Outcomes with newly proposed classification of acute respiratory deterioration in idiopathic pulmonary fibrosis.

BACKGROUND: Respiratory-related hospitalization, in particular acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), is common and associated with increasing mortality in patients with IPF. We aimed to evaluate the implications of a newly proposed framework of acute respiratory deterioration (ARD) and AE-IPF in hospitalized patients. METHODS: Using the data of an IPF cohort consisting of 225 consecutive patients, we retrospectively studied first hospitalizations from January 2008 to December 2017. We analysed the demographics and 90-day mortality of patients with AE-IPF and those with parenchymal cause of ARD other than AE. RESULTS: Among 122 patients with first hospitalization for ARD, 35 patients were diagnosed with AE-IPF, including 11 patients with triggered AE. Parenchymal cause of ARD other than AE was diagnosed in 71 patients, and extra-parenchymal cause in 16 patients. Almost all hospitalized patients (93%) underwent chest CT, and 83% of patients with AE-IPF underwent bronchoalveolar lavage. There was a significant difference in the anti-inflammatory therapy between the AE-IPF group and parenchymal cause of ARD other than AE group (p < 0.001). AE-IPF was independently associated with poor survival in multivariate Cox proportional regression analysis. CONCLUSIONS: AE-IPF accounted for about 30% of first hospitalizations for ARD, and differentiation between AE-IPF and the other categories in ARD is important from a therapeutic and a prognostic point of view.

Characterization of and risk factors for the acute-phase response after zoledronic acid.

CONTEXT: Intravenous aminobisphosphonates often cause an acute-phase response (APR), but the precise components of this, its frequency, and the risk factors for its development have not been systematically studied. OBJECTIVE: The objective of the study was to characterize the APR and determine its frequency and the risk factors for its development. DESIGN: The study was an analysis of adverse events from a large randomized trial. SETTING: This was a multicenter international trial. PATIENTS: Patients included 7765 postmenopausal women with osteoporosis. INTERVENTION: Zoledronic acid 5 mg annually or placebo was the intervention. MAIN OUTCOME MEASURE: Adverse events occurring within 3 d of zoledronic acid infusion were measured. RESULTS: More than 30 adverse events were significantly more common in the zoledronic acid group and were regarded collectively as constituting an APR. These were clustered into five groups: fever; musculoskeletal (pain and joint swelling); gastrointestinal (abdominal pain, vomiting, diarrhea); eye inflammation; and general (including fatigue, nasopharyngitis, edema). A total of 42.4% of the zoledronic acid group had an APR after the first infusion, compared with 11.7% of the placebo group. All APR components had their peak onset within 1 d, the median duration of the APR was 3 d, and severity was rated as mild or moderate in 90%. Stepwise regression showed that APR was more common in non-Japanese Asians, younger subjects, and nonsteroidal antiinflammatory drug users and was less common in smokers, patients with diabetes, previous users of oral bisphosphonates, and Latin Americans (P < 0.05 for all). CONCLUSION: This analysis identifies new components of the APR and provides the first assessment of risk factors for it. Despite its frequency, APR rarely resulted in treatment discontinuation in this study.

Paciente com reacao tipo I e tipo II e dez anos de seguimento / Type I and type II reactions in a patients with ten years of follow-up

Relata-se o caso de um individuo do sexo masculino, de 52 anos de idade, que desde 20 anos atras vinha apresentando sinais e sintomas de hanseniase multibacilar, mas so procurou tratamento apos 5 anos, quando apresentava manifestacoes de Eritema Nodoso Hansenico (ENH - Reacao tipo 1) inclusive com comprometimento articular. Instalado o tratamento (PQT/MB) o paciente passou a apresentar episodios de ENH, que se continuaram apos a alta medicamentosa alternando-se ou em concomitancia com episodios de reacao tipo 1 (reacao reversa) o que definiu como dimorfo. Assim permaneceu quase 10 anos, tendo apresentado, por algum tempo, esplenomegalia e sinais de hiperesplenismo. So melhorou, quando a deteccao de bacilos viaveis levou a reinstalacao da PQT. A discussao do caso ressalta alguns aspectos interessantes desta evolucao: 1) a demora no diagnostico leva pacientes dimorfos a adquirirem caracteristicas virchovianas com rica baciloscopia (virchovianos sub-polares); 2) estes pacientes tem maior possibilidade de albergarem bacilos persistentes que eventualmente se multiplicam e estimulam reacoes tipo I; 3) a alternancia de reacoes tipo 1 e tipo 2 pode indicar a participacao da imunidade celular no desencadeamento do ENH, onde a reacao granulomatosa romperia os infiltrados especificos regressivos, expondo antigenos intracelulares. Frente ao estado de hipersensibilidade humoral, haveria deposicao de complexos imunes e desencadeamento de reacao inflamatoria aguda; 4) a alta da PQT nao significa cura da hanseniase.

Stereotactic radiosurgery. VIII. The classification of postradiation reactions.

Postradiation reactions in the CNS are well described and catalogued in the conventional radiotherapy literature; acute, subacute and late CNS reactions are recognized. Tumours predispose to these normal tissue reactions by the oedema and pressure epiphenomena that occur in their environs, and probably by other mechanisms associated with tissue breakdown. That late normal tissue reactions (particularly permanent late sequelae--universally referred to as 'necrosis') occur in the normal nervous system is in the complication list of every radiosurgery centre. This article, for the first time, places postradiosurgery observations within or without the existing classification of reactions, and draws attention to the fact that previous 'radiosurgery risk factor' papers in the literature may be wrong to pool different 'reactions' in the formulation of risk formulae for normal brain damage following single shot radiotherapy. Acute reactions occur in the same manner as described for conventional radiotherapy, being a transient swelling phenomenon that occurs 12-48 h after therapy; they are fully reversible and do not usually augur late problems; routine administration of short duration steroids around the time of radiosurgery may prevent or delay the clinical signs. Subacute reactions occur 3-10 months later (a later time than the subacute reactions following conventionally fractionated radiotherapy), and may prove fully or partially reversible, or progress to permanent sequelae; the difference between these and late sequelae (which tend to be permanent themselves) then becomes blurred. That tumour swelling occurs in the subacute phase and is associated with oedema in the surrounding normal brain is an interesting observation (occurring in extra- and intra axial slow-growing tumours); it denotes tumour damage and has not been encountered in the conventionally-fractionated radiotherapy literature. Tumour shrinkage occurs later, with subsidence of the surrounding oedema, and this phenomenon may therefore be regarded (paradoxically) as a good prognostic sign, a point about which the referring clinician should be made aware. Similarly, contrast enhancement in the tumour perimeter at this time reflects a host reactive response and not tumour activity. Persistent clinical neurological signs and MRI changes (best seen on the T2 weighted sequences) beyond 2 years, indicate late damage or reaction. Usually, this represents scarring or coagulative necrosis without mass effect, but if there is a low signal area with mass effect and considerable surrounding oedema, liquefactive necrosis has occurred and (as in the brachytherapy literature) surgical decompression is very occasionally needed.