Large Cohort Of Unselected Patients Research Articles

Sequelae Treatment Needs Following Peripheral Facial Palsy: Retrospective Analysis of 525 Patients.

This study uses retrospective longitudinal data from a large unselected cohort of patients with peripheral facial paralysis to determine the prevalence and patient characteristic predictors of sequelae receiving intervention. Retrospective case review. Karolinska University Hospital in Stockholm Sweden serves as the only tertiary facial palsy center in the region. Here, patients are diagnosed, are followed up, and undergo all major interventions. All adult patients presenting with peripheral facial palsy due to idiopathic, zoster, or Borrelia origin at Karolinska, January 1, 2010 to December 31, 2011 with follow-up until December 2022. Patient charts were studied to identify patient characteristics, etiology, initial treatment, severity of palsy, and treatments targeting sequelae. Types of initial and late treatments were noted. Sunnybrook and/or House-Brackmann scales were used for palsy grading. Five hundred twenty-five patients were included. Thirty-three patients (6.3%) received botulinum toxin injections and/or surgical treatment. In this subgroup, 67% received corticosteroids compared to 85% of all patients ( p = 0.005), cardiovascular disease prevalence was higher (23 and 42%, respectively, p = 0.009). For 81 patients (15%), follow-up was discontinued although the last measurement was Sunnybrook less than 70 or House-Brackmann 3 to 6. Of patients with peripheral facial palsy, 6.3% underwent injections and/or surgical treatment within 12 years. However, due to a rather large proportion not presenting for follow-up, this might be an underestimation. Patients receiving late injections and/or surgical treatment had more comorbidities and received corticosteroid treatment to a significantly lower extent in the acute phase of disease.

Sex-related differences in the association between septal wall thickness and survival

Abstract Background Septal hypertrophy is associated with increased morbidity and mortality but data regarding the effect of sex on the association between septal wall thickness and survival is limited and uniform cutoffs in men and women are often used in clinical practice and research. Objective To investigate the differences between men and women in the association between septal wall thickness and survival. Methods A retrospective analysis of consecutive unselected patients undergoing echocardiography between March 2010 and February 2021 in a large tertiary referral center. Echocardiography studies were performed according to standard protocol. Survival data was validated against the ministry of health records. Cox regression analysis was used to evaluate the association between septal thickness and mortality. Results A total of 71,965 individuals were included. There were 32,419 (46%) female and 38,546 (54%) male examinees. Females were older than males (65 + 18 vs. 62 + 18, p < 0.001), less likely to have diabetes (16% vs. 19%, p<0.001) or ischemic heart disease (11% vs. 25%, p<0.001) but more frequently had atrial fibrillation (11% vs. 10%, p<0.001). Females had lesser septal wall thickness than males (10.3 + 2 vs. 11.1 + 2, p < 0.001), lower left ventricular mass index (89 + 29 vs. 102 + 33, p<0.001), lower left ventricular end diastolic and end systolic diameter index. Men had lower ejection fraction than women (55% + 9 vs. 58% + 6, p < 0.001). Over a mean follow-up of 59.1 ± 37 months there were 9631 (25%) and 8429 (26%) deaths in the male and female groups, respectively. In multivariate cox regression analysis, septal thickness was an independent predictor for all-cause mortality in both sexes (Table). When using a uniform cutoff of 12mm for septal thickness for both sexes, the multivariate adjusted HR was 1.00 (CI 95%: 0.94-1.08, p=0.83) for males and 1.15 (CI 95%: 1.07-1.25, p<0.001) for females. The Kaplan–Meier mortality-free survival curve by septal thickness and sex is shown (figure). Septal thickness had an incremental prognostic significance in both sexes. On multivariate analysis it became statistically significant in females at 11mm with HR 1.51 (CI95%:1.06-1.24, p<0.001) and in males at 13mm with HR 1.21 (CI95%: 1.12-1.36, p<0.001). When using indexed septal thickness for BSA, the statistically significant cutoff was 6mm/BSA for women, HR 1.08 (CI 95%: 1-1.17, p=0.04) and 6.2mm/BSA for men, HR 1.07 (CI 95%: 1-1.15, p=0.05). Conclusions In an large unselected cohort of patients, septal hypertrophy had an incremental prognostic significance in both sexes and was associated with increased mortality at a lower threshold in women than in men. This may at least partially explain the delayed diagnosis and worse prognosis reported in females in many conditions characterized by septal hypertrophy. Applying a lower absolute value or using indexed measurements may facilitate early diagnosis and improve prognostication in females.

Perioperative therapy with FLOT4 significantly increases survival in patients with gastroesophageal and gastric cancer in a large real-world cohort.

In 2019, the FLOT4 protocol was established as the new standard for perioperative therapy in patients with locally advanced gastroesophageal and gastric cancer. Whether this protocol is beneficial in a real-world setting remains a question with limited answers to date. In our study, a large cohort of unselected patients treated with FLOT4 was analyzed and compared to protocols based on 5-FU/platinum derivative. This retrospective analysis included patients with locally advanced gastroesophageal and gastric cancer treated with perioperative FLOT or 5-FU/platinum derivative at University Hospital, Bonn between 2010 and 2022 in a curative setting (n=99). Overall survival, disease-free survival, therapy response and therapy complications were analyzed. Patients treated with FLOT showed a statistically significant longer median overall survival of 57.8 vs 28.9 months (HR: 0.554, 95% CI: 0.317-0.969, P=.036). Moreover, pathological tumor regression (pTR) was significantly higher in the FLOT group compared to the 5-FU/platinum group (P=.001). Subgroup analysis showed a favorable survival benefit for the FLOT vs 5-FU/platinum derivate in patients with AEG and non-signet cell carcinoma. Overall, FLOT was tolerated well but CTCAE ≥3 grade neutropenia and diarrhea occurred more often within the FLOT group. Similar to the prospective phase II/III trials, FLOT4 was the best protocol for patients with locally advanced gastroesophageal and gastric cancer as perioperative therapy in terms of overall survival and pathological response rate compared to 5-FU/platinum derivative protocols. Interestingly, patients with gastroesophageal cancer benefitted more from this therapy. In contrast, patients with signet ring cells appear not to benefit from addition of docetaxel.

The success rate of robotic natural orifice intracorporeal anastomosis and transrectal extraction (NICE procedure) in a large cohort of consecutive unselected patients

BackgroundThe Robotic NICE procedure is a total intracorporeal natural orifice approach in which specimen extraction and anastomosis is accomplished without an abdominal wall incision other than the port sites themselves. We aim to present the success rate of the NICE procedure in a large cohort of unselected consecutive patients presenting with colorectal disease using a stepwise and reproducible robotic approach.MethodsConsecutive patients who presented with benign or malignant disease requiring left-sided colorectal resection and anastomosis between May 2018 and June 2021 were evaluated. Data abstracted included demographic, clinical data, disease features, intervention data, and outcomes data. The main outcome was success rate of Intracorporeal anastomosis (ICA), transrectal extraction of specimen (TRSE), and conversion rate.ResultsA total of 306 patients underwent NICE procedure. Diverticulitis was the main diagnosis (64%) followed by colorectal neoplasm (27%). Median operative time was 219 min, and the median estimated blood loss was 50 ml. ICA was achieved in all cases (100%). TRSE was successfully achieved in 95.4% of cases. In 14 patients (4.6%), an abdominal incision was required due to inability to extract a bulky specimen through the rectum. There overall postoperative complications rate was 12.4%. Eight patients (2.6%) experienced postoperative ileus. There were no superficial or deep surgical site infection (SSI). Eleven patients (3.6%) developed organ SSI space including 5 patients with intra-abdominal abscess and 4 patients with anastomotic leak. There was one mortality (0.3%) due to toxic megacolon from resistant Clostridium difficile. The 30-day reoperation rate was 2.9% (n = 9) including six patients presenting with organ space SSI and three patients with postoperative obstruction at the diverting loop ileostomy site.ConclusionThe NICE procedure is associated with a very high success rate for both intracorporeal anastomosis and transrectal specimen extraction in a large cohort of unselected patients.

Perforation and Fistula of the Gastrointestinal Tract in Patients With Necrotizing Pancreatitis: A Nationwide Prospective Cohort.

The aim of this study was to explore the incidence, risk factors, clinical course and treatment of perforation and fistula of the gastrointestinal (GI) tract in a large unselected cohort of patients with necrotizing pancreatitis. Perforation and fistula of the GI tract may occur in necrotizing pancreatitis. Data from large unselected patient populations on the incidence, risk factors, clinical outcomes, and treatment are lacking. We performed a post hoc analysis of a nationwide prospective database of 896 patients with necrotizing pancreatitis. GI tract perforation and fistula were defined as spontaneous or iatrogenic discontinuation of the GI wall. Multivariable logistic regression was used to explore risk factors and to adjust for confounders to explore associations of the GI tract perforation and fistula on the clinical course. A perforation or fistula of the GI tract was identified in 139 (16%) patients, located in the stomach in 23 (14%), duodenum in 56 (35%), jejunum or ileum in 18 (11%), and colon in 64 (40%). Risk factors were high C-reactive protein within 48 hours after admission [odds ratio (OR): 1.19; 95% confidence interval (CI): 1.01-1.39] and early organ failure (OR: 2.76; 95% CI: 1.78-4.29). Prior invasive intervention was a risk factor for developing a perforation or fistula of the lower GI tract (OR: 2.60; 95% CI: 1.04-6.60). While perforation or fistula of the upper GI tract appeared to be protective for persistent intensive care unit-admission (OR: 0.11, 95% CI: 0.02-0.44) and persistent organ failure (OR: 0.15; 95% CI: 0.02-0.58), perforation or fistula of the lower GI tract was associated with a higher rate of new onset organ failure (OR: 2.47; 95% CI: 1.23-4.84). When the stomach or duodenum was affected, treatment was mostly conservative (n=54, 68%). Treatment was mostly surgical when the colon was affected (n=38, 59%). Perforation and fistula of the GI tract occurred in one out of six patients with necrotizing pancreatitis. Risk factors were high C-reactive protein within 48 hours and early organ failure. Prior intervention was identified as a risk factor for perforation or fistula of the lower GI tract. The clinical course was mostly affected by involvement of the lower GI tract.

Multi-national survey on the methods, efficacy, and safety on the post-approval clinical use of pulsed field ablation (MANIFEST-PF).

AimsPulsed field ablation (PFA) is a novel atrial fibrillation (AF) ablation modality that has demonstrated preferential tissue ablation, including no oesophageal damage, in first-in-human clinical trials. In the MANIFEST-PF survey, we investigated the ‘real world’ performance of the only approved PFA catheter, including acute effectiveness and safety—in particular, rare oesophageal effects and other unforeseen PFA-related complications.Methods and resultsThis retrospective survey included all 24 clinical centres using the pentaspline PFA catheter after regulatory approval. Institution-level data were obtained on patient characteristics, procedure parameters, acute efficacy, and adverse events. With an average of 73 patients treated per centre (range 7–291), full cohort included 1758 patients: mean age 61.6 years (range 19–92), female 34%, first-time ablation 94%, paroxysmal/persistent AF 58/35%. Most procedures employed deep sedation without intubation (82.1%), and 15.1% were discharged same day. Pulmonary vein isolation (PVI) was successful in 99.9% (range 98.9–100%). Procedure time was 65 min (38–215). There were no oesophageal complications or phrenic nerve injuries persisting past hospital discharge. Major complications (1.6%) were pericardial tamponade (0.97%) and stroke (0.4%); one stroke resulted in death (0.06%). Minor complications (3.9%) were primarily vascular (3.3%), but also included transient phrenic nerve paresis (0.46%), and TIA (0.11%). Rare complications included coronary artery spasm, haemoptysis, and dry cough persistent for 6 weeks (0.06% each).ConclusionIn a large cohort of unselected patients, PFA was efficacious for PVI, and expressed a safety profile consistent with preferential tissue ablation. However, the frequency of ‘generic’ catheter complications (tamponade, stroke) underscores the need for improvement.

A multicenter retrospective study on 4480 implanted PICC-ports: A GAVeCeLT project.

PICC-ports may be defined as totally implantable central venous devices inserted in the upper limb using the current state-of-the-art techniques of PICC insertion (ultrasound-guided venipuncture of deep veins of the arm, micro-puncture kits, proper location of the tip preferably by intracavitary ECG), with placement of the reservoir at the middle third of the arm. A previous report on breast cancer patients demonstrated the safety and efficacy of these devices, with a very low failure rate. This retrospective multicenter cohort study-developed by GAVeCeLT (the Italian Group of Long-Term Venous Access Devices)-investigated the outcomes of PICC-ports in a large cohort of unselected patients. The study included 4480 adult patients who underwent PICC-port insertion in five Italian centers, during a period of 60 months. The primary outcome was device failure, defined as any serious adverse event (SAE) requiring removal. The secondary outcome was the incidence of temporary adverse events (TAE) not requiring removal. The median follow-up was 15.5 months. Device failure occurred in 52 cases (1.2%), the main causes being local infection (n = 7; 0.16%) and CRBSI (n = 19; 0.42%). Symptomatic catheter-related thrombosis occurred in 93 cases (2.1%), but removal was required only in one case (0.02%). Early/immediate and late TAE occurred in 904 cases (20.2%) and in 176 cases (3.9%), respectively. PICC-ports are safe venous access devices that should be considered as an alternative option to traditional arm-ports and chest-ports when planning chemotherapy or other long-term intermittent intravenous treatments.

Liver Injury at Presentation in COVID-19 is Associated with Immuno-Inflammatory Response

Background: SARS-CoV-2 has been shown to affect liver and GI tract in addition to primary involvement of lungs. Liver injury in COVID-19 is hypothesized to be multifactorial with 14- 73% of patients showing evidence of deranged liver functional. Data regarding the liver injury due to SARS CoV-2 infection in a large cohort of unselected patients, is limited, especially from India. So, we conducted a retrospective study among consecutive patients admitted with COVID-19 disease to a tertiary care hospital during the first wave of pandemic.

The majority of the patients with a monogenic predisposition for dementia did not fulfill current criteria for genetic testing.

Dementia in families can be caused by one genetic variant. Identifying these so-called monogenic causes of dementia is important, because it explains the origin of dementia in families and raises the possibility of predictive testing for relatives. Still, we do not know how frequent these monogenic causes are, due to strict selection criteria for DNA testing based on age at onset and a positive family history. We aimed to identify the mutation frequency of monogenetic dementia by screening a large, unselected cohort of patients from a memory clinic specialized in early onset dementia. Between 1-1-2010 and 1-7-2012, 1,138 patients visited the Alzheimer Center Amsterdam and all patients underwent the same diagnostic trajectory (van der Flier et al 2018). Of these, 1,093 (96%) consented to research and donated blood. An additional 73 patients (7%) were excluded because suboptimal DNA quality. Whole exome sequencing and C9orf72-repeat length analysis was performed in the remaining 1,020 patients (90% of all patients). All variants in 54 dementia related genes were analysed and classified. C9orf72 repeat length >30 repeat units was considered pathogenic. Variants classified as likely pathogenic and pathogenic were considered a monogenic cause of dementia. The average age at presentation was 62(±6SD) years and 419(41%) were female. We found a monogenic cause of dementia in 34 (3.4%) patients. The most frequently occurring (likely) pathogenic variants were found in the genes C9orf72, PSEN1, NOTCH3 and MAPT. These genes explained 65% of the (likely) pathogenic variants. The clinical characteristics of the patients screened positive; 50% were diagnosed with dementia and 50% had a first degree relative with dementia; and 40% had an age at presentation of <60 years and 44% was between 60 to 70 years, the remainder was older. Surprisingly, only 47% of the patients with a (likely) pathogenic variant fulfilled our current criteria (based on diagnosis, age and familial history) for offering diagnostic genetic testing (21% of patients). In our large unselected cohort of patients from a memory clinic specialized in early onset dementia, the majority of the patients with a monogenetic predisposition for dementia did not fulfill our current criteria for genetic testing.

Age Related Distribution of Cytogenetic Abnormalities in Multiple Myeloma

Introduction . Cytogenetic abnormalities (CA) detected by iFISH are among the most powerful prognostic factors in multiple myeloma (MM). With the advent of an unpreceded therapeutic armamentarium during the last years, a thoroughly assessment of individual patients characteristics is necessary in order to choose the best therapy. Among the former, age is an important biologic feature that stratifies patients with regard to treatment intensity.Aims . To study the distribution of individual CA by iFISH according to different age groups and to evaluate the relationship between age and different cytogenetic profiles.Materials and methods . We retrospectively evaluated 1116 patients (pts) analyzed in our laboratory between 01/2010 and 12/2016 for whom baseline cytogenetics by iFISH was available. iFISH was carried out on CD138 enriched plasma cells combined with immunofluorescent detection of light chain (LC) restricted plasma cells. The following CA were considered: gain(1q21), gain(9q34), del(13q14), del(17p13), t(4;14), t(11;14), t(14;16). Commercially available DNA probes were used according to manufacturer protocols (MetaSystems, Vysis). In house cutoff levels of 15% and 17% were set for chromosomal imbalances and IgH translocations respectively. Patients were stratified into 3 age groups: 1st group ≤ 45 years (y), 2nd group > 45y and ≤ 65y and 3th group > 65y. High risk cytogenetics (HRC) were defined according to IMWG criteria as at least one of the following by iFISH: del(17p), t(4;14) and t(14;16). Pairwise comparisons between subgroups were performed by the Mann-Whitney or Kruskal Wallis test for continuous variables and by Fisher's exact test for categorical variables. All statistical analyses were conducted in R, version 3.0.1.Results . The 1st group comprised 92 (8%) pts, the 2nd 581 (52%) pts and the 3rd 443 (40%) pts. The t(4;14) was detected in 109 (9.8%) pts with higher prevalence in the 2nd and 3rd groups (7.6% vs 10.3% vs 9.5%, p=0.67). The t(11;14) was detected in 198 (18%) pts with a higher prevalence in younger pts (26% vs 18 % vs 16%, p=0.15); age density plots showed two prevalence peaks at 45y and 65y respectively (Fig 1). The t(14;16) was identified in 26 pts (2.3%) and occurred more frequent under 65y (2.7% vs 4.2% vs 1.6%, p=0.11). Gain(9q) was identified in 365 (32%) of 781 evaluable patients occurring less frequently under the age of 45y (22% vs 35% vs 31%, p=0.4). Gain(1q) was detected in 249 (22%) pts with a trend towards higher prevalence in pts over 45y (14% vs 23% vs 23%, p=0.09). Del(17p) was detected in 153 pts (14%) slightly more frequent in the 2nd age group (13% vs 15% vs 12%, p=0.4). Del(13q) was more frequent in the 2nd group (32% vs 42% vs 37%, p=0.12).Next, we analyzed the distribution of HRC according to age category and identified 36 (21%) pts in the 1st group, 188 (26%) pts in the 2nd group and 119 (22%) pts in the 3rd group (p= 0.21). If gain(1q) was added to the HRC profile, the distribution of the HRC between groups differed significantly (27% vs 40% vs 34%, p=0.012).For the entire cohort, we further looked how t(4;14) and t(11;14) co-occur with gain(1q) and del(17p). Overall, 38% of the patients with t(4;14) had a gain(1q) (OR 2.8, p< 0.001). Conversely, no significant relation was detected for t(11;14) and for both translocations and del(17p). An inverse relation was found for del(17p) and gain(1q), with only 22% of pts with del(17p) harboring gain(1q) (OR 0.59, p=0.03). An interesting observation was the distribution of the k and λ LC across different CA. We found a significantly higher prevalence of k LC in MM with t(11;14) (60%, p=0.015), gain(1q) (54%, p=0.001) and HRC (67%, p<0.001). Regarding age, no significant difference was identified for the frequency of one type LC or another between age groups (p=0.978).Conclusion. In line with previous data,our study on a large unselected patient cohort suggests an age dependent distribution of CA. Though not reaching statistical significance, t(11;14) tends to occur more often in younger pts. The HRC profile is found more frequently in pts between 45y and 65y . Adding gain(1q) to the HRC panel delineates this group more clearly. Still, the prognostic value of 1q in the era of novel agents is controversial and might be related to the strong association with t(4;14). [Display omitted] DisclosuresKnop:Takeda: Consultancy.

Real-world outcomes for a complete nationwide cohort of more than 3200 teriflunomide-treated multiple sclerosis patients in The Danish Multiple Sclerosis Registry.

Teriflunomide is a once-daily, oral disease-modifying therapy (DMT) for relapsing forms of multiple sclerosis (MS). We studied clinical outcomes in a real-world setting involving a population-based large cohort of unselected patients enrolled in The Danish Multiple Sclerosis Registry (DMSR) who started teriflunomide treatment between 2013-2019. This was a complete nationwide population-based cohort study with prospectively enrolled unselected cases. Demographic and disease-specific patient parameters related to treatment history, efficacy outcomes, and discontinuation and switching rates among other clinical variables were assessed at baseline and during follow-up visits. A total of 3239 patients (65.4% female) started treatment with teriflunomide during the study period, 56% of whom were treatment-naïve. Compared to previously treated patients, treatment-naïve patients were older on average at disease onset, had a shorter disease duration, a lower Expanded Disability Status Scale score at teriflunomide treatment start and more frequently experienced a relapse in the 12 months prior to teriflunomide initiation. In the 3001 patients initiating teriflunomide treatment at least 12 months before the cut-off date, 72.7% were still on treatment one year after treatment start. Discontinuations in the first year were due mainly to adverse events (15.6%). Over the full follow-up period, 47.5% of patients discontinued teriflunomide treatment. Sixty-three percent of the patients treated with teriflunomide for 5 years were relapse-free, while significantly more treatment-naïve versus previously treated patients experienced a relapse during the follow-up (p<0.0001). Furthermore, 85% of the patients with available data were free of disability worsening at the end of follow-up. Solid efficacy and treatment persistence data consistent with other real-world studies were obtained over the treatment period. Treatment outcomes in this real-world scenario of the population-based cohort support previous findings that teriflunomide is an effective and generally well-tolerated DMT for relapsing MS patients with mild to moderate disease activity.

Profiling Oncogenic Germline Mutations in Unselected Chinese Lung Cancer Patients.

IntroductionEmerging evidence has suggested that inherited factors are also involved in lung cancer development. However, most studies focused on well-elucidated cancer predisposition genes, the majority of which are tumor suppressor genes. The profile of germline mutations in oncogenic driver genes remains unrevealed, which might also provide potential clinical implications for lung cancer management.MethodsSequencing data from 36,813 unselected lung cancer patients who underwent somatic mutation profiling were retrospectively reviewed. All recruited patients had matched white blood cell samples sequenced in parallel using a capture-based panel including eight key lung cancer driver genes (epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), MET proto-oncogene, receptor tyrosine kinase (MET), Kirsten rat sarcoma viral oncogene homolog (KRAS), Erb-B2 receptor tyrosine kinase 2(ERBB2), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), ret proto-oncogene (RET), and B-Raf proto-oncogene, serine/threonine kinase (BRAF)). Likely pathogenic/pathogenic (LP/P) variants were called according to the classification criteria of the American College of Medical Genetics and Genomics. Variants of uncertain significance (VUS) located in the kinase domains of driver genes and occurring recurrently (n ≥3) were also included for further analyses.ResultsSeven different LP/P variants in EGFR, MET, or RET were identified in 0.03% of lung cancer patients (n = 14) and 25 different VUS in the kinase domains of seven driver genes (except KRAS) were found with a prevalence of 0.3% (n = 117).Collectively, germline mutations were most frequently seen in ROS1 (n = 31, 0.084%), followed by MET (n = 23, 0.062%), EGFR (n = 22, 0.06%), ALK (n = 22, 0.06%) and RET (n = 17, 0.046%). LP/P variants and VUS fell the most commonly in EGFR (n = 10, 72%) and ROS1 (n = 31, 26%), respectively. Of the 10 patients with EGFR LP/P germline mutation, 70% also acquired somatic EGFR driver mutation exon21 p.L858R or exon19 deletion at baseline; while the three patients with pathogenic germline RET mutation displayed distinct baseline somatic profiles of rare EGFR mutation or KRAS exon2 p.G12C. We discovered 11 germline mutations that also occurred somatically, including four LP/P variants and seven VUS.ConclusionWe present the first study to systemically characterize the germline mutation in oncogenic driver genes in a large cohort of unselected patients with lung cancers.

Reoperations after decompression with or without fusion for L4–5 spinal stenosis with or without degenerative spondylolisthesis: a study of 6,532 patients in Swespine, the national Swedish spine register

Background and purpose — There are different opinions on how to surgically address lumbar spinal stenosis with concomitant degenerative spondylolisthesis (DS). We investigated reoperation rates at the index and adjacent levels after L4–5 fusion surgery in a large cohort of unselected patients registered in Swespine, the national Swedish spine register. Patients and methods — 6,532 patients, who underwent surgery for L4–5 spinal stenosis with or without DS between 2007 and 2012, were followed up to 2017 to identify reoperations at the index and adjacent levels. The reoperation rates for decompression and fusion were compared with the reoperation rates for decompression only and for patients with or without DS. Patient-reported outcome data were collected preoperatively, and at 1 and 2 years after surgery and used to evaluate differences in outcome between index operations and reoperations. Results — For spinal stenosis with DS, the reoperation rate at the index level was 3.0% for decompression and fusion and 6.0% for decompression only. At the adjacent level, the corresponding numbers were 9.7% and 4.2% respectively. For spinal stenosis without DS, the reoperation rate at the index level was 3.7% for decompression and fusion and 6.2% after decompression only. At the adjacent level, the corresponding numbers were 8.1% and 3.8% respectively. For the reoperations at the adjacent level, there was no difference in patient-reported outcome between extended fusion or decompression only. Interpretation — Single-level lumbar fusion surgery is associated with an increased rate of reoperations at the adjacent level compared with decompression only. When reoperations at the index level are included there is no difference in reoperation rates between fusion and decompression only.

Sustained virological response in patients with HCV treated with daclatasvir plus sofosbuvir, with or without ribavirin: a large, field-practice study.

BackgroundThe once-daily oral combination of daclatasvir (DCV) and sofosbuvir (SOF), with or without ribavirin (RBV), is effective and well tolerated in patients with hepatitis C virus (HCV). However, further field-practice studies are necessary to investigate the effectiveness and safety of the DCV+SOF combination in diverse subpopulations of patients with HCV, including those who are more challenging to treat such as patients with a genotype 3 (G3) infection. The aim of this retrospective, multicenter, field-practice study was to investigate the therapeutic efficacy and safety of the oral combination of DCV and SOF, with or without RBV (DCV+SOF±RBV), in a large unselected cohort of patients with chronic HCV infection (CHC).Patients and methodsConsecutive patients received DCV+SOF±RBV for 12 or 24 weeks. The efficacy endpoint was sustained virological response at 12 weeks after the end of treatment (SVR12). Safety factors were also considered.ResultsA total of 620 patients were included in this study; the predominant genotype was G3 (55.3%). Of the total sample, 248 (40%) patients were treated with DCV+SOF+RBV and 372 (60%) did not receive RBV. The majority of patients assessed at week 12 (98%, 596/608) achieved SVR12. Among G3 patients, 98.8% (335/339) achieved SVR12. The most common adverse event was elevated bilirubin (30.6%), recorded in 4.9% of cases as a grade 3–4 adverse event.ConclusionThis study shows the high pan-genotypic effectiveness and safety of the DCV+SOF±RBV combination in a large, unselected sample of CHC patients with G1–4, including a wide proportion of G3 CHC patients.

First Line Treatment with Hydroxyurea in Patients with Policitemia Vera: Evaluation of Efficacy in the Current Clinical Practice Beyond ELN Criteria

First Line Treatment with Hydroxyurea in Patients with Policitemia Vera: Evaluation of Efficacy in the Current Clinical Practice Beyond ELN Criteria

Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study

Background and aimsThere is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and resultsRetrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6–14.7 for age ≥85 vs 18–44 y); HR = 4.7; 2.9–7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m2; HR = 2.3; 1.5–3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses. ConclusionsImpaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.

All-cause and cause-specific mortality in microscopic colitis: a Danish nationwide matched cohort study.

The long-term natural history of microscopic colitis remains uncertain. To describe the mortality in a large unselected cohort of patients with microscopic colitis. All Danish patients above 18years with an incident diagnosis of microscopic colitis from 2001 to 2018 were identified from nationwide registries and compared to age- and sex-matched controls (variable 1:10 ratio). Patients were categorised according to subtypes: lymphocytic colitis and collagenous colitis. The relative risk of death by any cause was analysed with Cox regression models estimating both crude and comorbidity-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Cause-specific death was evaluated with cumulative incidence functions. An E-value was calculated to address the impact of unmeasured confounding. The final cohort consisted of 14024 patients with microscopic colitis. The mean follow-up was 5.8 (standard deviation SD, 2.9) years and the mean age at diagnosis was 61.1 (SD 13.9) years, 70% were women and 41% were diagnosed with lymphocytic colitis. The main results showed a 25% increased risk of all-cause death in patients with microscopic colitis; however, the relative risk was attenuated to 9% when adjusting for comorbidities (95% CI, 1.05-1.14). The E-value indicates that unmeasured confounding could explain the residual observed increased all-cause mortality. Mortality was significantly increased in patients with both lymphocytic colitis (HR 1.15; 95% CI, 1.08-1.23) and collagenous colitis (HR 1.06; 95% CI, 1.01-1.12) in fully adjusted analyses. The absolute difference in death between patients with microscopic colitis and matches was 0.9% at 1year, 2.8% at 5years, 5.0% at 10years and 3.0% at 15years. Cumulative incidence functions showed that patients with microscopic colitis were more likely to die due to smoking-related diseases including ischemic heart and lung diseases, but had a significant decreased risk of death due to colorectal cancers (P<0.0001). In an unselected large nationwide cohort of patients with microscopic colitis, the risk of death was significantly increased compared to the background population. However, the increased mortality seemed to be associated to a high burden of comorbidities and unmeasured life-style factors including smoking and not microscopic colitis per se.

Dynamic Changes in Prognosis with Elapsed Time on Ventilators among Mechanically Ventilated Patients.

Rationale: Previous outcome studies of mechanical ventilation usually adopted a static timeframe to observe the outcome and reported prognosis from the standpoint of the first ventilator day. However, patients and their families may repeatedly inquire about prognosis over time after the initiation of mechanical ventilation.Objectives: We aimed to describe dynamic changes in prognosis according to the elapsed time on a ventilator among mechanically ventilated patients.Methods: For this cohort study we used the entire population dataset of Taiwan’s National Health Insurance database. We enrolled adults who newly received invasive mechanical ventilation for at least two consecutive days between March 1, 2010, and August 31, 2011. For every single ventilator day after the initiation of mechanical ventilation, we estimated the cumulative probabilities of weaning success and death in the subsequent 90 days.Results: A total of 162,200 episodes of respiratory failure requiring invasive mechanical ventilation were included. The median age of the subjects was 72 years (interquartile range 57–81 yr) and the median follow-up time was 250 days (interquartile range 30–463 d). The probability curve of weaning success against the time on ventilation showed a unidirectionally decreasing trend, with a relatively sharp slope in the initial 2 months. The probabilities of weaning success in 90 days after the 2nd, 7th, 21st, and 60th ventilator days were 68.3% (95% confidence interval [CI], 68.1–68.5%), 62.6% (95% CI, 62.2–62.9%), 46.3% (95% CI, 45.8–46.8%), and 21.0% (95% CI, 20.3–21.8%), respectively. In contrast, the death curve showed an initial increase and then a decreasing trend after the 19th ventilator day. We also reported tailored prognosis information according to the age, sex, and ventilator day of a mechanically ventilated patient.Conclusions: This study provides ventilator-day–specific prognosis information obtained from a large cohort of unselected patients on invasive mechanical ventilation. The probability of weaning success decreased with the elapsed time on mechanical ventilation, and the decline was particularly remarkable in the first 2 months of ventilatory support.

Sex-Based Differences in Heart Failure Across the Ejection Fraction Spectrum: Phenotyping, and Prognostic and Therapeutic Implications

ObjectivesThis study assessed sex-related differences in a large cohort of unselected patients with heart failure (HF) across the ejection fraction (EF) spectrum. BackgroundFemales are under-represented in randomized clinical trials. Potential sex-related differences in HF may question the generalizability of trials. MethodsIn the Swedish Heart Failure Registry population multivariate Cox and logistic regression models were fitted to investigate differences in prognosis, prognostic predictors, and treatments across males and females. ResultsOf 42,987 patients, 37% were females (55% with HF with preserved EF [HFpEF], 39% with HF with mid-range EF [HFmrEF], and 29% with HF with reduced EF [HFrEF]). Females were older and more symptomatic and more likely to have hypertension and kidney disease but less likely to have diabetes and ischemic heart disease. After adjustments, females were more likely to use beta-blockers and digoxin but less likely to receive HF device therapy. Crude mortality/HF hospitalization rates for HFpEF (hazard ratio [HR]: 1.16) and HFmrEF (HR: 1.14) were significantly higher in females but lower in females with HFrEF (HR: 0.95). After adjustments, the risk was significantly lower in females regardless of EF (HR: 0.80 in HFrEF, HR: 0.91 in HFmrEF, and HR: 0.93 in HFpEF). The main sex-related differences in prognostic predictors concerned diabetes in HFrEF and anemia in HFmrEF. ConclusionsMales and females with HF showed different characteristics across the EF spectrum. Males reported a lower crude risk of mortality/morbidity in HFpEF and HFmrEF but higher risk of HFrEF, although after adjustments, prognosis was better in females regardless of EF. The observed sex-related differences highlight the need for an adequate representation of females in HF randomized controlled trials to improve generalizability.

Results of Minimally Invasive HVAD Insertion in a Large Cohort of Unselected Patients

Purpose Prior reports on minimally invasive LVAD insertion have focused on smaller and/or highly selected populations. Since 2016 we have used the lateral thoracotomy-hemisternotomy (LTHS) technique and the Heartware HVAD as our default approach for all patients. We compare these outcomes to our results with conventional sternotomy (CS). Methods Since April 2016, 58/61 HVAD patients (representing 61/62 total LVAD insertions) underwent LTHS. Two patients had CS due to stem-cell trial restrictions; one had a posterolateral thoracotomy due to hostile sternum . Outcomes of 60 LTHS procedures were compared to 52 CS dating to 2011. Results Preoperative characteristics (Table 1) were similar except for more males in the LTHS group. No patient was excluded from LTHS due to low Intermacs profile, presence of PFO/ASD, or high RV failure risk. Postoperative outcomes are shown in Table 2. Operative time was longer for LTHS. However, cardiopulmonary bypass (CPB) time, RVAD use, intraoperative red blood cell (RBC) transfusion ≥4U, reoperation for bleeding, operative mortality , and hospital length of stay (LOS) were all lower. One-year Kaplan-Meier estimated survival was 90% LTHS vs 65% CS (p=0.003). Conclusion Improved perioperative and long-term outcomes were observed when employing LTHS as the default technique in a large group of unselected patients.