Repeat-associated non-AUG translation induces cytoplasmic aggregation of CAG repeat-containing RNAs.

CAG trinucleotide repeat expansions cause several neurodegenerative diseases, including Huntington's disease and spinocerebellar ataxia. RNAs with expanded CAG repeats contribute to disease in two unusual ways. First, these repeat-containing RNAs may agglomerate in the nucleus as foci that sequester several RNA-binding proteins. Second, these RNAs may undergo aberrant repeat-associated non-AUG (RAN) translation in multiple frames and produce aggregation-prone proteins. The relationship between RAN translation and RNA foci, and their relative contributions to cellular dysfunction, are unclear. Here, we show that CAG repeat-containing RNAs that undergo RAN translation first accumulate at nuclear foci and, over time, are exported to the cytoplasm. In the cytoplasm, these RNAs are initially dispersed but, upon RAN translation, aggregate with the RAN translation products. These RNA-RAN protein agglomerates sequester various RNA-binding proteins and are associated with the disruption of nucleocytoplasmic transport and cell death. In contrast, RNA accumulation at nuclear foci alone does not produce discernable defects in nucleocytoplasmic transport or cell viability. Inhibition of RAN translation prevents cytoplasmic RNA aggregation and alleviates cell toxicity. Our findings demonstrate that RAN translation-induced RNA-protein aggregation correlates with the key pathological hallmarks observed in disease and suggest that cytoplasmic RNA aggregation may be an underappreciated phenomenon in CAG trinucleotide repeat expansion disorders.

Novel Surface Topographic Assessment of Lung Volume and Pulmonary Function Tests in Idiopathic Scoliosis: A Preliminary Study.

OBJECTIVE: Severe spinal deformity results in restrictive pulmonary disease from thoracic distortions and lung-volume limitations. Though spirometry and body plethysmography are widely accepted tests for pulmonary function tests (PFTs), they are time-consuming and require patient compliance. This study investigates whether surface topographic [surface topography (ST)] measurements of body volume difference (BVD) and torso volume difference between maximum inhale and exhale correlate to values determined on PFTs. METHODS: This study included patients with idiopathic scoliosis and thoracic/thoracolumbar curves ≥40 degrees. Patients received ST scans, clinical examinations, and EOS biplanar radiographs on the same day. PFTs were performed within 3 months of ST/radiographic analysis. Univariate linear regression analysis was used to examine relationships between BVD, PFT values, and mean curves. RESULTS: Sixteen patients (14.6 ± 2.2 y, 69% females) with idiopathic scoliosis and mean thoracic/thoracolumbar curves of 62 degrees ± 15˚ degrees (45 degrees to 93 degrees) were assessed. BVD displayed statistically high-positive positive correlations with forced vital capacity ( R = 0.863, P < 0.0001), forced expiratory volume in 1 second ( R = 0.870, P < 0.001), vital capacity ( R = 0.802, P < 0.0001), and TLC ( R = 0.831, P < 0.0001. Torso volume difference showed similarly high positive correlations to forced vital capacity, forced expiratory volume in 1 second, vital capacity, and TLC, but not residual volume. No correlations emerged between the mean thoracic/thoracolumbar curve and BVD or PFT values. CONCLUSION: This study strongly endorses further investigation into ST scanning as an alternative to traditional PFTs for assessing pulmonary volumes. The noncontact and noninvasive nature of ST scanning presents a valuable alternative method for analyzing thoracic volume, particularly beneficial for patients unable to cooperate with standard PFTs. LEVEL OF EVIDENCE: Level II-prognostic.

Exploring Correlations Between Pain and Deformity in Idiopathic Scoliosis With Validated Self-reported Pain Scores, Radiographic Measurements, and Trunk Surface Topographic Measurements.

BACKGROUND: Up to 75% of patients with idiopathic scoliosis (IS) report back pain, but the exact contributors are unclear. This study seeks to assess how pain correlates with demographics, radiographic and surface topographic (ST) measurements, and patient-reported outcome measures (PROMs) in patients with IS. METHODS: Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference (PI) and Scoliosis Research Society revised (SRS-22r) pain domain from an IRB approved prospectively collected registry containing patients 11 to 21 years old with IS were correlated (Spearman coefficients) with measurements from whole-body EOS radiography and ST scanning, PROMIS 1.0 PROMs, Trunk Appearance Perception Scale (TAPS), and SRS-22r domains. SRS-22r and PROMIS-PI were also compared between different sex, scoliosis severities, and primary curve locations with Mann-Whitney U or Kruskal-Wallis tests, and if significant differences were found, included with the 5 highest univariate correlated variables into stepwise multivariate linear regression models ( P <0.05 to enter, P >0.1 to remove) predicting SRS-22r pain and PROMIS-PI. RESULTS: One hundred and forty-nine patients (14.5 ± 2.0 y, body mass index 20.6 ± 4.1 kg/m 2 , 96 (64%) female, mean major coronal curve 40 ± 19 deg, range: 10 deg, 83 deg) reported mean PROMIS-PI of 42.2 ± 10.0 and SRS-22r pain of 4.4 ± 0.6. SRS-22r self-image was the most correlated variable with both SRS-22r pain (rho=0.519) and PROMIS-PI (rho=-0.594). Five variables, none of which were ST or radiographic measures, strongly predicted SRS pain domain (R=0.711, R2=0.505, N=138). Two variables (SRS-22r self-image and SRS-22r function) were utilized by a model correlated with PROMIS-PI (R=0.687, R2=0.463, N=124). CONCLUSIONS: SRS-22r function and self-image domains were more strongly correlated with SRS-22r pain and PROMIS-PI than any radiographic or ST measurements. LEVEL OF EVIDENCE: Level II-retrospective study.

α-Sheet secondary structure in amyloid ß-peptide drives aggregation and toxicity in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by the deposition of ß-sheet-rich, insoluble amyloid ß-peptide (Aß) plaques; however, plaque burden is not correlated with cognitive impairment in AD patients; instead, it is correlated with the presence of toxic soluble oligomers. Here, we show, by a variety of different techniques, that these Aß oligomers adopt a nonstandard secondary structure, termed "α-sheet." These oligomers form in the lag phase of aggregation, when Aß-associated cytotoxicity peaks, en route to forming nontoxic ß-sheet fibrils. De novo-designed α-sheet peptides specifically and tightly bind the toxic oligomers over monomeric and fibrillar forms of Aß, leading to inhibition of aggregation in vitro and neurotoxicity in neuroblastoma cells. Based on this specific binding, a soluble oligomer-binding assay (SOBA) was developed as an indirect probe of α-sheet content. Combined SOBA and toxicity experiments demonstrate a strong correlation between α-sheet content and toxicity. The designed α-sheet peptides are also active in vivo where they inhibit Aß-induced paralysis in a transgenic Aß Caenorhabditis elegans model and specifically target and clear soluble, toxic oligomers in a transgenic APPsw mouse model. The α-sheet hypothesis has profound implications for further understanding the mechanism behind AD pathogenesis.

Evaluating the serological status of COVID-19 patients using an indirect immunofluorescent assay, France.

An indirect in-house immunofluorescent assay was developed in order to assess the serological status of COVID-19 patients in Marseille, France. Performance of IFA was compared to a commercial ELISA IgG kit. We tested 888 RT-qPCR-confirmed COVID-19 patients (1302 serum samples) and 350 controls including 200 sera collected before the pandemic, 64 sera known to be associated with nonspecific serological interference, 36 sera from non-coronavirus pneumonia and 50 sera from patient with other common coronavirus to elicit false-positive serology. Incorporating an inactivated clinical SARS-CoV-2 isolate as the antigen, the specificity of the assay was measured as 100% for IgA titre ≥ 1:200, 98.6% for IgM titre ≥ 1:200 and 96.3% for IgG titre ≥ 1:100 after testing a series of negative controls. IFA presented substantial agreement (86%) with ELISA EUROIMMUN SARS-CoV-2 IgG kit (Cohen's Kappa = 0.61). The presence of antibodies was then measured at 3% before a 5-day evolution up to 47% after more than 15 days of evolution. We observed that the rates of seropositivity as well as the titre of specific antibodies were both significantly higher in patients with a poor clinical outcome than in patients with a favourable evolution. These data, which have to be integrated into the ongoing understanding of the immunological phase of the infection, suggest that detection anti-SARS-CoV-2 antibodies is useful as a marker associated with COVID-19 severity. The IFA assay reported here is useful for monitoring SARS-CoV-2 exposure at the individual and population levels.

Adherence to Pre-exposure Prophylaxis in Black Men Who Have Sex with Men and Transgender Women in a Community Setting in Harlem, NY.

While oral pre-exposure prophylaxis (PrEP) has proven efficacious for HIV prevention, consistent use is necessary to achieve its intended impact. We compared effectiveness of enhanced PrEP (enPrEP) adherence support to standard of care (sPrEP) among Black MSM and TGW attending a community clinic in Harlem, NY. EnPrEP included peer navigation, in-person/online support groups, and SMS messages. Self-reported adherence over previous 30 days, collected in quarterly interviews, was defined as ≥ 57%. Crude and adjusted analyses examined factors associated with adherence. A total of 204 participants were enrolled and randomized; 35% were lost to follow-up. PrEP adherence was 30% at 12-months; no intervention effect was observed (p = 0.69). Multivariable regression analysis found that lower adherence was associated with low education and depressive symptoms. We found that an enhanced adherence intervention did not improve PrEP adherence. Findings point to the need for innovative methods to improve PrEP adherence among Black MSM and TGW.Clinical Trial Registration NCT02167386, June 19, 2014.

Hepatitis A outbreak in HIV-infected patients in Southeastern France: questions and responses?

During the 2017 European hepatitis A (HA) outbreak we assessed HA incidence in our cohort of 2300 HIV-infected patients, implemented preventive measures and evaluated practices and knowledge on sexually transmitted diseases (STD). HA incidence was assessed between 1 January 2017 and 31 December 2017 and included all symptomatic patients with virologically confirmed HA. Preventive measures consisted in identifying at risk and not immunised patients to propose them a free HAV vaccination, and an anonymous survey related to transmission routes of STD and to sexual behaviours. Twenty HA were diagnosed. All were homosexual men recently diagnosed with HIV and another STD. None were vaccinated against hepatitis A virus (HAV). Hospitalisation was required for 52%. We identified 250 patients at risk to acquire HAV and invited them to a free immunisation program. A total of 110 (44%) were vaccinated, of whom 74 responded to our survey. A majority of them (84%) reported recent active anal and oral sexuality with multiple (52%) male partners (81%), and ChemSex consumption (14%). Internet was the meeting link for 58%. Another STD history was found in 69%. One third of these individuals had no idea about STD transmission modes. This HA outbreak pointed the insufficient vaccine coverage against HAV and knowledge on STD, which may be improved by Internet.

ScvO2 changes after red-blood-cell transfusion for anaemia in cardiothoracic and vascular ICU patients: an observational study.

BACKGROUND AND OBJECTIVES: Haemoglobin threshold for transfusion has been significantly decreased, but haemoglobin plasma concentration may not be sufficient to assess the need of red-blood-cell (RBC) transfusion. Central venous oxygen saturation (ScvO2 ) is a clue of metabolic matching between O2 transport and consumption, which could help to assess when transfusion is appropriate once anaemia has been diagnosed in ICU patients. MATERIALS AND METHODS: Adult patients admitted consecutively to a cardiothoracic and vascular ICU were included in a prospective, observational and single-centre study over a 6-month period (September 2014 to February 2015), provided they were transfused with RBC. Patients with active bleeding or in unstable condition were excluded. Haemoglobin and ScvO2 were collected through a central venous catheter before and after transfusion. In order to identify a ScvO2 threshold, analysis of ScvO2 changes after transfusion was performed. RESULTS: Fifty-three patients received 100 RBC transfusions. Haemoglobin at the time of transfusion was 7·2 g/dl [6·8-7·7], while ScvO2 was 66·9% [60-73]. A 5% increase in ScvO2 after transfusion has the best specificity and positive predictive values, with a ScvO2 threshold of 65%. After transfusion (RBC units, 2 [1-2]), ScvO2 increased only in patients with ScvO2 ≤65%, from 58% [53-62] to 69% [64-73] (P < 0·001). CONCLUSION: In anaemic patients, RBC transfusion induced a significant increase in ScvO2 , provided it was low before transfusion. A 65% cut-off value of ScvO2 before transfusion showed good specificity and good positive predictive value for a 5% increase after transfusion.

Postauthorization safety study of Clottafact® , a triply secured fibrinogen concentrate in acquired fibrinogen deficiency: a prospective observational study.

BACKGROUND AND OBJECTIVES: A postauthorization safety study was performed between 2009 and 2012 to describe the use of Clottafact® in acquired fibrinogen deficiency in real-life medical practice in France. MATERIALS AND METHODS: One hundred and fifty patients were planned for 28 days of prospective follow-up after infusion. The analysis of this observational study was descriptive and performed according to the type of treatment (curative or preventive) and the origin of the bleed. RESULTS: One hundred and fifty-six patients (16-87 years) were included in 13 centres and treated in five different medical bleeding situations: postpartum (59), other gynaecological/obstetrical (6), trauma (34), liver (13), cardiovascular (23) and other various bleeding situations (21). The mean follow-up time was 18·9 ± 12·3 days. Two patients presented adverse drug reactions: one a pulmonary embolism and the other a four-site venous thromboembolic episode. All were serious with a dubious causal relationship with the study treatment. Efficacy data were collected as a secondary objective. In 150 patients receiving curative treatment, 117 of 159 infusions (73·6%) were considered as successful by the investigators, 35 as moderate (22%) and seven as no response (4·4%). CONCLUSION: The Clottafact® safety profile observed during the study matched the known profile of fibrinogen during use.

Recombinant expression of Mimivirus L725 ORFan gene product.

Mimivirus was the first discovered amoebal giant virus. The Mimivirus virions are covered by a dense layer of approximately 130 nm-long fibers, the length and shape of which diverge from those of other viruses. Here, we aimed at expressing the L725 protein to further confirm and study its role as a fiber-associated protein. We report Escherichia coli expression of the L725 protein, which is encoded by a Mimivirus ORFan, was previously identified by proteomics in purified viral fibers and demonstrated to be a fiber-associated protein by RNA-silencing experiments. The expressed protein was recognized by anti-Mimivirus fiber or anti-Mimivirus L725 polyclonal antibodies. This study is the only expression, to our knowledge, of a product from a Mimiviral ORFan gene.

'Bedside assessment' of acute hantavirus infections and their possible classification into the spectrum of haemophagocytic syndromes.

Hantavirus infections, recently renamed 'hantavirus fever' (HTVF), belong to the most common but also most underestimated zoonoses in the world. A small number of reports described the so-called 'lipid paradox' in HTVF, i.e. the striking contrast between a very low serum total cholesterol and/or high-density lipoprotein cholesterol (HDLc), and a paradoxical concomitant hypertriglyceridaemia. In a prospective study, with patients being their own control after illness, we wanted to verify if this quick and easy 'bedside test' was robust enough to warrant a preliminary diagnosis of acute kidney injury (AKI) caused by HTVF. The study cohort consisted of 58 Belgian cases (mean age 44 years), admitted with varying degrees of AKI and of thrombocytopaenia, both characteristic for presumptive HTVF. All cases were sero-confirmed as having acute HTVF. At or shortly after hospital admission, a significant (p < 0.001) decrease of total cholesterol and HDLc was found in comparison with normalised levels in the same cohort, quantified a few days after spontaneous AKI recovery. Conversely, fasting triglyceride levels during HTVF infection were significantly (p < 0.001) higher during illness than after recovery. This 'lipid paradox' was most outspoken in severe HTVF cases, often accompanying, or even predicting, major kidney or lung complications. Thus, this 'bedside assessment' seems to hold even promise for presumptive diagnosis of more severe so-called 'hantavirus cardio-pulmonary syndrome' (HCPS) cases, mostly described hitherto in the New World. In more severe AKI cases, the mean total cholesterol was significantly lower (p = 0.02) than in milder cases, i.e. cases with peak serum creatinine levels of < 1.5 mg/dL. Thrombocytopaenia, generally accepted as the severity index in HTVF, appeared, moreover, significantly correlated with serum levels of total cholesterol (R = 0.52, p < 0.001) and with serum levels of HDLc (R = 0.45, p < 0.01). A link with the novel clinical entity of haemophagocytic syndromes, also characterised by manifest hypertriglyceridaemia, is discussed.

Difficult intubation in obese patients: incidence, risk factors, and complications in the operating theatre and in intensive care units.

BACKGROUND: Intubation procedure in obese patients is a challenging issue both in the intensive care unit (ICU) and in the operating theatre (OT). The objectives of the study were (i) to compare the incidence of difficult intubation and (ii) its related complications in obese patients admitted to ICU and OT. METHODS: We conducted a multicentre prospective observational cohort study in ICU and OT in obese (BMI≥30 kg m(-2)) patients. The primary endpoint was the incidence of difficult intubation. Secondary endpoints were the risk factors for difficult intubation, the use of difficult airway management techniques, and severe life-threatening complications related to intubation (death, cardiac arrest, severe hypoxaemia, severe cardiovascular collapse). RESULTS: In cohorts of 1400 and 11 035 consecutive patients intubated in ICU and in the OT, 282 (20%) and 2103 (19%) were obese. In obese patients, the incidence of difficult intubation was twice more frequent in ICU than in the OT (16.3% vs 8.2%, P<0.01). In both cohorts, risk factors for difficult intubation were Mallampati score III/IV, obstructive sleep apnoea syndrome, and reduced mobility of cervical spine, while limited mouth opening, severe hypoxaemia, and coma appeared only in ICU. Specific difficult airway management techniques were used in 66 (36%) cases of difficult intubation in obese patients in the OT and in 10 (22%) cases in ICU (P=0.04). Severe life-threatening complications were significantly more frequent in ICU than in the OT (41.1% vs 1.9%, relative risk 21.6, 95% confidence interval 15.4-30.3, P<0.01). CONCLUSIONS: In obese patients, the incidence of difficult intubation was twice more frequent in ICU than in the OT and severe life-threatening complications related to intubation occurred 20-fold more often in ICU. CLINICAL TRIAL REGISTRATION: Current controlled trials. Identifier: NCT01532063.

Differences and similarities between Monkeypox and Chickenpox in children during an outbreak.

INTRODUCTION: Herein, we described cases of children under 16 years old suspected to be infected with Monkeypox virus (MKPV) and diagnosed with chickenpox in public hospitals of Marseille, south of France. MATERIAL AND METHODS: We conducted a retrospective study from March 23rd, 2022 to October 20th, 2022 in our institution of results of MKPV DNA and varicella-zoster virus (VZV) DNA detection by PCR performed on cutaneous lesions swabs collected from children <16 years old. RESULTS: None of the cutaneous swabs collected from 14 children were positive for MKPV DNA. In contrast, 30/168 (17 %) cutaneous swabs collected from children were positive for VZV DNA. Of these 30 VZV-positive children, 7 had been suspected of MKPV infection because of their atypical rash, due to the location of the lesions and the chronology of their appearance. DISCUSSION: As in our cohort, pediatric cases of the 2022 Monkeypox outbreak in non-endemic developed countries have been very rare. This variant of MKPV does not normally spread easily and requires very close physical contact between an infected person (skin lesions, bodily fluids or respiratory droplets) and another person to be transmitted. It will nevertheless be a question of remaining vigilant as not to ignore the possibility of close contact or sexual transmission of Monkeypox in a child, or the possibility of a new and more contagious variant. CONCLUSION: It is difficult to differentiate Monkeypox infection from other infections associated with rashes, it is important to remember that viruses change as well as their forms of presentation.

Analysis of 5,070 consecutive pedicle screws placed utilizing robotically assisted surgical navigation in 334 patients by experienced pediatric spine deformity surgeons: surgical safety and early perioperative complications in pediatric posterior spinal fusion.

PURPOSE: This study evaluates the intraoperative and short-term complications associated with robotically assisted pedicle screw placement in pediatric posterior spinal fusion (PSF) from three surgeons at two different institutions. METHODS: We retrospectively reviewed 334 pediatric patients who underwent PSF with robotic-assisted navigation at 2 institutions over 3 years (2020-2022). Five thousand seventy robotically placed screws were evaluated. Data collection focused on intraoperative and early postoperative complications with minimum 30-day follow-up. Patients undergoing revision procedures were excluded. RESULTS: Intraoperative complications included 1 durotomy, 6 patients with neuromonitoring alerts not related to screw placement, and 62 screws (1.2%) with documented pedicle breaches, all of which were revised at time of surgery. By quartile, pedicle breaches statistically declined from first quartile to fourth quartile (1.8% vs. 0.56%, p < 0.05). No breach was associated with neuromonitoring changes or neurological sequelae. No spinal cord or vascular injuries occurred. Seventeen postoperative complications occurred in eleven (3.3%) of patients. There were five (1.5%) patients with unplanned return to the operating room. CONCLUSION: Robotically assisted pedicle screw placement was safely and reliably performed on pediatric spinal deformity by three surgeons across two centers, demonstrating an acceptable safety profile and low incidence of unplanned return to the operating room.

Pelvic Tilt in Adults With Cerebral Palsy and Its Relationship With Prior Hamstrings Lengthening.

BACKGROUND: Current studies assessing the change in pelvic tilt for ambulatory patients with cerebral palsy (CP) after surgical hamstring lengthening (SHL) lack a comparison cohort without prior SHL and are limited to younger patients. This study presents gait data of middle-aged adults with CP, primarily focusing on the pelvis, and compares pelvic tilt, trunk tilt, and knee flexion between those with and without prior SHL. MATERIALS AND METHODS: A consecutive series of 54 adults with CP, a mean age of 36±13 years, and Gross Motor Function Classification System (GMFCS) levels I-III were included. Thirty-two (59%) had SHL performed at a mean age of 8±5 years. Three-dimensional gait analysis data prospectively collected at a mean of 28±14 years postoperatively were retrospectively analyzed. Chi-square tests were used to compare demographic and surgical history data and statistical parameter mapping was used to compare knee flexion during stance and pelvic and trunk tilts during the gait cycle between SHL and SHL-naive groups. RESULTS: Age, GMFCS level, sex, race, topography, and ethnicity were not different between the groups (P=.217-.612). Anterior pelvic tilt throughout gait was significantly greater in the SHL group compared with the SHL-naive group (63%-87%; P=.033). This difference was augmented after accounting for other surgical history and revision SHL (0%-32%, P=.019; and 46%-93%, P=.007). CONCLUSION: Within a cohort of adults with CP, GMFCS levels I-III, and a mean age of 36 years, those with a history of SHL, performed a mean of 28 years prior to 3-dimensional gait analysis, walked with increased anterior pelvic tilt compared with those without a history of SHL. [Orthopedics. 202x;4x(x):xx-xx.].

The Longitudinal Effects of Posterior Spinal Fusion with Derotation on Axial Deformity in Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To characterize the change in angle of trunk rotation (ATR), axial vertebral rotation (AVR), and body surface rotation (BSR) in patients with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal fusion (PSF) with en-bloc derotation across multiple postoperative visits. SUMMARY OF BACKGROUND DATA: Previous research has documented ATR, AVR, and BSR correction for AIS patients after surgery. However, there is a lack of evidence on the sustainability of this correction over time. METHODS: This was a retrospective study from a single-center prospective surface topographic registry of patients with AIS, age 11-20 at time of surgery, who underwent PSF with en-bloc derotation. Patients with previous spine surgery were excluded. ATR was measured with a scoliometer, AVR through EOS radiographic imaging, and BSR via surface topographic scanning, Data collection occurred at: preoperative, six-week, three-month, six-month, one-year, and two-year postoperative visits. BSR and AVR were tracked at the preoperative apical vertebral level, and the level with maximum deformity, at each respective timepoint. Generalized estimating equations models were used for statistical analysis. Covariates included age, sex, and body mass index. RESULTS: 49 patients (73.4% female, mean age 14.6±2.2 years, mean preoperative coronal curve angle 57.9°±8.5, and 67% major thoracic) were evaluated. ATR correction was significantly improved at all postoperative timepoints and there was no significant loss of correction. AVR Max and AVR Apex were significantly improved at all timepoints but there was a significant loss of correction for AVR Apex between the six-week and one-year visit (P=0.032). BSR Max achieved significant improvement at the three-month visit. BSR Apex was significantly improved at the three-month and one-year visit. CONCLUSION: ATR and AVR demonstrated significant axial plane correction at two-years postoperative in patients undergoing PSF for AIS. BSR did not maintain significant improvement by the two-year visit.

Real-time laboratory surveillance of sexually-transmissible infections in Marseille University hospitals reveals rise of gonorrhoea, syphilis and human immunodeficiency virus seroconversions in 2012.

Real-time systematic monitoring of the number of infections diagnosed in our clinical microbiology laboratory in Marseille recently drew attention to the fact that the incidence of gonorrhoea was 10-fold greater from September through December 2012 than during same months of previous years. We also found an increase in the annual incidence of syphilis and human immunodeficiency virus seroconversion. Our system allowed timely identification of an increase in sexually-transmitted infections in Marseille for the whole year of 2012.

Changes in height, weight, and body mass index after posterior spinal fusion in juvenile and adolescent idiopathic scoliosis.

Purpose: Posterior spinal fusion for idiopathic scoliosis is known to increase spinal height, but the impacts on weight and resulting body mass index are unknown. This study assesses body mass index, weight, and height percentile changes over time after posterior spinal fusion for idiopathic scoliosis. Methods: Body mass index, weight, and height age- and sex-adjusted percentiles for patients with idiopathic scoliosis undergoing posterior spinal fusion between January 2016 and August 2022 were calculated based on growth charts from the Centers for Disease Control for Disease Control and compared to preoperative values at 2 weeks, 3 months, 6 months, 1 year, and 2 years. The data were analyzed for normality with a Shapiro-Wilk test, and percentiles were compared with the Wilcoxon signed-rank tests. Results: On average, 12.1 ± 2.3 levels were fused in 269 patients 14.4 ± 1.9 years, and percentiles for body mass index, weight, and height preoperatively were 55.5 ± 29.4%, 57.5 ± 28.9%, and 54.6 ± 30.4%, respectively. Body mass index and weight percentiles decreased at 2 weeks (-10.7%, p < 0.001; -4.6%, p < 0.001, respectively) and 3 months (-6.9%, p < 0.001; -3.2%, p < 0.001, respectively) postoperatively. Postoperative weight loss at 2 weeks averaged 2.25 ± 3.09% of body weight (0.98 ± 4.5 kg), normalizing by 3 months. Body mass index percentile normalized at 1 year, but height percentile was increased at 2 weeks (2.42 ± 1.72 cm, p < 0.001) and through 2 years. Conclusion: Despite initial height increase due to deformity correction, acute postoperative weight and body mass index percentile decreases postoperatively normalize by 1-year body mass index percentile. Physicians may benefit from utilizing this information when discussing the postoperative course of posterior spinal fusion with idiopathic scoliosis. Level of evidence: 4, Retrospective Case Series.

Clinical and virological factors associated with hepatitis B virus reactivation in HBsAg-negative and anti-HBc antibodies-positive patients undergoing chemotherapy and/or autologous stem cell transplantation for cancer.

We studied clinical outcome and clinico-virological factors associated with hepatitis B virus reactivation (HBV-R) following cancer treatment in hepatitis B virus surface antigen (HBsAg)-negative/anti-hepatitis B core antibodies (anti-HBcAb)-positive patients. Between 11/2003 and 12/2005, HBV-R occurred in 7/84 HBsAg-negative/anti-HBcAb-positive patients treated for haematological or solid cancer. Virological factors including HBV genotype, core promoter, precore, and HBsAg genotypic and amino acid (aa) patterns were studied. Patients presenting with reactivation were men, had an hepatitis B virus surface antibody (HBsAb) titre <100 IU/L and underwent >1 line of chemotherapy (CT) significantly more frequently than controls. All were treated for haematological cancer, 3/7 received haematopoietic stem cell transplantation (HSCT), and 4/7 received rituximab. Using multivariate analysis, receiving >1 line of CT was an independent risk factor for HBV-R. Fatal outcome occurred in 3/7 patients (despite lamivudine therapy in two), whereas 2/4 survivors had an HBsAg seroconversion. HBV-R involved non-A HBV genotypes and core promoter and/or precore HBV mutants in all cases. Mutations known to impair HBsAg antigenicity were detected in HBV DNA from all seven patients. HBV DNA could be retrospectively detected in two patients prior cancer treatment and despite HBsAg negativity. HBV-R is a concern in HBsAg-negative/anti-HBcAb-positive patients undergoing cancer therapy, especially in males presenting with haematological cancer, a low anti-HBsAb titre and more than one chemotherapeutic agent. HBV DNA testing is mandatory to improve diagnosis and management of HBV-R in these patients. The role of specific therapies such as rituximab or HSCT as well as of HBV aa variability deserves further studies.

Clinical efficacy of chloroquine derivatives in COVID-19 infection: comparative meta-analysis between the big data and the real world.

In the context of the current coronavirus disease 2019 (COVID-19) pandemic, we conducted a meta-analysis on the effects of chloroquine derivatives in patients, based on unpublished and published reports available publicly on the internet as of 27 May 2020. The keywords 'hydroxychloroquine', 'chloroquine', 'coronavirus', 'COVID-19' and 'SARS-Cov-2' were used in the PubMed, Google Scholar and Google search engines without any restrictions as to date or language. Twenty studies were identified involving 105 040 patients (19 270 treated patients) from nine countries (Brazil, China, France, Iran, Saudi Arabia, South Korea, Spain and the USA). Big data observational studies were associated with conflict of interest, lack of treatment dosage and duration, and absence of favourable outcome. Clinical studies were associated with favourable outcomes and details on therapy. Among clinical studies, three of four randomized controlled trials reported a significant favourable effect. Among clinical studies, a significant favourable summary effect was observed for duration of cough (OR 0.19, p 0.00003), duration of fever (OR 0.11, p 0.039), clinical cure (OR 0.21, p 0.0495), death (OR 0.32, p 4.1 × 10-6) and viral shedding (OR 0.43, p 0.031). A trend for a favourable effect was noted for the outcome 'death and/or intensive care unit transfer' (OR 0.29, p 0.069) with a point estimate remarkably similar to that observed for death (∼0.3). In conclusion, a meta-analysis of publicly available clinical reports demonstrates that chloroquine derivatives are effective to improve clinical and virological outcomes, but, more importantly, they reduce mortality by a factor of 3 in patients with COVID-19. Big data are lacking basic treatment definitions and are linked to conflict of interest. The retraction of the only big data study associated with a significantly deleterious effect the day after (June 5, 2020) the acceptance of the present work (June 4, 2020) confirms the relevance of this work.