Maternal diet modulates the infant microbiome and intestinal Flt3L necessary for dendritic cell development and immunity to respiratory infection.

Poor maternal diet during pregnancy is a risk factor for severe lower respiratory infections (sLRIs) in the offspring, but the underlying mechanisms remain elusive. Here, we demonstrate that in mice a maternal low-fiber diet (LFD) led to enhanced LRI severity in infants because of delayed plasmacytoid dendritic cell (pDC) recruitment and perturbation of regulatory T cell expansion in the lungs. LFD altered the composition of the maternal milk microbiome and assembling infant gut microbiome. These microbial changes reduced the secretion of the DC growth factor Flt3L by neonatal intestinal epithelial cells and impaired downstream pDC hematopoiesis. Therapy with a propionate-producing bacteria isolated from the milk of high-fiber diet-fed mothers, or supplementation with propionate, conferred protection against sLRI by restoring gut Flt3L expression and pDC hematopoiesis. Our findings identify a microbiome-dependent Flt3L axis in the gut that promotes pDC hematopoiesis in early life and confers disease resistance against sLRIs.

Female erectile tissues and sexual dysfunction after pelvic radiotherapy: A scoping review.

Sexual function is a vital aspect of human health and is recognized as a critical component of cancer survivorship. Understanding and evaluating the impacts of radiotherapy on female sexual function requires precise knowledge of the organs involved in sexual function and the relationship between radiotherapy exposure and sexual tissue function. Although substantial evidence exists describing the impact of radiotherapy on male erectile tissues and related clinical sexual outcomes, there is very little research in this area in females. The lack of biomedical data in female patients makes it difficult to design studies aimed at optimizing sexual function postradiotherapy for female pelvic malignancies. This scoping review identifies and categorizes current research on the impacts of radiotherapy on normal female erectile tissues, including damage to normal functioning, clinical outcomes of radiation-related female erectile tissue damage, and techniques to spare erectile tissues or therapies to treat such damage. An evaluation of the evidence was performed, and a summary of findings was generated according to Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Extension for Scoping Reviews guidelines. Articles were included in the review that involved normal female erectile tissues and radiotherapy side effects. The results show that little scientific investigation into the impacts of radiotherapy on female erectile tissues has been performed. Collaborative scientific investigations by clinical, basic, and behavioral scientists in oncology and radiotherapy are needed to generate radiobiologic and clinical evidence to advance prospective evaluation, prevention, and mitigation strategies that may improve sexual outcomes in female patients.

Bovine and human endometrium-derived hydrogels support organoid culture from healthy and cancerous tissues.

Organoid technology has provided unique insights into human organ development, function, and diseases. Patient-derived organoids are increasingly used for drug screening, modeling rare disorders, designing regenerative therapies, and understanding disease pathogenesis. However, the use of Matrigel to grow organoids represents a major challenge in the clinical translation of organoid technology. Matrigel is a poorly defined mixture of extracellular matrix proteins and growth factors extracted from the Engelbreth-Holm-Swarm mouse tumor. The extracellular matrix is a major driver of multiple cellular processes and differs significantly between tissues as well as in healthy and disease states of the same tissue. Therefore, we envisioned that the extracellular matrix derived from a native healthy tissue would be able to support organoid growth akin to organogenesis in vivo. Here, we have developed hydrogels from decellularized human and bovine endometrium. These hydrogels supported the growth of mouse and human endometrial organoids, which was comparable to Matrigel. Organoids grown in endometrial hydrogels were proteomically more similar to the native tissue than those cultured in Matrigel. Proteomic and Raman microspectroscopy analyses showed that the method of decellularization affects the biochemical composition of hydrogels and, subsequently, their ability to support organoid growth. The amount of laminin in hydrogels correlated with the number and shape of organoids. We also demonstrated the utility of endometrial hydrogels in developing solid scaffolds for supporting high-throughput, cell culture-based applications. In summary, endometrial hydrogels overcome a major limitation of organoid technology and greatly expand the applicability of organoids to understand endometrial biology and associated pathologies.

The aftermath of the COVID-19 pandemic on pediatric mental health: A pediatric emergency department's perspective.

BACKGROUND: Pediatric mental health visits in the United States has become a public health crisis. Pediatric emergency departments (PED) encounter these patients during mental health emergencies. The COVID-19 pandemic disrupted the social environment of pediatric patients which potentially lead to new and worsening mental health issues. This study examined the proportion of mental health visits to PED around the first wave of the COVID-19 pandemic. METHODS: This retrospective cohort study assessed the proportion of mental health visits at a urban, PED between September 2019 to February 2022. Inclusion criteria were subjects aged 6 to 18 years with a holding order assigned, and one of identified mental health International Classification of Disease, Tenth Division (ICD-10) codes: F01-F99, T14.19, R45, R46.89. Proportion of mental health visits were compared in 6-month periods with the first 6-months representing the pre-COVID-19 period. Secondary analysis compared demographic information and ICD-10 codes. RESULTS: A total of 1036 charts were studied: 126 charts from 2019 to 2020, 512 from 2020 to 2021, and 398 from 2021 to 2022. The proportion of mental health visits from September 2019 to February 2020 was 1.4%, and for the following 6-month periods, the proportion of mental health visits was 1.2%, 7.5%, 4.9%, and 5.7%. There was a statistically significant difference (p < 0.001) demonstrating a higher proportion of mental health visits after the start of the COVID-19 pandemic. Secondary analysis demonstrated statistically significant difference in both median age (p < 0.001) and median length of hospitalization (p < 0.001). CONCLUSION: This study demonstrated a significant increase in pediatric mental health visits following the start of the COVID-19 pandemic. We believe further investigation into the needs and management during acute surges will improve the care we provide to this vulnerable population.

Concurrent chemoradiation and Tumor Treating Fields (TTFields, 200 kHz) for patients with newly diagnosed glioblastoma: patterns of progression in a single institution pilot study.

Current standard of care for glioblastoma (GBM) includes concurrent chemoradiation and maintenance temozolomide (TMZ) with Tumor Treating Fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. We conducted a pilot clinical trial of concurrent chemoradiation with TTFields and report pattern of progression. MATERIALS AND METHODS: This is a single arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with KPS ≥ 60 with newly diagnosed GBM were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions), standard concurrent TMZ and TTFields. Maintenance therapy included standard TMZ and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. Incidence and location of progression was documented. Distant recurrence was defined as recurrence more than 2 cm from the primary enhancing lesion. RESULTS: Thirty patients were enrolled on the trial. Twenty were male with median age 58 years (19-77 years). Median KPS was 90 (70-100). Median follow-up was 15.2 months (1.7-23.6 months). Ten (33.3%) patients had a methylated promoter status. Twenty-seven patients (90%) had progression, with median PFS of 9.3 months (range 8.5 to 11.6 months). Six patients presented with distant recurrence, with median distance from primary lesion of 5.05 cm (2.26-6.95 cm). One infratentorial progression was noted. CONCLUSIONS: We observed improved local control using concurrent chemoradiation with TTFields for patients with newly diagnosed when compared to historical controls. Further data are needed to validate this finding. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT03477110.

Evaluating the safety and efficacy of daprodustat for anemia of chronic kidney disease: a meta-analysis of randomized clinical trials.

PURPOSE: Anemia of chronic kidney disease (CKD) has traditionally been treated with recombinant human erythropoietin (rhEPO). Recently, daprodustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor, has also been shown to increase hematocrit. It remains unclear whether daprodustat or rhEPO should be the treatment of choice for anemia of CKD. We aimed to assess the efficacy and cardiovascular safety of daprodustat versus rhEPO in CKD patients. METHODS: Online databases were queried in April 2022 for articles comparing the efficacy and safety of daprodustat in DD-CKD and NDD-CKD subgroups. Results from trials were pooled using a random-effects model. RESULTS: Data on 8245 CKD patients from eight clinical trials were included. Our results show that in comparison to rhEPO, daprodustat maintained the same efficacy in increasing hemoglobin levels in both the DD-CKD (MD: 0.10; 95% CI [- 0.13,0.34]; p = 0.50) and NDD-CKD (MD: - 0.01; 95% CI [- 0.38,0.35]; p = 0.95) subgroups. Daprodustat significantly lowered hepcidin levels and significantly increased TIBC in both subgroups. Additionally, daprodustat significantly reduced the incidence of major adverse cardiovascular events (MACE) (RR: 0.89; 95% CI: 0.89-0.98; p = 0.02) and its myocardial infarction (MI) component (RR: 0.74; 95% CI: 0.59-0.92; p = 0.006) in the DD-CKD subgroup. CONCLUSION: Daprodustat has similar efficacy compared to rhEPO for the treatment of anemia of CKD. On treatment, the reduced experience of MACE was reported in DD-CKD patients as compared to rhEPO. Furthermore, effects on iron metabolism varied by parameter, with daprodustat being superior to rhEPO in some cases and inferior in others.

ACE2 expression is elevated in airway epithelial cells from older and male healthy individuals but reduced in asthma.

BACKGROUND AND OBJECTIVE: COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter AEC. We determined what factors are associated with ACE2 expression particularly in patients with asthma and COPD. METHODS: We obtained lower AEC from 145 people from two independent cohorts, aged 2-89 years, Newcastle (n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC. RESULTS: Increased gene expression of ACE2 was associated with older age (P = 0.03) and male sex (P = 0.03), but not with pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma patients (P = 0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in patients with asthma (P = 0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface, was increased (P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthma patients. CONCLUSION: Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.

A phase II study to assess the safety and efficacy of the dual mTORC1/2 inhibitor vistusertib in relapsed, refractory DLBCL.

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are unfit for or relapsed postautologous stem-cell transplantation have poor outcomes. Historically, mTORC1 inhibitors have produced responses in approximately 30% of patients in this setting. mTORC1 inhibitor efficacy may be limited by resistance mechanisms including AKT activation by mTORC2. To date, dual mTORC1/2 inhibitors targeting both the TORC1 and TORC2 complexes have not been investigated in DLBCL. This phase II trial investigated the oral dual mTORC1/2 inhibitor vistusertib in an intermittent dosing schedule of 125 mg b.d. for 2 days per week. Thirty patients received vistusertib and six received vistusertib-rituximab for up to six cycles (28-day cycles). Two partial responses were achieved on monotherapy. Durations of response were 57 and 62 days, respectively, for these patients. 19% had stable disease within six cycles. In the monotherapy arm, the median progression-free survival was1.69 (95% confidence interval [CI] 1.61-2.14) months and median overall survival was 6.58 (95% CI 3.81-not reached) months, respectively. The median duration of response or stable disease across the trial duration was 153 days (95% CI 112-not reached). Tumour responses according to positron emission tomography/computed tomography versus computed tomography were concordant. There were no differences noted in tumour volume response according to cell of origin by either gene expression profiling or immunohistochemistry. Vistusertib ± rituximab was well tolerated; across 36 patients 86% of adverse events were grade (G) 1-2. Common vistusertib-related adverse events were similar to those described with mTORC1 inhibitors: nausea (47% G1-2), diarrhoea (27% G1-2, 6% G3), fatigue (30% G1-2, 3% G3), mucositis (25% G1-2, 6% G3), vomiting (17% G1-2), and dyspepsia (14% G1-2). Dual mTORC1/2 inhibitors do not clearly confer an advantage over mTORC1 inhibitors in relapsed or refractory DLBCL. Potential resistance mechanisms are discussed within.

High turnover of extracellular matrix reflected by specific protein fragments measured in serum is associated with poor outcomes in two metastatic breast cancer cohorts.

Increased extracellular matrix (ECM) formation and matrix metalloprotease (MMP)-mediated ECM degradation are parts of tumorgenesis and generates collagen fragments that are released into circulation. We evaluated the association of specific collagen fragments measured in serum with outcomes in two independent metastatic breast cancer (MBC) cohorts. ELISAs were used to measure C1M (MMP-generated type I collagen fragment), C3M (MMP-generated type III collagen fragment), C4M (MMP-generated type IV collagen fragment), and PRO-C3 (pro-peptide of type III collagen) in pretreatment serum from a phase 3 randomized clinical trial of second-line hormone therapy (HR+, n = 148), and a first-line trastuzumab-treated cohort (HER2+, n = 55). All sites of metastases were included. The collagen fragments were evaluated by Cox-regression analysis for their association with time-to-progression (TTP) and overall survival (OS). In the HR+ cohort, higher C1M and C3M levels (75th percentile cut-off) were associated with shorter TTP; all fragments were associated with shorter OS. In the HER2+ cohort, higher levels of all fragments were associated with shorter TTP; higher PRO-C3 was associated with shorter OS. In multivariate analysis of the HR+ trial for OS, higher levels of all fragments were significant for reduced OS when added separately (C1M HR = 2.1, p < 0.001; C3M HR = 1.8, p = 0.028; C4M HR = 1.8, p = 0.018; PRO-C3 HR = 1.8, p = 0.017); none other clinical covariates were significant. In conclusion, collagen fragments quantified in pretreatment serum was associated with shorter TTP and OS in two independent MBC cohorts receiving systemic therapy. If validated, quantification of ECM remodeling in serum has potential as prognostic and/or predictive biomarkers in MBC.

Malignant hyperthermia in a young adolescent: A case report.

A 15-year-old girl developed symptoms suggestive of malignant hyperthermia during a laparoscopic appendicectomy for acute appendicitis. The triad of masseter spasm, hypercarbia and hyperthermia within 30 minutes of exposure to triggering factors was present and was treated successfully with dantrolene. She is among a handful of cases known locally. The problems faced in the post-acute phase included the development of thrombophlebitis due to dantrolene use in our patient, as well as paucity of testing centres for malignant hyperthermia both locally and in the region. This prevented us from making a definitive diagnosis in our patient.

Long-Term Outcomes of Surgery and Radiation Treatment for Adult Patients with Craniopharyngioma.

OBJECTIVE: Treatment of craniopharyngioma typically entails gross total resection (GTR) or subtotal resection with adjuvant radiation (STR-RT). We analyzed outcomes in adults with craniopharyngioma undergoing GTR versus STR-RT. METHODS: This retrospective study enrolled 115 patients with craniopharyngioma in 5 institutions. Patients with STR received postoperative RT with stereotactic radiosurgery or fractionated radiation therapy per institutional preference and ability to spare optic structures. RESULTS: Median age was 44 years (range, 19-79 years). GTR was performed in 34 patients and STR-RT was performed in 81 patients with median follow-up of 78.9 months (range, 1-268 months). For GTR, local control was 90.5% at 2 years, 87.2% at 3 years, and 71.9% at 5 years. For STR-RT, local control was 93.6% at 2 years, 90.3% at 3 years, and 88.4% at 5 years. At 5 years following resection, there was no difference in local control (P = 0.08). Differences in rates of visual deterioration or panhypopituitarism were not observed between GTR and STR-RT groups. There was no difference in local control in adamantinomatous and papillary craniopharyngioma regardless of treatment. Additionally, worse local control was found in patients receiving STR-RT who were underdosed with fractionated radiation therapy (P = 0.03) or stereotactic radiosurgery (P = 0.04). CONCLUSIONS: Good long-term control was achieved in adults with craniopharyngioma who underwent STR-RT or GTR with no significant difference in local control. First-line treatment for craniopharyngioma should continue to be maximal safe resection followed by RT as needed to balance optimal local control with long-term morbidity.

Toolbox of individual-level interventions against online misinformation.

The spread of misinformation through media and social networks threatens many aspects of society, including public health and the state of democracies. One approach to mitigating the effect of misinformation focuses on individual-level interventions, equipping policymakers and the public with essential tools to curb the spread and influence of falsehoods. Here we introduce a toolbox of individual-level interventions for reducing harm from online misinformation. Comprising an up-to-date account of interventions featured in 81 scientific papers from across the globe, the toolbox provides both a conceptual overview of nine main types of interventions, including their target, scope and examples, and a summary of the empirical evidence supporting the interventions, including the methods and experimental paradigms used to test them. The nine types of interventions covered are accuracy prompts, debunking and rebuttals, friction, inoculation, lateral reading and verification strategies, media-literacy tips, social norms, source-credibility labels, and warning and fact-checking labels.

Using longitudinal data from the Health Survey for England to resolve discrepancies in thresholds for haemoglobin in older adults.

Anaemia increases with age and is common among older people. Due to its relationship with morbidity and mortality, accurate diagnosis is important. Thresholds defining the diagnosis of anaemia have been the subject of considerable scientific debate, with both higher and lower cut-offs proposed. High haemoglobin is also a health risk in some but not all studies. Using nationally representative data of 5,329 adults aged 65 + years (Health Survey for England 1998, 2005, 2006), linked to administrative mortality data, this paper describes the relationship between haemoglobin levels and mortality, adjusted for age and other confounders. Among men, a reverse J shaped relationship was observed: relative to the modal group (140-149 g/l), those with 'mild anaemia' of 120-129 g/l haemoglobin had a 56% (95% confidence interval 24-96%) greater mortality hazard, and those with 'severe anaemia', haemoglobin <120 g/l, had an 87% (39-153%) greater hazard. At the other end of the range, those with haemoglobin ≥160 g/l had 32% (2-70%) greater mortality hazard. Haemoglobin levels in women showed a similar but smaller, non-significant pattern: hazard ratio 1·32 (0·91-1·92) for severe anaemia (<110 g/l), and 1·30 (0·95-1·79) for high haemoglobin (≥150 g/l). This research supports the use of the World Health Organization thresholds (130 g/l for men, 120 g/l for women).

Prevalence of chronic kidney disease in patients undergoing cardiac rhythm device removal.

Cardiac implantable electronic device (CIED) leads can cause central venous stenosis (CVS). In addition, these devices can get infected. Both are critically important considerations in patients with chronic kidney disease (CKD) for at least two reasons: (i) central veins serve as the final pathway should these patients need an arteriovenous access to provide dialysis therapy; and (ii) the presence of renal failure increases the risk of CIED infection. In this analysis, we investigated the prevalence as well as the degree of chronic kidney disease in patients harboring a CIED. Patients undergoing CIED removal were evaluated from 2001 to 2011. The patients were categorized into CKD stage I-V based on National Kidney Foundation-Dialysis Outcomes Quality Initiative guidelines. A total of 503 patients underwent CIED removal. Demographic characteristics revealed that 30% had hypertension, 44% were diabetics, 77% had coronary artery disease, and 84% suffered from congestive heart failure. Ninety percent (452/503) of the patients had CKD (stage I = I9 [4.2%], stage II = 189 [41.8%], stage III A = 96 [21.2%], stage III B = 59 [13.0%], stage IV = 45 [9.9%], and stage V = 44 [9.7%]). Overall, 148 (32.7%) patients (stage III B, stage IV, and stage V) of 452 had advanced renal failure. The results of this study reveal that one-third of CIED patients undergoing device removal have advanced chronic kidney disease.

Biodegradation of low density polyethylene (LDPE) by mesophilic fungus 'Penicillium citrinum' isolated from soils of plastic waste dump yard, Bhopal, India.

Low density Polyethylene (LDPE) in various forms has become a part of life. Its accretion due to non degradable nature is concern, endangering life on earth. Amongst various methods of LDPE disposal bioremediation is regarded as ecofriendly & widely accepted. Current investigation was an attempt to isolate potent PE degrading fungus from municipal landfill soils of Bhopal, India loaded with plastic waste.16 fungal isolates were recorded from the site; PE deteriorating fungus was screened using mineral salt agar medium amended with 3% LDPE powder as sole carbon source. The isolate Penicillium citrinum showed fast fungal colony growth in screening medium was selected for biodegradation study. P.citrinum showed 38.82 ± 1.08% weight loss of untreated LDPE pieces; to improve the degradation capacity nitric acid pretreatment was performed; biodegradation was significantly stimulated by 47.22 ± 2.04% after it's pretreatment. Laccase, lipase, esterase & manganese peroxidase activities were assayed by spectrophotometer. LDPE biodegradation was analyzed by weight loss %, change in pH during fungal growth, field emission scanning electron microscopy (FE-SEM), fourier transform infrared spectroscopy (FTIR) & thermogravimetric analysis (TGA). FTIR spectra showed appearance of new functional groups assigned to hydrocarbon biodegradation, confirming enzymatic role in process. Changes in FTIR spectra of LDPE samples (untreated & pretreated) before & after biodegradation & surface changes in the biodegraded LDPE (indicated from FE-SEM) confirmed depolymerization of LDPE. Further changes in thermal decomposition rates of biodegraded samples in comparison to control, validate biodegradation. This is the first report signifying high competence of P.citrinum in LDPE degradation without prior pretreatment.

Benefits and Challenges of Video Consulting for Mental Health Diagnosis and Follow-Up: A Qualitative Study in Community Care.

Mental health services continue to experience rising demand that exceeds capacity. The COVID-19 pandemic exacerbated this crisis, with access to services being reduced. Although video consultations (VCs) are a solution, usage in UK community mental healthcare settings remains limited. This study aims to investigate psychiatrists' and general practitioners' (GPs) perceptions of the benefits and challenges of VC for the diagnosis and follow-up of general adult mental health patients in the community during the COVID-19 pandemic. Semi-structured interviews in NHS community mental healthcare settings were conducted. Psychiatrists (n = 11) and GPs (n = 12) were recruited through purposive sampling. An explorative qualitative approach was employed. Data were analysed using thematic analysis. Four key themes were identified: (1) patient access to VC, (2) suitability of VC for mental health consultations, (3) information gathering with VC and (4) clinician satisfaction with VC. This study provides valuable insights into the experiences of psychiatrists and GPs working in the UK during the COVID-19 pandemic. To facilitate a digital-first future for the NHS, greater investment in remote technologies is required, particularly in the context of growing mental healthcare demand. Though face-to-face consultations remain the gold standard, VC provides an efficient way of communicating with patients, particularly those with less severe forms of mental illness.

Diagnostic Accuracy of Bayley III Screening Tool to Detect Developmental Delay in Moderate to High-Risk Indian Preterm Children.

The present study aimed to evaluate the ability of the Bayley III screening tool to detect developmental delay in moderate to high-risk preterm children in India. In this cross-sectional study, 94 preterm babies were enrolled. The Bayley III screener (index test) and the gold-standard, Developmental assessment scale for Indian Infants (DASII) test were administered to all the enrolled children. Researchers were blinded while performing the tests. Diagnostic accuracy parameters were compared. The Bayley III screener's sensitivity and specificity for predicting the delay (with a DASII cut-off of <70) were 84.62% and 85.18% in the mental domain and 61.11% and 96.05% in the motor domain, respectively. When the DASII cut-off was raised to 85, the sensitivity and specificity in the mental domain were 60.61% and 95.08%, respectively, whereas they were 36.11% and 98.27%, respectively, in the motor domain. The Bayley III screener is found to have good specificity rather than sensitivity with good predictive values.

Multiple myeloma and its rare paraneoplastic manifestations simmering under the surface.

Paraneoplastic syndromes are complex clinical manifestations that occur because of the underlying malignancy in which the malignant cells produce hormones, cytokines, peptides or antibodies that causes symptoms and may affect multiple organ systems. These paraneoplastic conditions may be associated with different solid and hematological malignancies. Multiple Myeloma (MM) accounts for 10-15 % of hematological malignancies and 1-2 % of all malignancies. It is associated with some atypical clinical and laboratory paraneoplastic manifestations. Although there is a low incidence of these paraneoplastic, significant knowledge of these manifestations may assist in making a differential diagnosis in cases of doubt. The clinical presentation may vary and be evident even before or after the diagnosis of malignancy. These include vascular, neurological, dermatological, physiological, and other atypical conditions. Furthermore, these rare paraneoplastic manifestations need more valid, relevant scientific information, as most information about these conditions is derived from case reports. After the literature search, we have reported the paraneoplastic manifestations associated with multiple myeloma, published in the English literature, and the cognate management in this review article. To our knowledge, this is the first review article discussing various paraneoplastic manifestations of multiple myeloma.