Post-transplantation cyclophosphamide (PTCy)-based HCT has been associated with an increased frequency of hemorrhagic cystitis (HC), dominantly associated with BK viruria. We prospectively evaluated ...the incidence of BK viruria and HC in 115 patients (median age 20 years, 2-65), malignant(87) and non-malignant(28), undergoing PTCy-based haploidentical HCT with CTLA4Ig (n=71) or without (n=44). Conditioning was predominantly myeloablative (74%). As prophylaxis for HC, continuous infusion of Mesna was used from 30 minutes prior to PTCy at 50% of the daily dose of Cy every 8 hourly for 72 hours. Development of HC before day+15 was termed as ‘early HC’ and later was referred to as ‘HC’.
The overall incidence of BK viruria was 65.7%. None with BK viruria < 104 copies/ml developed clinical symptoms (n=65). The incidence of BK viruria ≥ 104 copies/ml (‘high BK viruria’) was 7.1 % (n=8) and 75% developed HC. The incidence of HC was 5.4 % at a median of 30 days. Only 3.1% (events-2/66) of patients greater than 18 years of age had high BK viruria compared to 12.4% (events-6/49) in those who were younger than 18 years (p=0.05). The overall incidence of grade 2-4 acute GVHD was 16.9% (95%CI, 13.4-20.4). Overall BK viruria was higher in those with acute GVHD (92.1% vs 60.6 in those without acute GVHD, p=0.002, Figure 1A). Acute GVHD preceded the development of high BK viruria in 7 out of 8 patients with a median onset at 22 days (14-36 days). The incidence of high BK viruria in patients with acute GVHD was 36.8% (95% CI 25.7-37.9), compared to 1.1% (95% CI 0.1-2.2) in those without acute GVHD (p=0.0001). The incidence of HC in those with acute GVHD was likewise significantly higher (26.7%; 95%CI, 16.5-36.9 vs 1.1%; 95% CI 0.1-2.2, p=0.0001, Figure 1B).
Overall BK viruria was significantly lower in those receiving CTLA4Ig (54.1% vs 89.4% in those without CTLA4Ig, p=0.001, Figure 2A). The incidences of both high BK viruria (4.3% with vs 11.9% without CTLA4Ig, p=0.08) and HC (2.9% with vs 9.5% without CTLA4Ig p=0.09, Figure 2B) tended to be lower in those receiving CTLA4Ig-based protocols. A higher NRM was observed in those with BK viruria ≥ 104 copies/ml, related to GVHD and its complications (41.7% vs 12.6%, p=0.04).
In conclusion, our study demonstrates that extended infusion of Mesna, along with reduction in alloreactivity with the use of CTLA4Ig were probably responsible for a much lower incidence of BK viruria and resultant HC, than previously reported following PTCy-based haploidentical HCT.
Primary small cell carcinoma of urinary bladder is a rare but aggressive disease with poor prognosis and a high mortality rate. It accounts for less than 1 % of all the primary cancers seen in the ...urinary bladder. Diagnosis and management of this entity poses a challenge to the clinician due to the lack of a standardized protocol for its treatment. Herein we discuss primary small cell carcinoma of the urinary bladder in its entirety.
Transplantable organs from pediatric donors have been contributing significantly to donor pool worldwide. Pediatric donors are excellent resources that should be procured whenever available, and with ...the recent increase in deceased donations in India, more pediatric donors will be available for organ harvesting. We share a rare instance of multi-organ harvesting from a 16-month old brain dead donor and implanting both kidneys en-bloc in an adult male, while liver went to a 4-year old child. The report provides the surgical illustration of salient steps of transplanting both kidneys from pediatric donor into an adult, in an en-bloc manner.
Rapid detection of DNA/RNA pathogenic sequences or variants through point-of-care diagnostics is valuable for accelerated clinical prognosis, as witnessed during the recent COVID-19 outbreak. ...Traditional methods relying on qPCR or sequencing are tough to implement with limited resources, necessitating the development of accurate and robust alternative strategies. Here, we report FnCas9 Editor Linked Uniform Detection Assay (FELUDA) that utilizes a direct Cas9 based enzymatic readout for detecting nucleobase and nucleotide sequences without trans-cleavage of reporter molecules. We also demonstrate that FELUDA is 100% accurate in detecting single nucleotide variants (SNVs), including heterozygous carriers, and present a simple web-tool JATAYU to aid end-users. FELUDA is semi-quantitative, can adapt to multiple signal detection platforms, and deploy for versatile applications such as molecular diagnosis during infectious disease outbreaks like COVID-19. Employing a lateral flow readout, FELUDA shows 100% sensitivity and 97% specificity across all ranges of viral loads in clinical samples within 1hr. In combination with RT-RPA and a smartphone application True Outcome Predicted via Strip Evaluation (TOPSE), we present a prototype for FELUDA for CoV-2 detection closer to home.
•FnCas9 based detection of SARS-CoV2 in patient samples with high specificity/sensitivity.•Based on direct Cas9 RNP : substrate binding independent of trans-cleavage activity.•Can accurately identify variants and distinguish zygosity in nucleotide sequences.•Low cost paper strip based readout amenable to home testing.•Augmented by JATAYU for crRNA design and TOPSE for LFA readout analysis.
We report an extremely rare case of primary adenoid cystic carcinoma (ACC) trachea presenting as midline swelling neck and mimicking thyroid tumor. A 44-year-old female presented with painless ...midline swelling neck without any respiratory complaints, hoarseness of voice or dysphagia etc. Fine needle aspiration cytology (FNAC) from swelling reveal features of papillary carcinoma thyroid. Subsequently the operative findings, bronchoscopy and histological diagnosis of excised mass, along with review of FNAC, revealed features of ACC of trachea with exra tracheal extension anteriorly into the soft tissue neck, without actual invasion of the thyroid gland. The world literature on extension of an ACC arising in the laryngotracheal complex to thyroid or soft tissue neck and clinical manifestation as a thyroid nodule or mass is reviewed. The cytological differential diagnosis of ACC and CT findings are also briefly discussed.
We describe the curation, annotation methodology, and characteristics of the dataset used in an artificial intelligence challenge for detection and localization of COVID-19 on chest radiographs. The ...chest radiographs were annotated by an international group of radiologists into four mutually exclusive categories, including “typical,” “indeterminate,” and “atypical appearance” for COVID-19, or “negative for pneumonia,” adapted from previously published guidelines, and bounding boxes were placed on airspace opacities. This dataset and respective annotations are available to researchers for academic and noncommercial use.
PDF
