Search

BackgroundNightmares are a hallmark symptom of posttraumatic stress disorder (PTSD). This strong association may reflect a shared pathophysiology in the form of altered autonomic activity and increased reactivity. Using an acoustic startle paradigm, we investigated the interrelationships of psychophysiological measures during wakefulness and PTSD diagnosis, posttraumatic nightmares, and nontraumatic nightmares.MethodsA community sample of 122 trauma survivors were presented with a series of brief loud tones, while heart rate (HRR), skin conductance (SCR), and orbicularis oculi electromyogram (EMGR) responses were measured. Prior to the tone presentations, resting heart rate variability (HRV) was assessed. Nightmares were measured using nightmare logs. Three dichotomous groupings of participants were compared: (1) current PTSD diagnosis (n = 59), no PTSD diagnosis (n = 63), (2) those with (n = 26) or without (n = 96) frequent posttraumatic nightmares, and (3) those with (n = 22) or without (n = 100) frequent nontraumatic nightmares.ResultsPTSD diagnosis was associated with posttraumatic but not with nontraumatic nightmares. Both PTSD and posttraumatic nightmares were associated with a larger mean HRR to loud tones, whereas nontraumatic nightmare frequency was associated with a larger SCR. EMGR and resting HRV were not associated with PTSD diagnosis or nightmares.ConclusionsOur findings suggest a shared pathophysiology between PTSD and posttraumatic nightmares in the form of increased HR reactivity to startling tones, which might reflect reduced parasympathetic tone. This shared pathophysiology could explain why PTSD is more strongly related to posttraumatic than nontraumatic nightmares, which could have important clinical implications.

Interventions to prevent HIV-1 infection and alternative tools in HIV cure therapy remain pressing goals. Recently, numerous broadly neutralizing HIV-1 monoclonal antibodies (bNAbs) have been developed that possess the characteristics necessary for potential prophylactic or therapeutic approaches. However, formulation complexities, especially for multiantibody deliveries, long infusion times, and production issues could limit the use of these bNAbs when deployed, globally affecting their potential application. Here, we describe an approach utilizing synthetic DNA-encoded monoclonal antibodies (dmAbs) for direct in vivo production of prespecified neutralizing activity. We designed 16 different bNAbs as dmAb cassettes and studied their activity in small and large animals. Sera from animals administered dmAbs neutralized multiple HIV-1 isolates with activity similar to that of their parental recombinant mAbs. Delivery of multiple dmAbs to a single animal led to increased neutralization breadth. Two dmAbs, PGDM1400 and PGT121, were advanced into nonhuman primates for study. High peak-circulating levels (between 6 and 34 μg/ml) of these dmAbs were measured, and the sera of all animals displayed broad neutralizing activity. The dmAb approach provides an important local delivery platform for the in vivo generation of HIV-1 bNAbs and for other infectious disease antibodies.

This is a case report of a patient who developed severe, irreversible hypocalcemia after receiving one dose of pamidronate 90 mg for hypercalcemia of malignancy. Hypocalcemia is a known risk of bisphosphonate treatments, but the incidence of severe hypocalcemia is rare, and the risk factors are well established. However, in the treatment of hypercalcemia of malignancy, the treatment objective is to reduce the elevated serum calcium level, and the bisphosphonate is usually given as one time dose only. The potential for developing severe hypocalcemia may not be considered a significant concern in this setting compared to the setting of the treatment of bone metastasis, where the baseline serum calcium level is not elevated and the bisphosphonate is administered at a regular interval of every three to four weeks. Furthermore, there is unawareness of prevalence of vitamin D deficiency in cancer patients, especially in those with advanced cancer, which may lead to inadvertent, severe hypocalcemia from bisphosphonate treatment. The objective of this case report is to bring awareness to the risk of severe hypocalcemia in patients with hypercalcemia of malignancy and the high prevalence of unrecognized vitamin D deficiency in cancer patients.

Vaccination of immunocompromised patients is recommended in many national guidelines to protect against severe or complicated influenza infection. However, due to uncertainties over the evidence base, implementation is frequently patchy and dependent on individual clinical discretion. We conducted a systematic review and meta‐analysis to assess the evidence for influenza vaccination in this patient group. Healthcare databases and grey literature were searched and screened for eligibility. Data extraction and assessments of risk of bias were undertaken in duplicate, and results were synthesised narratively and using meta‐analysis where possible. Our data show that whilst the serological response following vaccination of immunocompromised patients is less vigorous than in healthy controls, clinical protection is still meaningful, with only mild variation in adverse events between aetiological groups. Although we encountered significant clinical and statistical heterogeneity in many of our meta‐analyses, we advocate that immunocompromised patients should be targeted for influenza vaccination.

A number of chemotherapy drugs are well known to cause various histopathologic patterns of lung injury. The incidence of chemotherapy-induced infiltrative pneumonitis is rare and the diagnosis is difficult due to the nonspecific clinical and radiological presentations. However, it can cause significant morbidity and mortality in cancer patients. There is no consensus on the treatment of this adverse event, but prompt diagnosis and intervention is important as fatal outcomes have been reported. We present five cases of chemotherapy-induced infiltrative pneumonitis in breast cancer patients involving docetaxel, paclitaxel, gemcitabine and cyclophosphamide.

Pneumocystis jirovecii (formerly carinii) pneumonia (PJP) is an opportunistic infection well-recognized in patients with profound T cell immunodeficiency. It is much less common in patients with solid tumors unless they have other major predisposing factors such as prolonged treatment with corticosteroids or T4 lymphocyte counts of less than 200 cells/mm3. We present a previously unreported case of fatal PJP in a breast cancer patient with bone metastases who was receiving a first-line treatment with weekly paclitaxel, trastuzumab, and dexamethasone as premedication for paclitaxel. She had received eight doses of paclitaxel at 80 mg/m2, trastuzumab 2 mg/m2, and dexamethasone 10 mg for just over 7 weeks when she was diagnosed with PJP. While the patient’s granulocyte counts were normal throughout her treatment, the total lymphocyte counts reached the nadir of 400 cells/mm3 a few days after the eighth dose of chemotherapy – around the time of PJP diagnosis. Both dexamethasone and the total lymphocyte nadir predisposed this patient to PJP.

BackgroundImmunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events.Methodology/principal findingsElectronic databases and grey literature were searched and records were screened against eligibility criteria. Data extraction and risk of bias assessments were performed in duplicate. Results were synthesised narratively and meta-analyses were conducted where feasible. Heterogeneity was assessed using I(2) and publication bias was assessed using Begg's funnel plot and Egger's regression test. Many of the 209 eligible studies included an unclear or high risk of bias. Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR]=0.23; 95% confidence interval [CI]=0.16-0.34; pConclusions/significanceInfection prevention and control strategies should recommend vaccinating immunocompromised patients. Potential for bias and confounding and the presence of heterogeneity mean the evidence reviewed is generally weak, although the directions of effects are consistent. Areas for further research are identified.