The genetic variants of HLAs (human leukocyte antigens) play a crucial role in the virus–host interaction and pathology of COVID-19. The genetic variants of HLAs not only influence T cell immune responses but also B cell immune responses by presenting a variety of peptide fragments of invading pathogens. Peptide cocktail vaccines produced by using various conserved HLA-A2 epitopes provoke substantial specific CD8+ T cell responses in experimental animals. The HLA profiles vary among individuals and trigger different T cell-mediated immune responses in COVID-19 infections. Those with HLA-C*01 and HLA-B*44 are highly susceptible to the disease. However, HLA-A*02:01, HLA-DR*03:01, and HLA-Cw*15:02 alleles show resistance to SARS infection. Understanding the genetic association of HLA with COVID-19 susceptibility and severity is important because it can help in studying the transmission of COVID-19 and its physiopathogenesis. The HLA-C*01 and B*44 allele pathways can be studied to gain insight into disease transmission and physiopathogenesis. Therefore, integrating HLA testing is suggested in the ongoing pandemic, which will help in the rapid identification of highly susceptible populations worldwide and possibly acclimate vaccine development. Therefore, understanding the correlation between HLA and SARS-CoV-2 is critical in opening new insights into COVID-19 therapeutics, based on previous studies conducted. Full article

Early surgical treatment for patients with ileocecal Crohn’s disease (CD) could be an alternative to biological therapy. The aim of this study is to compare operative outcomes following ileocecal resection for patients with luminal and complicated CD. Patients operated for primary ileocecal CD during 8 years in one tertiary-referral hospital were allocated into 2 groups: those operated for early (luminal) disease (ECD), and for complications of CD (CCD). A retrospective comparative analysis was performed. A total of 273 patients were included in the analysis, 85 (31%) of which were in the ECD group. No difference was found regarding time from diagnosis to surgery. Surgical procedures were longer in the CCD group, with lower rates of laparoscopic approach (93 vs. 99%, p = 0.035) and higher conversion rates (20 vs. 2%, p < 0.001). ECD had non-significant differences in terms of major postoperative complications (9.4 vs. 14.9%, p = 0.215), shorter hospital stays, and lower rates of anastomotic leakage (3.5 vs. 6.8%, p = 0.285). Conversely, the CCD group had higher reoperation and re-hospitalization rates. Adequate timing for the indication of surgery in primary ileocecal CD, including an early discussion considering both medical and surgical treatment as options, could positively influence operative outcomes. Full article

Cardiogenic shock is a complex syndrome manifesting with distinct phenotypes depending on the severity of the primary cardiac insult and the underlying status. As long as therapeutic interventions fail to divert its unopposed rapid evolution, poor outcomes will continue challenging health care systems. Thus, early recognition in the emergency setting is a priority, in order to avoid delays in appropriate management and to ensure immediate initial stabilization. Since advanced therapeutic strategies and specialized shock centers may provide beneficial support, it seems that directing patients towards the recently described shock network may improve survival rates. A multidisciplinary approach strategy commands the interconnections between the strategic role of the ED in affiliation with cardiac shock centers. This review outlines critical features of early recognition and initial therapeutic management, as well as the utility of diagnostic tools and risk stratification models regarding the facilitation of patient trajectories through the shock network. Further, it proposes the implementation of precise criteria for shock team activation and the establishment of definite exclusion criteria for streaming the right patient to the right place at the right time. Full article

Vestibular schwannoma (VS) is an intracranial tumor that commonly presents with tinnitus and hearing loss. To uncover the molecular mechanisms underlying VS-associated tinnitus, we applied next-generation sequencing (Illumina HiSeq) to formalin-fixed paraffin-embedded archival VS samples from nine patients with tinnitus (VS-Tin) and seven patients without tinnitus (VS-NoTin). Bioinformatic analysis was used to detect differentially expressed genes (DEG; i.e., ≥two-fold change [FC]) while correcting for multiple comparisons. Using RNA-seq analysis, VS-Tin had significantly lower expression of GFAP (logFC = −3.04), APLNR (logFC = −2.95), PREX2 (logFC = −1.44), and PLVAP (logFC = −1.04; all p < 0.01) vs. VS-NoTin. These trends were validated by using real-time RT-qPCR. At the protein level, immunohistochemistry revealed a trend for less PREX2 and apelin expression and greater expression of NLRP3 inflammasome and CD68-positive macrophages in VS-Tin than in VS-NoTin, suggesting the activation of inflammatory processes in VS-Tin. Functional enrichment analysis revealed that the top three protein categories—glycoproteins, signal peptides, and secreted proteins—were significantly enriched in VS-Tin in comparison with VS-NoTin. In a gene set enrichment analysis, the top pathway was allograft rejection, an inflammatory pathway that includes the MMP9, CXCL9, IL16, PF4, ITK, and ACVR2A genes. Future studies are needed to examine the importance of these candidates and of inflammation in VS-associated tinnitus. Full article

Square-shaped and large moon-shaped faces are commonly observed in Asians, and the contour of the mandible is associated with the shape of the lower part of the face. Mandible contouring surgery is performed to create a softer impression for East Asians. Currently, most surgeries are performed using an intraoral approach. External approaches have not been cosmetically attempted because of possible damage to the facial nerve and visible scarring and have been limited to mandible bone fracture reduction. This study included 42 patients who underwent mandibular angle reduction via classical intraoral incision and retroauricular incision between April 2019 and October 2021. Clinical outcomes were assessed using the Global Aesthetic Improvement Scale and Visual Analog Scale. Surgery was successful in all cases, with no significant complications. An appropriate mandibular contour was achieved postoperatively. All patients were satisfied with the outcome. Some patients experienced short-term complications, such as hematoma and wound disruption of the skin above the incision line. However, these improved within 3 weeks, and no serious long-term complications were observed. Mandible angle resection with the retroauricular approach is a promising alternative for patients, allowing speedy recovery and the resumption of routine daily life. Full article

(1) Background: We constructed scores for moderate-to-severe and muscle-predominant types of Graves’ orbitopathy (GO) risk prediction based on initial ophthalmic findings. (2) Methods: 400 patients diagnosed with GO and followed up at both endocrinology and ophthalmology clinics with at least 6 months of follow-up. The Score for Moderate-to-Severe type of GO risk Prediction (SMSGOP) and the Score for Muscle-predominant type of GO risk Prediction (SMGOP) were constructed using the machine learning-based automatic clinical score generation algorithm. (3) Results: 55.3% were classified as mild type and 44.8% were classified as moderate-to-severe type. In the moderate-to-severe type group, 32.3% and 12.5% were classified as fat-predominant and muscle-predominant type, respectively. SMSGOP included age, central diplopia, thyroid stimulating immunoglobulin, modified NOSPECS classification, clinical activity score and ratio of the inferior rectus muscle cross-sectional area to total orbit in initial examination. SMGOP included age, central diplopia, amount of eye deviation, serum FT4 level and the interval between diagnosis of GD and GO in initial examination. Scores ≥46 and ≥49 had predictive value, respectively. (4) Conclusions: This is the first study to analyze factors in initial findings that can predict the severity of GO and to construct scores for risk prediction for Korean. We set the predictive scores using initial findings. Full article

Biomarkers that are able to predict the response to omalizumab (OMA) in chronic spontaneous urticaria (CSU) are highly valued. The aim of our study was to evaluate the UAS7 (urticaria activity score assessed for 7 days), DLQI (dermatology life quality index), SII (systemic immune-inflammation index), SIRI (systemic inflammation response index), PLR (platelet/lymphocyte ratio) and NLR (neutrophil/lymphocyte ratio) in a group of 46 CSU a patients treated for 24 weeks with OMA (300 mg every 4 weeks). There were no statistically significant differences observed at the start nor at the end of the treatment between the two groups (responders vs. non-responders) and SII, SIRI, PLR and NLR. However, a statistically significant correlation was observed between severity of urticaria expressed in UAS7 scores and the quality of life (evaluated by DLQI). Furthermore, at week 24, both groups demonstrated significant improvement in quality of life. Our single center study did not confirm the usefulness of SII, SIRI, NLR or PLR as predictors of the response to OMA in CSU. However, it is of importance that even patients who did not respond to the treatment presented a significant improvement in quality of life. Additionally, we also observed that the efficacy of treatment was unchanged amongst patients who underwent a second series of treatment in cases of relapse. Full article

Background: We evaluated whether the Walkaide^® device could effectively improve walking ability and lower extremity function in post-stroke patients with foot drop. Patients aged 20–85 years with an initial stroke within ≤6 months and a functional ambulation classification score of 3 or 4 were eligible. Materials and Methods: Patients were randomly allocated to the functional electrical stimulation (FES) or control group at a 1:1 ratio. A 40 min training program using Walkaide was additionally performed by the FES group five times per week for 8 weeks. The control group received the 40 min training program without FES. Results: A total of 203 patients were allocated to the FES (n = 102) or control (n = 101) groups. Patients who did not receive the intervention or whose data were unavailable were excluded. Finally, the primary outcome data of 184 patients (n = 92 in each group) were analyzed. The mean change in the maximum distance during the 6-MWT (primary outcome) was 68.37 ± 62.42 m and 57.50 ± 68.17 m in the FES and control groups (difference: 10.86 m; 95% confidence interval: −8.26 to 29.98, p = 0.26), respectively. Conclusions: In Japanese post-stroke patients with foot drop, FES did not significantly improve the 6 min walk distance during the convalescent phase. The trial was registered at UMIN000020604. Full article

The aim of this study was to evaluate the qualitative and quantitative differences between 20 and 85 kHz A-scan rate optical coherence tomography (OCT) images acquired by spectral domain OCT. The study included 60 healthy subjects analyzed with horizontal linear scans with a variable A-scan rate (SHIFT technology, Heidelberg Engineering, Heidelberg, Germany). The retinal thickness measurement of each retinal layer was performed in three different positions (subfoveal, nasal, and temporal). The qualitative assessment was performed by two independent observers who rated every image with a score ranging from 1 (“sufficient”) to 3 (“excellent”) on the basis of three parameters: visualization of the vitreo-retinal interface, characterization of the retinal layers, and visualization of the sclero-choroidal interface. No statistically significant differences in terms of retinal layer thickness between the two A-scan rate scans were observed (p > 0.05). The coefficient of variation of the retinal thickness values was lower in the 20 kHz group (25.8% versus 30.1% with the 85 kHz). The 20 kHz images showed a higher quality index for both observers. An inner plexiform layer (IPL) multilaminarity was detected in 78.3% of patients from the 20 kHz group and in 40% of patients from the 85 kHz group (p < 0.05). Full article

Gastric cancer treatments are evolving rapidly. For example, immune checkpoint inhibitors, especially those that target PD-1 or PD-L1, have long-term efficacy in a subset of gastric cancer patients, and are currently the first-line therapy. Immunotherapies approved for use in untreated gastric cancer patients include monotherapy and chemotherapy-immunotherapy combinations. Major clinical trials have reported efficacy and safety data suggesting that PD-L1 expression is important for regimen selection, although other biomarkers, clinicopathologic factors, and patient preference might also be relevant in other situations. Currently, several novel biomarkers and therapeutic strategies are being assessed, which might refine the current treatment paradigm. In this review, we describe the current treatment regimens for patients with gastric cancer and detail the approach we use for the selection of first-line immunotherapy regimens. Full article

Background: Empty nose syndrome (ENS) is a syndrome of paradoxical nasal obstruction that is thought to be mostly caused by inappropriate turbinate procedures. This study aimed to investigate depression- and anxiety-associated psychological symptoms in patients with ENS before and after surgical reconstruction, and to compare them with those of control subjects. Methods: Patients with ENS were prospectively enrolled. The Sino-Nasal Outcome Test-25 (SNOT-25), Empty Nose Syndrome 6-item questionnaire (ENS6Q), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI) were used to evaluate the participants before and after reconstruction surgery with submucosal Medpor implantation (Stryker, Kalamazoo, MI), as well as control subjects at enrollment. Results: Forty patients with ENS and forty age- and sex-matched controls were recruited. Patients with ENS experienced significant improvement in SNOT-25, ENS6Q, BDI-II, and BAI scores after surgery, but all were significantly greater than those in the control group. Nine patients with ENS (22.5%) had postoperative residual psychological symptoms. Preoperative BDI-II and BAI scores were significant predictors of postoperative residual psychological symptoms. The optimal cut-off value was BDI-II > 28.5 (sensitivity, 77.8%; specificity, 77.4%) in receiver operating characteristic curve analysis. Conclusions: The nasal and psychological evaluations in patients with ENS significantly improved after nasal reconstruction surgery, but both were significantly greater than those in the control group. Identifying individuals who may experience postoperative residual symptoms and providing a multimodal approach, including surgical reconstruction and psychiatric treatment, are suggested. Full article

Background: This study aimed to assess the pain experienced during micropulse transscleral laser therapy (MPTLT) and overnight thereafter and explore the factors associated with the pain. Methods: This prospective study included 100 eyes of 81 glaucoma patients undergoing MPTLT under retrobulbar anesthesia. All patients were asked to rate both types of pain using a numerical rating scale (NRS). The risk factors were explored using multivariable mixed-effects ordinal logistic regression. Results: The mean (SD) NRS pain score during the procedure was 3.57 (3.41) (range 0–10), which included no, mild, moderate, and severe pain in 30 (30%), 33 (33%), 17 (17%), and 20 (20%) eyes, respectively. The mean (SD) NRS score of overnight pain was 2.99 (2.28) (range 0–9), which included no, mild, moderate, and severe pain in 17 (17%), 59 (59%), 17 (17%), and 7 (7%) eyes, respectively. Twenty-seven (27%) eyes reported worse pain overnight than during the procedure. Increased age, initial intraocular pressure, and pain during the procedure were significantly associated with increased overnight pain (p < 0.05). Conclusions: Up to a fourth of eyes had worse pain after discharge. Older age, initial intraocular pressure, and pain during the procedure were risk factors for higher levels of overnight pain. Full article

The treatment of geriatric burn patients represents a major challenge in burn care. The objective of this study was to evaluate the efficacy of enzymatic debridement (ED) in geriatric burn patients. Adult patients who received ED for treatment of mixed pattern and full thickness burns (August 2017–October 2022) were included in this study and grouped in the younger (18–65 years) and geriatric (≥65 years) groups. Primary outcome was a necessity of surgery subsequent to ED. Both groups (patient characteristics, surgical and non-surgical treatment) were compared. Multiple logistic and linear regression models were used to identify the effect of age on the outcomes. A total of 169 patients were included (younger group: 135 patients, geriatric group: 34 patients). The burn size as indicated by %TBSA (24.2 ± 20.4% vs. 26.8 ± 17.1%, p = 0.499) was similar in both groups. The ASA (2.5 ± 1.1 vs. 3.4 ± 1.1, p < 0.001) and ABSI scores (6.1 ± 2.8 vs. 8.6 ± 2.3, p < 0.001) were significantly higher in the geriatric group. The %TBSA treated with ED (5.4 ± 5.0% vs. 4.4 ± 4.3%, p = 0.245) were similar in both groups. The necessity of additional surgical interventions (63.0 % vs. 58.8 %, p = 0.763) and the wound size debrided and grafted (2.9 ± 3.5% vs. 2.2 ± 2.1%; p = 0.301) were similar in both groups. Regression models yielded that age did not have an effect on efficacy of ED. We showed that ED is reliable and safe to use in geriatric patients. Age did not have a significant influence on the surgical outcomes of ED. In both groups, the size of the grafted area was reduced and, in many patients, surgery was avoided completely. Full article

Correction of cubitus varus is commonly attempted through supracondylar humeral osteotomy. We hypothesized that lateral distal humeral hemiepiphysiodesis (LDHH) could be used to gradually correct this deformity in children. We conducted a retrospective study including all patients who underwent LDHH with the eight-Plate system between 2008 and 2018, with a minimum 4-year follow-up. We collected demographic, fracture-related, pre- and postoperative clinical (carrying angle (CA), ROM), and radiological data (humeral-ulnar angle (HUA), Baumann angle (BA), shaft-condylar angle (SCA), lateral capitellohumeral angle (LCHA)), as well as data on complications and satisfaction at last follow-up. Fifteen patients were included, with a median follow-up of 81 (64–103) months. All the variables had improved significantly as follows: CA −16 (−18 to −9)°, HUA −16 (−19 to −12)°, BA −11 (−17 to −7)°, SCA 7.5 (3.3 to 13.8)°, LCHA −4.8 (−6.8 to 0.6), flexion 10 (0 to 24)°, and extension 10 (0 to 10)°. The annual correction rate in terms of HUA was 2.41° (1.9 to 3.2). There were 5 cases of aseptic screw loosening, 4 of them requiring replacement, without relation to age at surgery (p = 0.324). Most patients (86.67%) were satisfied, and a relationship was found with younger age at surgery (p = 0.037). In conclusion, preliminary results show that LDHH with the eight-Plate system is an effective technique for mild to moderate cubitus varus deformity correction in children. Patients should be advised of the relatively long duration of implant retention and the possibility of reoperation for screw replacement or implant removal. Full article

Objective: Intracerebral hemorrhage (ICH) has a high mortality and long-term morbidity and thus has a significant overall health–economic impact. Outcomes are especially poor if the exact onset is unknown, but reliable imaging-based methods for onset estimation have not been established. We hypothesized that onset prediction of patients with ICH using artificial intelligence (AI) may be more accurate than human readers. Material and Methods: A total of 7421 computed tomography (CT) datasets between January 2007–July 2021 from the University Hospital Basel with confirmed ICH were extracted and an ICH-segmentation algorithm as well as two classifiers (one with radiomics, one with convolutional neural networks) for onset estimation were trained. The classifiers were trained based on the gold standard of 644 datasets with a known onset of >1 and <48 h. The results of the classifiers were compared to the ratings of two radiologists. Results: Both the AI-based classifiers and the radiologists had poor discrimination of the known onsets, with a mean absolute error (MAE) of 9.77 h (95% CI (confidence interval) = 8.52–11.03) for the convolutional neural network (CNN), 9.96 h (8.68–11.32) for the radiomics model, 13.38 h (11.21–15.74) for rater 1 and 11.21 h (9.61–12.90) for rater 2, respectively. The results of the CNN and radiomics model were both not significantly different to the mean of the known onsets (p = 0.705 and p = 0.423). Conclusions: In our study, the discriminatory power of AI-based classifiers and human readers for onset estimation of patients with ICH was poor. This indicates that accurate AI-based onset estimation of patients with ICH based only on CT-data may be unlikely to change clinical decision making in the near future. Perhaps multimodal AI-based approaches could improve ICH onset prediction and should be considered in future studies. Full article