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.

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.

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.

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.

Zygomycosis Presenting as Acute Bilateral Renal Artery Thrombosis in a Healthy Young Male.

We present a case of acute renal artery thrombosis due to disseminated zygomycosis in a healthy young adult male.The diagnosis of renal artery occlusion was made on contrast-enhanced CT (CECT) and confirmation of etiology was made only on post mortem biopsy. We suggest that the presence of vascular thrombosis on CECT in a patient presenting with febrile illness should be regarded as an indicator of possible infection by angiotropic fungi, such as zygomycosis, which could help clinician to pursue histological diagnosis aggressively.

How common is hypothyroidism after external radiotherapy to neck in head and neck cancer patients?

PURPOSE: To identify the occurrence of clinical and subclinical hypothyroidism among head and neck cancer patients receiving radiation to the neck and to justify routine performing of thyroid function tests during follow-up. MATERIALS AND METHODS: This is a prospective nonrandomized study of 45 patients of head and neck cancer, receiving radiotherapy (RT). Thyroid stimulating hormone and T4 estimations were done at baseline and at 4 months and 9 months following RT. RESULTS: Of the 45 patients, 37(82.2 %) were males and eight (17.8 %) were females. All patients received radiation to the neck to a dose of >40Gy. 35.6% received concurrent chemotherapy. Two patients underwent prior neck dissection. Fourteen patients (31.1%) were found to have clinical hypothyroidism (P value of 0.01). Five (11.1%) patients were found to have subclinical hypothyroidism with a total 19 of 45 (42.2%) patients developing radiation-induced hypothyroidism. Nine of 14 patients with clinical hypothyroidism were in the age group of 51 to 60 years (P=0.0522). Five of 16 patients who received chemoradiation and nine of 29 who received RT alone developed clinical hypothyroidism. Above 40 Gy radiation dose was not a relevant risk factor for hypothyroidism. CONCLUSION: Hypothyroidism (clinical or subclinical) is an under-recognized morbidity of external radiation to the neck which is seen following a minimum dose of 40 Gy to neck. Recognizing hypothyroidism (clinical or subclinical) early and treating it prevents associated complications. Hence, thyroid function tests should be made routine during follow-up.

Magnitude of fatigue in cancer patients receiving radiotherapy and its short term effect on quality of life.

BACKGROUND: Fatigue is one of the most common, ongoing symptoms reported by patients undergoing radiotherapy and has profound effects on the quality of life. AIMS: This study attempts to identify the magnitude of fatigue and its implication on the quality of life during radiotherapy. METHODS AND MATERIALS: A prospective study was conducted from March 2004 to September 2005, on 90 patients with histologically proven cancer, receiving radiotherapy. Pretreatment and weekly assessment of fatigue and QOL was done during radiation treatment using Brief Fatigue Inventory Scale and EORTC QLQ C30 respectively and repeated one month after completion of radiotherapy. All the scores were measured in the 0 to 100 scale. STATISTICAL METHODS USED: Trimean, SPSS 11.0 and Sysstat 8.0 were used for statistical analysis. RESULTS: Fatigue was present in 87.8% of patients initially and increased gradually over the course of radiotherapy and peaked in the last week. However at follow up it was nearing the pretreatment level. There was significant reduction in the functional scores ( P < 0.001) of QOL (physical, role and emotional function), which returned to pretreatment level at follow up. In the seventh week impairment of cognitive function (P=0.059) was noted. Significant reduction of social function (P < 0.001) at second week and global health status (P < 0.001) at fifth week was noted while financial difficulty was seen from second week onwards. CONCLUSION: Fatigue is transiently increased by radiotherapy before reaching pretreatment level after few weeks of completion of radiotherapy. QOL is also affected by fatigue which follows the same pattern.

Positional variation of applicators during low dose rate intracavitary brachytherapy for cervical cancer: a prospective study.

PURPOSE: In order to know the effect of variation in position of applicators to the dose received by the tumor volume, critical organs such as rectum and bladder and the correlation of variation on the clinical outcome. MATERIAL AND METHODS: 36 patients with histologically proven cervical cancer, undergoing intracavitary brachytherapy (ICBT) from October 2005 to December 2006 were the subjects of the study. Two pairs of orthogonal X-ray films were taken: one prior to loading of sources and the other after removal of sources. These patients were followed up as per the RTOG criteria. RESULTS: The median duration of insertion was 25 hours with a median follow up period of 6.7 months. The translational variation of the applicator position for all patients was 3 mm and 1 mm (2 SD), respectively, in the patient's lateral and antero-posterior direction. The rotational variation was 3 and 4 degrees (2 SD) in the patient's transverse and sagittal planes. Detailed analysis of source movement showed following changes in median dose: point A: 14%, point B: 2%, point P: 1%, Rectum 1: 3.5%, Rectum 2: 4% and Bladder: 9.1%. The incidence of rectal toxicity was 6/36 (16.7%) and that of bladder was 1/36 (2.8%). When the variables were grouped to evaluate the relationship, our study showed statistically significant relationship between: R2 and rectal toxicity (p value: 0.002), point A and rectal toxicity (Pearson: 0.792), lateral displacement/anteroposterior displacement and rectal toxicity (p value: 0.012/0.003), beta angle and R2 (p value: 0.002). CONCLUSIONS: The geometric relationships between the ICBT applicators and the critical structures vary during the course of low dose rate brachytherapy. Source movement does result in significant dose alterations in terms of increased rate of complications, but its impact on cure rates needs to be studied in the future.

Efficacy of He-Ne Laser in the prevention and treatment of radiotherapy-induced oral mucositis in oral cancer patients.

OBJECTIVE: The objective of this study was to evaluate the efficacy of low-level lasers for the prevention and treatment of radiotherapy-induced oral mucositis in oral cancer patients. MATERIAL AND METHODS: Twenty-four hospitalized patients with oral cancer, scheduled to undergo radiotherapy at KMC, Manipal, were enrolled in the present study and assigned to laser (Group I)/control group (Group II). They were treated using He-Ne laser (lambda = 632.8nm, output = 10 mW and energy density = 1.8 J/cm(2)). Patients were subjected to treatment using laser scanner for 8 days and subsequently were treated using laser probe at 6 anatomic sites in the oral cavity for 5 minutes each. The patients were evaluated on each day of treatment for pain severity (NRS), functional impairment (FIS), and oral mucositis (RTOG) and were followed until the end of cancer treatment. Statistical analysis was done using SPSS version 10. RESULTS: Laser therapy applied prophylactically during radiotherapy can reduce the severity of oral mucositis, severity of pain, and functional impairment.

Nasopharyngeal angiofibroma treated with radiotherapy.

Nasopharyngeal angiofibroma is a rare, highly vascular, benign, locally aggressive tumor, affecting boys of adolescent age. The aggressiveness and high vascularity makes surgery and even a biopsy difficult in majority of cases. Although surgery is the treatment of choice in early cases, considerable debate exists regarding the treatment of advanced disease with intracranial extension. Radiotherapy provides a good response and also avoids surgery-associated morbidity. We are herewith reporting a case of nasopharyngeal angiofibroma who showed complete hemostasis and improvement in vision to radiotherapy.

Cosmetic and radiological outcome following the use of synthetic hydroxyapatite porous-dense bilayer burr-hole buttons.

BACKGROUND: Cranial neurosurgical procedures utilising burr-holes lead to development of cosmetically unacceptable puckered scars on the scalp over burr-hole sites. Ceramics, especially Hydroxyapatite (HA) are good bone substitutes owing to their biocompatibility and osteoconduction i.e. ability to lay down bone over the implant by fibrovascular invasion and later bone formation. The Sree Chitra Tirunal Institute for Medical Sciences and Technology in India has pioneered research in this direction and has developed a unique porous-dense bilayer HA burr-hole button. This study evaluates the safety, cosmetic effect, as well as the radiological outcome following implantation of these bilayer HA buttons. METHOD: Sixty-five HA buttons were implanted in 22 patients who underwent cranial neurosurgical procedures at the Sree Chitra Tirunal Institute for Medical Sciences and Technology. We assessed the cosmetic outcome (absence of puckered scar over burr hole sites, absence of allergic reactions or infections associated with the implant) as well as the radiological outcome with X-rays at specified intervals and looked for interference in the postoperative neurological imaging due to the implants. RESULTS: There were no adverse events related to the HA buttons in the form of allergic reactions or infections. The implants persisted as radio-dense opacities on skull X-rays of recipients for up to two years. It did not lead to artefacts on postoperative CT or MR imaging of the brain. In particular, the HA buttons could be subtracted on Digital Subtraction Angiography and did not obstruct visualisation of the cerebral vasculature. CONCLUSION: The bi-layer porous-dense HA buttons are useful in preventing cosmetic defects over burr-hole sites on the scalp after cranial neurosurgical procedures. It does not interfere with current radiological imaging methods in the postoperative phase.

A novel human fibroblast growth factor treats experimental intestinal inflammation.

BACKGROUND & AIMS: We recently identified a novel member of the human fibroblast growth factor (FGF) family of signaling molecules, designated FGF-20. In the present study, we examined the activity of this protein in 2 animal models of acute intestinal inflammation and in mechanistic studies in vitro. METHODS: In vivo experiments consisted of a murine dextran sulfate sodium (DSS) model of colitis and a rat indomethacin model of small intestinal ulceration/inflammation. Cell growth, restitution, gene expression (cyclooxygenase-2 [COX-2] and intestinal trefoil factor [ITF]), and prostaglandin E2 (PGE2) levels were examined in vitro. RESULTS: In the DSS-colitis model, prophylactic administration of FGF-20 significantly reduced the severity and extent of mucosal damage as indicated by a 55%-93% reduction in luminal blood loss, distal colonic edema, histologic inflammation, and epithelial cell loss relative to animals administered vehicle control. No toxicity was noted during administration of FGF-20 to normal controls. In addition, therapeutic administration of FGF-20 enhanced survival in this model. In the indomethacin-small bowel ulceration/inflammation model, administration of FGF-20 reduced small intestinal weight gain, necrosis, inflammation, and weight loss (36%-53% relative to vehicle control). In vitro studies demonstrated that FGF-20 stimulates growth, restitution, mRNA expression of COX-2 and ITF, and PGE2 levels in human intestinal epithelial cells and enhances the growth of human intestinal fibroblasts. CONCLUSIONS: FGF-20, having demonstrated therapeutic activity in 2 experimental models of intestinal inflammation, represents a promising new candidate for the treatment of human inflammatory bowel disease.

Angioarrestin: an antiangiogenic protein with tumor-inhibiting properties.

The angiopoietins comprise a family of proteins that have pro or antiangiogenic activities. Through a proprietary technology designed to identify transcripts of all expressed genes, we isolated a cDNA encoding an angiopoietin-related protein that we designate angioarrestin. The mRNA expression profile of angioarrestin was striking in that it was down-regulated in many tumor tissues when compared with adjacent nontumor tissue, suggesting a role for this protein in tumor inhibition. To test this hypothesis, we ectopically expressed angioarrestin in HT1080 tumor cells and measured pulmonary tumor nodule formation in nude mice. HT1080 cells expressing angioarrestin showed a marked reduction in the number and size of tumor nodules. In vitro, the recombinant protein was systematically tested in a number of endothelial cell assays and found to block critical processes involved in the angiogenic cascade, such as vascular endothelial growth factor/basic fibroblast growth factor-mediated endothelial cell proliferation, migration, tubular network formation, and adhesion to extracellular matrix proteins. These findings reveal a novel function for angioarrestin as an angiogenesis inhibitor and indicate that the molecule may be a potential cancer therapeutic.

Finite element analysis of a three unit fixed partial denture cast with nickel-chromium alloy.

A two dimensional mathematical model was generated, representing a three unit fixed-fixed partial denture and its supporting structures. Second premolar and second molar were used as abutments with first molar as pontic. A load of 1 kg was applied to the occlusal surface of the casting. Stresses and displacement developed at various regions were analyzed with STAAD III/ISDS program. Maximum stresses were developed in the pontic and connectors with distal connector experiencing the maximum stresses. Stresses transmitted to the dentin were comparatively lower and more of compressive in nature. The underying bone experienced moderate amount of both compressive and tensile stresses but the displacement in this tissue were minimal compared to the rest.

Exponential model for weight using 'RJ index'.

We screened a sample of 204 children between the age of 3 months to 5 years and 3 months were during a general health survey conducted by the Department of Community Medicine, Kasturba Medical College, Mangalore from March 1992 to December 1993 at Kumpala village under PHC Ullal about 10 kms from Mangalore City. We developed a new index RJ as RJ = Mid upper Arm Circumference x (Height)2 x 10(-4) and tested the correlation of RJ index and weight for age. We found the correlation coefficient (r = 0.8) to be very significant (P < 0.001). Thus we propose the model as Weight = A x exp (RJ x B). We found that the available data fit in this model. We hope that this study will be a new step in looking at arm circumference as a tool in estimating weight of pre-school children.