Daptomycin-Induced Pulmonary Toxicity: A Case Series.

Daptomycin is a bactericidal antibiotic used to treat methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE). Eosinophilic pneumonia is an uncommon but significant adverse effect of daptomycin. We present two patients treated with daptomycin who subsequently developed eosinophilic pneumonia (EP).

COVID-19 Vaccine Booster-Induced Dermatographism.

The urgent requirement for a preventative vaccination became more pressing due to the severe repercussions that the SARS-CoV-2 (COVID-19) virus had on society and the economy. The deployment of the COVID-19 vaccination program had to be expedited. As with all vaccinations, adverse events have been recorded with the COVID-19 vaccine. Some patients may experience cutaneous reactions such as rashes, itching, hives, and swelling after receiving the COVID-19 vaccine, but it is unclear how common these events are or how frequently they recur. This article discusses an unusual case of a young man who got chronic severe dermatographism after receiving a booster shot of the Moderna vaccine (Moderna, Inc., Cambridge, Massachusetts).

COVID-19 Vaccine-Induced Parsonage-Turner Syndrome: A Case Report and Literature Review.

All modern vaccines share the risk of neurological adverse effects. Only a few cases of Parsonage-Turner syndrome (PTS), an uncommon peripheral nerve condition associated with coronavirus disease 2019 (COVID-19) immunization, have been reported to date. We describe a case of COVID-19 vaccine-induced PTS and provide a brief literature review. A 78-year-old male non-smoker with a medical history of coronary artery disease presented with non-exertional, constant chest pain for one hour and new onset of bilateral hand weakness for three days. He had no neurological disease or allergies and denied any recent trauma or infection. Three weeks before the onset of the symptoms, the patient received a second dose of the BNT162b2 COVID-19 vaccine, which was administered 21 days after the first dose. Physical examination was significant for weakness in right-hand grip and wrist flexion. There were no other motor deficits, upper motor neuron signs, bulbar weakness, or sensory deficits. Diagnostic workup for the underlying diabetes mellitus, infections, or other autoimmune diseases was negative. Imaging workup revealed no demyelination, fracture deformity, traumatic subluxation, or compressive myelopathy. Nerve conduction studies, including needle electromyography, showed decreased motor unit recruitment in the bilateral first dorsal interosseous and right deltoid, biceps, and triceps muscles confirming PTS. The patient was treated with 40 mg/day of oral prednisone and occupational therapy to maintain range of motion and activities of daily living. PTS is also known as neuralgic amyotrophy, brachial plexus neuritis, brachial plexopathy, and shoulder-girdle syndrome. It is characterized by asymmetrical, chronic, resistant upper extremity neuropathic pain and neurological defects such as paralysis and paresthesia. There are two different types of PTS: non-hereditary and inherited. The etiology and pathophysiology of PTS are not fully understood. Various aspects such as genetic, environmental, and immunological predisposition may play a role in developing the syndrome. Infections, vaccines, and injuries are typical causes of non-hereditary forms. After the COVID-19 epidemic and the commencement of a global immunization effort, similar instances happened. Presently there is no available test that unequivocally confirms or excludes PTS itself. Electrodiagnostic study and imaging modalities help to rule out other differential diagnoses. Also, there is no specific treatment available; however, it may resolve independently of treatment with supportive care.

Myelomatous Pleural Effusion: A Rare Occurrence in Multiple Myeloma.

Various factors can cause pleural effusion in multiple myeloma patients. Myelomatous pleural effusion (MPE) is an uncommon but potentially life-threatening complication of multiple myeloma with a poor prognosis. After ruling out all other probable causes, the present case reports MPE in a patient with IgG kappa multiple myeloma.

Diffuse Alveolar Hemorrhage With Avelumab Maintenance Therapy.

Immune checkpoint blockade is a rapidly expanding therapeutic modality in oncology. However, its adverse effects extend beyond the cytotoxicity of conventional chemotherapy. Pneumotoxicity associated with immune checkpoint therapy presents a diagnostic conundrum that has been further complicated by the COVID-19 pandemic. We report a case of a patient with metastatic urothelial carcinoma who developed diffuse alveolar hemorrhage (DAH) following treatment with avelumab.

Valproate-induced fatal acute hyperammonaemia-related encephalopathy in late-onset ornithine transcarbamylase deficiency.

Ornithine transcarbamylase (OTC) deficiency is a genetic disorder of the urea cycle characterised by deficiency in the enzyme OTC, resulting in an accumulation of ammonia. Valproic acid (VPA), a commonly used medication in the treatment of neurologic and psychiatric conditions, has been known to cause episodes of acute hyperammonaemia in patients with OTC deficiency. We present the case of a 29-year-old man with a long history of non-specific psychiatric disorders, who suffered from a hyperammonaemic crisis following the administration of VPA, leading to the diagnosis of OTC deficiency. The patient's hospital course was complicated by progressive cerebral oedema, which resulted in worsening encephalopathy, seizures and death. We discuss the pathophysiology of hyperammonaemia in OTC deficiency, and various management strategies, including lactulose, levocarnitine, scavenger therapy and haemodialysis.

Refractory thoracic endometriosis.

Thoracic endometriosis syndrome (TES) is a rare entity caused by thoracic implantation of endometrial tissue, manifesting as catamenial pneumothorax, pleural effusion and haemoptysis in young female individuals. Its management and long-term prevention of recurrences, can be challenging. We present the case of a young woman who presented with recurrent pneumothorax, haemopneumothorax and pleural effusion. The diagnosis of TES was confirmed based on cytological findings of pleural fluid. She underwent treatment with mechanical pleurodesis twice but continued to have recurrences. Hormonal treatment failed to produce a satisfactory resolution. She underwent chemical pleurodesis, which successfully induced remission of her TES. A review of the literature suggests that chemical pleurodesis produces better results compared with mechanical pleurodesis and that hormonal treatment with gonadotropin-releasing hormone agonists is effective at preventing recurrences.

Pulmonary mucinous cystadenocarcinoma: an unusual presentation and literature review.

Cystic lung disease is a group of heterogeneous pulmonary diseases resulting from hereditary/congenital disorders, systemic disorders and infectious causes among others. Pulmonary mucinous cystic neoplasia is a spectrum of neoplastic cystic diseases with abundant mucin, of which pulmonary mucinous cystadenocarcinoma (PMC) is a rare malignant subtype. We present a case of a 66-year-old man who presented with dyspnoea, cough, fatigue and weight loss. Imaging of his chest showed numerous cavitary lesions, and the diagnosis of PMC was made based on lung biopsy. He received palliative chemotherapy and died 1 year later. We present a literature review of PMC based on 26 reported cases, including our own.

Recurrence Prophylaxis in Secondary Spontaneous Pneumothorax: A Nationwide Readmission Database Analysis.

BACKGROUND: Secondary spontaneous pneumothorax (SSP) is defined as a pneumothorax presenting as a complication of underlying lung disease. Due to the high recurrence rate and the possibility of life-threatening complications, same-admission recurrence prophylaxis (SARP) following the first occurrence of SSP is recommended by many experts. The rate of SARP in SSP admissions has not been reported. RESEARCH QUESTION: How often were SARP procedures performed in SSP admissions in the United States? How did outcomes differ between SSP admissions with SARP vs those without SARP? STUDY DESIGN AND METHODS: This study used the Nationwide Readmission Database to analyze 71,451,419 inpatient admissions in the United States in 2016 and 2017. SSP admissions with patients aged ≥ 18 years were included, and admissions with documented traumatic or iatrogenic causes of pneumothorax were excluded. Outcomes were compared between SSP admissions with and without SARP. Multivariate logistic analysis was used to model binary-dependent variables. RESULTS: There were 21,838 SSP admissions in 2016 and 2017 (30.56 per 100,000 admissions per year), among which 7,366 (33.73%) received SARP. SARP was associated with lower odds of in-hospital mortality (adjusted OR [aOR], 0.48; 95% CI, 0.34-0.70), 30-day mortality (aOR, 0.52; 95% CI, 0.35-0.77), 90-day mortality (aOR, 0.56; 95% CI, 0.40-0.79), and 1-year mortality (aOR, 0.28; 95% CI, 0.10-0.74). SARP was also associated with lower all-cause readmission at 30 days (aOR, 0.40; 95% CI, 0.40-0.49), 90 days (aOR, 0.47; 95% CI, 0.40-0.55), and 1 year (aOR, 0.46; 95% CI, 0.30-0.68), as well as lower rates of postdischarge pneumothorax recurrence in 30 days (aOR, 0.22; 95% CI, 0.11-0.44), 90 days (aOR, 0.26; 95% CI, 0.20-0.33), and 1 year (aOR, 0.22; 95% CI, 0.11-0.44). INTERPRETATION: The rate of SARP in SSP admissions was 33.73% in the United States in 2016 and 2017. SARP was associated with lower mortality, all-cause readmission, and pneumothorax recurrence in SSP admissions.

Severe hypothermia, bradycardia and cardiac arrest in association with risperidone.

Antipsychotic medications, including risperidone, are widely used in the treatment of psychiatric disorders, including schizophrenia. While hyperthermia is an establish adverse effect of these medications, less is known about the rare occurrence of hypothermia. We present two patients who developed hypothermia, bradycardia and cardiac arrest in association with risperidone. We briefly review previously similarly reported cases.

Effects of deep sedation on sleep in critically ill medical patients on mechanical ventilation.

Atypical EEG patterns not consistent with standard sleep staging criteria have been observed in medical intensive care unit (ICU) patients. Our aim was to examine the relationship between sleep architecture and sedation in critically ill mechanically ventilated patients pre- and post-extubation. We performed a prospective observational repeated measures study where 50 mechanically ventilated patients with 31 paired analyses were examined at an academic medical centre. The sleep efficiency was 58.3 ± 25.4% for intubated patients and 45.6 ± 25.4% for extubated patients (p = .02). Intubated patients spent 76.33 ± 3.34% of time in non-rapid eye movement (NREM) sleep compared to 64.66 ± 4.06% of time for extubated patients (p = .02). REM sleep constituted 1.36 ± 0.67% of total sleep time in intubated patients and 2.06 ± 1.09% in extubated patients (p = .58). Relative sleep atypia was higher in intubated patients compared to extubated patients (3.38 ± 0.87 versus 2.79 ± 0.42; p < .001). Eleven patients were sedated with propofol only, 18 patients with fentanyl only, 11 patients with fentanyl and propofol, and 10 patients had no sedation. The mean sleep times on "propofol", "fentanyl", "propofol and fentanyl," and "no sedation" were 6.54 ± 0.64, 4.88 ± 0.75, 6.20 ± 0.75 and 4.02 ± 0.62 hr, respectively. The sigma/alpha values for patients on "propofol", "fentanyl", "propofol and fentanyl" and "no sedation" were 0.69 ± 0.04, 0.54 ± 0.01, 0.62 ± 0.02 and 0.57 ± 0.02, respectively. Sedated patients on mechanical ventilation had higher sleep efficiency and more atypia compared to the same patients following extubation. Propofol was associated with higher sleep duration and less disrupted sleep architecture compared to fentanyl, propofol and fentanyl, or no sedation.

Phospholipid transfer protein and alpha-1 antitrypsin regulate Hck kinase activity during neutrophil degranulation.

Excessive neutrophil degranulation is a common feature of many inflammatory disorders, including alpha-1 antitrypsin (AAT) deficiency. Our group has demonstrated that phospholipid transfer protein (PLTP) prevents neutrophil degranulation but serine proteases, which AAT inhibits, cleave PLTP in diseased airways. We propose to identify if airway PLTP activity can be restored by AAT augmentation therapy and how PLTP subdues degranulation of neutrophils in AAT deficient subjects. Airway PLTP activity was lower in AAT deficient patients but elevated in the airways of patients on augmentation therapy. Functional AAT protein (from PiMM homozygotes) prevented PLTP cleavage unlike its mutated ZZ variant (PiZZ). PLTP lowered leukotriene B4 induced degranulation of primary, secondary and tertiary granules from neutrophils from both groups (n = 14/group). Neutrophils isolated from Pltp knockout mice have enhance neutrophil degranulation. Both AAT and PLTP reduced neutrophil degranulation and superoxide production, possibly though their inhibition of the Src tyrosine kinase, Hck. Src kinase inhibitors saracatinib and dasatinib reduced neutrophil degranulation and superoxide production. Therefore, AAT protects PLTP from proteolytic cleavage and both AAT and PLTP mediate degranulation, possibly via Hck tyrosine kinase inhibition. Deficiency of AAT could contribute to reduced lung PLTP activity and elevated neutrophil signaling associated with lung disease.

Obstructive sleep apnea and acute respiratory failure: An analysis of mortality risk in patients with pneumonia requiring invasive mechanical ventilation.

PURPOSE: Although obstructive sleep apnea (OSA) is common and pneumonia is a frequent cause of acute respiratory failure requiring admission to the intensive care unit, little is known about the effect of OSA on this patient population. This study examined outcomes associated with OSA in patients with pneumonia requiring invasive mechanical ventilation. MATERIALS AND METHODS: The Nationwide Inpatient Sample was investigated for discharges with a primary diagnosis of pneumonia requiring invasive mechanical ventilation between 2009 and 2011. Persons aged 18 to 75 years with OSA were compared with patients without OSA. Outcomes included in-hospital mortality and nonroutine discharges. RESULTS: Among 74032 hospitalizations, 13.8% (10227) were obese, and 10.3% (7610) had OSA. Obstructive sleep apnea patients had decreased in-hospital mortality (17.0% vs 25.8%; P < .01) and nonroutine discharge (74.4% vs 79.4%; P < .01) when compared with non-OSA patients. In adjusted logistic models, OSA was associated with a 27% decreased risk of in-hospital mortality (odds ratio, 0.73; 95% confidence interval, 0.68-0.79; P < .01) and a 21% decreased risk of nonroutine discharge (odds ratio, 0.79; 95% confidence interval, 0.74-0.84; P < .01). CONCLUSIONS: In mechanically ventilated patients with pneumonia, OSA was associated decreased in-hospital mortality and nonroutine discharge. It is possible that differences in treatment pattern may partially explain improved survival.

Pulmonary sarcoidosis and latent tuberculosis in a patient with psoriasis treated with adalimumab.

Tumor necrosis factor (TNF) inhibitors are powerful biologic medications that have been used successfully in the treatment of a variety of inflammatory conditions, including psoriasis. Although TNF inhibitors are generally well tolerated, their use increases the risk of infections such as tuberculosis (TB), and paradoxically, they have been associated with development of sarcoidosis. We report the case of a 54-year old man with plaque psoriasis who developed a positive TB test and pulmonary sarcoidosis after 12 months of adalimumab treatment. After stopping adalimumab, his psoriasis worsened and he was started on ustekinumab and narrowband UVB, with improvement in symptoms. We provide a review of the literature and discuss treatment challenges.

Rare coexistence of sarcoidosis and lung adenocarcinoma.

CASE: An eighty year old African-American female was evaluated for cough, chest pain, asymptomatic anemia and 21 pound weight loss over a six month period. Computerized tomography (CT) revealed a spiculated 2.8 cm right upper lobe lung nodule, other smaller nodules and lymphadenopathy. Gallium scan revealed abnormal uptake of radiotracer in lacrimal, hilar and mediastinal glands. Broncho-alveolar lavage showed CD4/CD8 ratio of 2:1 with 15% lymphocytes. Biopsy of right upper lobe lesion and mediastinoscopic lymph node biopsy showed numerous matured uniform non-caseating granulomatous inflammation, however stains and culture for Acid fast bacilli (AFB)/fungal organisms were negative. Patient improved on oral steroids. Six months later she returned with worsening dyspnea and chest X-ray showed bilateral pleural effusions. Thoracocentesis revealed Thyroid transcription factor 1 (TTF1) positive adenocarcinoma cells and Video assisted thoracic surgery (VATS) procedure revealed numerous pleural, pericardial, diaphragmatic metastasis. Biopsy also was positive for TTF1 adenocarcinoma and positive for Epidermal Growth Factor receptor (EGFR) mutation, however negative for Anaplastic Lymphoma Kinase (ALK). Talc pleurodesis was performed. She was treated with erlotinib while steroid was kept on hold. Initial tumor burden decreased but follow-up PET scan six months later showed progression of tumor with lymphadenopathy. After discussion with patient and family, patient opted for hospice care. DISCUSSION: Oncocentric theory postulates sarcoidosis as an immunological reaction to dispersal of tumor antigen. Sarcocentric theory postulates that cell-mediated immune abnormalities induced by sarcoidosis in CD4 and CD8 cells is involved in the onset of lung cancer. Thus considerable controversy exists regarding sarcoidosis and malignancy. In our case, TTF1 adenocarcinoma cells from thoracocentesis suggest peripheral nodules in right upper lobe and lingula were likely metastatic, presenting as malignant pleural effusions. However if noncaseating granulomatous inflammation is expected as an immunological reaction to tumor antigen, it is very interesting to observe that initial tissue biopsy of primary right upper lobe mass and mediastinal lymph nodes showed matured uniform non-caseating granulomatous inflammation and no evidence of adenocarcinoma. This being said, it would be highly unlikely for sarcoidosis to progress to lung adenocarcinoma within six months. This adds further controversy to whether granulomatous inflammation is a precursor to future malignancy or whether this elderly African-American female was predisposed to develop granulomatous inflammation in presence of a tumor antigen. One can also speculate whether repeat tissue sampling from right upper lobe mass would have shown granulomatous inflammation or TTF1 adenocarcinoma. CONCLUSION: While evidence is still lacking regarding association between sarcoidosis and lung adenocarcinoma, it is important for clinicians to exclude metastatic malignancy in patients exhibiting clinical and radiographic findings consistent with sarcoidosis.