Performance of amide proton transfer imaging to differentiate true progression from therapy-related changes in gliomas and metastases.

OBJECTIVES: Differentiating true progression or recurrence (TP/TR) from therapy-related changes (TRC) is complex in brain tumours. Amide proton transfer-weighted (APT) imaging is a chemical exchange saturation transfer (CEST) MRI technique that may improve diagnostic accuracy during radiological follow-up. This systematic review and meta-analysis elucidated the level of evidence and details of state-of-the-art imaging for APT-CEST in glioma and brain metastasis surveillance. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for original articles about glioma and metastasis patients who received APT-CEST imaging for suspected TP/TR within 2 years after (chemo)radiotherapy completion. Modified Quality Assessment of Diagnostic Accuracy Studies-2 criteria were applied. A meta-analysis was performed to pool results and to compare subgroups. RESULTS: Fifteen studies were included for a narrative synthesis, twelve of which (500 patients) were deemed sufficiently homogeneous for a meta-analysis. Magnetisation transfer ratio asymmetry performed well in gliomas (sensitivity 0.88 [0.82-0.92], specificity 0.84 [0.72-0.91]) but not in metastases (sensitivity 0.64 [0.38-0.84], specificity 0.56 [0.33-0.77]). APT-CEST combined with conventional/advanced MRI rendered 0.92 [0.86-0.96] and 0.88 [0.72-0.95] in gliomas. Tumour type, TR prevalence, sex, and acquisition protocol were sources of significant inter-study heterogeneity in sensitivity (I2 = 62.25%; p < 0.01) and specificity (I2 = 66.31%; p < 0.001). CONCLUSION: A growing body of literature suggests that APT-CEST is a promising technique for improving the discrimination of TP/TR from TRC in gliomas, with limited data on metastases. CLINICAL RELEVANCE STATEMENT: This meta-analysis identified a utility for APT-CEST imaging regarding the non-invasive discrimination of brain tumour progression from therapy-related changes, providing a critical evaluation of sequence parameters and cut-off values, which can be used to improve response assessment and patient outcome. KEY POINTS: Therapy-related changes mimicking progression complicate brain tumour treatment. Amide proton imaging improves the non-invasive discrimination of glioma progression from therapy-related changes. Magnetisation transfer ratio asymmetry measurement seems not to have added value in brain metastases.

Prevalence of Augmented Renal Clearance (ARC), Utility of Augmented Renal Clearance Scoring System (ARC score) and Augmented Renal Clearance in Trauma Intensive Care Scoring System (ARCTIC score) in Predicting ARC in the Intensive Care Unit: Proactive Study.

Objectives: We aimed to study the prevalence of augmented renal clearance (ARC) and validate the utility of ARC and ARCTIC scores. We also aimed to assess the correlation and agreement between estimated GFR (eGFR-EPI) and 8-hour measured creatinine clearance (8 hr-mCLcr). Study design and methodology: This was a prospective, observational study done in the mixed medical-surgical intensive care unit (ICU) and 90 patients were recruited. 8 hr-mCLcr, ARC, and ARCTIC scores and eGFR-EPI were calculated for all patients. ARC was said to be present if 8 hr-mCLcr was ≥ 130 mL/min. Results: Four patients were excluded from the analysis. The prevalence of ARC was 31.4%. The sensitivity, specificity, and positive and negative predictive values of ARC and ARCTIC scores were found to be 55.6, 84.7, 62.5, 80.6, and 85.2, 67.8, 54.8, and 90.9 respectively. AUROC for ARC and ARCTIC scores were 0.802 and 0.765 respectively. A strong positive correlation and poor agreement were observed between eGFR-EPI and 8 hr-mCLcr. Conclusion: The prevalence of ARC was significant and the ARCTIC score showed good potential as a screening tool to predict ARC. Lowering the cut-off of ARC score to ≥5 improved its utility in predicting ARC. Despite its poor agreement with 8 hr-mCLcr, eGFR-EPI with a cut-off ≥114 mL/min showed utility in predicting ARC. How to cite this article: Kanna G, Patodia S, Annigeri RA, Ramakrishnan N, Venkataraman R. Prevalence of Augmented Renal Clearance (ARC), Utility of Augmented Renal Clearance Scoring System (ARC score) and Augmented Renal Clearance in Trauma Intensive Care Scoring System (ARCTIC score) in Predicting ARC in the Intensive Care Unit: Proactive Study. Indian J Crit Care Med 2023;27(6):433-443.

Double Anti-neutrophil Cytoplasmic Antibody and Anti-glomerular Basement Membrane Antibody-positive Crescentic Glomerulonephritis, Following SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects kidneys mainly in the form of acute kidney injury but rarely can cause glomerular disease. On a very rare occasion, SARS-CoV-2 infection can be associated with anti-neutrophil cytoplasmic antigen (ANCA)-associated vasculitis and anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). We report a case of a 59-year-old man who presented with progressive renal failure 8 weeks after contracting the viral infection, which progressed slowly to severe renal dysfunction. Renal biopsy showed crescentic glomerulonephritis (CrGN) accompanied by interrupted linear IgG deposits along the glomerular basement membrane (GBM) on immunofluorescence (IF) staining with associated mild acute tubular injury. The serology for anti-myeloperoxidase (MPO), as well as anti-GBM antibodies, was positive. He was treated with steroid and pulse intravenous cyclophosphamide, following which there was a significant improvement in the renal function and serological resolution of both the antibodies 6 months post-treatment. To the best of our knowledge, this is the first reported case of "double-antibody" positive CrGN following SARS-CoV-2 infection.

Bilateral renal mucormycosis following COVID-19 infection: A therapeutic challenge.

India witnessed an epidemic of mucormycosis during the second wave of the COVID-19 pandemic. Renal mucormycosis has been reported rarely, mostly from India, but only 2 cases have been reported following COVID-19 infection to date. We report a case of mucormycosis predominantly affecting kidneys in a young and previously healthy male following COVID-19 pneumonia, for which he had received corticosteroid, remdesivir, and tocilizumab. He presented with hematuria, progressive oliguria, and severe acute kidney injury (AKI) requiring dialysis. The diagnosis was made on kidney biopsy and contrast-enhanced CT (CECT) showed segmental and subsegmental renal artery pseudoaneurysms with distal occlusion of both kidneys. He underwent bilateral nephrectomy and received high-dose amphotericin (AMB) and posaconazole. He developed cardiac arrhythmia and pulmonary edema attributed to AMB-related cardiotoxicity after a cumulative ABM dose of 2,450 mg. This is the first case report describing the survival of a patient with bilateral renal mucormycosis following COVID-19 infection. Our case report highlights the importance of considering mucormycosis in a patient with post-COVID-19 AKI to make an early diagnosis and aggressive management comprising of surgical debridement and high-dose AMB to improve survival.

Concurrent Gitelman Syndrome-like Tubulopathy and Grave's Disease.

Gitelman syndrome (GS) is a rare autosomal recessive disorder characterized by the loss of function mutation of the solute carrier family-12 member-3 (SLC12A3) gene, encoding for sodium-chloride cotransporter of the distal convolute tubule. GS is characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, and hypocalciuria. GS-like syndrome has been described rarely. Hyperthyroidism due to Grave's disease (GD) is characterized by the presence of autoantibodies to thyrotropin receptors. Concurrent occurrence of GS and GD is rarely reported, that too exclusively from far-east Asian populations. We describe a case of a 45-year-old man who presented with severe muscle weakness; the evaluation showed volume depletion, hypokalemia, hypomagnesemia, renal potassium and magnesium wasting, metabolic alkalosis, and hypocalciuria. He was also detected to have GD at the time of presentation. Genetic evaluation revealed a mutation in transient receptor potential melastatin 4 (TRPM4) gene. The clinical significance of this mutation in our patient remains unclear.

ISCCM Guidelines on Acute Kidney Injury and Renal Replacement Therapy.

Acute kidney injury (AKI) is a complex syndrome with a high incidence and considerable morbidity in critically ill patients. Renal replacement therapy (RRT) remains the mainstay of treatment for AKI. There are at present multiple disparities in uniform definition, diagnosis, and prevention of AKI and timing of initiation, mode, optimal dose, and discontinuation of RRT that need to be addressed. The Indian Society of Critical Care Medicine (ISCCM) AKI and RRT guidelines aim to address the clinical issues pertaining to AKI and practices to be followed for RRT, which will aid the clinicians in their day-to-day management of ICU patients with AKI. How to cite this article: Mishra RC, Sodhi K, Prakash KC, Tyagi N, Chanchalani G, Annigeri RA, et al. ISCCM Guidelines on Acute Kidney Injury and Renal Replacement Therapy. Indian J Crit Care Med 2022;26(S2):S13-S42.

Renal Replacement Therapy in Adult Intensive Care Unit: An ISCCM Expert Panel Practice Recommendation.

Acute kidney injury (AKI) contributes significantly to morbidity and mortality in ICU patients. The cause of AKI may be multifactorial and the management strategies focus primarily on the prevention of AKI along with optimization of hemodynamics. However, those who do not respond to medical management may require renal replacement therapy (RRT). The various options include intermittent and continuous therapies. Continuous therapy is preferred in hemodynamically unstable patients requiring moderate to high dose vasoactive drugs. A multidisciplinary approach is advocated in the management of critically ill patients with multi-organ dysfunction in ICU. However, an intensivist is a primary physician involved in life-saving interventions and key decisions. This RRT practice recommendation has been made after appropriate discussion with intensivists and nephrologists representing diversified critical care practices in Indian ICUs. The basic aim of this document is to optimize renal replacement practices (initiation and management) with the help of trained intensivists in the management of AKI patients effectively and promptly. The recommendations represent opinions and practice patterns and are not based solely on evidence or a systematic literature review. However, various existing guidelines and literature have been reviewed to support the recommendations. A trained intensivist must be involved in the management of AKI patients in ICU at all levels of care, including identifying a patient requiring RRT, writing a prescription and its modification as per the patient's metabolic need, and discontinuation of therapy on renal recovery. Nevertheless, the involvement of the nephrology team in AKI management is paramount. Appropriate documentation is strongly recommended not only to ensure quality assurance but also to help future research as well. How to cite this article: Mishra RC, Sinha S, Govil D, Chatterjee R, Gupta V, Singhal V, et al. Renal Replacement Therapy in Adult Intensive Care Unit: An ISCCM Expert Panel Practice Recommendation. Indian J Crit Care Med 2022;26(S2):S3-S6.

Pathways to care in children- perspectives from a child guidance clinic in South India.

PURPOSE: In India the pathways to care in children with mental health problems remain relatively unexplored. Investigating the factors that drive the pathway will help determine interventions and also draft policies for a streamlined Child and adolescent mental health service. METHOD: Children who attended the Child Guidance Clinic sampled by WHO Pathways Encounter questionnaire. Statistical tests applied to find key influencers like gatekeepers, intermediate points of care, symptoms initiating referral, duration of untreated illness, time to arrive at appropriate care and primary diagnosis. RESULTS: The most common diagnostic category was externalizing disorder 51(37.5 %). The gatekeepers identified were 111(81.6 %) Parents/Relatives/Guardians and teachers 25 (18.3 %). Academic concerns identified by teachers took a mean of 72 months (30.271) to arrive at appropriate care versus 50.4 months (23.18) when identified by Parents/Relatives/Guardians group. Significant delays were observed with Neurodevelopmental disorders arriving to care with delays up to 130.2 (70.11) months (p < 0.001) and having 64.2 (33.7) months (p < 0.001) duration of untreated illness. Externalizing disorders took a duration of 94.08 (54.17) months (p < 0.001) to arrive to appropriate care and had 54.2 (36.33) months (p < 0.001) duration of untreated illness. Teachers took longer time in detecting the indicators and this caused duration of untreated illness of 73.44 (36.05) months (p < 0.001) and a delay of 128.08 (71.23) months (p < 0.001) to arrive to appropriate care. CONCLUSIONS: The pathways to care in children are characterized by long duration of untreated illness and undue time to care. Gatekeepers like teachers and intermediary points of care were associated with inadvertent delays along the pathway.

Renal Microsporidiosis in Pediatric Bone Marrow Transplant Recipients: A Case Series.

Microsporidiosis is a rare, but emerging opportunistic infection in solid organ transplant and stem cell transplant recipients. Renal involvement in microsporidiosis is very rarely seen in these recipients. We describe two cases of pediatric renal microsporidiosis, diagnosed on renal biopsies, following bone marrow transplantation presenting as severe acute kidney injury. The first patient died, whereas the second survived due to early diagnosis based on high index of suspicion and prompt treatment with Albendazole. We believe these are the first such reported cases of renal microsporidiosis in pediatric bone marrow transplant recipients.

Electrically injected 1.64µm emitting In0.65Ga0.35As 3-QW laser diodes grown on mismatched substrates by MOVPE.

We report the characteristics of the strained In0.65Ga0.35As triple quantum well (QW) diode lasers grown by metalorganic vapor phase epitaxy (MOVPE) on lattice-mismatched substrates such as GaAs or Si, by utilizing InP metamorphic buffer layers (MBLs) in conjunction with InAs nanostructure-based dislocation filters. As the lattice-mismatch between the substrate and InP MBL increases, higher threshold current densities and lower slope efficiencies were observed, together with higher temperature sensitivities for the threshold current and slope efficiency. Structural analysis performed by both high-resolution X-ray diffraction (HR-XRD) and transmission electron microscopy indicates graded and/or rougher QW interfaces within the active region grown on the mismatched substrate, which accounts for the observed devices characteristics.

Membranous nephropathy due to chronic mercury poisoning from traditional Indian medicines: report of five cases.

Mercury contained in traditional medicines can cause chronic poisoning, which can cause membranous nephropathy (MN). We report five cases of nephrotic syndrome caused by MN with evidence of chronic mercury poisoning due to consumption of traditional Indian medicines such as Siddha and Ayurveda, which to our knowledge are the first such reports. All patients were seronegative for antibodies against phospholipase A2 receptor (PLA2R). Two patients, who had severe nephrotic syndrome, had received Siddha medicine for prolonged period and oral chelation with dimercaptopropane-1-sulfonic acid was successful in eliminating mercury, resulting in an improvement in nephrotic state in these patients. We suggest that mercury poisoning should be entertained in patients with anti-PLA2R antibody-negative MN, with history of consumption of traditional Indian medicines.

Axillary Artery Injury with Intact Radial Pulse following Fracture-Dislocation of Shoulder: A Case Report.

The occurrence of axillary artery injury following proximal humerus fracture dislocation in elderly patient with low velocity fall is uncommon. The patient could have diverse clinical presentations in spite of intact peripheral pulses. We report the case of an 85-year-old lady who presented to our emergency department with greater tuberosity fracture of the humerus with dislocation of the right shoulder. After closed manipulative reduction of the dislocation, it was observed that the patient had brachial plexus palsy with intact radial pulse. An expanding swelling and bruise around the shoulder was noted and a steady drop in haemoglobin level. CT angiogram revealed avulsion of the posterior circumflex artery which was then treated successfully with stenting.

Axillary Artery Injury with Intact Radial Pulse following Fracture-Dislocation of Shoulder: A Case Report

@#The occurrence of axillary artery injury following proximal humerus fracture dislocation in elderly patient with low velocity fall is uncommon. The patient could have diverse clinical presentations in spite of intact peripheral pulses. We report the case of an 85-year-old lady who presented to our emergency department with greater tuberosity fracture of the humerus with dislocation of the right shoulder. After closed manipulative reduction of the dislocation, it was observed that the patient had brachial plexus palsy with intact radial pulse. An expanding swelling and bruise around the shoulder was noted and a steady drop in haemoglobin level. CT angiogram revealed avulsion of the posterior circumflex artery which was then treated successfully with stenting.

Closed Intramedullary Locking Nailing for Metacarpal Fractures: A Retrospective Study of Sixty-Six Fractures.

Introduction: Metacarpal fractures are frequent injuries in the young male working population and the majority are treated non-operatively. There is a growing trend to surgically treat these fractures, with the aim of reducing the deformity and shortening the rehabilitation period. The aim of this retrospective case series is to report on our experience and clinical outcomes of using percutaneous flexible locking nails for the management of displaced metacarpal fractures. This study is a retrospective review of 66 fractures that were managed at our centre over a 7-year period. Materials and Methods: Records of 60 patients were retrospectively reviewed. Indications for surgery were a displaced metacarpal shaft or neck fracture with associated rotational deformity, or multiple metacarpal fractures. The fracture was reduced by closed manipulation, and a flexible pre-bent locked intramedullary nail (1.6mm diameter) was inserted through a percutaneous dorsal antegrade approach, facilitated by a specially designed pre-fabricated awl. The implant was removed at union. Patients were followed-up in clinic until the fracture had united. Results: The mean union time was seven weeks (range 2 to 22 weeks) and there were nine (14%) delayed unions (>3 months) and no non-unions. The nail had migrated in three cases (5%) and caused skin impingement in two cases (3%). There was one infected case (2%). Rotational clinical deformity was evident for two (3%) cases. Conclusion: The use of a minimally-invasive locked intramedullary nailing for unstable metacarpal fractures has a significantly low complication rate, with predictable union times and good functional outcomes.

Atraumatic Insufficiency Fractures of the Tarsal Bones - An Unusual Cause of Recurrent Heel Pain in a Patient with Rheumatoid Arthritis: A Case Report.

The incidence of insufficiency fractures is approximately 1% in rheumatoid arthritis patients. The predisposing factors are chronic inflammation, skeletal deformities, biomechanical stresses and osteoporosis. The medications used in the treatment of rheumatoid arthritis such as Glucocorticosteroids and Methotrexate also contribute to the development of osteoporosis and insufficiency fractures. A 68-year old lady who was suffering from rheumatoid arthritis and on long term Methotrexate was seen in the outpatient clinic with recurrent episodes of heel pain. Examination revealed diffuse tenderness around the heel with full range of ankle movements but painful limitation of subtalar joint movements. Radiographic examination of the ankle showed a highly suspicious fracture of the calcaneus and confirmed on MRI as an insufficiency fracture. She was treated successfully with oral bisphosphonates and moon boot brace. She presented after two years with recurrent episodes of heel pain. The plain radiograph and MRI scan confirmed an insufficiency fracture of the talus. She was treated non-operatively with intravenous Zolendronic acid and bracing. In chronic rheumatoid arthritis patients especially on Methotrexate and Glucocorticoids a high index of suspicion of insufficiency fractures should be considered if they present with bone pain. MRI scan is the investigation of choice and is conclusive.

Atraumatic Insufficiency Fractures of the Tarsal Bones-An Unusual Cause of Recurrent Heel Pain in a Patient with Rheumatoid Arthritis: A Case Report

@#The incidence of insufficiency fractures is approximately 1% in rheumatoid arthritis patients. The predisposing factors are chronic inflammation, skeletal deformities, biomechanical stresses and osteoporosis. The medications used in the treatment of rheumatoid arthritis such as Glucocorticosteroids and Methotrexate also contribute to the development of osteoporosis and insufficiency fractures. A 68-year old lady who was suffering from rheumatoid arthritis and on long term Methotrexate was seen in the outpatient clinic with recurrent episodes of heel pain. Examination revealed diffuse tenderness around the heel with full range of ankle movements but painful limitation of subtalar joint movements. Radiographic examination of the ankle showed a highly suspicious fracture of the calcaneus and confirmed on MRI as an insufficiency fracture. She was treated successfully with oral bisphosphonates and moon boot brace. She presented after two years with recurrent episodes of heel pain. The plain radiograph and MRI scan confirmed an insufficiency fracture of the talus. She was treated nonoperatively with intravenous Zolendronic acid and bracing. In chronic rheumatoid arthritis patients especially on Methotrexate and Glucocorticoids a high index of suspicion of insufficiency fractures should be considered if they present with bone pain. MRI scan is the investigation of choice and is conclusive.

Closed Intramedullary Locking Nailing for Metacarpal Fractures: A Retrospective Study of Sixty-six Fractures

@#Introduction:Metacarpal fractures are frequent injuries in the young male working population and the majority are treated non-operatively. There is a growing trend to surgically treat these fractures, with the aim of reducing the deformity and shortening the rehabilitation period. The aim of this retrospective case series is to report on our experience and clinical outcomes of using percutaneous flexible locking nails for the management of displaced metacarpal fractures. This study is a retrospective review of 66 fractures that were managed at our centre over a 7-year period. Materials and Methods: Records of 60 patients were retrospectively reviewed. Indications for surgery were a displaced metacarpal shaft or neck fracture with associated rotational deformity, or multiple metacarpal fractures. The fracture was reduced by closed manipulation, and a flexible pre-bent locked intramedullary nail (1.6mm diameter) was inserted through a percutaneous dorsal antegrade approach, facilitated by a specially designed pre-fabricated awl. The implant was removed at union. Patients were followed-up in clinic until the fracture had united. Results:The mean union time was seven weeks (range 2 to 22 weeks) and there were nine (14%) delayed unions (>3 months) and no non-unions. The nail had migrated in three cases (5%) and caused skin impingement in two cases (3%). There was one infected case (2%). Rotational clinical deformity was evident for two (3%) cases. Conclusion: The use of a minimally-invasive locked intramedullary nailing for unstable metacarpal fractures has a significantly low complication rate, with predictable union times and good functional outcomes.

Accelerated Radiation Therapy Using Weekend Boost with Concurrent Cisplatin in Head and Neck Squamous Cell Cancers: An Indian Institutional Experience.

PURPOSE: The purpose of the study was to evaluate the feasibility and efficacy of an accelerated radiotherapy schedule using weekend boost in terms of tumor response, compliance, and acute toxicities for head and neck squamous cell carcinoma, and to report long-term clinical outcomes. MATERIALS AND METHODS: Twenty-six patients with stages III-IV head and neck squamous cell carcinoma receiving radical chemoradiotherapy were accrued prospectively into the study. External beam radiation therapy to a total dose of 66-70 Gy in 33-35 fractions, 1.8-2.0 Gy per fraction along with concurrent weekly cisplatin was planned. Radiation regimen included delivery of six fractions per week, with boost field delivered as the sixth fraction on the weekend. The compliance, tumor response, and toxicities were recorded. Survival curves were estimated using the Kaplan-Meier method. RESULTS: Twenty-one of 26 patients (81%) completed treatment as planned and five patients died during the course of treatment. Sixteen patients (62%) completed treatment in less than 44 days and, at the end of 3 months' follow-up, 18 patients (69%) showed complete response and two patients (8%) showed partial response. The 2- and 5-year actuarial disease-free survival were 90% and 65%, respectively, and 2- and 5-year actuarial overall survival were 60% and 38%, respectively. CONCLUSION: Accelerated fractionation using weekend boost, along with concurrent weekly concurrent cisplatin, is an effective and promising approach with favorable impact on initial tumor response, comparable results, and acceptable toxicities.

Postoperative pain relief and functional outcome following total knee arthroplasty - a prospective comparative audit of three analgesic regimes.

Pain control plays a key role in joint-replacement -surgery. As a surgeon the challenge is to reduce pain to an acceptable level in the post-operative period. The aim of the study was to assess the efficacy of bolus -local anaesthesia, infusion in to the surgical site and nerve blocks with femoral nerve catheter and its functional outcome. A prospective audit of 114 patients undergoing total knee arthroplasty were carried out.The patients were divided in to three groups : Group 1 (n = 27) received a bolus injection of 20 ml 0.25% levobupivacaine + 10 ml 0.25%bupivacaine + adrenaline + 30 ml saline. Group 2 (n = 39) received a bolus injection as on group 1 with 240 ml 0.25% bupivacaine infusion and 5 ml/hour using a Pain Buster pump. Group 3 (n = 48) received 30 ml 0.125% levobupivacaine to femoral (3-in-1) block with 30 ml 0.25% levobupivacaine to -sciatic nerve and introduction of a femoral nerve catheter. All patients were prescribed paracetamol 1 g QDS, Oxycontin 20 mg BD and Ibuprofen post -operatively. Pain was assessed with a Visual Analog Scale (VAS). The incidence of PONV was measured by PONY intensity score. The mean post-op VAS score for Group 3 was 4. The demand of oxynorm and NSAID were minimal in Group 3. The mean in patient stay for Group 3 was 3.1 days. The PONV intensity score was > 50 for 9 (36%) in Group 1, 15 (40%) in Group 2 and 9 (20%) in Group 3. There was loss of 20-30 degrees of flexion movements in Group 3 in the first 4 to 6 days post-op. Our study demonstrated that Regime 3 with the use of nerve blocks and femoral nerve catheter has given the maximum pain relief and good functional outcome following total knee replacement.