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Article

Pre-Surgery Patient Health Contributes to Aggravated Sino-Nasal Outcome and Quality of Life after Pituitary Adenomectomy

by
Witold X. Chmielewski
1,2,3,*,†,
Sebastian Walbrodt
1,2,3,
Laurèl Rauschenbach
1,2,3,
Mehdi Chihi
1,2,3,
Oliver Gembruch
1,2,3,
Marvin Darkwah Oppong
1,2,3,
Sebastian Schroer
1,2,3,
Karsten H. Wrede
1,2,3,
Philipp Dammann
1,2,3,
Ramazan Jabbarli
1,2,3,
Ilonka Kreitschmann-Andermahr
1,2,3,
Taku Sato
1,2,3,4,
Nicole Unger
5,
Stefan Mattheis
6,
Ulrich Sure
1,2,3 and
Yahya Ahmadipour
1,2,3
1
Department of Neurosurgery and Spine Surgery, University Hospital Essen, 45147 Essen, Germany
2
German Cancer Consortium (DKTK) Partner Site, University Hospital Essen, 45147 Essen, Germany
3
Center for Translational Neuro- & Behavioral Sciences (C-TNBS), University Duisburg Essen, 47147 Duisburg, Germany
4
Department of Neurosurgery, Fukushima Medical University, Fukushima 960-1247, Japan
5
Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, 45147 Essen, Germany
6
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Essen, 45147 Essen, Germany
*
Author to whom correspondence should be addressed.
Address for correspondence: Witold X. Chmielewski, Cognitive Neuropsychology, Department of Neurosurgery and Spine Surgery, UK Essen, Hufelandstraße 55, 45147 Essen, Germany.
Medicina 2023, 59(1), 127; https://doi.org/10.3390/medicina59010127
Submission received: 4 November 2022 / Revised: 30 December 2022 / Accepted: 2 January 2023 / Published: 9 January 2023
(This article belongs to the Section Oncology)

Abstract

:
Objectives: The transphenoidal bi-nostril endoscopic resection of pituitary adenomas is regarded as a minimally invasive treatment nowadays. However, sino-nasal outcome and health-related quality of life (HRQoL) might still be impaired after the adenomectomy, depending on patients’ prior medical history and health status. A systematic postoperative comparison is required to assess differences in perceived sino-nasal outcome and HRQoL. Methods: In this single-center observational study, we collected data from 81 patients, operated between August 2016 and August 2021, at a 3–6-month follow-up after adenomectomy. We employed the sino-nasal outcome test for neurosurgery (SNOT-NC) and the HRQoL inventory Short Form (SF)-36 to compare sino-nasal and HRQoL outcome in patients with or without allergies, previous nose surgeries, presence of pain, snoring, sleep apnea, usage of continuous positive airway pressure (cpap), and nose drop usage. Results: At the 3–6-month follow-up, patients with previous nasal surgery showed overall reduced subjective sino-nasal health, increased nasal and ear/head discomfort, increased visual impairment, and decreased psychological HRQoL (all p ≤ 0.026) after pituitary adenomectomy. Patients with pain before surgery showed a trend-level aggravated physical HRQoL (p = 0.084). Conclusion: Our data show that patients with previous nasal surgery have an increased risk of an aggravated sino-nasal and HRQoL outcome after pituitary adenomectomy. These patients should be thoroughly informed about potential consequences to induce realistic patient expectations. Moreover, the study shows that patients with moderately severe allergies, snoring, and sleep apnea (± cpap) usually do not have to expect a worsened sino-nasal health and HRQoL outcome.

1. Introduction

With an estimated prevalence between 10% and 17% in the general population, pituitary adenomas are among the more common intracranial tumors [1]. In recent years, transsphenoidal endoscopic pituitary adenoma resection has become the primary treatment option for almost all pituitary adenomas requiring surgery, due to its minimally invasive surgical approach [2,3]. The recent advances in the endoscopic approach have led to a significant reduction in the probability and extent of postoperative sequelae, especially in light of continuous refinements of surgical techniques and equipment, as well as the usage of rhino-septal splints [4,5]. Despite these advances, surgery through the transsphenoidal pathway is still associated with a deterioration of sino-nasal health [6]. This is an important fact to consider, since sino-nasal health has a pronounced impact on patients’ HRQoL [7]. To date, short-term, as well as persistent long-term effects of transsphenoidal endoscopic pituitary adenoma resection on sino-nasal health and HRQoL have been observed in patients with skull base lesions [8,9]. In view of the persistence of the long-term effects on sino-nasal health, the question arises whether persistent pre-surgery patient health variables (i.e., allergies, previous nose surgeries, presence of pain, snoring, sleep apnea with or without usage of cpap, and nose drop usage) might also affect sino-nasal health and HRQoL in the follow-up in this patient cohort. Since this matter is of utmost importance for patient education and future studies, we examined sino-nasal health (SNOT-NC) and HRQoL (SF-36) in the follow-up after bi-nostril transsphenoidal endoscopic adenoma resection and compared patients based on their prior medical history and health status.

2. Materials and Methods

2.1. Questionnaires

2.1.1. Health-Related Quality of Life (HRQoL)

The German version of the self-report questionnaire SF-36 [10,11] was employed to assess HRQoL. The SF-36 is utilized as an outcome measure for the evaluation of health treatments. It measures HRQoL with 36 items in 8 z-standardized subdomains, i.e., general health, vitality, bodily pain, mental health, role physical, role emotional, as well as physical and social functioning, with higher scores indicating a greater HRQoL. Moreover, the SF-36 allows the reporting of summary measures for physical and mental health, based on the addition of the weighted scores of the 8 subdomains. In this study, we only examined the summary scores.

2.1.2. Sino-Nasal Outcome Test for Neurosurgery (SNOT-NC)

The SNOT-NC [7] is a self-report questionnaire, developed for the assessment of the (subjective) clinical sino-nasal outcome of patients undergoing transsphenoidal endoscopic skull base surgery. The questionnaire is partially derived from the SNOT-22 questionnaire [12,13,14], but was extended with additional items and domains in order to include potential consequences of this particular neurosurgical approach. By means of 23 items, the domains Nasal Discomfort, Sleep Problems/Reduced Productivity, Ear and Head Discomfort, Visual Impairment, and a sino-nasal total score are examined.

2.1.3. Clinical ad hoc Questions

To identify potential risk factors and pre-surgery impairments of nasal and overall health, which might impact the sino-nasal and HRQoL outcome measures, participants were asked to answer a clinical ad hoc questionnaire with 7 items. In this questionnaire, the presence of allergies, previous nose surgeries (nasal septum, paranasal sinuses, and turbinates), the presence of any pain, snoring, sleep apnea with or without usage of cpap, and nose drop usage (all yes or no) were queried.

2.2. Statistical Analyses

All statistical analyses were conducted with SPSS 27. The normal distribution of data was controlled for with the Kolmogorov–Smirnov test. In case of normal distribution, independent t-tests were used to compare groups based on the clinical ad hoc questions. The Leven’s test was used to control for equal variance. Non-normally distributed data were compared with Mann–Whitney U tests. Effect sizes were estimated using Cohen’s d (small < 0.2, medium < 0.5, and large effect > 0.5). For descriptive statistics, the mean and standard error of the mean are reported.

2.3. Sample

All 81 patients underwent surgery for the resection of pituitary adenoma via a bi-nostril transsphenoidal endoscopic approach and were consecutively treated at the Department of Neurosurgery and Spine Surgery at the University Hospital Essen between 1 August 2016 and 31 August 2021. Patients were only included in the 3–6-month follow-up if informed written consent was given. The study was conducted in accordance with the declaration of Helsinki and was approved by the institutional review board of the Medical Faculty of the University Hospital Essen (identification number: 14-5791-BO).

3. Results

3.1. Sample Characteristics

In total, 81 patients (40 female; mean age: 52.94 ± 1.64 years) participated in the study. A total of 4.94% of all patients classified for Cushing’s disease and 9.88% of all patients classified for acromegaly. Two patients were subsequently treated due to cerebrospinal fluid leakage. A total of 23.5% of patients had a KNOSP score of 0, 24.6% of 1, 14.9 of 2, 13.5 of 3 A or B, and the rest of the patients had a KNOSP score of 4.

3.2. SNOT-NC

SNOT-NC scores were analyzed in the follow-up to examine whether the subjective sino-nasal outcome is affected by pre-surgery patient health variables. Sino-nasal outcome scores were only affected in patients with previous nasal surgeries (n = 19). These patients exhibited significantly higher SNOT-NC total scores (53.57 ± 4.13 vs. 43.04 ± 1.79; t = 2.67; p = 0.009; d = 0.701), higher nasal discomfort (16.79 ± 1.40 vs. 13.77 ± 0.60; t = 2.27; p = 0.026; d = 0.595), higher ear/head discomfort (11.57 ± 1.13 vs. 8.96 ± 0.49; t = 2.12; p = 0.042; d = 0.632), and higher visual impairment (8.16 ± 0.80 vs. 6.42 ± 0.34; t = 2.32; p = 0.023; d = 0.608) than patients without previous surgeries. All other group comparisons based on pre-surgery variables yielded no significant group differences (all t ≤ 1.89; all p ≥ 0.063), even though trend-level significantly higher sleep problems/reduced productivity in patients with previous nasal surgeries (12.58 ± 1.06 vs. 10.19 ± 0.62; t = 1.89; p = 0.063; d = 0.248) were observed (see Figure 1). KNOSP scores did not differ between patients with or without tumors (without 1.88 ± 0.20 vs. with 1.82 ± 0.33; Z = −0.04; p = 0.969).
Moreover, trend-level higher visual impairment in patients with previous pain (6.49 ± 0.38 vs. 7.73 ± 0.62; t = 1.71; p = 0.092, d = −0.426) and trend-level lower visual impairment in patients with previous snoring (7.39 ± 0.54 vs. 6.25 ± 0.34; t = 1.78; p = 0.080; d = 0.394) were observed. All descriptive values are depicted in Table 1.

3.3. SF-36

SF-36 summary scores were analyzed in the follow-up based on the clinical ad-hoc questions for pre-surgery variables to examine whether HRQoL is affected. HRQoL summary scores were only affected in patients with previous nasal surgeries (n = 17), which exhibited a significantly decreased psychological HRQoL (37.31 ± 2.95 vs. 47.65 ± 1.44; t = 3.36; p = 0.001; d = 0.927) in comparison with patients without previous surgeries. All other group comparisons based on pre-surgery patient health variables yielded no significant group differences (all t ≤ 1.75; all p ≥ 0.084), even though trend-level significantly decreased physical HRQoL in patients reporting pain prior to the operation was observed (41.52 ± 2.97 vs. 46.48 ± 1.54; t = 1.75; p = 0.084; d = 0.475). All descriptive values are depicted in Table 2.

3.4. Correlation SNOT-NC and SF-36

Correlations between the SNOT-NC and SF-36 were analyzed to examine the connection between sino-nasal health and HRQoL. Regarding the correlation between SNOT-NC and SF-36, medium to large correlations were observed between all scores of the SNOT-NC and the physical and psychological summary scores of the SF-36 (all r ≤ −0.441, all p < 0.001). This indicated a highly significant connection between decreased physical and psychological health and subjectively perceived sino-nasal health in the follow-up (see Figure 2).

4. Discussion

In this study, we focused on the question of whether pre-surgery patient health variables (i.e., patients’ prior medical history and health status) might additionally affect long-term sino-nasal health and HRQoL in patients after bi-nostril transsphenoidal endoscopic adenomectomy. The aim of this study was to identify specific patient health variables which should be examined to ensure an adequate patient education and to avoid a potential bias of data in future studies. To this end, we examined the impact of allergies, previous nose surgeries, presence of pain, snoring, sleep apnea with or without usage of cpap, and nose drop usage on subjective sino-nasal health and HRQoL in the follow-up after transphenoidal endoscopic adenoma resection.
The results show that previous nasal surgeries can have a major impact on sino-nasal outcome and postoperative HRQoL. Patients with previous nasal surgeries had an overall reduced subjective sino-nasal health, increased nasal and ear/head discomfort, increased visual impairment, as well as decreased psychological HRQoL. As aggravated sino-nasal health and HRQoL [9,15] as well as increased visual impairment [16] have also been shown in patients after revision surgery for adenoma resection, this underlines the importance of addressing the impact of previous nasal surgeries on sino-nasal health and HRQoL in patient education and future studies. These group differences were not driven by tumor size, as KNOSP scores did not differ between patients with and without previous surgeries. This underlines the importance of assessing previous nasal surgeries and thoroughly informing patients with previous nose surgeries about potential consequences of endoscopic pituitary surgery. Moreover, in line with previous literature [17,18], the data indicated on a trend-level basis that previous pain (regardless of pain location) might be related to deteriorated physical HRQoL and visual impairment in patients after pituitary adenoma resection. This leads to the advice to consider previous pain when examining HRQoL in pituitary adenoma patients, particularly in regards to the medium to large correlations between subjective sino-nasal health and HRQoL. Interestingly, the data showed no significant effect of allergies, snoring, sleep apnea with or without usage of cpap, and nose drop usage on subjective sino-nasal health and HRQoL. The lacking effect of allergies might be explained by the fact that HRQoL is usually affected by more severe types of allergies, e.g., respiratory allergies, food allergies, urticaria, and drug and sting allergies [19], while our patients only experienced mild to moderate symptoms. Similarly, out of 18 patients with sleep apnea, only 8 patients experienced sufficiently severe symptoms to require the usage of a cpap. As sino-nasal health has been shown to be correlated to the severity of sleep apnea [20] and effects of sleep apnea on HRQoL are highly correlated to day-time sleepiness [21], our results suggest that sleep apnea only plays a role in sino-nasal health and HRQoL in severely affected pituitary adenoma patients. Snoring might also not be a factor, as only mild subjective, but not objective, effects of clinical significant snoring on HRQoL are reported [22]. Similarly, pre-surgery nose drop usage might only indicate nasal problems, which are not severe enough to translate into post-operation sino-nasal health and HRQoL. As this study can, however, not rule out a potential impact of more severe symptoms, this issue should be addressed in a study examining sino-nasal health and HRQoL in more or less severely affected patients. A potential limitation is that pre-surgery health might be differently affected in patients with different types of pituitary adenomas. In acromegaly for example, an increased likelihood of sleep disorders and prominent changes in olfaction after surgery have been reported [23,24]. Due to the small sample size of patients that were diagnosed with acromegaly, we cannot entirely statistically rule out that the specific type of diagnosis might have biased our results. Hence, we strongly recommend that future studies should examine the role of pre-surgery health variables on sino-nasal outcome and quality of life in patients with different types of pituitary adenomas (e.g., cushing’s disease or acromegaly). Additionally, the growth direction of the tumor should be examined in future studies, as it might play a role in the treatment strategy and the outcome of the surgery [25].

5. Conclusions

To sum up, our study shows that previous nasal surgeries are an indicator of aggravated sino-nasal health and HRQoL in patients after transphenoidal endoscopic pituitary adenoma resection and should thus be addressed in patient education and in future studies. The data also suggest that pre-surgery pain relates to post-operation HRQoL and should thus be controlled for in future studies. Moreover, the study shows that patient groups who are, for the most part, moderately affected by allergies, snoring, or sleep apnea with or without usage of cpap usually do not have to expect a worsened sino-nasal health and HRQoL outcome. Future studies are recommended to examine how the severity of such health problems relates to subjective sino-nasal health and HRQoL after pituitary adenoma resection.

Author Contributions

Conceptualization, Y.A.; methodology, Y.A.; software, W.X.C. and Y.A.; validation, W.X.C. and Y.A.; formal analysis, W.X.C. investigation, W.X.C. and Y.A.; resources, Y.A.; data curation, W.X.C., S.S. and Y.A.; writing—original draft preparation, W.X.C.; writing—review and editing, W.X.C., S.W., L.R., M.C., O.G., M.D.O., S.S., K.H.W., P.D., R.J., I.K.-A., T.S., N.U., S.M., U.S. and Y.A. and all other authors.; visualization, W.X.C., S.S. and Y.A.; supervision, W.X.C. and Y.A.; project administration, Y.A.; funding acquisition, W.X.C. and Y.A. All authors have read and agreed to the published version of the manuscript.

Funding

The authors received no financial support for the research and authorship. Publication of this article was supported by the Open Access Publication Fund of the University of Duisburg-Essen.

Institutional Review Board Statement

The study was conducted in accordance with the declaration of Helsinki and was approved by the institutional review board of the Medical Faculty of the University Hospital Essen (identification number: 14-5791-BO, 19 December 2016).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

Not applicable.

Acknowledgments

We would like to acknowledge the contribution of Janine Szybowicz in the data acquisition and organization. We acknowledge support by the Open Access Publication Fund of the University of Duisburg-Essen.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

HRQoLhealth-related quality of life
SNOT[-NC]sino-nasal outcome test [for neurosurgery]
SF-36HRQoL inventory Short Form

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Figure 1. Illustration of the SNOT-NC Total Score (left side) and SNOT-NC Sub-Scores (right side) comparison for patients with (black) and without previous nasal surgeries (grey). Asterisks * mark significant differences.
Figure 1. Illustration of the SNOT-NC Total Score (left side) and SNOT-NC Sub-Scores (right side) comparison for patients with (black) and without previous nasal surgeries (grey). Asterisks * mark significant differences.
Medicina 59 00127 g001
Figure 2. Pearsons’ r correlation coefficients for SNOT-NC Scores and SF-36 Psychological (black) and Physical HRQoL (grey). Double Asterisks ** mark highly significant correlations.
Figure 2. Pearsons’ r correlation coefficients for SNOT-NC Scores and SF-36 Psychological (black) and Physical HRQoL (grey). Double Asterisks ** mark highly significant correlations.
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Table 1. SNOT-NC Scores based on pre-surgery health variables.
Table 1. SNOT-NC Scores based on pre-surgery health variables.
Pre-Surgery Health VariableNon-Existent
(Mean ± SEM)
Existent
(Mean ± SEM)
t-Valuep-ValueCohen’s d
SNOT-NC Total Score
 Allergies43.77 ± 1.8446.35 ± 2.46−0.880.379−184
 Previous nose surgeries43.04 ± 1.7953.57 ± 4.13−2.670.009−0.701
 Presence of any pain44.37 ± 1.9448.56 ± 3.69−1.080.285−0.269
 Snoring46.47 ± 2.8344.53 ± 2.000.5600.5770.124
 Sleep apnea45.36 ± 1.7242.42 ± 2.570.950.3500.201
 Cpap44.85 ± 1.6443.75 ± 4.080.200.8420.074
 Nose drop usage45.54 ± 2.4744.49 ± 1.820.320.7500.071
SNOT-NC Nasal Discomfort
 Allergies13.89 ± 0.6214.78 ± 0.82−0.870.387−0.181
 Previous nose surgeries13.77 ± 0.6016.79 ± 1.40−2.270.026−0.595
 Presence of any pain14.21 ± 0.6615.18 ± 1.20−0.740.460−0.186
 Snoring14.39 ± 0.9514.56 ± 0.67−0.150.882−0.033
 Sleep apnea14.28 ± 0.5914.03 ± 0.810.250.8030.051
 Cpap14.22 ± 0.5614.25 ± 0.90−0.030.976−0.006
 Nose drop usage14.79 ± 0.8114.01 ± 0.620.710.4820.158
SNOT-NC Sleep Problems/ Reduced Productivity
 Allergies10.50 ± 0.5611.65 ± 0.86−1.160.249−0.242
 Previous nose surgeries10.19 ± 0.6212.58 ± 1.06−1.890.063−495
 Presence of any pain10.42 ± 0.6311.64 ± 1.09−0.990.324−0.248
 Snoring10.73 ± 0.8010.78 ± 0.74−0.040.969−0.009
 Sleep apnea11.13 ± 0.5510.16 ± 0.890.800.4260.204
 Cpap10.99 ± 0.5210.38 ± 1.270.350.7270.130
 Nose drop usage10.67 ± 0.7811.04 ± 0.59−0.340.732−0.077
SNOT-NC Ear/ Head Discomfort
 Allergies9.20 ± 0.529.52 ± 0.64−0.390.701−0.080
 Previous nose surgeries8.96 ± 0.4911.57 ± 1.13−2.120.044−632
 Presence of any pain9.18 ± 0.5010.62 ± 1.08−1.210.235−0.343
 Snoring10.32 ± 0.778.80 ± 0.521.630.1070.361
 Sleep apnea9.52 ± 0.468.47 ± 0.731.040.3030.264
 Cpap9.37 ± 0.449.25 ± 1.510.080.9380.029
 Nose drop usage9.71 ± 0.809.16 ± 0.460.630.5320.139
SNOT-NC Visual Impairment
 Allergies6.48 ± 0.356.68 ± 0.49−0.340.734−0.071
 Previous nose surgeries6.42 ± 0.348.16 ± 0.80−2.320.023−0.608
 Presence of any pain6.49 ± 0.387.73 ± 0.62−1.710.092−0.426
 Snoring7.39 ± 0.546.25 ± 0.341.780.0800.394
 Sleep apnea6.73 ± 0.335.79 ± 0.480.110.1900.337
 Cpap6.60 ± 0.326.13 ± 0.990.440.6580.164
 Nose drop usage6.25 ± 0.406.67 ± 0.36−0.670.505−0.150
Descriptive values for SNOT-NC group comparisons based on pre-surgery health variables for all SNOT-NC scores (SNOT-NC Total Score; SNOT-NC Nasal Discomfort; SNOT-NC Sleep Problems/ Reduced Productivity; SNOT-NC Ear/ Head Discomfort; SNOT-NC Visual Impairment). Bold: significant, italics trend level significant group differences.
Table 2. SF-36: HRQoL based on pre-surgery health variables.
Table 2. SF-36: HRQoL based on pre-surgery health variables.
Pre-Surgery Health VariableNon-Existent
(Mean ± SEM)
Existent
(Mean ± SEM)
t-Valuep-ValueCohen’s d
 Psychological HRQoL
 Allergies46.44 ± 1.7343.35 ± 2.291.080.2820.260
 Previous nose surgeries47.65 ± 1.4437.31 ± 2.953.360.0010.927
 Presence of any pain46.48 ± 1.5441.52 ± 2.971.550.1250.420
 Snoring46.78 ± 1.9844.10 ± 1.491.100.2770.232
 Sleep apnea45.32 ± 1.4045.55 ± 2.54−0.080.941−0.020
 Cpap45.39 ± 1.3543.41 ± 2.990.460.6440.172
 Nose drop usage46.96 ± 2.1844.65 ± 1.720.740.4610.194
Physical HRQoL
 Allergies44.59 ± 1.6842.98 ± 2.220.580.5610.140
 Previous nose surgeries45.01 ± 1.5740.54 ± 2.311.420.1600.393
 Presence of any pain45.29 ± 1.5339.91 ± 2.591.750.0840.475
 Snoring43.08 ± 1.7844.60 ± 1.56−0.650.520−0.137
 Sleep apnea43.32 ± 1.4046.10 ± 1.71−0.950.343−0.251
 Cpap43.60 ± 1.3345.91 ± 2.49−0.550.583−0.205
 Nose drop usage45.76 ± 2.1743.32 ± 1.640.810.4220.211
Descriptive values for HRQoL group comparisons based on pre-surgery health variables for the SF-36 summary scores (Psychological HRQoL; Physical HRQoL). Bold: significant -, italics trend level significant group differences.
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MDPI and ACS Style

Chmielewski, W.X.; Walbrodt, S.; Rauschenbach, L.; Chihi, M.; Gembruch, O.; Darkwah Oppong, M.; Schroer, S.; Wrede, K.H.; Dammann, P.; Jabbarli, R.; et al. Pre-Surgery Patient Health Contributes to Aggravated Sino-Nasal Outcome and Quality of Life after Pituitary Adenomectomy. Medicina 2023, 59, 127. https://doi.org/10.3390/medicina59010127

AMA Style

Chmielewski WX, Walbrodt S, Rauschenbach L, Chihi M, Gembruch O, Darkwah Oppong M, Schroer S, Wrede KH, Dammann P, Jabbarli R, et al. Pre-Surgery Patient Health Contributes to Aggravated Sino-Nasal Outcome and Quality of Life after Pituitary Adenomectomy. Medicina. 2023; 59(1):127. https://doi.org/10.3390/medicina59010127

Chicago/Turabian Style

Chmielewski, Witold X., Sebastian Walbrodt, Laurèl Rauschenbach, Mehdi Chihi, Oliver Gembruch, Marvin Darkwah Oppong, Sebastian Schroer, Karsten H. Wrede, Philipp Dammann, Ramazan Jabbarli, and et al. 2023. "Pre-Surgery Patient Health Contributes to Aggravated Sino-Nasal Outcome and Quality of Life after Pituitary Adenomectomy" Medicina 59, no. 1: 127. https://doi.org/10.3390/medicina59010127

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