therapy before surgery. Additionally, we evaluated the required PEGV dose to achieve insulin-like growth factor I (IGF-I) normalization in relation to the SSTR expression. MATERIALS AND METHODS: At our Pituitary Center Rotterdam, we selected acromegalic patients who underwent transsphenoidal neurosurgery. All patients were eventually treated with LA-SSA/PEGV combination therapy during their medical history. SSTR2 and SSTR5 expression in somatotroph adenoma tissues was determined using immunohistochemistry. RESULTS: Out of 39 somatotroph adenoma tissue samples, 23 were drug-naive, 9 received pretreatment with LA-SSA and 7 LA-SSA/PEGV combined treatment. SSTR2 expression was significantly higher in treatment-naive compared to combined treatment somatotroph adenomas (p = 0.048), while SSTR5 expression did not differ. Noteworthy, SSTR2 expression in naive somatotroph adenoma tissues was inversely correlated with the required PEGV dose to achieve IGF-I normalization during postsurgical medical treatment (ρ = -0.538, p = 0.024). CONCLUSION: In our specific cohort, the SSTR2 expression was lower in patients pretreated with LA-SSA/PEGV compared to the drug-naive acromegalic patients. Additionally, the SSTR2 expression in treatment-naive somatotroph adenoma tissues was inversely correlated with the required PEGV dose to achieve IGF-I normalization.

Using the Digits-In-Noise Test to Estimate Age-Related Hearing Loss.

OBJECTIVE: Age-related hearing loss is common in the elderly population. Timely detection and targeted counseling can lead to adequate treatment with hearing aids. The Digits-In-Noise (DIN) test was developed as a relatively simple test to assess hearing acuity. It is a potentially powerful test for the screening of large populations, including the elderly. However, until to date, no sensitivity or specificity rates for detecting hearing loss were reported in a general elderly population. The purpose of this study was to evaluate the ability of the DIN test to screen for mild and moderate hearing loss in the elderly. DESIGN: Data of pure-tone audiometry and the DIN test were collected from 3327 adults ages above 50 (mean: 65), as part of the Rotterdam Study, a large population-based cohort study. Sensitivity and specificity of the DIN test for detecting hearing loss were calculated by comparing speech reception threshold (SRT) with pure-tone average threshold at 0.5, 1, 2, and 4 kHz (PTA0.5,1,2,4). Receiver operating characteristics were calculated for detecting >20 and >35 dB HL average hearing loss at the best ear. RESULTS: Hearing loss varied greatly between subjects and, as expected, increased with age. High frequencies and men were more severely affected. A strong correlation (R = 0.80, p < 0.001) was found between SRTs and PTA0.5,1,2,4. Moreover, 65% of variance in SRT could be explained by pure-tone thresholds. For detecting mild or moderate hearing loss, receiver operating characteristics showed areas under the curve of 0.86 and 0.98, respectively. CONCLUSIONS: This study demonstrates that the DIN test has excellent test characteristics when screening for moderate hearing loss (or more) in an elderly population. It is less suited to screen for mild hearing loss. The test is easy to complete and should be suitable for implementation as an automated self-test in hearing screening programs. Ultimately, when combined with active counseling, hearing screening could lead to higher hearing aid coverage in the hearing impaired elderly.

Cockayne syndrome group B (Csb) and group a (Csa) deficiencies predispose to hearing loss and cochlear hair cell degeneration in mice.

Sensory hair cells in the cochlea, like most neuronal populations that are postmitotic, terminally differentiated, and non-regenerating, depend on robust mechanisms of self-renewal for lifelong survival. We report that hair cell homeostasis requires a specific sub-branch of the DNA damage nucleotide excision repair pathway, termed transcription-coupled repair (TCR). Cockayne syndrome (CS), caused by defects in TCR, is a rare DNA repair disorder with a broad clinical spectrum that includes sensorineural hearing loss. We tested hearing and analyzed the cellular integrity of the organ of Corti in two mouse models of this disease with mutations in the Csb gene (CSB(m/m) mice) and Csa gene (Csa(-/-) mice), respectively. Csb(m/m) and Csa(-/-) mice manifested progressive hearing loss, as measured by an increase in auditory brainstem response thresholds. In contrast to wild-type mice, mutant mice showed reduced or absent otoacoustic emissions, suggesting cochlear outer hair cell impairment. Hearing loss in Csb(m/m) and Csa(-/-) mice correlated with progressive hair cell loss in the base of the organ of Corti, starting between 6 and 13 weeks of age, which increased by 16 weeks of age in a basal-to-apical gradient, with outer hair cells more severely affected than inner hair cells. Our data indicate that the hearing loss observed in CS patients is reproduced in mouse models of this disease. We hypothesize that accumulating DNA damage, secondary to the loss of TCR, contributes to susceptibility to hearing loss.

A novel QTL underlying early-onset, low-frequency hearing loss in BXD recombinant inbred strains.

The DBA/2J inbred strain of mice has been used extensively in hearing research as it suffers from early-onset, progressive hearing loss. Initially, it mostly affects high frequencies, but already at 2-3 months hearing loss becomes broad. In search for hearing loss genes other than Cadherin 23 (otocadherin) and fascin-2, which make a large contribution to the high-frequency deficits, we used a large set of the genetic reference population of BXD recombinant inbred strains. For frequencies 4, 8, 16 and 32 kHz, auditory brainstem response hearing thresholds were longitudinally determined from 2-3 up to 12 weeks of age. Apart from a significant, broad quantitative trait locus (QTL) for high-frequency hearing loss on chromosome 11 containing the fascin-2 gene, we found a novel, small QTL for low-frequency hearing loss on chromosome 18, from hereon called ahl9. Real-time quantitative polymerase chain reaction of organs of Corti, isolated from a subset of strains, showed that a limited number of genes at the QTL were expressed in the organ of Corti. Of those genes, several showed significant expression differences based on the parental line contributing to the allele. Our results may aid in the future identification of genes involved in low-frequency, early-onset hearing loss.

Accelerated loss of hearing and vision in the DNA-repair deficient Ercc1(δ/-) mouse.

Age-related loss of hearing and vision are two very common disabling conditions, but the underlying mechanisms are still poorly understood. Damage by reactive oxygen species and other reactive cellular metabolites, which in turn may damage macromolecules such as DNA, has been implicated in both processes. To investigate whether DNA damage can contribute to age-related hearing and vision loss, we investigated hearing and vision in Ercc1(δ/-) mutant mice, which are deficient in DNA repair of helix-distorting DNA lesions and interstrand DNA crosslinks. Ercc1(δ/-) mice showed a progressive, accelerated increase of hearing level thresholds over time, most likely arising from deteriorating cochlear function. Ercc1(δ/-) mutants also displayed a progressive decrease in contrast sensitivity followed by thinning of the outer nuclear layer of the eyeball. The strong parallels with normal ageing suggest that unrepaired DNA damage can induce age-related decline of the auditory and visual system.

In vivo dynamic clamp study of I(h) in the mouse inferior colliculus.

Approximately half of the cells in the mouse inferior colliculus have the hyperpolarization-activated mixed cation current I(h), yet little is known about its functional relevance in vivo. We therefore studied its contribution to the processing of sound information in single cells by making in vivo whole cell recordings from the inferior colliculus (IC) of young-adult anesthetized C57Bl/6 mice. Following pharmacological block of the endogenous channels, a dynamic clamp approach allowed us to study the responses to current injections or auditory stimuli in the presence and absence of I(h) within the same neuron, thus avoiding network or developmental effects. The presence of I(h) changed basic cellular properties, including depolarizing the resting membrane potential and decreasing resting membrane resistance. Sound-evoked excitatory postsynaptic potentials were smaller but at the same time reached a more positive membrane potential when I(h) was present. With I(h), a subset of cells showed rebound spiking following hyperpolarizing current injection. Its presence also changed more complex cellular properties. It decreased temporal summation in response to both hyperpolarizing and depolarizing repetitive current stimuli, and resulted in small changes in the cycle-averaged membrane potential during sinusoidal amplitude modulated (SAM) tones. Furthermore, I(h) minimally decreased the response to a tone following a depolarization, an effect that may make a small contribution to forward masking. Our results thus suggest that previously observed differences in IC cells are a mixture of direct effects of I(h) and indirect effects due to the change in membrane potential or effects due to the co-expression with other channels.

Matching for HLA antigens of A, B, and DR loci in renal transplantation by Eurotransplant.

79 patients and their respective cadaveric kidney donors were typed for HLA-A, HLA-B, and HLA-DR antigens using frozen stored spleen lymphocytes and fresh peripheral-blood lymphocytes. The kidney-graft survival-rate at 3 to 18 months was highest when donor and recipient shared one or two DR antigens and three or four A and B antigens. The graft-survival rate was significantly higher (87 +/- 6%) at 18 months in these patients than in less well matched patients (48 +/- 9%).