Safety and Efficacy of Very Early Conversion to Belatacept in Pediatric Kidney Transplantation with Transplant-Associated Thrombotic Microangiopathy: Case Study and Review of Literature.

The inhibition of co-stimulation during T-cell activation has been shown to provide effective immunosuppression in kidney transplantation (KT). Hence, the conversion from calcineurin inhibitor (CNI) to belatacept is emerging as a potential alternate maintenance immunosuppressive therapy in those with transplant-associated thrombotic microangiopathy (TA-TMA) or in the prevention of TA-TMA. We present a 17-year-old male who presented with biopsy-proven CNI-associated TA-TMA immediately post-KT. The administration of eculizumab led to the reversal of TMA. Tacrolimus was converted to belatacept with excellent efficacy and safety during a short-term follow-up of one year. Further larger controlled studies are required to demonstrate the efficacy of this approach in children who present with early-onset TMA post-KT.

Our Experience with Sinonasal Glomangiopericytoma in North India: A Case Series.

Glomangiopericytoma (GPC) is a rare benign sinonasal tumor originating from Zimmerman's Pericytes surrounding capillaries and accounting for less than 0.05% of all sinonasal tumors. Glomangiopericytoma has low malignant potential (5-10%) and is mostly diagnosed in the 6th or 7th decade of age with slight female preponderance. We presented here a case series of 5 patients with sinonasal GPC. This research was conducted at a tertiary healthcare centre in North India. In our case series, all the patients were evaluated and underwent endoscopic surgical resection. All patients underwent digital subtraction angiography (DSA) and preoperative embolization. The coblation technique used for haemostasis proved very effective and time-saving. All patients exhibited cytoplasmic SMA positivity (a marker of GPC) and CD34 negativity, while one patient exhibited a high Ki-67 index (> 10%), which is a predictor of aggressive tumor behavior. None of the patients showed any recurrence in follow-up. We recommend performing complete endoscopic surgical excision to prevent recurrence. The use of DSA, preoperative embolization, and intraoperative use of the coblation technique provides a cleaner surgical field and reduced operating time.

Efficacy and Safety of Eculizumab in Enteroaggregative E. coli Associated Hemolytic Uremic Syndrome.

BACKGROUND: Hemolytic uremic syndrome (HUS) may present atypically without the full triad of classical HUS. Eculizumab has been shown to be efficacious in complement-mediated atypical HUS and some cases of Shiga-toxin (ST) associated HUS. We report the utility of eculizumab in enteroaggregative E. coli (EAEC) associated HUS. CASE SUMMARY: A female toddler presented with hemolytic anemia, oliguric acute kidney injury (AKI) without thrombocytopenia, and peripheral schistocytes. The stool examination for ST was negative but positive for EAEC. She required several hemodialysis sessions and received one dosage of eculizumab with rapid reversal of AKI and hemolytic markers. A kidney biopsy revealed acute tubular injury and segmental glomerular basement membrane splitting. Genetic testing was negative for complement mutations or deficiencies. A follow-up six months later showed persistently normal renal function and hematological markers. CONCLUSION: The clinical and histological manifestations of non-ST-associated diarrheal HUS and the role of eculizumab in this condition warrant future larger studies.

Role of methylene blue dye in sentinel node biopsy in N0 oral cavity squamous cell carcinoma.

BACKGROUND: Presence of neck nodes in cases of head neck squamous cell cancers is an adverse prognostic factor. Elective neck dissection is traditionally recommended along with primary disease resection. Sentinel lymph node (SLN) is the first draining node. Sentinel lymph node biopsy (SNB) is a minimally invasive technique to identify occult nodal metastasis in early HNSCC. METHODS: The objective of this study is to determine the identification rate of SNB using methylene blue dye (MBD) in N0 neck of Oral Squamous cell carcinoma (OSCC) and estimating specificity, sensitivity, negative predictive value and positive predictive value of SNB with frozen section (FS) analysis and in comparison to post-operative histopathological examination (HPE). It is a cross-sectional study conducted at a tertiary care centre, Lucknow, India. 21 patients of N0 OSCC from January 2019 to May 2020, were included. All patients underwent peritumoral injection with MBD. Sentinel nodes were harvested and sent for FS. Depending on FS findings, appropriate neck dissection was performed. RESULTS: SLN was identified at level Ib and II in 19 patients (90.47%). The sensitivity, specificity, PPV and NPV in identifying SLN using MBD versus FS were 100.00%, 11.11%, 15.79% and 100.00% respectively. Whereas, SLN using MBD versus HPE specimens were 100.00%, 10.52%, 10.52% and 100.00% respectively. CONCLUSION: Despite having 100% sensitivity, MBD alone has poor specificity. With this poor discriminatory power, it is unlikely to be employed as a diagnostic test alone. It is recommended to rely on per-operative FS for taking decision as far as extent of neck dissection in N0 neck is concerned.

An Unusual Cause of Fever, Bilateral Ear Discharge, Lung Nodules, and Polyuria in a Young Male Post Coronavirus Disease 19.

We present a case of a young male with pyrexia of unknown origin, bilateral ear discharge, lung nodules and polyuria within four weeks of recovering from a moderate Coronavirus disease-19 infection. To the best of our knowledge, this is the first case of post- Coronavirus disease-19 Granulomatosis with Polyangiitis with overlapping large vessel vasculitis with a favorable outcome.

Synthetic cannabinoid-associated acute interstitial nephritis: An emerging cause of pediatric acute kidney injury?

Synthetic cannabinoid (SCB) usage among children is a rapidly emerging public health concern in the United States. Acute kidney injury (AKI) is an uncommon manifestation of SCB usage, with acute tubular necrosis (ATN) as the predominant histology. Here we describe a 16-year-old adolescent who sustained severe non-oliguric AKI in association with SCB usage. Emesis, right flank pain, and hypertension were the presenting clinical features. There was no uveitis, skin rash, joint pains, or eosinophilia. Urinalysis showed absence of proteinuria or hematuria. Urine toxicology was negative. Renal sonogram showed bilateral echogenic kidneys. Renal biopsy demonstrated severe acute interstitial nephritis (AIN), mild tubulitis, and absence of ATN. AIN responded with pulse steroid followed by oral steroid. Renal replacement therapy was not required. Although the exact pathophysiology of SCB-associated AIN is not known, immune response elicited by the renal tubulointerstitial cells against the antigens present in the SCB is the most likely mechanism. A high index of suspicion for SCB-induced AKI is necessary in adolescents who present with AKI of unclear etiology.

Severe hypertriglyceridemia in an infant on chronic hemodialysis.

Severe hyperlipidemia is a risk factor for cardiovascular disease. Children with chronic kidney disease and end stage renal disease are at risk for development of hyperlipidemia. In this report, we describe a 7-month-old male infant with Denys-Drash syndrome who was found to have a "milky-layer" floating on the deaerator of the hemodialysis machine. Investigations showed severe hypertriglyceridemia of >1000 mg/dl. The patient had been on chronic continuous manual peritoneal dialysis until 6 months of age and recently had been switched to hemodialysis. Management included lowering of caloric intake and addition of medium chain triglyceride with reduction of the serum triglyceride levels to 300-400 mg/dl. Close monitoring of serum lipids and timely intervention is important to prevent serious complications associated with dyslipidemia. Observation of the "milky layer" in the deaerator of the hemodialysis machine may be an interesting visual clue of underlying severe hypertriglyceridemia.

Hyperinsulinemic Hypoglycemia Due to PMM2 Mutation in Two Siblings with Autosomal Recessive Polycystic Kidney Disease.

Background: Hyperinsulinemic hypoglycemia (HH) is an important cause of persistent hypoglycemia in newborns and infants. Recently, PMM2 (phosphomannomutase 2) mutation has been associated with HH, especially in conjunction with polycystic kidney disease (PKD). PMM2 deficiency is one of the most common causes of congenital disorder of glycosylation (CDG). Renal involvement in PMM2-CDG manifests as cystic kidney disease, echogenic kidneys, nephrotic syndrome or mild proteinuria. Case Summary: Here, we describe a pair of siblings with HH associated with autosomal recessive polycystic kidney disease (ARPKD) and PMM2 mutation. Two siblings with ARPKD presented during infancy and early toddler years with severe hypoglycemia. Both had inappropriately elevated serum insulin, low ß-hydroxybutyrate, a need for a high glucose infusion rate, positive glycemic response to glucagon, positive diazoxide response and PMM2 mutation. Conclusions: Although this combination of HH and PKD was recently described in patients of European descent who also had PMM2 mutation, our report is unique given that these non-consanguineous siblings were not exclusively of European descent. PMM2 mutation leading to abnormal glycosylation and causing cystic kidneys and the alteration of insulin secretion is the most likely pathogenesis of this clinical spectrum.

Polyethylene Glycol 3350 Crystal Nephropathy in Association With Glomerular Mesangial Immunoglobin A Deposition.

Polyethylene glycol (PEG) 3350, an active ingredient of over-the-counter MiraLAX, is a commonly used laxative in children and is produced by polymerization of ethylene glycol (EG). Masked EG toxicity secondary to contamination of PEG 3350 could occur. We present a 7-year-old child with developmental delay who presented with altered mental status and acute kidney injury (AKI) following intake of generic PEG 3350 for few days prior to presentation. There was high anion gap metabolic acidosis, hypernatremia, elevated osmolar gap, lactic acidosis, and AKI. Urinalysis showed tubular proteinuria, microscopic hematuria, and calcium oxalate crystals. Prior urinalyses were normal without hematuria or proteinuria. Renal biopsy revealed evidence of mesangial dominant immunoglobulin A (IgA) and complement 3 (C3) deposits along with dense tubular deposition of calcium oxalate crystals. He subsequently developed worsening oliguric AKI and required hemodialysis (HD) for several sessions. The AKI resolved within 2 weeks and further HD was not required. Mental status improved in few days. Follow-up urinalyses showed resolution of microscopic hematuria and crystalluria. We hypothesized that the generic PEG 3350 most likely was contaminated with EG leading to the presentation. A high index of suspicion of contamination of PEG 3350 with EG is required in patients presenting with unexplained high anion gap metabolic acidosis, elevated osmolar gap, lactic acidosis, AKI, calcium oxalate crystalluria, and oxalate crystals on renal biopsy. Further studies are needed to determine whether there is an association between transient glomerular mesangial IgA deposition and crystal nephropathy.

Evaluation of Eustachian Tube Function in Cases of Chronic Otitis Media by Dynamic Slow Motion Videoendoscopy and Impedance Audiometry.

Eustachian tube (ET) dysfunction is known to be a cause for various middle ear diseases. Dynamic slow motion videoendoscopy (DSVE) and impedance audiometry (IA) can both be employed to evaluate ET dysfunction. To assess the role of DSVE and IA for diagnosing ET dysfunction in cases of middle ear disorders. It is a prospective case control study. 102 ears with chronic otitis media were taken as cases and 102 healthy ears as controls. IA and DSVE were performed to assess ET function in both the groups. Sensitivity/ specificity of both the diagnostic tests were evaluated in case and control groups. Out of 102 ET of case group exposed to both tests, 87 were found to have ET dysfunction by DSVE and 80 by IA. Among 102 ET of control group 78 were identified as normal by DSVE while 87 by IA. On applying chi square test in both these groups, the associations were significant. (p value < 0.0001). Patients with grade 2B or higher on DSVE endoscopy had abnormal IA findings, indicating that higher the grade on DSVE, higher the chance of abnormal IA. DSVE and IA are potentially useful tools in evaluation of cases of COM and which provide information regarding functional and pathological factors responsible for ET dysfunction.

Drug-Induced Lupus Secondary to Ethosuximide in Association with Acute Tubulointerstitial Nephritis and Nephrotic Syndrome.

Background. Drug-induced lupus (DIL) is an autoimmune phenomenon where the patient develops lupus-like symptoms after exposure to a long-term medication. Case Summary. Here we describe a 10-year-old female with absence seizures who developed a lupus-like syndrome after being on ethosuximide for three months. She presented with nephrotic syndrome (NS) and acute kidney injury. Four weeks prior to presentation, she had been prescribed a seven-day course of oral amoxicillin for submental swelling after dental extraction. Investigations showed high titer of antinuclear antibody (ANA) and anti-double stranded DNA, elevated serum IgE level, and positive Coombs' test, along with positive anti-histone antibodies. Renal biopsy showed features of acute tubulointerstitial nephritis (TIN) and partial podocyte foot process effacement without evidence of lupus nephritis. The patient had an excellent response to the steroid therapy with remission within two weeks. The patient remained in remission for two months as evaluated during the most recent follow-up; the autoimmune antibodies and immunoglobulin E trended down. Ethosuximide has been reported to cause DIL, however its possible association with TIN has not been reported. Although amoxicillin could have caused the TIN and NS in this patient, a possible novel association of ethosuximide with this nephrotic-nephritic presentation (NNP) cannot be ruled out. Conclusions. A renal histology is important to determine the accurate etiology of NNP in patients with DIL. Further studies are necessary to determine any possible causal effect of ethosuximide with NNP.

Role of Octreotide in Conservative Management of Chyle Leak Post Neck Dissection in Cases of Head Neck Cancer: A Retrospective Analysis.

Chyle leak is a dreadful complication in patients undergoing neck dissections. Octreotide has been used in the management of chyle leak post neck dissections in head and neck cancer patients. Currently there is no consensus and practice guidelines on the same. (1) To study the role of octreotide in early cessation of post neck dissection chyle leak. (2) To study incidence of intra-operative and post-operative CL, its relation to the extent of nodal disease and neck dissection, prior radiotherapy. Retrospective analysis of 16 patients out of 529 neck dissection over a period of 03 years between Jan 2016 and Dec 2019 who developed post-operative chyle leak. All patients who had post-operative chyle leak were administered octreotide. Time taken for chyle leak to stop was primary outcome. Secondary outcomes were duration of hospitalization post-operatively, incidence of intra-operative and post-operative chyle leak, its relation to the extent of nodal disease, prior radiotherapy and type of neck dissection. 59 of 529 neck dissections (11.15%) were noted to have intra-operative chyle leak. 16 of 529 neck dissections (3.02%) developed post-operative chyle leak. On applying chi square test, prior multimodality and N plus neck were found to be significant risk factors in developing postoperative chyle leak. Considering only RT versus no RT in prior multimodality treated group, the difference was insignificant. Onset of chyle leak varied from 1 to 5 post-op day (mean 2.68 days). 15 (93.75%) patients responded to octreotide. Chyle leak resolved between 3 and 10 days (mean 5.18 days) and octreotide was given for 5-12 days (mean-7.18 days). Overall duration of hospitalization ranged from 09 to 18 days (mean 12.18 days). 01 patient (6.25%) had to be re-explored due to high volume leak despite using octreotide. Adverse effects of octreotide were minimal and tolerable. Octreotide is effective in reducing the duration of chyle leak, hospital stay and need for surgical intervention. It may be considered as suitable adjunct to conservative measures in the management for post-operative chyle leak.

Subcutaneous Emphysema: An Outlandish Hint to an Impacted Tracheobronchial Foreign Body.

Tracheobronchial foreign body aspiration amongst paediatric population is one of the commonest challenges faced by the otolaryngologist. Subcutaneous emphysema is an uncommon presentation of this condition and the ENT specialist needs to have a high index of clinical suspicion of a foreign body. We report a case of 2-year old child presented with subcutaneous emphysema later diagnosed with a foreign body in the bronchus.

Outcome of Universal Neonatal Hearing Screening Programme at a Tertiary Care Centre: A Prospective Study.

Hearing is an important sense organ for human beings essential for speech, language and overall development. Universal neonatal hearing screening programmes are mandatory in many developed countries. In India out of 1000 neonates approximately 5-6 infants are diagnosed with hearing impairment but still universal neonatal hearing screening programme is in its infancy. To screen all neonates delivered at our centre in three years, with secondary objective of determining the significance of risk factors with neonatal hearing loss and to provide appropriate intervention following the detection of a permanent hearing impairment. It is a non-randomised prospective cohort study conducted at a tertiary care centre to screen all neonates born between Jan 2017 and Dec 2019 with 2 stage protocol using distortion product otoacoustic emission and auditory brainstem response. The study population was also divided into two groups, ''at risk'' and ''no risk'' groups to determine the significance of risk factors on neonatal hearing loss. Total 2676 neonates were screened, OAE referral rate was 1.53%. There was a 94.12% follow up. The incidence of hearing impairment was found to be 7 per 1000(In the "no risk" group, 2.9 per 1000 and in the "at risk" group, 41.38 per 1000). Statistically, a significant difference was found in the incidence of hearing impairment between the two groups (p < 0.05, chi-square Test). Hospital based universal hearing screening of new born before discharge is feasible at a tertiary care centre. A high incidence of 0.7% congenital hearing impairment warrants universal newborn hearing screening programme. Considering the limitations and infrastructure in India, we should at least employ screening for all high risk neonates.

Collapsing Focal Segmental Glomerulosclerosis and Acute Kidney Injury Associated With Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: A Case Report.

Chimeric antigen receptor T (CAR-T) cell treatment is a rapidly emerging therapy for relapsed/refractory hematologic malignancies. Although cytokine release syndrome is a common complication, a concomitant development of biopsy-proven collapsing glomerulopathy and acute kidney injury (AKI) has not been described with CAR-T cell therapy. We report a man in his early 20s with relapsed/refractory pre-B-cell acute lymphoblastic leukemia and compensated liver cirrhosis who received 3 courses of CD19-directed CAR-T cells. After the third CAR-T cell therapy, he developed severe cytokine release syndrome accompanied by new onset of nephrotic syndrome and AKI. Cytokine release syndrome was treated with tocilizumab. His kidney biopsy showed collapsing glomerulopathy, glomerulitis, and interstitial nephritis along with complete podocyte foot-process effacement. Due to disease progression, he was subsequently treated with bispecific CD19-directed CD3 T-cell engager antibody, blinatumomab, during which he developed another episode of cytokine release syndrome with exacerbation of nephrotic-range proteinuria and his AKI progressed to stage 3 chronic kidney disease. Excess cytokine-induced podocyte and renal tubulointerstitial injury and/or "on-target off-tumor" direct renal cell toxicity are the probable mechanisms of kidney injury. Further such reports will increase our understanding of the pathophysiologic basis of kidney injury with CAR-T treatment.

Delayed Onset Minimal Change Disease as a Manifestation of Lupus Podocytopathy.

Lupus podocytopathy (LP) is an uncommon manifestation of systemic lupus erythematosus (SLE) and is not included in the classification of lupus nephritis. The diagnosis of LP is confirmed by the presence of diffuse foot process effacement in the absence of capillary wall deposits with or without mesangial immune deposits in a patient with SLE. Here we describe a 13-year-old female who presented with nephrotic syndrome (NS) seven years after the diagnosis of SLE. The renal function had been stable for seven years since the SLE diagnosis, as manifested by the normal serum creatinine, serum albumin and absence of proteinuria. Renal biopsy showed evidence of minimal change disease without immune complex deposits or features of membranous nephropathy. Renal function was normal. The patient had an excellent response to steroid therapy with remission within two weeks. The patient remained in remission five months later during the most recent follow-up. This report highlights the importance of renal histology to determine the accurate etiology of NS in patients with SLE. Circulating factors, including cytokines such as interleukin 13, may play a role in the pathophysiology of LP and needs to be studied further in future larger studies.

An Unusual Occurrence of Erythrocytosis in a Child with Nephrotic Syndrome and Advanced Chronic Kidney Disease.

Background: Anemia is common in patients with nephrotic syndrome (NS) for various reasons. Furthermore, anemia can occur in patients with chronic kidney disease (CKD) predominantly owing to inappropriately low erythropoietin (EPO) production relative to the degree of anemia. However, erythrocytosis is uncommon in patients with NS and advanced CKD who are not treated with exogenous erythropoietin stimulating agents, and when present, will necessitate exploration of the other etiologies. Case summary: Here, we describe an 8-year-old girl with erythrocytosis in association with NS and advanced CKD. The patient was found to have erythrocytosis during the evaluation for hypertensive urgency. She also had nephrotic range proteinuria without edema. Serum hemoglobin and hematocrit were 17 gm/dL and 51%, respectively, despite hydration. Renal function test showed an estimated glomerular filtration rate of 30 mL/min/1.73 m2. There was mild iron deficiency anemia with serum iron saturation of 18%. Serum EPO level was normal. Urine EPO was not measured. Renal biopsy showed evidence of focal segmental glomerulosclerosis. Genetic testing for NS showed mutations in podocyte genes: NUP93, INF2, KANK1, and ACTN4. Gene sequence analysis of genes associated with erythrocytosis showed no variants in any of these genes. She required chronic dialysis ten months later and, subsequently, a renal transplantation 14 months after the initial presentation. Conclusion: Since the serum EPO level was normal, an increased sensitivity to EPO is the most probable mechanism of erythrocytosis. The unusual association of erythrocytosis in patients with NS and advanced CKD needs to be studied further in larger studies.

Concomitant nephrotic syndrome and tubulointerstitial nephritis in a child with Epstein-Barr virus mononucleosis.

Acute kidney injury (AKI) and nephrotic syndrome (NS) are uncommon manifestations of Epstein-Barr virus (EBV) mononucleosis. We report a 4-year-old boy with Infectious mononucleosis (IM) who presented with dialysis-requiring AKI and NS. Renal biopsy showed severe acute tubular necrosis, mild chronic interstitial nephritis and focal podocyte foot processes effacement. EBV early RNA was not detected in the renal tissue. However, immunophenotyping of peripheral lymphocytes showed increased cytotoxic T cell activity and increased memory B cells. Treatment with steroid led to rapid resolution of NS within 3 weeks. Renal function stabilised. EBV viral capsid antigen (VCA) IgM remained elevated until 4 months before starting to decline when VCA IgG and nuclear antigen started appearing. B lymphocytes are the predominant target cells in EBV infection and additionally may also act as antigen presenting cells to T lymphocytes, thereby eliciting the strong immune response and leading to podocyte and tubulointerstitial injury.

Olfactory and Gustatory Dysfunction in COVID-19 Patients from Northern India: A Cross-Sectional Observational Study.

Olfactory dysfunction (OD) and gustatory dysfunction (GD) has been reported as one of the presenting symptoms amongst COVID-19 patients. However the literature available is disjunct on this aspect. This study is conducted to identify the prevalence of olfactory and/or gustatory dysfunction in patients with coronavirus disease in Northern part of India. It's a cross-sectional observation study, conducted over 387 COVID-19 positive patients, at ENT dept of tertiary care hospital. A retrospective survey was conducted using a pre designed questionnaire and details of Olfactory and Gustatory dysfunction was collected. The patient's demographic details, disease course and recovery time for olfactory (OD) and/or gustatory dysfunctions (GD) were collected. A total of 387 patients with COVID-19 completed the study. 228 (58.9%) patients suffered from influenza like illness (ILI) (fever, sore throat, dry cough, malaise, and myalgia). There was significant positive association seen between with ILI and OD and / or GD. 167/387 (43.15%) patients reported OD, and 153/387 (39.53%) reported GD. 43.71% and 50.3% patients had mild OD & GD respectively. Recovery rates for both OD and GD are high and almost similar, with 161 (96.4%) and 148 (96.73%) patients had complete recovery of smell and taste. Maximum recovery was noticed between 4 and 6 weeks. COVID-19 patients with habits have significantly high probability of developing OD &/or GD. There is a significant correlation between OD and GD and there is high probability that patients who reported to have OD will also have GD or vice versa. Prevalence of OD and GD in Indian population may not be as high as mentioned in western literature, however, both are frequent and early symptoms of COVID-19. Recent onset of these should be considered as red flag symptoms for COVID-19.