An Analysis of the VELNEZ Nasal Pack's Acceptability and Safety for Use During Nasal Surgery: A Prospective Study.

The primary function of nasal packs is to modulate the bleeding, prevent adhesions and obstruction, with least discomfort to the subjects without risking secondary infection. However, both packing and removal of the pack is an unpleasant experience, with the latter being extremely painful. Therefore the need of the hour is a dressing which prioritizes subject comfort without compromising other desired nasal pack properties. Twenty subjects were enrolled in this interventional, open label study. The subjects had 10 hospital visits, starting from baseline (Visit 1) to postoperative day 28 (Visit 10), at regular intervals. The proportion of the population with postoperative pain alleviation and bleeding control failure (within 10 min) were the main objectives. Within 10 min of VELNEZ administration, all 20 participants got their bleeding under control. With VELNEZ, the painful nasal pack removal method was totally avoided because it was biodegradable. No moderate/severe pain, infection and adhesions were reported in any of the subjects, but few subjects reported moderate obstruction until Visit 3 (Discharge Day). In the present study, for participants undergoing nasal surgery, VELNEZ proved to be a secure and reliable nasal pack. Trial Registration: CTRI/2021/09/036437, prospectively registered.

The multimodality cell segmentation challenge: toward universal solutions.

Cell segmentation is a critical step for quantitative single-cell analysis in microscopy images. Existing cell segmentation methods are often tailored to specific modalities or require manual interventions to specify hyper-parameters in different experimental settings. Here, we present a multimodality cell segmentation benchmark, comprising more than 1,500 labeled images derived from more than 50 diverse biological experiments. The top participants developed a Transformer-based deep-learning algorithm that not only exceeds existing methods but can also be applied to diverse microscopy images across imaging platforms and tissue types without manual parameter adjustments. This benchmark and the improved algorithm offer promising avenues for more accurate and versatile cell analysis in microscopy imaging.

Comprehensive germline profiling of patients with breast cancer: initial experience from a Familial Cancer Clinic.

Introduction: Breast cancer is the most common cancer among Indian females. There is limited data on germline profiling of breast cancer patients from India. Objective: The objective of the current study was to analyse the frequency and spectrum of germline variant profiles and clinicopathological characteristics of breast cancer patients referred to our Familial Cancer Clinic (FCC). Materials and methods: It is a single-centre audit of patients with a confirmed diagnosis of breast carcinoma referred to our FCC from January 2017 to 2020. All patients underwent pretest counselling. Genetic testing was done by multigene panel testing by next-generation sequencing along with reflex multiplication ligation-dependent probe amplification for BRCA1 and 2. The variants were classified based on American College of Medical Genetics guidelines. Demographic and clinicopathological details were extracted from the case record files. Results: One hundred and fifty-five patients were referred to the FCC and underwent pretest counselling. A total of 99 (63.9%) patients underwent genetic testing. Among them, 62 patients (62/99 = 62.6%) had a germline variant. A pathogenic/likely pathogenic (P/LP) germline variant was identified in 41 (41.4%) of the patients who underwent testing. Additional variants of unknown significance (VUS) were identified in seven patients who also carried a P/LP variant. VUS alone was detected in 21 patients (21/99 = 21.2%). Among the P/LP pathogenic variants (PV), BRCA 1 PV were seen in 27 patients (65.8%), BRCA 2 variants in 7 patients (17.1%), ATM variants in 3 patients (7.3%) and RAD51, TP53, CHEK2 and HMMR in 1 patient each. Variants were significantly more common in patients with a family history (FH) of malignancy than those without FH (58.5% versus 29.5%; p = 0.013). Age and triple-negative histology were not found to be significantly associated with the occurrence of P/LP PVs. Conclusion: We report a 41% P/LP variant rate in our selected cohort of breast cancer patients, with variants in BRCA constituting 83% and non-BRCA gene variants constituting 17%.

Assessment of Correlation Between Disease Specific Quality of Life and Endoscopy Score After 1 Month and 6 Months of Endoscopic Sinus Surgery (ESS) in Patients with Chronic Rhinosinusitis: A Prospective Study.

Rhinosinusitis is a prevalent condition worldwide affecting the developed and the third world countries alike. SNOT-22 is a validated disease-specific questionnaire designed to use in Chronic Rhino Sinusitis (CRS), which means to quantify patients perception of their disease burden. SNOT 22 questionnaire can chart patients nasal as well as psychological symptoms arising due to CRS and very well become marker of individual symptomatic improvement. To study the correlation between disease specific quality of life and endoscopy score after 1 month and 6 months of Endoscopic Sinus Surgery in patients with Chronic Rhinosinusitis. In the present study, ESS surgery showed improvement in Endoscopy score and all the symptoms assessed by SNOT-22. The total percentage of improvement in the SNOT-22 score was 70% after 1 month and 89% at the end of 6 months. We conclude that after the procedure of ESS not only endoscopic evaluation is necessary but also psychological and symptomatic assessment by SNOT 22 is very necessary as nasal and psychological factors were equally decisive for the seeking of the treatment (pharmacological/surgical) by the patient.

Balloon Sinuplasty: Our Experience.

Chronic rhino sinusitis (CRS) is a common disease. Maxillary sinusitis not cured by the medicines was addressed by the open surgical procedure namely Caldwell Luc operation. Thereafter introduction of nasal endoscopes in 1970's led to the minimally invasive surgery FESS which preserved the physiology of the nose and sinuses. In the year 2002 balloon sinuplasty was introduced in the western world and subsequently in India. Due to various logistics it was not performed and reintroduced in the year 2015 in India. It can be termed as micro minimally invasive surgery wherein anatomy as well as physiology of the nose and sinuses were preserved in cases of medically non responsive mild to moderate sinusitis. 20 cases were selected for exclusive balloon sinuplasty of maxillary sinus. Balloon sinuplasty is a relatively new procedure which can be termed as micro minimally invasive surgery addressing the CRS without the traditional forms for surgery like incision, cutting or microdebriding. The principle is causing microfractures by inflating the sinus opening and thus facilitating the drainage of the sinus contents. No immediate or late post operative complications were noted. Sinus patency 6 months later was present in 90% of the cases. Balloon sinuplasty is an excellent procedure for medically nonresponsive CRS without polyposis. The success rate is spectacular matching the FESS with almost no immediate post operative and late complication. The recurrence rate of sinusitis is low. We conclude that balloon sinuplasty is a micro invasive procedure which saves operating time, time of hospital stay of the patient and delivers excellent result with almost no complications. We hope it could be incorporated as a routine surgery for mild to moderate sinusitis not responding to medicines.

Immunophenotypic characterization of leukemic stem cells in acute myeloid leukemia using single tube 10-colour panel by multiparametric flow cytometry: Deciphering the spectrum, complexity and immunophenotypic heterogeneity.

INTRODUCTION: Despite extensive research, comprehensive characterization of leukaemic stem cells (LSC) and information on their immunophenotypic differences from normal haematopoietic stem cells (HSC) is lacking. Herein, we attempted to unravel the immunophenotypic (IPT) characteristics and heterogeneity of LSC using multiparametric flow cytometry (MFC) and single-cell sequencing. MATERIALS AND METHODS: Bone marrow aspirate samples from patients with acute myeloid leukaemia (AML) were evaluated using MFC at diagnostic and post induction time points using a single tube-10-colour-panel containing LSC-associated antibodies CD123, CD45RA, CD44, CD33 and COMPOSITE (CLL-1, TIM-3, CD25, CD11b, CD22, CD7, CD56) with backbone markers that is, CD45, CD34, CD38, CD117, sCD3. Single-cell sequencing of the whole transcriptome was also done in a bone marrow sample. RESULTS: LSCs and HSCs were identified in 225/255 (88.2%) and 183/255 (71.6%) samples, respectively. Significantly higher expression was noted for COMPOSITE, CD45RA, CD123, CD33, and CD44 in LSCs than HSCs (p < 0.0001). On comparing the LSC specific antigen expressions between CD34+ (n = 184) and CD34- LSCs (n = 41), no difference was observed between the groups. More than one sub-population of LSC was demonstrated in 4.4% of cases, which further revealed high concordance between MFC and single cell transcriptomic analysis in one of the cases displaying three LSC subpopulations by both methods. CONCLUSION: A single tube-10-colour MFC panel is proposed as an easy and reproducible tool to identify and discriminate LSCs from HSCs. LSCs display both inter- and intra-sample heterogeneity in terms of antigen expressions, which opens the facets for single cell molecular analysis to elucidate the role of subpopulations of LSCs in AML progression.

Analytical Appraisal of Hematogones in B-ALL MRD Assessment Using Multidimensional Dot-Plots by Multiparametric Flow Cytometry: A Critical Review and Update.

The spectrum of benign B-cell precursors, known as hematogones (HGs), shows a significant morphological and immunophenotypic overlap with their malignant counterpart i.e. B-lymphoid blasts (BLBs). This results in a diagnostic dilemma in assessment of cases wherein there is a physiological preponderance of HGs and also poses a significant challenge in measurable residual disease assessment in B-cell acute lymphoblastic leukaemia. Consequently, expression patterns of various immunophenotypic markers are considered the most important tool in identification and delineation of HGs from BLBs. However, certain aspects of B-cell compartment evaluation by flow cytometric immunophenotyping and its relevance in clinical scenarios is yet to be defined precisely. This review summarizes current flowcytometric data on HGs and its discrimination from BLBs based on thorough review of literature and evaluation of in-house data. Furthermore, it focuses on the utility of an additional analytical tool i.e., radar plot for a comprehensive representation of various subsets of the B-cell compartment and their differentiation from BLBs. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01696-5.

Cluster analysis and visualisation of electronic health records data to identify undiagnosed patients with rare genetic diseases.

Rare genetic diseases affect 5-8% of the population but are often undiagnosed or misdiagnosed. Electronic health records (EHR) contain large amounts of data, which provide opportunities for analysing and mining. Data mining, in the form of cluster analysis and visualisation, was performed on a database containing deidentified health records of 1.28 million patients across 3 major hospitals in Singapore, in a bid to improve the diagnostic process for patients who are living with an undiagnosed rare disease, specifically focusing on Fabry Disease and Familial Hypercholesterolaemia (FH). On a baseline of 4 patients, we identified 2 additional patients with potential diagnosis of Fabry disease, suggesting a potential 50% increase in diagnosis. Similarly, we identified > 12,000 individuals who fulfil the clinical and laboratory criteria for FH but had not been diagnosed previously. This proof-of-concept study showed that it is possible to perform mining on EHR data albeit with some challenges and limitations.

Myeloblastic meningeal neoplasm: an unusual natural history.

Myeloid sarcoma is a very rare extramedullary malignant tumour, most often associated with acute myeloid leukaemia. We report the case of a man in his early 20s who presented with chronic headache, raised intracranial pressure and progressive vision loss of 2 years duration with no systemic manifestations. He had a history of myeloid sarcoma of the left thigh 15 years ago, treated with external beam radiotherapy and in complete remission for more than 13 years. However, the progressive blindness remained unexplained for 2 years, and he was eventually diagnosed with isolated meningeal relapse without marrow or systemic involvement. Imaging revealed subarachnoid haemorrhage, diffuse leptomeningeal enhancement and involvement of lower dorsal cord and conus, and cerebrospinal fluid cytology showed myeloid blasts. He was managed with intrathecal chemotherapy and craniospinal irradiation, after which he had mild improvement in vision.

Porous SnO2 nanosheets for room temperature ammonia sensing in extreme humidity.

Gas sensors based on tin dioxide (SnO2) for the detection of ammonia (NH3) have become commercially available for environmental monitoring due to their reactive qualities when exposed to different gaseous pollutants. Nevertheless, their implementation in the medical field has been hindered by certain inherent drawbacks, such as needing to operate at high temperatures, lack of selectivity, unreliable operation under high-humidity conditions, and a lower detection limit. To counter these issues, this study created 2D nanosheets of SnO2 through an optimized solvothermal method. It was found that tuning the precursor solution's pH to either neutral or 14 led to aggregated or distributed, uniform-size nanosheets with a higher crystallinity, respectively. Remarkably, the SnO2 nanosheet sensor (SNS-14) displayed a much lower response to water molecules and specific reactivity to ammonia even when subjected to reducing and oxidizing agents at 25 °C due to the micropores and chemisorbed oxygen on the nanosheets. Furthermore, the SNS-14 was seen to have the highest sensitivity to ammonia at 100 ppm, with rapid response (8 s) and recovery times (55 s) even at a high relative humidity of 70%. Its theoretical detection limit was recorded to be 64 ppt, better than any of the earlier SnO2-based chemiresistive sensors. Its exceptional sensing abilities were credited to its optimal crystallinity, specific surface area, defects, chemisorbed oxygen, and porous structure. NH3-TPD measurements and computational simulations were employed to understand the ammonia interaction with atomistic details on the SnO2 nanosheet surface. A real time breath sensing experiment was simulated to test the efficacy of the sensor. Reaching this advancement is an achievement in bypassing past boundaries of SnO2-centered sensors, making it feasible to detect ammonia with enhanced precision, discrimination, dependability, and velocity for probable usages in medical diagnostics and ecological surveillance.

Enhancing the Efficiency of the Individual Case Safety Report (ICSR) Quality and Compliance through Automation.

BACKGROUND: Over the past few years, major inspection findings have been identified in the "management of adverse reactions" that may be due to increasing workload in pharmaceutical organizations impacting the correctness of information in individual case safety reports (ICSRs). Although retrospective quality check (Retro-QC) and late submission analyses are important steps in ensuring ICSR quality, their manual application poses several challenges that can be overcome through automation. OBJECTIVES: To improve the efficiency of the Retro-QC analysis and late submission analysis using a computer-operated tool called Compliance and Metrics Management (CMM) tool, and to measure the tool's effectiveness in terms of productivity, time, and cost savings by comparing against the manual process. METHODS: Time savings were calculated by measuring the difference in time taken during the manual process versus the automated process. Cost savings were measured in terms of hourly remuneration for the time saved. Productivity was calculated as the difference between the number of cases handled in the manual versus automated process. Thus, the overall efficiency was measured in terms of time and cost savings along with increased productivity. RESULTS: Automation resulted in time savings of 49% and cost savings of 43% for Retro-QC analysis, and the productivity level increased by 67%. For late submission analysis, the CMM tool resulted in time savings of 88% and cost savings of 87%. CONCLUSION: CMM tool enhanced the efficiency of both Retro-QC and late submission analyses by increasing productivity along with time and cost savings. It also reduced the number of errors, thereby enhancing the accuracy of the process and overall compliance.

Multiparametric Flow Cytometry in the Evaluation of Plasma Cell Proliferative Disorders: Current Paradigms for Clinical Practice.

Diagnosis of plasma cell proliferative disorders (PCPDs) is primarily based on the demonstration of monoclonal protein (M-Protein) in blood and/ or urine which often precedes clinical manifestations of the disease. The basic pathophysiology behind the M-protein presence is the proliferation of clonal plasma cells (PCs) in bone marrow or extramedullary sites and is assessed using cytomorphology and immunophenotyping. The role of multiparametric flow cytometry (MFC) for PC identification is technically the most valuable tool in this context as it characterizes as well as quantifies the clonal PCs based on differential expression of various immunophenotypic (IPT) markers. From a diagnostic perspective, MFC is critical in the definite identification of the clonal PCs and delineates benign and borderline entities at one end of the spectrum (MGUS, SMM) with lower clonal PC% and, malignant diseases at the other end (MM and PCL) with higher clonal PC fraction. The role of MFC in assessment of measurable residual disease (MRD) and monitoring of progression in MM and various PCPDs has been validated in multiple clinical studies and is probably one of the most promising tools for predicting treatment outcomes. Furthermore, MFC also plays a crucial role in disease prognostication based on specific IPT profiles. An additional role of MFC in the current clinical scenario is the evaluation of tumor microenvironment based on immune cell repertoire, which is reflecting encouraging results across. Thus, in the current review we concisely describe the role of MFC as a reliable and essential modality in PCPDs, from diagnosis to prediction of treatment outcome and disease monitoring.

Thickness-Dependent Charge Transport in Three Dimensional Ru(II)- Tris(phenanthroline)-Based Molecular Assemblies.

We describe here the fabrication of large-area molecular junctions with a configuration of ITO/[Ru(Phen)3]/Al to understand temperature- and thickness-dependent charge transport phenomena. Thanks to the electrochemical technique, thin layers of electroactive ruthenium(II)-tris(phenanthroline) [Ru(Phen)3] with thicknesses of 4-16 nm are covalently grown on sputtering-deposited patterned ITO electrodes. The bias-induced molecular junctions exhibit symmetric current-voltage (j-V) curves, demonstrating highly efficient long-range charge transport and weak attenuation with increased molecular film thickness (ß = 0.70 to 0.79 nm-1). Such a lower ß value is attributed to the accessibility of Ru(Phen)3 molecular conduction channels to Fermi levels of both the electrodes and a strong electronic coupling at ITO-molecules interfaces. The thinner junctions (d = 3.9 nm) follow charge transport via resonant tunneling, while the thicker junctions (d = 10-16 nm) follow thermally activated (activation energy, Ea ∼ 43 meV) Poole-Frenkel charge conduction, showing a clear "molecular signature" in the nanometric junctions.

Dual-Functional Electrochromic Smart Window Using WO3·H2O-rGO Nanocomposite Ink Spray-Coated on a Low-Cost Hybrid Electrode.

Electrochromic windows have gained growing interest for their ability to change their optical state in the visible and NIR ranges with minimal input power, making them energy-efficient. However, material processing costs, fabrication complexity, and poor electrochromic properties can be barriers to the widespread adoption of this technology. To address these issues, electrochromic material and fabrication processes are designed to realize their potential as a cost-effective and energy-efficient technology. In this work, an electrochromic composite material-based ink is synthesized consisting of WO3·H2O nanoplates supported on rGO (reduced graphene oxide) nanosheets (WH-rGO), wherein an optimized amount of rGO (0.05 to 0.5 wt %) is introduced for providing a higher conduction pathway for efficient charge transport without sacrificing the electrochromic performance of WO3·H2O nanoplates. The stable ink dispersion prepared in the study is deposited by spray coating on transparent conducting electrodes over large areas (25 cm2). The WH-rGO nanocomposite (0.4 wt %) results in 43% optical modulation at 700 nm, with bleaching and coloration times of 6 and 8 s, respectively. Interestingly, the device also possesses an electrochemical energy storage capability with an areal capacitance of 16.3 mF/cm2. The electrochromic composite material is successfully translated on tin doped indium oxide (ITO)-coated Al metal mesh hybrid electrodes (T = 80%, Rs = 40 Ω/□) to replace ITO. Finally, an electrochromic device of 5 × 5 cm2 is fabricated by spray-coating the ink on cost-effective ITO/Al-mesh hybrid electrodes. The device displays blue to colorless modulation with an excellent bleaching time of 0.43 s and a coloration time of 2.16 s, making it one among the fast-operating devices fabricated by complete solution processing. This work showcases the economical production of a dual-function electrochromic device, which can be a feasible option as an alternative to existing ITO-based devices in both automotive and infrastructure applications.

Donor-Derived Cell-Free DNA as a Non-Invasive Biomarker for Graft Rejection in Kidney Transplant Recipients: A Prospective Study among the Indian Population.

Monitoring graft health and detecting graft rejection is crucial for the success of post-transplantation outcomes. In Western countries, the use of donor-derived cell-free DNA (dd-cfDNA) has gained widespread recognition as a diagnostic tool for kidney transplant recipients. However, the role of dd-cfDNA among the Indian population remains unexplored. The recipients were categorized into two groups: the post-transplant recipient (PTR) group (n = 16) and the random recipient (RR) group (n = 87). Blood samples were collected daily from the PTR group over a 7-day period, whereas the RR group's samples were obtained at varying intervals. In this study, we used a targeted approach to identify dd-cfDNA, which eliminated the need for genotyping, and is based on the minor allele frequency of SNP assays. In the PTR group, elevated dd-cfDNA% levels were observed immediately after transplantation, but returned to normal levels within five days. Within the RR group, heightened serum creatinine levels were directly proportional to increased dd-cfDNA%. Sixteen recipients were advised to undergo biopsy due to elevated serum creatinine and other pathological markers. Among these sixteen recipients, six experienced antibody-mediated rejection (ABMR), two exhibited graft dysfunctions, two had active graft injury, and six (37.5%) recipients showed no rejection (NR). In cases of biopsy-proven ABMR and NR, recipients displayed a mean ± SD dd-cfDNA% of 2.80 ± 1.77 and 0.30 ± 0.35, respectively. This study found that the selected SNP assays exhibit a high proficiency in identifying donor DNA. This study also supports the use of dd-cfDNA as a routine diagnostic test for kidney transplant recipients, along with biopsies and serum creatinine, to attain better graft monitoring.

Establishing the Callus-Based Isolation of Extracellular Vesicles from Cissus quadrangularis and Elucidating Their Role in Osteogenic Differentiation.

Extracellular vesicles (EVs) are nano-sized vehicles secreted by all live cells to establish communication with adjacent cells. In recent years, mammalian EVs (MEVs) have been widely investigated for their therapeutic implications in human disease conditions. As the understanding of MEV composition and nature is advancing, scientists are constantly exploring alternatives for EV production with similar therapeutic potential. Plant-derived exosome-like nanovesicles (PDEVs) may be a better substitute for MEVs because of their widespread sources, cost-effectiveness, and ease of access. Cissus quadrangularis (CQ), known as "bone setter or Hadjod", is a perennial plant utilized for its osteogenic potential. Its crude powder extract formulations are widely used as tablets and syrups. The present work elucidates the isolation of exosome-like nanovesicles (henceforth exosomes) from the culture supernatants of an in vitro cultured callus tissue derived from CQ. The physical and biological properties of the exosomes were successfully investigated using different characterization techniques. The therapeutic potential of the CQ exosomes was found to ameliorate the wound scratch injury and oxidative stress conditions in human-derived mesenchymal stem cells (hMSCs) and the pre-osteoblast (MC3T3) cell line. These exosomes also induced the proliferation and differentiation of hMSCs, as observed by alkaline phosphatase activity. These findings may serve as a proof of concept for further investigating the CQ exosomes as a nanocarrier for drug molecules in various therapeutic bone applications.

Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY.

Background: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work. Methods: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022. Findings: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs).The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79-4.91; p < 0.001). STs were more frequent in males and patients with unmutated immunoglobulin heavy variable genes (OR = 1.77; 95% CI = 1.49-2.11; p < 0.001/OR = 1.89; 95% CI = 1.6-2.24; p < 0.001).CLL-directed treatment was associated with non-melanoma skin and prostate cancers (OR = 1.8; 95% CI = 1.36-2.41; p < 0.001/OR = 2.11; 95% CI = 1.12-3.97; p = 0.021). In contrast, breast cancers were more frequent in untreated patients (OR = 0.17; 95% CI = 0.08-0.33; p < 0.001).Patients with CLL and an OM had inferior overall survival (OS) than those without. AML and MDS conferred the worst OS (p < 0.001). Interpretation: OMs in CLL impact on OS. Treatment for CLL increased the risk for AML/MDS, prostate cancer, and NMSC. FCR was associated with increased risk for AML/MDS. Funding: AbbVie, and EU/EFPIAInnovative Medicines Initiative Joint Undertaking HARMONY grant n° 116026.

Autosomal Recessive Adolescent Syndromic Nephronophthisis Caused by a Novel Compound Heterozygous Pathogenic Variant.

BACKGROUND Nephronophthisis, an autosomal recessive ciliopathy involving mutations in primary cilium genes, is characterized by chronic tubulointerstitial nephritis and a defective urine concentrating capacity. It accounts for about 5% of renal failure in children and adolescents and usually progresses to end-stage renal disease before the age of 30 years. Nephronophthisis is associated with extrarenal manifestations, including retinitis pigmentosa in Senior-Loken syndrome (SLS), and liver fibrosis in 10-20% of cases. While some presenting patterns could be characteristic, patients may have atypical presentation, making diagnosis difficult. Tubulointerstitial fibrosis is the predominant feature on histology and as such, diagnosis depends mostly on genetic testing. Despite advances in renal genomics over the years with a better understanding of primary cilia and ciliary theory, about 40% of nephronophthisis cases go undiagnosed. As the underlying genetic etiologies are not fully understood, morphologic pathologic findings are non-specific, and treatment options are limited to dialysis and transplantation. CASE REPORT We describe a unique case of a patient with adolescent nephronophthisis who presented with advanced chronic kidney disease and severe pancytopenia, who progressed to end-stage renal disease at the age of 19, and was found to have syndromic nephronophthisis with compound heterozygous inheritance. CONCLUSIONS This report highlights the atypical presentation patterns that can be seen in syndromic nephronophthisis, the importance of genetic diagnosis when there is a high index of suspicion, and the need to further study genetic variants to better understand and diagnose the disease and to develop targeted therapy.

Impact of Life Cycle Costing in Procurement of Robotic Track-Based Central Laboratory at Apex Medical Institute in India.

Introduction Life cycle costing is an important management tool that takes into account the implications of planning, acquiring, operating, maintaining, and disposing of an asset during its complete life cycle. A major hindrance to the procurement of expensive equipment in developing countries is the lack of a reliable framework combining and integrating all the equipment life cycle aspects into procurement process. Methods The study was conducted from the data collected from the bids that were received for procurement of two robotic track-based central laboratories which were installed at All India Institute of Medical Sciences (AIIMS), New Delhi. The procurement was done as per the guidelines laid down under General Finance Rules (GFR) 2017 following the two bid systems: technical bid and price/commercial bid. Results A complete financial analysis of the robotic laboratory was done that involved gathering of all the pertinent financial information into one place and then using that data to analyze the feasibility of the bid. The life cycle costs of both the labs were calculated by assuming the life of equipment as 10 years and by factoring in cost of equipment including 5-year warranty, comprehensive maintenance from years 6 to 10, indicative cost of all reagents for 10 years, and indicative cost of all other consumables for 10 years. Conclusion Results showed that the cost of equipment alone should not be the sole predictor of making purchase decisions of equipment. Further research may additionally explore differences between processes being followed in government versus private organizations, as well as national guidelines and subnational practices.