Acute Interstitial Pneumonia (Hamman-Rich Syndrome) as a Cause of Idiopathic Acute Respiratory Distress Syndrome

Hamman-Rich syndrome, also known as acute interstitial pneumonia, is a rare and fulminant form of idiopathic interstitial lung disease. It should be considered as a cause of idiopathic acute respiratory distress syndrome. Confirmatory diagnosis requires demonstration of diffuse alveolar damage on lung histopathology. The main treatment is supportive care. It is not clear if glucocorticoid therapy is effective in acute interstitial pneumonia. We report the case of a 77-year-old woman without pre-existing lung disease who initially presented with mild upper respiratory tract infection and then progressed to rapid onset of hypoxic respiratory failure similar to acute respiratory distress syndrome with unknown etiology. Despite glucocorticoid therapy, she did not achieve remission and expired after 35 days of hospitalization. The diagnosis of acute interstitial pneumonia was supported by the histopathologic findings on her lung biopsy

A 19 Year Old Male With HIV Presents With Diffuse Lymphadenopathy

Background In 1872, Moritz Kaposi first described an idiopathic multiple pigmented sarcoma of the skin;\u27\u27 now identified as Kaposi\u27s sarcoma (KS).\u27 While multiple forms ofKSexist, over9S% of the cases diagnosed in the US since 1981 are of the AIDS associated variety.2 Kaposi originally described KS as skin lesions that can progress to visceral involvement. However, in a small number of cases, KS can appear in the viscera without skin involvement. These alternate presentations of KS are difficult to diagnose; therefore, it is critical to recognize them when considering differential diagnoses, particularly in patients with HIV. Case Presentation An 18-year-old African American male with a history ofHIV presented with progressive worsening of diffuse and painful lymphadenopathy fore five weeks prior to admission. The patient was diagnosed with HIV in 2010 and due to insurance issues, was never treated with highly active antiretroviral therapy (HAART). His last CD4 count (approximately two weeks prior to admission) was 411 and he had no history of opportunistic infections. He first noticed swelling in his neck, under his armpits and in his groin five weeks prior, which had become progressively more painful. The patient denied fevers, chills or weight loss, but did report significant night sweats and episodes ofhemoptysis with dots. He denied shortness ofbreath or chest pain. He also denied recent travel, history of incarceration, homelessness or exposure to active tuberculosis infection

Use of Machine Learning Consensus Clustering to Identify Distinct Subtypes of Black Kidney Transplant Recipients and Associated Outcomes

Importance: Among kidney transplant recipients, Black patients continue to have worse graft function and reduced patient and graft survival. Better understanding of different phenotypes and subgroups of Black kidney transplant recipients may help the transplant community to identify individualized strategies to improve outcomes among these vulnerable groups. Objective: To cluster Black kidney transplant recipients in the US using an unsupervised machine learning approach. Design, Setting, and Participants: This cohort study performed consensus cluster analysis based on recipient-, donor-, and transplant-related characteristics in Black kidney transplant recipients in the US from January 1, 2015, to December 31, 2019, in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Each cluster\u27s key characteristics were identified using the standardized mean difference, and subsequently the posttransplant outcomes were compared among the clusters. Data were analyzed from June 9 to July 17, 2021. Exposure: Machine learning consensus clustering approach. Main Outcomes and Measures: Death-censored graft failure, patient death within 3 years after kidney transplant, and allograft rejection within 1 year after kidney transplant. Results: Consensus cluster analysis was performed for 22 687 Black kidney transplant recipients (mean [SD] age, 51.4 [12.6] years; 13 635 men [60%]), and 4 distinct clusters that best represented their clinical characteristics were identified. Cluster 1 was characterized by highly sensitized recipients of deceased donor kidney retransplants; cluster 2, by recipients of living donor kidney transplants with no or short prior dialysis; cluster 3, by young recipients with hypertension and without diabetes who received young deceased donor transplants with low kidney donor profile index scores; and cluster 4, by older recipients with diabetes who received kidneys from older donors with high kidney donor profile index scores and extended criteria donors. Cluster 2 had the most favorable outcomes in terms of death-censored graft failure, patient death, and allograft rejection. Compared with cluster 2, all other clusters had a higher risk of death-censored graft failure and death. Higher risk for rejection was found in clusters 1 and 3, but not cluster 4. Conclusions and Relevance: In this cohort study using an unsupervised machine learning approach, the identification of clinically distinct clusters among Black kidney transplant recipients underscores the need for individualized care strategies to improve outcomes among vulnerable patient groups

Toxigenic Clostridium difficile colonization among hospitalised adults; risk factors and impact on survival

Objectives: To establish risk factors for Clostridium difficile colonization among hospitalized patients in England. Methods: Patients admitted to elderly medicine wards at three acute hospitals in England were recruited to a prospective observational study. Participants were asked to provide a stool sample as soon as possible after enrolment and then weekly during their hospital stay. Samples were cultured for C. difficile before ribotyping and toxin detection by PCR. A multivariable logistic regression model of risk factors for C. difficile colonization was fitted from univariable risk factors significant at the p < 0.05 level. Results: 410/727 participants submitted ≥1 stool sample and 40 (9.8%) carried toxigenic C. difficile in the first sample taken. Ribotype 106 was identified three times and seven other ribotypes twice. No ribotype 027 strains were identified. Independent predictors of colonization were previous C. difficile infection (OR 4.53 (95% C.I. 1.33–15.48) and malnutrition (MUST score ≥2) (OR 3.29 (95% C.I. 1.47–7.35)). Although C. difficile colonised patients experienced higher 90-day mortality, colonization was not an independent risk for death. Conclusions: In a non-epidemic setting patients who have previously had CDI and have a MUST score of ≥2 are at increased risk of C. difficile colonization and could be targeted for active surveillance to prevent C. difficile transmission

The host ubiquitin-dependent segregase VCP/p97 is required for the onset of human cytomegalovirus replication

The human cytomegalovirus major immediate early proteins IE1 and IE2 are critical drivers of virus replication and are considered pivotal in determining the balance between productive and latent infection. IE1 and IE2 are derived from the same primary transcript by alternative splicing and regulation of their expression likely involves a complex interplay between cellular and viral factors. Here we show that knockdown of the host ubiquitin-dependent segregase VCP/p97, results in loss of IE2 expression, subsequent suppression of early and late gene expression and, ultimately, failure in virus replication. RNAseq analysis showed increased levels of IE1 splicing, with a corresponding decrease in IE2 splicing following VCP knockdown. Global analysis of viral transcription showed the expression of a subset of viral genes is not reduced despite the loss of IE2 expression, including UL112/113. Furthermore, Immunofluorescence studies demonstrated that VCP strongly colocalised with the viral replication compartments in the nucleus. Finally, we show that NMS-873, a small molecule inhibitor of VCP, is a potent HCMV antiviral with potential as a novel host targeting therapeutic for HCMV infection

Genetic Association of Co‐Trimoxazole‐Induced Severe Cutaneous Adverse Reactions Is Phenotype‐Specific: HLA Class I Genotypes and Haplotypes

Co‐trimoxazole (CTX) causes various forms of severe cutaneous adverse reactions (SCARs). This case‐control study was conducted to investigate the involvement between genetic variants of human leukocyte antigen (HLA) and CYP2C9 in CTX‐induced SCARs, including Stevens‐Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) in Thai patients. Thirty cases of CTX‐induced SCARs were enrolled and compared with 91 CTX‐tolerant controls and 150 people from the general Thai population. Cases comprised 18 SJS/TEN and 12 DRESS patients. This study demonstrated that genetic association of CTX‐induced SCARs was phenotype‐specific. HLA‐B*15:02 and HLA‐C*08:01 alleles were significantly associated with CTX‐induced SJS/TEN, whereas the HLA‐B*13:01 allele was significantly associated with CTX‐induced DRESS. In addition, a significant higher frequency of HLA‐A*11:01‐B*15:02 and HLA‐B*13:01‐C*03:04 haplotypes were detected in the group of CTX‐induced Stevens‐Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and DRESS cases, respectively. Genetic association of CTX‐induced SCARs is phenotype‐specific. Interestingly, these association was observed only in HIV‐infected patients but not in non‐HIV‐infected patients

Epidemiology of Escherichia coli bacteraemia in England: results of an enhanced sentinel surveillance programme

Background: Escherichia coli causes over one third of the bacteraemia cases in England each year, and the incidence of these infections is increasing. Aim: To determine the underlying risk factors associated with E. coli bacteraemia. Methods: A three month enhanced sentinel surveillance study involving 35 National Health Service hospitals was undertaken in the winter of 2012/13 to collect risk factor information and further details on the underlying source of infection to augment data already collected by the English national surveillance programme. Antimicrobial susceptibility results for E. coli isolated from blood and urine were also collected. Findings: A total of 1,731 cases of E. coli bacteraemia were included. The urogenital tract was the most commonly reported source of infection (51.2% of cases) with prior treatment for a urinary tract infection being the largest independent effect associated with this infection source. Half of all patients had prior healthcare exposure in the month prior to the bacteraemia with antimicrobial therapy and urinary catheterisation being reported in one third and one fifth of these patients. Prior healthcare exposure was associated with a higher proportion of antibiotic non-susceptibility in the blood culture isolates (P=0.001). Conclusion: Analysis of risk factors suggests potential community and hospital-related interventions particularly better use of urinary catheters and improved antibiotic management of urinary tract infections. As part of the latter strategy, antibiotic resistance profiles need to be closely monitored to ensure treatment guidelines are up to date to limit inappropriate empiric therapy