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Background & Aim: The long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in a randomized, double-blind, placebo-controlled clinical trial (NCT 04288102). Methods, Results & Conclusion(s): A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4x107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. The outcomes measured included: 6-minute walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire, COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, MSC-related adverse events (AEs), and tumor markers. Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04-0.80, Fisher's exact test, p = 0.015). On the SF-36 questionnaire, a marginally higher general health score was received by the MSC group at month 18 compared with the placebo group (50.00 vs. 35.00;95% CI: 0.00-20.00, Wilcoxon rank sum test, p = 0.016). In contrast, there were no differences in the total severity score of lung imaging or the titer of neutralizing antibodies between the two groups. Meanwhile, there were no MSC-related AEs reported at the 18- or 24-month follow-ups. The serum levels of most of the tumor markers examined remained within normal ranges and were similar between the MSC and placebo groups. Long-term safety was observed for the COVID-19 patients who received MSC treatment. Yet few sustained efficacy of MSC treatment was observed at the end of the 2-year follow-up period. Funding(s): The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRCID202105,413FZT6). [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy
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In addition to its remarkable genome editing capability, the CRISPR-Cas system has proven to be very effective in many fields of application, including the biosensing of pathogenic infections, mutagenic defects, or early cancer diagnosis. Thanks to their many advantages in terms of simplicity, efficiency, and reduced time, several CRISPR-Cas systems have been described for the design of sensitive and selective analytical tools, paving the way for the development and further commercialization of next-generation diagnostics. However, CRISPR-Cas-based biosensors still need further research efforts to improve some drawbacks, such as the need for target amplification, low reproducibility, and lack of knowledge of exploited element robustness. This review aims to describe the latest trends in the design of CRISPR-Cas biosensing technologies to better highlight the insights of their advantages and to point out the limitations that still need to be overcome for their future market entry as medical diagnostics.Copyright © 2023 Elsevier B.V.
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Sarcomatoid urothelial carcinoma is a rare and aggressive variant. Serum beta-hCG levels are used as a tumor marker in gestational trophoblastic diseases and germ cell tumors, but may also be elevated in high-grade bladder cancers. Here, we report two urothelial carcinoma cases with sarcomatoid differentiation that relapsed early after surgery with elevated serum beta-hCG levels. The first case was a 65-year-old female and the second case was a 67-year-old man with sarcomatoid urothelial carcinoma located in the ureter and renal pelvicalyceal system, both of them relapsed with elevated beta-hCG serum level to 146.8 mIU/ mL and 242 mIU/mL, respectively. They died a few months after initial diagnosis;4.9 and 2.5 months respectively. Both sarcomatoid variant and beta-hCG expression were associated with poor prognosis and advanced stage. However, beta-hCG is not used as a tumor marker in urinary tract cancers yet, and its relationship with variant pathologies has not been clarified. We need multi-centered studies to reveal this relationship.Copyright © 2023, Derman Medical Publishing. All rights reserved.
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Background: Coronavirus disease (COVID 19) has been emerging as a major threat to humans all over the world. Severe Acute Respiratory Syndrome CoronaVirus 2 (nSARS-CoV-2) is the causative agent for the disease resulting in severe acute respiratory illness. Earlier, it took several years to come up with a vaccine or other sorts of treatments for viral diseases. But now with the advent of biotechnology and development of bio-informatic tools, the process has been accelerated. The WHO reports 39,806,488 affected cases and 1,112,208 deaths till today all over the world (17 Oct 2020). nSARS-CoV-2 has a greater influence on people with comorbidities mainly cancer. Objective(s): The study herein attempts to understand the binding affinity of the spike protein of the novel coronavirus with the lung and breast cancer marker proteins by docking and ClusPro analysis. Method(s): The analysis was conducted in reference to hACE2 (human Angiotensin Converting Enzyme 2), the receptor of nSARS-CoV-2. Total 22 different marker proteins were analyzed using ClusPro. Result(s): BRCA1 (Breast Cancer type 1 susceptibility protein) and CXCR4 (a chemokine receptor belong-ing to the G protein coupled receptor family) were found to exhibit higher binding affinities.-73.82 kcal/mol and-66.45 kcal/mol were the global energies they showed upon binding to S protein respective-ly. Conclusion(s): Therefore, novel SARS-CoV-2 has a higher chance of inducing cancer in non-cancerous individuals and aids in cancer acceleration in cancer patients. This poses a threat to cancer patients and immunocompromised individuals. The study can be exploited to identify the optimal drug delivery system for novel SARS CoV2.Copyright © 2022 Bentham Science Publishers.
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Cancer antigen 125 (CA-125) is a transmembrane glycoprotein, and it is known to be an essential biomarker in detecting treatment response and recurrence of ovarian cancer. It may also be used in monitoring colorectal cancer. It tends to rise in states of inflammation. Recent studies have demonstrated a temporary rise in CA-125 levels and other cancer biomarkers in patients suffering from coronavirus disease 2019 (COVID-19) infection. However, in the following case report, we hope to shed light on a possible association between CA-125 levels and the COVID-19 mRNA vaccine. We present the case of a 79-year-old woman with moderately differentiated adenocarcinoma of the right adnexa, who had a transient increase in CA-125 levels after a period, during which she underwent treatment for COVID-19 infection and received the first dose of COVID-19 mRNA (Pfizer-BioNTech) vaccine with no evidence of disease progression on imaging.
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Case report - Introduction: This case highlights the dilemma of keeping rheumatoid arthritis disease under control in active cancer cases and establishing a consistent multidisciplinary dialogue during a pandemic and staffing crises. During chemotherapy and active cancer treatment, disease-modifying therapies (conventional and biologic) are often stopped. In some cases, the potential benefits versus risks of restarting usual therapies have to be balanced against risks of suppressing disease activity with highdose steroids. Risks of infection (common and atypical) need to be considered. Case report - Case description: A is a 67-year-old female nonsmoker diagnosed with seropositive rheumatoid arthritis (RF, anti - CCP positive) in 2008. Other conditions include type 2 diabetes, atrial fibrillation (on warfarin), hypothyroidism and obstructive sleep apnoea. Due to active disease, despite triple therapy (methotrexate, sulphasalazine and hydroxychloroquine), anti-TNF therapy (etanercept) commenced in 2009 with primary non-response. However, she responded well to B-cell therapy (rituximab) in conjunction with oral methotrexate (25mg weekly) receiving annual infusions from 2010 to 2016. In 2017, an elective sleeve gastrectomy procedure for high BMI was abandoned after peritoneal deposits of concern were noted. Histology and CT imaging were consistent with a primary peritoneal malignancy (Stage 3c low-grade serous adenocarcinoma). Treatment involved debulking surgery (total abdominal hysterectomy, bilateral salpinoophorectomy, omentectomy) and tamoxifen. Treatment for rheumatoid arthritis stalled during this period but as frequent steroids were required for active joint inflammation, in agreement with the oncologists, she had a rituximab cycle in 2018. Unfortunately, in 2019 she had signs of cancer progression (elevated tumour markers, CT imaging) and has subsequently started carboplatin chemotherapy. She has been unable to continue methotrexate or rituximab pending completion of the chemotherapy cycles (ongoing). However, her arthritis is now uncontrolled without increased steroids. Due to recurrent flares, her maintenance dose has been increased from 5mg to 7.5-10mg prednisolone daily until we can establish if it is safe and appropriate to recommence her usual arthritis regime. Even without disease-modifying therapy like methotrexate and rituximab, risk of infection (including atypical ones) is still significant with the combination of chemotherapy and steroids. Risk of progressive joint damage and adverse quality of life with active arthritis also needs to be considered. Staffing crises, exacerbated by COVID pandemic issues, have added to complexity of decision making and coordination of regular multidisciplinary discussions regarding treatment. Case report - Discussion: Cancer is a known association in rheumatoid arthritis patients with a twofold higher risk of lymphoma compared to the general population. Whether condition or treatment affects risk remains unclear as immune dysregulation is relevant in both autoimmunity and cancer. Paraneoplastic, recent onset arthritis, chemotherapy- or immunotherapy-induced arthralgia/arthritis are also well documented. This case had a seropositive rheumatoid arthritis phenotype quite a few years prior to cancer diagnosis. Primary peritoneal cancer is uncommon, often presenting as in this case as an incidental finding. It is usually treated like ovarian cancer Whilst methotrexate has been implicated in lung cancer, melanoma and non-Hodgkin lymphoma, overall safety data suggest any risk is quite low (e.g., EBV-associated lymphoproliferative disorders usually resolve with drug discontinuation). It is also a known chemotherapeutic agent. Anti-TNF treatment algorithms generally exclude patients with recent cancer. Rituximab, originally developed as a cancer drug, is not thought to affect risk of cancer development or progression. Treatment with disease-modifying therapy (conventional and biologics) is often withheld in patients with active malignancy undergoing chemotherapy due to a theo etical risk of potentiated immunosuppression and toxicity, particularly cytopaenias. However, maintaining arthritis control with glucocorticoids also has short- and long-term risks. Combining chemotherapy agents like carboplatin with methotrexate has been used for urothelial carcinoma and can be well tolerated with close monitoring of haematological parameters. Thus, it could be argued this patient is at risk of infections whichever treatment approach is taken and regaining control of arthritis with recommencement of methotrexate and rituximab is much better for her quality of life. Regular multidisciplinary discussions are important to outline risks versus benefits of combined treatment. This may be difficult in practice during staffing crises. Covid risk in patients receiving rituximab and/or chemotherapy, timing and response to COVID vaccination are also important considerations. Case report - Key learning points: . Primary peritoneal cancer is uncommon and can present as an incidental finding . Whilst treatment for progressive cancer is important, withholding rheumatoid arthritis treatment can have a significant adverse impact on quality of life . Morbidity and mortality risks of stopping treatment versus combined treatment (cancer therapy and disease-modifying therapy) ideally needs to be fully discussed and agreed with the patient and all care providers - lack of "named" providers, restructuring, redeployment, multi-specialty care and a global pandemic can make coordination of this difficult.
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Background: Few cases of digital ischemia and gangrene associated with primary solid tumors have been described in literature[3]. The exact mechanism of severe occurrence has not been completely understood and the available treatment options have an extremely limited utility [1,2].In the most cases the patients were elderly women with adenocarcinomas of digestive or gynaecologic apparatuses [4]. Objectives: We describe a new case of digital gangrene as unusual presentation of ovarian cancer in a 36 years old woman. Methods: 36 years old female was admitted to our Reheumatology deparment with blackish Blackish discoloration of the toes of one week duration. She had history of COVID-19 infection 8 months prior to the presentation then developed hemoptysis, picture suggestive of ILD, generalized anasarca and skin rash;accordingly an initial diagnosis of post COVID-19 vasculitis was made by dermatologist. The blood tests were ESR:21 mm/hr, CRP:25.7, D.Dimer:8.8, Ferri-tin:575 ng/ml, lymphopenia:0.9, S.Creatinine:2, 24 h urinary protein: 325 mg/24h and all autoimmune markers were negative except anti nuclear antibody (ANA) with titer:1/160. Further assessment revealed that she had multiple site coag-ulopathy;internal jugular vein thrombosis, bilateral lower limbs Deep Venous Thrombosis (DVT). Neck ultrasound surprisingly showed bilateral enlarged suspicious looking supraclavicular lymph node with lost hilum which was Biopsied for histopathological correlation which revealed focally necrotizing adenocarci-noma with signifcant signet ring differentiation. Searching for the primary malignancy, tumor markers were sent CA125: 584 u/ml (up to 35), Pelvi-abdominal Magnetic resonance imaging (MRI) revealed Left ovarian mass measuring 3.6 x 3.4 x 4.4 cm highly suspicious of malignant neoplastic growth for histopatho-logical correlation, Suspicious looking pelviabdominal lymph nodes mostly representing malignant lymphadenopathy, Scattered peritoneal nodules suspicious of metastatic deposits. Results: During admision the patient received full dose anticoagulation (Low Molecular Weight Heparin: 60 iu/12 h). Upon diagnosis we arrange the transferal to the oncology department to continue her management plan. Unfortunately;the case was terminal for palliative therapy and she died after 2 weeks. Conclusion: Bluish discoloration of digits and toes may be a clue for diagnosis of many diseases not only vasculitis. Malignancy can disturb the immune system in a way that mimic any systemic connective tissue disease. Acute insult aggressive multiple site deep venous thrombosis (DVT) necessitate thinking outside the box and consider other causes of coagulopathy like visceral malignancy.
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Introduction: There are approximately 2,400 new cases of testicular cancer in the UK annually. NICE guidelines recommend all suspected patients to be referred on the 2 week-wait pathway, with a 31 day target to commence treatment following decision to treat. The COVID-19 pandemic has decimated routine hospital service provision and led to the cancellation of 36,000 cancer operations in the UK during the first wave. Our aim was to assess the impact of the pandemic on our testicular cancer patients. Patients and Methods: Eleven trusts in the West Midlands deanery performed a retrospective analysis of all testicular cancer patients between January 2015 to December 2020. The pre-COVID cohort (January 2015-February 2020) were compared to the COVID cohort (March 2020-December 2020). Parameters assessed included date of referral, first clinic appointment, operation, and post-operative tumour markers. Sperm banking and pathological stage was also compared. Results: A total of 830 patients were included. Pre- COVID n=753, COVID n=77. Conclusions: There was statistically no significant difference in time from initial referral to first clinic appointment, duration from clinic to theatre, timeliness of post-operative tumour markers and pathological stage of tumour. Sperm banking was performed significantly more in the COVID era (25.7 vs 10.3%). This reflects consistency in the management of testicular cancer patients during the COVID period. Of note less patients were assessed on average during the COVID era (92 v 146/year) implying that we may experience an increase in patients with later presentations and advanced disease;further analysis will be required to confirm this.
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Background-aim: Tumor markers (TM) in body fluids have been studied for years and several authors have proposed different cut-off. An apparently more accurate strategy is the one proposed by Molina et al. considering that the ratio TM in fluid with regard to TM in serum >1.2 indicates local production in the pleura, however if the ratio is <1.2 the presence of TM in the fluid would be explained by serum extravasation. Despite enough evidence to manage this biomarkers in body fluids, the practice is not widely extended in the clinical setting yet. Methods: AFP, CA19.9, CA15.3, CEA, CA125, PSA and SCC were analyzed in Alinity i platform (Abbott diagnostics) HCG and NSE was performed in Cobas e411 (Roche diagnostics). Results: Here we describe the case of a 69-year-old patient attending the Emergency Room due to pain in both hemythoraxes. Also remarkable was a wasting syndrome (5 kg weight loss in the past month). In Emergency blood analysis: VSG 50, PT 75%, DD 765 ng/mL, ferritin 368 ng/mL and LDH 385 U/L were outsdanding. Thorax radiology showed a pleural effusion. The patient was diagnosed with COVID19 bronchitis.TC scan evidenced pleural solid metastasis, multiple bone lesions and hepatic M1. Serum TM: AFP, CA19.9, PSA, NSE, SCC and HCG were normal. CA125 2992,60 U/mL (<35), CA15.3 614,70 U/mL (<32), CEA 400.82 ng/mL (<5). Pleural fluid TM: CEA 284.32 ng/mL;CA15.3 2210.3 U/mL. TM ratio: CA15.3: 3.6 (>1.2) this result indicates local synthesis of CA15.3, therefore pleural metastasis;CEA: 0.7 (<1.2) indicates that the CEA found un the fluid was extravasated from serum. Pathological examination was only positive for CK7 and mixt CK. All other markers were negative. It was concluded to be an undifferentiated carcinoma, cytologically reminding of an adenocarcinoma. Due to TTF1 and napsine negativity lung neoplasm could not be discarded.The patient was diagnosed with undifferentiated lung cancer stage IV. Conclusions: This a good example of different molecular patterns reflecting tumor heterogeneity evidenced by protein expression by each lesion: Pleural metastases expressed high amounts of CA15.3, however not CEA. Hepatic metastases and probably main tumor in the lung expressed CEA and CA15.3. It is arguable whether CA15.3 was expressed at lower quantities from the main tumor or the dilution of the protein in the bloodstream results in lower concentrations in relation to the ones found in the pleura.
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Background: Neuroendocrine cancer of the prostate can present in diverse clinical pictures, potentially hampering the diagnosis and probably leading to underdiagnosis. Methods: Two cases are presented corresponding respectively to two forms of the disease: de novo neuroendocrine cancer and dedifferenciation of an adenocarcinoma of the prostate to neuroendocrine cancer under long term luteinising hormone releasing hormone (LHRH) agonist treatment. Results: Suspicion of neuroendocrine cancer may be raised in prostate cancer patients presenting either clinical or radiological metastatic progression without prostate specific antigen (PSA) rise, or relatively extended metastatic disease right at diagnosis associated to relatively low PSA, yet any non-pulmonary visceral metastases. Neuroendocrine cancer of the prostate can also turn out to be the origin of an adenocarcinoma of unknown primary. Conclusion: In case these considerations are respected the risk of missing the correct diagnosis of a neuroendocrine cancer of the prostate may be minimised.
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Introduction: Systemic lupus erythematosus (SLE) is a chronic, multifaceted autoimmune inflammatory disease with a wide range of clinical presentations resulting from its effect on multiple organ systems. We report a case of SLE associated with autoimmune pancreatitis. Methods: In this study, we present a patient diagnosed as having SLE who developed acute auto-immune pancreatitis. Results: This is a 36-year-old woman, with lupus diagnosed since 2009. Initially, the manifestations of her disease were dermatological and articular. Then appeared the renal involvement with a lupus nephropathy class IV at the renal biopsy (PBR). She was previously treated with the NIH protocol then oral prednisolone with improvement in her symptoms. She continued these medications but was lost to follow-up since 2016 and presented after 6 years with pigmented skin lesions on her upper and lower limbs, abdominal pain and distension, vomiting, and an altered general condition. In biology, the patient presented a functional acute kidney failure, an elevated amylasemia (30 times normal), an elevated lipasemia (6 times normal), a normocytic normochromic hemolytic anemia with positive direct coombs test, lymphopenia, a positive immunological assessment (AAN, anti DNA AC, anti Sm, anti SSA, anti RNP), a low C3, a low C4. The patient presented a lupus flare with a SLEDAI score of 6 points: moderate lupus activity. Ultrasound confirmed a large abundance of ascites. Ascites fluid puncture showed an exudate with hyperleukocytosis with predominantly PNN and no germ on direct examination nor on culture.The infectious origin of the pancreatitis was eliminated (CMV, tuberculosis, covid19), as well as the tumoral origin (negative tumor markers, abdominal CT scan showed a swollen pancreas in its caudal portion with loss of physiological lobulations and normal spontaneous density.Necrosis flows difficult to individualize. In addition, no deep neoplastic focus). The autoimmune origin of the pancreatitis due to its lupus attack was retained. She was put on corticosteroids (500mg intravenously for 3 days) then relayed by oral route, albumin infusion, evacuation puncture. The subsequent evolution was marked by the progressive normalization of the pancreatic balance and the slower disappearance of the ascites. Conclusions: Acute pancreatitis is an unusual manifestation of SLE and it should be suspected in any SLE patient with these similar symptoms. In many cases, this complication has been attributed to the drugs administered. In our case, a favorable course of pancreatitis with corticosteroids adds further evidence to the idea that lupus-related pancreatitis is not a side effect of corticosteroid therapy. Moreover, treatment with these medications improves the prognosis. No conflict of interest
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Introduction: Collapsing Glomerulopathy (CG) is a rare entity presenting as nephrotic syndrome and rapidly progressive renal deterioration. It has been first identified among African-American patients with nephrotic syndrome. Subsequently, it has been called HIV-associated nephropathy (HIVAN) after a number of patients with HIV were found to have CG. It has re-emerged recently among patients with COVID-19 dubbing it as the new HIVAN. In the Philippines, Focal Segmental Glomerulosclerosis (FSGS) is the second most common glomerular disease but with no available data on the subtypes.To our knowledge, this is the first case of collapsing glomerulopathy in the country to be published. Methods: This is a case report of primary Collapsing Glomerulopathy seen in our institution. Results: The case is a 36 year-old Filipino female admitted due to edema which started 2 weeks post-partum. She is gravida 3 para 3 (1203), with no complications in all the pregnancies. She had no known comorbidities. Social history was negative for intravenous or illicit drug use. She initially sought consult with her obstetrician where work up showed hypoalbuminemia and diffuse hepatic disease on ultrasound. She was referred to a gastroenterologist where albumin infusion and paracentesis was done but with no improvement. She developed anasarca and was admitted in our institution. Paracentesis was attempted but only minimal ascitic fluid was obtained. Serum ascites albumin gradient was low and baseline laboratories showed high creatinine at 146 mmol/L, hypoalbuminemia at 16 g/L and +3 albumin on urinalysis. Further testing showed a 24-hour urine protein of 11 grams. ANA and anti-DsDNA were negative and c3 and c4 levels were normal. Hepatitis profile was negative for infection. Abdominal CT scan revealed a hypoenhancing pancreatic tail lesion, breast cyst and nodule. Tumor markers showed high CA-125, CA 19-9 and CA 15-3. Breast ultrasound showed simple breast cyst. Gyneocology consult was called where pap smear done was negative for malignancy. Surgery service recommended observation and monitoring for the pancreatic and breast lesions. Kidney biopsy was delayed due to new onset bacterial pneumonia. COVID-19 RT-PCR test was negative. Kidney biopsy was done after lysis of fever. Pending pathologic diagnosis, patient was discharged clinically improved with no edema. She was sent home on prednisone, ARB, statin, fenofibrate and anti-platelet. On follow up at the outpatient clinic, the kidney biopsy result came out to be collapsing glomerulopathy, acute tubular injury, mild interstitial fibrosis and atrophy. HIV test was done and came out negative. Bipedal edema has recurred and albumin/creatinine ration was 731mg/g. She was then started on tacrolimus. She has been on regular follow up and currently has no edema and has ACR of 79mg/g and normal creatinine level. Conclusions: This is an interesting case as the primary glomerular disease has been masked by the initial laboratory findings. The ultrasound showed parenchymal liver disease. Further work-up revealed multiple lesions in the pancreas, breasts and lymph nodes with high tumor-markers which led us to think of paraneoplastic nephrotic syndrome. The renal biopsy revealed a rare diagnosis with no previous local data. This serves as an index case for primary collapsing glomerulopathy in a Filipino patient on remission after being treated with tacrolimus. No conflict of interest