Dual anti-viral treatment for persistent COVID-19 in immunocompromised hemato-oncological patients is associated with a favorable prognosis and minor side effects.

In hemato-oncological patients, COVID-19 can present as a persistent infection with ongoing symptoms and viral replication over a prolonged period of time. Data are scarce on the preferred treatment options for these patients. We describe our experience with a five-day course of dual anti-viral treatment with remdesivir and nirmatrelvir/ritonavir for hemato-oncological immunocompromised patients with persistent COVID-19. Fifteen patients with a history of lymphoma, CLL, and MM were included. Eight were male, median age was 74. All patients had an immediate clinical and virological response. In 73 % of patients, PCR for SARS-CoV-2 became negative at the end of treatment and the rest had an increase in PCR cycle threshold (CT) values, with a median increase of 6 cycles. After a follow-up of three months, 60 % of patients remained in full clinical and virological remission. None required invasive mechanical ventilation or died. The side effects we observed, neutropenia, lactatemia and elevated transaminases, were mild and almost all transient in nature. We conclude that dual anti-viral treatment appears to be a valid treatment option for persistent COVID-19.

Outcomes of Enterobacter cloacae-Associated Periprosthetic Joint Infection Following Hip Arthroplasties.

Background: Periprosthetic joint infections (PJIs) represent a serious complication following total hip arthroplasty (THA) and are associated with significant morbidity. While recent data suggest that Enterobacter cloacae is an emerging source of PJI, characteristics and outcomes of E. cloacae-associated infections are rarely described. The study aimed to present and describe the findings and outcomes of E. cloacae-associated PJI in our department. Methods: This is a retrospective descriptive study of patients who underwent revision THA for E. cloacae-associated PJI between 2011 and 2020 and has a minimum follow-up of 2 years. Outcomes included organism characteristics as well as clinical outcomes, represented by the number of reoperations needed for PJI eradication and the Musculoskeletal Infection Society (MSIS) outcome reporting tool score. Of 108 revision THAs, 12 patients (11.1%) were diagnosed with E. cloacae-associated PJI. Results: The majority of cases had a polymicrobial PJI (n=8, 66.7%). Five E. cloacae strains (41.7%) were gentamicin-resistant. Six patients (50.0%) underwent 2 or more revisions, while 3 of them (25.0%) required 4 or more revisions until their PJI was resolved. When utilizing the MSIS outcome score, the first surgical intervention was considered successful (MSIS score tiers 1 and 2) for 5 patients (41.7%) and failed (tiers 3 and 4) for 7 patients (58.3%). Conclusions: E. cloacae is emerging as a common source of PJI following hip arthroplasty procedures. The findings of our study suggest that this pathogen is primarily of polymicrobial nature and represents high virulence and poor postoperative outcomes, as represented by both an increased number of required revision procedures and high rates of patients with MSIS outcome scores of 3 and 4. When managing patients with E. cloacae-associated PJI, surgeons should consider these characteristics and inform patients regarding predicted outcomes.

Effect of composite resin containing antibacterial filler on sugar-induced pH drop caused by whole saliva bacteria.

STATEMENT OF PROBLEM: Secondary caries around restorations is a major problem and can be attributed to bacteria invading microgaps formed at the tooth-restoration interface. An antibacterial composite resin containing quaternary ammonium silica (QASi) filler has been reported to inhibit enamel demineralization in situ. However, whether the prevention of enamel demineralization by QASi-containing composite resin is because of the reduced metabolic activity of acid-producing saliva bacteria is unclear. PURPOSE: The purpose of this study was to compare the effects of QASi-containing composite resin and 2 other restorative materials on the viability of salivary bacteria and sugar-induced acid production. MATERIAL AND METHODS: Whole saliva from each of the 30 study participants, 14 at high risk and 16 at low risk for caries, was brought into contact with quadruplicate specimens of 3 restorative materials, Infinix Flowable Composite, an anti-bacterial composite resin containing 1.5% QASi filler (Nobio), Filtek Supreme Flowable Restorative (3M), a conventional flowable composite resin, and dental amalgam (Silmet). Bacterial growth and sugar-induced acid production on each restorative material were measured every 20 minutes for 18 hours. Caries risk groups were compared using the t test and repeated measures analysis of variance (α=.05). When significant, Bonferroni multiple comparisons were used. RESULTS: On average, the saliva with the QASi-containing composite resin specimens maintained a near-neutral pH, not dropping below pH 6.0. The saliva associated with both conventional restorative materials exhibited a pH drop below 5.5 (P<.001), the critical threshold for tooth demineralization according to the Stephan curve. Virtually no growth was measured on the surface of the antibacterial composite resin, whereas bacteria grew on the conventional composite resin and dental amalgam (P<.001). No differences were observed between participants at high and low risk of caries. CONCLUSIONS: Unlike amalgam and conventional composite resin, the QASi-containing composite resin showed a near-complete shutdown of the metabolic activity of salivary bacteria upon contact and virtually no bacterial viability. This suggests that the prevention of tooth demineralization by QASi-containing restoratives is associated with a significant reduction in bacterial metabolic activity.

Refractory Pseudomonas aeruginosa infections treated with phage PASA16: A compassionate use case series.

BACKGROUND: A growing number of compassionate phage therapy cases were reported in the last decade, with a limited number of clinical trials conducted and few unsuccessful clinical trials reported. There is only a little evidence on the role of phages in refractory infections. Our objective here was to present the largest compassionate-use single-organism/phage case series in 16 patients with non-resolving Pseudomonas aeruginosa infections. METHODS: We summarized clinical phage microbiology susceptibility data, administration protocol, clinical data, and outcomes of all cases treated with PASA16 phage. In all intravenous phage administrations, PASA16 phage was manufactured and provided pro bono by Adaptive Phage Therapeutics. PASA16 was administered intravenously, locally to infection site, or by topical use to 16 patients, with data available for 15 patients, mainly with osteoarticular and foreign-device-associated infections. FINDINGS: A few minor side effects were noted, including elevated liver function enzymes and a transient reduction in white blood cell count. Good clinical outcome was documented in 13 out of 15 patients (86.6%). Two clinical failures were reported. The minimum therapy duration was 8 days with a once- to twice-daily regimen. CONCLUSIONS: PASA16 with antibiotics was found to be relatively successful in patients for whom traditional treatment approaches have failed previously. Such pre-phase-1 cohorts can outline potential clinical protocols and facilitate the design of future trials. FUNDING: The study was funded in part by The Israeli Science Foundation IPMP (ISF_1349/20), Rosetrees Trust (A2232), United States-Israel Binational Science Foundation (2017123), and the Milgrom Family Support Program.

Mpox proctitis as a likely predisposing factor for chlamydial perihepatitis in a male patient.

Perihepatitis (Fitz-Hugh-Curtis syndrome) is a rare complication of sexually transmitted infections, mostly seen in women. Only 12 male cases have been reported to date, of which Chlamydia trachomatis was confirmed in 2. We report a case of chlamydial perihepatitis in a male patient, occurring 1 month after Mpox and associated with the unusual LGV ST23 strain. Our case suggests that rectal Mpox lesions may facilitate chlamydial dissemination.

Nosocomial transmission of MPOX virus to health care workers -an emerging occupational hazard: A case report and review of the literature.

We present an unusual case of monkeypox (MPOX) virus transmission to a dermatology resident during examination of affected patients. Viral DNA sequencing led to the identification of the most likely contact. This case, along with a review of all published cases so far, emphasizes the possible hazard of MPOX transmission to health care personnel, even when wearing personal protective equipment. It also emphasizes the need for maintaining high index of suspicion when examining patients with new dermatological lesions and strict compliance with the revised Centers for Disease Control and Prevention recommendations for specimen collection from such patients.

Regional Antibiotic Delivery for Implanted Cardiovascular Electronic Device Infections.

BACKGROUND: Present guidelines endorse complete removal of cardiovascular implantable electronic devices (pacemakers/defibrillators), including extraction of all intracardiac electrodes, not only for systemic infections, but also for localized pocket infections. OBJECTIVES: The authors evaluated the efficacy of delivering continuous, in situ-targeted, ultrahigh concentration of antibiotics (CITA) into the infected subcutaneous device pocket, obviating the need for device/lead extraction. METHODS: The CITA group consisted of 80 patients with pocket infection who were treated with CITA during 2007-2021. Of them, 9 patients declined lead extraction because of prohibitive operative risk, and 6 patients had questionable indications for extraction. The remaining 65 patients with pocket infection, who were eligible for extraction, but opted for CITA treatment, were compared with 81 patients with pocket infection and similar characteristics who underwent device/lead extraction as primary therapy. RESULTS: A total of 80 patients with pocket infection were treated with CITA during 2007-2021. CITA was curative in 85% (n = 68 of 80) of patients, who remained free of infection (median follow-up 3 years [IQR: 1.0-6.8 years]). In the case-control study of CITA vs device/lead extraction, cure rates were higher after device/lead extraction than after CITA (96.2% [n = 78 of 81] vs 84.6% [n = 55 of 65]; P = 0.027). However, rates of serious complications were also higher after extraction (n = 12 [14.8%] vs n = 1 [1.5%]; P = 0.005). All-cause 1-month and 1-year mortality were similar for CITA and device/lead extraction (0.0% vs 3.7%; P = 0.25 and 12.3% vs 13.6%; P = 1.00, respectively). Extraction was avoided in 90.8% (n = 59 of 65) of extraction-eligible patients treated with CITA. CONCLUSIONS: CITA is a safe and effective alternative for patients with pocket infection who are unsuitable or unwilling to undergo extraction. (Salvage of Infected Cardiovascular Implantable Electronic Devices [CIED] by Localized High-Dose Antibiotics; NCT01770067).

Mpox Presenting as Proctitis in Men Who Have Sex With Men.

In our cohort of 70 patients of men who have sex with men (MSM) with mpox, more than one-third presented with proctitis. In two-thirds of proctitis patients, there was no typical rash upon presentation, and in one-fifth, there was no rash at all, making the diagnosis a challenge. A rectal swab for mpox polymerase chain reaction (PCR) can be diagnostic.

CT findings in temporal bone sites in skull base osteomyelitis from malignant otitis externa.

OBJECTIVES: To identify the earliest sites and spread patterns of bony erosions on high-resolution temporal bone computerized tomographic (HRTBCT) scans and conjugate the radiological findings with clinical/laboratory data for guiding the interpretation of CT images of skull base osteomyelitis (SBOM) from malignant otitis externa (MOE). STUDY DESIGN: Retrospective and prospective medical records analysis. METHODS: The medical records of all patients who presented to a referral medical center during 2015-2022 and initially diagnosed with SBOM. Radiological assessment of each sub-site was performed by 2 qualified neuro-radiologist, who were blind to the clinical data. RESULTS: 33 patients were enrolled. All patients suffered edema and exudates of the external auditory canal (EAC). The most common osseous markers for SBOM were dehiscence or irregularity of the anterior EAC wall and temporomandibular joint (TMJ) medial wall (21/33, 64% patients, each), followed by a fistula from the TMJ to the EAC (20/33, 61% patients). Eustachian tube bony walls and condylar irregularity and/or dehiscence were as prevalent as 16/33, 48% of patients, each. EAC inferior and posterior walls of the EACs were irregular or dehiscent in patients with more advanced disease. CONCLUSIONS: The high symptomatologic overlap between SBOM and other aural pathologies might cause diagnostic (and subsequent treatment) delay and result in dire complications. EAC edema and irregularity or dehiscence of the anterior EAC wall are the most common early CT findings associated with SBOM caused by MOE.

Antibiotic prophylaxis in orthopedic surgery; has the time to reconsider the current practice arrived?

Introduction: The current practice of antibiotic prophylaxis in orthopedic surgery has existed almost 50 years yet little changes have been made. The incidence of methicillin resistant Staphylococci and multi-drug resistant Gram-negative bacteria is growing. Methods: We studied the positive cultures after primary hip and knee joint replacement and trauma surgery at our department. Results: Our investigation substantiates the current reports of an increase in oxacillin resistance of Staphylococci and an increase in incidence of Gram-negative bacteria. Conclusions : The standard use of cephalosporins for prophylaxis does not provide the necessary protection that it used to. We suggest that the recommendations and practice of antibiotic prophylaxis should be reconsidered. Level of Evidence: Level III - retrospective cohort study.

Glycaemic control in the paediatric and young adult population with type 1 diabetes following a single telehealth visit - what have we learned from the COVID-19 lockdown?

AIMS: Children with chronic diseases were unable to receive their usual care during COVID-19 lockdown. We assessed the feasibility and impact of telehealth visits on the time-in-range (TIR) of paediatric individuals with type 1 diabetes (T1D). METHODS: An observational multicentre real-life study. Patients scheduled for an in-clinic visit during the lockdown were offered to participate in a telehealth visit. Sociodemographic, clinical, continuous glucose monitor and pump data were recorded 2 weeks prior and 2 weeks after telehealth visit. The primary endpoint was change in relative-TIR, i.e. change in TIR divided by the percent of possible change (∆TIR/(100-TIRbefore)*100). RESULTS: The study group comprised 195 individuals with T1D (47.7% males), mean±SD age 14.6 ± 5.3 years, and diabetes duration 6.0 ± 4.6 years. Telehealth was accomplished with 121 patients and their parents (62.0%); 74 (38.0%) did not transfer complete data. Mean TIR was significantly higher for the two-week period after the telehealth visit than for the two-week period prior the visit (62.9 ± 16.0, p < 0.001 vs. 59.0 ± 17.2); the improvement in relative-TIR was 5.7±26.1%. Initial higher mean glucose level, lower TIR, less time spent at <54 mg/dl range, longer time spent at 180-250 mg/dl range, higher daily insulin dose, and single-parent household were associated with improved relative-TIR. Multiple regression logistic analysis demonstrated only initial lower TIR and single-parent household were significant, odds ratio: -0.506, (95%CI -0.99,-0.023), p=0.04 and 13.82, (95%CI 0.621, 27.016), p=0.04, respectively. CONCLUSIONS: Paediatric and young adult patients with T1D benefited from a telehealth visit during COVID-19. However, this modality is not yet suitable for a considerable proportion of patients.

B-cell non-Hodgkin lymphoma linked to Coxiella burnetii.

Bacteria can induce human lymphomas, whereas lymphoproliferative disorders have been described in patients with Q fever. We observed a lymphoma in a patient with Q fever that prompted us to investigate the association between the 2 diseases. We screened 1468 consecutive patients of the 2004 to 2014 French National Referral Center for Q fever database. The standardized incidence ratios (SIRs) of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) were calculated comparatively to the 2012 Francim Registry. The presence of Coxiella burnetii was tested using immunofluorescence and fluorescence in situ hybridization using a specific 16S ribosomal RNA probe and genomic DNA probe. Seven patients (0.48%) presented mature B-cell lymphoma consisting of 6 DLBCL and 1 FL. An excess risk of DLBCL and FL was found in Q fever patients compared with the general population (SIR [95% confidence interval], 25.4 [11.4-56.4] and 6.7 [0.9-47.9], respectively). C burnetii was detected in CD68(+) macrophages within both lymphoma and lymphadenitis tissues but localization in CD123(+) plasmacytoid dendritic cells (pDCs) was found only in lymphoma tissues. Q fever patients with persistent focalized infection were found more at risk of lymphoma (hazard ratio, 9.35 [1.10-79.4]). Interleukin-10 (IL10) overproduction (P = .0003) was found in patients developing lymphoma. These results suggest that C burnetii should be added to the list of bacteria that promote human B-cell non-Hodgkin lymphoma, possibly by the infection of pDCs and IL10 overproduction. Screening for early lymphoma diagnosis should be considered in the management of patients with Q fever, especially those with persistent focalized infections.

Culture-negative prosthetic joint arthritis related to Coxiella burnetii.

BACKGROUND: The number of hip and knee arthroplasty procedures is steadily increasing as life expectancy increases. Coxiella burnetii may be responsible for culture-negative prosthetic joint arthritis and is associated with antibiotic failure and repeated surgeries. We report the first case series of C. burnetii-related culture-negative prosthetic joint arthritis. METHODS: Cases were retrieved from the French National Referral center for Q fever. Diagnosis was based on (18)fluorodeoxyglucose positron emission tomography, serology, broad-range polymerase chain reaction, and C. burnetii-specific polymerase chain reaction. RESULTS: Four cases of C. burnetii-related culture-negative prosthetic joint arthritis were found. Standard bacteriologic procedures would have missed the diagnosis in all cases. Etiologic diagnosis improved the outcome in all but 1 case. CONCLUSIONS: A systematic, comprehensive diagnostic strategy should be used in culture-negative prosthetic joint arthritis, including testing for C. burnetii in endemic areas.

Mutations in the sarcosine dehydrogenase gene in patients with sarcosinemia.

Sarcosinemia is an autosomal recessive metabolic trait manifested by relatively high concentrations of sarcosine in blood and urine. Sarcosine is a key intermediate in 1-carbon metabolism and under normal circumstances is converted to glycine by the enzyme sarcosine dehydrogenase. We encountered six families from two different descents (French and Arab), each with at least one individual with elevated levels of sarcosine in blood and urine. Using the "candidate gene approach" we sequenced the gene encoding sarcosine dehydrogenase (SARDH), which plays an important role in the conversion of sarcosine to glycine, and found four different mutations (P287L, V71F, R723X, R514X) in three patients. In an additional patient, we found a uniparental disomy in the region of SARDH gene. In two other patients, we did not find any mutations in this gene. We have shown for the first time that mutations in the SARDH gene are associated with sarcosinemia. In addition, our results indicate that other genes are most probably involved in the pathogenesis of this condition.

Preimplantation genetic haplotyping a new application for diagnosis of translocation carrier's embryos- preliminary observations of two robertsonian translocation carrier families.

PURPOSE: Preimplantation genetic diagnosis using fluorescence in-situ hybridization (PGD-FISH) is currently the most common reproductive solution for translocation carriers. However, this technique usually does not differentiate between embryos carrying the balanced form of the translocation and those carrying the homologous normal chromosomes. We developed a new application of preimplantation genetic haplotyping (PGH) that can identify and distinguish between all forms of the translocation status in cleavage stage embryos prior to implantation. METHODS: Polymorphic markers were used to identify and differentiate between the alleles that carry the translocation and those that are the normal homologous chromosomes. RESULTS: Embryos from two families of robertsonian translocation carriers were successfully analyzed using polymorphic markers haplotyping. CONCLUSIONS: Our preliminary results indicate that the PGH is capable of distinguishing between normal, balanced and unbalanced translocation carrier embryos. This method will improve PGD and will enable translocation carriers to avoid transmission of the translocation and the associated medical complications to offspring.

Is sperm donor karyotype analysis necessary?

A case study involving four female patients inseminated with sperm samples from the same donor is reported. Routine amniocentesis of one of the patients revealed that the fetus is a carrier of a balanced reciprocal translocation, 46,XY,t(1;10)(q12;q11.2), which was subsequently detected in the donor. Counselled amniocentesis in the three remaining patients led to the detection of an additional translocation carrier fetus. All four pregnancies resulted in live births. Fluorescence in-situ hybridization was applied to identify normal, balanced or imbalanced sperm cells of the donor. Accordingly, routine karyotype analysis of sperm donors was introduced, and is now recommended in the authors' unit.