Incidence, Risk Factors, Characteristics, and Outcome of Chronic Graft Versus Host Disease in Children Undergoing Haploidentical Peripheral Blood Stem Cell Transplant With Post-transplant Cyclophosphamide.

AIM: Chronic graft versus host disease (cGVHD) is a major cause of morbidity postallogeneic peripheral blood stem cell transplant (PBSCT). There is paucity of literature describing incidence, risk factors, characteristics, and outcome of cGVHD in children undergoing haploidentical PBSCT with post-transplant cyclophosphamide (PTCy). Here, we describe our experience from our center regarding the same. METHODS: All children who underwent haploidentical PBSCT with PTCy between January 2016 and December 2021 at our center and survived beyond day+100 post-transplant were included in this retrospective study. Conditioning regimens used were: Thiotepa-Fludarabine-Cyclophosphamide with 2 Gy single fraction total body irradiation, Thiotepa-Busulfan-Fludarabine, Fludarabine-total body irradiation and Fludarabine-Melphalan. Peripheral blood was used as stem cell source in all patients. GVHD prophylaxis was PTCy 50 mg/kg on day +3 and +4, Mycophenolate mofetil and Calcineurin inhibitors. Clinical and laboratory data was electronically retrieved and analyzed based on National Institute of Health Consensus Criteria-2014 at regular intervals. Impact of various patient, donor, and transplant-related factors on development of cGVHD were analyzed. Incidence of relapse, event free survival (EFS) and overall survival (OS) were calculated and compared between cGVHD and no cGVHD groups. Patients with rejection were excluded from risk factor analysis for cGVHD but were considered for survival analysis. RESULTS: Fifty-one children included in this study. Median age of transplant of our cohort was 7.5 years with male:female=1.6:1. Eight patients had rejection with autologous recovery. History of acute GVHD (aGVHD) was present in 15/51 (Grade III to IV in 7/51). cGVHD developed in 19/51 patients (mild-9/51, moderate-6/51, and severe-4/51). Skin was the most common organ involved (100%) followed by gastrointestinal tract (47.4%), liver (36.8%), eyes (21%), lungs (21%), mouth (15.7%), and joints (5.2%). Advanced donor age (>30 y) and previous aGVHD were found to be significantly associated with increased risk of developing cGVHD. At last follow-up, complete response and partial response of cGVHD was seen in 6/19 and 4/19 patients, respectively. Overall mortality was 15/51 (cause of mortality was relapse of cancer 8/15, cGVHD-3/15, other 4/15). EFS and OS of full cohort was 55% and 70.6%, respectively. Compared with patients without cGVHD, patients with cGVHD demonstrated a lower relapse (18.2% vs. 40%, P =0.2333), higher EFS (68.4% vs. 53.1%, P =0.283), and higher OS (73.7% vs. 68.8%, P =0.708). CONCLUSION: Incidence of cGVHD was high in children undergoing haploidentical PBSCT with PTCy. Other than PBSC graft source; donor age and previous aGVHD were the risks factors for development of cGVHD. Patients with cGVHD had lower incidence of relapse translating into better survival but this difference was not statistically significant.

Review of the unmet medical need for vaccination in adults with immunocompromising conditions: An Indian perspective.

Immunocompromised (IC) populations are at increased risk of vaccine-preventable diseases (VPDs). In India, the concern of VPDs in IC populations is particularly acute due to the prevalence of crowded living situations, poor sanitation and variable access to healthcare services. We present a narrative review of IC-related disease and economic burden, risk of VPDs and vaccination guidelines, based on global and India-specific literature (2000-2022). IC conditions considered were cancer, diabetes mellitus, chronic kidney disease, respiratory disorders, disorders treated with immunosuppressive therapy, and human immune deficiency virus (HIV). The burden of IC populations in India is comparable to the global population, except for cancer and HIV, which have lower prevalence compared with the global average. Regional and socioeconomic inequalities exist in IC prevalence; VPDs add to the burden of IC conditions, especially in lower income strata. Adult vaccination programs could improve health and reduce the economic impact of VPDs in IC populations.

What is the context?The population is aging, both globally and in India. Older age is associated with a weakened immune system. People with an immunocompromised (IC) status have a higher risk of contracting infections. The combination of these conditions greatly increases risk from infectious disease. A large percentage of infections, referred to as vaccine-preventable diseases (VPDs), could be avoided by vaccination. However, India-specific guidelines for adult immunization are limited and there is a low awareness of these recommendations among healthcare professionals and patients. What is new? The proportion of people with IC conditions in India is comparable to that seen in other countries. However, the risk of VPDs, such as influenza and bacterial pneumonia, is of particular concern in India; several factors, such as crowded living situation, poor hygienic conditions, and lack of access to healthcare may favor the spread of infections. The consequences of infections have the greatest impact on families with low income. Furthermore, only few India-specific guidelines exist with recommendations for adult immunization. What is the impact? There is a need to protect the growing IC populations against VPDs. The introduction of public healthcare and the experience from the nationwide COVID−19 immunization program in India provide an opportunity to extend adult vaccination programs covering other VPDs. Immunization programs could reduce the economic and disease burden associated with VPDs. Clear national guidelines and communication strategies are required to increase awareness of the benefit of vaccination.

Fatal Severe Cytokine Release Syndrome Post-haploidentical Stem Cell Transplant With Post-transplant Cyclophosphamide in an Infant With Severe Combined Immunodeficiency and Disseminated Bacille Calmette-Guérin Infection.

INTRODUCTION: Severe Combined Immunodeficiency (SCID) is a primary immunodeficiency disorder characterized by absent or dysfunctional T lymphocytes, leading to defective cellular and humoral immunity requiring urgent hematopoietic stem cell transplantation (HSCT). We report a case of SCID with disseminated Bacille Calmette-Guérin (BCG) infection who developed cytokine release syndrome (CRS) and possible Immune reconstitution inflammatory syndrome (IRIS) after Haploidentical HSCT with post-transplant cyclophosphamide. METHODS: Data were retrospectively retrieved from electronic medical records. RESULT: A 5-month-old male infant was referred with fever, cough, and generalized maculopapular rash for 15 days, and had pallor without hepatosplenomegaly or lymphadenopathy. He had a history of previous male sibling death at 6 months of age due to pneumonia. Investigations: hemoglobin: 4.7 g/dL, TLC-6.37×103/uL, absolute lymphocytes: 0.98×103/uL, platelets: 319×103/uL, bilateral patchy opacities in both lung fields, and low immunoglobulin levels. Lymphocyte subset analysis revealed T-, B+, NK- SCID. Genetic analysis showed a hemizygous mutation in IL2RG (c.314A>G). The child received intravenous (IV) antibiotics, antifungal, antitubercular drugs, irradiated blood products, and IV immunoglobulins. Urgent haploidentical HSCT from the mother was planned. Conditioning was Fludarabine-40 mg/m2/d for 4 days, cyclophosphamide: 14.5 mg/kg/d for 2 days. He received peripheral blood hematopoietic stem cells with CD34- 15×106 cells/kg and CD3- 805×106 cells/kg. Within 2 hours of stem cell infusion, he developed respiratory distress, fever, shock, and flaring of rash. Methylprednisolone was started in view of CRS. On day+2, he had sudden desaturation and bradycardia needing mechanical ventilation and inotropes. His inflammatory markers were elevated (Ferritin: 3640 ng/mL, IL-6:5000 pg/mL, CRP:255 mg/L). In view of high-grade CRS, he received an injection of tocilizumab 8 mg/kg on day +2 and day +4. He received post-transplant cyclophosphamide 5 mg/kg on day +3. The endotracheal secretion GeneXpert was positive for Mycobacterium supporting the diagnosis of disseminated tuberculosis. Our patient had disseminated BCG infection which could also be contributory in the initiation of IRIS as the mother was immunized with the BCG vaccine in childhood so she must be having cytotoxic T cells specific for BCG, which were transferred to the infant with peripheral blood stem cell product. He succumbed to severe acute respiratory distress syndrome and multiorgan dysfunction on day +5 post-transplant. CONCLUSIONS: In haploidentical HSCT of SCID, post-transplant course can be complicated by CRS and IRIS as these patients are inefficient in mounting any response to infused donor lymphocytes resulting in their unregulated growth.

Micro-dystrophin gene therapy demonstrates long-term cardiac efficacy in a severe Duchenne muscular dystrophy model.

Micro-dystrophin gene replacement therapies for Duchenne muscular dystrophy (DMD) are currently in clinical trials, but have not been thoroughly investigated for their efficacy on cardiomyopathy progression to heart failure. We previously validated Fiona/dystrophin-utrophin-deficient (dko) mice as a DMD cardiomyopathy model that progresses to reduced ejection fraction indicative of heart failure. Adeno-associated viral (AAV) vector delivery of an early generation micro-dystrophin prevented cardiac pathology and functional decline through 1 year of age in this new model. We now show that gene therapy using a micro-dystrophin optimized for skeletal muscle efficacy (AAV-µDys5), and which is currently in a clinical trial, is able to fully prevent cardiac pathology and cardiac strain abnormalities and maintain normal (>45%) ejection fraction through 18 months of age in Fiona/dko mice. Early treatment with AAV-µDys5 prevents inflammation and fibrosis in Fiona/dko hearts. Collagen in cardiac fibrotic scars becomes more tightly packed from 12 to 18 months in Fiona/dko mice, but the area of fibrosis containing tenascin C does not change. Increased tight collagen correlates with unexpected improvements in Fiona/dko whole-heart function that maintain impaired cardiac strain and strain rate. This study supports micro-dystrophin gene therapy as a promising intervention for preventing DMD cardiomyopathy progression.

Cytogenetic Risk Stratification of B-Acute Lymphoblastic Leukemia and Its Correlation with Other Prognostic Factors.

Purpose of current study was to categorize WHO defined B-Acute Lymphoblastic Leukemia (B-ALL) cases into 3 cytogenetic risk groups (good, intermediate and poor) and to see their correlation with age, NCI risk criteria and treatment response. Clinical and diagnostic details were collected for 78 newly diagnosed B-ALL patients which included bone marrow morphology, flow cytometry immunophenotyping, karyotyping, FISH and RT-PCR. Study cohort comprised 44/78 (56.4%) children including 3 infants and 34/78 (43.6%) adults. Median age for paediatric group was 6 years (3 months-17 years) and for adults was 40.5 years (18 to 75 years). According to NCI risk criteria, excluding infants, 54 (72%) were high risk and 21 (28%) were standard risk. Clonal cytogenetic abnormality was detected in 59/78 cases (75.6%), while 19/78 (24.4%) cases showed normal karyotype. There was significant association of cytogenetic risk groups to age distribution (p value < 0.001) and NCI risk groups (p value < 0.001). There was no significant correlation of CNS involvement with cytogenetic risk groups (p = 0.064). Association of Day 8 steroid response and Day 15 bone marrow status with cytogenetic risk groups was significant (p = 0.006 and p = 0.003 respectively). Post treatment bone marrow status on Day 33 and Day 79 was available for 52 and 42 cases respectively. 9 adults died during induction phase. Day 33 post induction morphological remission was achieved in 51/52 cases (98%) and 1/52 (2.0%) were not in remission. Day 79 post induction morphological remission was achieved in 41/42 cases (98%) and 1/42 (2.0%) were not in remission. Day 33 or End of induction flow MRD (measurable residual disease) was negative in 39/52 (75.0%) patients and positive in 13/52 (25.0%) patients. Day 79 flow MRD was negative in 37/42 (88.1%) and positive in 5/42 (11.9%). Cytogenetic risk groups showed statistically significant Day 33 and Day 79 treatment response (morphologic remission: p = 0.009 and 0.003, flow MRD: p = 0.004 and p = 0.012 respectively). We concluded that cytogenetic risk groups showed statistically significant association with age, NCI risk criteria and treatment response.

Impact of Conditioning Regimen and Graft-versus-Host Disease Prophylaxis on The Outcome of Haploidentical Peripheral Blood Stem Cell Transplantation for High-Risk Severe Aplastic Anemia in Children and Young Adults: A Report from the Pediatric Severe Aplastic Anemia Consortium of India.

Allogenic hematopoietic cell transplantation (HCT) is the best curative approach for patients with severe aplastic anemia (SAA). The outcomes of HCT from haploidentical family donors (HFDs) have improved, making it a feasible option for patients lacking an HLA-identical donor. However, data on HFD-HCT for younger patients with SAA is sparse. In this multicenter retrospective study, we evaluated the outcomes of 79 patients undergoing HFD-HCT for SAA. All the patients were heavily pretransfused, the median time to HCT was >12 months, and 67% had failed previous therapies. Conditioning was based on fludarabine (Flu)-cyclophosphamide (Cy)-antithymocyte globulin (ATG)/total body irradiation (TBI) with or without thiotepa/melphalan (TT/Mel). Post-transplantation Cy (PTCy) and calcineurin inhibitors (CNIs)/sirolimus were used as graft-versus-host disease (GVHD) prophylaxis with or without abatacept. The rate of primary graft failure (PGF) was 16.43% overall, lower in patients conditioned with TT/Mel. The incidences of acute and chronic GVHD were 26.4% and 18.9%, respectively. At a median follow-up of 48 months, the overall survival (OS) and event-free survival (EFS) were 61.6% and 58.1%, respectively. Both OS and EFS were better in the TT/Mel recipients and with abatacept as GVHD prophylaxis. On multivariate analysis, the use of abatacept was found to favorably impact the outcome variables, including GVHD and EFS. Our study suggests that PTCy-based HFD-HCT is a reasonable option for young patients with high-risk SAA, in whom optimization of conditioning and GVHD prophylaxis might further improve outcomes.

Myeloid mineralocorticoid receptors contribute to skeletal muscle repair in muscular dystrophy and acute muscle injury.

Suppressing mineralocorticoid receptor (MR) activity with MR antagonists is therapeutic for chronic skeletal muscle pathology in Duchenne muscular dystrophy (DMD) mouse models. Although mechanisms underlying clinical MR antagonist efficacy for DMD cardiomyopathy and other cardiac diseases are defined, mechanisms in skeletal muscles are not fully elucidated. Myofiber MR knockout improves skeletal muscle force and a subset of dystrophic pathology. However, MR signaling in myeloid cells is known to be a major contributor to cardiac efficacy. To define contributions of myeloid MR in skeletal muscle function and disease, we performed parallel assessments of muscle pathology, cytokine levels, and myeloid cell populations resulting from myeloid MR genetic knockout in muscular dystrophy and acute muscle injury. Myeloid MR knockout led to lower levels of C-C motif chemokine receptor 2 (CCR2)-expressing macrophages, resulting in sustained myofiber damage after acute injury of normal muscle. In acute injury, myeloid MR knockout also led to increased local muscle levels of the enzyme that produces the endogenous MR agonist aldosterone, further supporting important contributions of MR signaling in normal muscle repair. In muscular dystrophy, myeloid MR knockout altered cytokine levels differentially between quadriceps and diaphragm muscles, which contain different myeloid populations. Myeloid MR knockout led to higher levels of fibrosis in dystrophic diaphragm. These results support important contributions of myeloid MR signaling to skeletal muscle repair in acute and chronic injuries and highlight the useful information gained from cell-specific genetic knockouts to delineate mechanisms of pharmacological efficacy.

Wilms tumor with Mulibrey Nanism: A case report and review of literature.

BACKGROUND: Mulibrey-Nanism (Muscle-liver-brain-eye Nanism = dwarfism; MUL) is a rare genetic syndrome. The underlying TRIM37 mutation predisposes these children to develop tumors frequently. In the largest published series of MUL, 8% patients were reported to develop Wilms tumor (WT). The published literature lacks data regarding the best treatment protocol and outcome of this cohort of children with WT and MUL. We report here a 2-year-old boy with WT and MUL and present a review of literature on WT in MUL. CASE: Our patient had associated cardiac problems of atrial septal defect, atrial flutter and an episode of sudden cardiac arrest. We managed him successfully with chemotherapy, surgery and multi-speciality care. He is alive and in remission at follow-up of 6 months. CONCLUSION: A total of 14 cases (including present case) of WT have been reported in MUL and treatment details were available for six cases. They were managed primarily with surgery, chemotherapy with/without radiotherapy, and all achieved remission. The outcome data is available only for two cases, one has been followed up till 15 years post treatment for WT and other is our patient.

Soluble Interleukin-2 Receptor Level as a Marker of Hemophagocytic Lymphohistiocytosis in Children With Severe Dengue.

Dengue induced-hemophagocytic lymphohistiocytosis (HLH) is increasingly recognized as an important cause of secondary HLH. Early identification of dengue HLH and directed therapy for HLH may help to alter the outcomes in critically ill patients. Soluble interleukin-2 receptor (IL2R) is a useful inflammatory marker and is seen to correlate with HLH disease activity. There is scarcity of data on IL2R in pediatric dengue patients with HLH. All patients (age < 18 years) with severe dengue confirmed by positive dengue IgM ELISA admitted to PICU were retrospectively enrolled. Patientswere screened for presence of HLH according to HLH 2004 criteria. Hemogram, ferritin, fibrinogen, liver, and renal function tests were noted. Patients who met four or more HLH criteria were treated with steroids and IL2R levels were sent to confirm the diagnosis of HLH. Out of 15 patients, nine patients met the criteria of HLH. IL2R levels were high in all HLH patients (mean 51,711, range 18,000-98,715 pg/mL). Mean ferritin levels were high in the HLH group as compared to non-HLH group (mean ferritin 34,593 vs. 3,206 ng/mL; p-value 0.004). Liver dysfunction was notably higher in the HLH group compared to non-HLH group (mean alanine aminotransferase 6,621 U/L vs. 165.6 U/L; p-value 0.04, mean aspartate aminotransferase 2,145 U/L vs. 104.2 U/L; 0.04, bilirubin level 4.2 mg/dL vs. 0.7 mg/dL; p-value 0.03). Four patients in the HLH group had acute kidney injury (AKI) and two required renal replacement therapy in the form of sustained low efficiency dialysis (SLED). Requirement for invasive ventilation was exclusively seen in HLH group and three patients developed ARDS. Two patients each in HLH and non-HLH group had shock requiring vasoactive therapy in addition to fluids. Mean days of ICU and hospital stay were higher in HLH group vs. non-HLH group but not statistically significant (6.4 vs. 4.4; p-value 0.32 and 8.44 vs. 5.6; p-value 0.18 days, respectively). All children in HLH group received steroids as per HLH protocol. In the HLH group, seven survived while two died. In the non-HLH group, all five patients survived. We concluded that IL2R levels are high in dengue HLH and useful for definitive diagnosis. Early recognition of this condition in severe dengue and prompt steroid therapy improves chances of better outcome.

Bacillus cereus infection in pediatric oncology patients: A case report and review of literature.

INTRODUCTION: Bacillus Cereus infection can be life-threatening in immunocompromised patients. We report here a case of Bacillus Cereus septicemia in a child with relapsed acute lymphoblastic leukemia (ALL) and present review of literature. METHODS: We collected clinical, laboratory and outcome data of our patient with relapsed ALL and Bacillus Cereus infection. We reviewed literature for Bacillus Cereus infection in pediatric oncology patients by searching MED-LINE/PubMed/Google/Google Scholar/Cochrane and summarized the data obtained. Various risk factors like presence of gastrointestinal or central nervous system (CNS) symptoms, neutropenia, central venous catheter in-situ, corticosteroids use, intrathecal chemotherapy and outcomes were analyzed using Fisher Exact Chi Square test. RESULTS: A 15-years-old boy with relapsed ALL on induction chemotherapy presented with giddiness and difficulty in breathing. He had an episode of hematemesis followed by fainting at home. He had refractory shock which did not respond to fluid boluses, inotropes and hydrocortisone. He had severe metabolic acidosis with high lactate and ammonia and died within 36-hours of onset of symptoms. His blood culture was positive for Bacillus Cereus. We came across 36 published cases of Bacillus Cereus in children with cancer including present case. Of these, 28 had acute leukemia and rest 8 had other cancers. CNS symptoms were present in 13 patients. Overall mortality was 25%. Patients with multisystem involvement had significantly higher mortality compared to those having localized disease (p-value 0.033). CONCLUSION: In pediatric oncology patients on chemotherapy, cultures positive for Bacillus Cereus should be considered significant. Mortality is higher in those with multisystem involvement.

Peripheral blood stem cell mobilization with pegylated granulocyte colony stimulating factor in children.

BACKGROUND AND AIM: We report here our experience of using pegylated granulocyte colony stimulating factor (peg-GCSF) for peripheral blood stem cell (PBSC) mobilization in children. METHODS AND RESULTS: A total of nine children suffering from high-risk/relapsed solid tumors were mobilized with chemotherapy and peg-GCSF (100 microgram/kg single dose). Mean age was 7.7 years (range 2-15 years).The mean time from peg-GCSF administration to PBSC harvest was 9.7 days. Adequate stem cells (median dose 26.9 million/kg) could be harvested in all children by a single apheresis procedure. No major adverse events observed. CONCLUSION: It is feasible and safe to mobilize PBSC with peg-GCSF in children with cancer.

Clinico-pathological features in fatal COVID-19 infection: a preliminary experience of a tertiary care center in North India using postmortem minimally invasive tissue sampling.

OBJECTIVES: To study the histopathology of patients dying of COVID-19 using post-mortem minimally invasive sampling techniques. METHODS: This was a single-center observational study conducted at JPNATC, AIIMS. Thirty-seven patients who died of COVID-19 were enrolled. Post-mortem percutaneous biopsies were taken from lung, heart, liver, kidney and stained with hematoxylin and eosin. Immunohistochemistry was performed using CD61 and CD163. SARS-CoV-2 virus was detected using IHC with primary antibodies. RESULTS: The mean age was 48.7 years and 59.5% were males. Lung histopathology showed diffuse alveolar damage in 78% patients. Associated bronchopneumonia was seen in 37.5% and scattered microthrombi in 21% patients. Immunopositivity for SARS-CoV-2 was observed in Type II pneumocytes. Acute tubular injury with epithelial vacuolization was seen in 46% of renal biopsies. Seventy-one percent of liver biopsies showed Kupffer cell hyperplasia and 27.5% showed submassive hepatic necrosis. CONCLUSIONS: Predominant finding was diffuse alveolar damage with demonstration of SARS-CoV-2 protein in the acute phase. Microvascular thrombi were rarely identified in any organ. Substantial hepatocyte necrosis, Kupffer cell hypertrophy, microvesicular, and macrovesicular steatosis unrelated to microvascular thrombi suggested that liver might be a primary target of COVID-19.

Dengue virus transmission from donor to recipient during haploidentical stem cell transplantation.

Dengue fever is endemic in tropical and subtropical countries. Dengue virus transmission through hematopoietic stem cells is very rare and just two such cases have been reported previously. We report here only third case of dengue virus transmission in a 2-year-old child with thalassemia major who underwent hematopoietic stem cell transplant (HSCT) from a haploidentical related donor. One week after HSCT, the recipient developed fever, pancytopenia and signs of capillary leak. On day 10, his dengue NS1 antigen test was positive which confirmed diagnosis of dengue fever. Donor also had fever few days prior to stem cell donation which was later diagnosed to be due to dengue fever. Child had a severe clinical course of dengue leading to primary graft failure. However, he had autologous recovery of his own bone marrow and is alive and well on day+200 post HSCT. Our report highlights the transmission of dengue virus from donor to recipient through hematopoietic stem cell graft although rare but possible. We suggest that in tropical and subtropical countries where dengue is endemic, hematopoietic stem cell donors should be screened for it.

Assessment of healthcare worker's hand hygiene and infection prevention practices of their personal belongings in a healthcare setting: a survey in pre COVID-19 era and literature review on standard disinfection practices.

BACKGROUND: Healthcare workers' (HCW) hands and personnel belongings are vehicles of transmission of nosocomial infections. Knowledge, attitude, and practice of hand hygiene have been extensively studied suggesting adequate knowledge but poor compliance. Similar data on aprons, mobile phone and stethoscope disinfection practices are lacking. This becomes an extensively important topic of discussion in current COVID-19 pandemic where inadequacy in hygiene practices is devastating. AIM: To study the knowledge, attitude, and infection prevention practices of HCWs aprons, electronic devices, stethoscopes, and hands. METHODS: A cross sectional questionnaire-based survey was conducted among HCWs of Medicine ward and ICU. RESULTS: Sixty-six HCWs responded to the survey. Awareness that hands, aprons, mobile phones, stethoscopes could cause cross transmission and knowledge of correct practices was present in majority of the respondents. Hand hygiene was performed by 65.2% of the respondents before touching a patient and 54.5% after touching the patient surroundings while 13.6% performed only when it was visibly soiled. Mobile phones and stethoscopes were disinfected by 13.6 and 30.3% of the respondents after each patient encounter, respectively. Aprons were washed after using them at a stretch for a median duration of 5 days (1-30 days). Forgetfulness, lack of reinforcement, lack of time, inadequate awareness on standard disinfection practices and fear of damaging electronic devices from disinfectants use were reasons for poor compliance. CONCLUSIONS: There is an urgent need to spread awareness and formulate standard guidelines on disinfection practices especially for mobile phones, stethoscopes, and aprons in addition to reinforcing hand hygiene practices.

Fungal carriage on healthcare workers' hands, clothing, stethoscopes and electronic devices during routine patient care: a study from a tertiary care center.

BACKGROUND: Invasive fungal infections are a constant threat to immunocompromised and critically ill patients. Healthcare workers caring for such patients act as conduits of transmission through their contaminated hands and belongings causing nosocomial infections. Although bacterial contamination of healthcare workers is known, our knowledge about fungal carriage is sparse. Among the fungi, candida species colonization of hands of healthcare workers is known however it would be interesting to know the type of fungal carriage on their inanimate belongings. AIM: To study the prevalence and type of fungal carriage on healthcare workers hands, aprons/hospital scrubs, electronic devices, and stethoscopes. METHODS: Healthcare workers working in Medicine ward and ICU during November and December 2019 were sampled. Hand washes were collected in Brain Heart Infusion (BHI) broth with gentamycin. Direct impression smears on blood agar were taken from aprons/hospital scrubs. Electronic devices and stethoscopes were sampled using moist cotton swabs. Subculture and plating was done on Sabarouds Dextrose Agar (SDA). Yeasts were identified using Matrix Assisted Laser Desorption Ionisation Time of Flight (MALDI TOF) and moulds were identified using microscopy. FINDINGS: Out of 60 health care workers, 20 (33.3%) had fungal carriage. Aprons/hospital scrubs and hands were contaminated in 17 (28.3%) and 3 (5%) respectively. Aprons/hospital scrubs mainly constituted moulds belonging to species of Aspergillus. Hands were contaminated with Candida tropicalis, Candida parapsilosis and Candida auris. Electronic devices and stethoscopes had no fungal contamination. CONCLUSIONS: Active fungal surveillance provides prevalent carriage rates and serve as a feedback to improve our disinfection and hand hygiene practices. It also aids in identification of potential source of hospital outbreaks.

Myroides: A Rare but Hard-to-crack Villain in a Critical Care Setup.

How to cite this article: Mahendran AJ, Agrawal S, Rastogi N, et al. Myroides: A Rare but Hard-to-crack Villain in a Critical Care Setup. Indian J Crit Care Med 2021;25(6):735-736.

Profile of co-infections & secondary infections in COVID-19 patients at a dedicated COVID-19 facility of a tertiary care Indian hospital: Implication on antimicrobial resistance.

BACKGROUND: The COVID-19 pandemic has raised concerns over secondary infections because it has limited treatment options and empiric antimicrobial treatment poses serious risks of aggravating antimicrobial resistance (AMR). Studies have shown that COVID-19 patients are predisposed to develop secondary infections. This study was conducted to ascertain the prevalence and profiles of co- & secondary infections in patients at the COVID-19 facility in North India. METHODS: We studied the profile of pathogens isolated from 290 clinical samples. Bacterial and fungal pathogens were identified, and antimicrobial susceptibility was determined by the Vitek2® system. Additionally, respiratory samples were tested for any viral/atypical bacterial co-infections and the presence of AMR genes by FilmArray test. The clinical and outcome data of these patients were also recorded for demographic and outcome measures analyses. RESULTS: A total of 151 (13%) patients had secondary infections, and most got infected within the first 14 days of hospital admission. Patients aged >50 years developed severe symptoms (p = 0.0004) and/or had a fatal outcome (p = 0.0005). In-hospital mortality was 33%.K.pneumoniae (33.3%) was the predominant pathogen, followed by A. baumannii (27.1%). The overall resistance was up to 84%.Majority of the organisms were multidrug-resistant (MDR) harbouring MDR genes. CONCLUSION: A high rate of secondary infections with resistant pathogens in COVID-19 patients highlights the importance of antimicrobial stewardship programs focussing on supporting the optimal selection of empiric treatment and rapid-de-escalation, based on culture reports.

Micro-dystrophin gene therapy prevents heart failure in an improved Duchenne muscular dystrophy cardiomyopathy mouse model.

Gene replacement for Duchenne muscular dystrophy (DMD) with micro-dystrophins has entered clinical trials, but efficacy in preventing heart failure is unknown. Although most patients with DMD die from heart failure, cardiomyopathy is undetectable until the teens, so efficacy from trials in young boys will be unknown for a decade. Available DMD animal models were sufficient to demonstrate micro-dystrophin efficacy on earlier onset skeletal muscle pathology underlying loss of ambulation and respiratory insufficiency in patients. However, no mouse models progressed into heart failure, and dog models showed highly variable progression insufficient to evaluate efficacy of micro-dystrophin or other therapies on DMD heart failure. To overcome this barrier, we have generated the first DMD mouse model to our knowledge that reproducibly progresses into heart failure. This model shows cardiac inflammation and fibrosis occur prior to reduced function. Fibrosis does not continue to accumulate, but inflammation persists after function declines. We used this model to test micro-dystrophin gene therapy efficacy on heart failure prevention for the first time. Micro-dystrophin prevented declines in cardiac function and prohibited onset of inflammation and fibrosis. This model will allow identification of committed pathogenic steps to heart failure and testing of genetic and nongenetic therapies to optimize cardiac care for patients with DMD.