Intricate isavuconazole therapy of a subcutaneous nodule caused by Alternaria infectoria in a heart transplant recipient

Invasive fungal infections have appeared to be increasingly emergent in immunocompromised patients, especially in solid organ transplant (SOT) recipients. The Alternaria genus encompasses more than 80 dematiaceus species. Among them, Alternaria alternata and Alternaria infectoria are the most frequent isolated as responsible for infection in humans.To our knowledge, we report the first case of a heart transplant recipient suffering from subcutaneous nodule caused by Alternaria infectoria and who was treated with isavuconazole. Despite all the promises of this new azole drug, one should keep in mind the potential great variability of the inter-individual responses for such complex patients. We demonstrate herein how it can be challenging to manage Alternaria infection in SOT recipients. More comprehensive studies and recommendations are expected in the context of Alternaria infections.     

Diagnosis of hepatic fibrosis and cirrhosis by transient elastography in HIV/hepatitis C virus-coinfected patients

BACKGROUND: Chronic hepatitis C in HIV-infected patients is an increasing cause of death dependent on the development of liver fibrosis, which is currently assessed by liver biopsy despite its limitations. Liver stiffness measurement, a new noninvasive method, allows the evaluation of liver fibrosis. The aim of this prospective study was to assess the accuracy of liver stiffness measurement for the detection of fibrosis and cirrhosis in HIV/hepatitis C virus (HCV)-coinfected patients and to compare its accuracy with other noninvasive methods. METHODS: We studied 72 consecutive HIV patients with chronic hepatitis C who had a simultaneous liver biopsy and liver stiffness measurement by transient elastography (FibroScan; Echosens, Paris, France) for the assessment of liver fibrosis. RESULTS: Liver stiffness values ranged from 3.0 to 46.4 kilopascal. Liver stiffness was significantly correlated to fibrosis stage (Kendall tau-b = 0.48; P < 0.0001). The area under the receiver operating characteristic (AUROC) curve of liver stiffness measurement was 0.72 for F > or = 2 and 0.97 for F = 4. For the diagnosis of cirrhosis, AUROC curves of liver stiffness measurement were significantly higher than those for platelet count (P = 0.02), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (P = 0.0001), Aspartate aminotransferase-to-Platelet Ratio Index (APRI) (P = 0.01), and FIB-4 (P = 0.004). CONCLUSION: Liver stiffness measurement is a promising noninvasive method for the assessment of fibrosis in HIV-infected patients with chronic HCV infection. Its use for the follow-up of these patients should be further evaluated.     

Glucocorticoid receptor-dependent desensitization of 5-HT1A autoreceptors by sleep deprivation: studies in GR-i transgenic mice

Sleep deprivation for one night induces mood improvement in depressed patients, an action that probably involves the serotonergic (5-HT) system. In animals, sleep deprivation and pharmacologic treatment with antidepressants exert similar effects on 5-HT neurotransmission, notably functional desensitization of 5-HT1A autoreceptors located on 5-HT neurons in the dorsal raphe nucleus (DRN). However, in stressful conditions, corticosterone can also induce a desensitization of these autoreceptors. STUDY OBJECTIVES: To investigate the mechanisms of this adaptation during sleep deprivation and the possible involvement of corticosterone, we studied the effects of an 18-hour sleep deprivation, by forced locomotion, on 5-HT1A receptor-mediated firing response of DRN 5-HT neurons in transgenic mice with impaired glucocorticoid-receptor expression (GR-i) and in wild-type animals. We also examined the effects of chronic treatment with the antidepressant drug fluoxetine in the same paradigm. MEASUREMENTS AND RESULTS: In both wild-type and GR-i mice, the 18-hour sleep deprivation or fluoxetine treatment had no effect on the spontaneous firing of 5-HT neurons recorded under anesthesia. However, sleep deprivation decreased the potency of the 5-HT1A agonist 8-OH-DPAT to inhibit 5-HT neuronal firing in wild-type mice, whereas it had no effect in GR-i animals. Conversely, after chronic fluoxetine treatment, the induced reduction of this 5-HT1A autoreceptor-driven response was of larger amplitude in GR-i than in wild-type mice. CONCLUSIONS: These data suggest that glucocorticoid-receptor activation by corticosterone participates in the antidepressant-like adaptive changes in 5-HT1A autoreceptors in sleep-deprived mice. On the other hand, GR-i animals exhibited enhanced 5-HT1A autoreceptor desensitization induced by fluoxetine, in line with data in other animal models of depression.     

Pain perception in schizophrenia: no changes in diffuse noxious inhibitory controls (DNIC) but a lack of pain sensitization

BACKGROUND: Pain is a dynamic phenomenon resulting from the activity of both excitatory (e.g. sensitization) and inhibitory endogenous modulation systems. Preliminary experimental studies have shown diminished pain sensitivity in schizophrenia patients. The objective of the study was to investigate the role of excitatory and inhibitory systems on pain perception in schizophrenia. METHODS: Participants were 23 patients with a schizophrenia-spectrum disorder (DSM-IV criteria) and 29 healthy volunteers, who did not differ in age, sex or ethnicity. Excitatory and inhibitory systems were elicited using a temporal summation test (Peltier thermode) administered before and after activation of the diffuse noxious inhibitory control (DNIC) by means of a cold-pressor test. RESULTS: Time was a significant predictor of pain scores in controls, but not in patients. That is, pain ratings increased during the tonic thermal stimulation among controls but not in schizophrenia patients. When correlation coefficients (between time and pain ratings) for patients and controls were compared, the correlation coefficient emerged as significantly weaker in the schizophrenia group (Z=12.04; p=0.0001), suggesting a lack of sensitization in schizophrenia. DNIC was similar in magnitude in both patients and controls. CONCLUSIONS: Diminished pain sensitivity in schizophrenia may be related to abnormal excitatory mechanisms, but not to DNIC. More studies are needed to better characterize the neurophysiological and neurochemical mechanisms involved in the lack of sensitization in schizophrenia.     

The role of the O-antigen lipopolysaccharide on the colonization in vivo of the germfree chicken gut by Klebsiella pneumoniae

We isolated lipopolysaccharide and capsular polysaccharide (K antigen)-defective mutants from two Klebsiella pneumoniae parental strains, and compared their ability to colonize in vivo the germfree chicken gut. The high-molecular weight lipopolysaccharide (LPS) (O antigen) was found necessary for the colonization while the capsular polysaccharide (K2 or K29) was not of importance.     

Radiation-induced skin fibrosis after treatment of breast cancer: profilometric analysis

Background/aim: Treatment of breast cancer involves an association of conservative surgery and radiotherapy. This implies various cutaneous complications, well known for their clinical and histological aspects. Little data are available concerning modifications of the cutaneous microrelief after radiotherapy. We have done a profilometric analysis of the skin of breast cancer patients treated with surgery and radiotherapy. The results obtained on the irradiated breast have been compared with the ones of the controlateral normal breast. Methods: Twenty women, 43–55 year old were enrolled in the study 6–16 months after the end of a treatment associating conservative surgery and radiotherapy for breast cancer. Imprints using a silicone rubber material were performed over symmetrical areas of the treated breast and the controlateral one. All measures were performed over the upper‐medial quadrant of each breast. The imprints are then blindly analysed using an image analyser. The following parameters were measured: RA (average roughness of the skin), RZ (average of the furrows depth), RS (residual length), Rn (number of furrows) and AR (space between the furrows). Results: The comparison of the imprints shows important modifications of the microrelief after irradiation. We observe a slight increase of the skin roughness (RA: 26, 39 ± 2, 58 versus 21, 84 ± 1, 59), a significantly increase of the furrows depth (RZ: 121, 66 ± 10, 46 versus 101, 26 ± 6, 99) along with an increase of the residual length (RS: 580, 60 ± 60, 60 versus 450, 46 ± 48, 43). The number of furrows has not significantly decreased but the space between the furrows has increased on the irradiated breast. Conclusion: This study shows a breakdown effect of irradiation on the skin in correlation with the fibrosis inducing by ionising radiation. The imprints modifications are clearly different from those usually observed in the ageing process. Our results can be a basis for studying the effects of treatments on cutaneous complications linked to the radiation‐induced fibrosis.     

Efficacy of anti-interleukin-1 receptor antagonist anakinra (Kineret®) in a case of refractory Sweet's syndrome

Sweet's syndrome is a neutrophilic dermatosis characterized by fever, an elevated neutrophil count, and painful erythematous cutaneous lesions. Histopathological analysis reveals a neutrophilic dermal infiltrate. Systemic corticosteroid therapy remains the mainstay of treatment. We report the case of a 66-year-old male patient who had a 5-year history of Sweet's syndrome refractory to various conventional treatments. Anti-interleukin-1 receptor antagonist anakinra was initiated and this resulted in a dramatic clinical and biological improvement. Anakinra is a promising treatment for neutrophilic dermatoses and sheds light on the interleukin-1/inflammasome pathway as central in the physiopathology of neutrophilic dermatosis.     

Evidence-based surgery in chronic pancreatitis

BACKGROUND: In the past two decades our knowledge of the pathophysiology and surgical treatment options in chronic pancreatitis has improved substantially. Surgical treatment in chronic pancreatitis has evolved from extending to organ-preserving procedures. DISCUSSION: The classical Whipple resection is no longer a standard procedure in chronic pancreatitis, and is continuously being replaced by operations such as the duodenum-preserving pancreatic head resection and pylorus-preserving Whipple. These procedures allow the preservation of exocrine and endocrine pancreatic function, provides pain relief in up to 90% of patients, and contributes to an improvement in life quality. CONCLUSIONS: In addition to presently available results from randomized controlled trials, new studies comparing available surgical approaches in chronic pancreatitis are needed to determine which procedure is the most effective in the treating chronic pancreatitis.     

Tibial lengthening using a retrograde magnetically driven intramedullary lengthening device in 10 patients with preexisting ankle and hindfoot fusion

Background and purpose — Motorized intramedullary lengthening nails (ILNs) have been developed as an alternative to external fixators for long bone lengthening. The antegrade approach represents the standard method for tibial ILN insertion. In patients with preexisting ankle and hindfoot fusion a retrograde approach provides an alternative technique that has not been evaluated so far. We report the outcome of this method in 10 patients.Patients and methods — This retrospective study included 10 patients (mean age 18 years [13–25]) with preexisting ankle and hindfoot fusion who underwent tibial lengthening with a retrograde ILN (PRECICE). The mean leg length discrepancy (LLD) was 58 mm (36–80). The underlying conditions were congenital (n = 9) and post tumor resection (n = 1). The main outcome measures were: ILN reliability, distraction achieved, distraction index (DIX), time to bone healing, consolidation index (CIX), complications, and functional results.Results — All patients achieved the goal of lengthening (mean 48 mm [26–80]). Average DIX was 0.6 mm/day (0.5–0.7) and mean CIX was 44 days/cm (26–60). Delayed consolidation occurred in 2 patients and healed after ILN dynamization or nail exchange with grafting. Toe contractures in 2 other patients were resolved with physiotherapy or tenotomy. Until last follow-up (mean 18 months [12–30]) no true complications were encountered, knee motion remained unaffected, and full osseous consolidation occurred in all patients.Interpretation — In patients with LLD and preexisting ankle and hindfoot fusion distal tibial lengthening using a retrograde ILN is a reliable alternative to the standard approach with equivalent bone healing potential and low complication rates leaving the knee unaffected.

Fully implantable intramedullary lengthening nails (ILNs) with mechanical (Guichet and Casar 1997, Cole et al. 2001) and motorized (Baumgart et al. 1997, Schiedel et al. 2014) drive systems have been developed as an alternative to external fixators for bone lengthening (Mahboubian et al. 2012, Black et al. 2015, Laubscher et al. 2016). Recently, magnetically driven ILNs in particular have become increasingly popular (Kirane et al. 2014, Wagner et al. 2017) and in contrast to external fixation provide an equally safe and more comfortable option for limb lengthening and deformity correction (Szymczuk et al. 2019, Horn et al. 2019). Antegrade or retrograde femoral and antegrade tibial lengthening with the PRECICE limb lengthening system (NuVasive, San Diego, CA, USA) has been assessed by several studies (Kirane et al. 2014, Schiedel et al. 2014, Shabtai et al. 2014, Tiefenboeck et al. 2016, Wiebking et al. 2016, Fragomen and Rozbruch 2017, Wagner et al. 2017, Iobst et al. 2018, Cosic and Edwards 2020, Nasto et al. 2020).In tibial lengthening the antegrade approach represents the standard method for ILN implantation (Fragomen and Rozbruch 2017). In patients with preexisting ankle and hindfoot fusion a retrograde approach provides an alternative technique for tibial nail insertion. Approach-associated affections of the knee joint like anterior knee pain (Rothberg et al. 2019) and—in immature patients—damage to the proximal tibial growth plate (Wagner et al. 2017, Frommer et al. 2018) can be avoided. Despite these potential advantages, the use of a retrograde tibial nailing approach and distal tibial osteotomy in patients with preexisting ankle and hindfoot fusion has not been evaluated so far.     

The Cost Effectiveness of Three Different Measures of Breast Volume

Background Several methods including water displacement, casting, the Grossman–Roudner measuring device, photographs, mammograms, ultrasound, and magnetic resonance imaging (MRI) have been proposed for the measurement of breast volume. The most cost-effective method has not been determined. Methods This study compared breast volume measurements using the Grossman–Roudner measuring device (a piece of circular plastic with a cut along a radius line), plaster casting, and MRI. The Grossman–Roudner measuring device was formed into a cone around the breast, and the volume was read from a graduated scale on the overlapping edges. The volume of the cast was measured using a butter–sand mixture and water displacement. The volume from the MRI slices was calculated using the ANALYZE bioimaging software. For five women with breast sizes AA, A, B, C, and D, the three volume measures were repeated three times. For a single volume measurement, the cost of the time and materials was $1 for the Grossman–Roudner cone, $20 for the cast, and $1,400 for the MRI. Using the mean and standard deviations of the measurements, a power analysis determined the number of subjects needed to detect a 5% change in volume. The number of subjects was multiplied by the price per test to determine relative cost. Results As compared with the cost for the Grossman–Roudner cone method, the cost for the volume measurements was 64 to 189 times more using the cast and 373 to 33,500 more using MRI. Conclusions The Grossman–Roudner cone was clearly the most cost-effective method for determining breast volume changes in studies testing topical therapies to alter breast size.