Evaluation of Microbiological Culture and Antibiogram of the Patient with Corneal Ulcer due to Exposure Keratitis in the Intensive Care Unit in Sina Farshchian Hospital (2019-2020)

Background: Since patients admitted to the intensive care unit have a compromised im-mune system and are more prone to infection than other patients, timely diagnosis and treatment of corneal ulcers among this group of patients can prevent vision loss. Therefore, it is necessary to treat eye infections and corneal ulcers promptly and economize prohibitive costs. Objective(s): Appropriate treatment with the most effective antibiotic before the answer is available to prevent corneal ulcer complications and blindness. Method(s): This study was conducted from November 2019 to November 2020 and after approval by the ethics committee of Hamedan University of Medical Sciences with the code of ethics: IR.UMSHA.REC.1398.716. First, the corneal secretions of 121 patients admitted to the intensive care unit of Sina Hospital are prepared by an ophthalmologist (after anesthetizing the cornea with tetra-caine drops and sterile swabs) and culture in four growth mediums (blood agar, chocolate agar, thio-glycolate, and EMB). Microbial cultures are examined after 48 hours and a fungal culture is examined one week later. Disc diffusions are placed in positive microbial cultures. Antibiotic susceptibility or resistance of the antibiogram was recorded. Other demographic data, including patients' age and sex, are extracted from ICU files. Also, test results and patient identifications are recorded in a checklist designed for this purpose. Result(s): Of all the antibiotics used against common bacteria, vancomycin (84%), colistin (80.43%), cefazolin (80%), and levofloxacin (60%) had the highest sensitivity and gentamicin (93.75%), ceftazidime (86.42%) Erythromycin (85%) had the highest resistance against isolated bacteria. Conclusion(s): The data obtained from this study showed that the most common microorganisms in the age group under the age of 30 years were Acinetobacter Baumannii, in the group of 30-60 years old was Klebsiella pneumonia, and age group over 61 years old was Staphylococcus aureus, and the most sensitive antibiotics in the age group under 30 years were vancomycin and levofloxacin and the age group30-60 were colistin and vancomycin and in the age group over 61 years were vancomycin and cefazolin.Copyright © 2023 Bentham Science Publishers.

Integrated Lactate Is Improved with a Novel Pharmacologic Inducer of the Endogenous Cytoprotective Heat Shock Protein 70I Gga and Potential COVID Applications

Introduction: Lactate is a common biomarker used in multiple surgical subspecialties. No one has previously measured coronary sinus lactate reduction as a result of drug administration. We therefore tested the hypothesis that IV geranylgeranylacetone (GGA), a novel agent used to treat human peptic ulcer disease, would result in reduced coronary sinus lactate production. Method(s): New Zealand adult rabbits (N=5 each) received IV 50 mg/kg GGA 24 hours before intervention, which consisted of Langendorff perfusion, 30 min of global normothermic cardioplegic arrest, followed by reperfusion. Myocardial release of lactate was measured. HSP70 was quantified by western blot. Differences between GGA+ and GGA- groups pre- and post-ischemia were analyzed by unpaired t-tests. Result(s): In the GGA- group, lactate increased immediately at one minute and throughout the duration of reperfusion. However, in GGA+ hearts, lactate also increased at one min of reperfusion but then continued to decrease throughout the remainder of reperfusion. Lactate was significantly less at every time point of reperfusion in GGA+. Integrated lactate area was significantly less throughout reperfusion in GGA+. Conclusion(s): GGA induced caused a marked decrease in coronary sinus lactate release during reperfusion. Simultaneously intravenously GGA induced myocardial HSP70i and reduced myocardial damage. Further study of the effects and mechanisms involved is indicated. Application to other organs is useful as well. Heat shock proteins (HSPS) are also antithrombotic. Given the thrombotic nature of Covid, induction of HSPS may be beneficial in decreasing the cardiac thoracic and vascular complications of Covid and allowing faster resolution of this disease during to vascular complications.

Physical and mental condition and medicine consumption of frontline medical staff of shelter hospitals in Shanghai during the fight against the epidemic of coronavirus disease 2019.

Objective To investigate the physical and mental condition and medicine consumption of medical staff of shelter hospitals in Shanghai during the fight against the epidemic of coronavirus disease 2019 (COVID-19). Methods A total of 144 frontline medical staff who fighting against the COVID-19 epidemic from a tertiary first-class hospital from Apr. 4 to May 12, 2022 were surveyed by questionnaires online. Their physical condition including body weight change before the medical work and one month later, sleep quality and the medicine consumption during the medical work were collected and analyzed. Results The mean body weight of frontline doctors before the medical work and one month later were (69.80+/-8.35) kg and (68.60+/-7.37) kg, while those of nurses were (55.36+/-8.27) kg and (53.80+/-7.38) kg, both showing a decreasing trend but without significant difference (all P0.05). A total of 63.89% (92/144) frontline medical staff suffered from insomnia, of which 27.08% (39/144) needed drug intervention. The top 5 common diseases among frontline medical staff were sleep disorder (63.89%, 92/144), skin injury (25.69%, 37/144), body pain (23.61%, 34/144), oral ulcer (13.19%, 19/144), and acute upper respiratory tract infection (9.72%, 14/144). A total of 155 medical staff used drugs, and the top 5 common drugs were skin application (16.77%, 26/155), Ganmao'an granule (12.26%, 19/155), zolpidem tartrate tablets (11.61%, 18/155), Kangfuxin liquid (11.61%, 18/155), and celecoxib capsules (8.39%, 13/155). Conclusion Frontline medical staff in shelter hospitals are prone to have body weight change, sleep disorder, skin injury, body pain, oral ulcer, acute upper respiratory tract infection and so on, which suggests that in future similar large-scale medical support, it is necessary to pay sufficient attention to the physical condition of frontline medical staff and provide them sufficient medicine.Copyright © 2022, Second Military Medical University Press. All rights reserved.

Case Report of Succesful Multidisiplinary Treatment for Patient with Metastatic Lung Cancer and Relapsed/Refractory Chronic Lymphatic Leukemia/Small Lymphocytic Lymphoma

Introduction: Croatian National Cancer Registry of Croatian Institute for Public Health reported that in year 2020 lung cancer was the second most common cancer site diagnosed in men with 16% and the third most common in women with 10% incidence among all cancer sites. Unfortunatelly lung cancer has the highest mortality in both men and women. Haematological malignancies had 7% share in all malignancies in both male and female cances cases. In 2020 190 newly diagnosed cases of lymphatic leukemia in men and 128 cases in women were reporeted, meaning 1.5 and 1.2% of all malignancies, respectively. Chronic lymphatic leukemia (CLL) is an advanced age disease and incidence increases with age. Impaired immunity, T and B cell dysfunction in CLL, chromosomal aberations, long-term immunosuppressive therapy and genetic factors can all cause secondary malignancies. Co- occurence of solid tumors and CLL is very rare. Although patiens with CLL have an increased risk of developing second primary malignancies including lung carcinoma, the data about their clinical outcomes are lacking. Parekh et al. retrospectively analyzed patients with simultaneous CLL and lung carcinoma over a 20-year period, and they found that ~2% of patients with CLL actually developed lung carcinoma. The authors claimed that up to 38% of patients will also develop a third neoplasm more likely of the skin (melanoma and basal cell carcinoma), larynx (laryngeal carcinoma) or colon. Currently there are no specific guidelines for concurrent CLL and non-small cell lung carcinoma (NSCLC) treatment. Usually, when the tumors are diagnosed simultaneously, treatment is based to target the most aggressive malignancy, as the clinical outcomes depend on the response of the tumor with the poorest prognosis. For this reason, a multidisciplinary approach is mandatory. Case report: A patient with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation was diagnosed in 2019 (at the age of 71) with B chronic lymphocytic leukemia with bulky tumor (inguinal lymph nodes 8x5 cm), stage B according to Binet, intermediate risk. He was treated with 6 cycles of chemoimmunotherapy (rituximab/cyclofosfamid/fludarabine). In 10/2019 remission was confirmed, but MSCT described tumor in the posterior segment of upper right lung lobe measuring 20x17 mm and bilateral metastases up to 11 mm. Bronchoscopy and biopsy were performed, and EGFR neg, ALK neg, ROS 1 neg, PD-L1>50% adenocarcinoma was confirmed. He was referred to Clinical Hospital Center Osijek where monotherapy with pembrolizumab in a standard dose of 200 mg intravenously was started in 01/2020. Partial remission was confirmed in October 2020. Immunotherapy was discontinued due to development of pneumonitis, dysphagia and severe weight loss (20kg), but without radiologically confirmed disease progression. At that time he was referred to our hospital for further treatment. Gastroscopy has shown erosive gastritis with active duodenal ulcus, Forrest III. Supportive therapy and proton pump inhibitor were introduced. After complete regression of pneumonitis, improvement of general condition and resolution of dysphagia, no signs of lung cancer progression were found and pembrolizumab was reintroduced in 12/2021. Hypothyroidism was diagnosed in 01/2021 and levothyroxine replacement ther apy was started. In 03/2021 he underwent surgical removal of basal cell carcinoma of skin on the right temporal region with lobe reconstruction. From 02/2021, when pembrolizumab was reintroduced, regression in tumor size was continously confirmed with complete recovery of general condition. He was hospitalized for COVID 19 infection in 09/2021, and due to complications pembrolizumab was discontinued till 11/2021. Lung cancer immunotherapy proceeded till 11/2022, when Multidisciplinary team decided to finish pembrolizumab because of CLL relapse. CLL was in remission till August 2022 when due to B symptoms, lymphcytosis, anemia and generalized lymphadenopathy, hematological workup including biopsy of cervical lymph node was performed and CLL/SLL relapse was confirmed. Initially chlorambucil was introduced, but disease was refractory. Based on cytogenetic test results (IGHV unmutated, negative TP53) and due to cardiovascular comorbidity (contraindication for BTK inhibitors) venetoclax and rituximab were started in 01/2023. After just 1 cycle of treatment normal blood count as well as regression of B symptoms and peripheral lymphadenopathy occured, indicating the probability of complete disease remission. In our patient with metastatic lung adenocarcinoma excellent disease control is achieved during 41 month of treatment in first line setting. Furthermore, relapsed/refractory CLL/SLL is currently in confirmed remission. Conclusion(s): Successful treatment of patients with multiple primary malignancies is based on multidisciplinarity, early recognition and management of side effects, treatment of comorbidities with the aim of prolonging life, controlling symptoms of disease and preserving quality of life.

The Magnitude of Covid-19 Effect on Melanoma Diagnosis, Histopathologic Features and Stage of the Disease in University Hospital of Split

Introduction: Due to the COVID-19 pandemic, some planned medical activities have been postponed, for both national directives and out of concern of the patients who were afraid to go to hospitals. Skin cancers, especially melanomas, diagnosed during lockdown also differed from pre-lockdown tumors in several notable ways, such as number of newly diagnosed patients and histopathologic features. The primary tumor thickness (mm), ulceration (%), anatomic localization, and regional lymph node involvements are important elements for determining the melanoma staging and prognosis. Aim(s): The aim of this report was to investigate the difference in number of newly diagnosed melanoma patients, histopathological features and melanoma TNM-staging between comparable pre-pandemic (March 2019 until March 2020) and pandemic periods (March 2020 until March 2021). Method(s): We collected the data from hospital clinical and pathohistological databases on the total number of newly diagnosed patients with melanoma in University Hospital of Split. Comparative analyses were performed in a pre-pandemic and a pandemic cohort. Result(s): Comparing the first year of the pandemic (N=57) with the same period one year before (N=69), 17,4% decrease of melanoma cases was observed. Cohort analysis showed no differences in the distribution of age and sex. The median age of the melanoma patients in a pre-pandemic cohort was 66 years (29-86), and in pandemic cohort 68 years (31-88). The male gender predominated among melanoma patients. In a pre-pandemic cohort, 63,8% of melanoma patients were man, and in pandemic cohort 68,4%. Cohort analysis showed differences in the primary localization of skin melanoma. In pre-pandemic cohort, primary localization of melanoma were head and neck in 17 patients (25%), trunk in 26 patients (38%), upper extremities in 13 patients (19,1%), lower extremities in 10 patients (14.7%) and unknown primary site in 2 patients (2,9%). In pandemic cohort, primary localization of melanoma were head and neck in 10 patients (17,5%), trunk in 32 patients (56,1%), upper extremities in 8 patients (14%), lower extremities in 5 patients (8,8%) and unknown primary site in 2 patients (3,5%). Cohort analysis showed no differences in the pathohistological subtypes. The most common pathohistological subtypes in both cohorts were superficial spreading subtype (21,7% vs 25,8%), unclassified (21,7% vs 17,5%) and nodular subtype (14,5% vs 17,5%). In pandemic cohort we diagnosed patients with increased tumor thickness and positive lymph nodes. In pre-pandemic cohorts we had more patients with thickness less than 1 mm (40,6% vs 31,6%). We found more patients with tumor thickness between 1 to 2 mm (17,5% vs 4,3%) and more than 4 mm (25% vs 20%) in pandemic. Accordingly, in pandemic cohort we found more patients with positive lymph nodes then in pre-pandemic (22,9% vs 5,9%), and more patients with initially metastatic disease (22,8% vs 15,9%). We did not observed any differences in presence of ulceration among the studied cohorts (26% vs 28%). Conclusion(s): In the analysis conducted in University Hospital of Split, we observed a marked decrease of newly diagnosed melanoma patients in the first year of the pandemic compared to the same period before the pandemic. We observed increased tumor thickness, more patients with lymph nodes involvements and initially metastatic disease in post-lockdown period. These findings may be the result of delays in diagnosis due to the disruptions in routine dermatologic and oncologic care during Covid-19 pandemic. The further analyses are needed to fully understand the impact of the Covid-19 pandemic on melanoma outcomes.

Maxillary osteomyelitis secondary to mucormycosis, a sequel of COVID-19: a clinical case report

Introduction: One of the consequences of COVID-19 is the incidence of mucormycosis in the jaws and subsequent osteomyelitis in patients with undiagnosed or uncontrolled comorbidities, such as diabetes mellitus and associated immunosuppression. Case Report: A 52-year-old male patient with a history of COVID-19 two months ago presented a painful ulcerative lesion of insidious onset in the palatal raphe measuring approximately 2 mm. He referred to numbness of the palatal region of one month of evolution. During the physical examination, purulent content, multiple pustules in the anterior maxillary buccal mucosa, and mobility of upper anterior teeth were observed. The CT revealed isodense bilateral images in maxillary and ethmoidal sinuses, bone sequestrations, and partial loss of anterior vestibular cortical bone. Laboratory tests revealed no abnormality, except for HbH1c: 10.2gr/dl. The patient was hospitalized for control of newly diagnosed diabetes mellitus. Maxillary incisional biopsy was performed, and microscopic analysis showed a mixed inflammatory infiltrate, fibrin deposits with eosinophilic and birefringent ribbon-like hyphae, branched at right angles, compatible with maxillary osteomyelitis secondary to mucormycosis. The treatment started with antifungal and intravenous antibiotics, followed by surgical cleaning under general anesthesia. The patient progressed favorably. Conclusion(s): Immunosuppression resulting from COVID-19 and/or uncontrolled systemic diseases can condition the appearance of rare opportunistic microorganisms causing infections such as mucormycosis. Early diagnosis and treatment make a difference in the morbidity and mortality of patients.

Lymphoproliferation- a clue towards an underlying monogenic disorder of immune dysregulation- a retrospective analysis from a single center in India

Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.

Epidemiological and clinics characteristics of 414 cases of oral lesions and sensorial functions of COVID-19 in Brazil

Introduction: Several studies have evaluated the occurrence of oral lesions and changes in sensory functions in patients positive for COVID-19. Objective(s): To evaluate the manifestations of COVID-19, emphasizing olfactory and gustatory changes, xerostomia, and oral lesions. Material(s) and Method(s): A cross-sectional and observational study was conducted. Approved by the Institutional Ethics Committee (#46151121.6.0000.5141). All patients were diagnosed by reverse transcription-polymerase chain reaction assay (RT-PCR) and considered to have mild symptoms, according to the latest WHO joint report. The patients were evaluated at a reference Service for COVID-19 in Minas Gerais, Brazil. The oral cavity was evaluated for each patient on the second and seventh days. Result(s): A total of 414 patients older than 18 years were evaluated. One hundred thirty-nine presented at least one of the studied conditions, oral lesions (19.08%) were the most frequently observed, followed by gustatory disorders (18.11%), xerostomia (14.25%), and olfactory dysfunction (14%). Among the oral lesions, there were various anatomical locations and clinical presentations. The occurrence involving lips and tongue represented 49 oral lesions, the most prevalent being, respectively, ulcerations (n=51), candidiasis (n=8), and erythema or red plaques (n=7). Fifty patients died. Conclusion(s): This study represents, to date, the largest case series of oral lesions in Brazilian patients with COVID-19, and oral alterations were observed in an expressive percentage of patients with COVID-19. However, it cannot be concluded that SARS-CoV-2 directly causes them.

The Effect of COVID-19 on Care for Chronic Wounds Among Medicare Beneficiaries Using Medicare Claims - 2019, 2020, and 2021

Objectives: Examine the effect of COVID-19 on chronic wound care service provision for Medicare beneficiaries in 2019, 2020, and 2021. Method(s): This retrospective analysis of Medicare claims data included beneficiaries who received care for diabetic foot ulcers and infections, arterial ulcers;skin disorders and infections, surgical wounds and infections;traumatic wounds;venous ulcers and infections, unspecified chronic ulcers, and others. We extracted all claims for each targeted beneficiary across all care settings and from the Medicare Beneficiary Summary File for 2019 to 2021. The outcomes were: 1) prevalence of each wound type, 2) Medicare expenditures by wound type, and expenditures by type of service. Result(s): Over the 3-year period, the number of Medicare beneficiaries with a wound generally decreased in 2020, then increased in 2021 to a higher level than in 2019. In 2019, 16.4% of Medicare beneficiaries (10.6M) had at least one type of wound. In 2020, 14.9% of Medicare beneficiaries (9.8M) were diagnosed with wounds (a decrease of 7.1%), and in 2021, 16.1% of Medicare beneficiaries (10.8M) were diagnosed with wounds, an increase of 1.9% from 2019. In 2021, approximately 2.7% of beneficiaries had a claim with a wound diagnosis that had been added in FY2020, or 0.4% of all Medicare beneficiaries. The prevalence of COVID-19 among beneficiaries with chronic wounds was 896,198 (9.1%) in 2020, rising to 1.2M (11.1%) in 2021. Using our mid-range estimates of Medicare expenditures, wound care totaled $24.7B in 2019, $23.9B in 2020, and $26.3B in 2021. Conclusion(s): These results emphasize the ongoing prevalence of chronic wounds among Medicare beneficiaries and suggest the decrease in care during the pandemic contributed to a relative increase in care and expenditures in 2021. We found a shift in the site of care from skilled nursing facilities toward home health as individuals sought to avoid COVID-19 exposure.Copyright © 2023

Online survey about oral manifestations of COVID-19

Introduction: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 (Coronavirus type 2 causing severe acute respiratory syndrome) presents systemic manifestations such as fever, anosmia, cough, sore throat and headache, dyspnea, tiredness, malaise, diarrhea. There are reports of developing dysgeusia, xerostomia, and vesiculobullous lesions as oral manifestations related to COVID-19. Objective(s): To identify the most prevalent oral manifestations associated with COVID-19 in a group of Paraguayans. Material(s) and Method(s): An electronic survey was used from January to March 2022. Data were presented as frequencies and percentages and analyzed using the chi2 test. Statistical analysis was performed with R software version 4.0.3. Result(s): The sample consisted of 478 people, most female from 15 to 34 years old. 65.48% stated that they had had at least one oral symptom or sign during COVID-19. The loss in the sensation of bitter tastes (34.31%), the alteration of the taste of food (32.43%), and the loss of sweetness (32.01%) were the most prevalent symptoms. In addition, it was found that among the people who developed moderate to severe COVID-19, there was a more significant number (77.78%) of oral manifestations compared to the participants who developed it mildly (63.92%) (chi2;p= 0.044). Conclusion(s): More than half of the respondents presented oral manifestations, more frequent in those who developed moderate to severe COVID-19. Results will serve as a basis for future research and thus strengthen the surveillance of this disease.

BTKi-treated CLL patients have Favourable survival outcomes but concerning levels of second malignancies and COVID-related mortality

Introduction: Bruton's tyrosine kinase inhibitors (BTKi) are used extensively within the NHS to treat specific B-cell malignancies with patients stopping BTKi usually due to adverse events or disease progression. The objective of this study was to analyse effectiveness of BTKi therapy for chronic lymphocytic leukaemia (CLL) at our centre compared to previously published real-world data from the UKCLL Forum (Follows et al, Blood 2019). In addition, we investigated treatment-related adverse events (AE) and second malignancies. Method(s): This is a single-centre retrospective study of 112 CLL patients treated with a BTKi for a minimum of 4 weeks between 2014 and 2022 (ibrutinib n = 71, acalabrutinib n = 38, zanubrutinib n = 3). Treatment was first line (n = 39), second line (n = 44) and 3+ line (n = 29). Patient demographics, duration of BTKi therapy, Aes, discontinuation reasons and second malignancies were collected. Aes were compared with a parallel cohort of 53 non-CLL BTKi-treated patients. Result(s): Median age starting treatment was 73 years, and 71% were male. Primary outcomes were discontinuation-free survival (DFS) and overall survival (OS). With a median follow-up of 3.90 years, the median DFS was 4.18 years (95% CI: 3.52-4.91) with a median OS of 6.35 years (95% CI: 5.52-NA). These compare favourably with previous UKCLL forum data (median DFS = 2.79 years;median OS = 4.66 years), although our patients were more likely to receive BTKi earlier in treatment (3rd line or beyond: 26% of our patients vs. 78% in the UKCLL Forum). The most common Aes included bleeding, cytopenia, infection, cardiac events and mouth ulcers, with 21% stopping BTKi for CLL due to Aes whilst 15% of non-CLL BTKi patients stopped due to an AE. Second malignancies were reported in 49% of CLL patients, yet only 34% of non-CLL patients. Among patients with a confirmed cause of death, infection was the most common cause (39%), followed by CLL (33%), then second malignancy (18%). Of the 31 deaths in 2020 and 2021, 7/31 (23%) were due to, or in association with COVID-19 infection. No COVID-19 deaths were associated with BTKi in non-CLL patients. Conclusion(s): We demonstrate a favourable real-world DFS and OS for BTKi-treated CLL patients although a high number of patients still stop BTKi due to Aes. The very high incidence of second malignancies for all BTKi-treated patients and COVID-19 and infection-related deaths for CLL patients is concerning. As CLL is known to associate with high levels of second cancers, it remains unclear whether BTKi use increases this risk further.

Exploring the learning needs of clinicians in Belgium and Sweden regarding prone positioning and skin damage prevention: A qualitative study.

INTRODUCTION: During the coronavirus pandemic (COVID -19), the use of prone positioning in critically ill patients with acute respiratory distress syndrome (ARDS) increased substantially. As a result, clinicians had to (re)learn how to treat the patient in the prone position while preventing adverse events such as pressure ulcers, skin tears and moisture-associated skin damage. AIM: The purpose of the study was to determine participants' learning needs related to patients in the prone position and the prevention of skin damage, such as pressure ulcers, and what they perceived as a positive or negative learning experience. DESIGN: This study used a qualitative methodological framework and employed an exploratory design. PARTICIPANTS: A purposive sample of clinicians (n = 20) with direct or indirect work experience with prone ventilated patients was recruited in Belgium and Sweden. METHODS: Individual semi-structured interviews were conducted in Belgium and Sweden between February and August 2022. Data were analysed thematically using an inductive approach. The COREQ guideline was utilised to comprehensively report on the study. FINDINGS: Two themes were identified: 'Adapting to a crisis' and 'How to learn', with the latter having two subthemes: 'balancing theory and practice' and 'co-creating knowledge'. Unexpected circumstances necessitated a personal adaption, a change in learning methods and a pragmatic adaptation of protocols, equipment and working procedures. Participants recognised a multifaceted educational approach which would contribute to a positive learning experience regarding prone positioning and skin damage prevention. The importance of poising theoretical teaching with practical hands-on training was highlighted with an emphasis on interaction, discussion, and networking between peers. CONCLUSIONS: The study findings highlight learning approaches which may help inform the development of befitting educational resources for clinicians. Prone therapy for ARDS patients is not limited to the pandemic. Therefore, educational efforts should continue to ensure patient safety in this important area.

Perforated Stress Ulcer of the Duodenum: a Case of an Unexpected Diagnosis in a COVID-19 Patient Following Dilatation and Curettage Procedure.

Background: Stress ulcers in the upper gastrointestinal tract can arise from pathologies related to erosive or inflammatory insults in critically ill patients. The relationship between stressful bodily events and the ischemia and perforation of stress ulcers is poorly understood. Objective: We present a case of perforated stress ulcer following an abortion that was treated by dilatation and curettage (D&C) and complicated by a coronavirus disease 2019 (COVID-19) infection. Case presentation: A 40-year-old lady presented to the emergency room complaining of diffuse abdominal pain, she was recently diagnosed with an incomplete abortion and managed via a D&C procedure in an external hospital. A computed tomography (CT) scan was done at our center for the abdomen and pelvis, showing extensive pneumoperitoneum, which brought the radiologist's attention to suspect a small bowel perforation presumably accompanying a uterine perforation secondary to the D&C. There were no obvious signs of pelvic small bowel perforation in the initial CT images. The perforated duodenal stress ulcer was diagnosed the next day by a new CT scan following oral contrast ingestion and managed surgically by repair and omental patch, and no other bowel perforations were found upon surgical exploration. After the surgery, the patient was diagnosed with COVID-19, and her clinical status deteriorated gradually during the following week, and she passed away from a cardiac arrest. Conclusion: It is unclear whether septic abortion or COVID-19 has resulted in stress ulcer perforation in our patient. This case report highlights the importance of raising early suspicion in the diagnosis of stress ulcer perforation in critically ill patients to reduce the risk of morbidity and mortality.

A New-Onset Facial Lesion in a Hospitalized COVID-19 Patient.

Pressure ulcers form when skin is compressed against a bony prominence, often in the context of prolonged supine or prone-based care. Hospitalized, bedridden patients are at the highest risk of this complication, especially when preventative measures like regular rotational bed treatment are not employed. In this case report, we present a rare case of a COVID-19-related facial pressure ulcer that occurred in the context of regular rotational bed treatment. The lesion was managed by wound care and allowed to heal by secondary intention. Ultimately, we hope that this manuscript will raise awareness for this atypical ulcer location, especially as prone-position treatment approaches take hold.

Clinical and cost effectiveness of a system for turning and positioning intensive care unit patients, when compared to usual care turning and positioning devices, for the prevention of hospital-acquired pressure injuries. A randomised controlled trial.

Pressure injuries affect 13.1% to 45.5% of patients in the intensive care unit and lead to pain and discomfort for patients, burden on healthcare providers, and unnecessary cost to the health system. Turning and positioning systems offer improvements on usual care devices, however the evidence of the effectiveness of such systems is still emerging. We conducted an investigator initiated, prospective, single centre, two group, non-blinded, randomised controlled trial to determine the effectiveness of a system for turning and positioning intensive care unit patients, when compared to usual care turning and positioning devices, for preventing PIs. The trial was prematurely discontinued after enrolment of 78 participants due to COVID-19 pandemic related challenges and lower than expected enrolment rate. The study groups were comparable on baseline characteristics and adherence to the interventions was high. Four participants developed a PI (in the sacral, ischial tuberosity or buttock region), n = 2 each in the intervention and control group. Each participant developed one PI. As the trial is underpowered, these findings do not provide an indication of the clinical effectiveness of the interventions. There was no participant drop-out or withdrawal and there were no adverse events, device deficiencies, or adverse device effects identified or reported. The results of our study (in particular those pertaining to enrolment, intervention adherence and safety) provide considerations for future trials that seek to investigate how to prevent PIs among ICU patients.

Management of Acquired von Willebrand Syndrome During Prolonged VV-ECMO

Acquired von Willebrand syndrome (AVWS) contributes to bleeding during extracorporeal membrane oxygenation (ECMO) support. Although it is recognized that AVWS rapidly resolves after ECMO decannulation, this approach may often be clinically unsuitable. In such cases, optimal AVWS management during ECMO support is not well established. We report our approach to managing AVWS in a patient on veno-venous (VV) ECMO for 59 days. A 19-year-old male developed hypoxemic respiratory failure from SARS-CoV-2 pneumonia. Following intubation, he progressed to VV-ECMO support for refractory hypoxemia and was started on bivalirudin for systemic anticoagulation. Two days later, he developed refractory gastrointestinal and oro-nasopharyngeal bleeding despite blood product transfusions and discontinuing bivalirudin. He was started on pantoprazole along with infusions of octreotide and aminocaproic acid. Upper endoscopy on ECMO day 5 revealed an ulcerative bleeding vessel in the duodenum that was clipped. Recurrent mucosal bleeding precluded resumption of systemic anticoagulation. On ECMO day 23, AVWS was diagnosed based on elevated von Willebrand factor (VWF) activity (207%, normal 55-189%) and antigen (234%, normal 50-210%) levels with abnormally low VWF high-molecular-weight multimers. Factor VIII complex was administered twice over the following week. Between doses, the ECMO circuit was exchanged to empirically mitigate suspected shear-related VWF consumption from the fibrin burden, and a repeat endoscopy controlled additional intestinal bleeding with local hemostatic agents. He received 36 units of red blood cells, 2 units of platelets, 2 units of plasma, and 7 pooled units of cryoprecipitate over 31 days leading into these combined interventions. In the 28 days afterwards, he received 3 units of red blood cells, 3.5 pooled units of cryoprecipitate, and no additional platelets or plasma. Our patient was maintained off systemic anticoagulation for 54 of 59 days of VV-ECMO support without any thrombotic complications occurring. With no subsequent clinical evidence of bleeding, repeat VWF testing was done two months post-decannulation and showed near-normal VWF activity (54%) and normal multimer distribution. Our patient rehabilitated well without any neurologic deficits and on discharge was requiring supplemental oxygen with sleep and strenuous activity. Avoiding systemic anticoagulation, repleting VWF, maintaining circuit integrity, and providing local hemostasis, when possible, may be a safe and effective management strategy of AVWS on ECMO support when decannulation is not a viable option.

Esophageal Mucosal Calcinosis: A Rare Site of Calcium Deposition in End-Stage Renal Disease

Introduction: Calciphylaxis, otherwise known as calcium uremic arteriolopathy, is defined as calcium deposition around blood vessels in skin and fat tissue which occurs in 1-4% of patients with end-stage renal disease (ESRD). Calcium deposition in the esophagus is extremely rare;to date, there have been only 4 cases reported worldwide. We report the fifth case of esophageal mucosal calcinosis occurring in a young male with ESRD. Case Description/Methods: A 37-year-old Thai man with ESRD on peritoneal dialysis since 2005 presented with generalized weakness and odynophagia due to oral ulcers, resulting in poor PO intake. He denied drinking alcohol, illicit drug use, or smoking. On exam his abdomen was soft, non-distended, non-tender, without any guarding. Past medical history included hypertension and COVID-19 in January 2022. Laboratory tests revealed neutropenia and pancytopenia, hyperphosphatemia, and hypocalcemia. EGD revealed distal esophageal esophagitis and hemorrhagic erosive gastropathy. Biopsy showed ulcerative esophagitis with dystrophic calcification, consistent with esophageal mucosal calcinosis .No intestinal metaplasia was noted. Immunohistochemistry was negative for CMV, HSV1, and HSV2. The patient was treated with pantoprazole 40mg IV every 12 hours, Magic Mouthwash 5ml qid, and Carafate 10mg qid. He was transferred to a cancer center where he had a bone marrow biopsy formed which was negative. His symptoms resolved and the patient was discharged to home (Figure). Discussion(s): Esophageal mucosal calcinosis is extremely rare. It is due to a combination of factors involving acidosis and the phenotypic differentiation (and apoptosis) of vascular smooth muscle cells (VSMC) into chondrocytes or osteoblast-like cells. These changes, along with the passive accumulation of calcium and phosphate, induce calcification. Acidosis is well-known to promote inflammation of the arterial walls, releasing cytokines that induce vascular calcification. The benefits of treatment with sodium thiosulfate remain unclear. An ample collection of cases should help devise standardized treatment options and establish management guidelines for this condition.

Molecular genetics and genomics of the ABO blood group system

The A and B oligosaccharide antigens of the ABO blood group system are produced from the common precursor, H substance, by enzymatic reactions catalyzed by A and B glycosyltransferases (AT and BT) encoded by functional A and B alleles at the ABO genetic locus, respectively. In 1990, my research team cloned human A, B, and O allelic cDNAs. We then demonstrated this central dogma of ABO and opened a new era of molecular genetics. We identified four amino acid substitutions between AT and BT and inactivating mutations in the O alleles, clarifying the allelic basis of ABO. We became the first to achieve successful ABO genotyping, discriminating between AA and AO genotypes and between BB and BO, which was impossible using immunohematological/serological methods. We also identified mutations in several subgroup alleles and also in the cis-AB and B(A) alleles that specify the expression of the A and B antigens by single alleles. Later, other scientists interested in the ABO system characterized many additional ABO alleles. However, the situation has changed drastically in the last decade, due to rapid advances in next-generation sequencing (NGS) technology, which has allowed the sequencing of several thousand genes and even the entire genome in individual experiments. Genome sequencing has revealed not only the exome but also transcription/translation regulatory elements. RNA sequencing determines which genes and spliced transcripts are expressed. Because more than 500,000 human genomes have been sequenced and deposited in sequence databases, bioinformaticians can retrieve and analyze this data without generating it. Now, in this era of genomics, we can harness the vast sequence information to unravel the molecular mechanisms responsible for important biological phenomena associated with the ABO polymorphism. Two examples are presented in this review: the delineation of the ABO gene evolution in a variety of species and the association of single nucleotide variant (SNV) sites in the ABO gene with diseases and biological parameters through genome-wide association studies (GWAS).Copyright © Annals of Blood. All rights reserved.

Clinical Outcome of Systemic Lupus Erythematosus during the Covid-19 Omicron Variantwave Compared to Previous Periods: Results from a Single Center Cohort of Puerto Rico

Objectives: Variant-related differences of SARS-CoV-2 have been reported such as higher transmissibility but less disease severity in omicron sublineages when compared to other variants. Although some studies have examined the outcomes of COVID-19 in systemic lupus erythematosus (SLE), most were conducted during the initial waves. Thus, we sought to compare the clinical outcomes of SLE patients with COVID-19 during the omicron and pre-delta/delta periods. Method(s): A cohort of adults with SLE from a single center in Puerto Rico was studied. SARS CoV-2 infection was confirmed by polymerase chain reaction or antigen tests. The pre-delta/delta variants period was defined as March 2020 to November 2021 and the omicron period as December 2021 to October 2022. Demographic parameters, cumulative SLE manifestations, disease activity, disease damage, lupus treatments, comorbidities, COVID-19 symptoms, SLE exacerbations, and hospitalizations were compared between the study periods using bivariate and multivariate analyses. Result(s): Of the entire SLE cohort (n = 347), 151 patients (43.5%) had COVID-19. In those with COVID-19, the mean (SD) age was 46.7 (12.5) years and 96.0% were women. Overall, clinical outcomes were favorable with low rates of hospitalizations (2.6%), lupus flares (3.3%), and mortality (0.7%). In 14.6% of cases, COVID-19 occurred during the pre-delta/delta period and in 85.4% during the omicron wave. Patients that had COVID-19 during the predelta/ delta period were younger and had a significantly higher proportion of oral ulcers, psychosis, anti-Smith antibodies, coronary artery disease, and chronic kidney disease compared to those during the omicron wave. Among COVID-19 symptoms, runny nose, cough, and sore throat were more common in the omicron period, whereas anosmia and anorexia were more frequent in the pre-delta/delta period. In the multivariable analyses adjusted by age, all variables retained significance except for psychosis, anti-Smith antibodies, and coronary artery disease. No significant differences were observed for other variables. Conclusion(s): In this group of Puerto Ricans with SLE, a higher proportion had COVID-19 during the omicron wave compared to previous periods. No differences were seen for severe outcomes such as hospitalizations, lupus flares, and mortality. Furthermore, COVID-19 did not appear to have a negative impact on the short-term clinical outcomes of these patients, regardless of the variant period examined.