Peritoneal flap technique for abdominal wall expansion in the management of complex ventral hernias: a multicentre study from India.

INTRODUCTION: Large abdominal wall hernias often require techniques for wall expansion to improve surgical outcomes. The peritoneal flap hernioplasty (PF) is one such technique that utilizes the hernia sac to reconstruct the abdominal wall, however, with limited published data. It is a modification of the Rives-Stoppa mesh repair where a part of the bisected hernia sac is utilized to reconstruct the anterior fascia and the other part for the posterior fascia. We present a collated retrospective analysis of the outcomes from three centers performing PF with or without transverse abdominis release (TAR) in patients with complex ventral hernias. METHODS: The PF was performed in patients with incisional hernias, both midline and lateral. The primary outcome measured was hernia recurrence. The secondary outcomes were to evaluate pain, surgical site infection, seroma, hematoma, wound dehiscence, pseudo-recurrence, Clavien-Dindo score for complications, and the patient's reported quality of life. The quality of life was assessed by oral questionnaires in the follow-up period. RESULTS: We analyzed 63 patients (38 female, 25 male) with a mean width of hernia defect of 11 cm SD 4. Based on the European Hernia Society (EHS) classification 42 patients were W3 and 21 were W2 hernias. Fifty patients had a midline hernia, while the rest of the patients included transverse, subcostal, and rooftop incision hernias. The classical peritoneal flap procedure was done in 29 (46%) patients, while the peritoneal flap with TAR was done in 34 (54%) patients. Four patients had symptomatic seroma (6%), seven superficial surgical site infection (SSI) (11%), one deep SSI (1.5%), one skin necrosis (1.5%), and one anterior peritoneal flap necrosis (1.5%). No patient required postoperative ventilatory support. The mean pain score on day one was 3/10. There was no recurrence in the mean follow-up of 17 months (range 5 to 49 months). Overall, 58 of 63 (92%) patients reported being satisfied with their surgery. CONCLUSION: In our multicentre study, we found the PF technique with or without TAR for midline and non-midline ventral hernia leads to satisfactory outcomes in terms of low recurrence, low rate of complications, and a good quality of life in the medium to long term. It appears to be a useful technique in the surgeon's armamentarium to repair W2 and W3 hernias needing expansion of abdominal domain.

Single incision laparoscopy versus conventional multiport laparoscopy for colorectal surgery: a systematic review and meta-analysis.

INTRODUCTION: There has been an increase in colorectal cancer resections worldwide and in the UK. Initially conducted as an open procedure, this was replaced with the conventional multiport technique. Laparoscopic colectomy became the standard surgical technique in 1991. With innovation in surgical technology, single incision laparoscopy (SIL) has attracted more attention as the possible next step in colorectal resection. The aim of this review was to compare outcomes between SIL and conventional laparoscopy (CL). METHODS: A literature search was carried out in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. The PubMed®, MEDLINE®, Embase®, Google Scholar™ and Cochrane Library databases were used to extract randomised controlled trials (RCTs) published between January 2000 and May 2021. Statistical analysis was performed with RevMan software. RESULTS: A total of 11 RCTs were extracted with 1,370 patients (686 SIL, 684 CL). There was no significant difference between SIL and CL for operative time (standardised mean difference [SMD]: 0.01, 95% confidence interval [CI]: -0.19 to 0.22, z=0.11, p=0.91), length of hospital stay (SMD: -0.10, 95% CI: 0.22 to 0.02, z=1.61, p=0.11) or overall complications (odds ratio [OR]: 0.99, 95% CI: 0.75 to 1.30, z=0.09, p=0.93). SIL had a shorter mean incision (SMD: -0.99, 95% CI: -1.35 to -0.62, z=5.25, p<0.00001). Patients undergoing SIL had a higher conversion rate to CL or an open approach (OR: 3.10, 95% CI: 0.95 to 10.14, z=1.87, p=0.06) but this just missed statistical significance. CONCLUSIONS: SIL can be considered a safe alternative to CL if performed by experienced surgeons.

Manifestation of spatially varying demarcations in Indian rainfall trends through change-point analysis (1901-2020).

The rainfall over the Indian region, governed majorly by the monsoonal flow, is a point of research in the perspective of climate change. In this paper, we compute the change points in the rainfall series at every grid of the India Meteorological Department (IMD) daily gridded rainfall data for a period of 120 years (1901 to 2020). The map shows clearly demarcated regions indicating different zones, where the rainfall statistics have altered at different periods. It is observed that in a major part of central India, the shift in rainfall intensity is mainly associated with the time frame 1955-1965; in the Indo-Gangetic plain, the changes are found to be more recent (1990), while the latest changes (post 2000) are observed particularly for North Eastern region and some parts along the East Indian coast. The changeover years are significant at a 95% confidence level for most part of the Indian landmass. The causes may be surmised due to moisture transport from the Arabian Sea (Central India), the presence of aerosol (Gangetic Plain), and the possible revival of monsoon due to land-ocean gradient (Eastern coast and North East India). This is the first-ever study which provides a comprehensive daily rainfall change point map over India using 120 years of gridded station data.

A contemporary overview on the enigma of managing recalcitrant or intractable post-operative otorrhoea following middle-ear surgery: perspectives, principles and practices.

BACKGROUND: A common problem in otological surgeries is the persistence of ear discharge in a patient who has undergone middle-ear reconstructive surgery, despite an intact graft. There is a dearth of knowledge in the literature on treatment strategies in such post-operative cases of recalcitrant otorrhoea. METHOD: This was a retrospective observational descriptive study conducted on 45 patients who fitted the criteria for recalcitrant post-operative otorrhoea. All 45 patients showed no response to conservative treatment for 14 days from onset of discharge. Therefore, these patients were then given antiseptic ear drops. RESULTS: Thirty patients out of 45 showed a good response to antiseptic ear drops and achieved a dry ear at the end of the treatment. CONCLUSION: In patients with recalcitrant otorrhoea with or without granulations after middle-ear reconstruction surgery, this study found that topical antiseptic ear drops, particularly those using boric acid powder, are more effective than topical antibiotic drops.

Bilateral ganglion cysts at L4/5 causing central canal stenosis and producing sciatica and neurogenic claudication: a case report.

Symptomatic bilateral juxtafacet ganglion cysts are relatively uncommon in the degenerated spine. The literature describes 16 cases of bilateral ganglion or synovial cysts, none reported sciatica and neurogenic claudication simultaneously. We present a case of a 60-year-old woman who presented with symptoms of bilateral sciatica and neurogenic claudication. Magnetic resonance imaging of the lumbar spine revealed bilateral lesions related to the facet joints at the L4/5 level, causing bilateral lateral recess stenosis and narrowing of the central canal due to encroachment of these bilateral lesions at the same level. She underwent an elective central canal decompression of the L4/5 level and excision of the facet cysts bilaterally with lateral recess decompression, which resulted in good relief of both the radicular and claudication symptoms.

Photoredox catalyzed cascade CF3 addition/chemodivergent annulations of ortho-alkenyl aryl ureas.

Herein, we report a substrate-controlled cascade cyclization of o-alkenyl aryl ureas, an ambident nucleophile for constructing functionalized heterocycles such as 2-amino-1,3-benzoxazines and dihydroquinazolinones in a chemodivergent fashion using photoredox catalysis under mild conditions. The versatility of the method has been successfully demonstrated by applying this strategy to a wide range of substrates and for the synthesis of functionalized etifoxine drug derivatives.

Bilateral ganglion cysts at L4/5 causing central canal stenosis and producing sciatica and neurogenic claudication: a case report.

Symptomatic bilateral juxtafacet ganglion cysts are relatively uncommon in the degenerated spine. The literature describes 16 cases of bilateral ganglion or synovial cysts, none reported sciatica and neurogenic claudication simultaneously. We present a case of a 60-year-old woman who presented with symptoms of bilateral sciatica and neurogenic claudication. Magnetic resonance imaging of the lumbar spine revealed bilateral lesions related to the facet joints at the L4/5 level, causing bilateral lateral recess stenosis and narrowing of the central canal due to encroachment of these bilateral lesions at the same level. She underwent an elective central canal decompression of the L4/5 level and excision of the facet cysts bilaterally with lateral recess decompression, which resulted in good relief of both the radicular and claudication symptoms.

MGMT-inhibitor in combination with TGF-BRI inhibitor or CDK 4/6 inhibitor increases temozolomide sensitivity in temozolomide-resistant glioblastoma cells

Background Glioblastoma (GB) remains an incurable and deadly brain malignancy that often proves resistant to upfront treatment with temozolomide. Nevertheless, temozolomide remains the most commonly prescribed FDA-approved chemotherapy for GB. The DNA repair protein methylguanine-DNA methyl transferase (MGMT) confers resistance to temozolomide. Unsurprisingly temozolomide-resistant tumors tend to possess elevated MGMT protein levels or lack inhibitory MGMT promotor methylation. In this study, cultured human temozolomide resistance GB (43RG) cells were introduced to the MGMT inhibitor O6-benzylguanine combined with temozolomide and either LY2835219 (CDK 4/6 inhibitor) or LY2157299 (TGF-βRI inhibitor) seeking to overcome GB treatment resistance. Methods Treatment effects were assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, western blot, cell viability, and cell cycle progression. Results Our in vitro study demonstrated that sequential treatment of O6-Benzylguanine with either LY2385219 or LY2157299-enhanced temozolomide enhanced sensitivity in MGMT+ 43RG cells. Importantly, normal human neurons and astrocytes remained impervious to the drug therapies under these conditions. Furthermore, LY2835219 has additional anti-proliferative effects on cell cycling, including induction of an RB-associated G (1) arrest via suppression of cyclin D-CDK4/6-Rb pathway. LY2157299 enhances anti-tumor effect by disrupting TGF-β–dependent HIF-1α signaling and by activating both Smad and PI3K-AKT pathways towards transcription of S/G2 checkpoints. Conclusion This study establishes the groundwork for the development of a combinatorial pharmacologic approach by using either LY2385219 or LY2157299 inhibitor plus O6-Benzylguanine to augment temozolomide response in temozolomide-resistant GB cells (AU)

MGMT-inhibitor in combination with TGF-ßRI inhibitor or CDK 4/6 inhibitor increases temozolomide sensitivity in temozolomide-resistant glioblastoma cells.

BACKGROUND: Glioblastoma (GB) remains an incurable and deadly brain malignancy that often proves resistant to upfront treatment with temozolomide. Nevertheless, temozolomide remains the most commonly prescribed FDA-approved chemotherapy for GB. The DNA repair protein methylguanine-DNA methyl transferase (MGMT) confers resistance to temozolomide. Unsurprisingly temozolomide-resistant tumors tend to possess elevated MGMT protein levels or lack inhibitory MGMT promotor methylation. In this study, cultured human temozolomide resistance GB (43RG) cells were introduced to the MGMT inhibitor O6-benzylguanine combined with temozolomide and either LY2835219 (CDK 4/6 inhibitor) or LY2157299 (TGF-ßRI inhibitor) seeking to overcome GB treatment resistance. METHODS: Treatment effects were assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, western blot, cell viability, and cell cycle progression. RESULTS: Our in vitro study demonstrated that sequential treatment of O6-Benzylguanine with either LY2385219 or LY2157299-enhanced temozolomide enhanced sensitivity in MGMT+ 43RG cells. Importantly, normal human neurons and astrocytes remained impervious to the drug therapies under these conditions. Furthermore, LY2835219 has additional anti-proliferative effects on cell cycling, including induction of an RB-associated G (1) arrest via suppression of cyclin D-CDK4/6-Rb pathway. LY2157299 enhances anti-tumor effect by disrupting TGF-ß-dependent HIF-1α signaling and by activating both Smad and PI3K-AKT pathways towards transcription of S/G2 checkpoints. CONCLUSION: This study establishes the groundwork for the development of a combinatorial pharmacologic approach by using either LY2385219 or LY2157299 inhibitor plus O6-Benzylguanine to augment temozolomide response in temozolomide-resistant GB cells.

Evaluating anti-tumor activity of palbociclib plus radiation in anaplastic and radiation-induced meningiomas: pre-clinical investigations.

PURPOSE: Meningiomas are common brain tumors, the majority of which are considered benign. Despite surgery and/or radiation therapy, recurrence rates are approximately 8-10%. One likely cause is the dysregulation of cyclin D-cyclin-dependent kinases 4 and 6 (CDK4/6)-retinoblastoma (Rb) pathway, which controls the cell cycle restriction point. This pathway is commonly dysregulated in anaplastic meningioma cell lines (AM) and radiation-induced meningioma cells (RIM), making it a rational target for anti-meningioma therapy. In this study, we investigate the effect of a CDK4/6 inhibitor, palbociclib, with radiation in relevant pre-clinical models. METHODS: In vitro cell culture, ex vivo slice culture and in vivo cell line-derived orthotopic xenograft animal models of AM/RIM were utilized to assess treatment efficacy with palbociclib plus radiation. Treatment effects were examined by immunoblot, cell viability, apoptosis, and cell cycle progression. RESULTS: The in vitro and ex vivo studies demonstrate that palbociclib plus radiation treatment reduced proliferation and has additional effects on cell cycling, including induction of an RB-associated G (1) arrest in Rb+ AM and RIM cells, but not in Rb- cells. Our results also demonstrated reduced CDK4 and CDK6 expression as well as reduced E2F target gene expression (CCNA2 and CCNE2) with the combination therapy. MRI results in vivo demonstrated reduced tumor size at 5 weeks when treated with 14 days palbociclib (10 mg/kg) plus 6 Gy radiation compared to saline-treated tumors. Finally, no hepatic toxicity was found after treatments. CONCLUSION: A pre-clinical murine model provides preclinical evidence for use of palbociclib plus radiation as a therapeutic agent for Rb+ meningiomas.

Ganoderic acid A/DM-induced NDRG2 over-expression suppresses high-grade meningioma growth.

PURPOSE: N-myc downstream-regulated gene 2 (NDRG2) is down-regulated in grade-III meningioma [anaplastic meningioma (AM)] and associated with clinically aggressive behavior. Current therapies in the treatment of high-grade meningioma are lacking with limited success. This study aims to validate the effect of NDRG2-targeted therapy using structurally related bioactive triterpene compounds derived from the edible mushroom Ganoderma lucidum (ganoderic acid A:GA-A/ganoderic acid DM:GA-DM) in human AM in relevant pre-clinical models. METHODS: Tissue samples from the AM tumor regions of three human patients and control non-tumor samples were used to analyze the expression pattern of NDRG2. In vitro cell culture and in vivo cell-line-derived orthotopic xenograft animal models of AM were utilized to assess efficacy of treatment with GA-A/DM. RESULTS: Downregulation of NDRG2 expression was observed in surgically resected high-grade meningiomas compared to normal brain. These results prompt us to use NDRG2-targeting agents GA-A/DM. In vitro results showed that 72-h treatments of 25 µM GA-A/DM induced AM cell death, upregulate NDRG2 protein expression, downregulate NDRG2 promoter methylation in meningioma cells as compared to azacitidine and decitabine, the most commonly used demethylating agents. Our results also demonstrated that GA-A/DM does not have any detrimental effect on normal human neurons and arachnoid cells. GA-A/DM promoted apoptotic factors (Bax) while suppressing MMP-9, p-P13K, p-AKT, p-mTOR, and Wnt-2 protein expression. RNAi-mediated knockdown of NDRG2 protein expression increased tumor proliferation, while forced expression of wt-NDRG2 decreased proliferation in an in vitro model. Magnetic resonance (MR) imaging and Hematoxylin (H&E) staining demonstrated gross reduction of tumor volume in GA-A/DM treated mice at 5 weeks when compared with saline-treated orthotopic AM xenografted controls. There was an overall decrease in tumor cell proliferation with increased survival in GA-A/DM-treated animals. Enzyme assays showed that GA-A/DM did not negatively impact hepatic function. CONCLUSION: GA-A/DM may be a promising natural therapeutic reagent in the treatment of AM by suppressing growth via NDRG2 modulation and altering of intracellular signal pathways. We have shown it could potentially be an effective treatment for AM with decreased cellular proliferation in vitro, decreased tumor volume and increased survival in vivo.

Research protocol of two concurrent cluster-randomized trials: Real-life Effect of a CAMPaign with Measles Vaccination (RECAMP-MV) and Real-life Effect of a CAMPaign with Oral Polio Vaccination (RECAMP-OPV) on mortality and morbidity among children in rural Guinea-Bissau.

BACKGROUND: Measles and oral polio vaccinations may reduce child mortality to an extent that cannot be explained by prevention of measles and polio infections; these vaccines seem to have beneficial non-specific effects. In the last decades, billions of children worldwide have received measles vaccine (MV) and oral polio vaccine (OPV) through campaigns. Meanwhile the under-five child mortality has declined. Past MV and OPV campaigns may have contributed to this decline, even in the absence of measles and polio infections. However, cessation of these campaigns, once their targeted infections are eradicated, may reverse the decline in the under-five child mortality. No randomized trial has assessed the real-life effect of either campaign on child mortality and morbidity. We present the research protocol of two concurrent trials: RECAMP-MV and RECAMP-OPV. METHODS: Both trials are cluster-randomized trials among children registered in Bandim Health Project's rural health and demographic surveillance system throughout Guinea-Bissau. RECAMP-MV is conducted among children aged 9-59 months and RECAMP-OPV is conducted among children aged 0-8 months. We randomized 222 geographical clusters to intervention or control clusters. In intervention clusters, children are offered MV or OPV (according to age at enrolment) and a health check-up. In control clusters, children are offered only a health check-up. Enrolments began in November 2016 (RECAMP-MV) and March 2017 (RECAMP-OPV). We plan 18,000 enrolments for RECAMP-MV with an average follow-up period of 18 months and 10,000 enrolments for RECAMP-OPV with an average follow-up period of 10 months. Data collection is ongoing. The primary outcome in both trials is non-accidental death or non-accidental first non-fatal hospitalization with overnight stay (composite outcome). Secondary outcomes are: non-accidental death, repeated non-fatal hospitalizations with overnight stay, cause-specific primary outcome, outpatient visit, and illness. We obtained ethical approval from Guinea-Bissau and consultative approval from Denmark. DISCUSSION: Cluster randomization and minimum risk of loss to follow-up are strengths, and no placebo a limitation. Our trials challenge the understanding that MV and OPV only prevent measles and polio, and that once both infections are eradicated, campaigns with MV and OPV can be phased out without negative implications on child health and survival. TRIAL REGISTRATION: NCT03460002.

Production of lipid-containing microalgal biomass and simultaneous removal of nitrate and phosphate from synthetic wastewater.

The major concerns of the modern society such as increasing population, climate change and economic development are imposing continuous stress on water and energy resources. The present work deals with the cultivation of green algae Desmodesmus abundans for optimum biomass productivity and lipid content as well as simultaneous removal of nitrate and phosphate from synthetic wastewater. The algal biomass is characterized by ultimate analysis, scanning electron microscopic analysis and thermogravimetric analysis. The effect of time, inoculum concentration and nitrate concentration on four responses (biomass productivity, lipid content, removal of nitrate and removal of phosphate) are studied by response surface methodology using central composite design. The quadratic models are found to be suitable for each response. At optimized experimental conditions, the algae showed biomass productivity of 46.96 mg L-1 day-1, lipid content of 16.23%, nitrate removal of 86.64% and phosphate removal of 87.52% after 27 days, when the initial inoculum concentration was 6% and nitrate concentration was 1.25 g L-1.

The UK Neovascular AMD Database Report 3: inter-centre variation in visual acuity outcomes and establishing real-world measures of care.

PurposeInternational variations in visual acuity (VA) outcomes of eyes treated for neovascular age-related macular degeneration (nAMD) are well-documented, but intra-country inter-centre regional variations are not known. These data are important for national quality outcome indicators. We aimed to determine intra-country and inter-centre regional variations in outcomes for treatment of nAMD.Patients and methodsProspective multicentre national database study of 13 UK centres that treated patients according to a set protocol (three loading doses, followed by Pro-Re-Nata retreatment). A total of 5811 treatment naive eyes of 5205 patients received a total of 36 206 ranibizumab injections over 12 months.ResultsMean starting VA between centres varied from 48.9 to 59.9 ETDRS letters. Mean inter-centre VA change from baseline to 12 months varied from +6.9 letters to -0.6 letters (mean of +2.5 letters). The proportion of eyes achieving VA of 70 letters or more varied between 21.9 and 48.7% at 12 months. Median number of injections (visits) at each centre varied from 5 to 8 (9 to 12), with an overall median of 6 (11). Age, starting VA, number of injections, and visits, but not gender were significantly associated with variation in these VA outcomes (P<0.01). Significant variation between centres persisted even after adjusting for these factors.ConclusionThere are modest differences in VA outcomes between centres in the UK. These differences are influenced, but not completely explained, by factors such as patient age, starting VA, number of injections, and visits. These data provide an indication of the VA outcomes that are achievable in real-world settings.

Putative bacterial volatile-mediated growth in soybean (Glycine max L. Merrill) and expression of induced proteins under salt stress.

AIMS: Plant root-associated rhizobacteria elicit plant immunity referred to as induced systemic tolerance (IST) against multiple abiotic stresses. Among multibacterial determinants involved in IST, the induction of IST and promotion of growth by putative bacterial volatile compounds (VOCs) is reported in the present study. METHODS AND RESULTS: To characterize plant proteins induced by putative bacterial VOCs, proteomic analysis was performed by MALDI-MS/MS after exposure of soybean seedlings to a new strain of plant growth promoting rhizobacteria (PGPR) Pseudomonas simiae strain AU. Furthermore, expression analysis by Western blotting confirmed that the vegetative storage protein (VSP), gamma-glutamyl hydrolase (GGH) and RuBisCo large chain proteins were significantly up-regulated by the exposure to AU strain and played a major role in IST. VSP has preponderant roles in N accumulation and mobilization, acid phosphatase activity and Na(+) homeostasis to sustain plant growth under stress condition. More interestingly, plant exposure to the bacterial strain significantly reduced Na(+) and enhanced K(+) and P content in root of soybean seedlings under salt stress. In addition, high accumulation of proline and chlorophyll content also provided evidence of protection against osmotic stress during the elicitation of IST by bacterial exposure. CONCLUSIONS: The present study reported for the first time that Ps. simiae produces a putative volatile blend that can enhance soybean seedling growth and elicit IST against 100 mmol l(-1) NaCl stress condition. SIGNIFICANCE AND IMPACT OF THE STUDY: The identification of such differentially expressed proteins provide new targets for future studies that will allow assessment of their physiological roles and significance in the response of glycophytes to stresses. Further work should uncover more about the chemical side of VOC compounds and a detailed study about their molecular mechanism responsible for plant growth.

Functionalized celluloses and their nanoparticles: morphology, thermal properties, and solubility studies.

Agricultural residues derived cellulose was used to synthesize a new series of carboxy functionalized cellulosic nanoparticles (quasi-spherical shaped, 13.2-21.5% carboxyl content) and macro-sized 6-carboxycelluloses (long-fibril shaped, 1.7-22% carboxyl content). The DP (50-70) and yield (upto 46%) of nanoparticles were manipulated by controlling the reaction temperature and time. TGA/DTG thermographs of the carboxycelluloses gave thermostability data and co-related well with the residual crystalline, amorphous, and anhydroglucuronic acid content. The particle shape and size had no effect on the thermal stability. Some derivatives were fully or partially soluble in aqueous alkali and non-aqueous solvents, which can lead to increased versatility of these polymers.

Clinical assessment of the sensory ataxias; diagnostic algorithm with illustrative cases.

Ataxia is a common neurological syndrome resulting from cerebellar, vestibular or sensory disorders. The recognition and characterisation of sensory ataxia remains a challenge. Cerebellar ataxia is the more common and easier to identify; sensory ataxia is often mistaken for cerebellar ataxia, leading to diagnostic errors and delays. A coherent aetiological work-up is only possible if clinicians initially recognise sensory ataxia. We discuss ways to separate sensory from cerebellar ataxia, the causes of sensory ataxia and the clinico-neurophysiological syndromes causing the sensory ataxia syndromes. We summarise a logical tiered approach as a diagnostic algorithm.

Determinants of in-hospital death after acute spinal cord injury: a population-based study.

OBJECTIVES: First, to evaluate the influence of comorbid diseases and concomitant injuries on the risk of in-hospital death after traumatic spinal cord injury (TSCI). Second, to identify the risk characteristics of TSCI patients with likelihood of death. STUDY DESIGN: Population-based retrospective cohort study. SETTING: Sixty-two acute care hospitals in South Carolina, USA. METHODS: Records of 3389 TSCI patients hospitalized with acute TSCI were evaluated. Days elapsing from the date of injury to date of death established the survival time (T). Cox regression examined risk of in-hospital death as a function of counts of comorbid conditions and injuries along with their joint effects controlling for other covariates. RESULTS: Counts of comorbid conditions and injuries showed dose-dependent risk of death while in-hospital independent of demographical and clinical covariates. Hazard ratios (HR) for counts 3+, 2 and 1 comorbid conditions were 2.19 (P<0.001), 1.73 (P=0.005) and 1.20 (P=0.322), respectively. For counts of 4+, 3 and 2 other injuries were 1.85 (P<0.001), 1.81 (P<0.001) and 1.46 (P=0.022), respectively. The joint effect of the two was transadditive with statistically significant HR ranging from 1.72-3.14. CONCLUSION: Counts of comorbid conditions and injured body regions strongly indicate risk of in-hospital death after TSCI and their joint effects elicited dose-dependent gradient independent of demographical and clinical covariates. Assessing risk of in-hospital death based on joint use of counts of comorbid diseases and injuries is highly informative to target TSCI patients at high risk of dying.