Dalbavancin as salvage therapy in difficult-to-treat patients for diabetes-related foot osteomyelitis.

OBJECTIVES: We aimed to describe the efficacy and safety of dalbavancin in treatment of patients with diabetes-related foot osteomyelitis with bone culture confirmation. PATIENTS AND METHODS: Between January 2019 and December 2021, all consecutive patients receiving at least one 1500 mg dose of dalbavancin for diabetes-related foot osteomyelitis were included in a retrospective study. Remission was defined as absence of relapsing infection or need for surgery at the initial or a contiguous site during 6-month follow-up from the last dose of dalbavancin. RESULTS: Thirteen patients were included. Eleven (85%) patients were surgically treated. Six (46%) patients received dalbavancin as first-line treatment and 7 (54%) as second-line treatment due to adverse events related to previous treatments. One adverse event was reported. At 6-month follow-up, 11 patients were evaluable and 9 (82%) were in remission. CONCLUSIONS: In the study, dalbavancin was well-tolerated and showed microbiological and clinical efficacy.

Factors Associated With the Use of Hypothermic Machine Perfusion in Kidney Transplant Recipients: A Multicenter Retrospective Cohort Study.

Background: Delayed graft function (DGF) is associated with an increased risk of graft loss. The use of cold hypothermic machine perfusion (HMP) has been shown to reduce the incidence of DGF in kidney transplant recipients (KTRs), especially when extended-criteria donors (ECDs) are used. HMP can also improve graft survival. However, there is a paucity of data on the determinants of HMP use in clinical practice. Objective: We aimed to determine the factors associated with the use of HMP in a cohort of donors and KTRs. Design: Multicenter retrospective cohort study. Setting: 5 transplant centers in Quebec. Patients: 159 neurologically deceased donors (NDD) and 281 KTR. Measurements: Use of HMP. Methods: We collected data on consecutive NDD admitted to a dedicated donor unit in a single university-affiliated center and their KTRs between June 2013 and December 2018 in 5 adult transplant centers across the province of Quebec, Canada. All organs were recovered in a single hospital center where a HMP device was available for every organ recovered and the decision to use HMP was left at the discretion of the procurement surgeon. Generalized estimating equations were used to predict the use of HMP. Results: The cohort included 159 NDDs and their 281 KTRs. Thirty-three percent of donors were ECDs, and 59% of KTRs received organs placed on HMP. The median cold ischemia time (CIT) was 12.5 (IQR 7.9-16.3) hours. In univariate analysis, none of the donors' characteristics were associated with the use of HMP. ECD represented 33% of KTR on HMP vs 35% of those not placed on HMP (P = .77). In univariate analysis, the use of HMP was associated with KTR race (non-Caucasian), longer CIT, use of basiliximab/alemtuzumab, year of transplant, and transplant center. The use of HMP varied largely across transplant centers, ranging from 15% to 82%. In multivariate analysis, use of HMP was associated with longer CIT (odds ratio [OR] 1.15, 95% confidence interval [CI] = 1.07-1.25), transplant center as well as transplantations performed after 2013. Limitations: One dedicated donor unit including NDD only, absence of specific data on surgeons' experience and personal or logistic reasons for using or not HMP. Conclusions: We found that use of HMP remains low and varies largely across transplant centers. The use of HMP was strongly associated with the transplant center where the surgeons practiced, suggesting that surgeon preference/training plays an important role in determining the use of HMP. Availability of HMP at the time of organ procurement might also be limited by logistic issues such as difficulty in returning the device. Further studies aimed at determining the reasons underlying the barriers precluding the use of HMP could help increasing its use and improve transplant outcomes.

Contexte: Les retards dans la reprise de fonction du greffon (RRFG) sont associés à un risque accru d'échec de la greffe. Il a été démontré que la perfusion hypothermique mécanisée (PHM) peut réduire l'incidence d'un RRFG chez les receveurs d'une greffe rénale (RGR), particulièrement dans les cas où des donneurs à critères étendus (DCÉ) sont impliqués. La PHM pourrait également améliorer la survie du greffon. Il existe cependant peu de données sur les facteurs déterminant l'utilisation de la PHM dans la pratique clinique. Objectifs: Déterminer les facteurs associés à l'utilisation de la PHM dans une cohorte de donneurs et de RGR. Type d'étude: Étude de cohorte rétrospective multicentrique. Cadre: Cinq centres de transplantation au Québec. Sujets: L'étude a inclus 159 donneurs neurologiquement décédés (DND) et 281 RGR. Mesures: L'utilisation de la PHM. Méthodologie: Nous avons recueilli les données de DND consécutifs admis entre juin 2013 et décembre 2018 dans une unité spécialisée dans le don d'organes d'un centre hospitalier universitaire, de même que les données de leurs RGR respectifs. Les sujets provenaient de cinq centres de transplantation pour adultes de la province de Québec, au Canada. Tous les organes ont été prélevés dans un centre hospitalier où un dispositif de PHM était disponible pour chaque organe prélevé, et la décision de recourir à la PHM a été laissée à la discrétion du chirurgien chargé du prélèvement. Des équations d'estimation généralisées ont été employées pour prédire l'utilisation de la PHM. Résultats: La cohorte était composée de 159 DND et de leurs 281 RGR. Les DCÉ constituaient 33 % des DND et 59 % des RGR avaient reçu un organe placé sur PHM. La durée médiane de l'ischémie froide (DmIF) était de 12,5 heures (ÉIQ: 7,9-16,3 heures). Dans l'analyse univariée, aucune des caractéristiques des donneurs n'a été associée à l'utilisation de la PHM. Des RGR de la cohorte qui avaient reçu un rein provenant d'un DCÉ, 33 % ont reçu un organe qui avait été placé sous PHM et 35 % avaient reçu un rein non perfusé à froid (p = 0,77). L'analyse univariée a également révélé une association entre l'utilisation de la PHM et l'origine ethnique du RGR (non caucasien), une DmIF prolongée, l'administration de basiliximab/alemtuzumab, l'année de la greffe et le centre de transplantation. L'utilisation de la PHM variait grandement d'un centre à un autre, allant de 15 % à 82 %. Dans l'analyse multivariée, l'utilisation de la PHM a été associée à une DmIF prolongée (rapport de cotes [RC]: 1,15; [IC95 %]: 1,07-1,25), au centre de transplantation ainsi qu'aux transplantations réalisées après 2013. Limites: Étude tenue dans une seule unité spécialisée en don d'organes et portant uniquement sur des DND. Absence de données précises sur l'expérience des chirurgiens et sur les raisons personnelles ou logistiques justifiant l'utilisation ou non de la PHM. Conclusion: Nous avons constaté que l'utilisation de la PHM demeure faible et qu'elle varie fortement d'un centre de transplantation à un autre. L'utilisation de la PHM a été fortement associée au centre de transplantation où exerçaient les chirurgiens, ce qui laisse penser que les préférences personnelles et la formation du chirurgien sont des facteurs déterminants pour son utilisation. La disponibilité de la PHM au moment du prélèvement des organes peut également être limitée par des questions logistiques telles que la difficulté de retourner l'appareil. D'autres études se penchant sur les raisons sous-jacentes aux obstacles empêchant l'utilisation de la PHM pourraient aider à en accroître l'utilisation et à améliorer les résultats de la transplantation.

Acute Kidney Failure During SARS-CoV-2.

The occurrence of acute kidney injury (AKI) during COVID infection is associated with increased morbidity and mortality of patients. AKI can occur at any stage of COVID-19 infection; clinical judgment and the consideration of AKI risk factors along with early detection and diagnosis are essential to prevent short- and long-term complications. A review of the literature found that pre-existing chronic kidney disease, obesity, and the severe presentation of the illness appear to be risk factors; people who develop AKI during acutely severe disease may have slightly worse outcomes than patients without COVID-19 who develop AKI; and finally, certain genetic susceptibilities may play a role in developing COVID-19-related AKI. Nurses can assist in detecting, preventing, and treating AKI in patients with COVID-19. Nursing interventions can be implemented to optimize care for individuals and their families in the context of COVID-19 and kidney injury. Finally, discoveries from this critical situation can help health care facilities plan resources and prepare for the increased health care burden of survivors of AKI associated with COVID-19. This article discusses recent data about how the virus causes kidney injury and suggests nursing solutions to optimize care for patients with AKI.

Virological Outcome After Choice of Antiretroviral Regimen Guided by Proviral HIV-1 DNA Genotyping in a Real-Life Cohort of HIV-Infected Patients.

Issues have been raised concerning clinical relevance of HIV-1 proviral DNA genotypic resistance test (DNA GRT). To assess impact of DNA GRT on choice of antiretroviral therapy (ART) and subsequent virological outcome, we retrospectively reviewed decision-making and viral load (VL) evolution following DNA GRT performed in our center between January 2012 and December 2017, except those prescribed within the framework of a clinical trial. A total of 304 DNA GRTs were included, 185 (62%) performed in a context of virological success. Only 34% of tests were followed by ART change, more frequently in situation of virological success (39% vs. 26%, p = 0.02). In this situation, ART change guided by DNA GRT led to VL >20 copies/mL after 6 months in 5% of cases. In multivariate analysis, higher HIV DNA quantification (p = 0.01) was associated with occurrence of viremia. A higher nadir of CD4 count (p = 0.04) and a longer time with VL <20 copies/mL (p = 0.04) were independently associated with a lower risk of viremia. In situation of low-level viremia, ART change guided by DNA GRT led to VL <20 copies/mL after 6 months in 52% of cases, while decision to maintain the same treatment led to VL <20 copies/mL in 74% of cases. In multivariate analysis, longer time with VL >20 copies/mL (p = 0.02) was associated with persistence of virological replication. In conclusion, in situation of virological success, use of DNA GRT in addition to analysis of historical RNA GRT to guide ART optimization appears safe. Its prescription framework in situation of low-level viremia deserves to be better defined.

Clinical and virological features of acute hepatitis A during an ongoing outbreak among men who have sex with men in the North of France.

OBJECTIVES: Since February 2017, an increase of acute hepatitis A (AHA) cases has been notified in North of France. We aimed to report clinical and virological features of 49 cases treated in three hospitals in Lille European Metropolis (LEM). METHODS: All adult patients treated for AHA in 3 LEM hospitals between 20 February and 5 July 2017 were included. Demographic characteristics, exposure risk factors to hepatitis A virus (HAV), AHA manifestations and concomitant sexually transmitted infections (STI) were retrospectively recorded. RESULTS: Forty-nine cases of AHA were diagnosed among which 34 (69%) were hospitalised. Severe AHA occurred in 7 (14%) patients. The median age of cases was 36 years. All cases except 1 were men and 32 (65%) were identified as men having sex with men (MSM). Eleven (23%) patients were HIV-infected, 5 were under HIV pre-exposure prophylaxis (PrEP), 6 had a history of HIV postexposure prophylaxis and 19 had a history of at least one STI. Only three patients had received HAV vaccine. Proportion of patients tested for syphilis, chlamydial and gonococcal infections was 75% (18/24) in those seen by sexual health specialists and 21% (6/29) in those seen by other specialists. At least one concomitant STI was diagnosed in 13 out of 24 tested patients (54%). RT-PCR sequencing was available for 38 cases and confirmed co-circulation of 3 different strains of subgenotype IA (VRD 521 2016: n=24, RIVM-HAV16-090: n=13, V16-25801: n=1), already identified in several European countries. CONCLUSIONS: We are facing an outbreak of AHA among MSM in the North of France with a high rate of hospitalisation. Analysis of cases highlighted missed opportunities of vaccination and lack of concomitant STI screening. Awareness among healthcare providers and MSM should be increased and HAV vaccination promoted.

Organ donor management and delayed graft function in kidney transplant recipients: A multicenter retrospective cohort study.

Meeting donor management goals (DMGs) has been reported to decrease the incidence of delayed graft function (DGF) after kidney transplant, but whether this relationship is independent of cold machine perfusion is unclear. We aimed to determine whether meeting DMGs is associated with a reduced incidence of DGF, independent of the use of machine perfusion. We collected data on consecutive brain-dead donors and their KT recipients (KTRs) between June 2013 and December 2016 in 5 adult transplant centers. We evaluated whether DMGs were met at donor neurologic death (DND) and later time points. We defined a priori meeting optimal DMG as achieving ≥7 DMGs. Generalized estimating equations were used to predict DGF. Among 122 donors, 34% were extended-criteria donors (ECDs). The number of DMGs met increased over time (5.6 ± 1.4 at DND and 6.1 ± 1.3 at organ procurement [P < .001]). DGF occurred in 23% of 214 KTRs, and 55% received organs placed on machine perfusion. In multivariate analysis, ECD (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.13-4.45), use of machine perfusion (OR 0.45, 95% CI 0.22-0.94), and optimal DMG at DND (OR 0.39, 95% CI 0.16-0.99) were associated with DGF. Early achievement of DMGs was associated with a reduced risk of the development of DGF, independent of the use of machine perfusion.

Mycobacterium mucogenicum bacteremia: major role of clinical microbiologists.

INTRODUCTION: Mycobacterium mucogenicum is a rare but emerging cause of infections, especially in immunocompromised patients. CASE PRESENTATION: We describe a new case of M. mucogenicum catheter-related bloodstream infection in a 34-year-old woman with ovarian cancer. M. mucogenicum was at first considered as a contaminant, and susceptibility testing was not performed. Usual susceptibility of M. mucogenicum motivated prescription of clarithromycin and moxifloxacin. Finally, our isolate was confirmed susceptible to both drugs. Clinical outcome was favorable with no relapse of infection after antibiotics discontinuation despite concomitant chemotherapy. CONCLUSION: Our case illustrates the need for a clinician-microbiologist dialogue in case of suspected M. mucogenicum infection to avoid delaying appropriate management.

The human NAIP-NLRC4-inflammasome senses the Pseudomonas aeruginosa T3SS inner-rod protein.

While NLRC4-dependent sensing of intracellular Gram-negative pathogens such as Salmonella enterica serovar typhimurium is a beneficial host response, NLRC4-dependent sensing of the Pseudomonas aeruginosa type 3 secretion system (T3SS) has been shown to be involved in pathogenicity. In mice, different pathogen-associated microbial patterns are sensed by the combination of the NLRC4-inflammasome with different neuronal apoptosis inhibitory proteins (NAIPs). NAIP2 is involved in sensing PscI, an inner-rod protein of the P. aeruginosa T3SS. Surprisingly, only a single human NAIP (hNAIP) has been found. Moreover, there is no description of hNAIP-NLRC4 inflammasome recognition of T3SS inner-rod proteins in humans. Here, we show that the P. aeruginosa T3SS inner-rod protein PscI and needle protein PscF are both sensed by the hNAIP-NLRC4 inflammasome in human macrophages and PBMCs from healthy donors, allowing caspase-1 and IL-1ß maturation and resulting in a robust inflammatory response. TLR4 and TLR2 are involved in redundantly sensing these two T3SS components.

Retrospective Study Looking at Cinacalcet in the Management of Hyperparathyroidism after Kidney Transplantation.

Objectives. The primary objective of this study is to evaluate the use of cinacalcet in the management of hyperparathyroidism in kidney transplant recipients. The secondary objective is to identify baseline factors that predict cinacalcet use after transplantation. Methods. In this single-center retrospective study, we conducted a chart review of all patients having been transplanted from 2003 to 2012 and having received cinacalcet up to kidney transplantation and/or thereafter. Results. Twenty-seven patients were included with a mean follow-up of 2.9 ± 2.4 years. Twenty-one were already taking cinacalcet at the time of transplantation. Cinacalcet was stopped within the first month in 12 of these patients of which 7 had to restart therapy. The main reason for restarting cinacalcet was hypercalcemia. Length of treatment was 23 ± 26 months. There were only 3 cases of mild hypocalcemia. There was no statistically significant association between baseline factors and cinacalcet status a year later. Conclusions. Discontinuing cinacalcet within the first month of kidney transplantation often leads to hypercalcemia. Cinacalcet appears to be an effective treatment of hypercalcemic hyperparathyroidism in kidney transplant recipients. Further studies are needed to evaluate safety and long-term benefits.

Specific Polysaccharide Antibody Deficiency Revealed by Severe Bacterial Infections in Adulthood: A Report on 11 Cases.

We report on 11 cases of specific polysaccharide antibody deficiency (SPAD) revealed in adulthood by severe infections with encapsulated bacteria. Given that immunoglobulin replacement therapy can effectively prevent the recurrence of bacterial infections in this context, SPAD should be considered once other antibody deficiencies have been ruled out.

Nonopioid Management of Neonatal Abstinence Syndrome.

BACKGROUND: Current standard therapy for moderate to severe neonatal abstinence syndrome (NAS) includes opioid administration and often results in separation of mother and infant. Impaired maternal-infant bonding and extended neonatal opiate exposure may be associated with adverse developmental outcomes. Increased use of nonopioid adjunctive NAS therapies may decrease postnatal opioid exposure and length of stay (LOS), thereby promoting positive developmental outcomes for NAS-affected infants. PURPOSE: To review the efficacy of rooming-in care and acupuncture as nonpharmacologic adjunctive agents to reduce the magnitude of postnatal opioid exposure and LOS. METHODS: PubMed, Ovid Medline, Embase, and CINAHL databases were searched for primary studies on rooming-in care and acupuncture as adjunctive treatments for NAS; 8 are included in this review. FINDINGS: Rooming-in care may decrease postnatal opioid exposure and LOS in NAS-affected infants. Acupuncture is safe in NAS patients; however, its definitive effect on narcotic use and length of hospitalization are inconclusive. IMPLICATIONS FOR PRACTICE: Rooming-in care should be offered to NAS patients. Strong evidence does not exist to recommend acupuncture as a routine NAS treatment. IMPLICATIONS FOR RESEARCH: Additional randomized clinical trials are necessary to assess the efficacy of acupuncture and to confirm the effect of rooming-in care on NAS outcomes, and delineate optimal elements of a rooming-in care model.

Eculizumab for the Treatment of Severe Antibody-Mediated Rejection: A Case Report and Review of the Literature.

In renal transplantation, treatment options for antibody-mediated rejection are limited. Here, we report a case of severe AMR treated with eculizumab. A 50-year-old woman known for end stage kidney disease secondary to IgA nephropathy received a kidney transplant from a 50-year-old deceased donor. At 5 months after transplantation, she presented with acute graft dysfunction and biopsy showed a severe antibody-mediated rejection associated with thrombotic microangiopathy. Despite an aggressive conventional immunosuppressive regimen, signs of rejection persisted and the patient was treated with 3 doses of eculizumab. Following the therapy, markers of TMA improved and graft function stabilized. However, ongoing signs of rejection remained in the repeated biopsy. In kidney transplantation, eculizumab is an expensive treatment and its role in the treatment of antibody-mediated rejection remains to be determined.

Endoscopy-based management decreases the risk of postoperative recurrences in Crohn's disease.

AIM: To investigate whether an endoscopy-based management could prevent the long-term risk of postoperative recurrence. METHODS: From the pathology department database, we retrospectively retrieved the data of all the patients operated on for Crohn's disease (CD) in our center (1986-2015). Endoscopy-based management was defined as systematic postoperative colonoscopy (median time after surgery = 9.5 mo) in patients with no clinical postoperative recurrence at the time of endoscopy. RESULTS: From 205 patients who underwent surgery, 161 patients (follow-up > 6 mo) were included. Endoscopic postoperative recurrence occurred in 67.6%, 79.7%, and 95.5% of the patients, respectively 5, 10 and 20 years after surgery. The rate of clinical postoperative recurrence was 61.4%, 75.9%, and 92.5% at 5, 10 and 20 years, respectively. The rate of surgical postoperative recurrence was 19.0%, 38.9% and 64.7%, respectively, 5, 10 and 20 years after surgery. In multivariate analysis, previous intestinal resection, prior exposure to anti-TNF therapy before surgery, and fistulizing phenotype (B3) were postoperative risk factors. Previous perianal abscess/fistula (other perianal lesions excluded), were predictive of only symptomatic recurrence. In multivariate analysis, an endoscopy-based management (n = 49/161) prevented clinical (HR = 0.4, 95%CI: 0.25-0.66, P < 0.001) and surgical postoperative recurrence (HR = 0.30, 95%CI: 0.13-0.70, P = 0.006). CONCLUSION: Endoscopy-based management should be recommended in all CD patients within the first year after surgery as it highly decreases the long-term risk of clinical recurrence and reoperation.

Myenteric plexitis is a risk factor for endoscopic and clinical postoperative recurrence after ileocolonic resection in Crohn's disease.

BACKGROUND: As surgical resection is not curative in Crohn's disease, postoperative recurrence remains a crucial issue. The selection of patients, according to available risk factors, remains disappointing in clinical practice highlighting the need for better criteria, such as histologic features. AIMS: To investigate whether submucosal and myenteric plexitis increase the risk of endoscopic, clinical and surgical postoperative recurrence in Crohn's disease. METHODS: From the pathology department database, we retrospectively retrieved the data of all the patients who have undergone ileocolonic resection for Crohn's disease. Two pathologists, blinded from clinical data, reviewed all specimens to evaluate the presence of plexitis at the proximal resection margin. RESULTS: Of the 75 included CD patients, 19 (25.3%) had histological involvement of resection margin. Inflammatory cells count for myenteric and submucosal plexus were performed in 56 patients. In multivariate analysis, the myenteric plexitis was a risk factor for endoscopic postoperative recurrence (HR 8.83 CI95% [1.6-48.6], p=0.012), and the presence of at least one myenteric lymphocyte (HR 4.02 CI95% [1.4-11.2], p=0.008) was predictive of clinical postoperative recurrence. We observed no histologic predictor for surgical postoperative recurrence. CONCLUSION: Myenteric plexitis in proximal margins of ileocolonic resection specimens is independently associated with endoscopic and clinical postoperative recurrence in Crohn's disease.

Conversion from twice-daily to once-daily extended-release tacrolimus in renal transplant recipients: 2-year results and review of the literature.

OBJECTIVES: Tacrolimus extended-release formulation has been approved for use in Canada since October 2008. In initial studies, efficacy and safety profile were demonstrated as similar for both formulations (twice-daily tacrolimus and extended-release formula tacrolimus). To validate the safety and efficacy of extended-release formula tacrolimus, we conducted a prospective observational study. MATERIALS AND METHODS: At our institution, between January 2009 and January 2010, the switch from tacrolimus to extended-release formula tacrolimus was done in 130 stable kidney recipients. Clinical data were accessed at baseline (data before conversion), 1 to 2 weeks, 1 month, 3 months, 6 months, 12 months, and 24 months after conversion. RESULTS: One hundred thirty renal transplant recipients were included in the current study. During the observation period, we saw no acute rejection and no change in graft function (mean serum creatinine levels remained stable). However, compared with baseline, mean tacrolimus trough levels were significantly reduced at 1 to 2 weeks, at 1 month, 6 months, 12 months, and at 24 months after conversion. Regarding the safety profile, no significant changes were noted in blood glucose, potassium, and magnesium. Approximately 35% of recipients preferred the extended-release formula tacrolimus to twice-daily tacrolimus. CONCLUSIONS: Conversion from twice-daily tacrolimus to extended-release once-daily tacrolimus appears to be safe and convenient up to 2 years after conversion in some recipients.