Natural Evolution of Porcine Epidemic Diarrhea Viruses Isolated from Maternally Immunized Piglets

Simple SummaryDuring the long-term co-evolution of the virus and the host, even closely related vaccines may emerge with incomplete protective immunity due to the mutations or deletions of amino acids at specific antigenic sites. The mutation of PEDV was accelerated by the recombination of different strains and the mutation of the strains adapting to the environment. These mutations either cause immune escape from conventional vaccines or affect the virulence of the virus. Therefore, researching and developing new vaccines with cross-protection through continuous monitoring, isolation and sequencing are important to determine whether their genetic characteristics are changed and to evaluate the protective efficacy of current vaccines. The porcine epidemic diarrhea virus (PEDV) can cause severe piglet diarrhea or death in some herds. Genetic recombination and mutation facilitate the continuous evolution of the virus (PEDV), posing a great challenge for the prevention and control of porcine epidemic diarrhea (PED). Disease materials of piglets with PEDV vaccination failure in some areas of Shanxi, Henan and Hebei provinces of China were collected and examined to understand the prevalence and evolutionary characteristics of PEDV in these areas. Forty-seven suspicious disease materials from different litters on different farms were tested by multiplex PCR and screened by hematoxylin-eosin staining and immunohistochemistry. PEDV showed a positivity rate of 42.6%, infecting the small and large intestine and mesenteric lymph node tissues. The isolated strains infected Vero, PK-15 and Marc-145 multihost cells and exhibited low viral titers in all three cell types, as indicated by their growth kinetic curves. Possible putative recombination events in the isolates were identified by RDP4.0 software. Sequencing and phylogenetic analysis showed that compared with the classical vaccine strain, PEDV SX6 contains new insertion and mutations in the S region and belongs to genotype GIIa. Meanwhile, ORF3 has the complete amino acid sequence with aa80 mutated wild strains, compared to vaccine strains CV777, AJ1102, AJ1102-R and LW/L. These results will contribute to the development of new PEDV vaccines based on prevalent wild strains for the prevention and control of PED in China.

Prevalence of adverse drug reactions associated with emergency department visits and risk factors for hospitalization

Objective: Adverse drug reactions increase morbidity and mortality, prolong hospital stay and increase healthcare costs. The primary objective of this study was to determine the prevalence of emergency department visits for adverse drug reactions and to describe their characteristics. The secondary objective was to determine the predictor variables of hospitalization for adverse drug reactions associated with emergency department visits. Method(s): Observational and retrospective study of adverse drug reactions registered in an emergency department, carried out from November 15th to December 15th, 2021. The demographic and clinical characteristics of the patients, the drugs involved and the adverse drug reactions were described. Logistic regression was performed to identify factors related to hospitalization for adverse drug reactions. Result(s): 10,799 patients visited the emergency department and 216 (2%) patients with adverse drug reactions were included. The mean age was 70 +/- 17.5 (18-98) years and 47.7% of the patients were male. A total of 54.6% of patients required hospitalization and 1.6% died from adverse drug reactions. The total number of drugs involved was 315 with 149 different drugs. The pharmacological group corresponding to the nervous system constituted the most representative group (n = 81). High-risk medications, such as antithrombotic agents (n = 53), were the subgroup of medications that caused the most emergency department visits and hospitalization. Acenocumarol (n = 20) was the main drug involved. Gastrointestinal (n = 62) disorders were the most common. Diarrhea (n = 16) was the most frequent adverse drug reaction, while gastrointestinal bleeding (n = 13) caused the highest number of hospitalizations. Charlson comorbidity index behaved as an independent risk factor for hospitalization (aOR 3.24, 95% CI: 1.47-7.13, p = 0.003, in Charlson comorbidity index 4-6;and aOR 20.07, 95% CI: 6.87-58.64, p = 0.000, in Charlson comorbidity index >= 10). Conclusion(s): The prevalence of emergency department visits for adverse drug reactions continues to be a non-negligible health problem. High-risk drugs such as antithrombotic agents were the main therapeutic subgroup involved. Charlson comorbidity index was an independent factor in hospitalization, while gastrointestinal bleeding was the adverse drug reaction with the highest number of hospital admissions.Copyright © 2022 Sociedad Espanola de Farmacia Hospitalaria (S.E.F.H)

Use of Immunotherapy in Patients With Cancer During the COVID-19 Pandemic

During this process, type II transmembrane serine protease (TMPRSS2) expression seems to be important as a coadjuvant protein to assist SARS-CoV-2 in cell invasion.3,4 Patients who progress to the severe form of the disease have an inflammatory response that leads to a reduction of the expression of cytotoxic CD8+ and CD4+ T lymphocytes. (IFN-.), as well as others, increase.2,4,5 In this context, as with other viral infections, increased expression of regulatory molecules of inflammatory response, like PD-1 and PD-L1, occurs.2, 4-6 COVID19 and Cancer The morbidity and mortality of COVID-19 is higher in elderly and male patients, as well as in those with comorbidities. [...]only observational studies have raised the possibility of the protective effect of IMT, and further data are required to confirm this hypothesis and use it to guide the management of patients with cancer. In the case of SARS-CoV-2 infection in patients receiving IMT, the risk of cytokine release syndrome is high. [...]the second quandary oncologists face is the challenge to correctly diagnosis SARS-CoV-2 infection or IMT-induced pneumonitis.4,6,11 Another important consideration is controlling immune-related AEs in patients who need long-term immunosuppression therapy.

Tracing the Origin of Genotype II African Swine Fever Virus in China by Genomic Epidemiology Analysis

The pandemic spread of African swine fever (ASF) has caused serious effects on the global pig industry. Virus genome sequencing and genomic epidemiology analysis play an important role in tracking the outbreaks of the disease and tracing the transmission of the virus. Here we obtained the full-length genome sequence of African swine fever virus (ASFV) in the first outbreak of ASF in China on August 3rd, 2018 and compared it with other published genotype II ASFV genomes including 9 genomes collected in China from September 2018 to October 2020. Phylogenetic analysis on genomic sequences revealed that genotype II ASFV has evolved into different genetic clusters with temporal and spatial correlation since being introduced into Europe and then Asia. There was a strong support for the monophyletic grouping of all the ASFV genome sequences from China and other Asian countries, which shared a common ancestor with those from the Central or Eastern Europe. An evolutionary rate of 1.312 × 10−5 nucleotide substitutions per site per year was estimated for genotype II ASFV genomes. Eight single nucleotide variations which located in MGF110-1L, MGF110-7L, MGF360-10L, MGF505-5R, MGF505-9R, K145R, NP419L, and I267L were identified as anchor mutations that defined genetic clusters of genotype II ASFV in Europe and Asia. This study expanded our knowledge of the molecular epidemiology of ASFV and provided valuable information for effective control of the disease.

Clinical and radiological imaging as prognostic predictors in COVID-19 patients

BackgroundSince the announcement of COVID-19 as a pandemic infection, several studies have been performed to discuss the clinical picture, laboratory finding, and imaging features of this disease. The aim of this study is to demarcate the imaging features of novel coronavirus infected pneumonia (NCIP) in different age groups and outline the relation between radiological aspect, including CT severity, and clinical aspect, including age, oxygen saturation, and fatal outcome. We implemented a prospective observational study enrolled 299 laboratory-confirmed COVID-19 patients (169 males and 130 females;age range = 2–91 years;mean age = 38.4 ± 17.2). All patients were submitted to chest CT with multi-planar reconstruction. The imaging features of NCIP in different age groups were described. The relations between CT severity and age, oxygen saturation, and fatal outcome were evaluated.ResultsThe most predominant CT features were bilateral (75.4%), posterior (66.3%), pleural-based (93.5%), lower lobe involvement (89.8%), and ground-glass opacity (94.7%). ROC curve analysis revealed that the optimal cutoff age that was highly exposed to moderate and severe stages of NCIP was 38 years old (AUC = 0.77, p < 0.001). NCIP was noted in 42.6% below 40-year-old age group compared to 84% above 40-year-old age group. The CT severity was significantly related to age and fatal outcome (p < 0.001). Anterior, centrilobular, hilar, apical, and middle lobe involvements had a significant relation to below 90% oxygen saturation. A significant negative correlation was found between CT severity and oxygen saturation (r = − 0.49, p < 0.001). Crazy-paving pattern, anterior aspect, hilar, centrilobular involvement, and moderate and severe stages had a statistically significant relation to higher mortality.ConclusionThe current study confirmed the value of CT as a prognostic predictor in NCIP through demonstration of the strong relation between CT severity and age, oxygen saturation, and the fatal outcome. In the era of COVID-19 pandemic, this study is considered to be an extension to other studies discussing chest CT features of COVID-19 in different age groups with demarcation of the relation of chest CT severity to different pattern and distribution of NCIP, age, oxygen saturation, and mortality rate.

Predictors of Dengue Preventive Practices Based on Precaution Adoption Process Model among Health Care Professionals in Northwest of Iran

Background: Dengue fever as a mosquito-borne disease, has rapidly spread due to climate change, globalization, and human behavior. Iran is prone to dengue fever, as its vector recently has been found in the country. This study aimed to assess predictors of dengue preventive practices based on Precaution Adoption Process Model (PAPM) factors in West Azerbaijan province, northwest of Iran. Methods: This cross-sectional study conducted on 405 health professionals of communicable disease sector who were interested in study participation. Data-gathering instrument was an online researcher-made questionnaire consisting of demographic characteristics (11 items), questions based on PAPM, and dengue preventive practices (85 items). Content validity and reliability of the instrument, content validity ratio, content validity index, and Cronbach a were utilized, respectively. Descriptive, analytical, and regression analysis using SPSS and STATA were examined. Results: Regression analysis revealed that awareness of appropriate actions for dengue prevention was a stronger predictor of preventive practice in borderline and appropriate categories (ß= 4.09, p< 0.001) and (ß= 4.42, p< 0.001), re - spectively. Among factors of PAPM, beliefs about precaution effectiveness and difficulty in borderline (ß= 1.04, p= 0.04) and appropriate (ß= 1.12, p= 0.03) groups had direct and significant relation with dengue preventive practice. Conclusion: The highest mean score of beliefs about hazard likelihood and severity factor was related to dengue prevention. Therefore, theory-based interventions that address beliefs about precaution effectiveness and difficulty can lead to assistance in acting. To improve dengue preventive practices, a well-designed promotive intervention that addresses associated factors in a context-specific manner is essential.

Role of [18F] FDG PET-CT in detection of COVID-19 vaccine-associated hypermetabolic lymphadenopathy (VAHL) in lymphoma patients: with serologic testing correlation

BackgroundCOVID-19 vaccination of the population has a great importance, especially in oncological patients. The high incidence of vaccine-associated hypermetabolic lymphadenopathy (VAHL) makes a difficulty in the diagnosis of PET-CT of oncological patients. They should be vaccinated in the side opposite to the expected malignant LNs to avoid unnecessary biopsy and change in therapy. The aim of this study was to assess the role of PET-CT in detection of VAHL after the 2nd dose of Pfizer-BioNTech vaccine in lymphoma patients and compare the incidence of VAHL among lymphoma patients treated with B cell depletion therapy during the 6 months prior to vaccination and those treated > 6 months before vaccination.ResultsThis study comprised 120 lymphoma patients, referred for FDG PET/CT 1–3 weeks after the 2nd dose of Pfizer-BioNTech COVID-19 vaccine. Hypermetabolic LNs were identified in 55%. The incidence of VAHL in lymphoma patients treated with anti-CD20 antibody rituximab during the 6 months prior to vaccination (9%) was significantly lower compared with other lymphoma patients treated with anti-CD20 antibody rituximab > 6 months before vaccination (91%). The incidence and grades of VAHL are significantly high within the 1st week after the 2nd dose of Pfizer-BioNTech vaccine in patients younger than 60 years of age. Only 7 of 37 patients with negative serology had VAHL on PET-CT, whereas 10 of 26 patients with decreased anti-spike titers and 49 of 57 patients with increased anti-spike titers had VAHL on PET-CT.ConclusionsVAHL makes challenges in the interpretation of FDG PET/CT in oncology patients. Accurate data collection, regarding the time and site of COVID vaccination, is important to help radiologists in identifying the cause of abnormal nodal FDG uptake. We suggest to schedule FDG PET-CT for lymphoma patients at least 3 weeks after the 2nd dose of Pfizer-BioNTech vaccine.

Care of Patients with Haemato-Lymphoid Diseases During Covid: Challenges and Difficulties Faced by Non-Covid Patients in Accessing Health Care

Introduction: Since the national lock down was declared in March in response to the SARS COV-2 pandemic, there has been a concerted exercise to ramp up medical infrastructure and man power, with hospitals devising plans to prepare and allocate resources to organize themselves in managing the emerging cases efficiently. There was a growing concern that non COVID care and diseases could be affected. Inability to travel, limitation of financial support, lack of support services are among the many reasons that could limit non covid care. There is however a lack of information on this impact. Aims & Objectives: * To estimate the proportion of patients with benign hematological diseases whose care was affected during covid. * To estimate the proportion of patients with malignant hematological diseases whose care was affected during covid. Material(s) and Method(s): This was a cross-sectional study conducted among patients under the care of the Regional Advanced Center for Transplantation, Haemato-Lymphoid Oncology and Marrow Diseases (RACTHAM) at the Believers Church Medical College Hospital. Patients visiting the OP service were intervewed face to face. We report on our data collected in the intial phase of lockdown from April 1, 2020 through August 31, 2020. Result(s): A total of 505 patients were interviewed and 501 resposnes were recorded. The detailed characteristics are tabulated in Table 1. The majority, 375)74.8%) of patients were diagnosed with non malignat conditions. 256 (50.6%) of the resposndent were male. We noted that only 68 patients (13.5%) could not continue their care during the intial phase of the pandemic and lock down. 156 patients (30.*%) were able to continue their care elsewhere. There were 20 deaths during this period. Amongst those whose care was affected, 156 transferred care elsewehere. 27 (5.3&) patients were unalble to travel and 15 (2.9%) patients utilised telemedicine dservices to continue their care. ALl patients who required transfusion were able to access the same during this period. Conclusion(s): This study provides the first insight to the best of our knowledge on challenges to non covid care by patients with hematological diseases in our region. This study estimating the burden or proportion of patients with hematological diseases whose non covid care was affected has the potential to help in formulating national programs in times of pandemics.

A young girl with fever and atypical rash

Kawasaki disease Scarlet fever Multisystem inflammatory syndrome in children (MIS-C) Hand, foot and mouth disease (coxsackievirus) For answer see page 02 For question see page 01 Answer: C Multisystem inflammatory syndrome in children (MIS-C) was highly suspected because of the biological inflammatory syndrome and the Kawasaki-like dermatological presentation. Majority of published cases have positive serologic testing for SARS-CoV-2 (67%) and less commonly positive RT-PCR testing from nasopharyngeal testing (33%),2 suggesting that the pathogenesis of this syndrome involves post infection immune dysregulation rather than related to acute early infection.2 3 This affliction is life-threatening as it is usually associated with severe physiological impairment (hypotension, tachycardia) requiring admission in an intensive care unit in more than 50% of cases. Multi-System inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection: review of clinical presentation, hypothetical pathogenesis, and proposed management.

Myeloid Sarcoma Mimicking Dental Abscess in a Patient with Chronic Myeloid Leukemia: Diagnostic and Therapeutic Dilemma

Chronic myeloid leukemia (CML) is a hematologic malignancy that has significant improvement in its prognosis after the introduction of tyrosine kinase inhibitors. Transformation to accelerated phase or blast phase can happen. Myeloid sarcoma or chloroma is an uncommon extramedullary disease. It is very unusual for patients with CML to develop myeloid sarcoma. We report a young man with CML in the chronic phase who developed myeloid sarcoma. There were many difficulties in the diagnosis of myeloid sarcoma due to the simulation of other more common conditions like infections and other malignancies. In addition, there are treatment challenges because of lack of standardized treatment. The case shed light on this rare complication, the challenging diagnosis, and its implication in patients with CML.

HHV-8-associated multicentric Castleman disease with concurrent Kaposi sarcoma

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder typically manifesting with bulky lymphadenopathy in multiple lymph node stations. We describe an atypical presentation of human herpes virus 8 (HHV8)-associated MCD in a middle-aged man with no significant medical history who presented with 1 month of systemic symptoms. He was found to be HIV-1 positive. A physical examination did not reveal palpable lymphadenopathy. A contrast-enhanced CT scan was notable for hepatosplenomegaly and mildly enlarged scattered lymph nodes in the abdomen and pelvis. A positron emission tomography/CT scan demonstrated hypermetabolic cervical chain lymph nodes. Posterior cervical lymph node pathology showed HHV8-positive MCD with concurrent HIV-associated Kaposi sarcoma. The patient was treated with rituximab and liposomal doxorubicin without response. We emphasise the lack of the hallmark of bulky lymphadenopathy in this patient, and the importance of a timely pathological diagnosis in MCD.

Requirement for booster doses in healthy, cancer and immunosuppressed patients infected with the ancestral or variant SARS-CoV-2

Introduction: Current SARS-CoV-2 vaccines are effective at preventing COVID-19 or limiting disease severity in healthy individuals, but effectiveness is lower among patients with cancer or immunosuppression. Vaccine effectiveness wanes with time and varies by vaccine type. Moreover, current vaccines are based on the ancestral SARS-CoV-2 spike protein sequence, and emerging viral variants evade vaccine induced immunity. Booster doses partially overcome these issues, but there are limited clinical data on the durability of protection afforded by boosters - especially against SARS-CoV-2 variants. Methods: Here we describe a mechanistic mathematical model for vaccination-induced immunity in patients with cancer and use it to predict vaccine effectiveness taking into account current and possible future viral, host and vaccine characteristics. Crucially, this allows predictions over time frames currently not reported in the clinical literature. The model incorporates the infection of lung epithelium by SARS-CoV-2, the response of innate and adaptive immune cells to infection, the production of pro-and anti-inflammatory cytokines, the activation of the coagulation cascade. The model further accounts for the interactions between the virus, immune cells and tumor cells as well as for vaccination-induced immunity and anti-cancer therapies. Results: Model predictions were validated with available clinical data. The model predicts that for healthy individuals vaccinated and boosted with mRNA-1273, BNT-162b2a, and Ad26.COV2.S, robust immunogenicity against the ancestral and delta variant extends beyond a year. Immunogenicity is enhanced following booster vaccination in patients with cancer on various anti-cancer therapies and for patients without cancer on immunosuppressive agents. However, our model predicts that more than one booster dose will be required for patients with cancer, or on immunosuppression, to maintain protective immunity against current and hypothetical future variants. SARS-CoV2 variants with enhanced binding to target cells, reduced affinity for vaccine-generated antibodies or reduced immunogenicity resulted in lower antibody levels and more severe disease compared with variants with enhanced viral replication or internalization rates. Conclusion: For patients with cancer and immunosuppressed individuals, SARS-CoV2 variants with enhanced ability to bind to target cells, altered antibody affinity or reduced immunogenicity could lead to breakthrough infections even after a single booster dose. Our mathematical model is useful for anticipating and planning future vaccinations in patients with cancer.

A rare bladder diverticulum cancer and concomitant prostate adenocarcinoma case report

This report presents the case of a 65-year-old male diagnosed with two concomitant cancers: transitional cell carcinoma within bladder diverticulum (G3, pTa) and prostate adenocarcinoma cT2bN0M0 (Gleason 7 (3+4)). Due to specific location of the bladder cancer (within diverticulum) and the concomitant prostate adenocarcinoma, we decided to perform a single surgery to treat both diseases: 3D Laparoscopic cystoprostatectomy with pelvic lymphadenectomy and ileal conduit. Diverticulum bladder urothelial carcinoma in situ (pTisN0MxL0V0R0) and acinar prostate adenocarcinoma Gleason 7 (3+4) (pT2bN0MxL0V0R0), both with surgical negative margins, and 21 negative lymph nodes were reported in pathology. Seric PSA follow-up was undetectable 1 month after surgery. Clinical and therapeutic management of this disease are also discussed.

What Lies Behind the Cannonball Pulmonary Metastases: Hodgkin's Lymphoma?

The cannonball pulmonary appearance is hematogenous dissemination of various primary tumors but rarely a Hodgkin's lymphoma, a disease that most commonly manifests with lymphadenopathy, often affecting the mediastinum and supraclavicular or cervical lymph nodes. To date, to the best of our knowledge, no case has been reported where the investigation of a cannonball pulmonary appearance led to the diagnosis of Hodgkin's lymphoma. Hence, in our case report, we attempt to highlight the uncommon presentation of this disease in a 14-year-old girl who initially presented with dyspnea before her chest x-ray revealed a cannonball pulmonary appearance, which was later linked with Hodgkin's lymphoma after performing a biopsy of her axillary node.

Intestinal Tuberculosis Presenting with Gastrointestinal Bleeding in Patient on Warfarin Therapy

Background. Intestinal tuberculosis (ITB) constitutes less than 5% of overall cases of extrapulmonary disease and mostly affects the ileocecal region. The presentation and radiologic findings in enteric tuberculosis can mimic Crohn’s disease (CD). Case Presentation. We present a case report of an African woman who presented to a Kenyan hospital with lower gastrointestinal bleeding while on anticoagulation for valvular atrial fibrillation, and was diagnosed with intestinal tuberculosis after colonoscopy, biopsy, and positive staining for tuberculous bacilli. Conclusion. Intestinal tuberculosis causing gastrointestinal bleeding is rare but should be suspected in patients living in TB endemic regions.

Spontaneous Tumor Lysis Syndrome in a Patient with Bulky Chronic Lymphocytic Leukemia Diagnosed after Resolution of Symptoms

Tumor lysis syndrome (TLS) is an oncologic emergency characterized by the destruction of tumor cells leading to an influx of large amounts of uric acid, potassium, and phosphorus into systemic circulation. It most often occurs after the initiation of cytotoxic therapy in high-grade lymphomas and leukemias;however, rarely it may occur spontaneously. The authors report a case of spontaneous tumor lysis causing electrolyte abnormalities and acute kidney injury in a patient with subsequently diagnosed large chronic lymphocytic leukemia tumor burden. Spontaneous TLS can be the first presentation of underlying malignancy;therefore, physicians should be aware of the associated findings.

Primary Presentation of Neurosarcoidosis as a Pituitary Mass with Sinonasal Involvement

Objective: Sarcoidosis is a systemic granulomatous disease identified by noncaseating granulomas that can have central nervous system (CNS) involvement but rarely presents with primary CNS involvement. Neurosarcoidosis can present with or without systemic disease and can present with mass effect, endocrinopathies, and neuropathic symptoms. We report on an unusual case of neurosarcoidosis involving a pituitary adenoma. Case report: A 45-year-old African American man presented to ophthalmology clinic with a chief complaint of worsening field of vision. Magnetic resonance imaging (MRI) showed a 3.8-cm macroadenoma containing cystic and calcified components with optic chiasm compression, near-complete opacification of the maxillary sinuses, and mucosal thickening in the frontal sinuses. Due to the COVID-19 pandemic, follow-up was delayed for 4 months while the vision loss progressed to near blindness in his right eye. After thorough evaluation, the patient was found to have near-complete right sided blindness, diffuse lymphadenopathy. After interdisciplinary discussions surgery was recommended. The patient underwent endoscopic transsphenoidal resection of the pituitary tumor and concurrent endoscopic sinus surgery. During the approach sinus mucosa was grossly inflamed. Frozen section of the sinus mucosa revealed granulomatous disease. The suprasellar mass had both soft contents which could be suctioned and fibrotic tumor with dense septations. Final pathology showed a pituitary adenoma with non-necrotizing granulomas within in the pituitary adenoma. Post-operatively, the patient was started on steroids and reported gradual improvement in his visual fields. At 3-months post-operative, MRI showed significant reduction in macroadenoma with a 1.5 cm residual tumor remaining in the sella and a decompressed optic chiasm which retracted inferiorly without any evidence of other intercranial anomalies. Literature review: Sarcoidosis occurs mostly in African Americans and Northern European women in their 3rd and 4th decades and can affect any part of the body such as the lymphatic systems, skin, lungs, and liver. Sarcoidosis is estimated to be prevalent in up to 80 per 100,000 people. CNS involvement occurs in 5 to 15% of patients with systemic sarcoidosis and can present with cranial neuropathy such as 7th nerve palsy, anticonvulsant refractory seizures, visual changes, and headaches. Pituitary involvement occurs 0.5% of patients with sarcoidosis and can present with endocrine and water metabolism dysfunction while sinonasal sarcoidosis can occur in up to 4%. Sinonasal sarcoidosis most usually presents as chronic crusting rhinitis, nasal obstruction, anosmia, and epistaxis and can show clinically as mucosal hypertrophy and external nose deformity in ~10% of these patients. Discussion and Conclusion: Symptomatic pituitary mass as the initial presentation of sarcoidosis is extremely rare. This case of primary neurosarcoidosis is unusual with its initial presentation mimicking non-functional pituitary macroadenoma with optic chiasm compression and associated vision loss. Primary presentation of neurosarcoidosis as a pituitary mass is rare but should be included in the differential diagnosis of a patient presenting with a combination of a macroadenoma, chronic sinusitis, and lymphadenopathy.

The research progress on the influence of exercise on vaccine immune response

In order to systematically analyze and explore the effects and mechanisms of domestic and foreign sports interventions on the immune response after vaccination in the past 20 years, the results find that acute and chronic exercise interventions before or after vaccination can promote the body's immune system to produce a better immune response to the vaccine, make the titer of the antibody higher after vaccination, and increase faster, as well as have a longer-lasting immune protection effect on the host, especially in the elderly, frail, sick and female populations. At the same time, it can also alleviate the adverse reactions of vaccination. Its mechanism was related to inflammatory environment caused by exercise that can speed up blood circulation, increase the number of white blood cells in the circulating blood, change the content of cytokines or chemokines in the tissues and lymphatic circulation, as well as exercises that cause fine muscle fiber damage. The conclusions are beneficial to understand and participate in the current COVID-19 vaccination for the global population nowadays.

Risk factor modeled microenvironment effects lymphatics activity and IBC invasiveness and progression

Background. Lymphovascular invasion (LVI) and breast tumor emboli within dermal and breast lymphatic vessels are prognostic for metastatic spread and poor outcomes, and are abundant in Inflammatory breast cancer (IBC). IBC is an aggressive breast cancer that presents suddenly with breast swelling and redness due to tumor emboli in lymphatics. Lack of breast-feeding and obesity are IBC risk factors. We sought to demonstrate the combinatorial effects of a high-fat diet and nursing on lymphatic function and compare these to IBC tumor induced changes in lymphatic function. We hypothesize that risk factors for aggressive breast cancer may alter lymphatic function in the normal gland prior to tumor initiation. Methods. Following two rounds of pregnancy in 20 multiparous SCID Beige immunocompromised mice, half of the mice were force weaned while half nursed pups. Prior to forced weaning, half of each of these groups were fed a high fat diet (HFD: 60 Kcal %, N = 10) while the other half received a low-fat diet (LFD: 10 Kcal %, N = 10). Consecutive dynamic near-infrared fluorescence (NIRF) lymphatic imaging was performed at 6-7 months (covid interruption) and 14 months after initiating the diet by injecting a near-IR fluorophore into the mammary fatpad and recording lymphatic pulsing over 8 minutes using V++. Matlab and ImageJ were used to quantify pulsing rates on the ventral lymphatics in each animal. Fatpads were Ssubsequently inoculated with SUM149 IBC cells and imaging was repeated 16 months post diet initiation. Lymphatic imaging over time by HFD vs LFD was further studied in nulliparous animals. Tissues were collected for further analyses. ResultsData analysis prior to tumor injection, demonstrated lymphatic pulsing (pulses/4 minutes) increased over time in HFD force weaned (HFFW) and HFD nursing (HFN) animals only (65.5 vs 72.6, P=0.059;60.1 vs 76.6, P=0.0099, respectively). Comparing HFFW and HFN to matched LFD groups (LFFW and LFN), at 14 weeks HFD was associated with increased pumping after forced weaning (62.3 vs. 72.6, P=0.074), and nursing (62.5 vs 76.6, P=0.0023). There was an increase in pulsing after tumor initiation (16 months after initiation of diet) in all groups (80.1, 84.1, 83.2, 82.4, P > 0.05 all comparisons to initial timepoint). In a separate experiment examining HFD (N=5) vs LFD (N=5) in nulliparous mice, lymphatic contractile activity increased in all animals over. time, average ventral lymphatic contractile frequency for LFD and HFD at week 8, 11 and 14 weeks after diet initiation were 5, 8.64, 15.9 pumps/4 mins vs 11.8, 18.5, 28.2 pumps/4 mins, (P = 0.01, 0.05, and 0.0005 respectively). ConclusionsHFD increased lymphatic pulsing rate over time to a significantly greater extent than LFD continuing over 14 months independent of reproductive and nursing status. Tumor initiation prompted further increased pulsing rates beyond that observed after HFD across all groups. The magnitude of the effect of HFD on lymphatic pulsing approached the rate after tumor initiation, while reproductive variables did not impact lymphatic pulsing. Further studies are warranted to demonstrate the relationship if any between lymphatic pumping pre-initiation and LVI after tumor initiation and examine the role of intervention on reducing LVI.

A prospective phase 2 study testing high dose post-transplant cyclophosphamide as sole GHVD prophylaxis after matched allotransplant using baltimore-based reducedintensity conditioning regimens and PBSC as source of graft

Introduction: The use of high-dose post-transplant cyclophosphamide (PTCY) has revolutionized graft-versus-host disease (GVHD) prophylaxis and allowed to successfully reconsider haplotransplant in recent years. As this strategy significantly reduces the incidence of both acute and chronic GVHD, PTCY has been thereafter considered not only in matched settings but also as sole GVHD prophylaxis, at least when considering myeloablative allotransplant using matched sibling (MSD) or unrelated (MUD) donors and bone marrow as source of graft. Here, PTCY, as a sole GVHD prophylaxis, was tested in a reduced-intensity conditioning (RIC) setting, using peripheral blood stem cells (PBSC) as source of graft considering that this platform is currently broadly used worldwide in adults. Methods: This prospective monocentric phase 2 study was designed with the main objective to demonstrate the feasibility and safety of using only PTCY (without cyclosporine A nor mycophenolate mofetyl after transplant) in adults (18-70 years old) eligible for a RIC PBSC transplant with MSD or MUD. The Baltimore platform with 2 days of PTCY 50mg/kg/day on days 3 and 4 post infusion was considered as conditioning regimen, using fludarabine for lymphoid disease or clofarabine for myeloid disease. The primary objective was to appreciate the incidence of corticosteroid-resistant acute grade 3-4 GVHD (CR 3-4 GVHD) within 100 days post-transplant. According to statistical rules, patients have to be included in a step by step fashion (3, 3, 6, 15, 15 and 17 patients) for a total of 59 evaluable patients (meaning having received PTCY), in order to stop the protocol soon enough in case of excessive rate of deleterious severe acute GVHD (graded according to Mount Sinai International Consortium). Thus, the trial had to be stopped in case of documentation of > 2 CR 3-4 GVHD for the first 3 patients, >3 CR 3-4 GVHD for the first 6 patients, > 4 CR 3-4 GVHD for the first 12 patients, > 6 3-4 CR GVHD for the first 27 patients, > 8 CR 3-4 GVHD for the first 42 patients and finally as soon as > 9 CR 3-4 GVHD for the last included patients. All patients gave informed consent. The trial was registered at ClinicalTrials.gov Identifier: NCT03263767. Results: The results of the first 27 first patients (males n=17 and female n=10;median age: 59 years old (yo), range: 26-70) are reported here. They were included between February 2018 and November 2020. Diagnoses were AML (N=8), MDS (N=5), CMML (N=2), myelofibrosis (N=5), CML (N=1), DLBCL (N=1), T-cell lymphoma (N=1), Philadelphia positive B-ALL (N=1), CLL (N=1), lymphoblastic lymphoma (N=1) and mixed phenotype acute leukemia (N=1). Donors were MSD in 10 cases and MUD in 17. Only one primary graft failure was documented in a 61 yo MDS patient with active disease at transplant. He is however still alive in response after autologous reconstitution. With a median follow-up of 17.6 months (range: 10-42) for alive patients at the time of analysis (July 2021), 1-year and 2-year survivals were 80.9+7% and 74.7+9%, respectively, for both OS et DFS. GVHD-free/relapse-free survival (GRFS) at 1-year and 2-year was 58.7+9% and 52.2+10%, respectively. Three relapses (11%) and 6 deaths occurred. Deaths were due to acute GVHD in 4 patients (including 1 with sepsis and 1 with SARS-COVID 19 infection) and relapse in 2. Grade 2, 3 and 4 acute GVHD occurred in 11, 1 and 4 patients, respectively, for a total of 59% of grade 2-4 acute GVHD. CR 3-4 GVHD was observed in all of 5 patients with acute grade 3-4 GVHD and 4 died related to GVHD. Moderate/severe chronic GVHD occurred in 5/22 (22.7%) evaluable patients, including 4 still on immunosuppressive therapy at 40, 28, 25 and 16 months post-transplant. Overall non-relapse mortality (NRM) was 14.8% and related to acute GVHD. However, the number of cases conducting to stop the protocol was not reached. Conclusion: PTCY as a sole GVHD prophylaxis is here demonstrated as possible and relatively safe for adults receiving a matched PBSC Baltimore-based RIC allograft. The very good survivals reported he e may be related to a strong GVL effect associated with the high incidence of acute GVHD. However, because of this high incidence and the fact that NRM was related to GVHD after this first analysis, we have now made an amendment to test the addition to PTCY of one day of anti-thymoglobulin (ATG) 2.5 mg/kg on day-2 for the next 32 patients to be included. This second cohort receiving PTCY+ATG as a sole prophylaxis is ongoing.