Glucocorticoid hormones are vital; their accurate operation is a necessity at all ages and in all life situations. Glucocorticoids regulate diverse physiological processes and they use many signaling pathways to fulfill their effect. As the operation of these hormones affects many organs, the excess of glucocorticoids is actually detrimental to the whole human body. The endogenous glucocorticoid excess is a relatively rare condition, but a significant proportion of adult people uses glucocorticoid medication for the treatment of chronic illnesses, therefore they are exposed to the side effects of long-term glucocorticoid treatment. Our review summarizes the adverse effects of glucocorticoid excess affecting bones, adipose tissue, brain and skin, focusing on those effects which involve the Wnt/β-catenin pathway. Glucocorticoids (GCs) are pleiotropic hormones with an overall impact on different processes: cell proliferation and survival, growth, reproduction, metabolism and cardiovascular function essential for life. They are also responsible for the proper operation of the immune system and central nervous system ,2,3. GluEndogenous glucocorticoid excess, Cushing’s syndrome (CS), is a relatively rare disease, with an annual incidence of 0.7–2.4 cases per million population . GlucocoGlucocorticoid signaling engages many signaling pathways to exert its pleiotropic effect in the human body. The most studied pathways include the GH/IGF-1 axis, TGFβ-SMAD signaling, MAPK signaling, PI3/Akt signaling, Wnt-signaling and BMP signaling. All these at various levels can be responsible for signs observed in patients suffering from GC excess.The Wnt/β-catenin pathway is an ancient signaling cascade that controls numerous cell processes  during embryonic development and adult homeostasis . Its derWnt proteins are a family of small signaling glycoproteins, which bind to a member of the Frizzled (Fz) receptor family. In the absence of Wnt-ligand, β-catenin is constantly degraded by a destruction complex composed of Axin and Adenomatous polyposis coli (APC) which admit the phosphorylation of β-catenin by glycogen synthase kinase 3β (GSK-3β) and casein kinase 1 (CK1). Phosphorylated β-catenin is subjected to proteosomal degradation, resulting in low free cytoplasmic and nucleic β-catenin levels in the absence of Wnt-ligand binding. The binding of Wnt to the Fz receptor requires low-density lipoprotein receptor-related-protein 5 or 6 (LRP 5/6) as coreceptors. The formation of the Wnt-Fz-LRP 5/6 complex leads to the membrane recruitment of the Axin complex by Dishevelled proteins (Dvl), Axin being bound to a cytoplasmic tail of LRP 5/6. In the absence of the degrading complex, β-catenin escapes from phosphorylation and consequential ubiquitination. This leads to an increase in free β-catenin levels which form complexes in the nucleus with the DNA-bounded T cell factor/lymphoid enhancer factor (TCF/LEF) and activate Wnt target gene expression. Up to now,10 families of Wnt-pathway agonists were identified [The common occurrence of adrenal adenomas in patients with familial adenomatous polyposis highlighted the role of the Wnt/β-catenin pathway in adrenal tumorigenesis ,15. WithIn another study, genetic alterations were found in 5 of 33 adrenal adenomas (15%). Of these, three were cortisol-secreting, one aldosterone-producing and one nonfunctioning adenoma . In two Homeostasis of the adult skeleton depends on the balance between bone-forming and bone-resorbing processes and relies on the complex communication between osteoblasts, osteocytes and osteoclasts.Bone-forming osteoblasts are derived from mesenchymal stem cells (MSCs) located in the bone marrow. Master transcriptional regulator Runx controls the commitment of MSCs toward osteogenesis and the following differentiation processes . PreosteThe communication between bone cells is conducted partly through the production of cytokines. Osteoblasts release M-CSF, which binding to its cognate receptor on preosteoclasts, provides signals essential for the survival and proliferation of osteoclast precursors . The recGlucocorticoid-induced osteoporosis (GIO), the most common cause of secondary osteoporosis ,28, is cGC excess rapidly induces the apoptosis of osteoblastic cells as it was demonstrated on different cell lines and in patients with CS or receiving GC treatment. Sclerostin treatment of human osteoblastic cells initiates apoptosis through a caspase-activated mechanism . sFRP-1 Glucocorticoids are detrimental to osteo-anabolic processes through their effects on oxidative stress levels ,35. The Glucocorticoid excess enhances the expression of Wnt-inhibitors. Supraphysiological levels of glucocorticoids enhance sFRP-1 expression in primary mesenchymal cell cultures in vitro and in osteoblasts and bone marrow cells in vivo . The expWnt-pathway inhibition influences cell proliferation and maturation of cells from osteoblastic lineage. Dkk-1 expression in rat calvaria cells was associated with inhibited osteoblast differentiation and with the lack of mineralized nodules; parallelly, increased adipocyte differentiation could be detected in vitro . In Yao’The loss of osteocytes by GC-induced apoptosis damages the osteocyte-canalicular network and the mechanosensory ability of bone, which, in turn, decreases the capacity of osteocytes to regulate osteoclasts’ function. In mechanosensory osteocytes, the capacity to produce RANKL is much higher than that in osteoblasts . Mice laIntact Wnt-signaling exerts an indirect negative role on osteoclastogenesis: in pluripotent mesenchymal cells, and stromal cells Wnt3a upregulates OPG expression , therebyThe role of sFRP-1 in the regulation of osteoclasts now seems to be bidirectional: first, sFRP-1 inhibits osteoclast formation by preventing the fusion of osteoblast precursors , secondlRecently, Albers et al. demonstrated a direct effect of the Wnt-signaling pathway on osteoclastogenesis and bone resorption beside the indirect effects mediated by osteocytes . They foIn summary, we can conclude that the Wnt/β-catenin pathway is essential in normal bone homeostasis, and the harmful effects of GC excess are closely related to the inadequate operation of this pathway.Adipogenesis is a well-orchestrated process during which MSC-derived preadipocytes develop into mature adipocytes. This process involves the interplay of several transcription factors, from which PPARγ functions as a master regulator .Wnt10b gene detected in families with early-onset obesity represent additional evidence for the strong relation between PPAR- and Wnt-signaling [There is plenty of evidence for strong communication between adipose tissue and bones, based (partly) on the interaction between PPAR- and Wnt-signaling pathways. Sustained activation of the Wnt/β-catenin pathway by expression of Wnt10b and inhibiting expression of PPARγ-associated adipogenic genes, in murine preadipocytes, maintains preadipocytes in an undifferentiated state . Inverseignaling .Clinically, the strong but opposite-sign communication between adipogenesis and osteoblastogenesis appears most expressively in patients with Cushing’s syndrome presenting with osteoporosis, osteopenia and increased bone fragility associated with central obesity ,53. GC eGCs change the characteristics of adipose tissue differently in VAT and SAT, as it was demonstrated in methylprednisolone-treated rats . An incrAdipose tissue produces Wnt-inhibitors belonging to the sFRP family. Gene expression of all sFRPs (sFRP1-5) was analyzed in subcutaneous and visceral adipose tissues of obese and non-obese women . In SAT,Adipocytes secrete a variety of signaling proteins  and proinflammatory cytokines which are responsible for the auto-, para- and endocrine effects of adipose tissue. Adipose tissue-derived cytokines  were proved to affect the function of osteoblasts and/or osteoclasts ,59 and nLeptin is one of the first discovered adipokines and nowadays it is considered as the prototype of all signaling molecules produced by the adipose tissue. It is responsive to extensive communication between adipose tissue and brain, pancreas and reproductive organs . The relData from the last two decades have provided sufficient evidence for the role of Wnt-signaling in different processes of neurogenesis. Recently, Guo summarized these results and concluded that the Wnt/β-catenin signaling pathway plays a context-dependent role in oligodendrogenesis, oligodendrocyte differentiation and myelination. In addition, the effects associated with the Wnt/β-catenin pathway depend on the developmental stage of CNS, oligodendrocyte and CNS microenvironment .Detrimental effects of increased GC levels on brain structure, neurological function and emotional life have been demonstrated in numerous studies. GC excess negatively affects memory retrieval, cognitive functions and behavior and they have significant effects on brain structure ,67.Of brain regions, the hippocampus seems to be the most vulnerable to the neurotoxic effect of GCs ,68,69. MClinically, brain development and affective problems of preadolescent children with or without fetal exposure to synthetic GCs were evaluated by Davis et al. . A signiAccumulating evidence suggests that long-lasting effects of GCs on the brain are regulated through epigenetic mechanisms. Rat embryonic neural stem cells exposed to dexamethasone underwent heritable alterations; GC effects induced in parent cells were detectable in daughter cells which were never exposed directly to GCs . MethylaExtensive genome-wide alterations in promoter methylation, typically the hypomethylation of the affected promoters, were detected in the hippocampi of fetal guinea pigs treated prenatally with GCs . The samInhibitory effects of dexamethasone on the neural precursor cells and the role of the Wnt/β-catenin pathway in this process were described by Boku et al. . The negThe negative effects of GCs were demonstrated on human neural progenitor cells (hNPCs) responsible for the major cell types  of the brain. Treating hNPCs with dexamethasone caused a marked decrease in proliferation and neuronal differentiation of hNPCs while increased glial cell formation. Dexamethasone induced the upregulation of the Wnt-signaling inhibitor Dkk-1 which effect could be inhibited by adding a GR antagonist, mifepristone. The final conclusions were that Dkk-1 was the primary target for GR in hNPCs and the regulation of hNPCs by dexamethasone and Dkk-1 was mediated through the canonical Wnt-signaling pathway .High levels of GCs induced the generation of reactive oxygen species (ROS) in primary hippocampal and cortical cell cultures . AccordiSkin, besides its primary function of protecting the body, is an important part of immunological processes and extraadrenal steroidogenesis . RecentlKeratinocytes, one of the main cell types of the epidermis, synthesize cholesterol, the precursor of all steroids . EpidermRelated to Cushing’s syndrome, a part of the signs and symptoms are relatively common  and makes CS difficult to diagnose. Some of the skin-related manifestations  are between those signs which best discriminate Cushing’s syndrome from other diseases, while other skin-related signs  are very common in patients with CS  .GCs have profound effects on the different layers of the skin. In the epidermis, the decreased size of keratinocytes, the thinning of the epidermis and the diminution of the lamellar lipid bilayer in the stratum corneum are well-known histopathological features of GC excess . The molIn the dermis, GCs lead to a decreased number of fibroblasts with the rearrangement of the dermal fibrosis network . The antThere are only little data about the effect of GC excess on hypodermis, but we have to note the confusion in the literature related to the definition of skin-associated adipocyte layers. Traditionally, the thick layer of adipocytes underlining the reticular dermis has been called hypodermis or subcutis and it was considered that all skin-associated adipose tissues represent one depot . The preRelated to the effects of GC excess on skin compartments, it seems plausible that skin atrophy involves all skin layers, including dermal white adipose tissue. An indirect proof for this assumption was presented very recently by Baida et al. . They stEpidermal appendages are also influenced by GC excess. Based on the data of 481 patients published by the European Registry on Cushing’s syndrome, hair loss was present in 31% of patients . Female Ectopic expression of Wnt-inhibitor Dkk1 in epidermis drives to the lack of epidermal appendages: hair, whiskers, teeth and mammary gland . EpithelAs the canonical Wnt-signaling plays an important role in skin cells’ proliferation and differentiation, its impact on wound healing is self-evident. Wnt10a-deficient mice, besides their phenotype including alopecia and follicle growth failure, showed delayed wound healing compared to their wild-type littermates . De novoIn non-healing edges of venous ulcers, components of the Wnt-pathway were found to be deregulated: phosphorylated β-catenin was found mainly in the cytoplasm and nuclear; while in healthy skin specimens, β-catenin was present mostly at the membrane of the basal layer . Jozic eWe have to conclude that, related to GC excess-induced skin alterations, the sole role of the Wnt/β-catenin pathway has not yet proven in many processes, but its function obviously contributes to these phenotypes. Future research can clarify the bidirectional link between the Wnt-pathway and GC-induced skin lesions.Balanced operation of the Wnt/β-catenin pathway is indispensable for homeostatic processes in many tissues, including bones, brain, adipose tissue and skin .. HoweveSelective inhibition of sFRP-1 was also proposed as a potential tool to stimulate Wnt-signaling, thereby osteo-anabolic processes in bone ,108. In Wnt/β-catenin signaling can be stimulated by physical exercise. In a study conducted among women affected by abdominal obesity, osteoblast cell cultures were exposed to sera of these women at an initial timepoint and 4, 6 and 12 months after they attended a physical training program combined with a hypocaloric diet . ProteinA similar study was carried out among breast cancer survivors, where serum levels of Dkk-1 and sFRP-1 were followed before and after a 12-week long physical exercise training program. The conception of this study was based on the results of former studies showing that elevated serum Dkk-1 levels correlated with poor prognosis in certain types of cancer . SignifiAnother evidence for the beneficial effects of physical exercises on Wnt-pathway was the mechanosensitive expression of sclerostin (specific product of osteocytes). Mechanical unloading of wild-type mice caused downregulation of Wnt/ß-catenin signaling with the upregulation of the sclerostin levels . In SostThe beneficial effects of physical exercise were also highlighted by Chen, who recently reviewed the paradox of chronic stress and chronic exercise, both known to increase basal cortisol levels. Their metanalysis underlined that solely increased basal cortisol levels are not necessarily detrimental to the human body and their work suggested that other factors are also needed for the harmful effects of glucocorticoid excess . RelatedRelated to this, Noguchi et al. proved that the detrimental effects of the glucocorticoid excess on bone could be prevented by oxygen ultra-fine bubbles saline injection . In predSummarizing these results, it can be assumed that the restorative effects of physical exercise on Wnt/ß-catenin pathway can be linked partly to an enhanced oxygen supply, and inversely, deleterious effects of GC excess on Wnt-pathway are more pronounced when hypoxic conditions are present and probably the severity of the damaging effects is related to the degree of hypoxia.The relationship between GC excess and severe comorbidities is well-known: fractures occur in 30%–50% of the patients subjected to long-term hypercortisolism ; the rat


Advance care planning is the process of discussing health care treatment preferences based on patients’ personal values, and it often involves the completion of advance directives. In the first months of 2020, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began circulating widely in the American state of Colorado, leading to widespread diagnosis of coronavirus disease (COVID-19), hospitalizations, and deaths. In this context, the importance of technology-based, non–face-to-face methods to conduct advance care planning via patient portals has increased.The aim of this study was to determine the rates of use of a web-based advance care planning tool through a health system–based electronic patient portal both before and in the early months of the COVID-19 pandemic.In 2017, we implemented web-based tools through the patient portal of UCHealth’s electronic health record (EHR) for patients to learn about advance care planning and complete an electronically signed medical durable power of attorney (MDPOA) to legally appoint a medical decision maker. Patients accessing the portal can complete and submit a legally valid MDPOA, which becomes part of their medical record. We collected data on the patients’ date of MDPOA completion, use of advance care planning messaging, age, sex, and geographic location during the early phase of the COVID-19 pandemic .P<.001). The mean age of the advance care planning portal users was 47.7 years (SD 16.1), and 2206/3292 (67.0%) were female. Women were more likely than men to complete an MDPOA, particularly in younger age groups (P<.001). The primary use of the advance care planning portal tools was the completion of an MDPOA , compared to sending an electronic message . Over 50% of patients who completed an MDPOA did not have a prior agent in the EHR.Over a 5-month period that includes the early phase of the COVID-19 pandemic in Colorado, total monthly use of the advance care planning portal tool increased from 418 users in January to 1037 users in April and then decreased slightly to 815 users in May. The number of MDPOA forms submitted per week increased 2.4-fold after the stay-at-home order was issued in Colorado on March 26, 2020 (Use of a web-based patient portal to complete an MDPOA increased substantially during the first months of the COVID-19 pandemic in Colorado. There was an increase in advance care planning that corresponded with state government shelter-in-place orders as well as public health reports of increased numbers of COVID-19 cases and deaths. Patient portals are an important tool for providing advance care planning resources and documenting medical decision makers during the pandemic to ensure that medical treatment aligns with patient goals and values. On March 11, 2020, the World Health Organization characterized coronavirus disease (COVID-19) as a pandemic. At that time, approximately 118,000 cases had been reported in 114 countries, and 4291 people had died worldwide due to COVID-19. As of June 2020, the fatality rates for COVID-19 have been estimated to be between 0.6% and 5%; these rates are highest among older adults and people with chronic conditions [Advance care planning is the process of discussing medical treatment preferences based on personal values, and it often involves the completion of advance directives ,4. In thCOVID-19 has stimulated advance care planning in emergency departments and ICUs, indicating a need to provide advance care planning interventions and resources prior to hospital admission . TeleheaPatient portals provide patients with secure access to personal health information contained in their electronic health record . In addiThis retrospective observational study examined advance care planning by patients using web-based advance care planning tools available through the UCHealth patient portal that enable the completion of legally valid MDPOA forms. UCHealth is a regional health care system serving Colorado , southern Wyoming, and western Nebraska. In 2019, 1.9 million patients received care in 12 UCHealth hospitals and 800 outpatient clinics. My Health Connection is the UCHealth patient portal integrated within the Epic electronic health record ; as of May 2020, approximately 735,000 patients had a My Health Connection account. The Colorado Multiple Institutional Review Board approved this project as an evaluation of a clinical initiative.We previously developed and tested tools to conduct advance care planning using the My Health Connection patient portal ,23. BrieData were collected from December 29, 2019, to May 30, 2020, an approximately 5-month period that includes the 2 months prior to community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Colorado. These specific dates were chosen to enable comparison of 7-day weekly periods. The first COVID-19 diagnosis in Colorado was announced on March 5, 2020. Thus, January and February were effectively “pre–COVID-19” months in Colorado. Colorado implemented a statewide stay-at-home order on March 26, 2020. We collected data through chart review for UCHealth patients who interacted with the My Health Connection patient portal advance care planning tools, specifically by completing an electronic MDPOA form or by sending an electronic message to the advance care planning support team. Demographic information included age, sex, and geographic location . To explore how patients who submitted an electronic MDPOA were choosing their health care agents, we categorized patients into the following five groups: 1) first-time designation of an MDPOA, no prior agent  in the EHR; 2) prior orally appointed agent in the EHR who is retained in the electronic MDPOA; 3) prior MDPOA on file and the same agent is retained in the electronic MDPOA; 4) prior MDPOA on file and the electronic MDPOA names a new agent; and 5) prior orally appointed agent in the EHR and the electronic MDPOA names a new agent. A prior MDPOA could include any MDPOA form in the patient’s EHR (either a paper document that was scanned into the patient’s record or a previously submitted electronic MDPOA). We also identified invalid MDPOA submissions based on advance care planning support team review and discussion with the patient or their clinical team, as previously described . InvalidP value <.05 was considered statistically significant. All statistical analyses were performed using SAS version 9.4 (SAS Institute).We used descriptive analyses to describe the characteristics of the patient portal users and expressed them as frequencies with percentages. Age categories were chosen to align with state-based surveys of community-based advance care planning rates . We usedP<.001). The weekly rate was 2.4-fold higher in the 9 weeks after March 26 compared to the nine weeks prior to March 26. Over a 5-month timeframe that includes the early phase of the COVID-19 pandemic in Colorado, the number of user clicks on the UCHealth advance care planning patient portal page increased from 3511 in January to 6819 in April and 10,077 in May. The total number of monthly advance care planning portal tool users increased from 418 in January to 1037 in April, then slightly decreased to 815 users in May . Week-toP<.001), where the proportion of women who used the advance care planning portal tools was greater than that of men for all age groups and significantly greater in the younger age groups  with a mean age of 47.7 years (SD 16.1). The ages of patients who used the advance care planning portal tools were relatively evenly distributed between 25 years and ≥65 years . The lare groups . RegionaThe primary use of the advance care planning portal tools was the completion of a MDPOA . Of the Fewer than 5% of patient portal users who used the advance care planning tools sent an electronic message to a centralized advance care planning support team . The majority of these messages were questions related to how users could submit existing paper advance directives so that these directives would be available in the EHR (this feature is planned but not currently available).To our knowledge, this is the first study to identify a significant increase in patient-initiated completion of electronic MDPOAs through a patient portal during the COVID-19 pandemic. In the context of COVID-19, conducting advance care planning is increasingly important to ensure that patients have identified medical decision makers whom they trust and that they receive treatment that aligns with their values and preferences. Patient portals are a particularly useful tool for advance care planning during a pandemic because they are accessible 24 hours per day, do not require face-to-face contact, and are directly linked to health care providers and the EHR.A significant increase in advance care planning portal tool use was seen in April 2020, aligned with increased awareness of the surge in COVID-19 cases, hospitalizations, and deaths in Colorado, the State of Colorado’s stay-at-home order , and the widely publicized authorization of the state’s Crisis Standards of Care on April 5. The trend in increased MDPOA completion began in March, which is closely aligned with the announcement of the first COVID-19 case in Colorado . Although advance care planning is currently taking place in emergency departments and ICUs , these pApproximately half of the MDPOA forms submitted during this timeframe were new submissions, suggesting that in the setting of the COVID-19 pandemic, people are interested in advance care planning and documenting their health decision makers. COVID-19 has heightened patients’ awareness of the potential of becoming seriously ill. These findings show that patients are willing to act on this knowledge without marked investment in health system resources. While health care providers are calling for improved advance care planning during the pandemic, little is known about patient needs and preferences regarding COVID-19–specific advance care planning processes. The technology of the portal may be an important facilitator. An electronic MDPOA can overcome barriers related to lack of documentation access, lack of ability to share completed forms with the health care system, and perceived time, financial, or legal barriers. These users may welcome the ability to complete the MDPOA through the patient portal instead of with an attorney or health care practitioner because of the need for dedicated appointments, which are likely difficult to access due to stay-at-home orders and clinic preference for telehealth appointments.During a recent qualitative advance care planning patient portal study, older patients and their caregivers indicated a need for easy access to their current active MDPOA via the portal . Access Patients across the age spectrum used the advance care planning portal tools. Surprisingly, the largest age group of the users was 25 to 34 years, demonstrating that users in this age group are interested in engaging in advance care planning by choosing a medical decision maker. Advance care planning typically increases with age ,33. In CIn addition to advance care planning, age is associated with patient portal adoption and use ,36. HealIn this cohort, women were more likely to complete an MDPOA across all age groups; however, this difference was more pronounced in younger age groups. Gender differences have been found in both patient portal use and advance care planning, with women being more likely to engage with a portal  and withThere are limitations to our study. Our data lacked information on race, ethnicity, education status, and specific geographic location  to determine rurality, which are all known to impact access to health care, health technology use, and advance care planning engagement . We alsoThe use of a patient portal to complete a MDPOA form to choose a legal medical decision maker increased substantially during the first months of the spread of COVID-19 in the state of Colorado. With the currently increased interest in advance care planning among patients and health care providers, patient portals may be an important tool for advance care planning during the COVID-19 pandemic to enhance and supplement face-to-face advance care planning efforts in health systems.


This is explained by the formation of surfactant aggregates near the polyelectrolyte chains at concentrations much lower than the bulk critical micelle concentration and inhibition of the photo-isomerization kinetics due to steric hindrance within the densely packed aggregates.Ionic complexation of azobenzene-containing surfactants with any type of oppositely charged soft objects allows for making them photo-responsive in terms of their size, shape and surface energy. Investigation of the photo-isomerization kinetic and isomer composition at a photo-stationary state of the photo-sensitive surfactant conjugated with charged objects is a necessary prerequisite for understanding the structural response of photo-sensitive complexes. Here, we report on photo-isomerization kinetics of a photo-sensitive surfactant in the presence of poly. We show that the photo-isomerization of the azobenzene-containing cationic surfactant is slower in a polymer complex compared to being purely dissolved in aqueous solution. In a photo-stationary state, the ratio between the  A stock solution of different salts of 1105 mM was prepared and diluted to the required concentrations, ranging from 4 mM to 780 mM.λ = 365 nm, λ = 455 nm, λ = 490 nm, λ = 530 nm. Absorption spectra of the surfactant showing the different concentrations of trans/cis species at different illuminations can be seen in λ = 376 nm  until it reached the stationary state.Time resolved UV-Vis measurements were performed with a commercial Cary 5000 UV-Vis-NIR spectrophotometer instrument . A 1 cm thick rectangular quartz cuvette, transparent in all directions , was filled with 2 mL of aqueous solution and sealed in order to keep the concentration constant during the measurement. An LED lamp  (perpendicular to monitoring beam) illuminated the total volume of the sample holder for fixed wavelengths trans isomer concentration, cT,0, at the initial time of illumination. The absorbance was monitored at a wavelength of 376 nm to calculate the ratio of trans isomers cT(t)/cT,0. This particular wavelength was selected as the absorption of the cis isomer is minimal at this wavelength. cT(t)/cT,0 can be calculated as follows with Equation (1):0. The value of the absorbance mediated from the scattering of PAA only, AbsS, is obtained by recording the absorbance of the pure polymer at the same wavelength for the same polymer concentration :kTC and kCT being the isomerization rate constant and cT and cT,0 being concentrations of trans isomers at any time and initial time , respectively. Exposing the surfactant solution to light leads to concentration fractions of trans and cis isomers being in equilibrium, where both rates are equal, i.e., dcT/dt = −dcC/dt and results in a rate constant ratio X between kTC and kCT, X∙kTC = kCT. Then Equation (2) can be transformed into Equation (3):τ as shown in Equation (4):with cT,eq is the concentration of trans isomers at a photo-stationary state.where The photo-isomerization kinetic of a pure surfactant in bulk has been previously described in detail elsewhere . In shor6) forming a complex with poly(acrylic acid) salt as a function of polymer concentration, irradiation intensity and wavelength, as well as ionic strength for two different salts, NaBr and NaAc. The photo-isomerization was studied by the time-resolved UV-Vis absorbance, where the irradiation of the samples with different wavelengths and intensities is introduced in situ during simultaneous recording of the absorbance. The photo-isomerization of the surfactant is different for PAA-AzoC6 complexes in comparison to AzoC6 in bulk, where the isomerization rate is generally lower in PAA-AzoC6 complexes and yields different values of the equilibrium concentration. The concentration fraction of the trans and cis isomers at the photo-stationary state for PAA-AzoC6 is generally higher than for pure AzoC6. We have found also that the photo-isomerization kinetics vary with light intensity and wavelength. This suggests that it applies to surfactant complexes with maybe any polymers but strongly to weak polyelectrolytes since a surfactant is a surface-active material and will always have a certain tendency to aggregate at interfaces and macromolecules in a certain fashion.We report on isomerization kinetics of light responsive azobenzene-containing surfactants (AzoC


Photodynamic therapy (PDT) is a treatment modality that involves three components: combination of a photosensitizer, light and molecular oxygen that leads to localized formation of reactive oxygen species (ROS). The ROS generated from this promising therapeutic modality can be lethal to the cell and leads to consequential destruction of tumor cells. However, sometimes the ROS trigger a stress response survival mechanism that helps the cells to cope with PDT-induced damage, resulting in resistance to the treatment. One preferred mechanism of cell death induced by PDT is apoptosis, and B-cell lymphoma 2 (Bcl-2) family proteins have been described as a major determinant of life or death decision of the death pathways. Apoptosis is a cellular self-destruction mechanism to remove old cells through the biological event of tissue homeostasis. The Bcl-2 family proteins act as a critical mediator of a life–death decision of cells in maintaining tissue homeostasis. There are several reports that show cancer cells developing resistance due to the increased interaction of the pro-survival Bcl-2 family proteins. However, the key mechanisms leading to apoptosis evasion and drug resistance have not been adequately understood. Therefore, it is critical to understand the mechanisms of PDT resistance, as well as the Bcl-2 family proteins, to give more insight into the treatment outcomes. In this review, we describe the role of Bcl-2 gene family proteins’ interaction in response to disease progression and PDT-induced resistance mechanisms. Apoptosis is a self-limiting mechanism of cell death in which unwanted cells are removed in a biological manner, to maintain tissue homeostasis. This mechanism and its regulation are essential for normal cellular homeostasis and to prevent diseases like cancer from developing. In late 1980s, scientists successfully used molecular techniques to identify some machineries involved in apoptosis signal transduction pathway ,3.It has been well-established that photodynamic therapy (PDT) induces apoptotic cell death by changing the cell shape and structure. However, the cytoskeletons have been involved in the development of PDT resistance through signal transduction processes . PDT-treThe Bcl-2 is an oncogene that was identified in human B cell follicular lymphoma. The involvement of Bcl-2 in the apoptotic process was identified by Vaux and his co-workers in 1988 . Bcl-2 fProteins included in the Bcl-2 protein family are based on sequence homology of the founding member Bcl-2, in the four homologies of the BH region. Most members have a multiple binding membrane region on their carboxyl termini that facilitates binding of the proteins, and its location is on the MOM or to the endoplasmic reticulum (ER) membrane ,12,13. TL competes with Bax at the BH3 homology site, to favor the pro-survival Bcl-XL binding, thus causing the opposite of the first process [The multifaceted functions of Bcl-2 family members in cell death promotion and survival interaction mean that Bax can increase mitochondrial membrane permeability to release cytochrome c protein in response to an apoptotic stimuli . Moreove process . In aged process .The Bcl-2 family of proteins functions through mitochondrial binding interactions and permeability of its outer membrane, to regulate and control cell death activity. The regulation of MOM that favors the pro-apoptotic proteins family often results in membrane permeabilization and pore formation through which cytochrome c proteins are released for caspase cascades’ activation, to dismantle and destroy the cells . The regMany researchers have described a model that highlights the role of membrane as the locus of action of most Bcl-2 family proteins ,20. The Similarly, Korsmeyer and colleagues have proposed a model called the “rheostat model”, stating that apoptosis is determined through the amount of pro-apoptotic and survival proteins activated in a cell . This moThe pro-apoptotic Bcl-2 effector proteins are Bax and Bak, which contain the three BH domain and are the major inducers of MOMP . Under pL within the inner membrane [The fundamental function of Bcl-2 family proteins and its interaction with the shape changes, morphology and organelle localization in the mitochondria has been reported. Rolland and colleagues found that there is a close link between Bcl-2 family proteins and the dynamics of the GTPases Drp1 and Mfn1/2 that mediate the mitochondrial outer membrane fission and fusion process . This prmembrane . Anothermembrane .Photodynamic therapy is a treatment that combines the interaction of light and a photosensitizer in the presence of molecular oxygen, to generate ROS that cause oxidative damage . The pho1PS*). The 1PS* is unstable in the sense that it has a short half-life, and through fluorescence emission, it returns to the ground state or undergoes intersystem crossing to a long-lived triplet excited state (3PS*). This new excited triplet state can also return to the ground state through phosphorescence, or be combined with molecular oxygen in a photochemical reaction, to induce phototoxicity. In the photochemical reaction (type I), the 3PS* reacts directly by electron or hydrogen biomolecules transfer, to form peroxides, superoxide ions and hydroxyl radicals. Meanwhile, in (type II), the 3PS* undergoes chemical reaction with molecular oxygen (3O2) to produce the singlet oxygen (1O2). The 1O2 generated is a very toxic activated oxygen molecule that is the key to the photo-cytotoxicity reaction followed by the PDT treatment, because of its interaction with proteins, nucleic acids and lipid biomolecules [The photosensitizer that initiates the photochemical reaction always exists in the ground state, and upon specific wavelength light exposure, it absorbs light photon and becomes excited in singlet unstable state  are used in PDT treatments, in so far that the characteristic spectrum matches with the maximum absorption wavelength of the chosen PS. However, the lasers are most preferable because they precisely deliver the amount of light needed for PS activation and wavelengths specificity, unlike the LEDs, which are very difficult to use to deliver light in most anatomical areas .Multidrug resistance (MDR) is a phenomenon attributed to the overexpression of ATP-binding cassette (ABC) proteins that inhibit transport across membranes. It occurs when cancerous cell become resistance to one or two anticancer drugs with related chemical structures and mechanism of action. The ATP-binding cassette (ABC) transporter proteins  involved in MDR include p-glycoprotein (P-gp), multidrug resistance protein (MRP) and breast cancer resistance protein (BCRP) . Photosel-aspartyl chlorin e6 (NPe6-PDT). Both PSs have different structure that decrease and increase the production of ROS [Furthermore, the studies by Jonker and colleagues have demonstrated that mouse with overexpression of ABCG2 transporter has the ability to pump out a photosensitizer PpIX and protect against its phototoxicity . Their fn of ROS . Other fn of ROS . TherefoThe activation of anti-apoptotic Bcl-2 family proteins has been observed in PDT-treated resistant cells , which rThis involvement was supported by the protein expression level and its ability to suppress apoptosis in PDT-treated HL60 cells. The overexpressed anti-apoptotic protein blocks the release of the cytochrome c and activation of caspase proteins from the mitochondria . The detAs a tumor suppressor protein, p53 is the most common gene expressed in many tumors . Its oveCancer cell death mechanism after PDT can be classified as apoptotic and non-apoptotic, such as autophagic and necrotic cell death, depending on the type of stimuli and cellular damage ,64. ApopApoptotic responses to PDT are carried out primarily in the mitochondria, through the intrinsic pathway . It occuThe membrane of the outer mitochondria is regulated by the Bcl-2 family of regulatory proteins; thus, they are the central regulators of the cell death pathway implicated in PDT-induced apoptosis . StudiesDeath-receptor-mediated apoptotic pathway occurs when photosensitizers targeting the cell membrane are used. The PS activation triggers specific cell death ligands from the tumor necrosis factor (TNF) superfamily  or TNF-α), which interacts with their cell-surface receptors (Fas or TNF receptor-1 (TNFR1)) in the death domain of the cytoplasmic tail. One major receptor of the family is the Fas receptor, which is actively involved in PDT-induced apoptosis . The FasATG5 gene by pharmacological inhibitors substantially triggered apoptosis in resistant tumor cells [ATG5 gene knockout in HeLa and MCF-7 cells moderately increases the efficacy of photofrin-based PDT, thus suggesting involvement of the autophagy gene in PDT therapy [PDT induces cell death either by apoptosis or a non-apoptotic manner, depending on the cell type, photosensitizer localization and light fluency . In the or cells . Pharmacor cells . Another therapy . This sh therapy .In conclusion, the mechanisms through which Bcl-2 family proteins promote or antagonize cell death are still elusive and constantly attract research investigations. Reports have shown that most PSs localize in the mitochondria, which is vital for apoptotic induction. During PDT, the activated ROS causes damage to the mitochondria, which triggers a preferred cell-death mechanism. Nonetheless, the resistance mechanism of PDT is fast evolving and has been linked to PS-altered uptake and efflux within the cell. The apoptosis-regulating proteins of the Bcl-2 family in PDT-resistant cells, if profiled and analyzed, may hint at the molecular interactions that sustain cell survival after PDT, which might possibly offer an insight towards winning the risk of MDR in cancer treatment.As discussed above, the cancer cells resist treatment through anti-apoptotic adaptation mediated by Bcl-2 family proteins. This have increased the interest of most researchers to find possible ways of addressing the problem and bringing a lasting solution to cancer-therapy resistance. More recently, scientists have developed small molecules called BH3 mimetics, to inhibit and mimic the action of certain BH3-only proteins. These drugs show relatively low affinity to Bax/Bak but target the surface pocket of Bcl-2, to abrogate its function and encourage cancer regression. Some examples of the Bcl-2 inhibitors developed (obatoclax (GX-15-070), ABT-737, Navitoclax and venetoclax) have been found to be useful in predisposing cancer cells to apoptosis . Taking


From this panel, they identified several neutralizing antibodies, including pairs that do not compete for binding to the receptor binding domain. Baum et al. focused in on four of these antibodies. All four are effective against known spike variants. However, by growing a pseudovirus that expresses the spike in the presence of individual antibodies, the authors were able to select for spike mutants resistant to that antibody. In contrast, escape mutants are not selected when pseudovirus is grown in the presence of pairs of antibodies that either do not compete or only partially compete for binding to the RBD. Such a pair might be used in a therapeutic antibody cocktail.There is an urgent focus on antibodies that target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral spike and prevent the virus from entering host cells. Hansen Science, this issue p. 1010, p. 1014 A noncompeting antibody cocktail to SARS-CoV-2 spike protein safeguards against the ability of virus mutations to lead to antibody resistance. Neutralizing antibodies have become an important tool in treating infectious diseases. Recently, two separate approaches yielded successful antibody treatments for Ebola—one from genetically humanized mice and the other from a human survivor. Here, we describe parallel efforts using both humanized mice and convalescent patients to generate antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, which yielded a large collection of fully human antibodies that were characterized for binding, neutralization, and three-dimensional structure. On the basis of these criteria, we selected pairs of highly potent individual antibodies that simultaneously bind the receptor binding domain of the spike protein, thereby providing ideal partners for a therapeutic antibody cocktail that aims to decrease the potential for virus escape mutants that might arise in response to selective pressure from a single-antibody treatment. In the setting of the current coronavirus disease 2019 (COVID-19) pandemic, there has been urgency to develop potent antiviral treatments, and early efforts have hearkened back to the days of Emil von Behring, who won the Nobel prize for showing that antibodies can be transferred in serum. However, technological advances over the last century have allowed for the progression from using convalescent serum to the utilization of recombinant fully human antibodies. The proposal to genetically humanize the immune system of mice . The ability to derive antibodies using genetically humanized VI mice as well as B cells derived from convalescent patients enabled us to isolate a very large collection of fully human antibodies with diverse sequences, binding properties, and antiviral activities. The prospective goal of these parallel efforts was to generate a large and diverse collection so as to allow for the selection of pairs of highly potent individual antibodies that could simultaneously bind the critical receptor binding domain (RBD) of the spike protein, thereby providing ideal partners for a therapeutic antibody cocktail that would have the potential to decrease the likelihood of virus escape mutants that might arise in response to selective pressure from single-antibody treatments  of human donors previously infected with SARS-CoV-2. VI mice elicited a robust immune response against the SARS-CoV-2 spike protein after immunization. Titers of mice blood collected 7 days after the last boost were determined by enzyme-linked immunosorbent assay (ELISA) (fig. S1). Mice with the highest titers were used for antibody isolation. Spleens from these mice were subjected to biotin-labeled monomeric RBD antigen staining and fluorescence-activated single-cell sorting. In parallel, whole blood was collected from three patients 3 to 4 weeks after a laboratory-confirmed polymerase chain reaction (PCR) positive test for SARS-CoV-2 and after showing symptoms of COVID-19. PBMCs were isolated by ficoll gradient and RBD-specific B cells were fluorescence-activated single-cell sorted. The first sets of antibodies derived from these platforms are described here.To assess antigen-specific responses, naturally paired heavy and light chain cDNAs were cloned from the mice and human-derived B cells  (table S1), which supports ACE2 blockade as the primary mechanism for neutralization. The antibodies bound specifically and with high affinity to monomeric SARS-COV-2 RBD [dissociation constant (Kd) = 0.56 to 45.2 nM] and dimeric SARS-COV-2 RBD (Kd = 5.7 to 42.8 pM). Because recombinant ACE2 receptor is being considered as a COVID-19 therapeutic  largely paralleled the affinity against the RBD (table S3). Additionally, the potent neutralizing activity of these four antibodies was confirmed in the additional neutralization assays, including neutralization of pVSV-SARS-CoV-2-S(mNeon) in the human lung epithelial Calu-3 cell line, neutralization of replicating VSV-SARS-CoV-2-S in Vero cells, and neutralization of SARS-CoV-2 in VeroE6 cells  has resulted in the ability to effectively and indistinguishably mimic the antibody responses of normal humans. The genetically humanized–mouse approach has the advantages that it can potentially allow for further immunization optimization strategies and that it can be applied to noninfectious disease targets. By combining the efforts from two parallel and high-throughput approaches for generating antibodies to the RBD of the SARS-CoV-2 spike protein, we generated a sufficiently large collection of potent and diverse antibodies that we could meet our prospective goal of identifying highly potent individual antibodies that could be combined into a therapeutic antibody cocktail. Inclusion of such antibodies into an antibody cocktail may deliver optimal antiviral potency while minimizing the odds of virus escape (


The current situation around the COVID-19 pandemic and the measures necessary to fight it are creating challenges for psychotherapists, who usually treat patients face-to-face with personal contact. The pandemic is accelerating the use of remote psychotherapy . However, some psychotherapists have expressed reservations regarding remote psychotherapy. As psychotherapists are the individuals who determine the frequency of use of remote psychotherapy, the potential of enabling mental health care during the COVID-19 pandemic in line with the protective measures to fight COVID-19 can be realized only if psychotherapists are willing to use remote psychotherapy.This study aimed to investigate the experiences of psychotherapists with remote psychotherapy in the first weeks of the COVID-19 lockdown in Austria .Austrian psychotherapists were invited to take part in a web-based survey. The therapeutic orientations of the psychotherapists , their rating of the comparability of remote psychotherapy (web- or telephone-based) with face-to-face psychotherapy involving personal contact, and potential discrepancies between their actual experiences and previous expectations with remote psychotherapy were assessed. Data from 1162 psychotherapists practicing before and during the COVID-19 lockdown were analyzed.P<.001). Psychodynamic (P=.001) and humanistic (P=.005) therapists reported a higher comparability of telephone-based psychotherapy to in-person psychotherapy than behavioral therapists. Experiences with remote therapy (both web- and telephone-based) were more positive than previously expected (P<.001). Psychodynamic therapists reported more positive experiences with telephone-based psychotherapy than expected compared to behavioral (P=.03) and systemic (P=.002) therapists. In general, web-based psychotherapy was rated more positively  than telephone-based psychotherapy (P<.001); however, psychodynamic therapists reported their previous expectations to be equal to their actual experiences for both telephone- and web-based psychotherapy.Psychotherapy conducted via telephone or the internet was reported to not be totally comparable to psychotherapy with personal contact  to be better than expected but found that this mode was not totally comparable to face-to-face psychotherapy with personal contact. Especially, behavioral therapists were found to rate telephone-based psychotherapy less favorably than therapists with other theoretical backgrounds. Remote psychotherapy, in which psychotherapy is provided from a distance, includes a broad range of technologies, encompassing the use of telephones, videoconferencing, and email . Mental The current situation around the COVID-19 pandemic and the measures necessary to fight it have further accelerated the rapid expansion of the technology of remote psychotherapy . This isDue to the required reduction of personal contacts, psychotherapists are confronted with major challenges to delivery of care. In general, psychotherapists are the individuals who determine the frequency of use of remote psychotherapy. Thus, the potential of increasing access to mental health care during the COVID-19 pandemic while adhering to the protective measures to fight COVID-19 can be realized only if psychotherapists are willing to use remote psychotherapy. In this regard, it is important to investigate whether psychotherapists evaluate remote psychotherapy to be equal to face-to-face psychotherapy. Moreover, the potential of psychotherapists who have experience with remote psychotherapy to revise their attitudes based upon their recent experiences should be explored. A previous study suggested that health care providers who used telemedicine methods for the first time had more positive attitudes afterward . AdequatIn general, videoconferencing offers great potential for delivering psychotherapy from distance during the COVID-19 pandemic, as some evidence indicates comparable outcomes of providing psychotherapy remotely via the internet to in-person psychotherapy -15. HoweOverall, several previous studies focused on the attitudes, experiences, and effectiveness of remote psychotherapy at the patient level; however, less is known about the therapists’ perspective. In general, most studies comparing therapists’ attitudes toward remote psychotherapy and face-to-face therapy found a preference for conducting therapy in person .The acceptance and use of remote technologies by therapists may be affected by their theoretical background. Although there are hundreds of psychotherapeutic approaches and different ways to categorize them, they can be broadly categorized into four general schools of thought: behavioral, humanistic, psychodynamic, and systemic approaches. In brief, behavioral approaches mainly rely on behavioral techniques to change maladaptive patterns of behavior or thoughts to improve emotional responses and behaviors ,23. HumaTo the best of our knowledge, there are no previous studies on whether and to what degree psychotherapists perceive discrepancies in their actual experiences and previous expectations with remote psychotherapy in situations requiring a rapid adaption of therapeutic settings due to an ongoing public health emergency such as the COVID-19 outbreak. Therefore, the current study aimed to investigate how comparable psychotherapists experience remote psychotherapy compared to face-to-face psychotherapy and whether their actual experiences differ from their expectations. Furthermore, we were interested in potential differences among therapeutic orientations.The COVID-19 lockdown in Austria became obligatory on March 16, 2020 -35. In gAt the time of the study, an official Austrian guideline addressing the conduction of psychotherapy via the internet rejected this treatment modality . HoweverBased on the aforementioned literature, the following research questions (RQs) and hypotheses were addressed in the present study.RQ 1: How do psychotherapists in the early weeks of the COVID-19 lockdown rate the comparability of telephone-based therapy to in-person psychotherapy?RQ 1a: Do therapists rate telephone-based psychotherapy comparably to in-person psychotherapy? This RQ tested the hypothesis that psychotherapists would not rate telephone-based therapy to be equal to in-person therapy.RQ 1b: Does the therapeutic orientation of the therapist affect the rating? We hypothesized that behavioral therapists would rate the comparability of telephone-based psychotherapy more positively compared to other therapeutic orientations. Moreover, we hypothesized that psychodynamic therapists would rate the comparability lower than other therapeutic orientations.RQ 2: How much more negatively or positively do psychotherapists rate their actual experiences with telephone-based therapy in the early weeks of the COVID-19 lockdown compared to their previous expectations?RQ 2a: Do the actual experiences of psychotherapists regarding telephone-based psychotherapy differ from their previous expectations? This RQ tested the hypothesis that therapists would rate their actual experiences with telephone-based psychotherapy higher than they previously expected.RQ 2b: Is the discrepancy between actual experiences and previous expectations concerning telephone-based psychotherapy different between therapeutic orientations? We hypothesized that behavioral therapists would show a smaller discrepancy between their actual experiences and their previous expectations, whereas psychodynamic therapists would show the largest discrepancy.RQ 3: How do psychotherapists in the early weeks of the COVID-19 lockdown rate the comparability of web-based therapy to in-person psychotherapy?RQ 3a: Do therapists rate web-based psychotherapy comparably to in-person psychotherapy? This RQ tested the hypothesis that psychotherapists would not rate web-based therapy to be equal to in-person therapy.RQ 3b: Does the therapeutic orientation of the psychotherapist affect the rating? We hypothesized that behavioral therapists would rate the comparability of web-based interventions more positively than therapists with other therapeutic orientations. Moreover, we hypothesized that psychodynamic therapists would rate the comparability lowest compared to the other therapeutic orientations.RQ 4: How much more negatively or positively do psychotherapists rate their actual experiences with web-based therapy in the early weeks of the COVID-19 lockdown compared to their previous expectations?RQ 4a: Do the actual experiences of psychotherapists regarding web-based psychotherapy differ from their previous expectations? This RQ tested the hypothesis that psychotherapists would rate their actual experiences with web-based therapy more positively compared to their previous expectations.RQ 4b: Is the discrepancy between actual experiences and previous expectations different between therapeutic orientations? We hypothesized that behavioral therapists would show a smaller discrepancy between their actual experiences and their previous expectations, whereas psychodynamic therapists would show the largest discrepancy.RQ 5: Does the format of remote psychotherapy (telephone or internet) affect the rating of psychotherapists regarding the comparability between remote psychotherapy and in-person psychotherapy? Moreover, is there an interaction between the comparability of telephone-based psychotherapy versus the comparability of web-based psychotherapy with the therapists’ therapeutic orientations? We had no specific hypothesis here.RQ 6: Does the discrepancy between actual experiences and previous expectations regarding telephone-based psychotherapy differ from the discrepancy between actual experiences and previous expectations regarding web-based psychotherapy? In addition, is there an interaction between actual experiences compared to previous expectations for telephone-based psychotherapy versus actual experiences compared to previous expectations for web-based psychotherapy and therapeutic orientation? We had no specific hypothesis here.To investigate the use of remote psychotherapy during the first weeks of the COVID-19 lockdown in Austria, we conducted a cross-sectional survey from March 24 to April 1, 2020. The survey was designed in the Research Electronic Data Capture (REDCap) application and comprised 79 items focusing on the changes in the provision of psychotherapy, experiences with remote psychotherapy, fear of COVID-19 infection, adherence to protective measures against COVID-19 infection, perceived stress, job-related anxiety, and resilience, among others. More details on the conduction of the web-based survey have been published recently ,38.Eligible participants included all licensed Austrian psychotherapists registered in the list of psychotherapists of the Austrian Federal Ministry of Social Affairs, Health, Care, and Consumer Protection. All psychotherapists registered in the list who provided a valid email address  were invited to take part in the survey. A web-based invitation with a link to the web-based survey was sent to the therapists by the last author in cooperation with the Austrian Federal Association for Psychotherapy.The following items were analyzed in the current study: demographic information  as well as items regarding educational and professional background. More specifically, the psychotherapists were asked about their years in the profession  and about their psychotherapy method ; the laFour items focused on the expectations of the psychotherapists regarding telephone- and web-based therapies. These questions were only asked to psychotherapists who were treating at least one patient before the COVID-19 lockdown as well as after the COVID-19 lockdown.Psychotherapists were asked to rate whether they could treat their patients in a comparable manner with remote therapy compared to in-person therapy on a sliding scale ranging from 0  to 100 . Two separate questions were asked, one on telephone-based psychotherapy, and the other on web-based psychotherapy. The questions on the comparability of telephone- or web-based psychotherapy were only asked of psychotherapists who treated at least one patient via telephone or via the internet either before the COVID-19 lockdown or during the COVID-19 lockdown.Psychotherapists were asked to rate whether their actual experiences with remote psychotherapy during the actual situation around COVID-19 matched their previous expectations regarding remote psychotherapy on a sliding scale ranging from 0 (significantly more negative than expected) to 100 (significantly more positive than expected). Again, two separate questions were asked, focusing either on telephone- or web-based psychotherapy. The questions regarding actual experiences versus previous expectations for telephone- or web-based psychotherapy were only asked of psychotherapists who started to treat patients via telephone or the internet during the COVID-19 lockdown . Only “new starters” were asked these questions because they were the only respondents to show a change of attitude in a previous study focusing on health professionals in general .Statistical analyses were performed with SPSS version 25 (IBM Corporation).Descriptive statistics were calculated to characterize the participants. To evaluate differences in sociodemographic characteristics, univariate analysis of variance (ANOVA) and chi-square tests were conducted. Bonferroni corrections were applied for the pairwise post-hoc tests.t tests; the respective ratings were compared with a value of 100, as a value of 100 represents the maximum score of the used sliding scale and means “totally comparable to psychotherapy in personal contact.”The comparison of whether telephone- or web-based psychotherapy was regarded to be equal to psychotherapy in personal contact  was conducted using To evaluate possible discrepancies between actual experiences and previous expectations regarding the use of the telephone or internet for psychotherapy , the ratings were compared against a value of 50, as a value of 50 indicates “previous expectations=actual experiences.”To address RQ 1b, 2b, 3b, and 4b, univariate ANOVA was performed to investigate potential differences among the four therapeutic orientations of the psychotherapists  in the dependent variables . Bonferroni corrections were used for post-hoc comparisons.To address RQ 5 and RQ 6, mixed ANOVA was performed with one within-subject variable (two levels of treatment format: telephone-based psychotherapy and web-based psychotherapy) and one between-subject variable . For variables with a significant interaction between treatment format and therapeutic orientation, Bonferroni corrections were applied for the pairwise post-hoc tests. The dependent variables were the comparability of telephone- or web-based therapy to face-to-face therapy and actual experiences versus previous expectations for telephone- or web-based therapy.To evaluate whether the results are robust when accounting for the found differences in age and professional experience between the therapeutic orientations, we used analysis of covariance (ANCOVA) tests.P value <.05 indicating statistical significance.All statistical tests were two-tailed, with a P=.02); the excluded psychotherapists were older than the included psychotherapists. However, the effect size of this difference was small (g=0.14).In total, 1547 psychotherapists participated in the survey, corresponding to a response rate of approximately 25%. For the present study, only therapists practicing as psychotherapists in the months before the COVID-19 pandemic as well during the COVID-19 lockdown were analyzed to investigate the RQs. The description of the sample and comparisons between the included and excluded participants are shown in For the 1162 included psychotherapists, we also investigated the differences between the therapeutic orientations in terms of gender, age, and professional experience , with thP≤.001 for all pairwise post-hoc comparisons). Similarly, behavioral therapists had significantly fewer years in the profession than humanistic, systemic, and psychodynamic therapists .Behavioral therapists were significantly younger than humanistic, systemic, and psychodynamic therapists (P=.42).There was no difference regarding gender among the therapeutic orientations  stated that telephone-based psychotherapy is not totally comparable to in-person psychotherapy. The mean score of 50.2 (SD 26.00) was significantly lower than 100, P=.001). As summarized in P=.001) and a higher rating by humanistic therapists compared to behavioral therapists (P=.005). No differences were observed for the systemic orientation compared to the other three orientations.RQ 1b: The therapeutic orientation affected the rating of whether telephone-based psychotherapy is comparable to face-to-face psychotherapy .Psychotherapists who started to use telephone for psychotherapy during the COVID-19 lockdown (n=782) stated that their actual experiences with telephone-based psychotherapy were better than previously expected. The mean score of 64.2 (SD 19.12) was significantly higher than 50 (tP=.001). As summarized in P=.03, and systemic therapists, P=.002. No differences were observed for the humanistic orientation compared to the other three orientations.The therapeutic orientation affected the rating of whether telephone-based psychotherapy was experienced differently than expected .Psychotherapists who treated at least one patient with web-based psychotherapy either before or during the COVID-19 lockdown (n=733) stated that web-based psychotherapy is not comparable to in-person psychotherapy. The mean score of 61.5 (SD 24.38) was significantly lower than 100 (tP=.88), as summarized in The rating of whether web-based psychotherapy is comparable to face-to-face psychotherapy did not differ between therapeutic orientations .Psychotherapists who started to use internet for psychotherapy during the COVID-19 lockdown (n=614) stated that their actual experiences with web-based psychotherapy were better than previously expected. The mean score of 69.0 (SD 18.87) was significantly higher than 50 (tP=.71). The mean scores (SD) are summarized in The discrepancy between the actual experiences and previous expectations regarding web-based psychotherapy did not differ concerning the therapeutic orientation of the psychotherapists . No interaction between psychotherapy format (internet or telephone) and therapeutic orientation was observed  rated web-based psychotherapy to be more comparable to face-to-face psychotherapy than telephone-based psychotherapy . An interaction between the psychotherapy format (internet or telephone) and the therapeutic orientation was observed , humanistic (P=.005), and systemic (P<.001) psychotherapists reported that their actual experiences compared to their previous expectations were more positive for web-based therapy than for telephone-based therapy. However, the discrepancy between actual experiences and previous expectations with remote psychotherapy was not different between web- and telephone-based psychotherapy among psychodynamic therapists (P>.99).Psychotherapists of the four therapeutic orientations who started to treat at least one patient via telephone and at least one patient via the internet during the COVID-19 lockdown (n=422) reported that their actual experiences with web-based psychotherapy were more positive than their actual experiences with telephone-based psychotherapy compared to their previous expectations . As the study was conducted in Austria, the results may only apply to countries with similar mental health care systems and similar therapeutic orientations among psychotherapists. In Austria, internet-based psychotherapy was rejected by an official guideline at the time of the study [There are several limitations in this study. One limitation is that the survey was conducted on the web; this may have caused some respondent bias, such as higher participation of psychotherapists with a higher preference for new technologies. This bias may have contributed to the finding that providing psychotherapy remotely was rated more positively than expected. The web-based conduction of the survey may also have caused a selection bias toward participation by fewer older psychotherapists . A furthhe study . HoweverOur results confirm the hypothesis that psychotherapy via telephone or the internet is not regarded to be completely comparable to in-person psychotherapy by therapists. In agreement, most studies investigating experience with remote psychotherapy reported that a minority of therapists experienced remote psychotherapy to be equal to face-to-face encounters ,21,41. DOur results further confirm the hypothesis that therapists who started to use remote psychotherapy had better experiences with remote psychotherapy than previously expected; this was more pronounced for web-based psychotherapy than for telephone-based psychotherapy. This result is supported by previous studies showing positive experiences of therapists using remote psychotherapy -45. As rThe findings were also influenced by the participants’ therapeutic orientation. In contrast to previous findings, behavioral therapists reported less positive actual experiences compared to previous expectations and lower comparability of telephone-based psychotherapy to in-person therapy than psychodynamic therapists -30. ThisThe ratings of the comparability of web-based and in-person psychotherapy as well as the discrepancies in actual experiences and previous expectations regarding web-based psychotherapy did not differ regarding therapeutic background. This result rejects our hypothesis that behavioral psychotherapists would rate remote psychotherapy via internet more positively than psychodynamic therapists.In general, web-based psychotherapy was rated more positively (regarding comparability to face-to-face therapy and experiences vs expectations) than psychotherapy via telephone; however, this was not the case for psychodynamic therapists, who reported their previous expectations to be equal to their actual experiences for both telephone- and web-based psychotherapy. This confirms our hypothesis and is likely due to the potential of videoconferencing to provide several pieces of information regarding nonverbal behavior and of its greater comparability to face-to-face settings than telephone-based psychotherapy, which results in a greater loss of information.The experiences of psychotherapists with remote psychotherapy were better than their expectations but not totally comparable to face-to-face psychotherapy with personal contact. Adequate mental health care is of high importance during the COVID-19 pandemic, and the provision of psychotherapy at a safe distance seems to be the obvious solution to ensure sufficient psychotherapeutic support. This study provides important insights regarding psychotherapists’ experiences with and expectations of remote psychotherapy during the COVID-19 pandemic. Future studies should also consider patient perspectives.


Background: Periprosthetic joint infection (PJI) represents a serious complication following total knee arthroplasty. In the setting of chronic infections, the two-staged approach has traditionally been the preferred treatment method. The aim of this study was to determine the optimal period of rest between the first and second stage. Furthermore, we analyzed potentially outcome-relevant parameters, such as general and local conditions and the presence of difficult-to-treat or unidentified microorganisms, with regard to their impact on successful treatment of PJI.Patients and Methods: We performed a retrospective analysis of prospectively collected data for all patients treated for PJI at our institution. Seventy-seven patients who had undergone two-stage revision arthroplasty for PJI of the knee were included into the study. Antibiotic-loaded cement spacers were used for all patients.Results: After a median follow-up time of 24.5 months, infection had reoccurred in 14 (18.7%) patients. A prolonged spacer-retention period of more than 83 days was related to a significantly higher proportion of reinfections. Furthermore, significant compromising local conditions of the prosthetic tissue and surrounding skin, as well as repeated spacer-exchanges between first- and second-stage surgery, negatively influenced the outcome. Neither the patients' age nor gender exerted a significant influence on the outcome regarding reinfection rates for patients' age or gender.Conclusions: We observed the best outcome regarding infection control in patients who had undergone second-stage surgery within 12 weeks after first-stage surgery. Nearly 90% of these patients stayed free from infection until the final follow-up. An increased number of performed spacer-exchanges and a bad local extremity grade also had a negative impact on the outcome. Despite continuous innovations and improvements in knee arthroplasty, the occurrence of prosthetic joint infections (PJI) has not decreased. Although the overall PJI incidence following total knee arthroplasty is low 1-2%), PJI represents a serious complication with potentially devastating effects to the patients -2%, PJI In order to determine the optimal period of rest between the first and second stage, we analyzed the data of 77 consecutive patients who had undergone two-stage exchange arthroplasty for prosthetic knee joint infections with regard to successful infection control. Furthermore, we analyzed potentially outcome-relevant parameters  with regard to their impact on successful treatment of PJI.We included a consecutive series of 77 patients who had undergone two-stage revision arthroplasty for PJI in the study. The series comprised 35 men and 42 women with a mean age of 64.9 years . The right knee was affected in 37 cases, the left knee in 40 cases. The median observation period was 24.5 months .Currently, the Musculoskeletal Infection Society (MSIS) criteria is the gold standard for infection diagnosis Even if the causing bacteria could not be identified preoperatively, patient's history and clinical findings, as well as the presence of elevated inflammation markers and synovial WBC, were sufficient tools in order to obtain security about whether infection was present or not.In cases of inconclusive clinical, laboratory, or bacteriological findings (low-grade infections), we also performed a 99mTc-leukocyte scintigraphy. We diagnosed PJI according to the MSIS criteria. Furthermore, we documented the general health and local wound condition  for cultural examination, followed by a thorough debridement and removal of all implants, which we sent for sonication. Subsequently, we placed an antibiotic-loaded bone cement (polymethylmethacrylate [PMMA]) as a static spacer. We used 80-120 grams of PALACOS cement , which was loaded with 1 gram of vancomycin per 40g of Palacos in most of the cases (94.8%). In some cases, we used different antibiotics, according to the pathogen-specific antibiogram: Antibiotic loading of the spacer comprised vancomycin in almost all cases Tazobactam was applied in 2.6% of cases, while vancomycin/refobacin or teicoplanin and cefuroxime was each used in 1.3% of cases.A period of rest between first- and second-stage surgery has been considered necessary in order to ensure treatment success due to infection eradication Infection was considered to be eradicated with the resolution of clinical signs and symptoms, as well as improvement of laboratory infection values. According to our experience, although defining cut-off values has seemed to be challenging in the recent past, a linear decrease followed by steadiness of all infection values within the high-normal to slightly increased range appears to be indicative for treatment success If those criteria were met, we executed second-stage surgery. We again performed a thorough soft tissue debridement and synovectomy. We removed the joint spacer with care in order to preserve as much bone stock as possible. Finally, after careful debridement of the posterior joint, we performed revision arthroplasty  in all of the cases in order to achieve stability.The primary goal of the follow-up care was the early detection of re-infection. These follow-up assessments comprised physical examinations, regular laboratory tests , and imaging procedures, including plain radiographs of the knee in two planes after 6 weeks, 3, 6 and 12 months, and annually thereafter. All patients were followed up every six months for at least two years after second stage surgery.We entered data into a computerized database and analyzed it. Continuous variables are reported as the median with interquartile range (IQR) or range (minimum-maximum), except for the age, which is described as the mean with standard deviation (SD). Categorical data is displayed as frequencies with percentages in parentheses.This method locates the cut-point that maximizes a logrank test statistic as usually applied in connection with a time-to-event analysis. The effect of the spacer retention period on time to reinfection was therefore assessed with a Kaplan-Meier plot with Mantel-Cox logrank test and the hazard ratio for patients with a prolonged spacer retention period of getting a reinfection compared to patients with optimum spacer retention period was assessed with a Cox proportional hazard model adjusted for age and sex.To separate patients with an optimum spacer retention period from patients with a prolonged spacer retention period we used the “maximally selected rank statistic” method To determine the statistical significance of group differences, we used the Wilcoxon rank-sum test for metric parameters. The relationship between categorical parameters is presented in contingency tables and analyzed with Pearson's chi-squared test. In either case, we determined exact p values; we considered p ≤ 0.05 to be statistically significant. Computations were performed using the statistical package IBM SPSS Statistics for Windows  and R, version 3.3.0.Clinical manifestations ranged from reduced mobility, impaired range of motion, pain, swelling, and/or redness of the affected region to systemic signs of inflammation or even sepsis. The main clinical symptoms were pain, joint swelling and effusion, overheating, and movement restriction of the affected joint. The median time period between primary joint arthroplasty and onset of the symptoms was 23.6 months .The median preoperative C-reactive protein concentration was 61.1 mg/L, the median leukocyte count was 7920 cells/µL, the median fibrinogen concentration was 589 mg/dL, and the median IL-6 concentration was 31.5 pg/dL.We performed pre-operative joint-aspirations in all patients. An organism could be detected either for pre-operative or both pre- and intra-operative samples in 54 cases 70.1%). In 13 patients (16.9%), bacteria determination was exclusively by implant sonication. The most common identified organisms were staphylococci, followed by streptococci, gram negative rods, and mixed cultures of organisms . One additional spacer exchange was necessary in 15 patients (19.7%). Two exchanges were performed in two patients (2.6%) due to persisting signs and symptoms of infection. All patients underwent second-stage surgery.We observed an 18.7% (n = 14) rate of reinfection until a median time of 19.5 months . In 11 of these cases, we performed two-stage revision. Two patients underwent transfemoral amputation due to worse local and general conditions. One patient died before completion of the two-stage protocol. Most patients  stayed infection free until a median follow-up time of 24.6 months .The maximally selected rank statistic method yields a maximum cut-point at 83 days, indicating an optimum spacer retention period of less than 12 weeks. Thirty-nine patients had an optimal and 35 patients a prolonged (more than 12 weeks) spacer retention period. Time to event analysis shows that patients with an optimum spacer retention period have a higher probability of staying free from reinfections than patients with a prolonged spacer retention period (p=.005)  was significantly associated with a higher rate of reinfection  (p = 0.001; Table Although still controversial in the relevant literature, two-stage revision arthroplasty remains the most applied procedure for chronic periprosthetic infections. Antibiotic-loaded cement spacers have become an established method for infection control. The use of high-dose antibiotic-loaded cement as a temporary joint spacer seems to increase the potential for local infection eradication during the time between implant removal and before the second-stage surgery, which aims to restore function and mobility by the use of knee arthroplasty implants once again The goal of surgery must be the complete removal of all infected tissue and implants to eliminate the biofilm and ensure the efficacy of the postoperative antibiotic therapy Next to infection control, which is certainly the primary aim of all treatment protocols, additional goals should be the restoration of function and minimizing infection-related morbidity and mortality Although the technique of two-stage revision surgery seems to be well established for chronic PJI of the knee, different protocols exist among institutions with regard to debridement, spacer choice, and timing of reimplantation, as well as the definition or diagnostic tools used to indicate infection eradication. Failure rates of the two-stage protocol are between 10 and 40% according to recent studies Unfortunately, joint spacers, as they are used to bridge the time between implant removal and replantation, may also develop biofilms In our institutional review, we identified the following as risk factors for failure to achieve an infection-free two-stage revision: a prolonged spacer-retention, McPherson extremity grade 3, and unidentified/difficult-to-treat microorganisms. We observed the best outcome regarding infection-control in patients who had undergone second-stage surgery within 12 weeks of the first-stage surgery. Nearly 90% of these patients stayed free from infection until the final follow-up. Although most authors have suggested spacer-retention periods of 6 weeks, many of our patients exceeded this recommended period of time before completing the two-stage protocol We observed the best outcome regarding infection control in patients who had undergone second-stage surgery within 12 weeks after first-stage surgery. Nearly 90% of these patients stayed free from infection until final follow-up. An increased number of performed spacer-exchanges and a bad local extremity grade seemed to have a negative impact on the outcome regarding infection control.


COVID-19 pandemic has predisposed patients undergoing surgery to post-operative infection and resultant complications. Appendicitis is frequently managed by appendicectomy. After the onset of the pandemic, selected cases of appendicitis were managed with antibiotics which is a recognised treatment option. Our objective was to compare the management of appendicitis and post-operative outcomes between pre- and post-COVID-19.Ninety-six patients were identified from before the onset of the pandemic (November 2019) to after the onset of the pandemic (May 2020). Data were collected retrospectively from electronic records including demographics, investigations, treatment, duration of inpatient stay, complications, readmissions and compared between pre- and post-COVID-19 groups.One hundred percent underwent surgical treatment before the onset of pandemic, compared with 56.3% from the onset of the pandemic. A greater percentage of patients were investigated with imaging post-COVID-19 . There was no significant difference in the outcomes between the two groups.CT/MRI scan was preferred to laparoscopy in diagnosing appendicitis and conservative management of uncomplicated appendicitis was common practice after the onset of pandemic. Health boards can adapt their management of surgical conditions during pandemics without adverse short-term consequences. Long term follow-up of this cohort will identify patients suitable for conservative management. The Coronavirus (COVID-19) pandemic has resulted in the adoption of a change in the overall health care strategy that will reduce the spread of the virus. In the hospital setting several measures have been taken to avoid unnecessary procedures or environments where the risk of exposure is high.1 Appendicectomy is the preferred management for those patients with appendicitis, except in patients with significant co-morbidities or alternate patient preference.2 APPAC trial has shown that Computed tomography (CT)-proven uncomplicated acute appendicitis is not a surgical emergency and that antibiotic treatment is a safe first-line treatment for uncomplicated acute appendicitis.3 Conservative management with antibiotics for uncomplicated appendicitis has the risk of recurrent appendicitis, and ranges from 16% to 40% at one year after initial treatment.35Right iliac fossa pain with suspected appendicitis is a common cause for emergency general surgical admission.7 Patients with uncomplicated appendicitis were managed with non-operative treatment if possible, after the onset of the COVID-19 pandemic.The ongoing COVID-19 pandemic spread to the United Kingdom in late January 2020. The first COVID-19 patient was diagnosed in our region in March 2020. Non-essential operations were cancelled at our institution from the 21st of March. Our approach to managing appendicitis was modified recognising the risks of COVID-19 infection, such as avoiding aerosol generating procedures - in line with international and national guidelines.8 CT scan is avoided in younger patients in view of the risk of radiation; younger aged patients also have greater years remaining in which a radiation-induced malignancy may develop.9Before the onset of the pandemic, patients with a clinical diagnosis of appendicitis went on to have diagnostic laparoscopy. Young female patients had pelvic ultrasound and a urine pregnancy test to rule out gynaecological causes for the symptoms, before subjecting to laparoscopy. For older patients, or in cases where the diagnosis was unclear, a CT scan of the abdomen and pelvis was conducted to confirm the diagnosis of appendicitis, and rule out other sinister causes with similar presentations common in elderly patients.10 and 3, to rule out an active COVID-19 infection of the lungs.11 Patients with normal CT scan findings were discharged early to reduce spread of the virus.Clinical evaluation of patients has been modified since the onset of the COVID-19 pandemic. Adult patients admitted with a suspected diagnosis of appendicitis had a CT scan of the abdomen and pelvis irrespective of the age group, these patients also had a CT chest at the same time, to look for any signs of COVID-19 infection. The reason behind this approach is 1, to get a definite diagnosis, 2, to assess the severity of appendicitisPatients with confirmed CT scan findings of appendicitis were assessed for the suitability of conservative management based on the likelihood of intra-abdominal contamination due to perforation of the appendix and abscess formation. Decisions regarding the management strategy were made by the admitting surgeon depending on the clinical condition of the patient, taking into account the radiological findings and blood investigations.Patients who were treated with conservative management were discharged once symptoms had resolved, worsening advice was given on discharge, and follow-up arrangement was dependent on the decision of the admitting consultant. After appendicectomy, patients were not routinely followed-up.In this paper, our objective was to evaluate the change in our practice of managing patients admitted with acute appendicitis, and to investigate short-term outcomes after the onset of pandemic. As a more conservative approach was more likely to be adopted during the pandemic, our aim was to look into the outcomes of those patients treated for appendicitis pre COVID-19 pandemic and during the pandemic in the short term.Adult patients admitted to the acute surgical unit of our institution with a diagnosis of acute appendicitis between November 2019 and May 2020 were identified based on radiological diagnosis or operative findings. We collected data relating to demographics, co-morbidities, inflammatory markers and radiological findings for these patients. We recorded the management strategy for each patient and followed each patient up for thirty-days looking for post-operative complications, readmissions, further imaging and intervention. Data was collected retrospectively using electronic records .At our institution, surgical practice changed from the 21st of March, marking the beginning of the post-COVID-19 group in this study. Short term outcomes were compared between those managed by surgical treatment in the pre-COVID-19 period versus those managed with selective conservative and surgical treatment during the pandemic period. Diagnostic methods (laparoscopy versus imaging) and management strategy (operative or non-operative) were recorded during the two time periods. Duration of stay, use of antibiotics, complications and the rate of readmission were compared between pre- and post-COVID-19 groups. Comparisons were made using Fisher’s exact test, Chi-Squared, and Mann-Whitney U tests using the STATA IC 16.1 statistical package.A total of 96 adult patients  were identified from November 2019 to May 2020 . PatientCT scan was performed in 67.7% (65/96) and one patient had MRI (1.0%). Twelve (12.5%) patients had ultrasound, four of which also has a CT scan.Eighty-two patients (85.4%) had appendicectomy and the remaining 14.6% (14/96) patients were managed conservatively with antibiotics. Seven patients (7.3%) underwent an open appendicectomy, five of where were converted from a laparoscopic approach.Sixty four  were identified with a diagnosis of appendicitis from November 2019 until the change in management strategy at the onset of pandemic (21st March). Thirty-two patients  were identified from the onset of the pandemic time until 15th May, 2020.Pre-COVID-19, 60.9% of patients (39/64) had imaging prior to appendicectomy. One hundred percent (64/64) of patients had an appendicectomy for acute appendicitis before the change in our practice . One patPost-COVID-19, 100% (32/32) of patients had imaging, 31 with CT scan and one with MRI. None of the patients had positive findings on CT chest done during the post-COVID-19 period. Eighteen out of thirty-two patients (56.3%) of patients had an appendicectomy. Among them two patients had laparoscopy converted to open procedure. One patient was initially managed with laparoscopic washout and drain placement. This patient went on to have laparoscopic appendicectomy for perforated appendix during the same admission. The remaining 43.7% (14/32) patients were treated with antibiotics.A greater percentage of patients were investigated with imaging post-COVID-19 versus pre-COVID-19  The percentage of patients treated surgically reduced from the onset of COVID-19 (p < 0.00001). In the group of patients <40 years of age, 30.6% of patients had imaging pre-COVID-19 versus 100% of patients post-COVID-19 (p < 0.0001) and 100% of patients underwent surgical intervention versus 52.6%. There was no statistical difference in the rate of readmissions between groups.In the pre-COVID-19 period, post-operative ileus, collection requiring radiologically placed drain, and laparoscopic washout and adhesiolysis were causes of complicated admission and delayed discharge. There were no complications among patients managed conservatively or by operative treatment during the post-COVID-19 period.Eighty two patients were treated by surgical treatment  starting from November 2019. Fourteen patients were treated conservatively with antibiotics , all of which were in the post-COVID-19 period. Diagnosis of all those treated conservatively was made from imaging (CT scan & MRI). Among those treated conservatively, there were more female patients. No complications were recorded in those patients treated with non-operative management. One patient who was managed with antibiotics was readmitted with abdominal pain and was managed conservatively after CT scan did not show any complications.6 All necessary precautions were taken during this period to avoid exposure to the virus. Steps were also taken to avoid patients coming to the hospital. Those attending hospital for various reasons were discharged early after managing them appropriately.A conservative approach was adopted in managing an acute surgical condition recognising the risk of increased post-operative morbidity and mortality in COVID-19 infected patients.7 Clinical assessment including blood tests and radiological investigations with CT scan were used to diagnose and manage appendicitis. All patients were commenced on antibiotic treatment once a diagnosis was made. Decision regarding operative or conservative management was made by admitting surgeon based on signs of peritonism, sepsis and persistent symptoms.After the onset of COVID-19 pandemic, a conservative approach was adopted at our institution when possible in treating acute appendicitis, in line with the national guidelines.8 Before the onset of COVID-19 pandemic, our practice was to use CT selectively in diagnosing appendicitis and ruling out sinister causes with similar presentation in older patients. After the age of forty years the incidence of diverticulosis and malignancy increases which can present acutely with right iliac fossa pain.12 Laparoscopy was preferred in younger patients with suspected clinical diagnosis of appendicitis. CT scan is routinely used in some institution for all adult patients to confirm a clinical diagnosis of appendicitis. CT scan has high accuracy in diagnosing appendicitis and is used to assess the severity of appendicitis.14 Early appendicitis without intra-peritoneal contamination may be suitable for non-operative treatment with antibiotics.Appendicitis is a clinical diagnosis and imaging is helpful in older patients to rule out sinister causes of symptoms.15 however, laparoscopy is an invasive procedure and carries the risk of iatrogenic injury and anaesthetic complications.16 CT scan will also reduce the incidence of negative laparoscopy. In the present study, all patients under the age of 40 years underwent CT scan to diagnose appendicitis after the onset of COVID-19 pandemic. The risk of radiation exposure may not be significant considering that they do not require repeated scanning. MRI scan can be utilised in younger (less than 20 years) and pregnant patients to avoid radiation exposure in these patients.2 The role and risk of CT/MRI scan in diagnosing appendicitis should be discussed while consenting the patients for diagnostic laparoscopy.CT scan is avoided in younger patients in view of the risk of radiation,2 Ultrasound is most often the first line imaging modality for suspected appendicitis. Sensitivity of ultrasound is operator dependent. Swollen appendix was noted in seven of the twelve patients examined. Ultrasound was also used to rule out other causes of symptoms mostly in female patients.The reported sensitivity for ultrasound varies in the literature (71–94%) and is lower than CT scan.Adoption of a non-operative strategy and selective management with surgical treatment during the pandemic period may throw light on suitability of antibiotic treatment in patients with early appendicitis. Retrospective analysis of the outcome of conservative management at a later date will help in the grading of CT scan findings in selecting patients for non-operative treatment. This grading can be validated with a future prospective study.18This is not a randomised control study to assess the superiority of one modality of treatment over other; however, follow up of the patients with uncomplicated appendicitis treated with antibiotics will give an opportunity to understand the natural course of this disease. The role of antibiotics in halting the progress of this disease to a complicated appendicitis and recurrence may be studied by close follow-up of these patients. Identifying the risk factors for recurrence will help us in selecting patients who can be treated safely with antibiotics. Use of antibiotics has its own risk including clostridium difficile infection and emergence of resistant organisms.20 In our cohort, 0% of patients required operation over the 30 days follow-up.Patients were followed-up for a minimum period of 30 days. Long-term follow-up is required to evaluate long-term outcomes and will inform us the long-term effect of pandemics on surgical practice. Studies have shown that among patients treated with antibiotics, 17–64% required operation within 30 days of presentation.At our institution, patients who were managed conservatively had uncomplicated appendicitis with little evidence of intra-peritoneal contamination. Long-term outcomes (e.g. 1 year) will specifically demonstrate whether or not conservative management is a safe treatment option for uncomplicated appendicitis. The same patient group will be evaluated in one year to investigate for complications, further readmission and intervention.From the onset of the COVID-19 pandemic, patients with acute appendicitis were managed safely with good outcomes. Acute uncomplicated appendicitis was frequently managed non-operatively with antibiotic treatment. Patients with significant co-morbidities, those with local or general contamination, and those who failed medical management went on to have appendicectomy. Health boards can successfully adapt their management of surgical conditions, such as appendicitis, during pandemics without negative short-term outcomes. Long term follow-up of these patients will be useful in deciding the role of non-operative management in treating uncomplicated appendicitis.