Molecular cartography uncovers evolutionary and microenvironmental dynamics in sporadic colorectal tumors.

Colorectal cancer exhibits dynamic cellular and genetic heterogeneity during progression from precursor lesions toward malignancy. Analysis of spatial multi-omic data from 31 human colorectal specimens enabled phylogeographic mapping of tumor evolution that revealed individualized progression trajectories and accompanying microenvironmental and clonal alterations. Phylogeographic mapping ordered genetic events, classified tumors by their evolutionary dynamics, and placed clonal regions along global pseudotemporal progression trajectories encompassing the chromosomal instability (CIN+) and hypermutated (HM) pathways. Integrated single-cell and spatial transcriptomic data revealed recurring epithelial programs and infiltrating immune states along progression pseudotime. We discovered an immune exclusion signature (IEX), consisting of extracellular matrix regulators DDR1, TGFBI, PAK4, and DPEP1, that charts with CIN+ tumor progression, is associated with reduced cytotoxic cell infiltration, and shows prognostic value in independent cohorts. This spatial multi-omic atlas provides insights into colorectal tumor-microenvironment co-evolution, serving as a resource for stratification and targeted treatments.

GammaGateR: semi-automated marker gating for single-cell multiplexed imaging.

MOTIVATION: Multiplexed immunofluorescence (mIF) is an emerging assay for multichannel protein imaging that can decipher cell-level spatial features in tissues. However, existing automated cell phenotyping methods, such as clustering, face challenges in achieving consistency across experiments and often require subjective evaluation. As a result, mIF analyses often revert to marker gating based on manual thresholding of raw imaging data. RESULTS: To address the need for an evaluable semi-automated algorithm, we developed GammaGateR, an R package for interactive marker gating designed specifically for segmented cell-level data from mIF images. Based on a novel closed-form gamma mixture model, GammaGateR provides estimates of marker-positive cell proportions and soft clustering of marker-positive cells. The model incorporates user-specified constraints that provide a consistent but slide-specific model fit. We compared GammaGateR against the newest unsupervised approach for annotating mIF data, employing two colon datasets and one ovarian cancer dataset for the evaluation. We showed that GammaGateR produces highly similar results to a silver standard established through manual annotation. Furthermore, we demonstrated its effectiveness in identifying biological signals, achieved by mapping known spatial interactions between CD68 and MUC5AC cells in the colon and by accurately predicting survival in ovarian cancer patients using the phenotype probabilities as input for machine learning methods. GammaGateR is a highly efficient tool that can improve the replicability of marker gating results, while reducing the time of manual segmentation. AVAILABILITY AND IMPLEMENTATION: The R package is available at https://github.com/JiangmeiRubyXiong/GammaGateR.

Clinical spectrum, phenotypic and molecular characterization, and antifungal susceptibility of an emerging human pathogen, Acrophialophora, from India.

Acrophialophora is implicated in superficial and invasive infections, especially in immunosuppressed individuals. The present study was undertaken to provide clinical, microbiological, phylogenetic, and antifungal susceptibility testing (AFST) profile of Acrophialophora isolated from India. All the isolates identified as Acrophialophora species at National Culture Collection for Pathogenic Fungi, Chandigarh, India were revived. Phenotypic and molecular characterization was performed, followed by temperature studies, scanning electron microscopy (SEM) and AFST. We also performed systematic review of all the cases of Acrophialophora species reported till date. A total of nine isolates identified as Acrophialophora species were identified by molecular method as A. fusispora (n = 8) and A. levis (n = 1), from brain abscess (n = 4), respiratory tract (n = 3) and corneal scraping (n = 2). All patients but two had predisposing factors/co-morbidities. Acrophialophora was identified as mere colonizer in one. Temperature studies and SEM divulged variation between both species. Sequencing of the ITS ribosomal DNA and beta-tubulin loci could distinguish species, while the LSU ribosomal DNA locus could not. AFST showed lowest MICs for triazoles and highest for echinocandins. Systematic literature review revealed 16 cases (11 studies), with ocular infections, pulmonary and central nervous system infections, and A. fusispora was common species. All the patients except three responded well. High MICs were noted for fluconazole, micafungin and caspofungin. This is the first study delineating clinical, phenotypic, and genotypic characteristics of Acrophialophora species from India. The study highlights microscopic differences between both species and emphasizes the role of molecular methods in precise identification. Triazoles appear to be the most effective antifungals for managing patients.

We describe clinical, phenotypic, and genotypic characteristics of Acrophialophora species. This species causes mild infection to fatal infection in immunosuppressed individuals. Triazoles are effective in treating such infections.

Immune and metabolic perturbations in COVID-19-associated pulmonary mucormycosis: A transcriptome analysis of innate immune cells.

BACKGROUND AND OBJECTIVES: The mechanisms underlying COVID-19-associated pulmonary mucormycosis (CAPM) remain unclear. We use a transcriptomic analysis of the innate immune cells to investigate the host immune and metabolic response pathways in patients with CAPM. PATIENTS AND METHODS: We enrolled subjects with CAPM (n = 5), pulmonary mucormycosis (PM) without COVID-19 (n = 5), COVID-19 (without mucormycosis, n = 5), healthy controls (n = 5) without comorbid illness and negative for SARS-CoV-2. Peripheral blood samples from cases were collected before initiating antifungal therapy, and neutrophils and monocytes were isolated. RNA sequencing was performed using Illumina HiSeqX from monocytes and neutrophils. Raw reads were aligned with HISAT-2 pipeline and DESeq2 was used for differential gene expression. Gene ontology (GO) and metabolic pathway analysis were performed using Shiny GO application and R packages (ggplot2, Pathview). RESULTS: The derangement of core immune and metabolic responses in CAPM patients was noted. Pattern recognition receptors, dectin-2, MCL, FcRγ receptors and CLEC-2, were upregulated, but signalling pathways such as JAK-STAT, IL-17 and CARD-9 were downregulated; mTOR and MAP-kinase signalling were elevated in monocytes from CAPM patients. The complement receptors, NETosis, and pro-inflammatory responses, such as S100A8/A9, lipocalin and MMP9, were elevated. The major metabolic pathways of glucose metabolism-glycolysis/gluconeogenesis, pentose phosphate pathway, HIF signalling and iron metabolism-ferroptosis were also upregulated in CAPM. CONCLUSIONS: We identified significant alterations in the metabolic pathways possibly leading to cellular iron overload and a hyperglycaemic state. Immune responses revealed altered recognition, signalling, effector functions and a pro-inflammatory state in monocytes and neutrophils from CAPM patients.

A novel indirect ELISA for serodiagnosis of mucormycosis using antigens from Rhizopus arrhizus.

BACKGROUND: Due to a delay in diagnosis by conventional techniques and high mortality, the development of a standardised and rapid non-culture-based technique is an unmet need in pulmonary, gastrointestinal, and disseminated forms of mucormycosis. Though limited studies have been conducted for molecular diagnosis, there are no established serologic tests for this highly fatal infection. OBJECTIVE: To develop and evaluate an indirect in-house enzyme-linked immunosorbent assay (ELISA) utilising antigens of Rhizopus arrhizus for detecting anti-Rhizopus antibodies (IgG and IgM) in sera of patients with mucormycosis. METHODS: We extracted both secretory and mycelial Rhizopus antigens using standardised protocols. Bradford assay was used for protein quantification. We then standardised an indirect ELISA using R. arrhizus mycelial and secretory antigens (10.0 µg/mL in bicarbonate buffer pH 9.2) for detecting anti-Rhizopus IgG and IgM antibodies in patient sera. We included patients with mucormycosis, other fungal infections, and healthy controls. Antibody index value (E-value) was calculated for each patient sample. RESULTS: Asparagine broth culture filtrate utilising 85% ammonium sulphate salt fractionation and mycelial homogenate grown in yeast extract peptone dextrose (YPD) broth precipitated with trichloroacetic acid (TCA) yielded a large amount of good-quality protein for the assay. We included 55 patients with mucormycosis (rhino-orbito-cerebral mucormycosis [ROCM, n = 39], pulmonary [n = 15], gastrointestinal [n = 1]), 24 with other fungal infections (probable aspergillosis [n = 14], candidiasis [n = 10]), and healthy controls (n = 16). The sensitivity of the antibody test for diagnosing mucormycosis ranged from 83.6-92.7% for IgG and 72.7-87.3% for IgM, with a specificity of 91.7-92.5% for IgG and 80-82.5% for IgM. The sera from patients with other fungal infections and healthy individuals did not show significant cross-reactivity. CONCLUSION: The detection of anti-Rhizopus IgG antibody performed significantly better in comparison to IgM-based ELISA for diagnosing both ROCM (sensitivity of 84.6% vs. 69.2%) and pulmonary cases (86.6% vs. 80.0%). More extensive studies are required to confirm our findings.

Clinical and Mycologic Characteristics of Emerging Mucormycosis Agent Rhizopus homothallicus.

We retrospectively reviewed consecutive cases of mucormycosis reported from a tertiary-care center in India to determine the clinical and mycologic characteristics of emerging Rhizopus homothallicus fungus. The objectives were ascertaining the proportion of R. homothallicus infection and the 30-day mortality rate in rhino-orbital mucormycosis attributable to R. homothallicus compared with R. arrhizus. R. homothallicus accounted for 43 (6.8%) of the 631 cases of mucormycosis. R. homothallicus infection was independently associated with better survival (odds ratio [OR] 0.08 [95% CI 0.02-0.36]; p = 0.001) than for R. arrhizus infection (4/41 [9.8%] vs. 104/266 [39.1%]) after adjusting for age, intracranial involvement, and surgery. We also performed antifungal-susceptibility testing, which indicated a low range of MICs for R. homothallicus against the commonly used antifungals (amphotericin B [0.03-16], itraconazole [0.03-16], posaconazole [0.03-8], and isavuconazole [0.03-16]). 18S gene sequencing and amplified length polymorphism analysis revealed distinct clustering of R. homothallicus.

Scedosporium Infection in Recipients of Kidney Transplants from Deceased Near-Drowning Donor.

Scedosporium aurianticum infection developed in 2 recipients of kidney transplants in India, acquired from the same deceased near-drowning donor. Given the substantial risk for death associated with Scedosporium infection among solid-organ transplant recipients, safety protocols for organ transplantation from nearly drowned donors should be thoroughly revaluated and refined.

Development of single-tube real-time PCR assay for the rapid detection of Aspergillus and Fusarium-The two most common causative agents in fungal keratitis.

BACKGROUND: To compare the performance of conventional, semi-nested and real-time panfungal ITS PCRs for diagnosing fungal keratitis (FK) and develop genus-specific real-time PCR for the most common aetiology of FK. METHODS: This multicentric study includes 232 corneal samples from suspected FK patients from four centres across India between November 2019 through August 2021. A total of 87 corneal buttons were included for the comparison of conventional, semi-nested and real-time ITS PCRs, of which 68 were from confirmed FK patients. Of these 87 samples, 44 (microscopy and culture positive for Aspergillus sp. and/or Fusarium sp.) were used for the standardisation of genus-specific real-time primers/probes. Subsequently, the best method showing highest sensitivity and specificity was validated in 188 samples. RESULTS: On Bayesian comparison, conventional ITS2 PCR showed best performance (sensitivity and specificity of 55.88% and 100%, respectively). Since, real-time ITS2 PCR was also considerably efficient (sensitivity and specificity of 51.47% and 84.21%, respectively) in comparison with the conventional PCR but faster, cost-effective, and less labor-intensive, ITS-2 real-time PCR is a suitable method that can be applied along with culture and microscopy. During validation, real-time PCR with genus-specific primers showed 61.76% and 91.18% sensitivity with specificity of 98.05% and 79.22%, respectively, for Aspergillus sp. and Fusarium sp. Aspergillus probe, Fusarium probe and duplex PCR showed sensitivity of 52.94%, 50% and 54.41% with specificity of 92.86%, 82.47% and 75%, respectively. No cross-reactivity of genus-specific PCRs was observed during standardisation. CONCLUSIONS: ITS-2 real-time PCR can be applied as an adjunct with conventional methods for the diagnosis of FK. The genus-specific duplex real-time PCRs are rapid which reduces the turnaround time (TAT) avoiding the need for sequencing.

Saksenaea vasiformis infection: Extensive abdominal wall necrotizing fasciitis with systematic review and analysis of 65 cases.

INTRODUCTION: Saksenaea vasiformis is a rarely reported Mucorales causing mucormycosis in both immunocompromised and immunocompetent individuals. Due to few reported cases, the clinical characteristics and optimal management strategy for this rare agent are not clearly described. METHODS: We systematically reviewed Medline, EmBase and CINHAL for studies on S. vasiformis infections reported until 1 January 2022 and 57 studies (63 patients) were retrieved. Additionally, one more case of extensive abdominal wall necrotizing fasciitis managed by our team was also included. The clinical and demographic characteristics and outcomes were extracted and analysed. RESULTS: Out of the 65 included cases, the majority were reported from India (26.6%). The most common risk factors for infection were accidental trauma wounds (31.3%), health-care-related wounds (14.1%) and animal/insect bites (12.5%). Most common clinical presentation was subcutaneous mucormycosis (60.9%) followed by rhino-orbito cerebral mucormycosis (14%), necrotizing fasciitis (10%), disseminated infection (9.3%), pulmonary mucormycosis (3.2%) and osteomyelitis (1.6%). Mortality was observed in 24 (37.5%) patients and health care related injuries were significantly associated with higher mortality (p = .001). The use of posaconazole (p = .019) and the use of surgical management (p = .032) was associated with significantly better survival. DISCUSSION: In this study, we describe the largest compendium of mucormycosis due to S. vasiformis, which can be useful in increasing awareness regarding this rare Mucorales and guiding patient management.

Not all black fungus is mucormycosis: A challenging case of Medicopsis romeroi.

In this case of phaeohyphomycosis, fine needle aspiration cytology enabled a rapid diagnosis and prompt treatment. This infection is quite prevalent in immunocompromised individuals; however, the Medicopsis romeroi species is a rare causative agent. These cases are associated with inadequate response to standard antifungal therapy and require discussion.

Disseminated Cryptococcosis and Pulmonary Mucormycosis: Dealing with Dual Mycoses in a Renal Transplant Patient.

We describe a 36-year-old post-renal transplant patient diagnosed with a rare dual infection by Cryptococcus neoformans and Lichtheimia ramosa. The case highlights the significance of invasive samples and accurate interpretation of fungal biomarkers in the diagnosis of fungal infections in immunosuppressed patients. The mortality in such cases is high owing to delay in diagnosis, inability to perform surgical management or antifungal resistance.

Cladosporium halotolerans: Exploring an Unheeded Human Pathogen.

BACKGROUND: Cladosporium halotolerans is a saprobic fungus, rarely implicated in human infections. The identification is challenging due to non-specific phenotypic features. OBJECTIVE: To decipher clinical spectrum, microbiological and susceptibility profile of clinical and environmental isolates of Cladosporium halotolerans. METHOD: All the isolates identified as Cladosporium halotolerans deposited in National Culture Collection for Pathogenic Fungi (NCCPF), Postgraduate Institute of Medical Education and Research, Chandigarh, India were revived. Phenotypic and molecular characterization targeting internal transcribed spacer (ITS) region of ribosomal DNA, large subunit of ribosomal DNA (LSU; NL1 and NL4), actin (ACT) and beta-tubulin (TUB) was done. Scanning electron microscopy (SEM) was performed to determine any phenotypic variations. Antifungal susceptibility testing (AFST) was carried out for eight antifungal agents as per CLSI M38 Ed3 guidelines. We also performed systematic literature review of all the cases of Cladosporium halotolerans reported till date. RESULTS: A total of four isolates (clinical, n = 3; soil, n = 1) identified as Cladosporium halotolerans were included in the study. The clinical sites were skin, maxillary tissue and nail. All patients were apparently immunocompetent, and history of trauma was recorded in one patient. All patients improved on antifungal therapy. The cultures revealed growth of black mycelial fungus and microscopic examination demonstrated dematiaceous septate hyphae with erect conidiophores and conidia in branched acropetal chains. Based on molecular methods, all the four isolates were identified as C. halotolerans. SEM revealed no variation in length and width of the conidia, conidiophores, ramoconidium and hyphae among the isolates. All molecular targets, such as ITS region, LSU (partially sequenced), ACT and TUB were able to differentiate the isolates. Minimum inhibitory concentrations for antifungals were: triazoles (0.12-2 µg/ml), amphotericin B (4 µg/ml) and echinocandins (2-8 µg/ml). CONCLUSION: We report role of the rarely isolated dematiaceous fungus, C. halotolerans, in causing human infections. The study emphasizes the role of molecular methods in precisely identifying these species. Triazoles are more active against these black fungi compared to polyenes or echinocandins.

Correlation of Serum Vitamin D with Crestal Bone Level in Dental Implant Patients Using CBCT: A Clinical Retrospective Study.

AIM: The purpose of this study is to correlate the role of serum vitamin D levels associated with crestal bone in dental implant patients using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: This retrospective study enrolled patients among whom implants were placed after a detailed planning using CBCT and the delayed loading protocol was followed. After 3 months and 6 months of loading, CBCT evaluations were carried out, serum vitamin D levels were also tested at the end of 6 months of loading. A total of 30 patients were recruited with 15 patients in each group based on normal and deficient levels of vitamin D to correlate with crestal bone levels using CBCT. RESULTS: Clinically acceptable crestal bone loss (CBL) was visible with all the implants at different time intervals. Statistical analysis was done for intergroup and intragroup comparisons which showed significant p-value (< 0.05) for CBL at the time of loading, at 3 months, and at 6 months follow-up for both normal and deficient serum values. In the deficient group, the mean value at baseline was 9.69 mm ± 1.10 and the CBL at 6 months follow-up was 8.80 mm ± 1.10 whereas for the normal group at baseline, the mean was 9.08 mm ± 1.21 and at 6 months follow-up was 8.12 mm ± 1.25 which showed meaningful difference. CONCLUSION: There is a positive correlation seen between CBL on CBCT and vitamin D serum levels. The success of the implant is significantly affected by vitamin D as it regulates the bone physiology and has systemic effects on accelerating bone formation around titanium implants. CLINICAL SIGNIFICANCE: Vitamin D is essential in maintaining the balance of bone minerals and assists to preserve the crestal bone level making the implant treatment more predictable and successful.

Impact of FKS1 Genotype on Echinocandin In Vitro Susceptibility in Candida auris and In Vivo Response in a Murine Model of Infection.

Echinocandins are frontline antifungal agents in the management of invasive infections due to multidrug resistant Candida auris. The study aimed to evaluate echinocandin resistance in C. auris isolates of multicentric origin, identify the resistance mechanism, and analyze the pharmacodynamic response to caspofungin in a neutropenic mouse model of infection. A total of 199 C. auris isolates originating from 30 centers across India were tested for susceptibility to echinocandins. Isolates with reduced susceptibility were evaluated for FKS1 mutations and in vivo response to caspofungin in a murine model of disseminated candidiasis. In addition, the response to echinocandins was assessed in light of in vitro growth kinetics, chitin content; and transcript levels of chitin synthase and FKS1 genes. We report 10 resistant C. auris isolates with four FKS1 mutations: F635Y (n = 2), F635L (n = 4), S639F (n = 3), and R1354S (n = 1). Of these, F635Y and R1354S exhibited the most profound resistance in mouse model of disseminated infection. S639F and F635L mutations conferred a moderate in vivo resistance, whereas wild-type isolates exhibiting borderline MIC were susceptible in vivo. FKS1 genotype was more accurate predictor of in vivo response than the MIC of the isolates. Isolates with high basal or inducible chitin content exhibited higher in vitro MIC in FKS1 mutant compared to wild type. FKS1 mutations play a major role in clinically relevant echinocandin resistance in C. auris with differential in vivo outcomes. This study could have implications for clinical practice and, therefore, warrants further studies.

Exploring the TEMPO-Oxidized Nanofibrillar Cellulose and Short Ionic-Complementary Peptide Composite Hydrogel as Biofunctional Cellular Scaffolds.

Multicomponent self-assembly is an emerging approach in peptide nanotechnology to develop nanomaterials with superior physical and biological properties. Inspired by the multicomponent nature of the native extracellular matrix (ECM) and the well-established advantages of co-assembly in the field of nanotechnology, we have attempted to explore the noncovalent interactions among the sugar and peptide-based biomolecular building blocks as an approach to design and develop advanced tissue scaffolds. We utilized TEMPO-oxidized nanofibrillar cellulose (TO-NFC) and a short ionic complementary peptide, Nap-FEFK, to fabricate highly tunable supramolecular hydrogels. The differential doping of the peptide into the TO-NFC hydrogel was observed to tune the surface hydrophobicity, microporosity, and mechanical stiffness of the scaffold. Interestingly, a differential cellular response was observed toward composite scaffolds with a variable ratio of TO-NFC versus Nap-FEFK. Composite scaffolds having a 10:1 (w/w) ratio of TO-NFC and the Nap-FEFK peptide showed enhanced cellular survival and proliferation under two-dimensional cell culture conditions. More interestingly, the cellular proliferation on the 10:1 matrix was found to be similar to that of Matrigel in three-dimensional culture conditions, which clearly indicated the potential of these hydrogels in advanced tissue engineering applications. Additionally, these composite hydrogels did not elicit any significant inflammatory response in Raw cells and supported their survival and proliferation, which further emphasized their ability to form versatile scaffolds for tissue regeneration. This multicomponent assembly approach to construct biomolecular composite hydrogels to access superior physical and biological properties within the scaffold is expected to improve the scope for designing novel ECM-mimicking biomaterials for regenerative medicine.

Could cattle dung burning have contributed to the epidemic of COVID-19-associated mucormycosis in India? Results of an experimental aero-mycological study.

BACKGROUND: Several hypotheses have been proposed for explaining the outbreak of coronavirus disease 2019 (COVID-19)-associated mucormycosis in India, including the burning of cattle dung cakes, though no study has yet been conducted to support this claim. METHODS: We conducted an aero-mycological study to evaluate whether Mucorales in the air increased during or after burning cattle dung cakes. We further compared the growth of Mucorales in the indoor air samples from houses with and without cattle. We also cultured fresh and dried cattle dung and soil samples for Mucorales. RESULTS: We noted no significant difference in the proportion of air samples growing Mucorales during (4/22 [18.2%]) and after (3/2 [13.6%]) cattle dung burning than that collected immediately before (4/22 [18.2%]). Mucorales were isolated in 15.4% of the indoor air samples obtained from different houses (both rural and urban); the proportion of samples growing Mucorales was not significantly different in households with and without cattle. We also observed growth of Mucorales in 6 of the 8 [75%] fresh and 3 of the 6 [50%] dried dung samples. The most common Mucorales isolated from soil and dung samples was Lichtheimia corymbifera, while Rhizopus arrhizus was the most common species isolated from indoor air samples. CONCLUSIONS: We found no significant increase in the proportion of air samples growing Mucorales during or after burning cattle dung cake than that before. It seems unlikely that cattle dung burning contributes to the occurrence of mucormycosis.

Antifungal prescription practices and consumption in a tertiary care hospital of a developing country.

BACKGROUND: Antifungal stewardship is a less explored component of antimicrobial stewardship programmes, especially in developing countries. OBJECTIVE: We aimed to determine antifungal prescription practices in a tertiary centre of a developing country to identify the challenges for antifungal stewardship programmes. METHODS: Four single-day point prevalent surveys were performed in inpatient units and data were collected from medical records. Antifungal use was recorded in terms of consumption, therapeutic strategies and appropriateness. RESULTS: We found a 2.42%-point prevalence of antifungal prescriptions. Antifungal use was higher in children than adults (4.1% vs. 2.03%), medical than surgical units (3.7% vs. 1.24%) and ICUs than general wards (5.8% vs. 1.9%). The highest antifungal use was observed in the haematology-oncology units (29.3%) followed by emergency (16.2%) and gastroenterology units (11.6%). Among 215 prescriptions, amphotericin B was the most commonly prescribed (50.2%) followed by fluconazole (31.6%). The targeted antifungal therapy was practised more commonly (31.5%) than empiric (29.1%), pre-emptive (22.6%) and prophylactic (16.8%) therapy. Amphotericin B was commonly used for pre-emptive (p = .001) and targeted (p = .049) therapy, while fluconazole (p = .001) and voriconazole (p = .011) for prophylaxis. The prescriptions were inappropriate in 25.1% due to the wrong choice of antifungal (44.4%), indication (27.7%) and dosage (24%). The overall mean antifungal consumption was 2.71 DDD/1000 PD and 8.96 DOT/1000 PD. CONCLUSIONS: We report here the low prevalence of antifungal use at a tertiary care centre in a developing country. Though training for antifungal use would be important for antifungal stewardship, the challenge would remain with the affordability of antifungals.

Painful Purulent Nodules Caused by Mycobacterium at Site of Lipodissolve Injections.

ABSTRACT: "Lipodissolve" (LD) is a non-FDA-approved solution of phosphatidylcholine in deoxycholate that was developed around 2004. A study of its safety reported minor and uncommon side effects including pain, tender nodules, pigmentary alterations, and ulceration at the site of injection. We present a 53-year-old woman who received LD injections bilaterally to her proximal arms. One week later, she developed painful nodules at each injection site. She was treated with a 10-day course of trimethoprim/sulfamethoxazole without improvement. An incisional biopsy was performed and showed deep dermal suppurative inflammation with numerous neutrophils and granulomas. Stains for bacteria, fungus, and acid-fast organisms were negative. Cultures for acid-fast bacilli grew Mycobacterium abscessus, sensitive to amikacin and clarithromycin. The patient was subsequently treated with intravenous amikacin, azithromycin, and bedaquiline with symptom resolution. Investigation revealed 3 similar infections linked to LD injections originating from the same physician's office. The most common organism implicated in injection infections is Staphylococcus aureus. Infections at injection sites caused by atypical mycobacteria have been reported to occur after tattooing, other types of injections, and implants. Of atypical mycobacteria, M. abscessus accounts for the greatest number of postinjection or iatrogenic infections. Common antitubercular drugs are not effective for treating atypical mycobacteria, making species identification and sensitivity testing imperative for treatment. This case highlights an unusual infection caused by cosmetic injections of LD, previously reported to be associated with minimal side effects, and the importance of examination for acid-fast bacilli and follow-up with culture, even in the absence of organisms identified on stained sections.

Multiple Fusarium brain abscesses in a young child.

Isolated intracranial fungal infection is infrequent and mostly seen in high-risk, immunocompromised patients. Fusarium, a primary plant fungus, rarely contributes to such disease. Amongst the very few cases of Fusarium brain abscess that have been reported, the infection has occurred mostly in adults. We present a case of a 6-year-old boy with tuberculous meningitis diagnosed with multiple Fusarium brain abscess caused by Fusarium falciforme during his clinical course. An immunocompromised state secondary to tuberculous meningitis presumably led to this infection. After tapping the abscesses, the child was treated with a combination of amphotericin B, voriconazole and terbinafine. Despite an aggressive therapy, he remained in poor neurological state. This is the second report of an isolated Fusarium abscess in pediatric age and the first one in a young child and provides pertinent review of this unusual central nervous system fungal infection. Such unusual infectious spectrum should be borne in mind in patients with co-existent immunosuppression.

Pediatric case of conidiobolomycosis: A rare entity.

Conidiobolomycosis caused by Conidiobolus species is an uncommon infection restricted to tropical and subtropical regions, usually affecting immunocompetent individuals. More than half of pediatric cases of conidiobolomycosis across the globe are from India. We report a case of subcutaneous conidiobolomycosis in an adolescent with development delay who responded to combined therapy with itraconazole and saturated solution of potassium iodide.