The 6-minute walk test predicts mortality in a pulmonary nontuberculous mycobacteria-predominant bronchiectasis cohort.

BACKGROUND: Bronchiectasis is a chronic lung condition frequently associated with nontuberculous mycobacteria pulmonary (NTM) disease. Persons with these conditions are at increased risk of mortality. Patient reported outcome (PRO) instruments and the 6-minute walk test (6MWT) have been shown to predict mortality for several lung conditions, but these measures have not been fully evaluated for bronchiectasis and NTM. METHODS: We conducted a retrospective cohort study among adult patients enrolled in a natural history study of bronchiectasis at the National Heart, Lung, and Blood Institute. Electronic medical records were queried for demographic, clinical, microbiologic, radiographic, and PRO instrument data: St. George's Respiratory Questionnaire (SGRQ), Medical Research Council Dyspnea Scale, and the Pulmonary Symptom Severity Score (PSSS). The study baseline date was defined as the patient's first visit after January 1st, 2015 with a SGRQ or 6MWT completed. Follow-up was defined as the interval between the study baseline visit and date of death or December 31st, 2019. Sex-stratified Cox proportional-hazards regression was conducted to identify predictors of mortality. Separate models were run for each PRO and 6MWT measure, controlling for age, body mass index (BMI), fibrocavitary disease status, and M. abscessus infection. RESULTS: In multivariable Cox proportional-hazards regression models, the PSSS-severity (aHR 1.29, 95% CI 1.04-1.59), the 6MWT total distance walked (aHR 0.938, 95% CI 0.896-0.981) and distance saturation product (aHR 0.930, 95% CI 0.887-0.974) independently predicted mortality. In addition, BMI was significantly predictive of mortality in all models. CONCLUSIONS: The 6MWT and a PRO instrument capturing symptom severity are independently predictive of mortality in our cohort of bronchiectasis patients.

In-Hospital Cardiac Arrest (IHCA) and Outcomes in Patients Admitted With COVID-19 Infection.

During the COVID-19 pandemic, many patients are hospitalized, and those suffering from in-hospital cardiac arrest (IHCA) have been previously reported to have poor outcomes. This is a single-center, retrospective, observational study conducted at the Veterans Affairs Medical Center, Washington, DC, USA. The inclusion criteria were: patients admitted to the hospital with a diagnosis of COVID-19 who underwent cardiopulmonary resuscitation (CPR) for IHCA. Patients were labeled as COVID-19 positive based on a laboratory-confirmed positive polymerase chain reaction test. Patients with do-not-resuscitate (DNR) orders, those who were made comfort care, or enrolled in hospice were excluded. The study was approved by the hospital's institutional review board. A total of 155 patients with COVID-19 infection were admitted; 145/155 (93.5%) admitted to the medical floor and 10/155 (6.5%) to the medical intensive care unit (MICU). 36/145 (24.8%) floor patients were upgraded to MICU. Of the 46 patients treated in MICU, 17/46 (36.9%) were excluded for DNR status. From the remaining 29/46 (63.1%) patients, 19/29 (65.5%) patients survived, and 10/29 (34.5%) patients had IHCA. All 10/10 (100%) died after CPR without return of spontaneous circulation (ROSC). The initial rhythm was non-shockable in all patients, with pulseless electrical activity (PEA) in 7/10 (70%) and asystole in 3/10 (30%) patients. Patients with COVID-19 infection who had an IHCA and underwent CPR had a 0% survival at our hospital. Discussions on advanced care options, especially CPR, with COVID-19 patients and their families, are important as the overall prognosis after CPR for IHCA is poor.

Disappearing nodules: spontaneously regressing pulmonary amyloidosis.

A case report of spontaneous regression of pulmonary amyloidosis, diffuse interstitial pattern, in an elderly patient.

Pleural lipoma clinically mimicking the presentation of superior sulcus tumour upon initial evaluation.

Here we present a case of a large pleural lipoma which presented with paresthesias of the hand. This is an unusual presentation of an uncommon tumour.

Mycobacterium tuberculosis universal stress protein Rv2623 interacts with the putative ATP binding cassette (ABC) transporter Rv1747 to regulate mycobacterial growth.

We have previously shown that the Mycobacterium tuberculosis universal stress protein Rv2623 regulates mycobacterial growth and may be required for the establishment of tuberculous persistence. Here, yeast two-hybrid and affinity chromatography experiments have demonstrated that Rv2623 interacts with one of the two forkhead-associated domains (FHA I) of Rv1747, a putative ATP-binding cassette transporter annotated to export lipooligosaccharides. FHA domains are signaling protein modules that mediate protein-protein interactions to modulate a wide variety of biological processes via binding to conserved phosphorylated threonine (pT)-containing oligopeptides of the interactors. Biochemical, immunochemical and mass spectrometric studies have shown that Rv2623 harbors pT and specifically identified threonine 237 as a phosphorylated residue. Relative to wild-type Rv2623 (Rv2623WT), a mutant protein in which T237 has been replaced with a non-phosphorylatable alanine (Rv2623T237A) exhibits decreased interaction with the Rv1747 FHA I domain and diminished growth-regulatory capacity. Interestingly, compared to WT bacilli, an M. tuberculosis Rv2623 null mutant (ΔRv2623) displays enhanced expression of phosphatidyl-myo-inositol mannosides (PIMs), while the ΔRv1747 mutant expresses decreased levels of PIMs. Animal studies have previously shown that ΔRv2623 is hypervirulent, while ΔRv1747 is growth-attenuated. Collectively, these data have provided evidence that Rv2623 interacts with Rv1747 to regulate mycobacterial growth; and this interaction is mediated via the recognition of the conserved Rv2623 pT237-containing FHA-binding motif by the Rv1747 FHA I domain. The divergent aberrant PIM profiles and the opposing in vivo growth phenotypes of ΔRv2623 and ΔRv1747, together with the annotated lipooligosaccharide exporter function of Rv1747, suggest that Rv2623 interacts with Rv1747 to modulate mycobacterial growth by negatively regulating the activity of Rv1747; and that Rv1747 might function as a transporter of PIMs. Because these glycolipids are major mycobacterial cell envelope components that can impact on the immune response, our findings raise the possibility that Rv2623 may regulate bacterial growth, virulence, and entry into persistence, at least in part, by modulating the levels of bacillary PIM expression, perhaps through negatively regulating the Rv1747-dependent export of the immunomodulatory PIMs to alter host-pathogen interaction, thereby influencing the fate of M. tuberculosis in vivo.