Nevin Manimala

Int J Colorectal Dis. 2022 Apr 8. doi: 10.1007/s00384-022-04141-7. Online ahead of print.

ABSTRACT

PURPOSE: Delayed perineal wound healing is a common complication after abdominoperineal resection (APR) in rectal cancer. The primary aim of this study was to evaluate the number of patients with delayed wound healing after APR. Secondary aims were to identify risk factors, and describe treatment.

METHODS: Prospectively collected data from the Swedish Colorectal Cancer Registry (SCRCR) was used for retrospective analysis of APR performed at Skåne University Hospital Malmö between 2013 and 2018. Medical charts were retrospectively reviewed. Delayed healing was defined as non-healed perineal wound 30 days postoperatively. Patients undergoing extralevator APR requiring reconstruction were excluded. Statistical analysis was made using SPSS. Risk factors for impaired wound healing were analyzed using a multivariable model.

RESULTS: A total of 162 patients were included, of which 114 underwent standard APR (sAPR) and 48 patients intersphincteric APR (isAPR). In the total population, 69% (111/162) were male, with median age 71 (26-87). The overall healing rate was 52% (85/162); 44% (50/114) in sAPR vs 73% (35/48) in isAPR (P < 0.001). Risk factors for impaired healing after multivariable analysis were BMI > 30 (OR 7.0; CI 95% 1.8-26.2, P = 0.004), reoperation (OR 7.9; CI 95% 1.6-39.8, P = 0.013), neoadjuvant radiotherapy (OR 5.2; CI 95% 1.02-25.1, P = 0.047) and sAPR (OR 2.598; CI 95% 1.05-6.41, P = 0.038). Eight percent (13/162) required an intervention (Clavien-Dindo ≥ 3).

CONCLUSION: Delayed perineal wound healing is a frequent complication after APR but the majority could be treated conservatively. Several risk factors were identified. Further studies aiming at interventions reducing delayed perineal wound healing after APR are warranted.

PMID:35396618 | DOI:10.1007/s00384-022-04141-7

J Med Syst. 2022 Apr 8;46(5):26. doi: 10.1007/s10916-022-01815-1.

ABSTRACT

We investigated the impact of preoperative gabapentin on perioperative intravenous opioid requirements and post anesthesia care unit length of stay (PACU LOS) for patients undergoing laparoscopic and vaginal hysterectomies within an Enhanced Recovery After Surgery (ERAS) pathway. A multidisciplinary team retrospectively examined 2,015 patients who underwent laparoscopic or vaginal hysterectomies between October 2016 and January 2020 at a single academic institution. The average PACU LOS was 168 min among patients who did not receive gabapentin vs. 180 min both among patients who received ≤ 300 mg of gabapentin and patients who received > 300 mg of gabapentin. After adjusting for demographics and medical comorbidities, PACU LOS for patients given ≤ 300 mg gabapentin was 6% longer (rate ratio (RR) = 1.06, 95% CI = 1.01-1.11) than for patients who were not given gabapentin, and for patients who received > 300 mg of gabapentin was 7% longer (RR = 1.07, 95%CI = 1.01-1.13) than for those who did not receive gabapentin. Patients who received ≤ 300 mg gabapentin received 9% less perioperative intravenous hydromorphone than patients who did not receive gabapentin (RR = 0.91, 95% CI = 0.86 – 0.97); patients who received > 300 mg of gabapentin received 12% less perioperative intravenous hydromorphone than patients who did not receive gabapentin (RR = 0.88, 95% CI = 0.82 – 0.95). These findings represent an absolute difference of 0.09 mg intravenous hydromorphone. There were no statistically significant differences in total intravenous fentanyl received. Preoperative gabapentin given as part of an ERAS pathway is associated with statistically but not clinically significant increases in PACU LOS and decreases in total perioperative intravenous opioid use.

PMID:35396607 | DOI:10.1007/s10916-022-01815-1

Int Orthop. 2022 Apr 8. doi: 10.1007/s00264-022-05377-2. Online ahead of print.

ABSTRACT

PURPOSE: An investigation of arthroscopic surgery combined with coverage of the microfractured wound surface with platelet-rich plasma (PRP) and fibrin gels (FG) to treat knee cartilage defects.

METHODS: Between February 2017 and February 2020, 145 patients with knee cartilage defects were treated. Only isolated full-thickness cartilage defects were included, and 28 patients (12 men and 16 women) were included in this study. They were all treated with arthroscopic surgery on subchondral bones, filled with PRP and thrombin, and sealed with FG. The knee pain visual analogue scale (VAS) scores were measured after the patients climbed ten stairs up and down, and the Western Ontario and McMaster Universities osteoarthritis index and the area of cartilage defects were measured through the pre-operative and post-operative follow-up. The complication incidences were also observed.

RESULTS: All patients were followed up for ten to 15 months (median 12 months). The knee pain VAS scores decreased from 6.57 ± 1.07 pre-operatively to 2.09 ± 1.35 at the last follow-up. The WOMAC osteoarthritis index decreased from 44.32 ± 3.95 (mean ± sd) pre-operatively to 16.57 ± 2.20 by the last follow-up. The cartilage defect decreased from 2.93 ± 0.65 cm² pre-operatively to 1.09 ± 0.69 cm² at the last follow-up. All scores showed statistically significant improvements after surgery (p < 0.05). No complications were observed.

CONCLUSION: The combination therapy of arthroscopic surgery and covering the microfractured wound surface with PRP and FG can repair knee cartilage defects, relieve pain, and improve function, and is a safe and effective treatment.

PMID:35396606 | DOI:10.1007/s00264-022-05377-2

Ann Hematol. 2022 Apr 8. doi: 10.1007/s00277-022-04829-4. Online ahead of print.

ABSTRACT

In developing countries, anti-D has been used in immune thrombocytopenia (ITP) as a cheaper alternative to human immunoglobulin. We aim to analyze the response and safety profile of anti-D in patients with severe ITP. A retrospective study was conducted at a tertiary care hospital in Northern India. Patients received a single intravenous infusion of 75 μg/kg anti-D. In total, 36 patients (20 females) were included in this study. The median duration from ITP diagnosis to anti-D therapy was 235 days (range 1-1613 days). Four (11.1%) patients received anti-D as an upfront treatment. The patients’ platelet counts rose significantly by the end of day three and continued to be significantly high until day 30 of receiving anti-D (p ≤ 0.001). The overall response rate (ORR) by day seven was 88.89%. There was no effect of age, sex, duration of disease, prior therapy, and platelet count on the ORR. Patients were followed up for a median duration of 52 days (longest follow-up: 3080 days). Six (6/36, 16.67%) patients continued to be in remission till the last follow-up. The hemoglobin fall was statistically significant on day three and day seven (p < 0.001 and p = 0.001) and got normalized by day 30. We observed equally good ORR in mixed populations and different phases of ITP along with long-term sustained response. The study demonstrates a quick and high response rate along with good safety profile to anti-D in all forms of ITP.

PMID:35396605 | DOI:10.1007/s00277-022-04829-4

Pediatr Surg Int. 2022 Apr 8. doi: 10.1007/s00383-022-05117-y. Online ahead of print.

ABSTRACT

PURPOSE: Over the last few decades, several articles have examined the feasibility of attempting primary reduction and closure of gastroschisis without general anesthesia (GA). We aimed to systematically evaluate the impact of forgoing routine intubation and GA during primary bedside reduction and closure of gastroschisis.

METHODS: The primary outcome was closure success. Secondary outcomes were mortality, time to enteral feeding, and length of hospital stay.

RESULTS: 12 studies were included: 5 comparative studies totalling 192 patients and 7 descriptive case studies totalling 56 patients. Primary closure success was statistically equivalent between the two groups, but trended toward improved success with GA/intubation (RR = 0.86, CI 0.70-1.03, p = 0.08). Mortality was equivalent between groups (RR = 1.26, CI 0.26-6.08, p = 0.65). With respect to time to enteral feeds and length of hospital stay, outcomes were either equivalent between the two groups or favored the group that underwent primary closure without intubation and GA.

CONCLUSION: There are few comparative studies examining the impact of performing primary bedside closure of gastroschisis without GA. A meta-analysis of the available data found no statistically significant difference when forgoing intubation and GA. Foregoing GA also did not negatively impact time to enteral feeds, length of hospital stay, or mortality.

PMID:35396604 | DOI:10.1007/s00383-022-05117-y

J Pediatr Psychol. 2022 Apr 9:jsac025. doi: 10.1093/jpepsy/jsac025. Online ahead of print.

ABSTRACT

OBJECTIVE: The early expression of lifespan health and disease states can often be detected in early childhood. Currently, the Patient-Reported Outcome Measurement Information System (PROMIS®) includes over 300 measures of health for individuals ages 5 years and older. We extended PROMIS to early childhood by creating developmentally appropriate, lifespan coherent parent-report measures for 1-5-year-olds. This paper describes the psychometric approaches used for these efforts.

METHODS: 2 waves of data from parents of children ages 1-5 were collected via 2 internet panel companies. Wave 1 data (n = 1,400) were used to evaluate item pool unidimensionality, model fit, and initial item parameters. Combined data from wave 1 and wave 2 (reference sample; n = 1,057) were used to estimate final item parameters. Using item response theory methods, we developed and tested 12 item pools: Global Health, Physical Activity, Sleep Disturbance, Sleep-related Impairment, Anger/Irritability, Anxiety, Depressive Symptoms, Positive Affect, Self-Regulation, Engagement, Family Relationships, and Peer Relationships.

RESULTS: Wave 1 analyses supported the unidimensionality of Physical Activity, Positive Affect, Anger/Irritability, Anxiety, Depressive Symptoms, and Global Health. Family Relationships and Peer Relationships were combined to form “Social Relationships”; Sleep Disturbance and Sleep-related Impairment were combined to form “Sleep Problems.” Self-Regulation was divided into “Flexibility” and “Frustration Tolerance”; Engagement was divided into “Curiosity” and “Persistence.” Short forms were developed for item banks with more than 10 items; and.

CONCLUSIONS: Using rigorous mixed-methods, we successfully extended PROMIS to early childhood (1-5-year-olds). Measures are now publicly available in English and Spanish (www.healthmeasures.net).

PMID:35396597 | DOI:10.1093/jpepsy/jsac025

Acta Otorhinolaryngol Ital. 2022 Apr 8. doi: 10.14639/0392-100X-N1672. Online ahead of print.

ABSTRACT

OBJECTIVE: The PRO.M.E.THE.O. study (PredictiOn Models in Ent cancer for anti-EGFR based THErapy Optimization) aimed to develop a predictive model (PM) of overall survival (OS) for patients with locally advanced oropharyngeal cancer (LAOC) treated with radiotherapy (RT) and cetuximab (Cet) from an Italian dataset.

METHODS: We enrolled patients with LAOC from 6 centres treated with RT-Cet. Clinical and treatment variables were collected. Patients were randomly divided into training (TS) (80%) and validation (VS) (20%) sets. A binary logistic regression model was used on the TS with stepwise feature selection and then on VS. Timepoints of 2, 3 and 5 years were considered. The area under the curve (AUC) of receiver operating characteristic of 2, 3 and 5 year and confusion matrix statistics at 5-threshold were used as performance criteria.

RESULTS: Overall, 218 patients were enrolled and 174 (79.8%) were analysed. Age at diagnosis, gender, ECOG performance, clinical stage, dose to high-risk volume, overall treatment time and day of RT interruption were considered in the final PMs. The PMs were developed and represented by nomograms with AUC of 0.75, 0.73 and 0.73 for TS and 0.713, 0.713, 0.775 for VS at 2, 3 and 5 years, respectively.

CONCLUSIONS: PRO.M.E.THE.O. allows the creation of a PM for OS in patients with LAOC treated with RT-Cet.

PMID:35396587 | DOI:10.14639/0392-100X-N1672

Nature. 2022 Apr 8. doi: 10.1038/s41586-022-04434-5. Online ahead of print.

ABSTRACT

Schizophrenia has a heritability of 60-80%¹, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.

PMID:35396580 | DOI:10.1038/s41586-022-04434-5

Nature. 2022 Apr 8. doi: 10.1038/s41586-022-04556-w. Online ahead of print.

ABSTRACT

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, P < 2.14 × 10^-6) and 32 genes at a false discovery rate of <5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure and function of the synapse. The associations of the NMDA (N-methyl-D-aspartate) receptor subunit GRIN2A and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GRIA3 provide support for dysfunction of the glutamatergic system as a mechanistic hypothesis in the pathogenesis of schizophrenia. We observe an overlap of rare variant risk among schizophrenia, autism spectrum disorders¹, epilepsy and severe neurodevelopmental disorders², although different mutation types are implicated in some shared genes. Most genes described here, however, are not implicated in neurodevelopment. We demonstrate that genes prioritized from common variant analyses of schizophrenia are enriched in rare variant risk³, suggesting that common and rare genetic risk factors converge at least partially on the same underlying pathogenic biological processes. Even after excluding significantly associated genes, schizophrenia cases still carry a substantial excess of URVs, which indicates that more risk genes await discovery using this approach.

PMID:35396579 | DOI:10.1038/s41586-022-04556-w

J Perinatol. 2022 Apr 8. doi: 10.1038/s41372-022-01376-8. Online ahead of print.

ABSTRACT

OBJECTIVE: Increase the proportion of ≤33 weeks newborns exposed to mother’s own milk (MOM) oral care by 12 h of age by 20% over 2 years to support a healthier microbiome.

STUDY DESIGN: We implemented interventions to support early expression of colostrum and reliable delivery of resultant MOM to premature newborns. Statistical process control charts were used to track progress and provide feedback to staff. Proportions of newborns exposed to MOM by 12 h were compared relative to baseline.

RESULTS: There were 46, 66, and 46 newborns in the baseline, implementation, and sustainability periods, respectively. The primary outcome improved from 48% to 61% in the implementation period (relative change 1.27, 95% CI 0.89, 1.81, p = 0.2), to 69% in sustainability period (relative to baseline 1.45, 95% CI 1.02, 2.08, p = 0.03).

CONCLUSION: An interdisciplinary team-based, multicycle, quality improvement intervention resulted in increased rates of early exposure to MOM.

PMID:35396577 | DOI:10.1038/s41372-022-01376-8