Neuroblastoma: A Case of Massive Hepatomegaly.

Neuroblastoma is the most common embryonal tumor of childhood and has a variable presentation. Stage 4S neuroblastoma, described as a localized primary tumor in an infant with metastasis to skin, liver, or bone marrow, is an exception to the poor prognosis seen in widespread metastasis of neuroblastoma. Survival in infants with this stage of the disease is over 90%. Stage 4S with massive liver involvement, however, confers a poor prognosis. We need more research on the optimum treatment modality for patients with Stage 4S disease and massive hepatomegaly to improve patient outcomes.

The radiological presentation of Rasmussen aneurysm secondary to pulmonary tuberculosis and COVID-19: A case report.

Rasmussen aneurysm is rare diagnosis occurring in patients with long-standing tuberculosis. TB-COVID-19 co-infection in the context of Rasmussen aneurysm is a rare occurrence, yet new cases are emerging. An elderly male was recently diagnosed with TB-COVID-19 co-infection and presented with sudden onset massive hemoptysis. The patient was diagnosed with Rasmussen aneurysm after being evaluated by computed tomography pulmonary angiogram due to a suggestive clinical presentation. Interventional radiologists planned for embolization of pulmonary artery, with an unidentifiable source. It was suspected that the patient's source of bleeding was hampered due to local tamponade effect or thrombosis of the aneurysm. The patient remained stable after 24 hours on computed tomography pulmonary angiogram. Our case emphasizes the importance of Rasmussen aneurysm as a differential diagnosis when presented with a TB-COVID-19 co-infection and sudden onset of hemoptysis symptomatically and radiologically. The timely diagnosis and management are key to improve mortality.

Inhibition of Efferocytosis by Extracellular CIRP-Induced Neutrophil Extracellular Traps.

Phagocytic clearance of apoptotic cells by the macrophages (efferocytosis) is impaired in sepsis, but its mechanism is poorly understood. Extracellular cold-inducible RNA-binding protein (eCIRP) is a novel damage-associated molecular pattern that fuels inflammation. We identify that eCIRP-induced neutrophil extracellular traps (NETs) impair efferocytosis through a novel mechanism. Coculture of macrophages and apoptotic thymocytes in the presence of recombinant murine CIRP (rmCIRP)-induced NETs significantly inhibited efferocytosis. Efferocytosis was significantly inhibited in the presence of rmCIRP-treated wild-type (WT), but not PAD4-/- neutrophils. Efferocytosis in the peritoneal cavity of rmCIRP-injected PAD4-/- mice was higher than WT mice. Milk fat globule-EGF-factor VIII (MFG-E8), an opsonin, increased macrophage efferocytosis, whereas the inhibition of efferocytosis by NETs was not rescued upon addition of MFG-E8, indicating disruption of MFG-E8's receptor(s) αvß3 or αvß5 integrin by the NETs. We identified neutrophil elastase in the NETs significantly inhibited efferocytosis by cleaving macrophage surface integrins αvß3 and αvß5 Using a preclinical model of sepsis, we found that CIRP-/- mice exhibited significantly increased rate of efferocytosis in the peritoneal cavity compared with WT mice. We discovered a novel role of eCIRP-induced NETs to inhibit efferocytosis by the neutrophil elastase-dependent decrease of αvß3/αvß5 integrins in macrophages. Targeting eCIRP ameliorates sepsis by enhancing efferocytosis.

Extracellular CIRP and TREM-1 axis promotes ICAM-1-Rho-mediated NETosis in sepsis.

Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern (DAMP). Intercellular adhesion molecule-1 (ICAM-1) expressing neutrophils produce excessive amounts of neutrophil extracellular traps (NETs). We reveal that eCIRP generates ICAM-1+ neutrophils through triggering receptor expressed on myeloid cells-1 (TREM-1) and the ICAM-1+ neutrophils involve Rho GTPase to promote NETosis. Treatment of BMDN with rmCIRP increased the frequency of ICAM-1+ BMDN, while rmCIRP-treated TREM-1-/- BMDN or pretreatment of BMDN with TREM-1 inhibitor LP17 significantly decreased the frequency of ICAM-1+ neutrophils. The frequencies of ICAM-1+ neutrophils in blood and lungs were markedly decreased in rmCIRP-injected mice or septic mice treated with LP17. Coculture of ICAM-1-/- neutrophils or wild-type (WT) neutrophils with WT macrophages in the presence of a peptidylarginine deiminase 4 (PAD4) inhibitor reduced TNF-α and IL-6 compared to WT neutrophils treated with rmCIRP. Treatment of ICAM-1-/- neutrophils with rmCIRP resulted in reduced quantities of NETs compared to WT rmCIRP-treated neutrophils. Treatment of BMDN with rmCIRP-induced Rho activation, while blockade of ICAM-1 significantly decreased Rho activation. Inhibition of Rho significantly decreased rmCIRP-induced NET formation in BMDN. TREM-1 plays a critical role in the eCIRP-mediated increase of ICAM-1 expression in neutrophils, leading to the increased NET formation via Rho activation to exaggerate inflammation.

Cold-inducible RNA-binding Protein Induces Neutrophil Extracellular Traps in the Lungs during Sepsis.

Extracellular cold-inducible RNA-binding protein (CIRP) exaggerates inflammation and tissue injury in sepsis. Neutrophil extracellular traps (NETs) are released by activated neutrophils during sepsis. NETs contribute to pathogen clearance, but excessive NET formation (NETosis) causes inflammation and tissue damage. Peptidylarginine deiminase 4 (PAD4) is associated with NETosis by increasing histone citrullination and chromatin decondensation. We hypothesized that CIRP induces NETosis in the lungs during sepsis via upregulating PAD4 expression. Sepsis was induced in C57BL/6 wild-type (WT) and CIRP-/- mice by cecal ligation and puncture (CLP). After 20 h of CLP induction, NETs in the lungs of WT and CIRP-/- mice were quantified by flow cytometry by staining the single cell suspensions with MPO and CitH3 Abs. PAD4 expression in the lungs of WT and CIRP-/- mice after sepsis was assessed by Western blotting. In vitro effects of recombinant mouse (rm) CIRP for NETosis and PAD4 expression in the bone marrow-derived neutrophils (BMDN) were assessed by flow cytometry and Western blotting, respectively. After 20 h of CLP, NETosis in the lungs was significantly decreased in CIRP-/- mice compared to WT mice, which also correlated with the decreased PAD4 expression. Intratracheal administration of rmCIRP into WT mice significantly increased NETosis and PAD4 expression in the lungs compared to vehicle-injected mice. In vitro culture of BMDN with rmCIRP significantly increased NETosis and PAD4 expression compared to PBS-treated control. Fluorescence microscopy revealed typical web-like structures consistent with NETs in rmCIRP-treated BMDN. Thus, CIRP serves as a novel inducer of NETosis via PAD4 during sepsis.

Perforated obturator Littr hernia in an elderly woman.

Obturator hernia is an uncommon condition. It carries the highest mortality amongst abdominal wall hernias, usually presenting in elderly, multiparous and thin ladies. Meckel diverticulum is a rare cause of intestinal obstruction and its existence in an obturator hernia is extremely rare; our literature search revealed only two reported cases. We report the case of a 70-year-old woman who presented with signs and symptoms of intestinal obstruction and peritonitis. An exploratory laparotomy led to diagnosis of a strangulated obturator hernia. The sac contents included a Meckel diverticulum with a perforation at its base and a loop of the ileum. The ischemic ileal segment including the Meckel diverticulum was resected and a loop ileostomy was created.

Metastatic involvement of the spleen by endometrial adenocarcioma; a rare asylum for a common malignancy: a case report.

BACKGROUND: Metastatic involvement of the spleen by solid tumors is a rare clinical entity; those coming from endometrial adenocarcinomas are exceptionally rare. Spleen is an uncommon site for metastatic deposits due to its specific anatomy and microenvironment. Typically, splenic metastasis from endometrial carcinomas present months to years after curative surgery, chemotherapy or radiotherapy. The most common complaint in symptomatic patients is abdominal pain localized to the left hypochondrium. Most however, are asymptomatic only to be picked up on vigilant routine ultrasonography or computerized tomography during follow up. We report the case of a 54-year-old woman who presented to us after 50 months of total abdominal hysterectomy and bilateral salpingo-oophorectomy for an endometrial adenocarcinoma. She had severe abdominal pain localized to the left hypochondrium as the presenting complaint. To the best of our knowledge, this is the 1st case to be reported from Pakistan with 14 cases reported prior to our report. All past cases report the endometroid variant of endometrial adenocarcinoma as the primary tumor and our patient was a victim to the same variant. CASE PRESENTATION: A 54-year-old, nulliparous widowed woman presented with severe abdominal pain in the left hypochondrium for the last 4 months. The pain radiated to the left shoulder and was exacerbated with deep breathing. She had a history of total abdominal hysterectomy with bilateral salpingo-oophorectomy done 50 months back for stage 1a endometroid endometrial adenocarcinoma. Clinical examination revealed tenderness in the left hypochondrium but no visceromeglay was appreciable. Ultrasonography and computerized tomography revealed a space-occupying lesion within the spleen with associated splenomegaly. Computed tomography further suggested a large splenic abscess however the patient did not have fever, vomiting or leukocytosis which are the hallmarks of a splenic abscess. A splenectomy was performed for her complaints. On histopathology a metastatic adenocarcinoma was identified consistent with the primary tumor. The tumor was CK7, CA-125 and epithelial membrane antigen positive (EMA). The patient was then referred for further chemotherapy. CONCLUSION: From this case we conclude, that although very rare, the spleen is a potential site for metastasis in endometroid endometrial adenocarcinoma. Since most patients are asymptomatic, routine examinations and imaging can identify its presence and avoid complications. If the practice is employed with vigilance, we may expect the clinical event to be diagnosed more frequently. The standard treatment is a classic splenectomy followed by chemotherapy.

Hepatitis C in Pakistan: a review of available data.

Hepatitis C virus (HCV) infection is increasingly recognized as a major health care problem, and is found frequently in Pakistani settings. In this article we reviewed published and unpublished data related to the seroepidemiology of HCV infection in Pakistan. For this article, data from 132 published studies and three unpublished data sets published/ presented between the period 1992-2008 were utilized. Data of 1,183,329 individuals were gathered. Blood donors (982,481) and the general population (178,322) constituted the majority of these subjects. The frequency of HCV infection in blood donors and in the general population was 3.0 % (95% CI: 3.0- 3.1) and 4.7 (95% CI: 4.6 -4.8), respectively. The frequency among 6,148 pregnant females was 7.3% (95% CI = 6.7 - 8.0). The frequency in healthy children ranged from 0.4 to 4.1% (95% CI = 1.4 - 2.3). Pakistani HCV serofrequency figures are significantly higher (P < 0.0001) compared to those of the corresponding populations in surrounding countries like India, Nepal, Myanmar, Iran and Afghanistan.