Epidemiological and clinical characteristics of hospitalized human metapneumovirus patients in Israel, 2015-2021: A retrospective cohort study.

This study evaluated the epidemiological and clinical characteristics of human metapneumovirus (hMPV) infection among hospitalized patients with acute respiratory infections during 2015-2021 and assessed the impact of the coronavirus disease 2019 pandemic on hMPV infection. A single-center, retrospective cohort study was performed, including pediatric and adult patients with laboratory-confirmed hMPV. Of a total of 990 patients, 253 (25.6%), 105 (10.6%), 121 (12.2%), and 511 (51.6%) belonged to age groups 0-2, 3-17, 18-59, and ≥60 years, respectively. The highest percentage (23.0%) of patients were hospitalized during 2019 and the lowest (4.7%) during 2020. Patients < 18 years experienced high rates of comorbidities (immunodeficiencies: 14.4% and malignancies: 29.9%). Here, 37/39 (94.9%) of all bronchiolitis cases were diagnosed in patients < 2 years, whereas more patients in older age groups were diagnosed with pneumonia. A greater proportion of hMPV patients diagnosed with viral coinfection (mostly respiratory syncytial virus and adenovirus) were <18 years. The highest percentages of intensive care unit admissions were recorded among patients < 18 years. Our findings demonstrate that hMPV is an important cause of morbidity in young children and a possibly underestimated cause of morbidity among older adults.

Treatment of severe Kaposiform lymphangiomatosis positive for NRAS mutation by MEK inhibition.

BACKGROUND: Kaposiform lymphangiomatosis (KLA) is a complex lymphatic anomaly involving most commonly the mediastinum, lung, skin and bones with few effective treatments. In recent years, RAS-MAPK pathway mutations were shown to underlie the pathogenesis of several complex lymphatic anomalies. Specifically, an activating NRAS mutation (p.Q61R) was found in the majority of KLA patients. Recent reports demonstrated promising results of treatment with the MEK inhibitor, Trametinib, in patients with complex lymphatic anomalies harboring gain of function mutations in ARAF and SOS1, as well as loss of function mutation in the CBL gene, a negative regulator of the RAS-MAPK pathway. We present a 9-year-old child with a severe case of KLA harboring the typical NRAS (p.Q61R) mutation detected by plasma-derived cell free DNA, responsive to trametinib therapy. METHODS: The NRAS somatic mutation was detected from plasma cfDNA using droplet digital PCR. Concurrent in-vitro studies of trametinib activity on mutant NRAS affected lymphatic endothelial cells were performed using a three-dimensional spheroid sprouting assay. RESULTS: Trametinib treatment lead to resolution of lifelong thrombocytopenia, improvement of pulmonary function tests and wellbeing, as well as weaning from prolonged systemic steroid treatment. Concurrent studies of mutant NRAS-expressing cells showed enhanced lymphangiogenic capacity along with over activation of the RAS-MAPK and PI3K-AKT-mTOR pathways, both reversed by trametinib. CONCLUSIONS: Trametinib treatment can substantially change the prognosis of patients with RAS pathway associated lymphatic anomalies. IMPACT: This is the first description of successful trametinib treatment of a patient with KLA harboring the most characteristic NRAS p.Q61R mutation. Treatment can significantly change the prognosis of patients with RAS pathway-associated lymphatic anomalies. We devised an in vitro model of KLA enabling a reproducible method for the continued study of disease pathogenesis. Mutated NRAS p.Q61R cells demonstrated increased lymphangiogenic capacity.

Six-Lead Electrocardiography Enables Identification of Rhythm and Conduction Anomalies of Patients in the Telemedicine-Based, Hospital-at-Home Setting: A Prospective Validation Study.

BACKGROUND: The hospital-at-home (HAH) model is a viable alternative for conventional in-hospital stays worldwide. Serum electrolyte abnormalities are common in acute patients, especially in those with many comorbidities. Pathologic changes in cardiac electrophysiology pose a potential risk during HAH stays. Periodical electrocardiogram (ECG) tracing is therefore advised, but few studies have evaluated the accuracy and efficiency of compact, self-activated ECG devices in HAH settings. This study aimed to evaluate the reliability of such a device in comparison with a standard 12-lead ECG. METHODS: We prospectively recruited consecutive patients admitted to the Sheba Beyond Virtual Hospital, in the HAH department, during a 3-month duration. Each patient underwent a 12-lead ECG recording using the legacy device and a consecutive recording by a compact six-lead device. Baseline patient characteristics during hospitalization were collected. The level of agreement between devices was measured by Cohen's kappa coefficient for inter-rater reliability (Ϗ). RESULTS: Fifty patients were included in the study (median age 80 years, IQR 14). In total, 26 (52%) had electrolyte disturbances. Abnormal D-dimer values were observed in 33 (66%) patients, and 12 (24%) patients had elevated troponin values. We found a level of 94.5% raw agreement between devices with regards to nine of the options included in the automatic read-out of the legacy device. The calculated Ϗ was 0.72, classified as a substantial consensus. The rate of raw consensus regarding the ECG intervals' measurement (PR, RR, and QT) was 78.5%, and the calculated Ϗ was 0.42, corresponding to a moderate level of agreement. CONCLUSION: This is the first report to our knowledge regarding the feasibility of using a compact, six-lead ECG device in the setting of an HAH to be safe and bearing satisfying agreement level with a legacy, 12-lead ECG device, enabling quick, accessible arrythmia detection in this setting. Our findings bear a promise to the future development of telemedicine-based hospital-at-home methodology.

Remote Auscultation of Heart and Lungs as an Acceptable Alternative to Legacy Measures in Quarantined COVID-19 Patients-Prospective Evaluation of 250 Examinations.

The COVID-19 pandemic accelerated the assimilation of telemedicine platforms into medical practice. Nevertheless, research-based evidence in this field is still accumulating. This was a prospective, cross-sectional comparative assessment of a remote physical examination device used mainly for heart and lung digital auscultation. We analyzed usage patterns, user (physician) subjective appreciation and compared it to legacy measures. Eighteen physicians (median age 36 years (IQR 32-45): two interns, seven residents and nine senior physicians; eleven internists, five geriatricians and two pediatricians) executed over 250 remote physical examinations. Their median work duration with quarantined patients was 60 days (IQR 45-60). The median number of patients examined by a single physician was 17 (IQR 10-34). Regarding overall estimation, all participants tended to prefer the remote examination in the setting of quarantined patients (median 6, IQR 3.75-8), while no statistically significant difference was demonstrated compared to the indifference value (p = 0.122). Internists preferred tele-medical examination over non-internists, with significant differences between groups regarding heart auscultation, (median 7, (IQR 3-7) vs. median 2, (IQR 1-5, respectively)), p = 0.044. In the setting of quarantined patients, from the physicians' perspective, a digital platform for remote auscultation of heart and lungs was considered as an acceptable alternative to legacy measures.

Patient and clinician experience with a rapidly implemented large-scale video consultation program during COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has forced health-care providers to find creative ways to allow continuity of care in times of lockdown. Telemedicine enables provision of care when in-person visits are not possible. Sheba Medical Center made a rapid transition of outpatient clinics to video consultations (VC) during the first wave of COVID-19 in Israel. OBJECTIVE: Results of a survey of patient and clinician user experience with VC are reported. METHODS: Satisfaction surveys were sent by text messages to patients, clinicians who practice VC (users) and clinicians who do not practice VC (non-users). Questions referred to general satisfaction, ease of use, technical issues and medical and communication quality. Questions and scales were based on surveys used regularly in outpatient clinics of Sheba Medical Center. RESULTS: More than 1200 clinicians (physicians, psychologists, nurses, social workers, dietitians, speech therapists, genetic consultants and others) provided VC during the study period. Five hundred and forty patients, 162 clinicians who were users and 50 clinicians who were non-users completed the survey. High level of satisfaction was reported by 89.8% of patients and 37.7% of clinician users. Technical problems were experienced by 21% of patients and 80% of clinician users. Almost 70% of patients but only 23.5% of clinicians found the platform very simple to use. Over 90% of patients were very satisfied with clinician's courtesy, expressed a high sense of trust, thought that clinician's explanations and recommendations were clear and estimated that the clinician understood their problems and 86.5% of them would recommend VC to family and friends. Eighty-seven percent of clinician users recognize the benefit of VC for patients during the COVID-19 pandemic but only 68% supported continuation of the service after the pandemic. CONCLUSION: Our study reports high levels of patient satisfaction from outpatient clinics VC during the COVID-19 pandemic. Lower levels of clinician satisfaction can mostly be attributed to technical and administrative challenges related to the newly implemented telemedicine platform. Our findings support the continued future use of VC as a means of providing patient-centered care. Future steps need to be taken to continuously improve the clinical and administrative application of telemedicine services.

Establishing a COVID-19 treatment centre in Israel at the initial stage of the outbreak: challenges, responses and lessons learned.

Anticipating the need for a COVID-19 treatment centre in Israel, a designated facility was established at Sheba Medical Center-a quaternary referral centre. The goals were diagnosis and treatment of patients with COVID-19 while protecting patients and staff from infection and ensuring operational continuity and treatment of patients with non-COVID. Options considered included adaptation of existing wards, building a tented facility and converting a non-medical structure. The option chosen was a non-medical structure converted to a hospitalisation facility suited for COVID-19 with appropriate logistic and organisational adaptations. Operational principles included patient isolation, unidirectional workflow from clean to contaminated zones and minimising direct contact between patients and caregivers using personal protection equipment (PPE) and a multimodal telemedicine system. The ED was modified to enable triage and treatment of patients with COVID-19 while maintaining a COVID-19-free environment in the main campus. This system enabled treatment of patients with COVID-19 while maintaining staff safety and conserving the operational continuity and the ability to continue delivery of treatment to patients with non-COVID-19.

High-dose aspirin for Kawasaki disease: outdated myth or effective aid?

OBJECTIVES: To compare the efficacy and safety of intravenous immunoglobulin (IVIG) plus high-dose aspirin (HDA) vs. IVIG plus low-dose aspirin (LDA) for the treatment of Kawasaki disease, with an emphasis on coronary artery outcomes. METHODS: This study was a retrospective, medical record review of paediatric patients with Kawasaki disease comparing 6 centres that routinely used HAD for initial treatment and 2 that used LDA in 2004-2013. Treatment response and adverse events were compared. The primary outcome measure was the occurrence of coronary aneurysm at the subacute or convalescent stage. RESULTS: The cohort included 358 patients, of whom 315 were initially treated with adjunctive HDA and 43 with LDA. There were no demographic differences between the groups. Coronary aneurysms occurred in 10% (20/196) of the HDA group and 4% (1/24) of the LDA group (p=0.34). Equivalence tests indicate it is unlikely that the risk of coronary aneurysm in LDA exceeds HDA by more than 3.5%. There were no significant between-group differences in the need for glucocorticoid pulse therapy or disease recurrence. Coronary ectasia rate and hospitalisation time were significantly greater in the HDA group. Adverse events were similar in the two groups. CONCLUSIONS: We found no significant clinical benefit in using IVIG+HDA in Kawasaki disease compared to IVIG+LDA. The use of adjunctive HDA in this setting should be reconsidered.

BCGitis and BCGosis in children with primary immunodeficiency - imaging characteristics.

BACKGROUND: When administered to an immune-compromised patient, BCG (Bacille Calmette-Guérin) can cause disseminated and life-threatening infections. OBJECTIVE: To describe the imaging findings in children with primary immunodeficiency and BCG-related infections. MATERIALS AND METHODS: We reviewed the imaging findings of children with primary immunodeficiency treated at a children's hospital during 2012-2014 with localized or disseminated BCG infection. Imaging modalities included US, CT and radiography. RESULTS: Nine children with primary immunodeficiency had clinical signs of post-vaccination BCGitis; seven of these children showed disseminated disease and two showed only regional lesions with characteristic ipsilateral lymphadenopathy. Overall, lymphadenopathy was the most prevalent feature (n = 8) and characteristically appeared as a ring-enhancing hypodense (CT) or hypoechoic (US) lesion. Visceral involvement with multiple abscesses appeared in the spleen (n = 2), liver (n = 1) and bones (n = 1). All lesions regressed following appropriate anti-tuberculosis treatment. CONCLUSION: BCG infection needs to be considered in children with typical findings and with suspected primary immunodeficiency.

Association between White Matter T2 Hyper-Intense Signals in Fetal Brain Magnetic Resonance Imaging and Neurodevelopment of Fetuses with Cytomegalovirus Infection.

An association between subtle changes in T2 white matter hyper-intense signals (WMHSs) detected in fetal brain magnetic resonance imaging (fbMRI) and congenital cytomegalovirus (CMV) infection has been established. The research aim of this study is to compare children with congenital CMV infection with neurodevelopment outcome and hearing deficit with and without WMHSs in a historic prospective case study cohort of 58 fbMRIs. Of these, in 37 cases, fbMRI was normal (normal group) and WMHSs were detected in 21 cases (WMHS group). The median infection week of the WMHS group was earlier than the normal fbMRI group (8 and 17 weeks of gestation, respectively). The proportion of infants treated with valganciclovir in the WMHS group was distinctly higher. Hearing impairment was not significantly different between the groups. VABS scores in all four domains were within normal range in both groups. The median score of the motor skills corrected for week of infection was better in the WMHS group. A multivariate analysis using the week of infection interaction variable of WMHS and valganciclovir treatment showed better motor score outcomes in the valganciclovir treatment group despite an earlier week of infection. WMHSs were not associated with neurodevelopmental outcome and hearing deficit. In our cohort, valganciclovir treatment may have a protective effect on fetuses with WMHSs by improving neurodevelopmental outcome.

Integrating technologies to provide comprehensive remote fetal surveillance: A prospective pilot study.

OBJECTIVE: To determine the feasibility of extending remote maternal-fetal care to include fetus well-being. METHODS: The authors performed a prospective pilot study investigating low-risk pregnant participants who were recruited at the time of their first full-term in-person visit and scheduled for a follow-up telemedicine visit. Using novel self-operated fetal monitoring and ultrasound devices, fetal heart monitoring and amniotic fluid volume measurements were obtained to complete a modified biophysical profile (mBPP). Total visit length was measured for both the in-person first visit and the subsequent telemedicine encounter. A patient satisfaction survey form was obtained. RESULTS: Ten women between 40 + 1 and 40 + 6 weeks of gestation participated in telemedicine encounters. Nine women (90%) were able to complete remote mBPP assessment. For one participant, fetal assessment was not completed due to technically inconclusive fetal monitoring. Another participant was referred for additional assessment in the delivery room. Satisfactory amniotic fluid volume measurements were achieved in 100% of participants. The telemedicine encounter was significantly shorter (93.1 ± 33.1 min) than the in-person visit (247.2 ± 104.7 min; P < 0.001). We observed high patient satisfaction. CONCLUSION: Remote fetal well-being assessment is feasible and time-saving and results in high patient satisfaction. This novel paradigm of comprehensive remote maternal and fetal assessment is associated with important clinical, socioeconomic, and logistics advantages.

A Systematic Review and Clinical Presentation of Central Nervous System Complications of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospitalized Pediatric Patients During the Coronavirus Disease 2019 Pandemic in Israel.

BACKGROUND: Coronavirus disease-associated central nervous system complications (CNS-C) in hospitalized children, especially during the Omicron wave, and in comparison with influenza associated CNS-C, are not well understood. METHODS: The study population included 755 children aged <18 years hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Sheba Medical Center, during March 2020 to July 2022. A comparative cohort consisted of 314 pediatric patients with influenza during the 2018-2019 and 2019-2020 influenza seasons. RESULTS: Overall, 5.8% (n = 44) of patients exhibited CNS-C. Seizures at presentation occurred in 33 patients with COVID-19 (4.4%), with 2.6% (n = 20) experiencing nonfebrile seizures, 1.1% (n = 8) febrile seizures, and 0.7% (n = 5) status epilepticus. More patients with CNS-C experienced seizures during the Omicron wave versus the pre-Omicron period (77.8% vs 41.2%, P = 0.03). Fewer patients were admitted to the intensive care unit in the Omicron wave (7.4%) versus prior waves (7.4% vs 41.2%, P = 0.02). Fewer patients with SARS-CoV-2 experienced CNS-C (5.8%) versus patients with influenza (9.9%), P = 0.03. More patients with SARS-CoV-2 experienced nonfebrile seizures (2.6% vs 0.6%, P = 0.06), whereas more patients with influenza experienced febrile seizures (7.3% vs 1.1%, P < 0.01). CONCLUSIONS: The Omicron wave was characterized by more seizures and fewer intensive-care-unit admissions than previous waves. Pediatric patients with SARS-CoV-2 experienced fewer CNS-C and more nonfebrile seizures compared with patients with influenza.

Newborn screening for congenital cytomegalovirus using real-time polymerase chain reaction in umbilical cord blood.

BACKGROUND: Congenital cytomegalovirus (C-CMV) infection affects 0.4-2% of newborn infants in Israel, most of whom are asymptomatic. Of these, 10-20% will subsequently develop hearing impairment and may have benetitted from early detection by neonatal screeing. OBJECTIVES: To retrospectively anaIyze the results of a screening program for C-CMV performed at the Sheba Medical Center, Tel, Hashomer, during a 1 year period, using real-time polymerase chain reaction (rt-PCR) from umbilical cord blood. METHODS: CMV DNA was detected by rt-PCR performed on infants' cord blood. C-CMV was confirmed by urine culture (Shell-vial). All confirmed cases were further investigated for C-CMV manifestations by head ultrasound, complete blood count, liver enzyme measurement, ophthalmology examination and hearing investigation. RESULTS: During the period 1 June 2009 to 31 May 2010, 11,022 infants were born at the Sheba Medical Center, of whom 8105 (74%) were screened. Twenty-three (0.28%) were positive for CMV and 22 of them (96%) were confirmed by urine culture. Two additional infants, who had not been screened, were detected after clinical suspicion. All 24 infants were further Investigated, and 3 (12.5%) had central nervous system involvement (including hearing impairment) and were offered intravenous ganciclovir for 6 weeks. Eighteen infants (82%) would not otherwise have been diagnosed. CONCLUSION: The relatively low incidence of C-CMV detected in our screening program probably reflects the low sensitivity of cord blood screening. Nevertheless, this screening program reliably detected a non-negligible number of infants who could benefit from early detection. Other screening methods using saliva should be investigated further.

Designing for flexibility in hybrid care services: lessons learned from a pilot in an internal medicine unit.

Digital transformation in healthcare during the COVID-19 pandemic led to the development of new hybrid models integrating physical and virtual care. The ability to provide remote care by telemedicine technologies and the need to better manage and control hospitals' occupancy accelerated growth in hospital-at-home programs. The Sheba Medical Center restructured to create Sheba Beyond as the first virtual hospital in Israel. These transformations enabled them to deliver hybrid services in their internal medicine unit by managing inpatient hospital-care with remote home-care based on the patients' medical condition. The hybrid services evolved to integrate care pathways multiplied by the mode of delivery-physical (in person) or virtual (technology enabled)-and the location of care-at the hospital or the patient home. The study examines this home hospitalization program pilot for internal medicine at Sheba Medical Center (MC). The research is based on qualitative semi-structured interviews with Sheba Beyond management, medical staff from the hospital and the Health Maintenance Organization (HMO), Architects, Information Technology (IT), Telemedicine and Medtech organizations. We investigated the implications of the development of hybrid services for the future design of the physical built-environment and the virtual technological platform. Our findings highlight the importance of designing for flexibility in the development of hybrid care services, while leveraging synergies across the built environment and digital platforms to support future models of care. In addition to exploring the potential for scalability in accelerating the flexibility of the healthcare system, we also highlight current barriers in professional, management, logistic and economic healthcare models.

Risk Factors and Characteristics of Candidemia After Cardiac Surgery in Pediatric Patients in Central Israel.

BACKGROUND: Candidemia is a serious complication in pediatric patients with congenital heart defects (CHD) after cardiac surgery. Information about the epidemiology, clinical characteristics and risk factors for candidemia in this vulnerable population remains limited. METHODS: This retrospective case-control study was conducted in 2 pediatric intensive care units between 2004 and 2019. All patients <18 years old who developed candidemia following cardiac surgery were included. Each case was matched with 2 control patients based on age and date of surgery. Multivariable logistic regression analysis was conducted to determine the risk factors for postoperative candidemia. RESULTS: Thirty-five candidemia cases were identified and matched to 70 control cases. The incidence of candidemia was 6.3 episodes per 1000 admissions. The median age for candidemia cases was 4 months. The attributable mortality was 28.5%. The predominant (54%) pathogens isolated were non- albicans Candida species, of which C. parapsilosis isolates demonstrated high resistance to fluconazole (70%). Independent risk factors associated with candidemia included cumulative antibiotic exposure for ≥4 days [OR: -4.3; 95% confidence interval (CI): 1.3-14.6; P = 0.02], the need for total parenteral nutrition or peritoneal dialysis (OR: -6.1; 95% CI: 2-18.8; P = 0.001), male sex (OR: 6.2; 95% CI: 1.9-20.3; P = 0.002) and delayed sternal closure≥2 days (OR: -3.2; 95% CI: 1-11.2; P = 0.05). CONCLUSIONS: Postoperative candidemia in children with CHD is an uncommon but severe complication. Our study revealed an unexpectedly high frequency of fluconazole-resistant C. parapsilosis as the main cause of non- albicans candidemia. In addition to confirming previously recognized risk factors, our results reveal new potential risk factors such as delayed sternal closure and male sex.

Interpretation of Heart and Lungs Sounds Acquired via Remote, Digital Auscultation Reached Fair-to-Substantial Levels of Consensus among Specialist Physicians.

BACKGROUND: Technological advancement may bridge gaps between long-practiced medical competencies and modern technologies. Such a domain is the application of digital stethoscopes used for physical examination in telemedicine. This study aimed to validate the level of consensus among physicians regarding the interpretation of remote, digital auscultation of heart and lung sounds. METHODS: Seven specialist physicians considered both the technical quality and clinical interpretation of auscultation findings of pre-recorded heart and lung sounds of patients hospitalized in their homes. TytoCareTM system was used as a remote, digital stethoscope. RESULTS: In total, 140 sounds (70 heart and 70 lungs) were presented to seven specialists. The level of agreement was measured using Fleiss' Kappa (FK) variable. Agreement relating to heart sounds reached low-to-moderate consensus: the overall technical quality (FK = 0.199), rhythm regularity (FK = 0.328), presence of murmurs (FK = 0.469), appreciation of sounds as remote (FK = 0.011), and an overall diagnosis as normal or pathologic (FK = 0.304). The interpretation of some of the lung sounds reached a higher consensus: the overall technical quality (FK = 0.169), crepitus (FK = 0.514), wheezing (FK = 0.704), bronchial sounds (FK = 0.034), and an overall diagnosis as normal or pathological (FK = 0.386). Most Fleiss' Kappa values were in the range of "fare consensus", while in the domains of diagnosing lung crepitus and wheezing, the values increased to the "substantial" level. CONCLUSIONS: Bio signals, as recorded auscultations of the heart and lung sounds serving the process of clinical assessment of remotely situated patients, do not achieve a high enough level of agreement between specialized physicians. These findings should serve as a catalyzer for improving the process of telemedicine-attained bio-signals and their clinical interpretation.

Respiratory cryptosporidiosis detected by commercial multiplex-PCR in immunosuppressed pediatric patients.

We report the off-label use of a commercial gastrointestinal protozoa multiplex-PCR panel for bronchoalveolar lavage samples, detecting respiratory cryptosporidiosis in 2 immunocompromised pediatric patients. We suggest that implying this readily available assay in cases in which systemic cryptosporidiosis is suspected, may widen our understanding regarding this rarely reported syndrome.

Technologically assisted intensive home treatment: feasibility study.

Introduction: In recent year, many attempts have been made to provide patients with alternatives to psychiatric hospitalization during acute distress. Although several hospitalization alternatives have been offered, most of them still require patients to be distanced from their families, friends, and the social environment. Methods: In this report we describe the implementation of a novel approach to psychiatric care termed "Technologically assisted Intensive Home Treatment", where patients arriving to emergency settings are directed to home care with technological aids that enable close monitoring and ongoing contact with their therapists. Results: We describe the rationale and treatment principles of the treatment, and provide an elaborative description of the implementation process during the first year of implementation. Discussion: Additional attention is given to factors associated with early dropout from the program, in order to inform readers of predictors to optimal care. Limitations and directions for future research and practice are discussed.Clinical Trial Registration: The study was registered in the database of clinical trials (registration number SHEBA-19-6555-MW-CTIL) and in the Ministry of Health (registration number MOH_2022-08-22_011992).

[Combination antifungal therapy in hematopoietic stem cell transplantation patients].

Invasive fungal infections are a major cause of morbidity and mortality in hematopoietic stem cell transplantation patients. In recent years, new resistant fungal strains have emerged, requiring physicians to use new generation antifungal drugs or drug combinations. We report a case of invasive Fusarium infection involving the nasopharynx, skin and lungs, following haploidentical hematopoietic stem cell transplantation in an 8-year old patient with recurrent leukemia. The patient was treated with combination antifungal treatment of amphotericin B and voriconazole, as well as supportive care, with the improvement of his symptoms and home discharge. We reviewed the history of combination antifungal therapy. Combination antifungal treatment has been used since 1979, especially in immunocompromised patients. Although randomized controlled trials are lacking, reports favoring combination, especially for invasive mold infections, are increasingly published.