Treating Helicobacter pylori and Clostridioides difficile coinfection presents a challenging clinical dilemma. Treating H. pylori may increase the risk of C. difficile, and antibiotics generally have been shown to increase the risk of C. difficile infection/recurrence. While it may be reasonable to delay H. pylori treatment, this is especially challenging when there is an acute indication to treat H. pylori such as peptic ulceration or bleeding. There are no guidelines on the management of H. pylori and C. difficile coinfection. We report a patient who had H. pylori and recurrent C. difficile coinfection and suggest a management algorithm based on literature review and our institutional experience. Our patient received quadruple therapy for H. pylori along with vancomycin prophylaxis, taper, and a dose of bezlotoxumab and experienced good outcomes with resolution of his gastrointestinal bleeding and diarrhea.

暂无摘要。

Coronavirus disease 2019(COVID-19) is prevalent around the world, and pre-existing ILD is associated with increased severity and mortality of COVID-19. However, the current knowledge on the management strategy for COVID-19 patients with pre-existing interstitial lung disease (ILD) is very limited. There is still a need for consensus on treatments for these patients. In addition, ILD that occurs after the acute phase of COVID-19 (Post-acute Covid-19 ILD, PC-ILD) is also very common, and how to manage PC-ILD is also under debate. Therefore, a consensus was established by experts from the related disciplines in the field of ILD based on available scientific evidence and experience of the expert working group. This consensus elucidated 22 practical questions for practicing physicians, such as clinical characteristics, risk factors and treatment of COVID-19 patients with pre-existing ILD and PC-ILD patients. Finally, 15 recommendations were made regarding the diagnosis and management of COVID-19 patients with pre-existing ILD and PC-ILD patients. We hope to assist physicians in making appropriate decisions, thereby improving the management of COVID-19 with pre-existing ILD and PC-ILD.Recommendation 1: It is recommended to differentiate COVID-19 from ILD with acute/subacute onset based on duration, exposure history, symptoms and signs, chest high-resolution CT (HRCT) features, and laboratory tests.Recommendation 2: According to the guidelines on the diagnosis and treatment of new coronavirus pneumonia (version 10) issued by the National Health Commission of China on January 6th, 2023, we recommended the following disease severity definition and management for the COVID-19 patients with pre-existing ILD.Recommendation 3: ILD is an independent risk factor for severe/critical COVID-19. We recommend antiviral treatment for COVID-19 patients with pre-existing ILD as early as possible after symptoms onset, ideally within 5 days.Recommendation 4: We recommend that the use of systemic corticosteroids in COVID-19 patients with pre-existing ILD who had no indications for corticosteroids therapy should follow the guidelines of COVID-19 for the general population. Those with pre-existing ILD who need to start or are already on systemic corticosteroids are recommended to start or continue corticosteroids if they develop COVID-19. The dose adjustment is based on the severity of COVID-19 with pre-existing ILD: For the patients with severe/critical COVID-19 with pre-existing ILD but no AE-ILD, the use of corticosteroids should follow the guidelines of COVID-19 in the general population; the patients with AE-ILD are recommended to follow the use of corticosteroids in AE-ILD.Recommendation 5: There is no evidence available for the use of interleukin-6 receptor blockers in COVID-19 patients with pre-existing ILD. Recommendations regarding interleukin-6 receptor blockers in COVID-19 patients with pre-existing ILD may follow the guideline of COVID-19 in the general population.Recommendation 6: There is no evidence to support the use of Janus kinase inhibitors in COVID-19 patients with pre-existing ILD. The use of Janus kinase inhibitors in COVID-19 patients with pre-existing ILD is recommended to follow the guideline of COVID-19 in the general population.Recommendation 7: For patients who have not started immunosuppressants/biological agents for pre-existing ILD at the time of COVID-19, delayed initiation of immunosuppressants/biological agents is recommended, if the risk of ILD progression in the short term is low. For patients who are already on immunosuppressants/biological agents, a multidisciplinary discussion with rheumatologists is recommended to weigh the benefits and risks of discontinuing immunosuppressants/biological agents. It is recommended to discontinue immunosuppressants/biological agents for pre-existing ILD in acute phase of COVID-19 unless short-term discontinuation affects control of underlying ILD or connective tissue disease.Recommendation 8: It is recommended that the COVID-19 patients with pre-existing ILD who are on anti-fibrotic medication should continue to take anti-fibrotic medication. For COVID-19 patients with newly diagnosed fibrotic ILD who need to start anti-fibrotic therapy, it is recommended to start anti-fibrotic treatment as early as possible.Recommendation 9: It is recommended to investigate and monitor co-infections and secondary infections in COVID-19 patients with pre-existing ILD, and to promptly prevent and treat co-infections and secondary infections such as bacteria, fungi, Pneumocystis jirovecii, and cytomegalovirus.Recommendation 10: Anticoagulation therapy for the COVID-19 patients with pre-existing ILD is recommended to be used in accordance with guideline of COVID-19 in general population.Recommendation 11: For COVID-19 patients with pre-existing ILD, we recommend follow-up at 4 weeks after recovery (non-hospitalized patients) or 4 weeks after discharge (hospitalized patients), and then the routine monitoring frequency for ILD once stable, i.e. every 3 to 6 months. Pulmonary function testing is a routine investigation. Chest HRCT is suggested when clinically indicated. Arterial blood gas analysis, echocardiography, CT pulmonary angiography, and blood examinations can be selected when necessary.Recommendation 12: Severe/critical COVID-19 survivors are the main target population for rehabilitation intervention. Rehabilitation therapy should be administered individualized.Recommendation 13: Healthcare providers should fully inform patients with pre-existing ILD about the benefits and risks of vaccination, and involve patients in a shared decision-making process to discuss whether or not to receive a COVID-19 vaccine.Recommendation 14: For PC-ILD patients with persistent or progressive respiratory symptoms, persistent interstitial lung abnormalities and lung function impairment following acute COVID-19 pneumonia, may be treated with glucocorticoids after exclusion of other causes such as infection.Recommendation 15: For PC-ILD patients who have recovered from severe/critical COVID-19, anti-fibrotic medications may be administered after discussing disease-and treatment-related factors with patients. The optimal timing and duration of anti-fibrotic treatment are still uncertain. We conditionally recommend against anti-fibrotic medications in patients who have recovered from mild or moderate COVID-19. This recommendation does not apply to patients with pre-existing fibrotic ILD.
新型冠状病毒感染（coronavirus disease 2019，COVID-19）在世界范围内流行，然而目前对于如何管理间质性肺疾病（interstitial lung disease，ILD）合并COVID-19患者的临床认识非常有限。另一方面，急性COVID-19后发生的ILD（post-acute covid-19 ILD，PC-ILD）也很常见，如何规范管理也是临床面临的问题。为此，中国研究型医院学会呼吸分会邀请国内ILD领域专家组成共识编写组，充分收集临床意见，基于临床收集问题，组织专家讨论，最终确定纳入了22个问题，主要包括ILD合并COVID-19患者临床特征、重症/死亡风险和风险因素、治疗管理、PC-ILD临床特征、风险因素和治疗等方面。基于国内外指南、临床研究数据等证据，经过多次讨论和投票表决，形成15条推荐意见，共同制定了《新型冠状病毒感染疫情下间质性肺疾病患者临床管理中国专家共识》，旨在提升对ILD合并COVID-19以及PC-ILD的认识，为临床决策提供依据，提高临床救治水平。推荐意见1：新冠肺炎与急性/亚急性起病的ILD建议从暴露史、症状体征、肺高分辨率CT（HRCT）特征、实验室检查5个方面鉴别。推荐意见2：参考新型冠状病毒感染诊疗方案（试行第十版），对ILD合并COVID-19疾病严重程度分级及管理。推荐意见3：ILD是COVID-19重症/危重症独立危险因素，ILD合并COVID-19患者应尽早进行抗病毒治疗，最佳使用时机为出现症状5 d以内。推荐意见4：基础ILD无激素治疗指征者急性COVID-19时激素使用遵照COVID-19激素使用原则。基础ILD需开始或已使用激素者出现急性COVID-19时可继续使用激素，剂量调整依据基础ILD和COVID-19病情需要：重型/危重型ILD合并COVID-19但不符合SARS-Cov-2 触发AE-ILD者激素使用遵照重型/危重型COVID-19使用原则；符合AE-ILD者按AE-ILD处理。推荐意见5：IL-6抑制剂在COVID-19合并ILD人群中的使用尚无针对此类人群的临床研究证据，建议参照一般COVID-19患者使用原则。推荐意见6：JAK抑制剂在COVID-19合并ILD患者中的使用也无针对此类人群的临床研究证据，建议参照一般COVID-19患者使用原则。推荐意见7：对于出现COVID-19时尚未使用免疫抑制剂/生物制剂的ILD患者，若短期ILD进展的可能性低，可适当延迟启动免疫抑制剂/生物制剂治疗至COVID-19急性期后。对于已使用免疫抑制剂/生物制剂患者，建议采取多学科讨论方式，与风湿免疫科医生共同讨论，根据个体评估结果，权衡免疫抑制剂继续使用的获益和风险，COVID-19急性期可暂停免疫抑制剂，除非短期停用影响基础ILD或结缔组织疾病病情控制。推荐意见8：基础ILD使用抗纤维化药物者出现COVID-19时应继续使用抗纤维化药物，对于新诊断的纤维化性ILD需要使用抗纤维化药物的患者，建议及早启动抗纤维化治疗。推荐意见9：ILD合并COVID-19患者应积极进行病原学检查监测合并和（或）继发感染，及时应用抗感染药物预防或治疗细菌、真菌、耶氏肺孢子菌、巨细胞病毒等感染。推荐意见10：ILD合并COVID-19患者抗凝治疗建议按照一般患者原则使用。推荐意见11：在起病后（未住院患者）或出院后（住院患者）4周时随访。若病情稳定，可参照普通ILD患者诊疗常规，每3~6个月随访1次。胸部HRCT和肺功能是常规随访项目。动脉血气分析、心脏超声、CT肺动脉造影、血液学检查根据患者病情需要酌情选择。推荐意见12：胸部CT明显异常、肺功能受损严重的重型/危重型COVID-19患者，是康复干预的主要目标人群。康复治疗应遵循个体化治疗原则。推荐意见13：医务工作者和疫苗接种人员应让患者充分知情接种疫苗的获益及风险，并与患者共同讨论决策是否接种疫苗。推荐意见14：对于急性COVID-19后仍有持续或进展的呼吸道症状，肺间质病变范围仍较大者，在排除感染等其他病因后可加用激素治疗。推荐意见15：重症/危重症COVID-19后PC-ILD患者可加用抗纤维化药物治疗，但需要基于纤维样病变的范围、药物副作用、超适应症用药等问题，与患者协商后个体化决定。用药最佳时机、疗程尚不确定。对于轻、中型COVID-19后患者不倾向加用抗肺纤维化药物，可随访监测，基础存在纤维化性ILD患者除外。.

Adults with tuberculosis-human immunodeficiency virus coinfection require professional nurses\' support to manage their illness, treatment and its effect on their daily lives. This scoping review maps recommendations in clinical or best practice guidelines that guide professional nurses to provide self-management support to adults with tuberculosis-human immunodeficiency virus coinfection in primary healthcare settings.
We conducted a scoping review by searching for guidelines in six online databases, guideline clearing houses and search engines from 16th April 2022 to 25th May 2022. The title, abstract and full-text screening of guidelines were conducted independently and in duplicate by two reviewers based on predetermined eligibility criteria. The guidelines were critically appraised with the Appraisal of Guidelines Research and Evaluation (AGREE) II instrument. Relevant data regarding the characteristics of the guideline, recommendations and underlying evidence were extracted, analysed and reported.
The six guidelines on self-management support found were developed in four high-income countries. Five of the guidelines recorded <60% across all six domains of the AGREE II instrument. One high-quality guideline scored >60% in all AGREE II domains but was informed by outdated evidence produced between 1977 to 2010. Twenty-five practice, education and organisational/policy recommendations were extracted from the high-quality guideline. The guidelines did not report evidence-to-decision frameworks and the strength of the recommendations. The guidelines also lacked direct underlying evidence on the effectiveness and cost of self-management support. Lastly, the review found a paucity of contextual (equity, acceptability and feasibility) evidence on self-management support among adults with tuberculosis-human immunodeficiency virus in the guidelines.
There is a dearth of updated and relevant high-quality guidelines that guide healthcare professionals to provide self-management support to adults with tuberculosis-human immunodeficiency virus coinfection in primary healthcare settings. Systematic reviews of effectiveness, economic and contextual evidence related to self-management support interventions are required for guideline production.

Coinfection with two SARS-CoV-2 viruses is still a very understudied phenomenon. Although next generation sequencing methods are very sensitive to detect heterogeneous viral populations in a sample, there is no standardized method for their characterization, so their clinical and epidemiological importance is unknown.
We developed VICOS (Viral COinfection Surveillance), a new bioinformatic algorithm for variant calling, filtering and statistical analysis to identify samples suspected of being mixed SARS-CoV-2 populations from a large dataset in the framework of a community genomic surveillance. VICOS was used to detect SARS-CoV-2 coinfections in a dataset of 1,097 complete genomes collected between March 2020 and August 2021 in Argentina.
We detected 23 cases (2%) of SARS-CoV-2 coinfections. Detailed study of VICOS\'s results together with additional phylogenetic analysis revealed 3 cases of coinfections by two viruses of the same lineage, 2 cases by viruses of different genetic lineages, 13 were compatible with both coinfection and intra-host evolution, and 5 cases were likely a product of laboratory contamination.
Intra-sample viral diversity provides important information to understand the transmission dynamics of SARS-CoV-2. Advanced bioinformatics tools, such as VICOS, are a necessary resource to help unveil the hidden diversity of SARS-CoV-2.

暂无摘要。

The commonest causes of mortality in people living with HIV (PLHIV) are preventable and the majority can be attributed to undiagnosed tuberculosis (TB). National HIV/AIDS control programs are encouraged to implement the WHO package of interventions to improve survival among PLHIV. We assessed the implementation of the WHO TB-related package of care for Advanced HIV Disease (AHD) and its impact on treatment outcomes among HIV/TB patients in Tanzania.
A retrospective cohort study was employed among HIV/AIDS patients on antiretroviral therapy from 21 public health facilities in three regions (Dar es Salaam, Coastal, and Morogoro) of Tanzania. Patients enrolled in care between January 2013- June 2017 (before the introduction of the WHO guidelines) and July 2017-Sept 2018 (during the implementation of the guidelines) were recruited. Data abstraction was done from patient hospital files using a structured questionnaire uploaded on a tablet.
Data from 2624 patients records were collected. Overall, 50% of patients with HIV had AHD with 7.8% of these co-infected with TB. Among AHD participants, 58.3% were female, 80.7% were from urban areas and 40.0% visited care and treatment centres as self-referrals. Implementation of the WHO AHD package of care was very low, ranging from 0% for Urine LF-LAM test done among patients with symptoms and signs of TB to 39.7% AHD concurrent with TB patients whose ART initiation was deferred for 2 weeks. Overall, the Proportion of AHD patients diagnosed with TB was 4.8%, Of which sputum Xpert as the first test for TB diagnosis was 4.4%. Five patients (0.6%) were documented to have received IPT at enrolment. Tailored counselling to ensure optimal adherence to ART for viral suppression was given to 12.1%. AHD patients co-infected with TB were retained in care more before the introduction of WHO AHD guideline (82.1%) compared to the period after the introduction of the guideline (53.9%) (p = 0.008). Clinical failure at 6 months among AHD patients was 10.6% before the guideline and 11.4% after the guideline. Immunological failure was observed in 1 patient (9.1%) before the guideline and 1 patient (7.1%) after the guideline. After the introduction of the guideline, mortality was 5.9% and no mortality was observed before the guideline. All the differences were not statistically significant.
Implementation of the TB related WHO packages of care for AHD is very low. Except for TB diagnosis, other parameters did not improve with the introduction of the guidelines. More research is recommended to ascertain the effectiveness of guidelines as well as an understanding of the mechanisms involved.

BACKGROUND: We aimed to determine how emerging evidence over the past decade informed how Ugandan HIV clinicians prescribed protease inhibitors (PIs) in HIV patients on rifampicin-based tuberculosis (TB) treatment and how this affected HIV treatment outcomes.
METHODS: We reviewed clinical records of HIV patients aged 13 years and above, treated with rifampicin-based TB treatment while on PIs between1st-January -2013 and 30th-September-2018 from twelve public HIV clinics in Uganda. Appropriate PI prescription during rifampicin-based TB treatment was defined as; prescribing doubled dose lopinavir/ritonavir- (LPV/r 800/200 mg twice daily) and inappropriate PI prescription as prescribing standard dose LPV/r or atazanavir/ritonavir (ATV/r).
RESULTS: Of the 602 patients who were on both PIs and rifampicin, 103 patients (17.1% (95% CI: 14.3-20.34)) received an appropriate PI prescription. There were no significant differences in the two-year mortality (4.8 vs. 5.7%, P = 0.318), loss to follow up (23.8 vs. 18.9%, P = 0.318) and one-year post TB treatment virologic failure rates (31.6 vs. 30.7%, P = 0.471) between patients that had an appropriate PI prescription and those that did not. However, more patients on double dose LPV/r had missed anti-retroviral therapy (ART) days (35.9 vs 21%, P = 0.001).
CONCLUSIONS: We conclude that despite availability of clinical evidence, double dosing LPV/r in patients receiving rifampicin-based TB treatment is low in Uganda\'s public HIV clinics but this does not seem to affect patient survival and viral suppression.

BACKGROUND: Local transmission of seasonal influenza viruses (IVs) can be difficult to resolve. Here, we study if coupling high-throughput sequencing (HTS) of hemagglutinin (HA) and neuraminidase (NA) genes with variant analysis can resolve strains from local transmission that have identical consensus genome. We analyzed 24 samples collected over four days in January 2020 at a large university in the US. We amplified complete hemagglutinin (HA) and neuraminidase (NA) genomic segments followed by Illumina sequencing. We identified consensus complete HA and NA segments using BLASTn and performed variant analysis on strains whose HA and NA segments were 100% similar.
RESULTS: Twelve of the 24 samples were PCR positive, and we detected complete HA and/or NA segments by de novo assembly in 83.33% (10/12) of them. Similarity and phylogenetic analysis showed that 70% (7/10) of the strains were distinct while the remaining 30% had identical consensus sequences. These three samples also had IAV and IBV co-infection. However, subsequent variant analysis showed that they had distinct variant profiles. While the IAV HA of one sample had no variant, another had a T663C mutation and another had both C1379T and C1589A.
CONCLUSIONS: In this study, we showed that HTS coupled with variant analysis of only HA and NA genes can help resolve variants that are closely related. We also provide evidence that during a short time period in the 2019-2020 season, co-infection of IAV and IBV occurred on the university campus and both 2020/2021 and 2021/2022 WHO recommended H1N1 vaccine strains were co-circulating.

Severe acute respiratory syndrome coronavirus 2 causes direct damage to the airway epithelium, enabling aspergillus invasion. Reports of COVID-19-associated pulmonary aspergillosis have raised concerns about it worsening the disease course of COVID-19 and increasing mortality. Additionally, the first cases of COVID-19-associated pulmonary aspergillosis caused by azole-resistant aspergillus have been reported. This article constitutes a consensus statement on defining and managing COVID-19-associated pulmonary aspergillosis, prepared by experts and endorsed by medical mycology societies. COVID-19-associated pulmonary aspergillosis is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Recommended first-line therapy is either voriconazole or isavuconazole. If azole resistance is a concern, then liposomal amphotericin B is the drug of choice. Our aim is to provide definitions for clinical research and up-to-date recommendations for clinical management of the diagnosis and treatment of COVID-19-associated pulmonary aspergillosis.