Recombinant interferon alfa in BCR/ABL-negative chronic myeloproliferative neoplasms.

The treatment landscape for BCR/ABL-negative myeloproliferative neoplasms (MPNs), driven by JAK2, CALR, and MPL mutations, has evolved significantly over the last decade. Recent regulatory approvals in polycythemia vera (PV) include the JAK inhibitor ruxolitinib, and more recently, a novel recombinant interferon alfa-2 (IFN-α) therapeutic agent. Many clinical trials have documented the safety and efficacy of IFN-α therapy in PV and essential thrombocythemia, the classical BCR/ABL-negative MPNs. Used off-label for more than 30 years as a cytoreductive agent, IFN-α therapy promotes significant clinical, hematologic, and molecular responses. In some IFN-α-treated patients, partial or complete reduction of the mutant JAK2 allele burden may lead to a durable measurable residual disease state, owing to the ability of long-term IFN-α therapy to selectively deplete mutant JAK2-harboring hematopoietic stem cells. Pegylated IFN-α forms were developed to improve the drug stability and tolerability of first-generation IFN-α therapeutics. More recently, a novel pegylated IFN-α, ropeginterferon alfa-2b, received approval for PV by the European Medicines Agency and the US Food and Drug Administration in 2019 and 2021, respectively. This article reviews the clinical research and recent advances that led to the first regulatory approval of IFN-α in a BCR/ABL-negative MPN and its future promise as a disease-modifying therapeutic agent.

Smooth Muscle Cell Relaxation Worsens Aortic Dilatation and Clinical Presentation in a BAPN/Angiotensin II-Induced Aortic Dissection Model in Rats.

INTRODUCTION: Beta-aminopropionitrile (BAPN) administration is a chemically induced model for preclinical aortic pathologies research. Angiotensin II (AngII) has been widely used to promotes aortic dissections in mice. Here, we provide insight on a modified aortic dissection model in rats. The effect of smooth muscle cell (SMC) relaxation with vasodilators is studied in this model. METHODS: Forty Sprague-Dawley rats were divided in 4 groups: control, isosorbide dinitrate (ISDN, 30 mg/kg/day) in the drinking water, BAPN (0.02%) in the food, BAPN + ISDN (same doses). Thoracic and abdominal aortic diameters were evaluated through transthoracic ultrasound echography. After 6 weeks, all rats were infused with AngII (1 mg/kg/day) subcutaneously. Survival and type of aortic events were numbered. Histological and histochemical analyses of aorta were performed. RESULTS: Initial telesystolic ascending aorta diameters were equal in all groups and became significantly larger in the BAPN + ISDN group compared to the BAPN group (control: 3.37 ± 0.17 mm, ISDN: 3.49 ± 0.16 mm, BAPN: 3.53 ± 0.13 mm, BAPN + ISDN: 3.61 ± 0.16 mm, analysis of variance p < 0.0001). BAPN followed by AngII infusion showed a significant lower survival rate (p = 0.029) and produced a large panel of aortic events. Association of ISDN and BAPN significantly reduces survival (p = 0.001) and provides more aortic events compared to BAPN alone (p = 0.031). In both BAPN-treated groups, orcein staining revealed split and dissected elastic fibers in the media, alcian blue staining showed mucoid degeneration of the aortic wall, and Perls-diaminobenzidine staining revealed an accumulation of Fe2+. CONCLUSION: SMC relaxation with ISDN increases aortic dilatation, worsens aortic prognosis, and reproduces human histological findings in a low-dose BAPN/AngII-induced aortic dissection model in rats.

Granulomatous Diverticulitis: Who Would Have Thought!

Diverticular disease (DD) can have different presentations, including chronic colitis. However, diverticular disease-associated colitis (DAC) is a separate entity that can be associated with a granulomatous inflammation. DAC usually affects the left colon with no involvement of the cecum and the ascending colon. In this setting, Crohn's disease is high in the differential diagnosis. Although granulomatous colitis associated with diverticulosis has been previously described, this is the first case affecting the right colon to be reported in the English literature according to our search of the PubMed database. The patient presented with a tumor-like mass abutting the right colon that was further diagnosed as a granulomatous reaction secondary to DAC.

Renal Tubular Acidosis an Adverse Effect of PD-1 Inhibitor Immunotherapy.

Immune checkpoint blockade therapy is gaining popularity among oncologists for treatment of solid and hematologic malignancies. The widespread use of these agents resulted in increasing incidence of renal immune-related adverse events. Reported renal toxicity described so far includes acute interstitial nephritis, minimal change disease, and immune complex glomerulonephritis. We report the case of a 79-year-old female with metastatic non-small cell lung cancer on anti-PD-1 therapy nivolumab. After the 4th administration of nivolumab, the treatment course was complicated with normal anion gap metabolic acidosis. Urine and blood studies were in favor of distal renal tubular acidosis (RTA). Following a negative workup for an underlying etiology, immunotherapy-induced RTA was suspected. Withholding of the offending agent and initiation of steroid therapy resulted in adequate response. The present report provides the first presentation of RTA as a renal immune-related adverse event secondary to nivolumab. Nephrologists and oncologists should be familiar with potentially life-threatening renal side effects induced by immune checkpoint inhibitors.

Diverticular Disease-associated Colitis: What Do We Know? A Review of Literature.

Diverticular disease (DD) is a leading cause of hospitalizations in developed countries affecting 30-50% of individuals older than 60 years. Identified as a distinct entity since 1980, diverticular disease-associated colitis (DAC) describes the occurrence of mucosal inflammation in a colon segment affected with DD with relative sparing of the rectum and proximal colon. Its prevalence is suggested around 1.3-3.8%. Pathogenesis is multifactorial with multiple reports noting clinicopathological overlap between DAC and inflammatory bowel disease (IBD) especially in patients with granulomatous colitis. In this setting, caution should be exercised to avoid an inappropriate diagnosis of IBD. Recurrence rates and long-term outcomes of DAC are not well defined and could range from a benign course to an overt IBD. More studies are needed in order to further characterize this entity.

Desmoid Tumor as an Initial Presentation of Familial Adenomatous Polyposis: A Review of the Literature.

Desmoid tumors (DTs) are rare soft tissue neoplasms, especially when originating from the small bowel. An association with familial adenomatous polyposis (FAP) of the colon has been well documented. Within the FAP population, there is a strong correlation between prophylactic procto-colectomy and subsequent development of DTs. Very few reports describe cases of FAP initially presenting with desmoid-related complications. Therefore, we underwent a review of the literature in order to delineate the characteristics of desmoid tumors occurring as an initial presentation of FAP.

Spinal Muscular Atrophy: The Treatment Approved.

Spinal muscular atrophy (SMA) is a rare genetic neuromuscular disorder resulting in progressive muscle weakness and atrophy. It is universally fatal, especially if the respiratory muscles are involved leading to repetitive aspiration and respiratory failure. Historically, the treatment for this disease was only supportive. Herein we describe an adult patient who presented with worsening weakness and fatigue and was subsequently diagnosed with spinal muscular atrophy. Increased awareness of this condition and a new treatment modality is required.

Intercostal Artery Laceration: Rare Complication of Thoracentesis and Role of Ultrasound in Early Detection.

Hemothorax is a rare but potentially fatal postthoracentesis complication. Early clinical signs may be nonspecific resulting in diagnostic delay. A high index of suspicion is vital for early diagnosis and intervention to avoid further bleeding. Following procedure, early bedside ultrasound findings can be vital for early detection. We report a case of massive hemothorax in a 63-year-old male following therapeutic thoracentesis. Diagnosis was made following highly suggestive sonographic findings prompting thoracotomy and lacerated intercostal artery cauterization.

Fungal Bezoar: A Rare Cause of Ureteral Obstruction.

A 52-year-old male, with diabetes mellitus and alcoholic liver disease, presented to the Emergency Room for right flank pain of 3 days' duration, associated with dysuria. Physical examination revealed right flank tenderness with fever and hypotension; laboratory findings showed acute kidney injury and large blood and leucocytes in the urine. A CT abdomen and pelvis showed hydronephrosis of the right collecting system of a horseshoe kidney with air and hyperdense debris in the renal pelvis. Patient was treated for multisensitive Proteus mirabilis emphysematous pyelonephritis, and a right nephrostomy tube was inserted. Symptoms recurred in 4 weeks, and repeated urine culture grew Candida albicans and CT scan showed same high density material within the right moiety of the horseshoe kidney. Patient underwent ureteroscopy, and a white fluffy material was aspirated from the right renal pelvis. Pathology of the aspirate confirmed the presence of fungal balls. Patient was given 2 weeks of oral fluconazole. Fungal pyelonephritis is unusual and difficult to treat. Candida species is responsible for the clear majority of the cases. A fungus ball should be managed with surgical and medical therapy. This patient had an endoscopic procedure to remove the fungus ball and received fluconazole. His symptoms resolved and urine culture was done before termination of the treatment was negative.

What we know about surgical therapy in early-stage non-small-cell lung cancer: a guide for the medical oncologist.

Lung cancer remains the leading cause of death in cancer patients. The gold standard for the treatment of early-stage non-small-cell lung cancer is lobectomy with mediastinal lymph-node dissection or systematic lymph-node sampling. The evidence behind this recommendation is based on the sole randomized controlled trial conducted to date, done by the Lung Cancer Study Group and published in 1995, which found a superiority for lobectomy over sublobar resection with regard to local recurrence rate and improved survival. The population studied at that time were medically fit patients at low risk for surgery with a stage IA non-small-cell lung carcinoma, ie, a solitary tumor less than 3 cm in size. In practice, however, thoracic surgeons have continued to push the limit of a more conservative surgical resection in this patient population. Since then, several retrospective studies have attempted to identify the ideal population to benefit from sublobar resection without it affecting survival or local recurrence. Several variables have been studied, including tumor size, patient age, surgical approach, histological and radiological properties, and optimal surgical resection margin, as well as promising prognostic biomarkers. In this review, we summarize the data available in the literature regarding the surgical approach to patients with stage IA non-small-cell lung cancer studying all the aforementioned variables.