COVID-19 associated mucormycosis surge: A review on multi-pathway mechanisms.

Mucormycosis is a fungal infection caused by moulds from the Mucorales order. Concerns have been mounting due to the alarming increase in severe morbidity and mortality associated with mucormycosis during the COVID-19 pandemic. This condition, known as COVID-19-associated mucormycosis (CAM), has been linked to various environmental, host-related, and medical factors on a global scale. We have categorized the most significant potential risk factors for developing mucormycosis in individuals with a previous history of coronavirus infection into 10 major categories. These categories include acute hyperglycemia, the impact of cytokine release, immune response deficiencies in COVID-19 patients, microvasculopathy and dysfunction of endothelial cells, imbalances in iron metabolism, metabolic acidosis, organ damage resulting from COVID-19, underlying health conditions (such as diabetes), environmental factors, and medical treatments that can be iatrogenic in nature (such as inappropriate glucocorticoid use). Many of these factors can lead to potentially life-threatening infections that can complicate the treatment of COVID-19. Physicians should be vigilant about these factors because early detection of mucormycosis is crucial for effective management of this condition.

Factors Influencing Mortality in COVID-19-Associated Mucormycosis - The International ID-IRI Study.

The emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), triggered a global pandemic. Concurrently, reports of mucormycosis cases surged, particularly during the second wave in India. This study aims to investigate mortality factors in COVID-19-associated mucormycosis (CAM) cases, exploring clinical, demographic, and therapeutic variables across mostly Asian and partly African countries. A retrospective, cross-sectional analysis of CAM patients from 22 medical centers across eight countries was conducted, focusing on the first three months post-COVID-19 diagnosis. Data collected through the IDI-IR included demographics, comorbidities, treatments, and outcomes. A total of 162 CAM patients were included. The mean age was 54.29±13.04 years, with 54% male. Diabetes mellitus (85%) was prevalent, and 91% had rhino-orbital-cerebral mucormycosis (ROCM). Surgical debridement was performed in 84% of the cases. Mortality was 39%, with advanced age [Hazard Ratio (HR)=1.06, (p<0.001)], rituximab use (HR=21.2, p=0.05), diabetic ketoacidosis (HR=3.58, p=0.009) identified as risk factors. The mortality risk increases by approximately 5.6% for each additional year of age. Surgical debridement based on organ involvement correlated with higher survival (HR=8.81, p<0.001). The utilization of rituximab and diabetic ketoacidosis along with advancing age, has been associated with an increased risk of mortality in CAM patients. A combination of antifungal treatment and surgical intervention has demonstrated a substantial improvement in survival outcomes.

Over a third of patients who developed mucormycosis after COVID-19 died. Older people, those on specific immunosuppressive treatments and those with diabetic ketoacidosis had a higher risk of death. However, undergoing surgery as part of treatment significantly improved survival.

Delayed Diagnosis of Chronic Necrotizing Granulomatous Skin Lesions due to TAP2 Deficiency.

Major histocompatibility complex class I (MHC-I) deficiency, also known as bare lymphocyte syndrome type 1 (BLS-1), is a rare autosomal recessively inherited immunodeficiency disorder with remarkable clinical and biological heterogeneity. Transporter associated with antigen processing (TAP) is a member of the ATP-binding cassette superfamily of transporters and consists of two subunits, TAP1 or TAP2. Any defect resulting from a mutation or deletion of these two subunits may adversely affect the peptide translocation in the endoplasmic reticulum, which is an important process for properly assembling MHC-I molecules. To date, only 12 TAP2-deficient patients were reported in the literature. Herein, we described two Iranian cases with 2 and 3 decades of delayed diagnosis of chronic necrotizing granulomatous skin lesions due to TAP2 deficiency without pulmonary involvement. Segregation analysis in family members identified 3 additional homozygous asymptomatic carriers. In both asymptomatic and symptomatic carriers, HLA-I expression was only 4-15% of the one observed in healthy controls. We performed the first deep immunophenotyping in TAP2-deficient patients. While total CD8 T cell counts were normal as previously reported, the patients showed strongly impaired naïve CD8 T cell counts. Mucosal-associated invariant T (MAIT) cells and invariant natural killer T (iNKT) cell counts were increased.

Classical fever of unknown origin in 21 countries with different economic development: an international ID-IRI study.

Fever of unknown origin (FUO) is a serious challenge for physicians. The aim of the present study was to consider epidemiology and dynamics of FUO in countries with different economic development. The data of FUO patients hospitalized/followed between 1st July 2016 and 1st July 2021 were collected retrospectively and submitted from referral centers in 21 countries through ID-IRI clinical research platform. The countries were categorized into developing (low-income (LI) and lower middle-income (LMI) economies) and developed countries (upper middle-income (UMI) and high-income (HI) economies). This research included 788 patients. FUO diagnoses were as follows: infections (51.6%; n = 407), neoplasms (11.4%, n = 90), collagen vascular disorders (9.3%, n = 73), undiagnosed (20.1%, n = 158), miscellaneous diseases (7.7%, n = 60). The most common infections were tuberculosis (n = 45, 5.7%), brucellosis (n = 39, 4.9%), rickettsiosis (n = 23, 2.9%), HIV infection (n = 20, 2.5%), and typhoid fever (n = 13, 1.6%). Cardiovascular infections (n = 56, 7.1%) were the most common infectious syndromes. Only collagen vascular disorders were reported significantly more from developed countries (RR = 2.00, 95% CI: 1.19-3.38). FUO had similar characteristics in LI/LMI and UMI/HI countries including the portion of undiagnosed cases (OR, 95% CI; 0.87 (0.65-1.15)), death attributed to FUO (RR = 0.87, 95% CI: 0.65-1.15, p-value = 0.3355), and the mean duration until diagnosis (p = 0.9663). Various aspects of FUO cannot be determined by the economic development solely. Other development indices can be considered in future analyses. Physicians in different countries should be equally prepared for FUO patients.

Meningoencephalitis caused by Fusarium proliferatum: an unusual case.

Meningoencephalitis can be a diagnostic dilemma and one of its etiology are infectious causes including fungal agents. Fusarium species have attracted much attention as one of the invasive fungal infections. Major clinical manifestations of infections due to Fusarium spp. are broad such as keratitis, endophthalmitis, sino-pulmonary and central nervous system (CNS) infections. However, CNS fusariosis is rare and often happens due to hematogenous dissemination from other sites. Herein, we describe an unusual case of meningoencephalitis caused by Fusarium proliferatum, in a patient with rheumatoid arthritis.

An extremely rare mucocutaneous adverse reaction following COVID-19 vaccination: Toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), is a type of delayed hypersensitivity reaction that requires urgent medical intervention. In the COVID-19 era, COVID-19 vaccines are currently being widely administered and mucocutaneous adverse reactions following vaccination have been reported; however, severe cutaneous adverse reactions associated with COVID-19 vaccines including SJS/TEN, are extremely rare. Herein, we describe a case of COVID-19 vaccination induced TEN which developed 1 day after receiving the first dose of Sinopharm COVID-19 vaccine with favorable clinical outcome.

Relationship between CT Severity Score and Capillary Blood Oxygen Saturation in Patients with COVID-19 Infection.

Background: COVID-19 pneumonia is responsible for the latest pandemic. Usage of pulmonary computed tomography (CT) scan is known to be an important method in the diagnosis of COVID-19. Here, we aimed to evaluate the relationship between CT severity score and capillary blood oxygen saturation in patients with COVID-19 infection. Methods and material: This is a cross-sectional study performed in 2020 on patients with COVID-19 infection. All patients underwent pulmonary CT scan and CT severity score was calculated. The initial capillary oxygen saturation by the time of admission was also collected. Data were collected and analyzed. Results: A total number of 270 patients diagnosed with COVID-19 infection entered the study. The initial mean capillary oxygen saturation was 89.65 ± 8.09%. The mean score in patients was 15.16 ± 8.08. We also indicated that 27 patients had hypoxia by the time of admission and these patients had significantly higher CT severity scores (p = 0.001). Diabetes mellitus (p = 0.001), hypertension (p = 0.001), and chronic obstructive pulmonary disease (COPD) (p = 0.03) and totally having an underlying disease (p < 0.001) were significantly associated with decreased capillary oxygen saturation. Patients with hypertension (p = 0.001) and patients with the previous medical disease (p = 0.01) had significantly higher CT severity scores than others. There was a significant reverse relationship between CT severity score and capillary oxygen saturation (r = -0.44, p < 0.001). Conclusions: We showed that there was a significant reverse relationship between CT severity score and capillary oxygen saturation which has great clinical importance. Furthermore, we indicated that previous medical history could also play an important role in CT severity score. How to cite this article: Aalinezhad M, Alikhani F, Akbari P, Haji Rezaei M, Soleimani S, Hakamifard A. Relationship between CT Severity Score and Capillary Blood Oxygen Saturation in Patients with COVID-19 Infection. Indian J Crit Care Med 2021;25(3):279-283.

Comparison of two therapeutic approaches for the management of ventilator-associated pneumonia due to multidrug-resistant Acinetobacter: a randomized clinical trial study.

Management of ventilator-associated pneumonia (VAP) is a puzzling issue for infectious disease specialist. The present clinical trial study was aimed to comparing the effects of injectable colistin plus nebulized colistin and injectable colistin plus nebulized tobramycin on management of patients with VAP due to multidrug-resistant Acinetobacter. VAP patients were randomly divided into two groups (n = 30/each): Group 1 - patients that received intravenous (IV) meropenem, injectable colistin plus nebulized colistin, as a routine treatment, and Group 2 - patients that received IV meropenem, injectable colistin plus nebulized tobramycin. A total of 14 days of therapeutic intervention are required for every case. Follow-up for subjects was performed at five time-points: days 1, 3, 5, 7, and 14 after intervention. Also, a mean of creatinine levels of patients was determined in five times. In the present study, the clinical pulmonary infection score (CPIS) was determined on the basis of points assigned for various clinically manifestations of VAP. Based on our statistical analysis, there was no significant difference between CPIS and creatinine level in both Groups 1 and 2 (p > .05). CPIS and other clinical investigation appeared effectiveness of the treatment with injected colistin plus nebulized tobramycin; on the other hand, the results of present clinical trial showed that aforementioned therapeutic approach can be used as an alternative treatment for the management of infection in VAP patients.

The heel amelanotic melanoma, a rare subtype of skin cancer misdiagnosed as foot ulcer: A case report.

Amelanotic melanoma (AM) of the heel is a very rare subtype of malignant melanoma in which the tumour cells, unlike other types of melanoma, are characterised by little or no melanin pigmentation. AM resembles many benign dermatological complications that often lead to late diagnosis of lesions, poor prognosis, and occasionally misdiagnosis at an early stage of the disease. We report a case of a 73-year-old man with a heel ulcer who was admitted to Al-Zahra Hospital (Isfahan, Iran). Chronic osteomyelitis was considered the primary diagnosis, and several courses of antibiotics were prescribed for the patient. The ulcer failed to improve after 9 months' of therapy, and because of an increase in the size of the ulcer and the growth of two tumours in the right heel, a biopsy of the lesion was conducted. The pathology report confirmed invasive AM. The present report emphasises the necessity to biopsy all skin lesions, even with low clinical significance, to avoid wrong subsequent treatments, prevent a delay in diagnosis, reduce misdiagnosis, and improve the survival rate of patients.

Cerebral phaeohyphomycosis due to Rhinocladiella mackenziei in Persian Gulf region: A case and review.

Cerebral phaeohyphomycosis is frequently a fatal disease caused by truly neurotropic dematiaceous fungi. Although rare, this infection occurs especially among immunocompetent patients, and the clinical symptoms are often misdiagnosed as a cerebral tumour or bacterial brain abscess. The appropriate diagnosis and therapy of cerebral infections by melanized fungi are very challenging if they are caused by mysterious fungi with unknown ecological niche. We reported the second case of cerebral phaeohyphomycosis due to Rhinocladiella mackenziei in Iran and the first culture-confirmed case. In this report, the differential diagnosis and histopathological findings are discussed and a review of the literature is provided.

Candida endophthalmitis and Candida pneumonia after trans-urethral lithotripsy: A case report.

Key Clinical Message: Invasive candidiasis may be one of the serious complications of transurethral lithotripsy. Candiduria before this procedure should be assessed, and antifungals should be prescribed. Abstract: This case is about a 44-year-old diabetic female patient who, after trans-urethral lithotripsy with double-J stent insertion, was diagnosed with Candida pneumonia and Candida endophthalmitis.

Sequential therapy versus quadruple therapy for Helicobacter pylori eradication: A prospective double-blinded randomized controlled trial.

Backgrounds and Aims: This controlled randomized clinical trial was designed to compare effectiveness, side effects, and severity of symptoms before and after therapy between quadruple (QT) and sequential regimens (SQ) for Helicobacter Pylori (H. pylori). Methods: Patients were randomly allocated into two groups. Group A received a 14-day QT including pantoprazole 40 mg q12 h, bismuth subcitrate 240 mg q12 h, clarithromycin 500 mg q12 h, and amoxicillin 1000 mg q12 h and group B received ST including pantoprazole 40 mg q12 h and amoxicillin 1000 mg q12 h for the initial 5 days followed by pantoprazole 40 mg q12 h, clarithromycin 500 mg q12 h and tinidazole 500 mg q12 h for the next 5 days. Adverse drug reactions and patients' compliance were assessed after finishing the treatment course and also 4 weeks after. All patients were naive, therefore ST and QT were first-line therapies. To evaluate severity of symptoms we used Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ) before taking the first dose of regimens, at the end of therapy, and also 4 weeks after (follow-up). Results: The mean age in Group A (n = 83) was 48.55 ± 12.56 and 47.24 ± 12.78 in Group B (n = 79). No statistically significant differences were observed between the two groups regarding age, gender, endoscopic findings, and also eradication rate. The analysis demonstrated a significant decrease in SF-LDQ score between baseline and after therapy and baseline and follow-up in both regimen groups. Both regimens were well tolerated by the majority of patients, and there were no significant differences between the two groups in terms of adverse drug reactions. Conclusion: This study showed that ST can be used as an alternative first-line therapy to QT in patients with H. pylori infection.

Infectious causes of fever of unknown origin in developing countries: An international ID-IRI study.

Background: Fever of unknown origin (FUO) in developing countries is an important dilemma and further research is needed to elucidate the infectious causes of FUO. Methods: A multi-center study for infectious causes of FUO in lower middle-income countries (LMIC) and low-income countries (LIC) was conducted between January 1, 2018 and January 1, 2023. In total, 15 participating centers from seven different countries provided the data, which were collected through the Infectious Diseases-International Research Initiative platform. Only adult patients with confirmed infection as the cause of FUO were included in the study. The severity parameters were quick Sequential Organ Failure Assessment (qSOFA) ≥2, intensive care unit (ICU) admission, vasopressor use, and invasive mechanical ventilation (IMV). Results: A total of 160 patients with infectious FUO were included in the study. Overall, 148 (92.5%) patients had community-acquired infections and 12 (7.5%) had hospital-acquired infections. The most common infectious syndromes were tuberculosis (TB) (n=27, 16.9%), infective endocarditis (n=25, 15.6%), malaria (n=21, 13.1%), brucellosis (n=15, 9.4%), and typhoid fever (n=9, 5.6%). Plasmodium falciparum, Mycobacterium tuberculosis, Brucellae, Staphylococcus aureus, Salmonella typhi, and Rickettsiae were the leading infectious agents in this study. A total of 56 (35.0%) cases had invasive procedures for diagnosis. The mean qSOFA score was 0.76±0.94 {median (interquartile range [IQR]): 0 (0-1)}. ICU admission (n=26, 16.2%), vasopressor use (n=14, 8.8%), and IMV (n=10, 6.3%) were not rare. Overall, 38 (23.8%) patients had at least one of the severity parameters. The mortality rate was 15 (9.4%), and the mortality was attributable to the infection causing FUO in 12 (7.5%) patients. Conclusions: In LMIC and LIC, tuberculosis and cardiac infections were the most severe and the leading infections causing FUO.

Adult-onset still's disease and budd-chiari syndrome: A case report.

Adult onset still's disease (AOSD) is a rare autoinflammatory disease displaying with a wide range of non-specific symptoms and budd-chiari syndrome (BCS) is an uncommon disorder characterized by obstruction of hepatic venous outflow. We present the case of a young patient who presented with persistent fever, sore throat, elbow, hand fingers and knees arthralgia with abdominal pain. The patient's symptoms had started 7 days before the referral. Imaging and laboratory data led to the diagnosis of BCS in the context of AOSD. The patient treated with corticosteroid in combination of warfarin with favorable outcome and complete improvement of signs and symptoms. We came to this conclusion AOSD complicated with BCS is a rare but potentially life-threatening entity. Clinicians should be aware of this complication.

Electrolyte abnormalities in hospitalized COVID-19 patients at tertiary referral centers in Tehran: Hypermagnesemia as a marker of fatality: A retrospective cross-sectional study.

Background and Aims: To evaluate biochemical abnormalities and their association with the outcome of hospitalized coronavirus disease 2019 (COVID-19) patients at a tertiary referral center in Iran. Methods: This retrospective study was conducted on COVID-19 patients who were admitted at tertiary referral centers in Tehran, Iran, from March 2021 to 2022. Demographic and biochemical laboratory data of the patients including blood sodium, potassium, calcium, and magnesium were collected from patient treatment sheets of severe COVID-19 patients admitted to a different ward of the hospital. A logistic regression model was fitted to identify the associated parameters with mortality. Results: Four hundred and ninety-nine patients with COVID-19, including 287 males (57.5%), who had a mean age of 58.95 ± 16.60 years, were enrolled. Thirty-eight patients (7.62%) died during hospitalization. The factors we found to be independently associated with an increased risk of in-hospital death were having comorbidity (mortality of 94.7%, vs. 61% among those without comorbidity; odds ratio, 17.71; 95% confidence interval [CI], 3.81-82.37), hypermagnesemia (34.2%, vs. 26.2% among those with normal magnesium; odds ratio, 9.71; 95% CI, 2.958-31.91), and having a male gender (34.2%, vs. 26.2% among those were female; odds ratio, 9.71; 95% CI, 2.958-31.91). Conclusions: Hypermagnesemia, having a male gender, and the existence of comorbidity in patients with COVID-19 is associated with an increase in mortality. Further studies on the pathogenic mechanisms and therapeutic implications need to be done.

The effectiveness of colistin/levofloxacin compared to colistin/meropenem in the treatment of ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii: a randomized controlled clinical trial.

Background and purpose: The treatment of ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is still a great challenge. This study evaluated the effectiveness of the colistin/levofloxacin regimen compared to the usual colistin/meropenem regimen in the treatment of patients with VAP caused by CRAB. Experimental approach: The patients with VAP were randomly assigned to experimental (n = 26) and control (n = 29) groups. The first group received IV colistin 4.5 MIU every 12 h + levofloxacin 750 mg IV daily, and the second group received IV colistin with the same dose + meropenem 1 g IV every 8 h for 10 days. The clinical (complete response, partial response, or treatment failure) and microbiological responses at the end of the intervention were recorded and compared between the two groups. Findings/Results: The complete response rate was higher (n = 7; 35%) and the failure rate was lower (n = 4; 20%) in the experimental group than in the control group (n = 2; 8%, and n = 11; 44%, respectively), but the differences were not statistically significant. Even though the microbiological response rate was higher in the experimental group (n = 14; 70%) than in the control group (n = 12; 48%), the difference was not statistically significant. The mortality rate was 6 (23.10%) and 4 patients (13.8%) in the experimental and control groups, respectively (P = 0.490). Conclusion and implication: The levofloxacin/colistin combination can be considered an alternative regimen to meropenem/colistin in the treatment of VAP caused by CRAB.

Evaluation of Synbiotics in the Prevention of Ventilator-Associated Pneumonia: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial.

Background: Ventilator-associated pneumonia (VAP) is one of the most common nosocomial infections. The role of probiotics in preventing VAP is still questionable. This study aimed at evaluating the effect of synbiotic FamiLact 2plus on the prevention of VAP in patients admitted to the intensive care unit (ICU). Methods: A total of 80 mechanically ventilated patients were included and divided into two groups of 40. Group 1 received FamiLact 2plus, and group 2 received placebo. The outcome variables were compared, including the incidence of VAP, the time interval between the onset of ventilation and VAP, the duration of mechanical ventilation, and the length of stay in the ICU. Results: VAP is documented in four patients (10%) in group 1 and 11 patients (27.5%) in group 2 (P = 0.045). The length of stay in the ICU in group 1 was significantly shorter than in group 2, and the time interval between the start of intubation and the onset of VAP in group 1 was longer than in the placebo group. During the intervention, 15 patients in group 1 (37.5%) and 26 patients in group 2 (65%) developed diarrhea, which was a significant difference (P = 0.02). Conclusions: Synbiotic is associated with a reduction in the incidence of VAP as well as a reduction in ICU stay and delayed VAP.

Comparing inhaled colistin with inhaled fosfomycin/tobramycin as an adjunctive treatment for ventilator-associated pneumonia: An open-label randomized controlled trial.

PURPOSE: Although investigations are limited, adjunctive aerosolized antibiotics have been advised in the setting of gram-negative ventilator-associated pneumonia (VAP). This study aimed to compare the efficiency of inhaled colistin with inhaled fosfomycin/tobramycin in treating VAP due to extensively drug-resistant (XDR) Acinetobacter baumannii. METHODS: This single center open-label randomized controlled trial included 60 patients who developed XDR A. bumannii VAP. Eligible participants were randomly assigned to two groups (no. 30). Regardless of the assignment, all participants received meropenem (2 g as a 3-h extended infusion every 8 h) plus intravenous colistin (a loading dose of 9 million IU and then 4.5 million IU every 12 h). The control group was given inhaled colistin (1 million IU every 8 h), and the case group received inhaled tobramycin/fosfomycin (300 mg every 12 h/80 mg every 12 h) as adjunctive therapy. The primary outcome was treatment duration, and the secondary outcomes were Clinical Pulmonary Infection Score (CPIS) trend and mortality rate in the groups. The decision to stop treatment was made by the treating physician. RESULTS: The mean treatment duration was 13.73 ± 3.22 days in the colistin group and 10.85 ± 2.84 days in the tobramycin/fosfomycin group; the mean treatment duration in the latter group was lower significantly (P = 0.001). CPIS was decreased in the groups significantly (P < 0.001), but the mean changes of CPIS were significantly different between the groups, and in the inhaled tobramycin/fosfomycin group, a greater reduction (P = 0.005) was observed. Two (6.67%) patients in the control group and three (10%) patients in the case group died. CONCLUSION: The use of inhaled tobramycin/fosfomycin in cases with XDR A. bumannii VAP was associated with a shorter treatment duration in this open-label trial.

Modulation of long non-coding RNAs by resveratrol as a potential therapeutic approach in cancer: A comprehensive review.

LncRNAs, or long non-coding RNAs, are a subset of RNAs that play a regulatory role in a wide range of biological functions, including RNA processing, epigenetic regulation, and signal transduction. Recent research indicates that lncRNAs play a key role in the development and spread of cancer by being dysregulated in the disease. In addition, lncRNAs have been linked to the overexpression of certain proteins that are involved in tumor development and progression. Resveratrol has anti-inflammatory and anti-cancer properties that it exerts through regulating different lncRNAs. By the regulation of tumor-supportive and tumor-suppressive lncRNAs, resveratrol acts as an anti-cancer agent. By downregulating the tumor-supportive lncRNAs DANCR, MALAT1, CCAT1, CRNDE, HOTAIR, PCAT1, PVT1, SNHG16, AK001796, DIO3OS, GAS5 and H19, and upregulating MEG3, PTTG3P, BISPR, PCAT29, GAS5, LOC146880, HOTAIR, PCA3, NBR2, this herbal remedy causes apoptosis and cytotoxicity. For the purpose of using polyphenols in cancer therapy, it would be helpful to have more in-depth knowledge about lncRNA modulation via resveratrol. Here, we discuss the current knowledge and future promise of resveratrol as modulators of lncRNAs in different cancers.