Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Longitudinal changes in Langerhans cell density of the cornea and conjunctiva in contact lens-induced dry eye

<b>BACKGROUND</b>\ud \ud - The aim was to determine longitudinal changes in <i>Langerhans cell density (LCD)</i> in the human cornea and conjunctiva during asymptomatic and symptomatic contact lens wear.\ud \ud <b>METHODS</b>\ud \ud - Twenty-five participants with <i>contact lens-induced dry eye (CLIDE)</i> and 35 without CLIDE (NO-CLIDE), diagnosed using a range of symptom questionnaires and objective tests (tear film break up, cotton thread tear test and corneal staining) were enrolled. The central cornea and nasal bulbar conjunctiva were examined using a Heidelberg laser scanning confocal microscope at baseline and following one, four and 24 weeks wear of daily disposable hydrogel contact lenses. Twenty-three non-contact lens-wearing controls were also examined. Langerhans cells were counted manually from randomly selected images.\ud \ud <b>RESULTS</b>\ud \ud - In the cornea, mean and standard error of the mean LCD was greater after one week of lens wear in CLIDE (55 ± 7 cells/mm<small>²</small> ) versus NO-CLIDE (43 ± 4 cells/mm<small>²</small> ) (p = 0.041) and controls (27 ± 4 cells/mm<small>²</small> ) (p < 0.001). LCD was also greater in NO-CLIDE versus controls (p = 0.010). At week 4, LCD was greater in CLIDE (41 ± 6 cells/mm<small>²</small> ) versus controls (27 ± 4 cells/mm<small>²</small> ) (p = 0.004). There were no other significant differences between groups at weeks four or 24. In the conjunctiva, LCD was greater after one week of lens wear in CLIDE (17 ± 1 cells/mm<small>²</small> ) (p = 0.003) and NO-CLIDE (17 ± 3 cells/mm<small>²</small> ) (p = 0.001) versus controls (7 ± 1 cells/mm<small>²</small> ). There were no significant differences between groups at weeks four or 24.\ud \ud <b>CONCLUSIONS</b>\ud \ud - The initial transient increase in corneal and conjunctival LCD in CLIDE (versus NO-CLIDE) suggests an inflammatory component in the aetiology of this condition

The relationship between corneal nerve morphology and inflammatory mediators and neuropeptides in healthy individuals

SIGNIFICANCE This study set out to explore the relationship between the ocular surface immune and nervous systems by exploring corneal nerve structure and the presence of inflammatory mediators and neuropeptides in the tear film. PURPOSE The purpose of this study was to determine the association between corneal nerve morphology and tear film inflammatory mediators and a neuropeptide in healthy individuals. METHODS Flush tears were collected from both eyes of 21 healthy participants aged 39.7 ± 9.9 years (10 females, 11 males) and analyzed for substance P, matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), tumor necrosis factor and interleukin 6. In vivo central corneal confocal microscopy was performed on the right eye, and eight images were captured. Variables measured were corneal nerve fiber length (CNFL), corneal nerve density (CNFD), corneal nerve branch density, fiber total branch density, corneal nerve fiber area, corneal nerve fiber width (CNFW), and corneal nerve fractal dimension (CNFrac). For each eye, the average across the images and the maximum and minimum values were determined for each variable. Pearson correlation analysis was performed to test for associations. RESULTS Substance P correlated with CNFrac (max) (r = -0.48, P =.03) and CNFW (min) (r = -0.52, P =.02). TIMP-1 correlated with CNFD (average) (r = -0.53, P =.03), CNFL (average) (r = -0.49, P =.05), CNFrac (max) (r = -0.49, P =.05), and CNFD (min) (r = -0.55, P =.02). Interleukin 6 correlated with CNFW (average) (r = -0.49, P =.05), the standard deviation of CNFL (r = -0.51, P =.04), CNFL (max) (r = -0.50, P =.04), CNFrac (max) (r = -0.50, P =.04), and CNFW (min) (r = -0.55, P =.02). Tumor necrosis factor matrix metalloproteinase-9, and its ratio with TIMP-1 did not correlate with any corneal nerve parameters. CONCLUSIONS Both inflammatory mediators and neuropeptides correlated with measures of corneal nerve morphology, supporting the link between the inflammatory and nervous systems.</p

Time course of changes in goblet cell density in symptomatic and asymptomatic contact lens wearers

<b>Purpose</b>\ud \ud - To investigate longitudinal changes in <i>goblet cell density (GCD)</i> in contact lens (CL) wearers who do and do not develop symptoms of dry eye (DE).\ud \ud <b>Methods</b>\ud \ud - Sixty healthy individuals fitted with daily disposable hydrogel CLs and 23 age-balanced non-CL–wearing controls underwent assessment using the 5-item dry eye questionnaire, noninvasive tear film break-up time measurement, ocular surface assessment, and phenol red thread test evaluation. <i>Laser scanning confocal microscopy (LSCM)</i> and <i>conjunctival impression cytology (CIC)</i> were used to assess GCD at baseline and follow-up visits at 1 week and 1 and 6 months. After 1 week, all CL wearers were categorized as those who were and were not symptomatic based on responses to the CL dry eye questionnaire-8 (CLDEQ-8). A linear mixed-model was used to examine changes in GCD over time.\ud \ud <b>Results</b>\ud \ud - The global mean GCD of the 83 participants at baseline (before CL wear) was 476 ± 41 and 467 ± 52 cells/mm<small>²</small> using LSCM and CIC, respectively. After 6 months of CL wear, GCD was reduced by approximately 13% and 29% in asymptomatic (N = 29) and symptomatic (N = 17) CL wearers (all P < 0.001), respectively, observed with both LSCM and CIC.\ud \ud <b>Conclusions</b>\ud \ud - Contact lens wear induces a reduction of GCD over 6 months, which is exacerbated in those with DE symptoms. Either LSCM or CIC can be used to assess GCD in the conjunctiva

Development of feasible methods to image the eyelid margin using in vivo confocal microscopy

PURPOSE: To develop a feasible method to image eyelid margin structures using in vivo confocal microscopy (IVCM) for use in clinical research. Second, to assess the association between IVCM and meibography images. METHODS: IVCM was performed on the central upper eyelid margin of 13 healthy participants (31 ± 5 years). Overall morphology montages (1600 × 1600 μm) were created of 3 participants. Single frames (400 × 400 μm) of 10 participants were imaged to determine the feasibility of measuring eyelid features. Meibography was performed with EASYTEARview+ in the same 10 participants. ImageJ software was used to quantify image structures. RESULTS: In the montages, structures of rete ridges, meibomian gland openings, and the lid wiper region were observed. The maximum possible montage size, using multiple single frames, was approximately 5200 × 1500 × 150 μm in the X, Y, and Z directions, respectively. The mean number, density, area, perimeter, and shortest and longest diameters of rete ridges of the 9 nonoverlapped frames were 12 ± 2/frame, 73 ± 5/mm, 2504 ± 403 μm, 250 ± 33 μm, 40 ± 6 μm, and 84 ± 13 μm, respectively. Sampling analysis determined at least 5 nonoverlapped frames were necessary to accurately represent the parameters of the ridges. The mean areas of 3 meibomian openings were 785 ± 784 μm, 1036 ± 963 μm, 950 ± 1071 μm, 848 ± 954 μm, 737 ± 831 μm, 735 ± 743 μm, and from 30 μm to 130 μm at 20-μm depth intervals, respectively. No significant association between IVCM and meibography parameters (P = 0.53) was found. CONCLUSIONS: Imaging rete ridges with IVCM should include at least 5 nonoverlapping single frames in the upper eyelid margin. At least 3 openings imaged between 30 and 130 μm at 20-μm depth intervals are recommended to determine the opening area.</p

Lid Margin Score Is the Strongest Predictor of Meibomian Area Loss

PURPOSE: Although meibography provides direct evidence of gland dropout in meibomian gland dysfunction, this specialized technique is not available in most clinics. The primary aim was to determine which clinical ocular marker was most related to meibomian area loss. A secondary aim was to determine associations with confocal microscopy imaging of the lid margin. METHODS: One hundred participants from age 18 to 65 years were recruited. Measurements of the right eye and its upper eyelid, where relevant, included noninvasive tear break-up time, bulbar and limbal redness scores, blepharitis score, lipid layer thickness, number of parallel conjunctival folds, tear osmolarity, corneal fluorescein staining, phenol red thread test, lid margin score, meibography, and in vivo confocal microscopy. Participants also completed the Ocular Surface Disease Index questionnaire. The relationships between the measurements were determined using the Spearman correlation. The receiver operating characteristic curve and area under the receiver operating characteristic curve were used to determine the cutoff value of clinical markers. RESULTS: Significant correlations were found between meibomian area and lid margin score (r = -0.47, P < 0.01), and meibomian tortuosity and lid signs of blepharitis (r = -0.32, P < 0.01). Area under the receiver operating characteristic curve analysis revealed that a lid margin score of ≥1.70 detected meibomian area loss with a sensitivity of 0.58 and a specificity of 0.86. There were significant correlations between meibomian area and orifice area at 30 μm depth (r = -0.25, P = 0.01). CONCLUSIONS: The lid margin score was most related to the meibomian area and thus the best predictor of undiagnosed meibomian area loss.</p

Characterization of goblet cells in a pterygium biopsy using laser scanning confocal microscopy and immunohistochemistry

<b>PURPOSE</b>\ud \ud - To confirm that structures presumed to be GCs observed using <i>laser scanning confocal microscopy (LSCM)</i> are actually GCs.\ud \ud <b>METHODS</b>\ud \ud - A single tissue sample was obtained from a pterygium that was freshly excised from a 33-year-old male. After viewing what were believed to be GCs in the tissue sample using LSCM, the same sample was observed using laboratory confocal microscopy and immunohistochemistry. GCs were identified by a combination of classic morphologic appearance and the use of immunofluorescence to antibodies for mucin 5AC and cytokeratin-7. The LSCM and immunohistochemistry results were compared.\ud \ud <b>RESULTS</b>\ud \ud - Using LSCM, GCs were observed between 7 and 41 μm deep, at the level of the superficial basal cells of the tissue sample. GCs were estimated to have a diameter of 35-40 μm near the surface and 20-30 μm in the deeper layers. A small dark dot was visible in some GCs, indicating cell nuclei and/or the opened apical portion of cells representing the site of mucin release. GCs were more reflective and larger than the surrounding cells. Positively stained GCs in immunofluorescence showed a similar distribution pattern to those observed with LSCM. The tissue sample stained intensely for GC-specific mucin type 5AC.\ud \ud <b>CONCLUSIONS</b>\ud \ud - The pattern of discrete, large reflective cells observed using LSCM are likely to be GCs

Association between conjunctival goblet cells and corneal resident dendritic cell density changes in new contact lens wearers

Background: To explore the interlink between conjunctival goblet and corneal dendritic cell density after six months of lens wear and to predict dendritic cell migration to the central cornea based on goblet cell loss in the conjunctiva as a response to contact lens wear. Methods: Sixty-nine subjects who had never previously worn contact lenses were observed for six months; 46 were fitted with contact lenses and 21 served as a control group. Corneal confocal microscopy was used to quantify goblet and dendritic cell density before and after six months of daily lens wear. Symptomatic and asymptomatic groups were identified in the lens-wearing group using a combination of signs and symptoms present. Pearson's correlation was used to determine associations between the total change of cell densities after six months of lens wear. Results: At baseline, there was no association between conjunctival goblet and corneal dendritic cell density (p > 0.05). After six months, there was an inverse association between the absolute change of conjunctival goblet and corneal dendritic cell density (ρ = −0.34, p = 0.03) in all participants (n = 69). Dendritic cell density in the central cornea was increased by 1.5 cells/mm2 for every decrease of 1 goblet cell/mm2 in the conjunctiva. Conclusions: After six months of wear, contact lens-induced goblet cell loss can partially predict resident corneal dendritic cell migration to the central cornea (observed as an increase in dendritic cell density). The associations between total cell density change after six months was established in wearers regardless of lens symptomatology, suggesting that cell density changes as a physiological adaptation to regulate the effect of contact lens wear on the ocular surface.</p

In vivo immune cell dynamics in the human cornea

In vivo confocal microscopy (IVCM) allows the evaluation of the living human cornea at the cellular level. The non-invasive nature of this technique longitudinal, repeated examinations of the same tissue over time. Image analysis of two-dimensional time-lapse sequences of presumed immune cells with and without visible dendrites at the corneal sub-basal nerve plexus in the eyes of healthy individuals was performed. We demonstrated evidence that cells without visible dendrites are highly dynamic and move rapidly in the axial directions. A number of dynamic cells were observed and measured from three eyes of different individuals. The total average displacement and trajectory speeds of three cells without visible dendrites (N = 9) was calculated to be 1.12 ± 0.21 and 1.35 ± 0.17 μm per minute, respectively. One cell with visible dendrites per cornea was also analysed. Tracking dendritic cell dynamics in vivo has the potential to significantly advance the understanding of the human immune adaptive and innate systems. The ability to observe and quantify migration rates of immune cells in vivo is likely to reveal previously unknown insights into corneal and general pathophysiology and may serve as an effective indicator of cellular responses to intervention therapies.</p