Cytotoxic T‐lymphocyte associated protein‐4 (CTLA‐4) and the Programmed Death Receptor 1 (PD‐1) are immune checkpoint molecules that are well‐established targets of antibody immunotherapies for the management of malignant melanoma. The monoclonal antibodies, Ipilimumab, Pembrolizumab, and Nivolumab, designed to interfere with T cell inhibitory signals to activate immune responses against tumors, were originally approved as monotherapy. Treatment with a combination of immune checkpoint inhibitors may improve outcomes compared to monotherapy in certain patient groups and these clinical benefits may be derived from unique immune mechanisms of action. However, treatment with checkpoint inhibitor combinations also present significant clinical challenges and increased rates of immune‐related adverse events. In this review, we discuss the potential mechanisms attributed to single and combined checkpoint inhibitor immunotherapies and clinical experience with their use.

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We report two cases of children who presented with acute abdomen due to gall bladder perforation and biliary peritonitis. Cholecystectomy with peritoneal lavage proved curative.

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Objective:To analyze immediate and long-term results of lipomeningomyelocele (LMM) repair in asymptomatic patients.Materials and Methods:Seventeen patients of LMM presented to Department of Paediatric Surgery over a period from 2011 to 2015 were evaluated preoperatively by magnetic resonance imaging of whole spine, and pre- and post-operative Ultrasound of kidney, ureter, bladder, and neurosonogram. Surgical procedure involved total excision of lipoma in 15 patients and near total excision in 2 patients. Division of filum terminale could be done in 15 out of 17 patients. Follow-up varied from 1 to 3.5 years (mean 1.9 years).Results:This study included 10 (58.8%) patients of lumbosacral LMM, 5 (29.4%) patients of sacral, and 2 (11.7%) patients of thoracolumbar LMM. About 13 (76.4%) patients were operated before 3 months of age, 2 (23.5%) patients were operated between 3 and 6 months, and two patients were operated between 6 and 11 months. None of the patients had bladder/bowel dysfunction preoperatively. Preoperative lower limb power was normal in all patients. Objective improvement in lower limb motor function was observed in 3 (17.6%) patients and three patients had decreased lower limb power. Two patients developed altered sensations and weakness of lower limb about 2.5-3 years after initial LMM repair. They needed repeat detethering of cord. Two patients had fecal pseudoincontinence, whereas one patient developed constipation. Bowel dysfunction was managed by rectal washouts, and oral laxatives were added if required. One (5.8%) patient of lumbosacral LMM and 1 (5.8%) patient of sacral LMM had urinary incontinence postoperatively. This was managed by clean intermittent catheterization with continuous overnight drainage. Conservative management of bladder and bowel dysfunction was effective in all patients till the last follow-up. Two patients developed hydrocephalus after LMM repair for which low-pressure ventriculoperitoneal shunt was inserted. Wound infection occurred in 1 (5.8%) patient, whereas 7 (41.1%) patients developed seroma in wound which responded to repeated aspirations under aseptic precautions.Conclusion:With total excision of lipoma and division of filum terminale satisfactory outcome for asymptomatic patients of LMM can be achieved. Authors recommend early surgery for LMM even in asymptomatic patients. Patients with residual lipoma and undivided filum terminale should be observed closely for the development of progressive neurological changes.