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Purpose: Outcomes of unresectable biliary tract cancer (BTC) with varying extents of liver involvement remain unclear. We evaluated characteristics and outcomes of BTC patients with liver metastases who underwent chemotherapy. Methods: We retrospectively reviewed consecutive BTC patients with synchronous or metachronous intrahepatic metastases who started first-line chemotherapy at our institution between January 2016 and December 2021. Results: Ninety-six patients were included, of which 57 only had liver metastases and 39 had multiorgan involvement. The liver only group had longer median overall survival (OS) (11.8 vs. 7.4 months, P = 0.006) and median progression-free survival (PFS) (4.1 vs. 2.7 months, P = 0.035) than the multiorgan group. Patients with oligometastases (defined as no more than three liver metastases) achieved longer OS than those with polymetastases (four or more liver metastases) in the entire cohort. Within the liver only group, there were no significant differences in OS or PFS between the oligometastasis and polymetastasis groups. Patients who underwent subsequent surgery had significantly longer median OS than those who did not (44.4 vs. 7.7 months, P < 0.001). Age ≥ 75 years, liver-only metastasis, modified Glasgow prognostic score ≥ 1 carcinoembryonic antigen ≥ 5 μg/L, and subsequent surgery were independent predictors of OS. Liver oligometastasis was only a significant predictor of longer OS in univariate Cox analysis. Conclusions: Outcomes in BTC patients with metastases limited to the liver, particularly those with oligometastasis, were more favorable than those with multiorgan metastases. Selected cases, generally with liver oligometastases, may achieve prolonged OS through subsequent surgery. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4-related Disease (IgG4-RD) is an immune-mediated fibroinflammatory disease that affects multiple organs, resulting in tumefactive lesions and/or organ dysfunction. This chronic, multiorgan inflammatory process is characterised by the infiltration of IgG4-positive plasma cells and has a variable clinical presentation depending on the organ involved. The present case series discusses four cases (two males and two females) of IgG4-RD involving different sites in patients presented to present Institution. The authors reviewed four cases of IgG4-RD, including clinical details, biochemical, radiological, and histopathological features. The case series includes IgG4-RD masquerading as meningioma, IgG4-related sclerosing cholangitis, IgG4-RD of the thyroid gland, and IgG4-RD of the lacrimal gland. Since IgG4-RD has non specific clinical features, histopathological analysis and immunohistochemistry play a pivotal role in diagnosis. Despite its diagnostic difficulties, earlier recognition is crucial to prevent significant morbidity and extensive fibrosis leading to organ failure.

Immunoglobulin G4-related Disease (IgG4-RD) is an immune-mediated fibroinflammatory disease that affects multiple organs, resulting in tumefactive lesions and/or organ dysfunction. This chronic, multiorgan inflammatory process is characterised by the infiltration of IgG4-positive plasma cells and has a variable clinical presentation depending on the organ involved. The present case series discusses four cases (two males and two females) of IgG4-RD involving different sites in patients presented to present Institution. The authors reviewed four cases of IgG4-RD, including clinical details, biochemical, radiological, and histopathological features. The case series includes IgG4-RD masquerading as meningioma, IgG4-related sclerosing cholangitis, IgG4-RD of the thyroid gland, and IgG4-RD of the lacrimal gland. Since IgG4-RD has non specific clinical features, histopathological analysis and immunohistochemistry play a pivotal role in diagnosis. Despite its diagnostic difficulties, earlier recognition is crucial to prevent significant morbidity and extensive fibrosis leading to organ failure. [ABSTRACT FROM AUTHOR]

Background: Post-acute COVID-19 is known to affect multiple organs. It is essential to determine factors that affect post-acute COVID-19 syndrome and medications needed by patients for optimized care. Methods: A prospective cohort study was conducted among patients recruited by stratified sampling from two COVID-19 hospitals in Malaysia. Patients were followed up for 6 months using a standard questionnaire to identify demographics, symptoms, medications taken, and factors associated with post-acute COVID-19 syndrome. Results: A total of 388 were successfully followed up. The most frequently reported symptom was respiratory symptoms (N = 168, 43.30%), of which cough (N = 134, 34.54%) was the most common. After 12 weeks of follow-up, respiratory syndrome (N = 56,14.43%) was frequently reported, of which cough (N = 41, 10.57%) was the most common. For respiratory syndrome, patients were commonly managed with diphenhydramine cough suppressants (N = 6, 1.55%, month 4) and metered dose inhaler (MDI) salbutamol (N = 7, 1.8%, month 4). The risk factors for post-acute COVID-19 syndrome were increased by 1.02 times (95% CI: 1.01, 1.04) with each advanced year of age and 2.87 times (95%CI: 1.51–5.48) in the presence of co-morbidities. Conclusions: Post-acute COVID-19 causes multiorgan involvement, and symptoms may remain for months, with patients taking various medications. Patients with risk factors should be monitored closely for post-acute COVID-19 symptoms.

Background: Nonalcoholic steatohepatitis (NASH) is a severe form of fatty liver disease that has been shown to be associated with chronic kidney disease (CKD). Mechanism for the association of NASH with CKD remains unclear. In this study, we examined the association between NASH severity and kidney glucose uptake and the liver-secreted signaling molecule fibroblast growth factor 21 (FGF21). Methods: Kinetic parameters for kidney glucose transport rate (K1) and standardized uptake value (SUV) were determined using dynamic positron emission tomography after injection of 18F-fluorodeoxyglucose. Liver biopsies were scored for NASH activity (inflammation and ballooning), fibrosis, and steatosis FGF21 was measured from fasting serum samples. Patients were categorized by liver biopsy and multivariate analyses were performed to evaluate the associations. Results: Of 41 NASH patients 73% were females, 71% white, 51% with steatosis ≥2, 39% with NASH activity ≥4 and fibrosis ≥3. With severe NASH activity, kidney SUV significantly increased even when adjusted for underlying insulin-resistant (IR) state. Kidney K1 decreased significantly in higher liver activity in unadjusted models but not when adjusted for IR. FGF21 decreased with severe liver activity in adjusted models (P

As a new type of anti-cancer therapy, immune checkpoint inhibitors (ICIs) have transformed the treatment of various cancers. However, ICIs are associated with many potential complications, namely immune-related adverse events (irAEs) , possibly involving the nervous, cardiac, pulmonary, cutaneous, renal, gastrointestinal, hepatic, and hematologic systems. Although a series of guidelines for the management of irAEs have been issued, early identification, diagnosis and treatment of irAEs in clinical practice are still not standardized enough due to different levels of awareness and attention regarding the disease across clinicians. We analyzed the clinical data of a patient with severe multisystem irAEs developed after treatment with cindilimab, and reviewed relevant literature, then summarized the benefits and limitations of treatments for irAEs, providing ideas for better managing multisystem irAEs clinically.

Background: Post-acute COVID-19 is known to affect multiple organs. It is essential to determine factors that affect post-acute COVID-19 syndrome and medications needed by patients for optimized care. Methods: A prospective cohort study was conducted among patients recruited by stratified sampling from two COVID-19 hospitals in Malaysia. Patients were followed up for 6 months using a standard questionnaire to identify demographics, symptoms, medications taken, and factors associated with post-acute COVID-19 syndrome. Results: A total of 388 were successfully followed up. The most frequently reported symptom was respiratory symptoms (N = 168, 43.30%), of which cough (N = 134, 34.54%) was the most common. After 12 weeks of follow-up, respiratory syndrome (N = 56,14.43%) was frequently reported, of which cough (N = 41, 10.57%) was the most common. For respiratory syndrome, patients were commonly managed with diphenhydramine cough suppressants (N = 6, 1.55%, month 4) and metered dose inhaler (MDI) salbutamol (N = 7, 1.8%, month 4). The risk factors for post-acute COVID-19 syndrome were increased by 1.02 times (95% CI: 1.01, 1.04) with each advanced year of age and 2.87 times (95%CI: 1.51-5.48) in the presence of co-morbidities. Conclusions: Post-acute COVID-19 causes multiorgan involvement, and symptoms may remain for months, with patients taking various medications. Patients with risk factors should be monitored closely for post-acute COVID-19 symptoms. [ABSTRACT FROM AUTHOR]

Dengue is the most rapid mosquito-borne disease in the world. As per the WHO guidelines for dengue fever, a list of atypical or unusual manifestations, also termed 'Expanded Dengue Syndrome' (EDS), is mentioned. Pregnancy increases the risk of expanded dengue syndrome. A 32-year-old woman with IUFD (twin) at 36 weeks gestation with H/O 1 C/S was reported with expanded dengue syndrome with multiorgan involvement. She was referred to a tertiary centre with H/O high fever, loose emotion, less fetal movement, and dengue NS 1 antigen positive. She was eventually diagnosed as having expanded dengue syndrome with multiorgan involvement with IUFD (twin) at 36 weeks. The decision of LSCS was taken by a multidisciplinary approach. She was managed with FFP, platelet apheresis, therapeutic plasma exchange, and I/V antibiotics, in addition to liver & neurological support in the ICU unit. This case emphasised the hazards of dengue infection in pregnant women, which needs special consideration. Early recognition with careful monitoring and multidisciplinary management are the key factors in a favourable outcome for a dengue patient. [ABSTRACT FROM AUTHOR]

Zinc Phosphide(Zn3P2) is a common rodenticide freely available in Nigeria for use against rodents. Occasionally human consumption occurs either accidentally or intentionally with potential consequences of multiorgan toxicity and death. An 11-year-old boy consumed an unknown quantity of zinc phosphide marketed as Push Out® with the intention of committing suicide and killing some members of the family as his response to chastisement for a misdemeanour. Patient presented in the hospital 4 days after ingestion of zinc phosphide with a history of profound vomiting and abdominal pain. Laboratory evaluation showed evidence of hepatic dysfunction, acute kidney injury and elevated serum amylase. He was managed conservatively and discharged home after two weeks of admission. We report this case to emphasise the need for Paediatricians to consider ingestion of rodenticides as a differential diagnosis of hepatoxicity and pancreatic enzyme elevation, as well as to highlight the possibility of suicide among children. There is need to control the indiscriminate use of rodenticides, strengthen public health education on poisoning as well as establish Poison Information Centres in our environment.

Abstract Background Dengue is a mosquito-borne viral infection that typically occurs in tropical and subtropical countries. The clinical manifestations of dengue infection range from an asymptomatic subclinical course to severe dengue shock syndrome. Besides, dengue can affect any organ in the body and can present with atypical manifestations. Case presentation We report a 6-year-old previously healthy Tamil child who had dengue complicated with multiorgan involvement. She initially presented with high fever, headache, body aches for 5 days, blood and mucus diarrhea, hematuria, and right knee joint swelling for 2 days. Dengue NS1 antigen was positive on day 2 of febrile illness. She was managed symptomatically in the local hospital for 3 days and transferred to the tertiary care hospital for further management. She was eventually diagnosed as having dengue hemorrhagic fever complicated with multiorgan involvement including acute liver failure, pancreatic involvement, coagulopathy, arthritis, acute kidney injury, and multiple intracranial hemorrhages. The constellation of disease manifestations was identified as expanded dengue syndrome. She was managed with fresh blood, platelet, and cryoprecipitate transfusions and intravenous antibiotics in addition to renal and liver support in the intensive care unit. On day 14 of illness, she deteriorated while on the ventilator and died due to multiple intracranial hemorrhages. Conclusion The reported child with dengue hemorrhagic fever developed several unusual presentations such as acute liver and renal failure, disseminated intravascular coagulopathy, pancreatic involvement, and multiple intracranial hemorrhages, which form part of expanded dengue syndrome. In the seriously unwell child, it is important to look for unusual complications actively to improve outcomes.

Aim: Echinococcosis with multi‐organ/disseminated involvement is rare in childhood. We aimed to evaluate the clinical and laboratory characteristics and prognosis in paediatric patients with echinococcosis having multiorgan/disseminated involvement. Method: We evaluated retrospectively children with echinococcosis with involvement of three or more organs. Results: Thirteen patients were included in the study. The median age was 120 (range 71–189) months. Three (23%) were diagnosed incidentally. Abdominal pain was seen in 5 (38.4%) patients, vomiting in 4 (30.7%), headache in 3 (23%), cough in 2 (15.3%), groin pain in 1 (7.6%), 1 (7.6%) had jaundice and 1 (7.6%) had fever. The median duration of complaints was 48 (0–140) days. The most common tripartite organ was 38.4% (5/13) liver, lung and spleen. Isolated abdominal dissemination was detected in two patients. Two patients had multi‐organ involvement and multiple cysts with dissemination. Cyst rupture was observed in three of the patients; recurrent urinary tract infection, hydroureteronephrosis, secondary peritonitis with intra‐abdominal abscess, and biliary tract fistula were each observed in one patient. Relapse developed in 3 (23%) patients. Conclusion: Echinococcosis is a very slow growing and complex parasitic disease that affects many organs and tissues. In our study, eosinophilia, recurrence, and complications were seen at a higher rate in paediatric patients with multiorgan involvement, who required repetitive surgeries and long‐term medical treatment. However, there are scanty data on risk factors, optimum treatment and prognosis. [ABSTRACT FROM AUTHOR]

Hydatid cyst is a parasitic infection transmitted by oral ingestion of Echinococcus granulosus eggs. Hydatid cyst of the genital tract is rare and the occurrence in the uterus is an extreme rarity. We present an 8-yr-old girl with complaints of swelling of lower abdomen, pollakiuria and bilateral flank pain was brought to Emergency Department of Harran University, Turkey, in Jun 2019. The patient had simultaneous hydatid cysts of the liver, mesentery and uterus. We performed abdominal exploration and completely removed the inner germinal layer of cyst through an incision made in the anterior of the uterine fundus. Then, we applied total excision to the two cysts in the right and left colon mesentery. Finally, we performed partial cystectomy to the cyst in the liver, and we removed the cyst membrane totally. In endemic regions, hydatid cysts should be considered for the diagnosis of children with cystic mass lesions. Uterine-sparing approach should be kept in mind as an option, especially in young women. Early surgical treatment of large pelvic cysts that cause obstructive uropathy may prevent the progression of renal damage. [ABSTRACT FROM AUTHOR]

Hydatid cyst is a parasitic infection transmitted by oral ingestion of Echinococcus granulosus eggs. Hydatid cyst of the genital tract is rare and the occurrence in the uterus is an extreme rarity. We present an 8-yr-old girl with complaints of swelling of lower abdomen, pollakiuria and bilateral flank pain was brought to Emergency Department of Harran University, Turkey, in Jun 2019. The patient had simultaneous hydatid cysts of the liver, mesentery and uterus. We performed abdominal exploration and completely removed the inner germinal layer of cyst through an incision made in the anterior of the uterine fundus. Then, we applied total excision to the two cysts in the right and left colon mesentery. Finally, we performed partial cystectomy to the cyst in the liver, and we removed the cyst membrane totally. In endemic regions, hydatid cysts should be considered for the diagnosis of children with cystic mass lesions. Uterine-sparing approach should be kept in mind as an option, especially in young women. Early surgical treatment of large pelvic cysts that cause obstructive uropathy may prevent the progression of renal damage.

Point-of-care ultrasonography (POCUS) is performed by a treating clinician at the patient's bedside, provides a acquisition, interpretation, and immediate clinical integration based on ultrasonographic imaging. The use of POCUS is not limited to one specialty, protocol, or organ system. POCUS provides the treating clinician with real-time diagnostic and monitoring information. Visual rounds based on multiorgan POCUS act as an initiative to improve clinical practice in the Intensive Care Unit and are urgently needed as part of routine clinical practice.

Corona disease 2019 (COVID‐19) affects multiple organ systems. Recent studies have indicated perturbations in the circulating metabolome linked to COVID‐19 severity. However, several questions pertain with respect to the metabolome in COVID‐19. We performed an in‐depth assessment of 1129 unique metabolites in 27 hospitalized COVID‐19 patients and integrated results with large‐scale proteomic and immunology data to capture multiorgan system perturbations. More than half of the detected metabolic alterations in COVID‐19 were driven by patient‐specific confounding factors ranging from comorbidities to xenobiotic substances. Systematically adjusting for this, a COVID‐19‐specific metabolic imprint was defined which, over time, underwent a switch in response to severe acute respiratory syndrome coronavirus‐2 seroconversion. Integration of the COVID‐19 metabolome with clinical, cellular, molecular, and immunological severity scales further revealed a network of metabolic trajectories aligned with multiple pathways for immune activation, and organ damage including neurological inflammation and damage. Altogether, this resource refines our understanding of the multiorgan system perturbations in severe COVID‐19 patients. [ABSTRACT FROM AUTHOR]

Hydatid disease (HD) is a zoonosis caused by the larval form of the Echinococcus granulosus parasites in which human is the intermediate host. Hydatid cysts mainly develop in the liver and lungs. However, they can be found in all anatomical locations, especially in endemic areas. Herein, we present a case of HD involving the liver, kidney and breast with the findings of mammography, ultrasonography and computed tomography.

Abstract Sarcoidosis, a systemic inflammatory disease of unknown etiology, can affect any site in the body. A bone lesion was unexpectedly detected by fluorodeoxyglucose position emission tomography/computed tomography (FDG PET/CT) in a patient with multiorgan sarcoidosis. FDG PET/CT should be considered for the detection of clinically silent lesions of sarcoidosis.

COL4A1/2 variants are associated with highly variable multiorgan manifestations. Depicting the whole clinical spectrum of COL4A1/2-related manifestations is challenging, and there is no consensus on management and preventative strategies. Based on a systematic review of current evidence on COL4A1/2-related disease, we developed a clinical questionnaire that we administered to 43 individuals from 23 distinct families carrying pathogenic variants. In this cohort, we extended ophthalmological and cardiological examinations to asymptomatic individuals and those with only limited or mild, often nonspecific, clinical signs commonly occurring in the general population (i.e., oligosymptomatic). The most frequent clinical findings emerging from both the literature review and the questionnaire included stroke (203/685, 29.6%), seizures or epilepsy (199/685, 29.0%), intellectual disability or developmental delay (168/685, 24.5%), porencephaly/schizencephaly (168/685, 24.5%), motor impairment (162/685, 23.6%), cataract (124/685, 18.1%), hematuria (63/685, 9.2%), and retinal arterial tortuosity (58/685, 8.5%). In oligosymptomatic and asymptomatic carriers, ophthalmological investigations detected retinal vascular tortuosity (5/13, 38.5%), dysgenesis of the anterior segment (4/13, 30.8%), and cataract (2/13, 15.4%), while cardiological investigations were unremarkable except for mild ascending aortic ectasia in 1/8 (12.5%). Our multimodal approach confirms highly variable penetrance and expressivity in COL4A1/2-related conditions, even at the intrafamilial level with neurological involvement being the most frequent and severe finding in both children and adults. We propose a protocol for prevention and management based on individualized risk estimation and periodic multiorgan evaluations., (© 2024 The Author(s). American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals LLC.)

Summary: Rates of simultaneous liver kidney (SLK) transplantation in the United States have progressively risen. On 8/10/17, the Organ Procurement and Transplantation Network implemented a policy defining criteria for SLK, with a "Safety Net" to prioritize kidney allocation to liver recipients with ongoing renal failure. We performed a retrospective review of the United Network for Organ Sharing (UNOS) database to evaluate policy impact on SLK, kidney after liver (KAL) and kidney transplant alone (KTA). Rates and outcomes of SLK and KAL transplants were compared, as was utilization of high‐quality kidney allografts with Kidney Donor Profile Indices (KDPI) <35%. Here, SLK transplants comprised 9.0% and 4.5% of total postpolicy liver and kidney transplants compared to 10.2% and 5.5% prior. Policy enactment did not affect 1‐year graft or patient survival for SLK and KAL populations. Less postpolicy SLK transplants utilized high‐quality kidney allografts; in all transplant settings, outcomes using high‐quality grafts remained stable. These findings suggest that policy implementation has reduced kidney allograft use in SLK transplantation, although both SLK and KAL rates have recently increased. Despite decreased high‐quality kidney allograft use, SLK and KAL outcomes have remained stable. Additional studies and long‐term follow‐up will ensure optimal organ access and sharing. [ABSTRACT FROM AUTHOR]

IgG4-related disease (IgG4-RD) is an immune-mediated multi-organ inflammatory disorder caused by tissue infiltration of lymphocytes with IgG4-secreting plasma cells. Herein, we discuss a case of a patient with IgG4-RD who had involvement of multiple organs: the kidneys, lymph nodes, bone marrow (biopsy performed), lungs, liver, and small intestine (imaging abnormalities). Although several case reports and series of IgG4-RD involving different organ involvement are in the literature, our patient has extensive simultaneous multi-organ involvement. We utilized the four domains (serologic, pathologic, radiologic, and pathologic) as discussed in the new 2019 ACR/EULAR classification criteria to provide a useful framework in considering an alternative tool for IgG4-RD in multi-organ involvement, where biopsy is more invasive and not always accessible. We highlight the findings of each organ involved that increase the likelihood that the patient has IgG4-RD. In our patient, the IgG4-RD classification criteria was fulfilled with total points adding up to 48. Our case meets the classification criteria for IgG4-RD, since at least one organ is involved to meet entry criteria (biopsy proven), no exclusion criteria are present, and the total points are ≥ 20. When such extensive involvement of IgG4-RD occurs, early diagnosis and treatment are recommended to avoid irreversible organ damage and better outcomes. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the impact of the heart allocation policy change in 2018 on the characteristics and outcomes of multiorgan transplants involving heart allografts. Methods: Adults undergoing multiorgan heart transplantation from 2010 to 2020 were identified from the United Network for Organ Sharing (UNOS) registry. Transplants were stratified into occurring before versus after the October 2018 heart allocation change. The primary outcome was 1‐year survival following transplantation. A Cox proportional hazards model was used to evaluate the risk‐adjusted effect of the allocation policy change on outcomes between cohorts. Results: A total of 1832 patients underwent multiorgan heart transplantation during the study period with 245 (13.37%) undergoing heart‐lung transplantation, 244 (13.32%) undergoing heart‐liver transplantation, and 1343 (73.31%) undergoing heart‐kidney transplantation. There was a higher utilization of temporary MCSDs as well as longer ischemic times for all three types of transplantation following the policy change. Heart‐lung and heart‐liver recipients had a similar 1‐year survival before and after the policy change (each p >.05). Renal failure requiring dialysis (29.5% vs. 39.4%, p =.001) as well as 1‐year survival (88% vs. 82%; log‐rank p =.01) were worse in the heart‐kidney cohort after the organ allocation system modification. Conclusions: This study demonstrates similar trends in multiorgan transplants as has been observed in isolated heart transplants following the allocation change, including more frequent utilization of temporary mechanical support and longer ischemic times. Although outcomes have remained comparable in the new allocation era with heart‐lung and heart‐liver transplants, heart‐kidney recipients have a worse 1‐year survival following the change. [ABSTRACT FROM AUTHOR]

Despite major advances in neonatal intensive care, infants born at extremely low birth weight still face an increased risk for chronic illness that may persist into adulthood. Pulmonary, retinal, and neurocognitive morbidities associated with preterm birth remain widespread despite interventions designed to minimize organ dysfunction. The design of therapeutic applications for preterm pathologies sharing common underlying triggers, such as fluctuations in oxygen supply or in the inflammatory state, requires alternative strategies that promote anti-inflammatory, pro-angiogenic, and trophic activities—ideally as a unitary treatment. Mesenchymal stem/stromal cell-derived extracellular vesicles (MEx) possess such inherent advantages, and they represent a most promising treatment candidate, as they have been shown to contribute to immunomodulation, homeostasis, and tissue regeneration. Current pre-clinical studies into the MEx mechanism of action are focusing on their restorative capability in the context of preterm birth-related pathologies, albeit not always with a multisystemic focus. This perspective will discuss the pathogenic mechanisms underlying the multisystemic lesions resulting from early-life disruption of normal physiology triggered by high oxygen exposures and pro-inflammatory conditions and introduce the application of MEx as immunomodulators and growth-promoting mediators for multisystem therapy.

Objective: Fasting regimens can promote health, mitigate chronic immunological disorders, and improve age-related pathophysiological parameters in animals and humans. Several ongoing clinical trials are using fasting as a potential therapy for various conditions. Fasting alters metabolism by acting as a reset for energy homeostasis, but the molecular mechanisms underlying the beneficial effects of short-term fasting (STF) are not well understood, particularly at the systems or multiorgan level. Methods: We performed RNA-sequencing in nine organs from mice fed ad libitum (0 h) or subjected to fasting five times (2–22 h). We applied a combination of multivariate analysis, differential expression analysis, gene ontology, and network analysis for an in-depth understanding of the multiorgan transcriptome. We used literature mining solutions, LitLab™ and Gene Retriever™, to identify the biological and biochemical terms significantly associated with our experimental gene set, which provided additional support and meaning to the experimentally derived gene and inferred protein data. Results: We cataloged the transcriptional dynamics within and between organs during STF and discovered differential temporal effects of STF among organs. Using gene ontology enrichment analysis, we identified an organ network sharing 37 common biological pathways perturbed by STF. This network incorporates the brain, liver, interscapular brown adipose tissue, and posterior-subcutaneous white adipose tissue; hence, we named it the brain-liver-fats organ network. Using Reactome pathways analysis, we identified the immune system, dominated by T cell regulation processes, as a central and prominent target of systemic modulations during STF in this organ network. The changes we identified in specific immune components point to the priming of adaptive immunity and parallel the fine-tuning of innate immune signaling. Conclusions: Our study provides a comprehensive multiorgan transcriptomic profiling of mice subjected to multiple periods of STF and provides new insights into the molecular modulators involved in the systemic immunotranscriptomic changes that occur during short-term energy loss.

Hydatid disease (HD) is a zoonosis caused by the larval form of the Echinococcus granulosus parasites in which human is the intermediate host. Hydatid cysts mainly develop in the liver and lungs. However, they can be found in all anatomical locations, especially in endemic areas. Herein, we present a case of HD involving the liver, kidney and breast with the findings of mammography, ultrasonography and computed tomography. [ABSTRACT FROM AUTHOR]

Abstract Inherited disorders that affect mitochondrial function are a diverse group of conditions with different pathophysiological mechanisms and highly variable clinical phenotypes. Affected children may present with a defined clinical syndrome or, more commonly, with non-specific signs of mitochondrial disease. Recognition of mitochondrial disease relies on having a high index of suspicion when faced with a multisystem disorder of unclear aetiology, in addition to knowledge of the various defined mitochondrial clinical syndromes. Evidence of mitochondrial dysfunction should be sought from a variety of organ systems using both functional and biochemical testing. Recent advances in genomic technology are changing the approach to diagnosis. Treatment of mitochondrial disease requires multi-disciplinary supportive management to address multi-systemic features. Disease-specific therapies are available for a small number of conditions, and a number of novel therapies are under evaluation. [ABSTRACT FROM AUTHOR]

A 3 year old healthy female baby had been stung with a swarm of wasps on her entire body while passing a coconut tree containing wasp nest at Chakoria, Cox’s Bazar. She developed severe pain and itching at the site of stings and swelling of the body within minutes. Immediately she was seen by a local physician and was treated with the injection of hydrocortisone and pheniramine maleate. On the following day, she gradually developed yellowish tint of the whole body (Figure 1), followed by passage of reddish scanty urine. For these reasons, she was referred to Chittagong Medical College and Hospital and was treated with injection cefotaxime, flucloxacillin, hydrocortisone and dopamine.

Abstract A 2-month-old Andalusian colt in central Spain presented dyspnea, diarrhea, and depression. Despite the initial treatment for presumptive pneumonia caused by Rhodococcus equi, after 1 hour, the colt showed signs of shock and died. The necropsy revealed multiple abscesses in the lung, as well as enlarged mesenteric lymph nodes, and hemorrhagic peritonitis. Samples were taken from trachea, lung parenchyma, small intestine, and colon. All samples yielded a pure culture of Streptococcus equi spp. zooepidemicus, whereas R. equi was excluded by using a specific qPCR performed on all samples. Isolates from all samples were characterized by pulse-field gel electrophoresis and the representative strain was identified by MALDI-TOF and qPCR. Its genome was sequenced, assembled, and annotated; multilocus sequence typing data assigned the strain to sequence type 70 and genes related to adhesion, bacteriocins, invasion, antimicrobial resistance, toxins, and superantigens szeN and szeP were identified in the assembled genome. The strain was susceptible to all antimicrobials tested. Our findings support the inclusion of S. zooepidemicus on an endemic farm where R. equi has been ruled out via PCR testing. S. zooepidemicus can cause multiorgan disease in foals, similar to infection in humans. The presence of superantigens in this S. zooepidemicus strain may have contributed to the fatal outcome in this clinical case. Highlights • Streptococcus zooepidemicus should be in the differential diagnoses when R. equi is ruled out by PCR testing. • S. zooepidemicus can cause multiorgan disease in foals, similar to infection in humans. • The presence of superantigens in the strain may have contributed to fatal outcome. [ABSTRACT FROM AUTHOR]

Human parvovirus B19 (B19V) causes myriads of clinical diseases; however, owing to lack of awareness and undetermined clinical impact, it has failed to become a virus pathogen of global concern. Cryptically, B19V causes significant morbidity and mortality. Half of the world population and 60 per cent of Indians are known to be serologically naive and are at risk of acquiring B19V infections. Cumulatively, our data showed 21.3 per cent B19V-infected patients with juvenile chronic arthropathy, recurrent abortions, multi-transfused thalassaemia and leukaemia. In addition, B19V-infected cases that ended fatally included patients with pure red cell aplasia, fulminant hepatitis and haemophagocytic syndrome. Novel clinical associations of B19V observed were amegakaryocytic thrombocytopaenia, myositis and non-occlusive ischaemic gangrene of bowel. B19V possesses multiple receptors which are distributed widely in human tissues. Vascular endothelial cell infection by B19V causes endothelialitis and vasculitic injuries besides antibody-dependent enhancement which empowered B19V to cause multiorgan diseases. Owing to lack of suitable animal model for B19V, true causal role remains to be determined, but numerous reports on B19V infections substantiate a causal role in multiorgan diseases. Hence, B19V infections need to be recognized, investigated and treated besides making efforts on vaccine developments. [ABSTRACT FROM AUTHOR]

Objective This study aims to determine the proportion of cases of neonatal sepsis developing acute kidney injury (AKI). Methods This is a prospective observational study conducted in the nursery of a tertiary care center in Northern India during October 2012 to March 2014. Newborns with symptoms suggestive of sepsis were investigated. Those with congenital renal anomalies and negative for sepsis were excluded fromthe study. Newborns with sepsis were treated accordingly and observed for AKI until discharge or death. Acute Kidney Injury Network definition was used to define AKI in this study. Results A total of 310 neonates with sepsis were enrolled out of which 3.87% neonates developed AKI. Factors such as maternal age, sex, birth weight, gestational age, asphyxia, the risk factor of sepsis in the mother, meconium-stained liquor, and mode of delivery were not found to be associated with AKI. Meningitis (p < 0.05) was found to be significantly associated with AKI. Duration of stay was longer for those with AKI (p < 0.01), but the mortality rate did not differ significantly among those with AKI and those without AKI. Around 25% of cases were found to be AKI stage 1, 25% of cases were AKI stage 2, and 50% of cases were AKI stage 3. Conclusion It is difficult to predict AKI based on clinical features, so it is better to screen all the neonates with sepsis for AKI so that they can be managed accordingly, as AKI detected early has a better prognosis. [ABSTRACT FROM AUTHOR]

Objectives: Mitochondrial disorders (MIDs) frequently present as mitochondrial multiorgan disorder syndrome (MIMODS) at onset or evolve into MIMODS during the course. This study aimed to find which organs and/or tissues are most frequently affected by MIMODS, which are the most frequent abnormalities within an affected organ, whether there are typical MIMODS patterns, and to generate an MIMODS score to assess the diagnostic probability for an MID. Methods: This is a retrospective evaluation of clinical, biochemical, and genetic investigations of adult patients with definite MIDs. A total of 36 definite MID patients, 19 men and 17 women, aged 29-82 years were included in this study. The diagnosis was based on genetic testing (n=21), on biochemical investigations (n=17), or on both (n=2). Results: The number of organs most frequently affected was 4 ranging from 1 to 9. MIMODS was diagnosed in 97% of patients. The organs most frequently affected were the muscle (97%), central nervous system (CNS; 72%), endocrine glands (69%), heart (58%), intestines (55%), and peripheral nerves (50%). The most frequent CNS abnormalities were leukoencephalopathy, prolonged visually evoked potentials, and atrophy. The most frequent endocrine abnormalities included thyroid dysfunction, short stature, and diabetes. The most frequent cardiac abnormalities included arrhythmias, systolic dysfunction, and hypertrophic cardiomyopathy. The most frequent MIMODS patterns were encephalomyopathy, encephalo- myo-endocrinopathy, and encepalo-myo-endocrino-cardiopathy. The mean ± 2SD MIMODS score was 35.97±27.6 (range =11-71). An MIMODS score >10 was regarded as indicative of an MID. Conclusion: Adult MIDs manifest as MIMODS in the vast majority of the cases. The organs most frequently affected in MIMODS are muscles, CNS, endocrine glands, and heart. An MIMODS score >10 suggests an MID. [ABSTRACT FROM AUTHOR]

Abstract Hemorrhagic pustules with a “blueberry muffin” appearance accompanied by respiratory failure in a neonate present a challenging differential diagnosis that includes infections and neoplasms. We present a case of multiorgan, multisite Langerhans cell histiocytosis (LCH), positive for the oncogenic BRAF V600E mutation, in a preterm neonate. Infants with LCH pose a diagnostic challenge due to their heterogeneous presentations. This case is unusual in that the newborn presented with severe multiorgan involvement. Due to the rare incidence, wide spectrum of clinical manifestations, and high mortality rate, clinicians must maintain a high index of suspicion for LCH.

Background: To analyze the spectrum of challenges faced in the treatment of Langerhen Cell Histiocytosis resource limited settings lacking salvage therapy. Methods: In this observational study , 42 patients of Langerhans cell histiocytosis were enrolled. Risk organ involvement, treatment course and outcome were analyzed.The patients were treated with vinblastine and prednisolone as first line given weekly for 6 weeks and then 3-weekly as a continuation therapy up to 6-12 months. Doses were calculated according to body surface area. Intravenous Cytarabine pulses used for 5 days 3-weekly apart and Japanese Protocol used for refractory cases. The salvage therapy available in developed countries in the form of 2-CdA (2-chlorodeoxyadenosine) and RIC -SCT reduced-intensity conditioning stem cell transplantation not available in our center. In our study Group A include patients who refused enucleation and opted out of recommended treatment plan and Group B patients had enucleations done and followed treatment plans. Results: Age of the patients range from< 1 to 10 years (19% 6 months after the onset of symptoms in 30/42 (72%) of cases with 100% expiries in this group and 89% of abandonment. The children presenting at younger age had risk of having MS-LCH 75% as compared to 36% in age >2years. Conclusion: Treatment abandonment, delayed diagnosis and poor social support are major challenges in treating LCH in developing countries. Early diagnosis and timely treatment with effective infection control measures and strong social support are of utmost importance to improve long term overall survival.

Hydatidosis is endemic in Iran. This disease frequently invades the liver and lungs. The frequency of multiple organ involve¬ment ranges between 11% and 30%. This study revealed a five -year-old female with missed multifocal and multior¬gan localization of hydatic cyst. The patient presented with a complaint of persistent fever and respiratory distress. In compute¬rized tomography (CT) of the thorax and abdomen, cystic lesions of different sizes in both lungs, massive pleural effusion were observed. Albendazole, praziquantel, cephazolin and aminoglycoside was started before surgery. Surgical intervention was planned for pleuropulmonary lesions of this patient. With early diagnosis and proper managements, hyda¬tid cyst in children has an excellent outcome. Today, it is believed that if the operation is performed after a brief course of albendazole or mebendazole, the success rates will be higher.

Background: To analyze the spectrum of challenges faced in the treatment of Langerhen Cell Histiocytosis resource limited settings lacking salvage therapy. Methods: In this observational study, 42 patients of Langerhans cell histiocytosis were enrolled. Risk organ involvement, treatment course and outcome were analyzed. The patients were treated with vinblastine and prednisolone as first line given weekly for 6 weeks and then 3-weekly as a continuation therapy up to 6-12 months. Doses were calculated according to body surface area. Intravenous Cytarabine pulses used for 5 days 3-weekly apart and Japanese Protocol used for refractory cases. The salvage therapy available in developed countries in the form of 2-CdA (2-chlorodeoxyadenosine) and RIC-SCT reducedintensity conditioning stem cell transplantation not available in our center. In our study Group A include patients who refused enucleation and opted out of recommended treatment plan and Group B patients had enucleations done and followed treatment plans. Results: Age of the patients range from< 1 to 10 years (19% <2 yrs). M: F Ratio was 2:1. Majority (72%) of the patients presented with multisystem-LCH (MS-LCH) with100% mortality in MS-LCH group (p-value=0.045) and 18/42 (43%) had risk organ involvement with 72% mortality. Twenty nine (70%) had bone lesions and 12(29%) had central nervous system involvement. Fifty five percent completed treatment, 2/42 (5%) are on treatment, 9/42 (21%) abandoned treatment and 8/42 (19%) expired due to progressive disease and worsening infection. Sixteen (38%) had reactivations of disease requiring therapy for more than one year. Twenty four percent of cases received two cycles of initiation therapy before continuation therapy started. The treatment initiated >6 months after the onset of symptoms in 30/42 (72%) of cases with 100% expiries in this group and 89% of abandonment. The children presenting at younger age had risk of having MS-LCH 75% as compared to 36% in age >2years. Conclusion: Treatment abandonment, delayed diagnosis and poor social support are major challenges in treating LCH in developing countries. Early diagnosis and timely treatment with effective infection control measures and strong social support are of utmost importance to improve long term overall survival. [ABSTRACT FROM AUTHOR]

Most of patients after the Fontan operation can reach their adulthood, however, the management strategy for this complex pathophysiology has not been yet established. In general, elevated central venous pressure (CVP) and low cardiac output (CO) due to impaired ventricular preload characterize the Fontan circulation and the ideal hemodynamics could be a combination of a lower CVP with a higher CO. Thus, preserved functional systemic ventricle with low pulmonary artery resistance is thought to be crucial for better long-term outcome. However, on the other hand, because of the unique hemodynamics, these patients have significantly higher incidence of complications, sequelae, and even mortality. The major complications are supraventricular arrhythmias, heart failure, and Fontan-related problems, including protein-losing enteropathy and pulmonary arteriovenous fistulae, both of which are refractory to the treatments, and most of these “Fontan inconveniences” increase as patients age. In addition, one of the recent emerging problems is Fontan-associated liver disease that includes liver cirrhosis and hepatocellular carcinoma. Furthermore, women with Fontan circulation also reach childbearing age and there have been increasing numbers of reports showing a high incidence of pregnancy-associated complications. All these problems may be a part of “Fontan inconveniences” because most of the current Fontan patients are still “young” i.e. in their twenties or thirties and it may be not surprising that more new Fontan-associated pathophysiology emerges as patients age. Recent evidence reminds us of the concept that adult Fontan pathophysiology is not just a cardiovascular disease, rather, a multiorgan disease with many interactions between cardiovascular and non-cardiovascular organs. Therefore, a multidisciplinary approach is mandatory to take care of and anticipate the better long-term outcome. [ABSTRACT FROM AUTHOR]

Sarcoidosis, a systemic inflammatory disease of unknown etiology, can affect any site in the body. A bone lesion was unexpectedly detected by fluorodeoxyglucose position emission tomography/computed tomography (FDG PET/CT) in a patient with multiorgan sarcoidosis. FDG PET/CT should be considered for the detection of clinically silent lesions of sarcoidosis. [ABSTRACT FROM AUTHOR]

Inherited disorders that affect mitochondrial function are an exceedingly diverse group of conditions with different pathophysiological mechanisms and highly variable clinical phenotypes. Paediatric patients may present with a defined clinical syndrome or, more commonly, with non-specific signs of mitochondrial disease. Recognition of mitochondrial disease relies on having a high index of suspicion when faced with a multisystem disorder of unclear aetiology, in addition to knowledge of the various defined mitochondrial clinical syndromes. However, diagnosis remains a particular challenge, owing to the lack of sensitive and specific biomarkers. Evidence of mitochondrial dysfunction should be sought from a variety of organ systems using both functional and biochemical testing, although recent advances in genomic technology are changing the approach to diagnosis. Treatment of mitochondrial disease also presents a significant challenge, since although a few disease specific therapies exist, treatment remains predominantly supportive. Some cofactors, vitamins and antioxidants are commonly used to enhance mitochondrial function, although there is little evidence to support their efficacy. [ABSTRACT FROM AUTHOR]

Hydatidosis is endemic in Iran. This disease frequently invades the liver and lungs. The frequency of multiple organ involve¬ment ranges between 11% and 30%. This study revealed a five -year-old female with missed multifocal and multior¬gan localization of hydatic cyst. The patient presented with a complaint of persistent fever and respiratory distress. In compute¬rized tomography (CT) of the thorax and abdomen, cystic lesions of different sizes in both lungs, massive pleural effusion were observed. Albendazole, praziquantel, cephazolin and aminoglycoside was started before surgery. Surgical intervention was planned for pleuropulmonary lesions of this patient. With early diagnosis and proper managements, hyda¬tid cyst in children has an excellent outcome. Today, it is believed that if the operation is performed after a brief course of albendazole or mebendazole, the success rates will be higher.

Hydatid disease is endemic in some parts of the world. This disease can occur in any organ. We present a 22-year-old farmer who was suffering from hydatidosis for 4 years. He was admitted to the hospital because of fever, cough, and chest pain in 2004. A chest radiograph revealed multiple nodules in both of lungs. A transthoracic echocardiogram showed cystic lesion in the apex of right ventricle. IgG Ab ELISA for hydatid cyst was positive and albendazole was administrated. One year later, he was admitted to the hospital because of hemoptysis, a transthoracic lung biopsy was performed. Pathologic examination revealed laminated membrane of hydatid cyst in associated with fibrinoleukocytic exudates. Three years after the second admission, he was admitted to the hospital because of dyspnea. Iranian people especially who live in village need more information about the routes of prevention because therapy is difficult in some cases. [ABSTRACT FROM AUTHOR]

Abstract: Estrogen exposure during the adult period is widely known to promote tumor development in the female genital system, as well as in the mammary gland in experimental animals, but its carcinogenic potential with exposure at the prepubertal stage, for 6 weeks after birth, is not completely understood. In the present study, we therefore evaluated the modifying effects of prepubertal ethinyl estradiol (EE) treatment on susceptibility to multiple organ carcinogenesis with subsequent carcinogen exposure in F344 rats. Dams during the lactation period and their weaned offspring until postnatal-week 6 were fed diet containing 0, 0.2 or 1.0ppm EE. The offsprings were then administered 7,12-dimethylbenz[a]anthracene (DMBA, 50mg/kg body weight) by gavage for mammary tumor induction in week 7 and given free access to drinking water containing N-bis (2-hydroxypropyl)nitrosamine (DHPN, 0.2%) for wide spectrum tumor induction in organs such as the thyroid, liver, lung and kidney from weeks 6–14. Male and female offspring were euthanized at weeks 27 and 36, respectively, for histopathological examination. While the incidence and multiplicity of mammary tumors showed a tendency for increase in females of the 0.2 and 1.0ppm EE groups, this was without statistical significance. Furthermore, prepubertal EE exposure did not affect tumor induction in the thyroid, liver, lung, kidney, esophagus, ovary and lymphoid tissue in either sex. The present results thus indicate a lack of influence of estrogen early in life on carcinogenic susceptibility, although the possible impact on mammary carcinogenesis requires further examination. [Copyright &y& Elsevier]