Multi-organ failure with atypical liver granulomas following intravesical Bacillus Calmette-Guerin instillation

Bacillus Calmette-Guerin(BCG) intravesical instillation has been adopted in the treatment of patients with superficial bladder cancer.BCG-induced disseminated infection,though rare,has been associated with the histological finding of epithelioid granulomas in different organs,including the liver.We report the case of an adult patient with multi-organ failure,who developed sepsis,acute respiratory failure and acute hepatic failure with encephalopathy whose liver biopsy confirmed the presence of atypical,granulomatous-like lesions.Recovery was observed only after empirical therapy for Mycobacterium bovis with isoniazid,rifampicin,ethambutol and steroids was introduced.This case highlights the importance of a thorough patient assessment in order to exclude other more common causes of hepatic granulomas and to confirm diagnosis.Histological findings may be non-specific when the liver is involved in BCGinduced disseminated infection.

Spontaneous septicaemia with multi-organ dysfunction - a new face for Pantoe agglomerans?

Pantoe agglomerans (P. agglomerans) is an unusual cause for sepsis in immunocompetent individuals, especially in the absence of characteristic risk factors. We report one such case occurring in a farmer, manifesting with severe illness. The severe nature of illness and the apparently spontaneous origin of septicemia underline the pathogenic potential of this organism. When coupled with the ubiquity of the organism, there is a definite possibility that this disease may become increasingly frequent in the near future, especially in agronomic countries like India. Further studies on the epidemiology and natural history of this disease are required.

Comparative transcriptomic evidence of physiological changes and potential relationships in vertebrates under different dormancy states

Dormancy represents a fascinating adaptive strategy for organisms to survive in unforgiving environments.After a period of dormancy,organisms often exhibit exceptional resilience.This period is typically divided into hibernation and aestivation based on seasonal patterns.However,the mechanisms by which organisms adapt to their environments during dormancy,as well as the potential relationships between different states of dormancy,deserve further exploration.Here,we selected Perccottus glenii and Protopterus annectens as the primary subjects to study hibernation and aestivation,respectively.Based on histological and transcriptomic analysis of multiple organs,we discovered that dormancy involved a coordinated functional response across organs.Enrichment analyses revealed noteworthy disparities between the two dormant species in their responses to extreme temperatures.Notably,similarities in gene expression patterns pertaining to energy metabolism,neural activity,and biosynthesis were noted during hibernation,suggesting a potential correlation between hibernation and aestivation.To further explore the relationship between these two phenomena,we analyzed other dormancy-capable species using data from publicly available databases.This comparative analysis revealed that most orthologous genes involved in metabolism,cell proliferation,and neural function exhibited consistent expression patterns during dormancy,indicating that the observed similarity between hibernation and aestivation may be attributable to convergent evolution.In conclusion,this study enhances our comprehension of the dormancy phenomenon and offers new insights into the molecular mechanisms underpinning vertebrate dormancy.

Severe scrub typhus infection: Clinical features, diagnostic challenges and management

Scrub typhus infection is an important cause of acute undifferentiated fever in South East Asia. The clinical picture is characterized by sudden onset fever with chills and non-specific symptoms that include headache, myalgia, sweating and vomiting. The presence of an eschar, in about half the patients with proven scrub typhus infection and usually seen in the axilla, groin or inguinal region, is characteristic of scrub typhus. Common laboratory findings are elevated liver transaminases, thrombocytopenia and leukocytosis. About a third of patients admitted to hospital with scrub typhus infection have evidence of organ dysfunction that may include respiratory failure, circulatory shock, mild renal or hepatic dysfunction, central nervous system involvement or hematological abnormalities. Since the symptoms and signs are non-specific and resemble other tropical infections like malaria, enteric fever, dengue or leptospirosis, appropriate laboratory tests are necessary to confirm diagnosis. Serological assays are the mainstay of diagnosis as they are easy to perform; the reference test is the indirect immunofluorescence assay(IFA) for the detection of Ig M antibodies. However in clinical practice, the enzyme-linked immuno-sorbent assay is done due to the ease of performing this test and a good sensitivity and sensitivity when compared with the IFA. Paired samples, obtained at least two weeks apart, demonstrating a ≥ 4 fold rise in titre, is necessary for confirmation of serologic diagnosis. The mainstay of treatment is the tetracycline group of antibiotics or chloramphenicol although macrolides are used alternatively. In mild cases, recovery is complete. In severe cases with multi-organ failure, mortality may be as high as 24%.

Predictive value of cytokines for developing complications after polytrauma

AIM: To investigate posttraumatic cytokine alterations and their value for predicting complications and mortality in polytraumatized patients. METHODS: Studies on the use of specific cytokines to predict the development of complications and mortality were identified in MEDLINE, EMBASE, Web of Science and the Cochrane Library. Of included studies, relevant data were extracted and study quality was scored.RESULTS: Forty-two studies published between 1988 and 2015 were identified, including 28 cohort studies and 14 "nested" case-control studies. Most studies investigated the cytokines interleukin(IL)-6, IL-8, IL-10 and tumor necrosis factor(TNF-a). IL-6 seems related to muliorgan dysfunction syndrome, multiorgan failure(MOF) and mortality; IL-8 appears altered in acute respiratory distress syndrome, MOF and mortality; IL-10 alterations seem to precede sepsis and MOF; and TNF-a seems related to MOF. CONCLUSION: Cytokine secretion patterns appear to be different for patients developing complications when compared to patients with uneventful posttraumatic course. More research is needed to strengthen the evidence for clinical relevance of these cytokines.

Acute liver injury in COVID-19 patients hospitalized in the intensive care unit:Narrative review

In recent years,humanity has been confronted with a global pandemic due to coronavirus disease 2019(COVID-19),which has caused an unprecedented health and economic crisis worldwide.Apart from the respiratory symptoms,which are considered the principal manifestations of COVID-19,it has been recognized that COVID-19 constitutes a systemic inflammatory process affecting multiple organ systems.Across the spectrum of organ involvement in COVID-19,acute liver injury(ALI)has been gradually gaining increasing attention by the international scientific community.COVID-19 associated liver impairment can affect a considerable proportion of COVID-19 patients and seems to correlate with the severity of the disease course.Indeed,COVID-19 patients hospitalized in the intensive care unit(ICU)run a greater risk of developing ALI due to the severity of their clinical condition and in the context of multi-organ failure.The putative pathophysiological mechanisms of COVID-19 induced ALI in ICU patients remain poorly understood and appear to be multifactorial in nature.Several theories have been proposed to explain the occurrence of ALI in the ICU setting,such as hypoperfusion and ischemia due to hemodynamic instability,passive liver congestion as a result of congestive heart failure,ischemia-reperfusion injury,hypoxia due to respiratory failure,mechanical ventilation itself,sepsis and septic shock,cytokine storm,endotheliitis with concomitant coagulopathy,druginduced liver injury,parenteral nutrition and direct cytopathic viral effect.It should be noted that no specific therapy for COVID-19 induced ALI exists.Therefore,the therapeutic approach lies in preventive measures and is exclusively supportive once ALI ensues.The aim of the current review is to scrutinize the existing evidence on COVID-19 associated ALI in ICU patients,explore its clinical implications,shed light on the underlying pathophysiological mechanisms and propose potential therapeutic approaches.Ongoing research on the particular scientific field will further elucidate the pathophysiology behind ALI and address unresolved issues,in the hope of mitigating the tremendous health consequences imposed by COVID-19 on ICU patients.

Pancreatic transplant surgery and stem cell therapy:Finding the balance between therapeutic advances and ethical principles

The latest achievements in the field of pancreas transplantation and stem cell therapy require an effort by the scientific community to clarify the ethical implications of pioneering treatments,often characterized by high complexity from a surgical point of view,due to transplantation of multiple organs at the same time or at different times,and from an immunological point of view for stem cell therapy.The fundamental value in the field of organ transplants is,of course,a solidarity principle,namely that of protecting the health and life of people for whom transplantation is a condition of functional recovery,or even of survival.The nature of this value is that of a concept to which the legal discipline of transplants entrusts its own ethical dignity and for which it has ensured a constitutional recognition in different systems.The general principle of respect for human life,both of the donor and of the recipient,evokes the need not to put oneself and one’s neighbor in dangerous conditions.The present ethical reflection aims to find a balance between the latest therapeutic advances and several concepts including the idea of the person,the respect due to the dead,the voluntary nature of the donation and the consent to the same,the gratuitousness of the donation,the scientific progress and the development of surgical techniques,and the policies of health promotion.

Paraneoplastic syndromes in cholangiocarcinoma

Paraneoplastic syndromes are the symptoms or signs which result from damage to tissues that are distant from the site of malignancy,due to complex interactions between the body’s immune system and malignant neoplasm.Cholangiocarcinoma(CCA)is an aggressive epithelial malignancy of hepatobiliary tree and it is found to be associated with various paraneoplastic syndromes.These syndromes can present as dermatological,neurological,renal,hematological,or multi-systemic manifestations.Clinical suspicion and timely recognition of these syndromes can lead to early diagnosis of covert malignancies like CCA.The management plan remains the removal of the underlying cause which in this case is CCA.

A DNA tetrahedron-based nanosuit for efficient delivery of amifostine and multi-organ radioprotection

Unnecessary exposure to ionizing radiation(IR)often causes acute and chronic oxidative damages to normal cells and organs,leading to serious physiological and even life-threatening consequences.Amifostine(AMF)is a validated radioprotectant extensively applied in radiation and chemotherapy medicine,but the short half-life limits its bioavailability and clinical applications,remaining as a great challenge to be addressed.DNAassembled nanostructures especially the tetrahedral framework nucleic acids(tFNAs)are promising nanocarriers with preeminent biosafety,low biotoxicity,and high transport efficiency.The tFNAs also have a relative long-term maintenance for structural stability and excellent endocytosis capacity.We therefore synthesized a tFNA-based delivery system of AMF for multi-organ radioprotection(tFNAs@AMF,also termed nanosuit).By establishing the mice models of accidental total body irradiation(TBI)and radiotherapy model of Lewis lung cancer,we demonstrated that the nanosuit could shield normal cells from IR-induced DNA damage by regulating the molecular biomarkers of anti-apoptosis and anti-oxidative stress.In the accidental total body irradiation(TBI)mice model,the nanosuit pretreated mice exhibited satisfactory alteration of superoxide dismutase(SOD)activities and malondialdehyde(MDA)contents,and functional recovery of hematopoietic system,reducing IRinduced pathological damages of multi-organ and safeguarding mice from lethal radiation.More importantly,the nanosuit showed a selective radioprotection of the normal organs without interferences of tumor control in the radiotherapy model of Lewis lung cancer.Based on a conveniently available DNA tetrahedron-based nanocarrier,this work presents a high-efficiency delivery system of AMF with the prolonged half-life and enhanced radioprotection for multi-organs.Such nanosuit pioneers a promising strategy with great clinical translation potential for radioactivity protection.

Clinical Value of rhBNP in the Treatment of Patients with Stanford Type B Aortic Dissection

Objective:To determine the clinical value of rhBNP in the treatment of patients with Stanford type B aortic dissection.Methods:From June 2018 to October 2021,162 patients with Stanford type B aortic dissection were selected from the Cardiology Department of Henan Provincial Chest Hospital and randomly divided into two groups:control group(81 patients)and observation group(81 patients).The patients in the control group were treated with conventional therapy.On the basis of the control group,the patients in the observation group were treated with rhBNP.The cardiac function,renal function,pulmonary function,and inflammatory indices before and after treatment for 72 hours,as well as the incidence of adverse reactions between the two groups were compared.Results:After treatment,the cardiac function(LVEF and NT-pro BNP),renal function(urine output for 24 hours,SCr,and Cys-C),pulmonary function(PaO_(2),SPO_(2),and PaO_(2)/FiO_(2)),and inflammatory(IL-6,hsCRP,and MCP-1)indices of the observation group improved significantly compared to those of the control group(p<0.05).Conclusion:rhBNP can improve cardiac function,renal function,and pulmonary function,as well as alleviate inflammation in patients with Stanford type B aortic dissection.Hence,in the treatment of patients with Stanford type B aortic dissection,rhBNP provides multi-organ protection.

Multi-organ site metastatic reactivation mediated by non-canonical discoidin domain receptor 1 signaling

With the support of the National Natural Science Foundation of China and the Ministry of Science and Technology of China,the research teams led by Prof.Gao Hua(高华)from Tongji University,and Prof.Filippo Giancotti at Memorial Sloan Kettering Cancer Center,reported recently on the mechanism of multiorgan site metastatic creactivation,which was published in Cell(2016,166:47—62).

Impact of liver enzymes on SARS-CoV-2 infection and the severity of clinical course of COVID-19

Background and aim Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the virus responsible for the current pandemic,can have multi-organ impact.Recent studies show that liver injury could be a manifestation of the disease,and that liver disease could also be related to a worse prognosis.Our aim was to compare the characteristics of patients with severe coronavirus disease 2019(COVID-19)due to SARS-CoV-2 who required intubation versus stable hospitalized patients to identify the early biochemical predictive factors of a severe course of COVID-19 and subsequent requirement for intubation,specifically in Mexican.Methods This was an observational case-control study nested in a cohort study.Complete medical records of patients admitted for confirmed COVID-19 at a tertiary level center in Mexico City were reviewed.Clinical and biochemical data were collected,and the characteristics of patients who required invasive mechanical ventilation(IMV)(cases)were compared with stable hospitalized patients without ventilation(controls).Results We evaluated 166 patients with COVID-19 due to SARS-CoV-2 infection;114(68.7%)were men,the mean age was 50.6±13.3 years,and 27(16.3%)required IMV.The comparative analysis between cases and controls showed(respectively)significantly lower blood oxygen saturation(SpO_(2))(73.5±12.0%vs.83.0±6.8%,P<0.0001)and elevated alanine aminotransferase(ALT)(128(14–1123)IU/L vs.33(8–453)IU/L,P=0.003),aspartate aminotransferase(AST)(214(17–1247)vs.44(12–498)IU/L,P=0.001),lactic dehydrogenase(LDH)(764.6±401.9 IU/L vs.461.0±185.6 IU/L,P=0.001),and D-dimer(3463(524–34,227)ng/mL vs.829(152–41,923)ng/mL,P=0.003)concentrations.Patients in the cases group were older(58.6±12.7 years vs.49.1±12.8 years,P=0.001).Multivariate analysis showed that important factors at admission predicting the requirement for IMV during hospitalization for COVID-19 were AST≥250 IU/L(odds ratio(OR)=64.8,95%confidence interval(CI)7.5–560.3,P<0.0001)and D-dimer≥3500 ng/mL(OR=4.1,95%CI 1.2–13.7,P=0.02).Conclusions Our study confirms the importance of monitoring liver enzymes in hospitalized patients with COVID-19;seriously ill patients have significantly elevated AST and D-dimer concentrations,which have prognostic implications in the SARS-CoV-2 disease course.

Atrial Septal Defect, Neuromuscular Junction and Skeletal Abnormalities in Spinal Muscular Atrophy Type Ⅲ

Spinal muscular atrophy （SMA） is a genetic disorder which is clinically characterized by progressive muscle weakness and atrophy and is associated with the degeneration of spinal and lowers bulbar motor neurons. SMAis the most common genetic cause of infant mortality, and seems to be present in general populations. The clinical spectrum of SMA ranges from early infant death to normal adult life with only mild weakness. Approximately 81.2–95.0% of cases of SMA resulted from homozygous deletion of survival of motor neuron 1 （SMN1） and 5.0% were compound heterozygous patients.[1] SMA might manifest not only the dysfunction of pure motor neurons but also abnormalities in neuromuscular junction （NMJ）, osteoporotic bone formation, cardiac abnormalities, and vascular defects.[2] These phenomena have been described in severe SMA （Type I, II） patients and in mouse models while data from SMA Type III individuals are not available. Patients with SMA Type III demonstrate progressive proximal weakness affecting the legs more severely than the arms, and might ultimately end up in the wheelchair. Herein, we report one patient with SMA Type III manifesting an atrial septal defect （ASD）, NMJ defect, short stature, and thick toes.

Defense of COVID-19 by Human Organoids

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),has created an immense menace to public health worldwide,exerting huge effects on global economic and political conditions.Understanding the biology and pathogenesis mechanisms of this novel virus,in large parts,relies on optimal physiological models that allow replication and propagation of SARS-CoV-2.Human organoids,derived from stem cells,are three-dimen-sional cell cultures that recapitulate the cellular organization,transcriptional and epigenetic signatures of their counterpart organs.Recent studies have indicated their great values as experimental virology platforms,making human organoid an ideal tool for investigating host-pathogen interactions.Here,we summarize research developments for SARS-CoV-2 infection of various human organoids involved in multiple systems,including lung,liver,brain,intestine,kidney and blood vessel organoids.These studies help us reveal the pathogenesis mechanism of COVID-19,and facilitate the development of effec-tive vaccines and drugs as well as other therapeutic regimes.