SUIHTER: a new mathematical model for COVID-19. Application to the analysis of the second epidemic outbreak in Italy.

The COVID-19 epidemic is the latest in a long list of pandemics that have affected humankind in the last century. In this paper, we propose a novel mathematical epidemiological model named SUIHTER from the names of the seven compartments that it comprises: susceptible uninfected individuals (S), undetected (both asymptomatic and symptomatic) infected (U), isolated infected (I), hospitalized (H), threatened (T), extinct (E) and recovered (R). A suitable parameter calibration that is based on the combined use of the least-squares method and the Markov chain Monte Carlo method is proposed with the aim of reproducing the past history of the epidemic in Italy, which surfaced in late February and is still ongoing to date, and of validating SUIHTER in terms of its predicting capabilities. A distinctive feature of the new model is that it allows a one-to-one calibration strategy between the model compartments and the data that are made available daily by the Italian Civil Protection Department. The new model is then applied to the analysis of the Italian epidemic with emphasis on the second outbreak, which emerged in autumn 2020. In particular, we show that the epidemiological model SUIHTER can be suitably used in a predictive manner to perform scenario analysis at a national level.

AT-101 simultaneously triggers apoptosis and a cytoprotective type of autophagy irrespective of expression levels and the subcellular localization of Bcl-xL and Bcl-2 in MCF7 cells.

The effects of autophagy on cell death are highly contextual and either beneficial or deleterious. One prime example for this dual function of autophagy is evidenced by the cell responses to the BH3 mimetic AT-101 that is known to induce either apoptotic or autophagy-dependent cell death in different settings. Based on previous reports, we hypothesized that the expression levels of pro-survival Bcl-2 family members may be key determinants for the respective death mode induced by AT-101. Here we investigated the role of autophagy in the response of MCF7 breast cancer cells to AT-101. AT-101 treatment induced a prominent conversion of LC3-I to LC3-II and apoptotic cell death characterized by the appearance of Annexin-positive/PI-negative early apoptotic cells and PARP cleavage. Inhibition of the autophagy pathway, either through application of 3-MA or by lentiviral knockdown of ATG5, strongly potentiated cell death, indicating a pro-survival function of autophagy. Overexpression of wild type Bcl-xL significantly diminished the net amount of AT-101-induced cell death, but failed to alter the death-enhancing effects of the ATG5 knockdown. This was also observed with the organelle-specific variants Bcl-xL-ActA and Bcl-2-ActA (mitochondrial) as well as Bcl-xL-cb5 and Bcl-2-cb5 (ER) which all reduced AT-101-induced cell death, but did not affect the death-enhancing effects of 3-MA. Collectively, our data indicate that in apoptosis-proficient MCF7 cells, AT-101 triggers Bcl-2- and Bcl-xL-dependent apoptosis and a cytoprotective autophagy response that is independent of the expression and subcellular localization of Bcl-xL and Bcl-2.

Lumbar spine surgery in patients 80 years of age or older: morbidity and mortality.

INTRODUCTION: The life expectancy increased significantly during last four decades and is associated with an increasing quality of life. The purpose of this study was to determine morbidity and mortality of degenerative lumbar spine surgery in patients 80 years of age or older. METHODS: A consecutive retrospective review evaluated 121 consecutive patients, who had undergone posterior decompression associated or not with lumbar instrumentation. The average age at the time of surgery was 83.2 ± 2.4 years. The study analyzed the comorbidities, the operative procedure and postoperative morbidity and mortality. RESULTS: Blood loss increased significantly with instrumentation (538 vs. 280 mL, p < 0.0001). The average operative time was 103 ± 38 min and increased significantly with instrumentation (131.2 vs. 84 min, p = 0.003), blood loss (p < 0.0001) and dural tears (p = 0.05). Dural tears occurred in 19 patients (15.7%) and were associated significantly with previous lumbar surgery (33.3 vs. 12.4%, p = 0.017) and major complications (30 vs. 9.9%, p = 0.01). Major complications occurred in 16 patients (13%). Minor complications occurred in 36 patients (29.7%). The delirium was associated with instrumentation (22 vs. 7%, p = 0.017) and blood loss (520 vs. 348 mL, p = 0.034). The average hospital stay was 11.3 ± 8.1 days. No patients died after a postoperative period of 1 year. The average follow-up was 24.3 ± 16.5 months. CONCLUSIONS: The morbidity of degenerative lumbar spine surgery in patients 80 years of age or older was high. Blood loss, operative time, instrumentation, previous surgery and dural tears increased significantly the morbidity. This surgery must be decided very carefully and requires to inform the patient and his family of the high rate of complications.

[Impaction posterior wedge osteotomy for the treatment of postsurgical flatback: 22 cases]. / Ostéotomie de fermeture postérieure par impaction intracorporéale pour dos plat postopératoire: à propos d'une série de 22 cas.

PURPOSE OF THE STUDY: There is increasing interest in sagittal balance as an important element when planning treatment of spinal deformations. Posture disorders, particularly flatback, can be observed after surgical treatment of scoliosis. The frequency of flat back syndrome has increased with the development of spinal surgery. MATERIAL AND METHODS: Posterior osteotomy is designed to resolve these problems. Two techniques are used: the Smith-Petersen procedure and transpedicular subtraction osteotomy. We adopted the second procedure, adding two technical modifications: installation on an orthopaedic table and intracorporeal cancellous impaction. We performed closed posterior osteotomy by intracorporeal impaction and report here our results in a series of 22 patients with postoperative flat back treated between July 1999 and June 2002. Mean age at surgery was 52 years. There were sixteen women and six men. All patients had a history of spinal surgery with fusion. They had had 2.1 spinal operations on average with a maximum of seven. All patients complained of severe postural pain. They had difficulty bending forward and standing back up. Radiographically, we noted altered spinal and pelvic angles and an abnormal plumb line from C7 to the promontory. RESULTS: We analyzed outcome at 21 months on average. Preoperatively five patients had 12 levels of non-union. Osteotomy was performed at L4 in nineteen patients and L3 in three. A rigid instrumentation was used in all cases. Osteosynthesis material was implanted after correction of the deformation with no particular problem for spinal stability or reduction. Mean operative time was 180 minutes and mean blood loss was 1680 ml. A complementary anterior approach was required in one patient. Intraoperative complications were dominated by dural breaches in five patients, high paraplegia not directly related to the osteotomy in one patient, regressive S1 paresia occurred in one patient and transient cruralgia which regressed in 4 to 6 months in four patients. We also observed functional intestinal obstruction in one patient and severe depression in another. There were no infections or deaths. We also observed two cases of predominant correction at the discal level and not the vertebral level. All operated patients felt their posture was improved and were able to maintain the upright position for prolonged periods. Flexion of the lower limbs was improved. Mean correction of lumbar lordosis was 25.1 degrees (range 12-39). Mean sacral slope was 33 degrees . Mean correction of the position of C7 on the promontory plumb line was 72 mm. This variable was highly altered preoperatively (95.6 mm) and was improved after osteotomy in all patients. At last follow-up, there was one case of nonunion which had been successfully revised. DISCUSSION: The literature on osteotomy for the treatment of flat back is sparse. Our series of subtraction osteotomy is the largest reported to date. Preoperative and intraoperative planning remain a topic of debate and require further study.

Posterior cervicothoracic instrumentation in spine tumors.

STUDY DESIGN: We retrospectively review 32 patients who underwent posterior fixation for cervicothoracic junctional tumors. All patients possessed unstable or potential after surgery unstable spines as a result of either their tumors or the surgery performed. We examined cervicothoracic spine stability, maintenance of alignment, and associated complications. OBJECTIVES: To review our experience with 3 different posterior osteosynthesis systems applied to the cervico-thoracic junction for spinal tumors. Our review includes surgical outcomes and complications. The evolution through 3 different systems between 1994 and 1997 reflects our attempts to improve accuracy in light of variable facet and pedicle interspaces. Our goal is not to compare the efficacy of the systems but to assess the efficiency of cervicothoracic facet and transpedicular screw and plate or rod fixation. However, we will comment on why the evolution occurred. The 3 different systems share a similar characteristic. Each system employs posterior cervical facet screw fixation and thoracic trans-pedicular screw fixation. SUMMARY OF BACKGROUND DATA: Spinal disorders involving the cervicothoracic junction and specific instrumentation to this region have been sparsely described in the literature. METHODS: Between June 1994 and June 2000, 32 patients underwent surgery for spinal tumors involving the cervicothoracic junction at our institution. There were 27 males and 5 females. The ages ranged from 17 to 72 years with a mean age of 52 years. A total of 32 cervicothoracic instrumentations were performed. We used the R. Roy-Camille thoracolumbar plate in 20 patients, the cervico-thoracic plate in 8, and the Agora rod system in 4. In all, 96 lateral mass screws were implanted from C4 to C6, 54 into C7, and 180 pedicle screws from T1 to T8. Nineteen patients had lung cancer with vertebral body invasion (Pancoast tumors), 11 had metastasis to the cervicothoracic junction, 1 had a chondrosarcoma, and 1 had myeloma. In a first group consisting of 19 patients, a combination of anterior and extended posterior surgical approaches allowed complete en bloc resection of the tumors, including all invaded vertebrae. Four total vertebrectomies and 15 partial vertebrectomies were performed. A second group of 13 patients had only posterior palliative stabilizing procedures with laminectomy and cervicothoracic fixation. RESULTS: The follow-up period varied from 3 to 54 months, average 15 months. The average duration of survival for patients who underwent partial or total vertebrectomy was 16 months (range 3-54 months). The average duration of survival for patients who underwent palliative decompression and stabilization was 11 months (range 5-19 months). No changes in the sagittal alignment occurred during the immediate postoperative period for 30 patients. However, 2 mechanical failures occurred. Two patients experienced a clinically significant early increase in thoracic kyphosis and required revision of the posterior instrumentation. A 21-month minimum follow-up was available for 6 patients, in whom all implants were stable. We noted no screw, plate, or rod breakage in this series. No neurologic complications, including root impingement or spinal cord injury, or vertebral artery injury occurred related to screw insertion into either the thoracic pedicles (180 screws) or the cervical lateral masses (96 screws in C4-C5-C6 and 54 screws in C7). CONCLUSIONS: Posterior plate or rod and screw fixation is a good method of treatment for cervicothoracic instability in spine tumors. Facet screw fixation in the cervical spine with Roy-Camille drilling technique and transpedicular screw fixation in the thoracic spine provides an efficacious means by which to stabilize the cervicothoracic junction. This stabilization technique was effective even in cases of high postoperative instability, such as with partial or total vertebrectomy. This screw-type stabilization is clinically effective and well documented. The evolution through 3 different systems reflects our attempts to improve accuracy in light of variable facet and pedicle interspaces. Importantly, posterior instrumentation will not interfere with subsequent laminectomy or more extreme surgical procedures.

[Systematic circumferential (360 degree) decompression treatment of major arthrotic cervical stenosis]. / Abord circonférenciel (360 degrees) systématique dans le traitement des sténoses cervicales arthrosiques majeures.

PURPOSE OF THE STUDY: Worsening and irreducible evolution of neural involvement in cervical stenosis requires cord decompression. Different techniques have been proposed. We associated a dual posterior then anterior approach to achieve 360 degrees decompression. We evaluated results on the basis of neurological and mechanical outcome. MATERIAL AND METHODS: Twenty-eight patients, 16 men and 12 women, mean age 60.2 years (range 40-82) underwent surgery between 1989 and 1999 for severe cervical canal stenosis. Patients were referred for neurological symptoms: 20 for radicular symptoms (8 pain, 11 motor deficit, 12 sensitive deficit). Fifteen patients presented myelopathic symptoms. Pyramidal syndrome in 11 and tetraparesia in 3. Neurological involvement was scored according to Nurick (average 1.74) and JOA (average 12.6). Pain was scored on the Robinson scale. Levels to decompress were identified on static and dynamic plain x-rays, CT scans and MRI. Myelography was rarely used (first case only). MRI demonstrated preoperative myelomalacia in 5 patients and syringomyelia in 2. The surgical technique for 360 degrees fusion involved two steps, performed with a 1-week interval for 12 patients and during the same procedure for the others. The first approach was posterior enabling spine fixation with bilateral Roy-Camille plates and decompression by laminectomy using the lobster shell technique. The anterior approach consisted in corpectomy with the Simmons technique (22 cases or multilevel interbody fusion according to Robinson. Iliac bone grafting was used in all but one patient who had a fibular bone graft. Mean follow-up was 18.5 months (6-78). RESULTS: Neurological improvement was 1.74 to 0.92 on the Nurick sclae and from 12.6 to 15.2 on the JOA scale at last follow-up. Fusion was obtained in all cases. There were 2 cases of neurological worsening and one transient dysphagia. Operative bleeding for the two steps was 700 ml (150 ml for the posterior procedure and 400 ml for the anterior procedure). CONCLUSION: 360 degrees arthrodesis for severe cervical canal stenosis provides a satisfactory solution to mechanical problems and substantial neurological improvement. Fusion is regularly obtained without complementary anterior instrumentation. Neurological improvement is correlated with disease duration and the degree of deficit at onset. Anteroposterior decompression and 360 degrees fusion provide cure for all the components of stenotic disease. The dual approach is indicated in severe cases with cord involvement as recognized by myleopathic clinical manifestations and on the MRI.

[Congenital hypoplasia of lumbosacral articular process: report of a case, review of the literature, and therapeutic proposition]. / Hypoplasie congénitale d'un massif articulaire lombosacré: rapport d'un cas, revue de la littérature et proposition thérapeutique.

Congenital hypoplasia of the lumbosacral process is an uncommon cause of recurrent lumbalgia. The 37 cases reported in the literature illustrate the complexity of the pathological implications of these anomalies. We report another case and our diagnostic methodology. We propose lumbosacral arthrodesis which provided complete relief in our patient. This satisfactory outcome has been maintained at one year.

Arthrodesis of lumbar spine transverse processes using nacre in rabbit.

This study compares the osteogenic effects of nacre and autogenous bone grafts in a rabbit model of lumbar spine transverse process arthrodesis. A total of 15 rabbits were processed for arthrodesis between the fifth and sixth lumbar vertebrae using nacre powder mixed with autologous blood or autogenous iliac crest bone. Control rabbits were sham operated. Sample vertebrae were removed from the nacre-implanted rabbits at 2, 5, and 11 weeks postsurgery. The autogenous bone graft and sham-operated groups were processed for histological study 11 weeks postsurgery. The results for the three groups were compared at 11 weeks. The nacre-implanted samples taken at 2 weeks showed that the nacre was well tolerated by the host tissue. Endochondral bone formation was seen in the region of the dissolving nacre particles by 5 weeks. The newly formed bone formed a solid fusion between the transverse processes in one-third of the rabbits. There was still new bone formation at 11 weeks at the nacre implant site. Two-thirds of the rabbits had formed a solid fusion. Light microscopy also showed new bone formation 11 weeks after the autologous bone graft. All rabbits had a solid fusion. This initial study indicates that nacre can induce spinal fusion in an acceptable percentage of cases.