Xanthogranulomatous pyelonephritis - A diagnostic and therapeutic dilemma.

Xanthogranulomatous pyelonephritis (XGP) is a rare variant of chronic pyelonephritis, occurring in the setting of obstructive uropathy and recurrent urinary tract infections (UTIs). It is difficult to diagnose as it can be asymptomatic until late-stage disease. Localized symptoms such as flank pain and dysuria may be attributed to nephrolithiasis or UTIs without prompting need for further workup. Extrarenal manifestations, most notably fistula formation, may present distal to the kidney and not be readily attributed to a renal pathology. The only known definitive therapy is nephrectomy. A delay in diagnosis can lead to fulminant complications or a more technically difficult nephrectomy. We present three cases of XGP, which serve to highlight the possibility of earlier diagnosis and resultant management options, including the potential for nephron-saving strategies. Early clinical and radiologic suspicion through awareness of risk factors may play an important role in preventing disease progression, avoiding late-stage complications, and improving treatment outcomes.

Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease.

BACKGROUND: Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification. METHODS: Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid. RESULTS: No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4 cases, but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these. CONCLUSIONS: Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections.

Whistling Scrotum: An Unusual Presentation of Pneumomediastinum in the Setting of an Open Scrotal Wound.

BACKGROUND Pneumoscrotum is a rare clinical occurrence in which air accumulates in the scrotum. The origin of air is primarily from trauma, but spontaneous pneumoscrotum can develop from gastrointestinal or pulmonary sources. Physical examination of pneumoscrotum typically includes crepitus of the perineal region and scrotal swelling and associated findings depending on the origin of the free air. However, pneumoscrotum in the setting of a scrotal wound, which allows air to pass freely outside the body, has not been previously documented in the literature. CASE REPORT A 72-year-old man who recently underwent a scrotal incision and drainage for recurrent epididymitis presented to a local emergency room with chief concerns of "whistling scrotum" and dyspnea. The chest CT revealed bilateral pneumothoraces, pneumomediastinum, and excessive subcutaneous emphysema throughout his abdomen, perineum, and scrotum. His scrotum had a dehiscent wound without any gross edema or air trapping contained within the scrotum. He received bilateral chest tubes and subcutaneous air drains with complete resolution of his pneumothoraces. The pneumoscrotum and associated subcutaneous emphysema of the perineum and thighs resolved after a prolonged period, and necessitated additional scrotal surgery. CONCLUSIONS Prompt evaluation for source control is necessary with pneumoscrotum, as the source likely requires immediate stabilization or surgical intervention. This case report describes a unique presentation of a common entity (pneumothorax) within pulmonology/critical care in a patient with an open scrotal wound from a recent scrotal procedure, which allowed the air to escape from his abdominal compartment, and resulted in his "scrotal whistling." It is unclear how the air passing through the scrotum affected the patient's presentation, such as allowing more air to build up in the subcutaneous tissues versus developing critical illness.

New Therapies for Hepatitis C Virus.

Hepatitis C virus (HCV), the major etiologic agent of "non-A, non-B hepatitis" was discovered 26 years ago. Even before its discovery, interferon-α (IFN) was already being used for treatment of this infection. The next two decades saw a series of incremental improvements of the IFN therapies by extending the duration of therapy, using IFN in combination with oral ribavirin, using pegylated IFN with ribavirin, and most recently adding oral compounds that inhibit the HCV replication (directly acting antivirals - DAAs) to that regimen. DAAs target multiple steps in the HCV life cycle and are now used in combination to treat HCV infection without the need of IFN. These IFN-free, oral DAAs regimens are highly efficacious, have minimal toxicity and are given for short duration. Approved DAAs can cure more then 90% of persons with chronic HCV infection, thereby reducing the risk of death from cirrhosis and hepatocellular carcinoma. However, these drugs are very expensive, and currently their exorbitant cost significantly restricts the access to this therapy for many HCV infected patients.

The use of ivacaftor in an adult with severe lung disease due to cystic fibrosis (ΔF508/G551D).

We report on an adult with cystic fibrosis (ΔF508/G551D) with severe lung disease (forced expiratory volume (FEV1) in one second 24% predicted) who was admitted for a pulmonary exacerbation. He was managed with maximal medical therapy, but did not have significant improvement until after he was started on ivacaftor on hospital day 15. He subsequently had significant improvement in lung function with normalization of hypercarbia, oxygen saturation on room air, and increase in FEV1 to 36% predicted. Prior to use of ivacaftor he was being assessed for a lung transplant. However, after ivacaftor therapy for 6 months, he is no longer considering this treatment modality due to his improvement of lung function and functional status.

Cyclo-oxygenase II inhibitors in the treatment of neoplastic fever.

Neoplastic fever is relatively common in cancer patients. Naproxen is one of the most commonly used non-steroidal anti-inflammatory drugs for the treatment of neoplastic fever. Naproxen is associated with platelet dysfunction and gastrointestinal side effects. We substituted rofecoxib, a cyclooxygenase-II inhibitor, for naproxen in patients with a previous history of, or a newly diagnosed, neoplastic fever in whom naproxen was relatively contraindicated. In all patients the fever resolved completely without any side effects.