Tuberculosis and Immune Reconstitution Inflammatory Syndrome in Patients With Inflammatory Bowel Disease and Anti-TNFα Treatment: Insights From a French Multicenter Study and Systematic Literature Review With Emphasis on Paradoxical Anti-TNFα Resumption.

Background: The advent of anti-tumor necrosis factor α (anti-TNFα) has revolutionized the treatment of inflammatory bowel disease (IBD). However, susceptibility to active tuberculosis (TB) is associated with this therapy and requires its discontinuation. The risk of immune reconstitution inflammatory syndrome (IRIS) in this population is poorly understood, as is the safety of resuming anti-TNFα. Methods: This French retrospective study (2010-2022) included all TB cases in patients with IBD who were treated with anti-TNFα in 6 participating centers. A systematic literature review was performed on TB-IRIS and anti-TNFα exposure. Results: Thirty-six patients were included (median age, 35 years; IQR, 27-48). TB was disseminated in 86% and miliary in 53%. IRIS occurred in 47% after a median 45 days (IQR, 18-80). Most patients with TB-IRIS (93%) had disseminated TB. Miliary TB was associated with IRIS risk in univariate analysis (odds ratio, 7.33; 95% CI, 1.60-42.82; P = .015). Anti-TB treatment was longer in this population (median [IQR], 9 [9-12] vs 6 [6-9] months; P = .049). Anti-TNFα was resumed in 66% after a median 4 months (IQR, 3-10) for IBD activity (76%) or IRIS treatment (24%), with only 1 case of TB relapse. Fifty-two cases of TB-IRIS in patients treated with anti-TNFα were reported in the literature, complicating disseminating TB (85%) after a median 42 days (IQR, 21-90), with 70% requiring anti-inflammatory treatment. Forty cases of TB-IRIS or paradoxical reaction treated with anti-TNFα were also reported. IRIS was neurologic in 64%. Outcome was mostly favorable (93% recovery). Conclusions: TB with anti-TNFα treatment is often complicated by IRIS of varying severity. Restarting anti-TNFα is a safe and effective strategy.

First case of bloodstream infection due to Caulobacter spp. associated with a postoperative meningitis.

Caulobacter species are aerobic Gram-negative bacilli initially isolated from aquatic environments and are an uncommon cause of human infection. We report a case of bloodstream infection and postoperative meningitis caused by Caulobacter spp. that occurred in a 53-year old woman two weeks after surgery for a breast carcinoma cerebral metastasis. Polymerase chain reaction (PCR) amplification and sequencing of the 16 S ribosomal DNA identified Caulobacter spp. in three blood cultures and two cerebrospinal fluid (CSF) cultures. Based on our susceptibility results, the patient was successfully treated by a 2-week course of iv imipenem followed by a 4-week course of oral trimethoprim-sulfamethoxazole.

Clinical Features and Outcome of Multidrug-Resistant Osteoarticular Tuberculosis: A 12-Year Case Series from France.

The optimal treatment for osteoarticular infection due to multidrug-resistant tuberculosis strains (MDR-OATB) remains unclear. This study aims to evaluate the diagnosis, management and outcome of MDR-OATB in France. We present a case series of MDR-OATB patients reviewed at the French National Reference Center for Mycobacteria between 2007 and 2018. Medical history and clinical, microbiological, treatment and outcome data were collected. Twenty-three MDR-OATB cases were reported, representing 3% of all concurrent MDR-TB cases in France. Overall, 17 were male, and the median age was 32 years. Six patients were previously treated for TB, including four with first-line drugs. The most frequently affected site was the spine (n = 16). Bone and joint surgery were required in 12 patients. Twenty-one patients (91%) successfully completed the treatment with a regimen containing a mean of four drugs (range, 2-6) for a mean duration of 20 months (range, 13-27). Overall, high rates of treatment success were achieved following WHO MDR-TB treatment guidelines and individualized patient management recommendations by the French National TB Consilium. However, the optimal combination of drugs, duration of treatment and role of surgery in the management of MDR-OATB remains to be determined.

A nomogram to predict the risk of unfavourable outcome in COVID-19: a retrospective cohort of 279 hospitalized patients in Paris area.

OBJECTIVE: To identify predictive factors of unfavourable outcome among patients hospitalized for COVID-19. METHODS: We conducted a monocentric retrospective cohort study of COVID-19 patients hospitalized in Paris area. An unfavourable outcome was defined as the need for artificial ventilation and/or death. Characteristics at admission were analysed to identify factors predictive of unfavourable outcome using multivariable Cox proportional hazard models. Based on the results, a nomogram to predict 14-day probability of poor outcome was proposed. RESULTS: Between March 15th and April 14th, 2020, 279 COVID-19 patients were hospitalized after a median of 7 days after the first symptoms. Among them, 88 (31.5%) patients had an unfavourable outcome: 48 were admitted to the ICU for artificial ventilation, and 40 patients died without being admitted to ICU. Multivariable analyses retained age, overweight, polypnoea, fever, high C-reactive protein, elevated us troponin-I, and lymphopenia as risk factors of an unfavourable outcome. A nomogram was established with sufficient discriminatory power (C-index 0.75), and proper consistence between the prediction and the observation. CONCLUSION: We identified seven easily available prognostic factors and proposed a simple nomogram for early detection of patients at risk of aggravation, in order to optimize clinical care and initiate specific therapies. KEY MESSAGES Since novel coronavirus disease 2019 pandemic, a minority of patients develops severe respiratory distress syndrome, leading to death despite intensive care. Tools to identify patients at risk in European populations are lacking. In our series, age, respiratory rate, overweight, temperature, C-reactive protein, troponin and lymphocyte counts were risk factors of an unfavourable outcome in hospitalized adult patients. We propose an easy-to-use nomogram to predict unfavourable outcome for hospitalized adult patients to optimize clinical care and initiate specific therapies.

Different kinetics of infectious processes in vertebral osteomyelitis of pyogenic or tuberculous origin explain different timing of surgery.

Background: Whether surgery modalities vary according to kinetics of pathological processes responsible for vertebral osteomyelitis (VO) is unclear. We therefore compared surgical modalities in patients with haematogenous pyogenic VO (HPVO) or tuberculous VO (TVO).Methods: Patients who had surgery for HPVO or TVO between January 1997 and June 2018 in a university hospital were included. Surgical indications, timing, and procedures and outcomes were evaluated at the end of treatment.Results: Seventy-eight patients (50 men) were included: 39 with HPVO and 39 with TVO; median age was 64 and 41 years, respectively. In patients with HPVO, surgery was performed early: 17 (44%) had surgery within 72 h of admission; main indication for surgery was neurological deficit in 29 patients that persisted in 12 patients (27%). In patients with TVO, surgery was performed later (p<.001), after two weeks in 20 patients (51%), and was indicated by a neurological deficit in 23 patients; among them, only one (4%) had residual deficit.Conclusions: Different kinetic profiles of the infectious processes explain the more rapid indication for surgery in patients with HPVO and the more favourable neurological recovery in patients with TVO.

More complications in cervical than in non-cervical spine tuberculosis.

Purpose: Cervical spine tuberculosis (CST) is a rare disease that may lead to severe neurological complications. The goal of the study was to compare the characteristics of patients with CST with those of patients with non-cervical spine tuberculosis (NCST).Methods: Between 1997 and 2016, we reviewed all cases of proven tuberculosis from a cohort of spine infections in a tertiary care hospital. Clinical, biological, and imaging data were collected at baseline and after treatment.Results: Fifty-one cases of spine tuberculosis were included: 14 with CST on imaging (27%) and 37 with no cervical localization. Median age was 39 y. Demographic characteristics, duration of symptoms and neurological findings of spine compression were similarly present at presentation in CST and NCST patients. On imaging, lesions were more often multifocal in CST than in NCST patients (9/14 [64%] versus 10/37 [27%], p = .014). Spinal surgery was required in 32/51 (63%) patients. At the end of follow-up (median: 20 months), cure rates were similar in CST and NCST patients but motor and/or sensitive functional sequel were more frequent in CST than NCST patients (6/14 [43%] versus 2/37 [5%], p = .003).Conclusions: Cervical involvement is present in more than a quarter of patients with spinal tuberculosis. Patients with CST had more frequent neurological sequelae than patients with NCST. This was mainly due to a more multifocal disease at presentation. Screening for cervical localization should be systematic in patients with spinal tuberculosis even in the absence of cervical symptoms.

Surgery is safe and effective when indicated in the acute phase of hematogenous pyogenic vertebral osteomyelitis.

BACKGROUND: The overall benefit of surgical management in the acute phase of hematogenous pyogenic vertebral osteomyelitis remains difficult to evaluate because of the balance between potential functional benefit versus complications of surgery. METHODS: Between 2000 and 2013, in a tertiary care hospital, we analyzed a cohort of patients with hematogenous pyogenic vertebral osteomyelitis treated surgically and compared them to those treated medically. Neurologic deficit (using the ASIA impairment scale) and pain (using the analgesic level required) 4 months later, recurrences and infection-related deaths 12 months later were evaluated. A propensity score was developed to adjust for nonrandomized allocation to surgery. RESULTS: Ninety patients were included (mean age 64 years, 63% male); 28 (31%) were treated surgically. After adjustment for the propensity score, the improvement in neurological deficit at 4 months did not differ between surgical and medical treatment (p = .82), but the reduction of pain tended to be greater in surgical versus medical treatment (p = .051). Recurrences of infection (5%) and infection-related deaths (12%) occurred at similar rates in both groups at 12 months (p = 1.00 for both). CONCLUSIONS: Patients with hematogenous pyogenic vertebral osteomyelitis requiring surgery improved equally as non-surgical patients in terms of neurological deficit and residual pain. This result was not hampered by increased complications related to surgery. When indicated, surgery is safe and effective in patients suffering from hematogenous pyogenic vertebral osteomyelitis.

Characteristics of and risk factors for severe neurological deficit in patients with pyogenic vertebral osteomyelitis: A case-control study.

Severe neurological deficit (SND) is a rare but major complication of pyogenic vertebral osteomyelitis (PVO). We aimed to determine the risk factors and the variables associated with clinical improvement for SND during PVO.This case-control study included patients without PVO-associated SND enrolled in a prospective randomized antibiotic duration study, and patients with PVO-associated SND managed in 8 French referral centers. Risk factors for SND were determined by logistic regression.Ninety-seven patients with PVO-associated SND cases, and 297 controls were included. Risk factors for SND were epidural abscess [adjusted odds ratio, aOR 8.9 (3.8-21)], cervical [aOR 8.2 (2.8-24)], and/or thoracic involvement [aOR 14.8 (5.6-39)], Staphylococcus aureus PVO [aOR 2.5 (1.1-5.3)], and C-reactive protein (CRP) >150 mg/L [aOR 4.1 (1.9-9)]. Among the 81 patients with PVO-associated SND who were evaluated at 3 months, 62% had a favorable outcome, defined as a modified Rankin score ≤ 3. No factor was found significantly associated with good outcome, whereas high Charlson index [adjusted Hazard Ratio (aHR) 0.3 (0.1-0.9)], low American Spinal Injury Association (ASIA) impairment scale at diagnosis [aHR 0.4 (0.2-0.9)], and thoracic spinal cord compression [aHR 0.2 (0.08-0.5)] were associated with poor outcome. Duration of antibiotic treatment was not associated with functional outcome.SND is more common in cervical, thoracic, and S. aureus PVO, in the presence of epidural abscess, and when CRP >150 mg/L. Although neurological deterioration occurs in 30% of patients in early follow-up, the functional outcome is quite favorable in most cases after 3 months. The precise impact of optimal surgery and/or corticosteroids therapy must be specified by further studies.

Invasive actinomycosis: surrogate marker of a poor prognosis in immunocompromised patients.

OBJECTIVES: Actinomycosis is a rare disease favored by disruption of the mucosal barrier. In order to investigate the impact of immunosuppression on outcome we analyzed the most severe cases observed in patients hospitalized in three tertiary care centers. METHODS: We reviewed all cases of proven invasive actinomycosis occurring over a 12-year period (1997 to 2009) in three teaching hospitals in the Paris area. RESULTS: Thirty-three patients (16 male) were identified as having an invasive actinomycosis requiring hospitalization. The diagnosis was made by microbiological identification in 26 patients, pathological examination in eight patients, and by both methods in one. Twenty patients (61%) were immunocompromised. Actinomycosis localization was abdominal or pelvic in 17 patients, thoracic in 11, cervicofacial in three, and neurological in two. Twenty patients (61%) underwent surgery. All strains were susceptible to amoxicillin. All patients were treated with a beta-lactam antibiotic, for a median length of 82 days. Twenty-eight patients (85%) were considered as cured. Overall mortality at hospital discharge was 21% (7/33). Mortality was higher in immunocompromised patients (7/20; 21%) compared to non-immunocompromised patients (0/13) (p=0.027). However, six of seven deaths were directly related to the underlying disease. CONCLUSIONS: Actinomycosis is a cause of severe infection in immunocompromised patients and a surrogate marker of a poor prognosis in this specific population.

[Neurosurgical material-associated infections]. / Infections liées aux matériels neurochirurgicaux.

Cerebrospinal fluid shunts (CSF) are frequently implanted in acute or chronic hydrocephalus. Intraoperative contamination is the main cause of infection of these devices. Causative germs are found mostly saprophytic (including Staphylococcus sp). The diagnosis can be easy, especially referred to a febrile meningeal syndrome, but also less intense, resulting in valve dysfunction. Therefore, in practice, any patient with CSF shunt should be suspected of being infected thereof, in case of fever and/or new or reappearing neurological symptoms, and until proven otherwise. The treatment is based on high-doses parenteral antibiotherapy, and more often removing the CSF shunt. Infections of cochlear implant are less common, and rarely deep. They are treated surgically by cleaning the surgical site, and in combination with systemic antibiotics. Their conservative treatment can be a concern.

Prevalence, correlates and outcomes of gastric antral vascular ectasia in systemic sclerosis: a EUSTAR case-control study.

OBJECTIVE: To estimate the prevalence, determine the subgroups at risk, and the outcomes of patients with systemic sclerosis (SSc) and gastric antral vascular ectasia (GAVE). METHODS: We queried the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) network for the recruitment of patients with SSc-GAVE. Each case was matched for cutaneous subset and disease duration with 2 controls with SSc recruited from the same center, evaluated at the time the index case made the diagnosis of GAVE. SSc characteristics were recorded at the time GAVE occurred and the last observation was collected to define the outcomes. RESULTS: Forty-nine patients with SSc and GAVE were included (24 with diffuse cutaneous SSc) and compared to 93 controls with SSc. The prevalence of GAVE was estimated at about 1% of patients with SSc. By multivariate analysis, patients with SSc-GAVE more frequently exhibited a diminished (< 75%) DLCO value (OR 12.8; 95% CI 1.9-82.8) despite less frequent pulmonary fibrosis (OR 0.2; 95% CI 0.1-0.6). GAVE was also associated with the presence of anti-RNA-polymerase III antibodies (OR 4.6; 95% CI 1.2-21.1). SSc-GAVE was associated with anemia (82%) requiring blood transfusion (45%). Therapeutic endoscopic procedures were performed in 45% of patients with GAVE. After a median followup of 30 months (range 1-113 months), survival was similar in patients with SSc-GAVE compared to controls, but a higher number of scleroderma renal crisis cases occurred (12% vs 2%; p = 0.01). CONCLUSION: GAVE is rare and associated with a vascular phenotype, including anti-RNA-polymerase III antibodies, and a high risk of renal crisis. Anemia, usually requiring blood transfusions, is a common complication.

Clinical outcome after a totally implantable venous access port-related infection in cancer patients: a prospective study and review of the literature.

Morbidity and mortality after a totally implantable venous access port (TIVAP)-related infection in oncology patients have rarely been studied. We conducted this study to assess the incidence and factors associated with the following outcome endpoints: severe sepsis or septic shock at presentation, cancellation of antineoplastic chemotherapy, and mortality at week 12. We conducted a prospective single-center observational study including all adult patients with solid cancer who experienced a TIVAP-related infection between February 1, 2009, and October 31, 2010. Patients were prospectively followed for 12 weeks. Among 1728 patients receiving antineoplastic chemotherapy during the inclusion time, 72 had an episode of TIVAP-related infection (4.2%) and were included in the study (median age, 60 yr; range, 28-85 yr). The incidence of complications was 18% for severe sepsis or septic shock (13/72 patients), 30% for definitive cancellation of antineoplastic chemotherapy (14/46 patients who still had active treatment), and 46% for death at week 12 (33/72 patients). Factors associated with severe sepsis or septic shock were an elevated C-reactive protein (CRP) level and an infection caused by Candida species; 4 of the 13 severe episodes (31%) were due to coagulase-negative staphylococci (CoNS). Factors associated with death at week 12 were a low median Karnofsky score, an elevated Charlson comorbidity index, the metastatic evolution of cancer, palliative care, and an elevated CRP level at presentation. Hematogenous complications (that is, infective endocarditis, septic thrombophlebitis, septic pulmonary emboli, spondylodiscitis, septic arthritis, or organ abscesses) were found in 8 patients (11%). In conclusion, patients' overall condition (comorbidities and autonomy) and elevated CRP level were associated with an unfavorable clinical outcome after a TIVAP-related infection. Candida species and CoNS were responsible for severe sepsis or septic shock.