Left Ventricular Gene Expression in Heart Failure With Preserved Ejection Fraction-Profibrotic and Proinflammatory Pathways and Genes.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent and has few treatments. The molecular mechanisms and resultant signaling pathways that underlie the development of HFpEF are poorly defined. It has been proposed that activation of proinflammatory pathways plays a role in the development of cardiac fibrosis. The signature of gene expression (transcriptome) of previously validated left ventricular biopsies obtained from patients with HFpEF and matched referent controls allows for an unbiased assessment of proinflammatory and profibrotic signaling pathways and genes. METHODS: Epicardial left ventricular biopsies from stringently selected HFpEF patients (HFpEF, n=16) and referent control patients (CTR, n=14) were obtained during aortocoronary bypass surgery. The subepicardial myocardium was flash-frozen to build a repository that was parallel-processed for RNA sequencing to allow for an unsupervised in-depth comparison of the left ventricular transcriptome. RESULTS: The average patient age was 67±10 years. When compared with controls, patients with HFpEF were hypertensive with a higher body mass index (kg/m2: 30±5 versus 37±6; P<0.01) and elevated NT-proBNP levels (pg/mL: 155 [89-328] versus 1554 [888-2178]; P<0.001). The transcriptome analysis revealed differential expression of 477 genes many of which were involved in profibrotic pathways including extracellular matrix production and posttranslational modification but no proinflammatory signature. CONCLUSIONS: The transcriptome analysis of left ventricular myocardial samples from patients with HFpEF confirms an overabundant extracellular matrix gene expression, the basis of myocardial fibrosis, without a signature of activated proinflammatory pathways or genes.

Comparison of quality of life, symptom and functional outcomes following surgical treatment for colorectal neoplasia.

BACKGROUND: Colorectal surgical procedures can have a significant impact on quality-of-life (QoL), functional and symptom outcomes. This retrospective study conducted in a tertiary care center evaluated the influence of four colorectal surgical procedures on patient-reported outcome measures (PROMs). METHODS: 512 patients undergoing colorectal neoplasia surgery between June 2015 and December 2017 were identified via the Cabrini Monash Colorectal Neoplasia database. Primary outcomes measured were the mean changes in PROMs following surgery utilizing the International Consortium of Health Outcome Measures colorectal cancer (CRC) PROMs. RESULTS: 242 patients from 483 eligible patients responded (50% participation rate). Responders and non-responders were comparable in median age (72 vs. 70 years), gender (48% vs. 52% male), time from surgery (<1 and >1 year), overall stage at diagnosis and type of surgery. Respondents underwent either a right hemicolectomy, ultra-low anterior resection, abdominoperineal resection or a transanal endoscopic microsurgery/transanal minimally invasive surgery. Right hemicolectomy patients reported the best post-operative function and reduced symptoms, significantly better (P < 0.01) than ultra-low anterior resection patients who reported the worst outcomes in multiple areas (body image, embarrassment, flatulence, diarrhoea, stool frequency). Furthermore, patients undergoing an abdominoperineal resection reported the worst scores for body image, urinary frequency, urinary incontinence, buttock pain, faecal incontinence and male impotence. CONCLUSIONS: The differences in PROMs in CRC surgical procedures is demonstrable. The worst post-operative functional and symptom scores were reported after either an ultra-low anterior resection or an abdominoperineal resection. Implementation of PROMs will identify and aid early patient referral to allied health and support services.

Initial presentation of granulomatosis with polyangiitis as urethral mass mimicking urethral cancer: A case report.

Granulomatosis with polyangiitis (GPA) is a type of vasculitis in which granulomas deposit in small and medium-size vessels causing inflammation. It frequently affects the respiratory tract, both upper and lower tracts. Glomerulonephritis commonly occurs as well, and other systems can be affected such as the integumentary system and peripheral nervous system. Rarely, urogenital signs and symptoms are present. This report describes a case of a 19-year-old woman who presented with lower urinary tract symptoms and a urethral mass and was subsequently diagnosed with GPA. She responded well to treatment with corticosteroids, rituximab, and avacopan. This case highlights the importance of considering alternative diagnoses when a young woman presents with refractory urinary symptoms. It also highlights fertility issues relative to treatment of GPA that are of interest to the practicing obstetrician/gynecologist.

Robotic colon surgery in obese patients: a systematic review and meta-analysis.

BACKGROUND: Colon cancer resection can be technically difficult in the obese (OB) population. Robotic surgery is a promising technique but its benefits remain uncertain in OB patients. The aim of this study is to compare OB versus non-obese (NOB) patients undergoing robotic colon surgery, as well as OB patients undergoing robotic versus open or laparoscopic colonic surgery. METHODS: A systematic review and meta-analysis was performed. Primary outcome measures included length of stay (LOS), surgical site infection (SSI) rate, complications, anastomotic leak and oncological outcomes. RESULTS: A total of eight studies were included, with five comparing OB and NOB patients undergoing robotic colon surgery included in meta-analysis. A total of 263 OB patients and 400 NOB patients formed the sample for meta-analysis. There was no significant difference between the two groups in operative time, conversion to open, LOS, lymph node yield, anastomotic leak and postoperative ileus. There was a trend towards a significant increase in overall complications and SSI in the OB group (32.3% OB versus 26.8% NOB for complications, 14.2% OB versus 9.9% NOB for SSI). The three included studies comparing surgical techniques were too heterogeneous to undergo meta-analysis. CONCLUSION: Robotic colon surgery is safe in obese patients, but high-quality prospective evidence is lacking. Future studies should report on oncological safety and the cost-effectiveness of adopting the robotic technique in these challenging patients.

Detection of human adenovirus F41 in wastewater and its relationship to clinical cases of acute hepatitis of unknown aetiology.

As of 8 July 2022, the World Health Organization (WHO) have reported 1010 probable cases of acute hepatitis of unknown aetiology in children worldwide, including approximately 250 cases in the United Kingdom (UK). Clinical presentations have often been severe, with liver transplantation a frequent clinical outcome. Human adenovirus F41 (HAdV-F41) has been detected in most children with acute hepatitis, but its role in the pathogenesis of this infection has yet to be established. Wastewater-based epidemiology (WBE) has become a well-established tool for monitoring the community spread of SARS-CoV-2, as well as other pathogens and chemicals. In this study, we adopted a WBE approach to monitoring levels of HAdV-F40/41 in wastewater before and during an acute hepatitis outbreak in Northern Ireland. We report increasing detection of HAdV-F40/41 in wastewater, concomitant with increasing numbers of clinical cases. Amplicon whole genome sequencing further classified the wastewater-derived HAdV as belonging to the F41 genotype which in turn was homologous to clinically derived sequences. We propose that WBE has the potential to inform community surveillance of HAdV-F41 and can further contribute to the ongoing global discussion supporting HAdV-F41 involvement in acute hepatitis cases.

Growth hormone receptor antagonism downregulates ATP-binding cassette transporters contributing to improved drug efficacy against melanoma and hepatocarcinoma in vivo.

Knockdown of GH receptor (GHR) in melanoma cells in vitro downregulates ATP-binding cassette-containing (ABC) transporters and sensitizes them to anti-cancer drug treatments. Here we aimed to determine whether a GHR antagonist (GHRA) could control cancer growth by sensitizing tumors to therapy through downregulation of ABC transporters in vivo. We intradermally inoculated Fluc-B16-F10 mouse melanoma cells into GHA mice, transgenic for a GHR antagonist (GHRA), and observed a marked reduction in tumor size, mass and tumoral GH signaling. Moreover, constitutive GHRA production in the transgenic mice significantly improved the response to cisplatin treatment by suppressing expression of multiple ABC transporters and sensitizing the tumors to the drug. We confirmed that presence of a GHRA and not a mere absence of GH is essential for this chemo-sensitizing effect using Fluc-B16-F10 allografts in GH knockout (GHKO) mice, where tumor growth was reduced relative to that in GH-sufficient controls but did not sensitize the tumor to cisplatin. We extended our investigation to hepatocellular carcinoma (HCC) using human HCC cells in vitro and a syngeneic mouse model of HCC with Hepa1-6 allografts in GHA mice. Gene expression analyses and drug-efflux assays confirm that blocking GH significantly suppresses the levels of ABC transporters and improves the efficacy of sorafenib towards almost complete tumor clearance. Human patient data for melanoma and HCC show that GHR RNA levels correlate with ABC transporter expression. Collectively, our results validate in vivo that combination of a GHRA with currently available anti-cancer therapies can be effective in attacking cancer drug resistance.

The National Aeronautics and Space Administration-task load index: NASA-TLX: evaluation of its use in surgery.

BACKGROUND: The technical difficulty an operation creates for a surgeon is difficult to measure. Current measures are poor surrogates. In both research and teaching settings it would be valuable to be able to accurately measure this degree of difficulty. The National Aeronautics and Space Administration Task Load Index (NASA TLX) is a multi-dimensional scale designed to obtain workload estimates relating to a task. This study aimed to evaluate the NASA TLX as an objective measure of technical difficulty of an operation. METHODS: Seven surgeons performed 127 pre-defined operations (minimally invasive right hemicolectomy & re-do bariatric surgery) and recorded a NASA TLX score after each operation. These scores were compared to numerous clinical parameters and the score was correlated with the subjective measure of whether the surgeon categorized the operation as "easy", "moderate" or "difficult". RESULTS: The NASA TLX score was significantly correlated with operative duration, blood loss, previous abdominal surgery and the surgeons' assessment of difficulty. It did not correlate with intra-operative or post-operative complications, conversion to open surgery or length of stay. CONCLUSIONS: The NASA TLX score provides a graded numerical score that that correlated significantly with the surgeon's assessment of the technical difficulty, and with operative duration, intra-operative blood loss and previous abdominal surgery. This novel application of this tool could be employed in both research and teaching settings to score surgical difficulty and monitor a trainee's proficiency over time.

Modeling colorectal cancer: A bio-resource of 50 patient-derived organoid lines.

BACKGROUND AND AIM: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. To improve outcomes for these patients, we need to develop new treatment strategies. Personalized cancer medicine, where patients are treated based on the characteristics of their own tumor, has gained significant interest for its promise to improve outcomes and reduce unnecessary side effects. The purpose of this study was to examine the potential utility of patient-derived colorectal cancer organoids (PDCOs) in a personalized cancer medicine setting. METHODS: Patient-derived colorectal cancer organoids were derived from tissue obtained from treatment-naïve patients undergoing surgical resection for the treatment of CRC. We examined the recapitulation of key histopathological, molecular, and phenotypic characteristics of the primary tumor. RESULTS: We created a bio-resource of PDCOs from primary and metastatic CRCs. Key histopathological features were retained in PDCOs when compared with the primary tumor. Additionally, a cohort of 12 PDCOs, and their corresponding primary tumors and normal sample, were characterized through whole exome sequencing and somatic variant calling. These PDCOs exhibited a high level of concordance in key driver mutations when compared with the primary tumor. CONCLUSIONS: Patient-derived colorectal cancer organoids recapitulate characteristics of the tissue from which they are derived and are a powerful tool for cancer research. Further research will determine their utility for predicting patient outcomes in a personalized cancer medicine setting.

Latest evidence on the management of early-stage and locally advanced rectal cancer: a narrative review.

Rectal cancer is a challenging disease process to manage, with a rising incidence in young adults. Several clinical advances have been made in the past decade with regards to optimal treatment strategies in early-stage (T1-2, node negative tumours) and locally advanced cancers (T3-4 and/or nodal positivity) utilizing a multimodal approach of surgery, neoadjuvant chemoradiotherapy, and adjuvant chemotherapy, all aiming to optimize oncological outcomes, while minimizing associated morbidity. This narrative review aimed to summarize trial level evidence apropos the management of early and locally advanced rectal cancer. All relevant prospective clinical trials were identified through a computer-assisted search of PubMed, EMBASE, Medline databases between 1990 and 30 June 2021. With regards to early rectal cancer, there is limited trial-level evidence in the literature. Total mesorectal excision (TME) is the current standard of care, but local excision could be considered in select patients with pT1 tumours, or patients with near or complete clinical response to neoadjuvant CRT. As for locally advanced rectal cancer, the current standard of care consists of long-course chemotheradiotherapy or short-course radiotherapy, followed by TME. However, the role of total neoadjuvant therapy is promising, with respect to both oncological outcomes, as well as in reducing toxicity. Both induction and consolidation chemotherapy treatment approaches have been described in literature, with encouraging early results. The optimal management of rectal cancer is constantly evolving. More research is needed to investigate the long-term oncological and functional outcomes following new multimodal therapies in the management of early-stage and locally advanced rectal cancer.

Applications of three-dimensional printing in ophthalmology.

Three-dimensional (3D) printing is increasingly used to produce customized objects and is a promising alternative to traditional manufacturing methods in diverse fields, such as dentistry and orthopedics. Already in use in other medical specialties, adoption in ophthalmology has been limited to date. This review aims to provide an overview of 3D printing technology with respect to current and potential applications in ophthalmic practice. Medline, Embase, and Internet searches were performed with "3D printing," "ophthalmology," "dentistry," "orthopaedics" and their synonyms used as main search terms. In addition, search terms related to clinical applications such as "surgery" and "implant" were employed. 3D printing has multiple applications in ophthalmology, including in diagnosis, surgery, prosthetics, medications, and medical education. Within the past decade, researchers have produced 3D printed models of objects such as implants, prostheses, anatomical models and surgical simulators. Further development is necessary to generate optimal biomaterials for various applications, and the quality and long-term performance of 3D models needs to be validated.

The Reliability and Accuracy of Endoscopic Items and Scores Used in the Assessment of the Ileoanal Pouch and Cuff.

BACKGROUND AND AIMS: Currently used endoscopic items for the assessment of pouchitis and cuffitis have deficiencies in reliability and validation. We assessed the reliability and accuracy of new endoscopic items for pouchitis and of the Ulcerative Colitis Endoscopic Index of Severity [UCEIS] for cuffitis. METHODS: Three new endoscopic items were assessed and included in the Monash pouchitis endoscopic subscore: bleeding [absent/contact/spontaneous]; erosions [absent/<10/≥10]; and ulceration [absent/<10%/≥10%]. Three raters evaluated 44 pouchoscopy videos in duplicates, in random order. Intra- and inter-rater reliability of all endoscopic items and UCEIS were assessed. Clinical and histological pouchitis disease activity index [PDAI] subscores were also assessed and faecal calprotectin was measured. RESULTS: All three Monash endoscopic items had substantial intra-rater reliability with intraclass correlation coefficients [ICCs] >0.61 [95% CI >0.61], compared with only ulcers from the currently used PDAI endoscopic subscore, but inter-rater reliability was only substantial for ulceration and no better than those of the currently used endoscopic items. The Monash endoscopic subscore had a strong positive correlation with the reference standard global endoscopic lesion severity r = 0.80 [95% CI 0.80-0.80] and the reference standard PDAI endoscopic subscore r = 0.70 [95% CI 0.67-0.73], which was higher than the correlation observed for the currently used PDAI endoscopic subscore. The UCEIS had substantial intra-rater reliability, but only fair inter-rater reliability and poor diagnostic performance for cuffitis. CONCLUSIONS: The Monash endoscopic items, and endoscopic subscore they generate, have enhanced overall performance compared with the currently used PDAI items and subscore. Further validation and responsiveness to change in disease state are indicated.

Comparison of colorectal cancer outcomes in young adults and octogenarians.

BACKGROUND: This study aimed to characterise the outcomes associated with colorectal cancer (CRC), comparing young adults (<50 years), patients of screening age (50-79 years), and octogenarians (>80 years). METHODS: All consecutive CRC resections with curative intent were recruited into this study from a prospectively maintained CRC database at a tertiary academic centre. RESULTS: A total of 745 eligible cases were identified. Five-year survival in young adults was poorer than that of patients of screening age. Young adults had the highest incidence of rectal cancer resections, and presented with the most advanced tumour stages. Independent associations for poorer survival in young adults were increased nodal stage, the presence of distal metastases, and loss of MLH1/PMS2 staining on immunohistochemistry. Young adults had similar survival to octogenarians, when comparing patients treated with curative intent, regardless of oncological treatment.

Mice with gene alterations in the GH and IGF family.

Much of our understanding of GH's action stems from animal models and the generation and characterization of genetically altered or modified mice. Manipulation of genes in the GH/IGF1 family in animals started in 1982 when the first GH transgenic mice were produced. Since then, multiple laboratories have altered mouse DNA to globally disrupt Gh, Ghr, and other genes upstream or downstream of GH or its receptor. The ability to stay current with the various genetically manipulated mouse lines within the realm of GH/IGF1 research has been daunting. As such, this review attempts to consolidate and summarize the literature related to the initial characterization of many of the known gene-manipulated mice relating to the actions of GH, PRL and IGF1. We have organized the mouse lines by modifications made to constituents of the GH/IGF1 family either upstream or downstream of GHR or to the GHR itself. Available data on the effect of altered gene expression on growth, GH/IGF1 levels, body composition, reproduction, diabetes, metabolism, cancer, and aging are summarized. For the ease of finding this information, key words are highlighted in bold throughout the main text for each mouse line and this information is summarized in Tables 1, 2, 3 and 4. Most importantly, the collective data derived from and reported for these mice have enhanced our understanding of GH action.

Growth hormone receptor gene disruption in mature-adult mice improves male insulin sensitivity and extends female lifespan.

Studies in multiple species indicate that reducing growth hormone (GH) action enhances healthy lifespan. In fact, GH receptor knockout (GHRKO) mice hold the Methuselah prize for the world's longest-lived laboratory mouse. We previously demonstrated that GHR ablation starting at puberty (1.5 months), improved insulin sensitivity and female lifespan but results in markedly reduced body size. In this study, we investigated the effects of GHR disruption in mature-adult mice at 6 months old (6mGHRKO). These mice exhibited GH resistance (reduced IGF-1 and elevated GH serum levels), increased body adiposity, reduced lean mass, and minimal effects on body length. Importantly, 6mGHRKO males have enhanced insulin sensitivity and reduced neoplasms while females exhibited increased median and maximal lifespan. Furthermore, fasting glucose and oxidative damage was reduced in females compared to males irrespective of Ghr deletion. Overall, disrupted GH action in adult mice resulted in sexual dimorphic effects suggesting that GH reduction at older ages may have gerotherapeutic effects.

Predictive factors for distant recurrence of colorectal cancer in patients after curative resection for stage I-III colorectal cancer in Australia.

PURPOSE: Distant recurrence is a devastating occurrence after colorectal cancer resection. This study aimed to identify the risk factors for distant recurrence following surgery. METHODS: All consecutive colorectal cancer resections with curative intent were included from a prospectively maintained colorectal cancer database. The primary outcome was to identify predictive factors for distant recurrence of colorectal cancer. RESULTS: A total of 670 eligible cases were identified with 88 (13.1%) developing distant recurrence during the follow-up period. The median time to distant recurrence was 1.2 years with the most common sites of distant recurrence being the lung (44.3%) and liver (44.3%). Predictive factors for distant recurrence in colon cancer included a high tumor, nodal, and overall stage of the primary cancer (p < 0.001 for all). Surgical complications (p = 0.007), including anastomotic leak (p = 0.023), were associated with a higher risk of developing distant recurrence in rectal cancer patients. Independent variables associated with distant recurrence included tumor stage (OR 1.61, p = 0.011), nodal stage (OR 2.18, p < 0.001), and both KRAS (OR 11.04, p < 0.001) and MLH/PMS2 (OR 0.20, p = 0.035) genetic mutations. Among patients with distant recurrence, treatment with surgery conferred the best survival, with patients < 50 years of age having the best overall 5-year survival. CONCLUSION: Predictive factors for distant recurrence include advanced tumor and nodal stages, and the presence of KRAS and MLH/PSM2 mutations. Clinicians should be cognizant of these risk factors, and instate close surveillance plans for patients exhibiting these features.

A Rare Case of a Patient With Hairy Cell Leukemia Developing Blastoid Marginal Zone B-Cell Lymphoma.

There have been several case reports associating hairy cell leukemia (HCL) with non-Hodgkin's lymphoma. However, it remains unclear whether these rare phenomena represent disease transformation or the coexistence of two separate disease entities. De novo marginal zone lymphoma can be routinely seen in elderly patients; however, in a patient with a history of HCL, a transformation is more likely than de novo blastoid marginal zone lymphoma. In this report, we present a rare case of a patient with HCL developing a high-grade blastoid marginal zone B-cell lymphoma (MZBCL).

The impact of the COVID-19 pandemic on colorectal cancer diagnosis and management: a Binational Colorectal Cancer Audit study.

BACKGROUND: The COVID-19 pandemic has resulted in global disruptions to the delivery of healthcare. The national responses of Australia and New Zealand has resulted in unprecedented changes to the care of colorectal cancer patients, amongst others. This paper aims to determine the impact of COVID-19 on colorectal cancer diagnosis and management in Australia and New Zealand. METHODS: This is a multicentre retrospective cohort study using the prospectively maintained Binational Colorectal Cancer Audit (BCCA) registry. Data is contributed by over 200 surgeons in Australia and New Zealand. Patients receiving colorectal cancer surgery during the pandemic were compared to averages from the same period over the preceding 3 years. RESULTS: There were fewer operations in 2020 than the historical average. During April to June, patients were younger, more likely to have operations in public hospitals and more likely to have urgent or emergency operations. By October to December, proportionally less patients had Stage I disease, proportionally more had Stage II or III disease and there was no difference in Stage IV disease. Patients were less likely to have rectal cancer, were increasingly likely to have urgent or emergency surgery and more likely to have a stoma created. CONCLUSION: This study shows that the response to COVID-19 has had measurably negative effects on the diagnosis and management of colorectal cancer in two countries that have had significantly fewer COVID-19 cases than many other countries. The long-term effects on survival and recurrence are yet to be known, but could be significant.

A Rare Case of Double Antibody-Positive Rapidly Progressive Glomerulonephritis: A Therapeutic Challenge.

Crescentic glomerulonephritis, also known as rapidly progressive glomerulonephritis, is a syndrome characterized by progressive and rapid deterioration of renal function over the course of weeks to months. Oliguria, hematuria, azotemia, and hypertension are characteristic features of this condition. Crescentic glomerulonephritis is further classified according to the staining pattern on immunofluorescence. In rare instances, a mixed pattern of injury is encountered as in the case of double antibody-positive rapidly progressive glomerulonephritis (RPGN). This case illustrates the challenge in treatment of double antibody-positive RPGN in an elderly female with no previous renal disease. The patient was found to be positive for anti-GBM antibody and MPO-ANCA. Treatment was initially targeted against MPO-ANCA as the biopsy was most consistent with this process; however, the patient failed to respond to treatment and was subsequently transitioned to oral cyclophosphamide directed against anti-GBM disease. In cases of doubly antibody-positive RPGN with anti-GBM disease and ANCA-associated vasculitis, initial treatment should focus on inducing remission of anti-GBM disease as double antibody-positive disease often presents with the aggressive morbidity and mortality seen in anti-GBM disease, and the chronic risk of relapse seen in ANCA-mediated vasculitis.

An Unusual Case of Prolymphocytic Leukemia Transformation in a Patient With Chronic Lymphocytic Leukemia.

B-cell prolymphocytic leukemia (B-PLL) is a rare leukemia characterized by rapidly increasing leukocytosis with splenomegaly and lymphadenopathy. Treatment strategies are largely based on studies of chronic lymphocytic leukemia (CLL). Antibodies against the cell surface protein CD20 are considered to be first-line therapy. A 76-year-old male with known CLL presented 2 weeks after starting chemoimmunotherapy for newly refractory CLL after failing ibrutinib therapy. White blood cell count was elevated at 226.7 × 103/µL. Fluorescent in situ hybridization analysis of a bone marrow specimen showed new development of complex cytogenetics. Flow cytometry revealed B cells appearing slightly dimmer on CD45 and brighter on CD20 compared with typical B-CLL suggestive of less mature lymphocyte forms. The patient was diagnosed with B-PLL and started on obinutuzumab and venetoclax with rapid normalization of white blood cells. This case recapitulates the challenges in diagnosing and treating B-PLL. Ibrutinib resistance is a growing area of study with several proposed mechanisms of acquired resistance. The pathogenesis of B-PLL is not completely understood, although mutations in MYC are presumed to play a role.

A case of immunotactoid glomerulopathy in a patient with monoclonal gammopathy of renal significance.

Monoclonal gammopathy of renal significance is a relatively new diagnosis that attributes kidney disease to damage caused by a monoclonal protein. There is growing recognition of this disease in patients previously diagnosed with monoclonal gammopathy of undetermined significance, as they increasingly develop clinically significant renal impairment requiring treatment. We outline a case of a patient presenting with worsening renal function, found to have a circulating monoclonal protein and ultimately diagnosed with a subtype of monoclonal gammopathy of renal significance referred to as immunotactoid glomerulopathy. Abbreviations: MGUS: Monoclonal gammopathy of undetermined significance; M-protein: Monoclonal protein; MM: Multiple myeloma; MGRS: Monoclonal gammopathy of renal significance; MGCS: Monoclonal gammopathy of clinical significance; CKD: Chronic kidney disease; C3 and C4: Complement 3 and complement 4, respectively; EF: Ejection fraction; CT: Computed tomography; IgG: Immunoglobulin G; GFR: Glomerular filtration rate; PET: Positron emission tomography; MRI: Magnetic Resonance Imaging.