Multiple mononeuritis with peripheral blood eosinophilia in a patient with Q fever: An unusual presentation: Case report and review of the literature.

Coxiella burnetii is a gram-negative bacterium that typically lives and multiplies within monocytes and macrophages of the host, being the etiologic agent of the zoonosis Q fever. Q fever is usually divided into acute and chronic forms, with a significant percentage of patients being asymptomatic. In the wide spectrum of the disease, neurological involvement seems to be extremely rare and peripheral neuropathy presenting with mononeuritis multiplex is one of the possible presentations with low rates of occurrence. Hereby, we present an unusual case of a 55-year-old male with fever and multiple mononeuritis attributed to Q fever and we summarize a short review of C. burnetii infection.

Clostridioides difficile infection in a patient with immunoglobulin A vasculitis: a triggering factor or a rare complication of the disease? A case-based review.

IgA vasculitis, formerly known as Henoch-Schonlein purpura (HSP), is the most common form of systemic vasculitis in children and is characterized by inflammation of the small vessels with typical deposition of IgA immune complexes. It is a leukocytoclastic type of vasculitis and is characterized by a tetrad of clinical manifestations: non-thrombocytopenia or coagulopathy-induced palpable purpura, arthritis, or arthralgia, gastrointestinal, and renal involvement. The exact cause of IgA vasculitis is not known yet, although infections, vaccinations and insect bites have been implicated in the appearance of the disease. The main risk factors for Clostridioides difficile infection (CDI) are previous CDI, age > 65 years old, pharmacologic agents (antibiotics, PPIs, histamine-2 receptor antagonists, glucocorticoids, and chemotherapy), prior hospitalization, the presence of co-morbidities, especially inflammatory bowel diseases and chronic kidney disease (CKD) and immunosuppression. Oral vancomycin or fidaxomicin are the gold standard of the therapy, with metronidazole being an alternative choice. The purpose of this study was to describe a case of IgA vasculitis and Clostridioides difficile infection to see whether there is any association between the two distinct clinical entities. Herein, we describe a 17-year old patient with IgA vasculitis and bloody diarrhea due to Clostridioides difficile infection and we discuss the co-existence of these two pathological conditions. The patient presented to the hospital with diffuse abdominal pain, nausea, vomiting, and two episodes of bloody diarrhea. Stools tested positive for Clostridioides difficile toxins, while he remained afebrile with hs-CRP = 1.5 mg/dL (normal range < 0.5 mg/dL). Direct immunofluorescence from the extremities' purplish eruption showed leukocytoclastic vasculitis with IgA deposition. Whether co-existence of the two above-mentioned distinct clinical entities is just a co-incidence or CDI is a triggering factor for IgA vasculitis remains to be elucidated in future large-scale studies.

Low dose dabigatran versus uninterrupted acenocoumarol for peri-procedural anticoagulation in atrial fibrillation catheter ablation.

BACKGROUND: Left atrial ablation for atrial fibrillation (AF) is associated with a transiently increased risk of thromboembolic and hemorrhagic events. We tested the hypothesis that the low dose dabigatran [110mg twice a day (bid)] can be safely used as an alternative to uninterrupted acenocoumarol for periprocedural anticoagulation in left atrial ablation procedures. METHODS AND RESULTS: A total of 149 consecutive patients undergoing pulmonary vein antral isolation for AF were included; 64 patients were on low dose dabigatran (110mg bid) and 85 patients were on acenocoumarol with therapeutic international normalized ratios. Two doses of dabigatran were withheld before the procedure and the drug was restarted 4hours after vascular hemostasis. Overall, the two groups were well-matched. Hemorrhagic and thromboembolic complications were similar in both groups within 90days from the procedure (4.7% for the dabigatran group versus 9.4% for the acenocoumarol group; P=0.275). Major hemorrhage occurred in 1.6% in the dabigatran group versus 3.5% in the acenocoumarol group (P=0.462). A single thromboembolic event occurred in the dabigatran group (1.6%) versus 2 (2.4%) in the acenocoumarol group (P=0.734). Despite higher doses of intraprocedural heparin (P<0.01), the mean activated clotting time was significantly lower in patients who were on dabigatran than those on acenocoumarol (P<0.01). CONCLUSIONS: The low dose dabigatran regimen provides safe and effective peri-procedural anticoagulation in patients undergoing left atrial ablation for AF compared with uninterrupted acenocoumarol therapy.

Coexistence of Hodgkin and Non-Hodgkin Lymphoma; Composite Lymphoma [CL] in a Patient Presenting with Waxing and Waning Lymphadenopathy.

BACKGROUND: The coexistence of two or more types of lymphoma within the same organ at the same time of diagnosis is defined as composite lymphoma, a rare disease that has recently been identified in the literature. Pointedly, the concurrence may be Hodgkin lymphoma with a Non-Hodgkin lymphoma [NHL], either B or T cells, or two different entities of NHLs. Furthermore, this condition has been described concurrently or sequentially. In order for the diagnosis to be established, two or more distinct clones should be proven by morphological and laboratory tests. CASE PRESENTATION: Herein, we cite a seventy-three-year old female patient with low-grade fever, waxing and waning cervical lymphadenopathy, whose biopsy of an axillary lymph node demonstrated the rare coexistence of Hodgkin and NHL, known as composite lymphoma. CONCLUSION: Composite lymphomas pose a particular diagnostic challenge, and currently, there are no agreed standards for treatment.

Analgesic activity of high-dose intravenous calcitonin in cancer patients with bone metastases.

We undertook a prospective, nonrandomized study with the objective to evaluate the efficacy of salmon calcitonin (sCT) in controlling pain secondary to bone metastases. Our study population consisted of 45 cancer patients with bone metastases (26 men) with a mean age of 64 years (range, 48-70) who had completed chemotherapy, hormonal therapy and radiation therapy at least 30 days prior to enrollment in the study, and had intractable pain despite the use of common analgesics (acetaminophen, nonsteroidal anti-inflammatory agents, opioids) and bisphosphonates. The study medication was a 300-IU dose of sCT administered intravenously daily for 5 consecutive days and repeated every two weeks until no response was noticeable. The analgesic efficacy of sCT was evaluated by means of Huskisson's visual analogue scale and Keele's pain scale; the daily consumption of analgesic drugs and performance status were also monitored. None of the patients managed to completely discontinue the use of other analgesics, but 5 patients (11% of the total number) had an analgesic response that lasted 4 weeks and less than 5% of the patients continued to respond for 6 weeks. No significant side effects were observed. Our data show that intravenous calcitonin administered in a relatively high dose has a very limited therapeutic potential as an adjuvant analgesic for a short period of time in selected cancer patients with bone metastases.

A simplified premedication schedule for 1-hour paclitaxel administration.

Many investigations have focused on an optimal dosing schedule for paclitaxel since its regulatory approval. Paclitaxel is generally administered at a dose of 175 mg/m2 IV over 3 hours or 135-175 mg/m2 IV over 24 hours, every 3 weeks. The purpose of this study was to simplify the administration of paclitaxel to make it suitable and practical in the outpatient setting. Using this rationale, the duration of administration was decreased to 1 hour, with a minimized premedication regimen. Fifty-two patients scheduled to receive paclitaxel-based chemotherapy were entered into the study. Tumor types included non-small cell lung cancer, small cell lung cancer, breast cancer, head and neck cancer, and ovarian cancer. Twelve patients received paclitaxel 175 mg/m2 IV, and the remaining 40 patients received paclitaxel 225 mg/m2 IV. Premedication consisted of IV dexamethasone 20 mg over 5-10 minutes, given 30-60 minutes before infusion of paclitaxel,followed by IV dimethindene maleate 4 mg and IV ranitidine 50 mg over 30 minutes. Paclitaxel always was administered before other chemotherapeutic agents. Hypersensitivity reactions were recorded in 4 patients (7.7%) and were not influenced by age, gender, disease, dose schedule, or number of cycles of therapy; no serious hypersensitivity reactions were observed. The present study supports the efficacy and safety of a short premedication schedule; with further study, this schedule might become a standard premedication protocol prior to paclitaxel administration.

Raltitrexed (Tomudex) administration in patients with relapsed metastatic colorectal cancer after weekly irinotecan/5-Fluorouracil/Leucovorin chemotherapy.

PURPOSE: The present study aimed at evaluating the efficacy of Raltitrexed, a specific thymidilate synthase inhibitor, in patients with advanced colorectal cancer (ACC) in relapse (>8 weeks) after a prior response or disease stabilization to first-line chemotherapy combination with lrinotecan+5-Fluorouracil (5-FU)+Leucovorin (LV). METHODS: Twenty-five patients with metastatic ACC entered; 17 males/8 females, median age 61 (range: 47-70), median Karnovsky PS: 80 (70-90), and sites of metastases; liver: 21, lung: 4, lymph nodes: 7, peritoneal: 5 and a life expectancy of at least 3 months, were entered in the present pilot study. All patients had progressed after prior chemotherapy with lrinotecan+5-FU+LV. Raltitrexed was administered at a dose of 3 mg/m2 i.v. every 21 days. RESULTS: Three patients (12%) achieved a partial response (PR), 8 (32%) had stable disease (SD), and the remaining 14 (56%) developed progressive disease (PD). Median time-to-progression (TTP) was 5.5 months (range, 2-8.5), and median overall survival (OS) 8 months (range, 4.0-12.5). Toxicity was generally mild; it consisted mainly of myelosuppression; neutropenia grade 1-2: 52%-grade 3: 28%, and anemia grade 1-2 only: 36%. Mild mucositis grade 1-2 occurred in 13.5% of patients and was the principal non-hematologic toxicity. CONCLUSION: Response to treatment with Raltitrexed is limited in patients with ACC failing after an initial response or non-progression to the weekly lrinotecan+5-FU+LV combination. However, it appears that a limited number of patients with PR/SD may derive clinical benefit, but final proof would require a randomized study.

Amifostine, in a reduced dose, protects against severe diarrhea associated with weekly fluorouracil and folinic acid chemotherapy in advanced colorectal cancer: a pilot study.

Fifty-two consecutive patients with advanced colorectal cancer who developed persistent diarrhea following chemotherapy with 5-fluorouracil despite dose reduction were treated with amifostine 800, 500 or 150 mg/m(2). The administered dose of 5-fluorouracil was significantly greater during amifostine treatment. Amifostine 800 mg/m(2) was associated with complete elimination of diarrhea, but 76.3% of patients developed infusion-related hypotension. At a dose of 500 mg/m(2), diarrhea was significantly reduced and milder compared with baseline and the incidence of hypotension was 54.2%. At the lowest dose of amifostine, 17.1% of patients developed Grade 1 diarrhea, a significant reduction over baseline, and hypotension occurred in 25.2% of patients. Treatment with amifostine also improved mucositis but had no effect on the relatively mild nausea and vomiting due to 5-fluorouracil. In this study, amifostine reduced the incidence and severity of diarrhea associated with 5-fluorouracil in patients with advanced colorectal cancer, with acceptable efficacy at a reduced dose that offered better tolerability.

Pegylated liposomal doxorubicin in the CHOP regimen for older patients with aggressive (stages III/IV) non-Hodgkin's lymphoma.

Pegylated liposomal doxorubicin is associated with a lower risk of cardiotoxocity than conventional formulations of doxorubicin, allowing the use of higher cumulative doses. In this Phase II study, 25 patients aged over 70 years (median 79, range 75-82 years) with aggressive non-Hodgkin's lymphoma (NHL) (International Prognostic Index (IPI) -2, 12 (48%); IPI-3, 10 (40%); IPI-4, 3 (12%)) received CHOP with pegylated liposomal doxorubicin. All completed 6 treatment cycles and were evaluable for efficacy and safety. A complete response was achieved in 13 (52%) patients and a partial response in 12 (48%) patients, which was maintained for at least 12 months. The median time to progression was 26 months (range 14->42) and median overall survival was 32 months (range 26-48). No Grades III/IV toxicity occurred; adverse events included neutropenia, anaemia, nausea and vomiting, diarrhoea and constipation in 16-29% of the cycles. Pegylated liposomal doxorubicin is an effective and well-tolerated component that may be substituted for doxorubicin in the CHOPC (cyclophosphanide, doxorubicin, vincristine, prednizolone) regimen for the treatment of aggressive NHL in elderly people.

Docetaxel and epirubicin supported by granulocyte colony-stimulating factor first-line in advanced breast cancer.

This phase II trial studied the efficacy and toxicity of docetaxel-epirubicin, supported by granulocyte colony-stimulating factor, as first-line chemotherapy in metastatic breast cancer. Patients received epirubicin (60 mg/m2) followed 1 hour later by docetaxel (80 mg/m2) every 3 weeks for a maximum of 8 cycles or until disease progression. Prophylactic granulocyte colony-stimulating factor (5 micrograms/kg) was administered daily for 5 days. Sixty-nine patients were evaluable for efficacy and toxicity. Objective responses occurred in 45 patients (65%; 95% confidence interval: 53-76%), with 11 (16%) complete responses and 34 (49%) partial responses. Responses were observed at all metastatic sites. The median response duration was 8 months (range 4-68), median time to progression was 10 months (range 4-68) and median overall survival was 24 months (range 7-68): neutropenia was dose limiting (46% grade 3-4 toxicity). The left ventricular ejection, fraction measured in 50 patients, fell below normal in 14 patients (28%), 8 patients had grade 1 and 6 grade 2 cardiotoxicity, but none developed congestive cardiac failure. The docetaxel-epirubicin regimen is extremely effective in poor prognosis breast cancer patients with visceral metastases, with significant overall and complete responses, followed by prolonged survival in responders. Although myelosuppression remains the major toxicity, prophylactic GCSF administration was associated with a small percentage of neutropenic fever.

Predictors of atrial fibrillation recurrence in patients with long-lasting atrial fibrillation.

BACKGROUND: Limited data are available on the predictors of atrial fibrillation (AF) recurrence in patients with chronic AF. OBJECTIVES: To evaluate potential clinical, echocardiographic and electrophysiological predictors of AF recurrence, after internal cardioversion for long-lasting AF. METHODS: A total of 99 consecutive patients (63 men and 36 women, mean age 63.33+/-9.27 years) with long-standing AF (52.42+/-72.02 months) underwent internal cardioversion with a catheter that consisted of two defibrillating coils. Shocks were delivered according to a step-up protocol. Clinical follow-up and electrocardiographic recordings were performed on a monthly basis for a 12-month period or whenever patients experienced symptoms suggestive of recurrent AF. RESULTS: Ninety-three patients (93.94%) underwent a successful uncomplicated cardioversion, with a mean atrial defibrillation threshold of 10.69+/-6.76 J. Immediate reinitiation of AF was observed in 15 patients (15.78%) of whom a repeated cardioversion restored sinus rhythm in 13 cases. Early recurrence of AF (within one week) was observed in 12 of 93 patients (12.90%). At the end of the 12-month follow-up period, during which seven patients were lost, 42 of the 86 remaining patients (48.84%) were still in sinus rhythm. Multivariate regression analysis showed that left atrial diameter (OR 1.126, 95% CI 1.015 to 1.249; P=0.025) and mitral A wave velocity (OR 0.972, 95% CI 0.945 to 0.999; P=0.044) were significant and independent predictors of AF recurrence, whereas age, left ventricular ejection fraction and AF cycle length were not predictive of arrhythmia recurrence. CONCLUSION: The present study showed that the left atrial diameter and mitral A wave velocity are the only variables associated with AF recurrence after successful cardioversion.

Comparison of two oral regimens for the outpatient treatment of low-risk cancer patients with chemotherapy-induced neutropenia and fever: ciprofloxacin plus cefuroxime axetil versus ciprofloxacin plus amoxicillin/clavulanate.

The objective of this investigation was to assess retrospectively the safety and the efficacy of oral ciprofloxacin plus cefuroxime axetil compared to the combination of oral ciprofloxacin plus amoxicillin/clavulanate, as initial outpatient treatment, in low-risk cancer patients with fever and neutropenia. We analysed retrospectively 120 episodes of febrile neutropenia, treated on an outpatient basis at 2 different oncology units; 63 episodes were treated with the oral regimen of ciprofloxacin plus amoxicillin/clavulanate and 57 were treated with the combination of oral ciprofloxacin plus cefuroxime. 20 treatment failures were recorded-2 of them among patients receiving ciprofloxacin plus amoxicillin/clavulanate and 18 in the ciprofloxacin plus cefuroxime group. Univariate analysis showed that the administration of ciprofloxacin plus cefuroxime was associated with a worse outcome compared to the regimen ciprofloxacin plus amoxicillin/clavulanate (OR 11, CI 2.42-49.9, p =0.002). In the multivariate model, after adjusting for the absolute number of neutrophils and the duration of neutropenia, the effect of the antibiotic regimen on the outcome disappeared, and no significant differences between the 2 regimens were noted, although the regimen of ciprofloxacin plus cefuroxime was associated with a trend to a worse outcome (OR 4.74, CI 0.72-31.1, p =0.10). In conclusion, the 2 regimens appeared equally safe and effective but prospective studies are needed to confirm these results.

Cardiotoxicity following different doses and schedules of 5-fluorouracil administration for malignancy -- a survey of 427 patients.

BACKGROUND: Although cardiotoxicity associated with 5-Fluorouracil (5-FU) administration is infrequent, there are case reports of acute coronary syndromes. We report on patients undergoing 5-FU chemotherapy who developed cardiac symptoms during its administration. MATERIAL/METHODS: In patients receiving 5-FU who experienced cardiac-related symptoms, ECG and serum cardiac enzyme determination were performed. If cardiotoxicity was detected, 5-FU infusion was interrupted, and the patients received sublingual nitrates and cardiac monitoring, while patients with more than 2-fold elevated enzyme levels were monitored in a coronary care unit for at least 72 hours. In cases of acute myocardial infarction, 5-FU was terminated. RESULTS: Of 427 patients entering the study, 17 (4%) developed clinical symptoms and ECG abnormalities indicating 5-FU cardiotoxicity. Patients with continuous infusion (c.i.) of 5-FU had a higher incidence of cardiotoxicity (12/197, 6%) than the remaining (5/235, 2.1%) (p=0.067), but more toxicity was encountered in patients with c.i. of 5-FU+LV for 24 hours for 5 days than in patients with the same regimen of 5-FU without LV (p<0.027) or patients with short 5-FU+LV administration (p=0.024). Seven of the 17 patients with 5-FU cardiotoxicity had an acute myocardial infarction, 4 developed ischemic changes, while 4 more patients had ECG abnormalities consistent with coronary vasospasm, of whom one subsequently died. CONCLUSIONS: The present study supports the toxic effect of 5-FU on myocardium, which is largely schedule-dependent. Considerable vigilance is required when using this drug, and its toxic effect on the coronary endothelium and myocardium merit further investigation.

Etoposide added to weekly leucovorin (LV)/5-fluorouracil (5-FU) in LV/5-FU pre-treated patients with advanced colorectal cancer.

BACKGROUND: We evaluated the efficacy and safety of the weekly combination of etoposide, leucovorin (LV) and 5-fluorouracil (5-FU) when administered as second-line chemotherapy in patients with relapsed/refractory advanced colorectal cancer (ACC), previously treated with weekly LV + 5-FU. MATERIAL/METHODS: Etoposide was administered at 3 different dose levels (DL), in 3 groups of patients (total=60): DL-I - etoposide 80 mg/m2, 45 min i.v. infusion, DL-II - etoposide 120 mg/m2, and DL-III - etoposide 180 mg/m2. In all three levels etoposide was followed by LV 100 mg/m2 i.v., 1-hour infusion, and 5-FU 500 mg/m2 i.v. bolus. Treatment was administered until disease progression or unacceptable toxicity. RESULTS: No patients responded at DL-I, while 2 patients at DL-II and 3 at DL-III had a partial response (PR) (P<0.1). Two patients had stable disease (SD) at DL-I, 8 at DL-II, and 9 at DL-III (P<0.01). More patients progressed at DL-I (n=19) compared to DL-II (n=10) and DL-III (n=8) (p<0.0007). The time to progression was 17, 15, and 14 weeks, respectively, for DL-I, -II, and -III (P=0.9). Median survival was 30, 30, and 32.5 weeks, respectively, for DL-I, -II, and -III (P= 0.27). Toxicity was mainly neutropenia, diarrhea and mucositis at all DLs, significantly more intense in DL-III. No difference was noticed in responses between DL-II and DL-III, but toxicity in DL-III was more severe. CONCLUSIONS: The combination of etoposide with LV+5-FU has limited activity when administered after failure of weekly LV+5-FU in patients with ACC.

A phase I-II study of docetaxel-ifosfamide-cisplatin (DIP) combination chemotherapy regimen in advanced nonsmall cell lung cancer.

In an attempt to develop more effective chemotherapy regimens in advanced nonsmall cell lung cancer (NSCLC), we evaluated docetaxel-ifosfamide-cisplatin (DIP) based on our previous experience with paclitaxel-ifosfamide-cisplatin. Patients with advanced NSCLC (stages III-IV), WHO-PS< or =2, no prior chemotherapy and unimpaired hematopoietic and organ function were eligible. Chemotherapy was administered in successive dose levels (DLs) and included docetaxel (80-100 mg/m2 day 1), ifosfamide (4-5 g/m2) and cisplatin (80-100 mg/m2), both divided over days 1 and 2 every 21 days. G-CSF (lenograstin) was administered from days 4-13. Fifty-five patients were accrued (phase I: 15; phase II: 40) and all are evaluable for response and toxicity: median age = 58 (40-72); PS = 1 (0-2); gender = 48 males, 7 females; stages IIIA = 8, IIIB = 19, IV = 28; and histologies were adenocarcinoma (29), squamous (20), large cell (6). Metastatic sites at diagnosis included lymph nodes (33), bone (8), liver (6), brain (6), lung nodules (9), adrenals (7) and soft tissue (1). The dose-limiting toxicity (DLT) was reached at DL4 (Docetaxel: 100 mg/m2-Ifosfamide: 5 g/m2-Cisplatin: 100 mg/m2) consisting of 2 cases of febrile neutropenia (FN), and DL3 (Docetaxel: 100 mg/m2-Ifosfamide: 5 g/m2-Cisplatin: 80 mg/m2) was considered as the maximum tolerated dose (MTD) and recommended for further phase II testing. Among evaluable patients in phase II, 31/46 (67%; CI = 54-81%) responded; 4 were complete responses, 27 partial responses, 12 with stable disease and 3 with progressive disease. The median response duration was 7 months (2-21+), median time to progression (TTP) 8 months (1-23+) and median overall survival (OS) 13 months (2-23+). The 1-year survival was 57%. Grade (Gr) 3/4 toxicities included neutropenia 39/46 with 27 developing Gr4 (< or =7 days) and 20% FN managed successfully with broad-spectrum antibiotics, thrombocytopenia Gr3 3/46-Gr4 1/46, no Gr3 neuropathy, Gr1-2 CNS toxicity in 12, no renal toxicity, 15 Gr2 myalgias, 17 Gr2 diarrhea and 10 Gr3 vomiting. In the present phase I-II study, DIP appears highly active and tolerable in advanced NSCLC in the outpatient setting. Randomized comparisons to current standard 2-drug regimens will be warranted.