Diagnostic efficacy of chest CT imaging in diagnosis of COVID-19 cases based on duration of symptoms.

Background: Chest computed tomography (CT) imaging provides results more rapidly and with higher sensitivity than reverse transcription polymerase chain reaction in diagnosis of COVID-19. Aim: To evaluate diagnostic efficacy of chest CT imaging in diagnosis of COVID-19 cases based on age and duration of symptoms. Materials and Methods: A retrospective study conducted during December 2020 to June 2021 in a tertiary care hospital, India. Total 495 patients with typical clinical symptoms of COVID-19, reverse transcription polymerase chain reaction positive for COVID-19 and had undergone chest CT imaging were included. Descriptive statistical analysis was performed for all the variables. Receiver operating characteristic curve analysis was used to determine threshold value of chest CT severity score (CT_SS) based on duration of symptoms and age to diagnose COVID-19. Results: Mean age of patients was 61.86 ± 10.77 years and 367 (71.4%) patients were male. Ground glass opacities were observed in 456 (92.1%) patients and in 332 (67.1%) patients, multilobes were affected. Total CT_SS showed positive correlation with age (r = 0.257) and duration of symptoms (r = 0.625). Total CT_SS >6 after a duration of 2 days of symptoms identified COVID-19 cases with sensitivity 90.8% (95% confidence interval [CI]: 87.5%-93.5%) and specificity 84.6% (95% CI: 76.2%-90.9%). Total CT_SS >11 in patients aged more than 60 years identified COVID-19 cases with sensitivity 47.4% (95% CI: 41.2%-53.6%) and specificity 87.3% (95% CI: 82.3%-91.4%). Conclusion: Threshold value of CT_SS determined will help to expedite diagnosis of COVID-19 patients by the clinicians in an early stage especially in India and other developing countries which have a high patient volume and limited health resources.

Case Report of Male Pseudohermaphroditism (Androgen Insensitivity Syndrome): Congenital Disorder of Sexual Differentiation.

INTRODUCTION: A broad spectrum of anomalies of sexual differentiation may exist at birth, which can be unreported until adolescence. A 17-year-old patent with female phenotype came with complaints of primary amenorrhea. On imaging (ultrasound and MRI) uterus and bilateral ovaries were absent. Small blind-ending vaginal pouch was noted along with features suggesting bilateral cryptorchidism. No definite male external genitalia/scrotal sac was seen except for subtle rudimentary bulbo-cavernous muscles. Karyotyping confirmed 46 XY consistent with Male Pseudohermaphroditism. MATERIALS: Male pseudohermaphroditism refers to a condition that affects 46, XY individuals with differentiated testes who exhibit varying degrees of feminization. In these cases there is a spectrum of external genitalia; some individuals are completely phenotypically female. Androgen insensitivity syndrome (AIS), also known as the testicular feminization syndrome, results from end-organ resistance to androgens, particularly testosterone. As the appearance of the external genitalia often is not distinctive enough to make a specific diagnosis, this must be accomplished by clinical findings along with a combination of imaging, cytogenetic and biochemical studies. Ultrasound and MRI studies are extremely useful to diagnose such conditions at the earliest as these patients have an increased incidence of malignancy in the undescended testes. The treatment is influenced by genital tissue responsiveness to androgens and reconstructive surgical procedures. There is a need for counselling regarding pubertal development, sexual performance and fertility. RESULT: A 17year old patent came with complaints of primary amenorrhea. On examination patient has normal external female genitalia, with developed breast. On laboratory correlation, it shows high testosterone level: 881 ng/dL and Normal progesterone level: 0.182 ng/mL. On karyotyping, it shows 46XY karyotype. On USG: Uterus is not well appreciated. There is iso-echogenic oval shaped soft tissue seen in bilateral inguinal regions with vascularity within-likely to be gonads. On MRI: Absence of uterus and bilateral ovaries are confirmed with evidence of symmetrical oval-shaped soft tissue lesions identified within bilateral inguinal canals - consistent with bilateral cryptorchidism. Male pseudohermaphroditism refers to a condition that affects 46, XY individuals with differentiated testes who exhibit varying degrees of feminization. CONCLUSION: In cases of male pseudohermaphroditism, there is a spectrum of external genitalia; some individuals are completely phenotypically female, whereas others appear to be normal males with varying spermatogenesis and/or pubertal virilization. As the appearance of the external genitalia often is not distinctive enough to make a specific diagnosis, this must be accomplished by clinical findings along with a combination of cytogenetic, biochemical, and radiologic studies. Sonographic and radiographic studies are often used initially to evaluate such conditions. Male pseudohermaphrodites all possess testes yet exhibit incomplete virilization of the genital ducts and/or external genitalia. The findings depend on the underlying defect. Complete androgen insensitivity (testicular feminization) is an X-linked recessive disorder in which the absence of cytoplasmic testosterone receptors prevents specific gene activation and subsequent differentiation of the external genitalia. In this disorder, the external genitalia are completely feminized, while in the other forms of male pseudohermaphroditism various degrees of virilization occur. The absence of internal female genital tract structures reflects the synthesis of active Mullerian regression factor by the testes, which may be maldescended. Multiplanar MR images will confirm the absence of a uterus and demonstrate intraabdominal or inguinal testes. Integrated imaging in the form of ultrasound, genitography and MRI is important in demonstrating the anatomy, classification, possible effects or congenital malformations in other organs, warning patients of any risk of neoplasia and guiding the clinician to plan other investigations, hormonal replacement or reconstruction surgery if required. References Tanaka YO, Mesaki N, Kurosaki Y, et al. Testicular feminization: role of MRI in diagnosing this rare male pseudohermaphroditism. J Comput Assist Tomogr 1998;22(6):884-888. Nakhal RS, Hall-Craggs M, Freeman A, et al. Evaluation of retained testes in adolescent girls and women with complete androgen insensitivity syndrome. Radiology 2013;268(1):153-160.

(Cd,Mg)Te crystals for picosecond-response optical-to-x-ray radiation detectors.

We demonstrate a photodetector sensitive to both optical and x-ray picosecond pulses based on our in-house grown cadmium magnesium telluride (Cd,Mg)Te single crystal. Specifically, we developed In-doped Cd0.96Mg0.04Te material and discuss its femtosecond optical photoresponse, as well as the detector performance, such as <100-pA dark current and up to 0.22-mA/W responsivity for 780-nm wavelength optical radiation. The detector exposed to Ti fluorescence (K alpha) x-ray pulses at 4.5 keV, generated by a free-electron laser beam with the central energy of 9.8 keV and <100 fs pulse width, exhibited readout-electronics-limited 200-ps full-width-at-half-maximum photoresponse, demonstrating that it is suitable for coarse timing in free-electron laser x-ray/optical femtosecond pump-probe spectroscopy applications.

Performance of prognostic scores in prediction of 30-day postoperative mortality in COVID-19 patients after emergency surgery: A retrospective cohort study.

Background: : Risk assessment with prognostic scoring, though important, is scarcely studied in emergency surgical patients with COVID-19 infection. Methods and Material: We conducted a retrospective cohort study on adult emergency surgical patients with COVID-19 infection in our institute from 1 May 2020 to 31 October 2021 to find the 30-day postoperative mortality and predictive accuracy of prognostic scores. We assessed the demographic data, prognostic risk scores (American Society of Anesthesiologists-Physical Classification (ASA-PS), Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), Physiologic and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) and Portsmouth-POSSUM (P-POSSUM) scores), surgical and anesthetic factors. We assessed the postoperative morbidity using the Clavien-Dindo scale and recorded the 30-day mortality. Correlation of prognostic scores and mortality was evaluated using Univariate Cox proportional hazards regression, receiver operating characteristic curve (ROC), Youden's index and Hosmer- Lemeshow goodness of fit model. Results: Emergency surgery was performed in 67 COVID-19 patients with postoperative complication and 30-day mortality rate of 33% and 19%, respectively. A positive qSOFA and ASAPS IIIE/IVE had a 9.03- and 12.7-times higher risk of mortality compared to a negative qSOFA and ASA-PS IE/IIE (P < 0.001), respectively. Every unit increase of SOFA, POSSUM and P-POSSUM scores was associated with a 50%, 18% and 17% higher risk of mortality, respectively. SOFA, POSSUM and P-POSSUM AUCROC curves showed good discrimination between survivors and non-survivors (AUC 0.8829, 0.85 and 0.86, respectively). Conclusions: SOFA score has a higher sensitivity to predict 30-day postoperative mortality as compared to POSSUM and P-POSSUM. However, in absence of a control group of non-COVID-19 patients, actual risk attributable to COVID-19 infection could not be determined.

Diversity of rumen microbiota using metagenome sequencing and methane yield in Indian sheep fed on straw and concentrate diet.

An in vivo study aiming to investigate the rumen methanogens community structure was conducted in Mandya sheep fed on straw and concentrate diet. The ruminal fluid samples were collected and processed for unravelling the rumen microbiota and methanogens diversity. Further, the daily enteric methane emission and methane yield was also quantified using the SF6 tracer technique. Results indicated that the Bacteroidetes (∼57%) and Firmicutes (25%) were two prominent affiliates of the bacterial community. Archaea represented about 2.5% of the ruminal microbiota. Methanobacteriales affiliated methanogens were the most prevalent in sheep rumen. The study inveterate that the ruminal archaea community in sheep is composed of 9 genera and 18 species. Methanobrevibacter represented the largest genus of the archaeome, while methylotrophs genera constituted only 13% of the community. Methanobrevibacter gottschalkii was the prominent methanogen, and Methaobrevibacter ruminantium distributed at a lower frequency (∼2.5%). Among Methanomassiliicoccales, Group 12 sp. ISO4-H5 constituted the most considerable fraction (∼11%). KEGG reference pathway for methane metabolism indicated the formation of methane through hydrogenotrophic and methylotrophic pathways, whereas the acetoclastic pathway was not functional in sheep. The enteric methane emission and methane yield was 19.7 g/d and 20.8 g/kg DMI, respectively. Various species of Methanobrevibacter were differently correlated, and the distribution of hydrogenotrophic methanogens mainly explained the variability in methane yield between the individual sheep. It can be inferred from the study that the hydrogenotrophic methanogens dominate the rumen archaeal community in sheep and methylotrophic/aceticlastic methanogens represent a minor fraction of the community. Further studies are warranted for establishing the metabolic association between the prevalent hydrogenotrophs and methylotrophs to identify the key reaction for reducing methane emission.

Effect of silkworm (Bombyx mori) pupae oil supplementation on enteric methane emission and methanogens diversity in sheep.

In vitro and in vivo studies were conducted to examine the effect of silkworm pupae oil on methane (CH4) emission and methanogens diversity. Five graded levels (2, 4, 6, 8 and 10%) of silkworm pupae oil were tested in vitro. Eighteen Mandya adult sheep were divided into three groups. All the animals were fed on similar basal diet except the oil supplementation in test groups. Oil level for supplementation was decided on the basis of in vitro study. In vitro study indicated a reduction of 22% in CH4 production with 2% oil supplementation. Animals in test groups were supplemented with oil (2%) either daily (CON) or intermittently (INT) on every alternate week for all the seven days. A significant reduction of 17-20% in enteric CH4 emission (g/d) was achieved due to oil supplementation in sheep. However, No variation was established between test groups CON and INT. In present study, Methanobrevibacter was major genus contributed ∼90% of the total rumen methanogens; whilst Methanobrevibacter gottschalkii was the most abundant methanogens species. Abundance of Methanobrevibacter ruminantium was affected with the oil supplementation. It can be concluded that the silkworm pupae oil at 2% can decrease CH4 emission by 15-20%.

Observational study to compare the effect of altitude on cardiopulmonary reserves of different individuals staying more than 6 weeks at 10,000 ft and 15,000 ft.

BACKGROUND: The variation in heights beyond high altitude has different effects on the cardiorespiratory profile of individuals because of variation in oxygen density with every thousand feet. This study was planned to analyze and compare the effects of difference in altitudes on cardiorespiratory profile from anesthesiologist's point of view. METHODS: A multicenter observational study was done involving two different groups of 600 patients at 10,000 ft (Group A) and 15,000 ft (Group B). Observation and comparison of oxygen saturation, 6-min walk test, and breath holding time was carried out. RESULTS: Fifty-five percent of subjects in Group A had oxygen saturation of more than 93% in comparison to 5.5% in Group B. This was statistically significant (P < 0.001). Two percent of subjects in Group A in comparison to 63.5% of Group B had oxygen saturation of less than 88% (P < 0.001). Percentage increase of more than 15% of heart rate was found to be statistically significant in all the age groups. Overall, 3.8% of individuals in Group A had breath holding time less than 15 s in comparison to 16.6% of individuals in Group B (P value < 0.001). CONCLUSION: The study demonstrates that there is a significant fall in oxygen saturation, significant rise in the heart rate in 6-min walk test, and significant fall in the breath holding time in the group located at 15,000 ft. Heights beyond 10,000 ft should be restricted to life and limb saving surgeries, and logistics should be focused more on "scoop and run" than "stay and play" policy.

Comparison of enteric methane yield and diversity of ruminal methanogens in cattle and buffaloes fed on the same diet.

An in vivo study was conducted to compare the enteric methane emissions and diversity of ruminal methanogens in cattle and buffaloes kept in the same environment and fed on the same diet. Six cattle and six buffaloes were fed on a similar diet comprising Napier (Pennisetum purpureum) green grass and concentrate in 70:30. After 90 days of feeding, the daily enteric methane emissions were quantified by using the SF6 technique and ruminal fluid samples from animals were collected for the diversity analysis. The daily enteric methane emissions were significantly greater in cattle as compared to buffaloes; however, methane yields were not different between the two species. Methanogens were ranked at different taxonomic levels against the Rumen and Intestinal Methanogen-Database. The archaeal communities in both host species were dominated by the phylum Euryarchaeota; however, Crenarchaeota represented <1% of the total archaea. Methanogens affiliated with Methanobacteriales were most prominent and their proportion did not differ between the two hosts. Methanomicrobiales and Methanomassillicoccales constituted the second largest group of methanogens in cattle and buffaloes, respectively. Methanocellales (Methanocella arvoryza) were exclusively detected in the buffaloes. At the species level, Methanobrevibacter gottschalkii had the highest abundance (55-57%) in both the host species. The relative abundance of Methanobrevibacter wolinii between the two hosts differed significantly. Methanosarcinales, the acetoclastic methanogens were significantly greater in cattle than the buffaloes. It is concluded that the ruminal methane yield in cattle and buffaloes fed on the same diet did not differ. With the diet used in this study, there was a limited influence (<3.5%) of the host on the structure of the ruminal archaea community at the species level. Therefore, the methane mitigation strategies developed in either of the hosts should be effective in the other. Further studies are warranted to reveal the conjunctive effect of diet and geographical locations with the host on ruminal archaea community composition.

The effect of therapeutic hypothermia on heart rate variability.

OBJECTIVE: Heart rate variability (HRV) reflects integrity of the autonomic nervous system. However, no study has investigated the impact of therapeutic hypothermia (TH) on HRV measures in infants with hypoxic-ischemic encephalopathy (HIE). In this study, we evaluate the influence of temperature on measures of HRV for a group of infants with favorable outcomes, as compared with a control group of infants with unfavorable outcomes. STUDY DESIGN: Term-born infants with moderate-severe HIE underwent standard TH treatment and prospective electroencephalography (EEG) and electrocardiogram (ECG) recording. Infants with favorable outcome (no seizures, normal/mild EEG scores at 96 h, no magnetic resonance imaging brain injury and normal neurodevelopmental scores at 18 to 24 months) were matched on gestational age, sex and worst encephalopathy score to a group of infants with unfavorable outcomes. Time- and frequency-domain HRV measures were calculated from 60 min of ECG data obtained at three time points: 24 h (hypothermia), 48 h (hypothermia) and 96 h (normothermia). The effect of time and temperature were evaluated using repeated-measures analysis of variance. RESULTS: Sixteen infants were included (8 favorable, 8 unfavorable). For both groups of infants, an increase in the HR, RR and HF power was associated with an increase in temperature, but was not associated with any other HRV measure. In contrast, measures of HRV increased over time, as encephalopathy decreased, for infants with favorable outcomes (reflecting increased cortical-autonomic integration), but not for those with unfavorable outcomes. CONCLUSIONS: In general, the effect of hypothermia on measures of HRV is limited to changes in heart rate (bradycardia) and respiratory rate, as opposed to changes in true variability. This supports the hypothesis that persistent changes in HRV are driven by the underlying brain injury and not by the process of TH.

Phase II trial of post-operative radiotherapy with concurrent cisplatin plus panitumumab in patients with high-risk, resected head and neck cancer.

BACKGROUND: Treatment intensification for resected, high-risk, head and neck squamous cell carcinoma (HNSCC) is an area of active investigation with novel adjuvant regimens under study. In this trial, the epidermal growth-factor receptor (EGFR) pathway was targeted using the IgG2 monoclonal antibody panitumumab in combination with cisplatin chemoradiotherapy (CRT) in high-risk, resected HNSCC. PATIENTS AND METHODS: Eligible patients included resected pathologic stage III or IVA squamous cell carcinoma of the oral cavity, larynx, hypopharynx, or human-papillomavirus (HPV)-negative oropharynx, without gross residual tumor, featuring high-risk factors (margins <1 mm, extracapsular extension, perineural or angiolymphatic invasion, or ≥2 positive lymph nodes). Postoperative treatment consisted of standard RT (60-66 Gy over 6-7 weeks) concurrent with weekly cisplatin 30 mg/m2 and weekly panitumumab 2.5 mg/kg. The primary endpoint was progression-free survival (PFS). RESULTS: Forty-six patients were accrued; 44 were evaluable and were analyzed. The median follow-up for patients without recurrence was 49 months (range 12-90 months). The probability of 2-year PFS was 70% (95% CI = 58%-85%), and the probability of 2-year OS was 72% (95% CI = 60%-87%). Fourteen patients developed recurrent disease, and 13 (30%) of them died. An additional five patients died from causes other than HNSCC. Severe (grade 3 or higher) toxicities occurred in 14 patients (32%). CONCLUSIONS: Intensification of adjuvant treatment adding panitumumab to cisplatin CRT is tolerable and demonstrates improved clinical outcome for high-risk, resected, HPV-negative HNSCC patients. Further targeted monoclonal antibody combinations are warranted. REGISTERED CLINICAL TRIAL NUMBER: NCT00798655.

Early hyperoxia burden detected by cerebral near-infrared spectroscopy is superior to pulse oximetry for prediction of severe retinopathy of prematurity.

OBJECTIVE: Fractional tissue oxygen extraction (FTOE) is a measure derived from cerebral near-infrared spectroscopy (NIRS) and simultaneous pulse oximetry (SpO2), capturing the proportion of oxygen delivered in arterial blood that is used by the target tissue. FTOE may provide a better proxy measurement of retinal hyperoxia than pulse oximetry alone and could provide insight into the risk for retinopathy of prematurity (ROP). In this study, we directly compared hyperoxia burden calculated from FTOE with hyperoxia burden calculated from SpO2 alone in order to assess the strength of association between hyperoxia and severe ROP. STUDY DESIGN: Infants born before <30 weeks and weighing <1500 g underwent synchronized SpO2 and FTOE recording over the first 4 days following birth. After error correction of the raw recording, hyperoxia burden was calculated as the percentage of the total SpO2 or FTOE recording with measurements exceeding defined thresholds (90/93/95% and 20/15/10%, respectively) and was compared with the outcome of severe ROP, defined as ROP requiring laser therapy, after controlling for important covariates. RESULT: A total of 63 infants were included with a mean±s.d. gestational age of 25.8±1.5 weeks and birth weight of 898.5±206.9 g; 13/63 (20%) had severe ROP. SpO2 hyperoxia burden was not associated with severe ROP at any threshold. FTOE hyperoxia burden was associated with severe ROP at the 15% (P=0.04) and 10% (P=0.03) thresholds. Infants with severe ROP spent 20% and 50% more time exceeding the 15% and 10% thresholds, respectively, as compared with those without severe ROP. CONCLUSION: In the first 96 h of life, FTOE but not SpO2 hyperoxia burden is associated with severe ROP. These preliminary results suggest that NIRS may be a viable alternative technology for targeted oxygen saturation guidelines.

Clinical and radiographic evaluation of effect of risedronate 5 mg as an adjunct to treatment of chronic periodontitis in postmenopausal women (12-month study).

UNLABELLED: Bisphosphonates are beneficial to women, after menopause, in treatment of gum diseases. In this study, significant improvement in the disease condition was found and that no further progress was noted, and no side effects were reported. Bisphosphonates can be safely and successfully be used to support oral health procedures. INTRODUCTION: The purpose of this study was to evaluate host modulating effect of bisphosphonate adjunct with the treatment of chronic periodontitis in osteopenic and osteoporotic postmenopausal women. METHODS: Twenty-two osteopenic and osteoporotic postmenopausal women with moderate to severe chronic periodontitis were selected for the study. On intraoral examination, periodontal parameters like probing depth (PD), clinical attachment level (CAL), Plaque Index (PI) and Gingival Index (GI) were recorded. Scaling and root planing were done. Intraoral periapical X-rays were taken, and alveolar bone density (ABD) was measured with cone beam computed tomography (CBCT), and then, medications (risedronate 5 mg once daily (OD), calcium citrate 250 mg OD, vitamin D 400 IU OD) were given. Patients were recalled for follow-up at 3, 6 and 12 months. Intraoral periapical (IOPA) X-rays were taken at 6 and 12 months and ABD was measured at baseline and 12 months. RESULTS: There was a significant improvement in all the parameters. There was an increase of 0.02 ± 0.001 cm on CT scan and 0.38 ± 0.005 mm on IOPA in bone height over 12 months from baseline. Bone density increased by 118.56 ± 3.251 Hounsfield units (HU). There was no progress in the disease, and further bone loss was not noticed. This is in correlation with clinical parameters which showed highly significant gain in CAL (3.57 ± 0.234 mm) and reduction in PD (2.20 ± 0.229 mm) CONCLUSIONS: Bisphosphonate therapy as an adjunct to scaling and root planing may have significant beneficial clinical effects on the periodontium of postmenopausal women with moderate to severe chronic periodontitis.

Response to dopamine in prematurity: a biomarker for brain injury?

OBJECTIVE: To identify factors associated with responsiveness to dopamine therapy for hypotension and the relationship to brain injury in a cohort of preterm infants. STUDY DESIGN: The pharmacy database at St Louis Children's Hospital was retrospectively queried to identify infants who (a) were born <28 weeks gestation between 2012 and 2014, (b) received dopamine and (c) had blood pressure measurements from an umbilical arterial catheter. A control group was constructed from contemporaneous infants who did not receive dopamine. Mean arterial blood pressure (MABP) at baseline, 1 h and 3 h after initiating dopamine were obtained for each dopamine-exposed infant. MABP measurements at matched time points were obtained in the control group. RESULT: Sixty-nine dopamine-treated and 45 control infants were included. Mean ΔMABP at 3 h was 4.5±6.3 mm of Hg for treated infants vs 1±2.9 for the control. Median dopamine starting dose was 2.5 µg kg(-1) min(-1). Dopamine-treated infants were less mature and of lower birth weight while also more likely to be intubated at 72 h, diagnosed with intraventricular hemorrhage (IVH) and to die. Failure to respond to dopamine was associated with greater likelihood of developing IVH (odds ratio (OR) 5.8, 95% confidence interval (CI) 1.1-42.3), while a strong response (ΔMABP>10 mm Hg) was associated with a reduction in risk of IVH (OR 0.1, 95% CI 0.01-0.8). CONCLUSION: Low-moderate dose dopamine administration results in modest blood pressure improvements. A lack of response to dopamine is associated with a greater risk of IVH, whereas a strong response is associated with a decreased risk. Further research into underlying mechanisms and management strategies is needed.

EGFR-targeted mAb therapy modulates autophagy in head and neck squamous cell carcinoma through NLRX1-TUFM protein complex.

Epidermal growth factor receptor (EGFR)-targeted therapy in head and neck squamous cell carcinoma (HNSCC) patients frequently results in tumor resistance to treatment. Autophagy is an emerging underlying resistance mechanism, however, the molecular autophagy machinery in HNSCC cells and potential biomarkers of patient response to EGFR-targeted therapy remain insufficiently characterized. Here we show that the EGFR blocking with cetuximab leads to varied autophagic responses, which modulate cancer cell susceptibility to EGFR inhibition. Inhibition of autophagy sensitizes HNSCC cells to EGFR blockade. Importantly, we identify a novel signaling hub centering on the NLRX1 (nucleotide-binding, lots of leucine-rich repeats-containing protein member X1)-TUFM (Tu translation elongation factor mitochondrial) protein complex, promoting autophagic flux. Defects in the expression of either NLRX1 or TUFM result in compromised autophagy when treated with EGFR inhibitors. As a previously undefined autophagy-promoting mechanism, we found that TUFM serves as a novel anchorage site, recruiting Beclin-1 to mitochondria, promoting its polyubiquitination, and interfering with its interaction with Rubicon. This protein complex is also essential for endoplasmic reticulum stress signaling induction, possibly as an additional mechanism to promote autophagy. Utilizing tumor specimens from a novel neoadjuvant clinical trial, we show that increased expression of the autophagy adaptor protein, SQSTM1/p62, is associated with poor response to cetuximab therapy. These findings expand our understanding of the components involved in HNSCC autophagy machinery that responds to EGFR inhibitors, and suggest potential combinatorial approaches to enhance its therapeutic efficacy.

Severe non-infective systemic inflammatory response syndrome, shock, and end-organ dysfunction after zoledronic acid administration in a child.

INTRODUCTION: Zoledronic acid is an intravenous bisphosphonate used to increase bone mineral density and reduce the risk of fractures. Its safety profile compares well with pamidronate in pediatric patients. We describe an acute, severe, life-threatening, inflammatory reaction in a child. METHODS: A 7-year-old boy with complex medical problems and chronic ventilator requirements was admitted to the pediatric intensive care unit (due to ventilator needs) for zoledronic acid infusion and subsequent monitoring. His history was significant for osteoporosis secondary to immobilization with multiple fractures since 2 years of age, hypoxic-ischemic encephalopathy, quadriplegic cerebral palsy, seizure disorder, ventilator dependence, and pulmonary hypertension. He had previously been treated with four cycles of pamidronate without adverse events. He received 0.013 mg/kg of zoledronic acid infused over 30 minutes. Beginning 3 hours after completion of the infusion, he developed progressive tachycardia, fever, hypotension requiring vasopressor infusion, and increasing oxygen requirements. Laboratory studies revealed leukopenia, thrombocytopenia, elevated C-reactive protein, abnormal coagulation profile, metabolic acidosis, and negative cultures. The following day, he developed moderate acute respiratory distress syndrome and pulmonary hemorrhage requiring higher ventilatory settings, and subsequently diarrhea and abdominal distension. Initial clinical resolution was noted from the third day onward, and he was discharged on the sixth day after zoledronate administration. RESULTS: Our pediatric patient demonstrated an acute, severe, life-threatening reaction to zoledronic acid requiring intensive cardiorespiratory support without an underlying pre-existing inflammatory disorder. CONCLUSION: Our case highlights the importance of careful monitoring of children following zoledronic acid therapy. We recommend inpatient observation after an initial infusion of zoledronic acid in medically complex children. Children and their parents should be thoroughly counseled on the potential risks of bisphosphonate treatment, which can sometimes be severe and life threatening.

A Rare Case of Anomalous Origin of First Lumbrical from the Tendon of Flexor Digitorum Superficialis to Index Finger.

Human hand is involved in variety of precision work which requires a combined effort of forearm muscles as well as intrinsic muscles of hand. Lumbricals along with interossei muscles connect the tendons of flexor and extensor muscles and thus play a key role in the characteristic movements of human hands. Lumbricals originate from long flexor tendon and is inserted into dorsal digital expansion. Any variation in the attachment of these muscles can lead to deviation from the normal actions of the fingers and their proximal extension into carpal tunnel and might lead to carpal tunnel syndrome. An extremely rare case of first lumbrical taking origin solely from first tendon of Flexor Digitorum Superficialis (FDS) and having proximal attachment extending into carpal tunnel was noticed bilaterally in cadaveric dissection. These variations are always challenging for clinicians and surgeons during hand surgeries.

The longest tumor diameter in one dimension as a predictor for skeletal metastasis in renal cell carcinoma.

INTRODUCTION: Renal cell carcinoma (RCC) comprises a diverse group of malignant neoplasms that have multifarious histopathological features and biological behavior. One-third of RCC patients develops skeletal metastasis with a poor 5-year survival rate. Data explaining how some of these tumors show sooner bony metastasis than expected is sparse. The objective of this study was to identify whether tumor size can act as a predictor of bony metastases among patients of RCC. MATERIALS AND METHODS: We retrospectively reviewed contrast enhanced computed tomography (CECT) scan and clinical records of 66 patients with RCC, who fulfilled specified inclusion criteria. Patients who had bony metastasis at the time of presentation were selected as case and those without skeletal metastasis were referred to as controls. Receiver operating characteristic (ROC) curve analysis was used to determine the appropriate cut-off value for tumor size, which was measured as the longest tumor diameter (LTD) in one-dimensional (1D). RESULTS: Of the 66 patients selected, 30% developed bone metastasis. The tumor size of RCCs significantly correlated with the presence of skeletal metastasis in our study. None of the patients with 1D LTD <4.8 cm on CECT were found to have skeletal metastasis. ROC analysis revealed that the accuracy of the LTD in predicting bone metastasis was high with an area under ROC curve of 0.823. A cut-off value of 7.5 cm had a sensitivity of 78.9% and specificity of 80.9%. CONCLUSION: The 1D LTD with a cut-off value of 7.5 cm, at the time of presentation is an important predictor of skeletal metastasis. The result of this study may have role in triage of patients into a subgroup which mandates more aggressive treatment and monitoring.