Ram Venkatesh Anantha

CD1d- and MR1-Restricted T Cells in Sepsis

Dysregulated immune responses to infection, such as those encountered in sepsis, can be catastrophic. Sepsis is typically triggered by an overwhelming systemic response to an infectious agent(s) and is associated with high morbidity and mortality even under optimal critical care. Recent studies have implicated unconventional, innate-like T lymphocytes, including CD1d- and MR1-restricted T cells as effectors and/or regulators of inflammatory responses during sepsis. These cell types are typified by invariant natural killer T (iNKT) cells, variant NKT (vNKT) cells, and mucosa-associated invariant T (MAIT) cells. iNKT and vNKT cells are CD1d-restricted, lipid-reactive cells with remarkable immunoregulatory properties. MAIT cells participate in antimicrobial defense, and are restricted by major histocompatibility complex-related protein 1 (MR1), which displays microbe-derived vitamin B metabolites. Importantly, NKT and MAIT cells are rapid and potent producers of immunomodulatory cytokines. Therefore, they may be considered attractive targets during the early hyperinflammatory phase of sepsis when immediate interventions are urgently needed, and also in later phases when adjuvant immunotherapies could potentially reverse the dangerous state of immunosuppression. We will highlight recent findings that point to the significance or the therapeutic potentials of NKT and MAIT cells in sepsis and will also discuss what lies ahead in research in this area.

Familial syndromes associated with intracranial tumours: a review

BackgroundMost cancers of the central nervous system (CNS) occur sporadically in the absence of any known underlying familial disorder or multi-systemic syndrome. Several syndromes are associated with CNS malignancies, however, and their recognition has significant implications for patient management and prognosis. Patients with syndrome-associated CNS malignancies often have multiple tumours (either confined to one region or distributed throughout the body), with similar or different histology.ObjectiveThis review examines syndromes that are strongly associated with CNS cancers: the phakomatosis syndromes, familial syndromes such as Li–Fraumeni and familial polyposis syndromes and dyschondroplasia.

Fournier’s gangrene of the penis caused by Streptococcus dysgalactiae subspecies equisimilis: case report and incidence study in a tertiary-care hospital

BackgroundFournier’s gangrene is a rare necrotizing soft tissue infection of the scrotum and penis. We report, to our knowledge, the first case of Fournier’s gangrene caused by Streptococcus dysgalactiae subsp. equisimilis (SDSE), a strain of pyogenic β-hemolytic streptococci that is increasingly being recognized as an important human pathogen.Case presentationWe describe a healthy 59 year-old Caucasian male who presented to the emergency department with Fournier’s gangrene of the penis and scrotum, with extension to the anterior abdominal wall. He underwent urgent surgical debridement of his scrotum, penis, and anterior abdomen. Swabs from the scrotum grew Gram-positive cocci, which were initially identified as Streptococcus anginosus group by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). However, polymerase chain reaction (PCR) amplification and sequencing of the 16S rRNA gene identified the isolate as Streptococcus dysgalatiae subspecies equisimilis (SDSE). The incidences of invasive S. anginosus group and SDSE infections at the London Health Sciences Centre, a tertiary-care institution in southwestern Ontario, were determined between August 1, 2011 and August 31, 2012, revealing a slightly lower rate of SDSE (3.2 cases per 100,000 population) than other studies.ConclusionsThis case highlights a unique disease manifestation of the emerging human pathogen Streptococcus dysgalatiae subspecies equisimilis that has not been previously reported. This case also underscores the limitations of MALDI-TOF MS in differentiating between closely-related streptococcal species which may have different pathogenic profiles.

Analgesia in the management of paediatric and adolescent trauma during the resuscitative phase: The role of the pediatric trauma centre

BACKGROUND The objective of this study was to evaluate the use of analgesia in the resuscitative phase of severely injured children and adolescents. METHODS A retrospective cohort of paediatric (age<18 years), severely injured (ISS≥12) patients were identified from the London Health Sciences Centres Trauma Registry from 2007 to 2010. Variables were compared between Analgesia and Non-analgesia groups with Pearson Chi-square and Mann-Whitney U tests. Resuscitative analgesia use was assessed through multivariable logistic regression controlling for age, gender, mechanism, arrival and Trauma Team Activation (TTA). RESULTS Analgesia was used in 32% of cases. Univariate analysis did not reveal any differences in gender, age, injury type, injury profile and arrival patterns. Significant differences were found with analgesia used more frequently in patients injured in a motor vehicle collision (58% vs. 42%, p=0.026) and having parents in the resuscitation room (17% vs. 6%, p=0.01). Analgesia patients were more injured (median ISS 22 vs. 17, p=0.027) and had 2.25 times more TTA (39% vs. 17%). Logistic regression revealed patients arriving directly to a trauma centre had a higher incidence of receiving analgesia (OR 2.01, 95% CI: 1.03-3.93), as did TTA (OR 2.18, 95% CI: 1.01-4.73) and having parents in resuscitation room (3.56, 95% CI: 1.23-10.33). Narcotics were most commonly used (85%), followed by benzodiazepines (16%), with 66% given during the primary survey. CONCLUSION Use of analgesia is important in the acute management of paediatric trauma. Direct presentation to a level I trauma centre, TTA and the presence of parents lead to higher appropriate use of analgesia in paediatric trauma resuscitation.

Abdominal cocoon syndrome caused by Mycobacterium bovis from consumption of unpasteurised cow's milk.

A 12-year-old girl presented to the emergency room with severe abdominal pain, non-bilious emesis, and a 3-month history of progressively worsening lower abdominal pain, malaise, night sweats, and 4 kg weight loss. She had emigrated from Iraq 2 years earlier, and had been fed cow’s milk—often taken directly from the udder—after birth because her mother was unable to breastfeed. In the emergency room, her lower abdomen was tender, without peritonitis, and distended. Her white blood cell count, erythrocyte sedimentation rate, and C-reactive protein concentration were raised, whereas tests for hepatitis A, B, and C, HIV, and tuberculosis were negative. MRI of her abdomen and pelvis revealed extensive thickening of the bowel mesentery, peritoneum, and greater omentum, with a complex right-sided adnexal mass (appendix). We did an exploratory laparotomy to assess the mass, and encountered a dense, thick rind of tissue that was studded with tubercles and encased the peritoneal cavity (fi gure). A diagnosis of abdominal cocoon syndrome was made, and the abdomen was closed due to the extreme diffi culty in separating the fi brotic tissue from the abdominal wall. Frozen-section biopsy samples revealed caseating granulomas consistent with tuberculosis. A culture of the peritoneal fl uid grew Mycobacterium bovis subspecies bovis after 4 weeks and was resistant to pyrazinamide. The girl stayed in hospital for 3 months because she had recurrent episodes of partial or complete bowel obstruction that resolved with conservative, non-operative management. She was given isoniazid, rifampicin, and moxifl oxacin for 6 months while in hospital, followed by isoniazid and rifampicin for a further 12 months. On her last follow-up visit, she was no longer receiving antibiotic therapy, and was functioning normally. No further surgical intervention was planned for her, even though a repeat MRI of her abdomen and pelvis continued to show the thickened peritoneum and adnexal mass.

Recalcitrant Prosthetic Valve Endocarditis Requiring Repeated Reconstruction: Running Out of Options

In this report we describe a previously healthy 36-year-old man who presented with septic shock secondary to bacterial endocarditis with multiple cerebral, mesenteric, and peripheral embolic phenomena. He underwent emergent porcine prosthetic valve replacement with aortic annular reconstruction. Subsequently, he developed recalcitrant Candida parapsilosis endocarditis requiring treatment with multiple antifungal agents and 4 repeated complex reconstructions of the aortic root and fibrous trigones over 3 years, before the infection was successfully controlled. This case underscores the significant morbidity associated with fungal endocarditis and importance of an early combined medical and surgical approach.

Surgical intervention in pediatric trauma at a level 1 trauma hospital: a retrospective cohort study and report of cost data

BACKGROUND Given that the management of severely injured children requires coordinated care provided by multiple pediatric surgical subspecialties, we sought to describe the frequency and associated costs of surgical intervention among pediatric trauma patients admitted to a level 1 trauma centre in southwestern Ontario. METHODS All pediatric (age < 18 yr) trauma patients treated at the Childrens Hospital - London Health Sciences Centre (CH-LHSC) between 2002 and 2013 were included in this study. We compared patients undergoing surgical intervention with a nonsurgical group with respect to demographic characteristics and outcomes. Hospital-associated costs were calculated only for the surgical group. RESULTS Of 784 injured children, 258 (33%) required surgery, 40% of whom underwent orthopedic interventions. These patients were older and more severely injured, and they had longer lengths of stay than their nonsurgical counterparts. There was no difference in mortality between the groups. Seventy-four surgical patients required intervention within 4 hours of admission; 45% of them required neurosurgical intervention. The median cost of hospitalization was

The Future Liver Remnant in Patients Undergoing the Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy (ALPPS) Maintains the Immunological Components of a Healthy Organ.

27 571 for the surgical group. CONCLUSION One-third of pediatric trauma patients required surgical intervention, of whom one-third required intervention within 4 hours of arrival. Despite the associated costs, the surgical treatment of children was associated with comparable mortality to nonsurgical treatment of less severely injured patients. This study represents the most recent update to the per patient cost for surgically treated pediatric trauma patients in Ontario, Canada, and helps to highlight the multispecialty care needed for the management of injured children.

Laparoscopic removal of an occult foreign body causing penetrating abdominal trauma in a child

Background and Aims A short-interval, two-stage approach termed associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) increases the number of patients with extensive malignant disease of the liver and a small future liver remnant (FLR) that can undergo liver resection. While this approach results in accelerated liver hypertrophy of the FLR, it remains unknown whether this phenomenon is restricted to liver parenchymal cells. In the current study, we evaluated whether ALPPS alters the immunological composition of the deportalized lobe (DL) and the FLR. Methods In this prospective, single-center study, liver tissue from the DL and the FLR were collected intra-operatively from adult patients undergoing ALPPS for their liver metastases. The extent of hypertrophy of the FLR was determined by volumetric helical computed tomography. Flow cytometry and histological analyses were conducted on liver tissues to compare the frequency of several immune cell subsets, and the architecture of the liver parenchyma between both stages of ALPPS. Results A total of 12 patients completed the study. Histologically, we observed a patchy peri-portal infiltration of lymphocytes within the DL, and a significant widening of the liver cords within the FLR. Within the DL, there was a significantly higher proportion of B cells and CD4+ T cells as well innate-like lymphocytes, namely mucosa-associated invariant T (MAIT) cells and natural killer T (NKT) cells following ALPPS. In contrast, the frequency of all evaluated immune cell types remained relatively constant in the FLR. Conclusion Our results provide the first description of the immunological composition of the human liver following ALPPS. We show that following the ALPPS procedure, while the immune composition of the FLR remains relatively unchanged, there is a moderate increase in several immune cell populations in DL. Overall, our results support the continued utilization of the ALPPS procedure.

A robust scoring system to evaluate sepsis severity in an animal model

An otherwise healthy four-year-old boy was brought to the emergency department by his mother several hours after he had an unwitnessed fall at home. He had been playing with his friends, when they found him bleeding through his shirt. He had no relevant past medical or surgical history, medication