Valproate, risperidone, and paliperidone: A case of valproate-induced hyperammonemic encephalopathy.

Hyperammonemia is a well-known adverse effect of valproate that can progress to a potentially fatal condition known as valproate-induced hyperammonemic encephalopathy (VHE). VHE is more common when valproate is used in combination therapy with other antiepileptic medications. A growing number of case reports have pointed to a possible interaction with the antipsychotic risperidone leading to an increased risk of VHE. We present a case of VHE in which a 20-year-old male patient with bipolar affective disorder developed VHE when on concomitant valproate, risperidone, and paliperidone palmitate. On the seventh day of treatment with oral risperidone, oral divalproex sodium was added. Intramuscular paliperidone palmitate was initiated on day 13, and oral risperidone was discontinued after the second loading dose on day 16. The following day, the patient displayed worsening psychomotor retardation, swaying gait, drowsiness, and vomiting. The patient was found to have hyperammonemia and transferred to the emergency department for treatment of suspected VHE.

Minimally Invasive Treatment for Nonunion in an Unusual Pattern of Neuropathic Calcaneal Fracture: A Case Report.

Neuropathic arthropathy is the painless destruction of weight-bearing bones and joints that is caused by a neurosensory deficit. Minimally displaced neuropathic fractures may be managed non-operatively. However, larger displacements often require surgical fixation. Nonunion is a rare entity in calcaneal fractures, and its occurrence in a neuropathic setting is an even rarer scenario. An unusual clinical scenario means there is a paucity of literature to guide the optimum treatment. Here we describe a patient with neuropathic arthropathy due to meningomyelocele in childhood, presenting with neuropathic nonunion of the calcaneum, managed with a minimally invasive surgical approach using an arthroscopic burr and fixation with percutaneous screws. Despite the high risk of complications in the operative treatment of neuropathic fractures, good functional results and successful limb salvage may be achieved with minimally invasive techniques.

High risk of relapsed disease in patients with NK/T-cell chronic active Epstein-Barr virus disease outside of Asia.

Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is characterized by high levels of EBV predominantly in T and/or natural killer cells with lymphoproliferation, organ failure due to infiltration of tissues with virus-infected cells, hemophagocytic lymphohistiocytosis, and/or lymphoma. The disease is more common in Asia than in the United States and Europe. Although allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only curative therapy for CAEBV, its efficacy and the best treatment modality to reduce disease severity prior to HSCT is unknown. Here, we retrospectively assessed an international cohort of 57 patients outside of Asia. Treatment of the disease varied widely, although most patients ultimately proceeded to HSCT. Though patients undergoing HSCT had better survival than those who did not (55% vs 25%, P < .01), there was still a high rate of death in both groups. Mortality was largely not affected by age, ethnicity, cell-type involvement, or disease complications, but development of lymphoma showed a trend with increased mortality (56% vs 35%, P = .1). The overwhelming majority (75%) of patients who died after HSCT succumbed to relapsed disease. CAEBV remains challenging to treat when advanced disease is present. Outcomes would likely improve with better disease control strategies, earlier referral for HSCT, and close follow-up after HSCT including aggressive management of rising EBV DNA levels in the blood.

Preventable iatrogenic cause of foot-drop in knee injuries with literature review.

PURPOSE: Common peroneal nerve palsy is quite disabling and every effort should be made to prevent its injury during the treatment. METHODS: We retrospectively reviewed the prospectively collected data of 7 cases of tibial plateau fractures in association with proximal fibula fracture from January 2019 to September 2019 who presented to emergency room of our hospital. RESULTS: In addition to fibular neck fracture, the first case had type 6 tibial plateau displaced fracture and the second case had displaced acetabular fracture with instability of knee with tibial tuberosity avulsion. common peroneal nerve palsy developed following application of distal tibial skeletal traction in both the cases. Other 6 such cases remained neurologically intact as traction was not applied to them. CONCLUSION: Such iatrogenic complication could have been prevented if the injury pattern of "concomitant medial and lateral columns" of the proximal leg is kept in mind by the treating surgeon before applying skeletal traction.

Adrenocortical Function in Children With Brain Tumors and Pediatric Hematopoietic Cell Transplantation Recipients.

Adrenocortical insufficiency (AI) is a clinical condition defined by deficient production of glucocorticoids that can result in life-threatening complications. We examined the prevalence of AI in children with brain tumors and those undergoing hematopoietic cell transplantation. Adrenocorticotropic hormone stimulation (stim) testing was used for the assessment of adrenocortical function. On the basis of 155 stim tests in 117 patients, AI was diagnosed in 27.4% of patients with brain tumors and in 21% of hematopoietic cell transplantation recipients. A number of risk factors associated with AI were identified. Adrenocorticotropic hormone stim testing led to a definitive diagnosis of AI or recovery of adrenal function and unambiguous medical management.

Is Revision Bankart Repair with Remplissage a Viable Option for Failed Bankart Repair in Non-contact Sports Person Aiming to Return to Sports?

PURPOSE: Failure of a well-executed Bankart repair in non-contact athletes is difficult to predict and its management is a lesser investigated area with uncertain outcome in terms of return to sports (RTS). This study analyses effectiveness of revision Bankart repair with remplissage for failed Bankart repair in non-contact athletes, focusing on time and level of RTS. MATERIALS AND METHODS: Fifty-five consecutive non-contact athletes with evidence of instability after primary arthroscopic Bankart repair having glenoid loss < 25% and off-track Hill-Sachs lesion were included in the study according to algorithm mentioned. All cases underwent revision arthroscopic Bankart repair with remplissage and followed-up for 24 months. Rowe, UCLA, WOSI and Quick-DASH scores were recorded preoperative and at 24 months. RTS was allowed after unilateral seated shot-put test. RESULTS: Out of 55 cases, 6 were excluded because of poor tissue quality, 7 were lost to follow-up. Forty-two cases with a mean age of 28.2 ± 5.2 years were included. Mean duration between primary surgery and failure was 7.3 ± 1.4 months with a mean 1.9 redislocations. The mean Rowe, WOSI, UCLA, Quick-DASH scores improved from 37 to 89, 39.3 to 83.7%, 18.4 to 30.5, 45.3 to 18.7 at 24 months. Thirty-five cases could RTS in a mean time 15.4 ± 1.4 months. Out of seven cases who could not RTS, four had instability, one had pain and two voluntarily quit sports. CONCLUSION: Revision Bankart repair with remplissage is a feasible option for failed primary Bankart repair in non-contact athletes who have glenoid bone loss < 25% with off-track Hill-Sachs. LEVEL OF EVIDENCE: Level IV.

Tisagenlecleucel infusion in patients with relapsed/refractory ALL and concurrent serious infection.

BACKGROUND: Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy, has demonstrated durable efficacy and a manageable safety profile in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) in the ELIANA pivotal trial and real-world experience. Experience from investigator-led studies prior to ELIANA suggests that infections and inflammatory conditions may exacerbate the severity of cytokine release syndrome (CRS) associated with CAR-T cell therapy, leading to extreme caution and strong restrictions for on-study and commercial infusion of tisagenlecleucel in patients with active infection. CRS intervention with interleukin (IL)-6 blockade and/or steroid therapy was introduced late in the course during clinical trials due to concern for potential negative effect on efficacy and persistence. However, earlier CRS intervention is now viewed more favorably. Earlier intervention and consistency in management between providers may promote broader use of tisagenlecleucel, including potential curative therapy in patients who require remission and recovery of hematopoiesis for management of severe infection. MAIN BODY: Patient 1 was diagnosed with B-ALL at 23 years old. Fourteen days before tisagenlecleucel infusion, the patient developed fever and neutropenia and was diagnosed with invasive Mucorales infection and BK virus hemorrhagic cystitis. Aggressive measures were instituted to control infection and to manage prolonged cytopenias during CAR-T cell manufacturing. Adverse events, including CRS, were manageable despite elevated inflammatory markers and active infection. The patient attained remission and recovered hematopoiesis, and infections resolved. The patient remains in remission ≥1 year postinfusion.Patient 2 was diagnosed with pre-B-ALL at preschool age. She developed severe septic shock 3 days postinitiation of lymphodepleting chemotherapy. After receiving tisagenlecleucel, she experienced CRS with cardiac dysfunction and extensive lymphadenopathy leading to renovascular compromise. The patient attained remission and was discharged in good condition to her country of origin. She remained in remission but expired on day 208 postinfusion due to cardiac arrest of unclear etiology. CONCLUSIONS: Infusion was feasible, and toxicity related to tisagenlecleucel was manageable despite active infections and concurrent inflammation, allowing attainment of remission in otherwise refractory pediatric/young adult ALL. This may lead to consideration of tisagenlecleucel as a potential curative therapy in patients with managed active infections.

A multicenter report on the safety and efficacy of plerixafor based stem cell mobilization in children with malignant disorders.

BACKGROUND: Pleraxifor for peripheral blood stem cell (PBSC) mobilization in children with malignancies is often given following failure of standard mobilization (SM) rather than as a primary mobilizing agent. STUDY DESIGN AND METHODS: In this retrospective multicenter study, we report the safety of plerixafor-based PBSC mobilization in children with malignancies and compare outcomes between patients who received plerixafor upfront with SM (Group A) with those who received plerixafor following failure of SM (Group B). In the latter pleraxifor was given either following a low peripheral blood (PB) CD34 (<20 cells/cu.mm) (Group B1) or as a second collection process due to an unsuccessful yield (CD34 + < 2 × 106 /kg) (Group B2) following failed SM and first apheresis attempts. RESULTS: The study cohort (n = 47) with a median age of 8 (range 0.6-21) year, comprised 19 (40%) Group A and 28 (60%) Group B patients (B1 = 12 and B2 = 16). Pleraxifor mobilization was successful in 87.2% of patients, similar between Groups A and B (84.2% vs 89.2%) and resulted in a median 4-fold increase in PB CD34. Median number of apheresis attempts was 2 in Groups A and B1 but 4 in Group B2. In Group B2, median total CD34+ yield post-plerixafor was 9-fold higher than after SM (P = .0013). Mild to moderate transient adverse events affected 8.5% of patients. Among patients who proceeded to autologous transplant (n = 39), all but one engrafted. CONCLUSION: Plerixafor-based PBSC collection was safe and effective in our cohort and supports consideration as a primary mobilizing agent in children with malignancies.

Decreased motion with normal strength after Latarjet procedure has minimal impact on return to activity.

PURPOSE: The Latarjet procedure can affect the range of motion (ROM) and strength of the shoulder, which determine the time to return to the preinjury level of activity. This study prospectively assessed whether the Latarjet procedure leads to a decrease in range of motion and muscle strength, affecting the time to return to the previous level of activity. METHODS: Fifty-one consecutive patients who underwent the Latarjet procedure for recurrent dislocation of the shoulder were included prospectively. The ROM, strength, Walch-Duplay score, and Rowe score were measured every 3 months for 1 year and then every 6 months for 2 years. Radiological assessments were performed to confirm the graft location, union, and the humeral head position in abduction and external rotation (ER). RESULTS: Out of 51 patients, 49 completed all follow-ups. The median age was 27 years (17-45 years), and the dominant side was involved in 36 patients. The median number of dislocations was 11 (5-50). Twelve patients were sleep dislocators. There was a significant loss (p < 0.0001) of abduction, forward flexion (FF), ER, and internal rotation (IR) in the affected shoulder compared to the contralateral shoulder. Recovery plateaued at 12 months. There was near complete recovery of muscle strength after the Latarjet procedure, and the difference between the affected and contralateral shoulders was not significant (n.s.). The modified Rowe score was excellent in 44 (90%) patients, and the Walch-Duplay score was excellent in 43 patients (88%) at 24 months. Suboptimal results were associated with non-compliance with rehabilitation in two (4%) patients and neglected unreduced dislocation in one (2%) patient. The coracoid graft position was below the equator in 44 patients (90%). Forty-six patients (94%) could return to the previous level of activity. CONCLUSION: The Latarjet procedure results in a restricted ROM of the shoulder, but there is no loss of muscle strength. LEVEL OF EVIDENCE: III.

Giant Cell Tumor of the Ring Finger Distal Phalanx.

Giant cell tumor (GCT) is a benign but locally aggressive neoplasm generally located in the epiphysis and metaphysis of the long bones. Its occurrence in the bones of the hand is rare. Giant cell tumors occurring in the hand account for only 2% of all the GCTs reported. The epimetaphyseal region of short long bones is a common site of GCTs in the hand; however, a phalangeal GCT originating in the distal phalanx is extremely rare. We present the clinical, radiological and histopathological findings of a case of GCT of the distal phalanx of the left ring finger presenting with a fungating mass and treated with en bloc resection by disarticulation of the distal interphalangeal joint.

Determination of outcomes of complex upper end tibial fractures in squatting and cross leg sitting South Asian population.

INTRODUCTION: Treatment of complex upper end tibial fractures has always been a challenge to orthopaedic surgeons. Though the roentgenogram results are satisfactory, the clinical and functional outcomes especially in terms of squatting/cross-leg sitting after long term follow-up are little known. Hence, we have done this study with a primary aim to assess the clinico-radiological and functional outcomes after operative fixation (mostly by locking plates) in complex upper end tibial fractures and a secondary aim to analyze correlation between functional outcome scores/range of motion (ROM) and the ability to squat & sit cross-legged in post-operative period. MATERIALS AND METHODS: This prospective study included a total of 33 patients who were mainly treated with locking plates. In the follow-up, patients were assessed clinico-radiologically and outcome measurements were determined using the Tegner-Lysholm (T-L) Knee Score. Patients were categorized according to their ability to squat/sit cross-legged and a subgroup analysis was performed by comparing mean ROM and T-L score in each group. RESULTS: Majority of patients were in young and adult age group with a male to female ratio of 4.5:1. The average age was 42.39 ±14.64 years. Road traffic accident was the most common mode of injury. Average time interval between injury and surgery was 5.8±4.4 days. All the fractures united by 5-9 months. Mean ROM and T-L score at last follow-up were 120.94°±13.63° and 88.12±7.24 respectively. Average shortening, varus and valgus deformity were 0.43±0.09 cm, 2.12°±0.62° and 1.06°±0.45° respectively. 14 patients (42.42%) were able to squat and 15 (45.45%) were able to sit cross-legged postoperatively. Upon subgroup analysis, difference of mean ROM in those who could squat/sit cross-legged was found statistically significant (p≤0.05), however the difference in mean functional scores was not significant (p≥0.05). CONCLUSION: Complex upper tibial fractures are a difficult entity to deal with. Anatomical locking plates take care of the alignment, articular congruity as well as ligamentous balancing thus giving good mid-term outcomes after ORIF/MIPO. However, applicability of the present functional outcome scores in assessing squatting/cross leg sitting remains doubtful. More weightage needs to be given to these activities to evaluate the outcome in South Asian population.

Anemia in Children With Inflammatory Bowel Disease: A Position Paper by the IBD Committee of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition.

Anemia is one of the most common extraintestinal manifestations of inflammatory bowel disease (IBD). It can be asymptomatic or associated with nonspecific symptoms, such as irritability, headaches, fatigue, dizziness, and anorexia. In IBD patients, the etiology of anemia is often multifactorial. Various causes include iron deficiency, anemia of inflammation and chronic disease, vitamin deficiencies, hemolysis, or myelosuppressive effect of drugs. Anemia and iron deficiency in these patients may be underestimated because of their insidious onset, lack of standardized screening practices, and possibly underappreciation that treatment of anemia is also required when treating IBD. Practitioners may hesitate to use oral preparations because of their intolerance whereas intravenous preparations are underutilized because of fear of adverse events, availability, and cost. Several publications in recent years have documented the safety and comparative efficacy of various intravenous preparations. This article reviews management of anemia in children with IBD, including diagnosis, etiopathogenesis, evaluation of a patient, protocol to screen and monitor patients for early detection and response to therapy, treatment including parenteral iron therapy, and newer approaches in management of anemia of chronic disease. This report has been compiled by a group of pediatric gastroenterologists serving on the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) IBD committee, in collaboration with a pediatric hematologist, pharmacist, and a registered dietician who specializes in pediatric IBD (IBD Anemia Working Group), after an extensive review of the current literature. The purpose of this review is to raise awareness of under-diagnosis of anemia in children with IBD and make recommendations for screening, testing, and treatment in this population.

Unusual Occurrence of Tenosynovial Giant Cell Tumor in Hoffa's Fat Pad: A Potential Differential Diagnosis for Nontraumatic Knee Swelling and Pain.

A tenosynovial giant cell tumor (TGCT) is a benign lesion whose presence in Hoffa's pad has rarely been reported. This unique case report discusses a 33-year-old female patient who presented with swelling and pain in her left knee. Clinical and MRI findings were used to make the diagnosis, which was confirmed on a histopathological basis. The patient had a large tumor (5 × 3 × 3 cm) in Hoffa's fat pad, which was diagnosed as TGCT and managed with open resection due to its size. At follow-up after 20 months, the patient was asymptomatic, and there was no local recurrence of the tumor.

Neglected Two-Week-Old Unstable Fracture-Dislocation of the Hip in a 60 Years Old, Managed with Hip Preservation Surgery.

INTRODUCTION: Hip joint fracture-dislocations are rare injuries and usually result from high energy trauma. Femoral head fractures account for only 7-16% of all hip fracture-dislocations. There is always a controversy regarding optimal surgical treatment modality and approach for the treatment of Pipkin type IV fractures. In a 60 years old individual, various reports favor primary hip arthroplasty as compared to open reduction and internal fixation (ORIF). The posterior approach is preferred because it provides adequate exposure of the acetabular fracture and an opportunity for simultaneous repair of the femoral head and acetabular fractures. Another benefit is that anterior vascular supply to the femoral head and abductor function can be preserved. CASE REPORT: In this case report, we present a neglected 15 days old rare injury (Pipkin type IV femoral head fracture) in a 60 years old male patient that was given a trial of hip preservation surgery by ORIF through posterior (Kocher-Langenbeck) approach. CONCLUSION: A neglected case of Pipkin type IV injury with chances of avascular necrosis and arthritis can be given a trial of hip preservation surgery because in an Indian scenario sitting cross legged and squatting are indispensable activities of daily lifestyle and appropriate surgical technique, adequate exposure, anatomic reduction, and stable internal fixation of the fractures are critical to achieve satisfactory clinical results.

Ganglion cyst of Hoffa's fat pad of knee-a rare cause of knee pain and swelling-a case report and literature review.

Ganglion cysts around knee joint are uncommon and that from Hoffa's fat pad are even rarer. We present a case of 30 year old male patient with complaint of pain and swelling in left knee joint. Radiograph did not show any bony abnormality. MRI showed large tubulocystic lesion within Hoffa's fat pad which showed low signal intensity on T1-weighted images and high signal intensity on T2-STIR images. Open excision of the lesion was done. Histopathology of the specimen confirmed the diagnosis of the ganglion cyst. In follow-up, patient had asymptomatic left knee with full range of motion and did not show any sign of recurrence. Ganglion cysts from fat pad though very rare but should be considered in differential diagnosis to have an early diagnosis and management. Symptomatic ganglion cyst should be excised by open procedure or arthroscopically depending upon the size and extent of the lesion.

Related and unrelated donor transplantation for ß-thalassemia major: results of an international survey.

We studied 1110 patients with ß-thalassemia major aged ≤25 years who received transplants with grafts from HLA-matched related (n = 677; 61%), HLA-mismatched related (n = 78; 7%), HLA-matched unrelated (n = 252; 23%), and HLA-mismatched unrelated (n = 103; 9%) donors between 2000 and 2016. Ninety percent of transplants were performed in the last decade. Eight-five percent of patients received ≥20 transfusions and 88% were inadequately chelated. All patients received myeloablative-conditioning regimen. Overall and event-free survival were highest for patients aged ≤6 years and after HLA-matched related and HLA-matched unrelated donor transplantation. The 5-year probabilities of overall survival for patients aged ≤6 years, 7 to 15 years, and 16 to 25 years, adjusted for donor type and conditioning regimen were 90%, 84%, and 63%, respectively (P < .001). The corresponding probabilities for event-free survival were 86%, 80%, and 63% (P < .001). Overall and event-free survival did not differ between HLA-matched related and HLA-matched unrelated donor transplantation (89% vs 87% and 86% vs 82%, respectively). Corresponding probabilities after mismatched related and mismatched unrelated donor transplantation were 73% vs 83% and 70% vs 78%. In conclusion, if transplantation is considered as a treatment option it should be offered early (age ≤6 years). An HLA-matched unrelated donor is a suitable alternative if an HLA-matched relative is not available.

Outcomes of Hematopoietic Cell Transplantation in Patients with Germline SAMD9/SAMD9L Mutations.

Germline mutations in SAMD9 and SAMD9L genes cause MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) (OMIM: *610456) and ataxia-pancytopenia (OMIM: *611170) syndromes, respectively, and are associated with chromosome 7 deletions, myelodysplastic syndrome (MDS), and bone marrow failure. In this retrospective series, we report outcomes of allogeneic hematopoietic cell transplantation (HCT) in patients with hematologic disorders associated with SAMD9/SAMD9L mutations. Twelve patients underwent allogeneic HCT for MDS (n = 10), congenital amegakaryocytic thrombocytopenia (n = 1), and dyskeratosis congenita (n = 1). Exome sequencing revealed heterozygous mutations in SAMD9 (n = 6) or SAMD9L (n = 6) genes. Four SAMD9 patients had features of MIRAGE syndrome. Median age at HCT was 2.8 years (range, 1.2 to 12.8 years). Conditioning was myeloablative in 9 cases and reduced intensity in 3 cases. Syndrome-related comorbidities (diarrhea, infections, adrenal insufficiency, malnutrition, and electrolyte imbalance) were present in MIRAGE syndrome cases. One patient with a familial SAMD9L mutation, MDS, and morbid obesity failed to engraft and died of refractory acute myeloid leukemia. The other 11 patients achieved neutrophil engraftment. Acute post-transplant course was complicated by syndrome-related comorbidities in MIRAGE cases. A patient with SAMD9L-associated MDS died of diffuse alveolar hemorrhage. The other 10 patients had resolution of hematologic disorder and sustained peripheral blood donor chimerism. Ten of 12 patients were alive with a median follow-up of 3.1 years (range, 0.1 to 14.7 years). More data are needed to refine transplant approaches in SAMD9/SAMD9L patients with significant comorbidities and to develop guidelines for their long-term follow-up.